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fix: complete reference detection fixes — 5 problem families

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LLLin000 2026-07-03 01:46:09 +08:00
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129 changed files with 117275 additions and 15 deletions
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537
audit/24A2QUAH/audit_report.json Normal file
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{
"paper_key": "24A2QUAH",
"mode": "high-risk",
"status": "READY",
"focus": [],
"artifact_fingerprint": {
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}
},
"artifact_freshness": {
"missing": [],
"mismatches": [
"document_structure older than blocks_structured",
"figure_inventory older than blocks_structured",
"table_inventory older than blocks_structured",
"reader_figures older than figure_inventory",
"resolved_metadata older than blocks_structured"
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"annotated_pages_rendered": [
"page_001.png",
"page_002.png",
"page_003.png",
"page_004.png",
"page_005.png",
"page_006.png",
"page_007.png",
"page_008.png",
"page_009.png",
"page_010.png",
"page_011.png",
"page_012.png"
]
},
"reviewed_pages": [
1,
3,
4,
5,
6,
7,
8,
9
],
"reviewed_blocks": [
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"p1:1",
"p1:2",
"p1:3",
"p1:4",
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"p1:6",
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"p1:8",
"p1:9",
"p1:10",
"p1:11",
"p1:12",
"p1:13",
"p1:14",
"p1:15",
"p1:16",
"p1:17",
"p1:18",
"p1:19",
"p3:0",
"p3:1",
"p3:2",
"p3:3",
"p3:4",
"p3:5",
"p3:6",
"p3:7",
"p3:8",
"p3:9",
"p3:10",
"p4:0",
"p4:1",
"p4:2",
"p4:3",
"p4:4",
"p4:5",
"p4:6",
"p4:7",
"p4:8",
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"p5:0",
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"p7:3",
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"p7:6",
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"p7:9",
"p7:10",
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"p8:0",
"p8:1",
"p8:2",
"p8:3",
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"p8:5",
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"p9:0",
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"p9:2",
"p9:3",
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"p9:5",
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"p9:9",
"p9:10",
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"p9:12",
"p9:13",
"p9:14",
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"p9:16",
"p9:17",
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"p9:19",
"p9:20",
"p9:21",
"p9:22",
"p9:23",
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"p9:29",
"p9:30",
"p9:31",
"p9:32",
"p9:33",
"p9:34",
"p9:35"
],
"findings": [
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:9"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:10"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:11"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:12"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:13"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:14"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:15"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:16"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:17"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:18"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:19"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:20"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:21"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:22"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:23"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:24"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:25"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:26"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:27"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p9:28"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "frontmatter_error",
"severity": "major",
"block_ids": [],
"truth": "page 1 should have clearer frontmatter role resolution",
"pipeline_behavior": "frontmatter page retains elevated unknown_structural density",
"root_cause_hypothesis": "frontmatter anchor or noise routing weakness",
"evidence": {
"annotated_page": "annotated_pages/page_001.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_009.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
"p1:0",
"p1:3",
"p1:4",
"p1:5",
"p1:6",
"p1:7",
"p1:8",
"p1:9",
"p1:10",
"p1:11",
"p2:12",
"p3:2",
"p3:3",
"p3:10",
"p4:2",
"p4:10",
"p5:4",
"p5:12",
"p6:2",
"p6:12"
],
"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
"annotated_page": null,
"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

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audit/24A2QUAH/audit_report.md Normal file
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# OCR Truth Audit Report - 24A2QUAH
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 3, 4, 5, 6, 7, 8, 9]
- Reviewed blocks: 129
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `frontmatter_error`: frontmatter page retains elevated unknown_structural density
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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audit/24A2QUAH/audit_scope.json Normal file
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{
"mode": "high-risk",
"selected_pages": [
1,
3,
4,
5,
6,
7,
8,
9
],
"required_block_ids": [
"p1:0",
"p1:1",
"p1:2",
"p1:3",
"p1:4",
"p1:5",
"p1:6",
"p1:7",
"p1:8",
"p1:9",
"p1:10",
"p1:11",
"p1:12",
"p1:13",
"p1:14",
"p1:15",
"p1:16",
"p1:17",
"p1:18",
"p1:19",
"p3:3",
"p3:5",
"p4:3",
"p5:2",
"p5:5",
"p6:3",
"p7:3",
"p7:5",
"p8:3",
"p8:5",
"p9:4",
"p9:9",
"p9:10",
"p9:11",
"p9:12",
"p9:13",
"p9:14",
"p9:15",
"p9:16",
"p9:17",
"p9:18",
"p9:19",
"p9:20",
"p9:21",
"p9:22",
"p9:23",
"p9:24",
"p9:25",
"p9:26",
"p9:27",
"p9:28",
"p9:29",
"p9:30",
"p9:31",
"p9:32",
"p9:33",
"p9:34"
],
"required_blocks": [
{
"block_id": "p1:0",
"page": 1,
"required_reason": [
"frontmatter"
],
"minimum_fields": [
"block_id",
"page",
"review_status",
"truth_role",
"truth_zone",
"truth_reference_membership"
]
},
{
"block_id": "p1:1",
"page": 1,
"required_reason": [
"frontmatter",
"needs_resolution"
],
"minimum_fields": [
"block_id",
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]
},
{
"block_id": "p1:2",
"page": 1,
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"frontmatter",
"needs_resolution"
],
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"page",
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]
},
{
"block_id": "p1:3",
"page": 1,
"required_reason": [
"frontmatter",
"needs_resolution"
],
"minimum_fields": [
"block_id",
"page",
"review_status",
"truth_role",
"truth_zone",
"truth_reference_membership"
]
},
{
"block_id": "p1:4",
"page": 1,
"required_reason": [
"frontmatter"
],
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"block_id",
"page",
"review_status",
"truth_role",
"truth_zone",
"truth_reference_membership"
]
},
{
"block_id": "p1:5",
"page": 1,
"required_reason": [
"frontmatter"
],
"minimum_fields": [
"block_id",
"page",
"review_status",
"truth_role",
"truth_zone",
"truth_reference_membership"
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Biochemistry Research International
Volume 2020, Article ID 9659412, 12 pages
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1,5,text,"Xiangbo Meng $ ^{ID} $ $ ^{1,2} $ Reihane Ziadlou, $ ^{3} $ Sibylle Grad, $ ^{3} $ Mauro Alini, $ ^{3} $ Chunyi Wen $ ^{ID} $ $ ^{4} $ Yuxiao Lai, $ ^{2} $ Ling Qin, $ ^{2,5} $ Yanyan Zhao $ ^{ID} $ $","[166.0, 417.0, 1032.0, 477.0]",authors,0.8,"[""page-1 zone author_zone: Xiangbo Meng $ ^{ID} $ $ ^{1,2} $ Reihane Ziadlou, $ ^{3} $ ""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
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1,11,text,Correspondence should be addressed to Yanyan Zhao; zhaoyany606@163.com and Xinluan Wang; xl.wang@siat.ac.cn,"[168.0, 681.0, 1039.0, 705.0]",frontmatter_support,0.78,"[""first-surviving-page support text: Correspondence should be addressed to Yanyan Zhao; zhaoyany6""]",frontmatter_support,0.78,frontmatter_main_zone,support_like,none,True,True
1,12,text,Received 21 October 2019; Accepted 7 January 2020; Published 28 January 2020,"[169.0, 721.0, 757.0, 744.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Received 21 October 2019; Accepted 7 January 2020; Published""]",frontmatter_noise,0.8,frontmatter_main_zone,support_like,none,False,False
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2,4,paragraph_title,2. Selection Criteria and Critical Size,"[96.0, 746.0, 484.0, 772.0]",section_heading,0.85,"[""paragraph_title label with numbering: 2. Selection Criteria and Critical Size""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
2,5,text,"2.1. General Selection Criteria. The ideal animal model should be as close to the clinical setting as possible, have biological similarity, and be a suitable model for cartilage physiology [11, 12]. A","[96.0, 788.0, 587.0, 1228.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
2,6,text,"2.2. Critical Size of OCD. The critical size defect is defined as the smallest defect size (in diameter) the animal cannot self-repair without intervention [19]. In animal experiments, the understandi","[95.0, 1265.0, 587.0, 1499.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
2,7,text,,"[611.0, 141.0, 1104.0, 673.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
2,8,paragraph_title,3. Small Animal Models,"[613.0, 694.0, 866.0, 720.0]",section_heading,0.85,"[""paragraph_title label with numbering: 3. Small Animal Models""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
2,9,text,"Small animal models are crucial in “proof-of-concept” studies, especially for testing biosafety. In these studies, concepts are validated and in vitro results are first translated in vivo. Small anima","[611.0, 735.0, 1103.0, 990.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,10,text,"3.1. Rats. The rat models used for OCD regeneration have several advantages, as rats are inexpensive, easy to handle and house, and clinically more relevant than mice. The skeletal maturity of rats is","[611.0, 1024.0, 1104.0, 1417.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
2,11,text,"3.1.1. Experimental Protocol of Animal Surgeries. In typical procedures, animals were anaesthetized and shaved and the","[611.0, 1449.0, 1104.0, 1498.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
2,12,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1162.0, 31.0, 1181.0, 1576.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
3,0,header,Biochemistry Research International,"[98.0, 86.0, 399.0, 109.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,1,number,3,"[1087.0, 87.0, 1101.0, 106.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,2,figure_title,"TABLE 1: Comparison of age, cartilage, and defect size in different species.","[319.0, 142.0, 878.0, 165.0]",table_caption,0.9,"[""table prefix matched: TABLE 1: Comparison of age, cartilage, and defect size in di""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
3,3,table,<table><tr><td>Species</td><td>Age of skeletal maturity</td><td>Cartilage thickness</td><td>Cartilage volume</td><td>Critical-sized defect</td><td>Common defect depth</td></tr><tr><td>Rat</td><td>7 mo,"[98.0, 171.0, 1103.0, 393.0]",media_asset,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
3,4,figure_title,TABLE 2: Examples of studies using rat osteochondral defect models.,"[341.0, 432.0, 857.0, 454.0]",table_caption,0.9,"[""table prefix matched: TABLE 2: Examples of studies using rat osteochondral defect ""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
3,5,table,<table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Lee and Im [35]</td><td>12 weeks</td><td>,"[99.0, 461.0, 1101.0, 704.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
3,6,text,"knee was disinfected. A medial temporal medial longitudinal incision was made to expose the synovium of the knee joint, and then the trochlear groove was further exposed after the lateral patellar lux","[96.0, 740.0, 588.0, 927.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,7,text,"3.1.2. Applications of Rat OCD Model for Testing of Osteochondral Repair Materials. Using a 12-week-old rat model, Lee and Im [35] found that SOX trio-co-transduced adipose tissue derived stem cells (","[95.0, 968.0, 588.0, 1499.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
3,8,text,,"[611.0, 741.0, 1104.0, 904.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
3,9,text,"3.2. Rabbit. The rabbit model provides a suitable small animal model for assessing the repair of OCD, as rabbits have larger joints for surgical procedures [41]. The age of skeletal maturity in rabbit","[611.0, 946.0, 1105.0, 1497.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
3,10,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1163.0, 32.0, 1181.0, 1577.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
4,0,number,4,"[99.0, 88.0, 115.0, 107.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,1,header,Biochemistry Research International,"[801.0, 86.0, 1102.0, 110.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
4,2,figure_title,TABLE 3: Examples of studies using rabbit osteochondral defect models.,"[330.0, 142.0, 868.0, 166.0]",table_caption,0.9,"[""table prefix matched: TABLE 3: Examples of studies using rabbit osteochondral defe""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
4,3,table,<table><tr><td>Authors</td><td>Age/ weight</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Liao et al. [42]</td><td>2-2.5 kg,"[98.0, 171.0, 1101.0, 435.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
4,4,text,"3.2.1. Experimental Protocol of Animal Surgeries. In most studies, the creation of an OCD was based on the following protocol. The rabbits were anaesthetized; then, a medial peripatellar incision was ","[95.0, 473.0, 587.0, 705.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
4,5,text,"3.2.2. Applications of Rabbit OCD Models for Testing of Osteochondral Repair Materials. Liao et al. [42] prepared a novel hybrid scaffold composed of methacrylated chondroitin sulfate (CSMA), poly(eth","[95.0, 738.0, 588.0, 1498.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
4,6,paragraph_title,4. Large Animal Models,"[612.0, 474.0, 866.0, 501.0]",section_heading,0.85,"[""paragraph_title label with numbering: 4. Large Animal Models""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
4,7,text,"The large animals, such as goats, sheep, pigs, dogs, and horses, have the advantages of joint size and cartilage thickness and also have the most similar clinical lesions to humans [55]. Although larg","[610.0, 516.0, 1104.0, 863.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,8,text,4.1. Dog. The dog is considered to be a very friendly and loving partner over the world. The social and ethical issues associated with the use of dogs as preclinical and translational animal models ar,"[611.0, 902.0, 1104.0, 1295.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
4,9,text,4.1.1. Experimental Protocol of Animal Surgeries. Dogs were anaesthetized intravenously. The dog was fixed on the operating table in a supine position and the hair was shaved over the knee joint. The ,"[610.0, 1335.0, 1104.0, 1498.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
4,10,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1162.0, 30.0, 1181.0, 1576.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
5,0,header,Biochemistry Research International,"[98.0, 86.0, 399.0, 109.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
5,1,number,5,"[1087.0, 87.0, 1102.0, 107.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,2,image,,"[256.0, 144.0, 942.0, 356.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
5,3,figure_title,FIGURE 1: The process of the OCD regeneration in rabbits. A: the OCD were generated by electric drill in the femoral patellar groove; B: a 3.2 mm in diameter and 3.0 mm deep OCD was obtained; C: the b,"[97.0, 366.0, 1103.0, 411.0]",figure_caption,0.92,"[""figure_title label: FIGURE 1: The process of the OCD regeneration in rabbits. A:""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
5,4,figure_title,TABLE 4: Examples of studies using dog osteochondral defect models.,"[337.0, 443.0, 860.0, 465.0]",table_caption,0.9,"[""table prefix matched: TABLE 4: Examples of studies using dog osteochondral defect ""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
5,5,table,<table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Lv and Yu [59]</td><td>12 months</td><td>,"[98.0, 469.0, 1100.0, 694.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
5,6,text,"concurrently and medial tibial plateau. Scaffolds were implanted, and the wound layer was sutured [59].","[96.0, 731.0, 587.0, 780.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,7,text,4.1.2. Applications of Dog OCD Models for Testing of Osteochondral Repair Materials. Lv and Yu [59] investigated the articular OCD (6 mm diameter and 12 mm depth) repair using a composite lamellar sca,"[96.0, 813.0, 588.0, 1254.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
5,8,text,"4.2. Pig. Pigs are considered to be a suitable animal model for mimicking human diseases and have widely been used in biomedical research [63, 64]. The pig joint size, weight requirements, and cartila","[95.0, 1289.0, 587.0, 1499.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
5,9,text,,"[610.0, 731.0, 1103.0, 986.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
5,10,text,"4.2.1. Experimental Protocol of Animal Surgeries. After animals were anaesthetized, a 5 cm incision was created in the skin to expose the medial condyle. A cylindrical OCD was created in the knee join","[611.0, 1021.0, 1103.0, 1186.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
5,11,text,4.2.2. Applications of Pig OCD Models for Testing of Osteochondral Repair Materials. Several studies on cartilage and cartilage defects have been reported using min-pig. Christensen and coauthors [68],"[610.0, 1219.0, 1105.0, 1498.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
5,12,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1163.0, 31.0, 1181.0, 1576.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
6,0,number,6,"[99.0, 88.0, 115.0, 107.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,1,header,Biochemistry Research International,"[801.0, 86.0, 1102.0, 110.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
6,2,figure_title,TABLE 5: Examples of studies using pig osteochondral defect models.,"[340.0, 142.0, 857.0, 166.0]",table_caption,0.9,"[""table prefix matched: TABLE 5: Examples of studies using pig osteochondral defect ""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
6,3,table,<table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Christensen et al. [68]</td><td>19.8 mont,"[98.0, 172.0, 1101.0, 371.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
6,4,text,enhance the mechanical properties and histological appearance of cartilage regenerates in mini-pig OCD models.,"[95.0, 404.0, 586.0, 453.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,5,text,"4.3. Sheep. Sheep is one of the commonly used animal models in orthopaedic research. The anatomy of the knee is similar to humans. However, due to the thinness of the cartilage, most of the defects ar","[96.0, 485.0, 587.0, 877.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
6,6,text,"4.3.1. Experimental Protocol of Animal Surgeries. The sheep were anaesthetized; then, sheep were placed in dorsal recumbency. The skin on the right knee was sterilized and was ready for sterile surger","[95.0, 909.0, 587.0, 1120.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
6,7,text,4.3.2. Applications of Sheep OCD Models for Testing of Osteochondral Repair Materials. Schlichting et al. [70] created an 8 mm in diameter and 15 mm deep OCD in the femoral condyles of 24 sheep to pro,"[95.0, 1150.0, 588.0, 1499.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
6,8,text,,"[611.0, 402.0, 1104.0, 569.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
6,9,text,"4.4. Goat. Goats are similar to sheep and are easy to raise and manage. The skeletal maturity of goats is similar to that of sheep, namely, about 2 to 3 years [11]. Goats aged between 2 and 4 years ha","[611.0, 600.0, 1104.0, 1061.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
6,10,text,"4.4.1. Experimental Protocol of Animal Surgeries. Surgery was performed under general anesthesia via joint surgery. Using retractors with the limb placed at maximal flexion, the implantation site was ","[611.0, 1093.0, 1104.0, 1278.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
6,11,text,4.4.2. Applications of Goat OCD Models for Testing of Osteochondral Repair Materials. Goat has been successfully used as a model for OCD to evaluate new implants. Zhang et al. [76] fabricated BMSC-int,"[611.0, 1309.0, 1105.0, 1499.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
6,12,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1162.0, 31.0, 1182.0, 1576.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
7,0,header,Biochemistry Research International,"[98.0, 86.0, 400.0, 110.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
7,1,number,7,"[1086.0, 86.0, 1102.0, 107.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
7,2,figure_title,TABLE 6: Examples of studies using sheep osteochondral defect models.,"[330.0, 142.0, 867.0, 166.0]",table_caption,0.9,"[""table prefix matched: TABLE 6: Examples of studies using sheep osteochondral defec""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
7,3,table,<table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Schlichting et al. [70]</td><td>2 and 3 y,"[99.0, 170.0, 1099.0, 413.0]",media_asset,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
7,4,figure_title,TABLE 7: Examples of studies using goat osteochondral defect models.,"[336.0, 452.0, 863.0, 476.0]",table_caption,0.9,"[""table prefix matched: TABLE 7: Examples of studies using goat osteochondral defect""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
7,5,table,<table><tr><td>Authors</td><td>Age/ weight</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Zhang et al. [76]</td><td>12 mont,"[97.0, 482.0, 1100.0, 743.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
7,6,text,found that PRP would further enhance the regenerative capacity of DBM. Kon et al. [78] created critical-sized defects of 6 mm diameter and 10 mm depth in the medial femoral condyle of the knee joint. ,"[95.0, 782.0, 588.0, 1130.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,7,text,"4.5. Horse. As horses are robust and long-lived animals, they are suitable models for assessing the repair of superficial cartilage and subchondral bone in chronic injuries in weight-bearing condition","[95.0, 1174.0, 588.0, 1499.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
7,8,text,,"[611.0, 781.0, 1104.0, 1015.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
7,9,text,4.5.1. Experimental Protocol of Animal Surgeries. Horse was positioned in dorsal recumbence. General anesthesia was maintained and a 5 cm incision made between the middle and medial patellar ligaments,"[611.0, 1047.0, 1104.0, 1278.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
7,10,text,4.5.2. Applications of Horse OCD Models for Testing of Osteochondral Repair Materials. Bolanos et al. [84] used a horse model to investigate the effect of decellularized cartilage-derived matrix (CDM),"[611.0, 1310.0, 1104.0, 1499.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,heading_numbered,True,True
7,11,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1162.0, 31.0, 1181.0, 1577.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
8,0,number,8,"[99.0, 87.0, 115.0, 106.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
8,1,header,Biochemistry Research International,"[801.0, 86.0, 1102.0, 109.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
8,2,figure_title,TABLE 8: Examples of studies using horse osteochondral defect models.,"[331.0, 142.0, 867.0, 165.0]",table_caption,0.9,"[""table prefix matched: TABLE 8: Examples of studies using horse osteochondral defec""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
8,3,table,<table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Seo et al. [83]</td><td>3.6 $ \pm $ 2.3 ,"[98.0, 171.0, 1099.0, 394.0]",media_asset,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
8,4,figure_title,TABLE 9: Examples of studies using monkey cartilage or osteochondral defect models.,"[277.0, 438.0, 920.0, 462.0]",table_caption,0.9,"[""table prefix matched: TABLE 9: Examples of studies using monkey cartilage or osteo""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
8,5,table,<table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Treatment</td></tr><tr><td>Buckwalter et al. [90]</td><td>—</td><td>3.2 mm,"[98.0, 468.0, 1101.0, 649.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
8,6,text,and platelet-rich plasma (PRP) for repairing of OCD in horses. The results showed that the GT/MSCs/BMP-2/PRP implantation promoted osteochondral regeneration in the equine model. McCarrel et al. [85] ,"[95.0, 684.0, 588.0, 963.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,7,paragraph_title,5. Nonhuman Primate Model,"[97.0, 993.0, 406.0, 1018.0]",section_heading,0.85,"[""paragraph_title label with numbering: 5. Nonhuman Primate Model""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
8,8,text,"Most animal models differ in biomechanical functions and/or physiological responses from human, limiting the ability to extrapolate data to clinical practice. The nonhuman primate (NHP) models overcom","[96.0, 1035.0, 588.0, 1497.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,9,text,,"[609.0, 685.0, 1104.0, 1054.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
8,10,paragraph_title,6. Selecting an Appropriate Animal Model Based on Multiple Factors,"[612.0, 1083.0, 1052.0, 1136.0]",section_heading,0.85,"[""paragraph_title label with numbering: 6. Selecting an Appropriate Animal Model Based on Multiple F""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
8,11,text,"The selection of animal models is critical to promote translational research to the clinical application of biomaterials. Generally, small animal models including rats and rabbits are beneficial for e","[609.0, 1151.0, 1105.0, 1500.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,12,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1162.0, 31.0, 1181.0, 1576.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
9,0,header,Biochemistry Research International,"[99.0, 86.0, 398.0, 109.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
9,1,number,9,"[1087.0, 88.0, 1101.0, 105.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
9,2,text,"should be considered for selecting the appropriate animal models to achieve specific study objectives, such as the size and location of the defect, age, study duration, and surgical considerations. Be","[97.0, 143.0, 586.0, 283.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,3,paragraph_title,7. Conclusion,"[98.0, 304.0, 244.0, 328.0]",section_heading,0.85,"[""paragraph_title label with numbering: 7. Conclusion""]",section_heading,0.85,body_zone,heading_like,heading_numbered,True,True
9,4,text,"In this review, we summarize the benefits and limitations of each species for reproducing specific defects, analyze and compare the similarities between animal models and human clinical situations, an","[96.0, 345.0, 586.0, 531.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,5,paragraph_title,Conflicts of Interest,"[98.0, 552.0, 312.0, 576.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Conflicts of Interest""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
9,6,text,The authors declare that they have no conflicts of interest.,"[97.0, 593.0, 583.0, 617.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,7,paragraph_title,Acknowledgments,"[98.0, 639.0, 292.0, 664.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgments""]",sub_subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
9,8,text,"This work was supported by the National Natural Science Foundation of China (81773964), Sino-Swiss collaborative project from Ministry of Science and Technology (2015DFG32200), the Swiss National Scie","[96.0, 681.0, 587.0, 887.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,9,paragraph_title,References,"[99.0, 909.0, 216.0, 934.0]",reference_heading,0.9,"[""references heading: References""]",reference_heading,0.9,reference_zone,heading_like,short_fragment,True,True
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9,35,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1164.0, 34.0, 1181.0, 1570.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
10,0,number,10,"[100.0, 87.0, 124.0, 107.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
10,1,header,Biochemistry Research International,"[802.0, 87.0, 1102.0, 109.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
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12,0,number,12,"[100.0, 87.0, 124.0, 107.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
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12,2,reference_content,"with mesenchymal stem cells, bone morphogenetic protein-2, and platelet rich plasma on equine osteochondral defects,"" Research in Veterinary Science, vol. 101, pp. 140–143, 2015.","[135.0, 145.0, 584.0, 206.0]",reference_item,0.85,"[""reference content label: with mesenchymal stem cells, bone morphogenetic protein-2, a""]",reference_item,0.85,reference_zone,unknown_like,none,True,True
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12,4,reference_content,"[85] T. M. McCarrel, S. L. Pownder, S. Gilbert et al., “Two-year evaluation of osteochondral repair with a novel biphasic graft saturated in bone marrow in an equine model,” Cartilage, vol. 8, no. 4, ","[102.0, 312.0, 585.0, 394.0]",reference_item,0.85,"[""reference content label: [85] T. M. McCarrel, S. L. Pownder, S. Gilbert et al., \u201cTwo-""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,5,reference_content,"[86] U. Maninchedda, O. M. Lepage, M. Gangl et al., “Development of an equine groove model to induce metacarpophalangeal osteoarthritis: a pilot study on 6 horses,” PLoS One, vol. 10, no. 2, Article I","[101.0, 396.0, 585.0, 478.0]",reference_item,0.85,"[""reference content label: [86] U. Maninchedda, O. M. Lepage, M. Gangl et al., \u201cDevelop""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,6,reference_content,"[87] I. Messaoudi and D. K. Ingram, “Overview of aging research using nonhuman primate models,” Age, vol. 34, no. 5, pp. 1047–1049, 2012.","[102.0, 480.0, 584.0, 540.0]",reference_item,0.85,"[""reference content label: [87] I. Messaoudi and D. K. Ingram, \u201cOverview of aging resea""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,7,reference_content,"[88] R. M. Anderson and R. J. Colman, “Prospects and perspectives in primate aging research,” Antioxidants & Redox Signaling, vol. 14, no. 2, pp. 203–205, 2011.","[102.0, 543.0, 585.0, 603.0]",reference_item,0.85,"[""reference content label: [88] R. M. Anderson and R. J. Colman, \u201cProspects and perspec""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,8,reference_content,"[89] S. Kagimoto, T. Takebe, S. Kobayashi et al., “Auto-transplantation of monkey ear perichondrium-derived progenitor cells for cartilage reconstruction,” Cell Transplantation, vol. 25, no. 5, pp. 95","[102.0, 605.0, 585.0, 687.0]",reference_item,0.85,"[""reference content label: [89] S. Kagimoto, T. Takebe, S. Kobayashi et al., \u201cAuto-tran""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,9,reference_content,"[90] J. A. Buckwalter, J. A. Martin, M. Olmstead, K. A. Athanasiou, M. P. Rosenwasser, and V. C. Mow, “Osteochondral repair of primate knee femoral and patellar articular surfaces: implications for pr","[102.0, 690.0, 586.0, 791.0]",reference_item,0.85,"[""reference content label: [90] J. A. Buckwalter, J. A. Martin, M. Olmstead, K. A. Atha""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,10,reference_content,"[91] A. Ma, L. Jiang, L. Song et al., “Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates,” International Immunopharma","[102.0, 793.0, 585.0, 876.0]",reference_item,0.85,"[""reference content label: [91] A. Ma, L. Jiang, L. Song et al., \u201cReconstruction of car""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,11,reference_content,"[92] L. Jiang, A. L. Ma, L. J. Song et al., “Cartilage regeneration by selected chondrogenic clonal mesenchymal stem cells in the collagenase-induced monkey osteoarthritis model,” Journal of Tissue En","[102.0, 878.0, 586.0, 981.0]",reference_item,0.85,"[""reference content label: [92] L. Jiang, A. L. Ma, L. J. Song et al., \u201cCartilage regen""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,12,reference_content,"[93] L. Cong, F. A. Ran, D. Cox et al., “Multiplex genome engineering using CRISPR/Cas systems,” Science, vol. 339, no. 6121, pp. 819–823, 2013.","[101.0, 982.0, 584.0, 1043.0]",reference_item,0.85,"[""reference content label: [93] L. Cong, F. A. Ran, D. Cox et al., \u201cMultiplex genome en""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,13,reference_content,"[94] I. Tessaro, V. T. Nguyen, A. Di Giancamillo et al., “Animal models for cartilage repair,” Journal of Biological Regulators and Homeostatic Agents, vol. 32, no. 6 Suppl. 1, pp. 105–116, 2018.","[101.0, 1045.0, 586.0, 1125.0]",reference_item,0.85,"[""reference content label: [94] I. Tessaro, V. T. Nguyen, A. Di Giancamillo et al., \u201cAn""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
12,14,aside_text,"9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile","[1164.0, 34.0, 1181.0, 1571.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
1 page block_id raw_label content_preview bbox role role_confidence evidence seed_role seed_confidence zone style_family marker_type render_default index_default
2 1 0 header Hindawi Biochemistry Research International Volume 2020, Article ID 9659412, 12 pages https://doi.org/10.1155/2020/9659412 [97.0, 96.0, 376.0, 174.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
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4 1 2 header_image [996.0, 97.0, 1105.0, 205.0] unknown_structural 0.2 ["unrecognized label 'header_image'"] unknown_structural 0.2 frontmatter_main_zone support_like empty False True
5 1 3 text Review Article [98.0, 270.0, 308.0, 305.0] unknown_structural 0.3 ["short text, uncertain role"] unknown_structural 0.3 frontmatter_main_zone support_like short_fragment False True
6 1 4 doc_title Animal Models of Osteochondral Defect for Testing Biomaterials [97.0, 316.0, 1103.0, 354.0] paper_title 0.8 ["page-1 zone title_zone: Animal Models of Osteochondral Defect for Testing Biomateria"] paper_title 0.8 frontmatter_main_zone support_like none True True
7 1 5 text Xiangbo Meng $ ^{ID} $ $ ^{1,2} $ Reihane Ziadlou, $ ^{3} $ Sibylle Grad, $ ^{3} $ Mauro Alini, $ ^{3} $ Chunyi Wen $ ^{ID} $ $ ^{4} $ Yuxiao Lai, $ ^{2} $ Ling Qin, $ ^{2,5} $ Yanyan Zhao $ ^{ID} $ $ [166.0, 417.0, 1032.0, 477.0] authors 0.8 ["page-1 zone author_zone: Xiangbo Meng $ ^{ID} $ $ ^{1,2} $ Reihane Ziadlou, $ ^{3} $ "] authors 0.8 frontmatter_main_zone support_like none True True
8 1 6 text $ ^{1} $College of Pharmaceutical Sciences, Hebei University, Baoding, China [168.0, 493.0, 689.0, 515.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{1} $College of Pharmaceutical Sciences, Hebei University"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
9 1 7 text Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China [169.0, 530.0, 852.0, 554.0] affiliation 0.8 ["page-1 zone affiliation_zone: Shenzhen Institutes of Advanced Technology, Chinese Academy "] affiliation 0.8 frontmatter_main_zone support_like none True True
10 1 8 text $ ^{3} $AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland [170.0, 558.0, 775.0, 579.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{3} $AO Research Institute Davos, Clavadelerstrasse 8, 72"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
11 1 9 text $ ^{4} $Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China [170.0, 580.0, 1076.0, 622.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{4} $Department of Biomedical Engineering, Faculty of Eng"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
12 1 10 text $ ^{5} $Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China [169.0, 624.0, 1075.0, 667.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{5} $Musculoskeletal Research Laboratory, Department of O"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
13 1 11 text Correspondence should be addressed to Yanyan Zhao; zhaoyany606@163.com and Xinluan Wang; xl.wang@siat.ac.cn [168.0, 681.0, 1039.0, 705.0] frontmatter_support 0.78 ["first-surviving-page support text: Correspondence should be addressed to Yanyan Zhao; zhaoyany6"] frontmatter_support 0.78 frontmatter_main_zone support_like none True True
14 1 12 text Received 21 October 2019; Accepted 7 January 2020; Published 28 January 2020 [169.0, 721.0, 757.0, 744.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Received 21 October 2019; Accepted 7 January 2020; Published"] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
15 1 13 text Academic Editor: Paul W. Doetsch [168.0, 759.0, 433.0, 781.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Academic Editor: Paul W. Doetsch"] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
16 1 14 text Copyright © 2020 Xiangbo Meng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any me [167.0, 798.0, 1102.0, 842.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Copyright \u00a9 2020 Xiangbo Meng et al. This is an open access "] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
17 1 15 abstract The treatment of osteochondral defects (OCD) remains a great challenge in orthopaedics. Tissue engineering holds a good promise for regeneration of OCD. In the light of tissue engineering, it is criti [168.0, 854.0, 1103.0, 1129.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 frontmatter_main_zone support_like none True True
18 1 16 paragraph_title 1. Introduction [99.0, 1208.0, 261.0, 1233.0] section_heading 0.85 ["paragraph_title label with numbering: 1. Introduction"] section_heading 0.85 body_zone heading_like heading_numbered True True
19 1 17 text Osteochondral defects (OCD) are a common condition caused by severe trauma, sports injuries, or physical diseases, leading to joint pain, deformity, and dysfunction [1]. Joint injuries caused by traum [95.0, 1253.0, 586.0, 1484.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
20 1 18 text [611.0, 1206.0, 1104.0, 1435.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 frontmatter_main_zone support_like empty True True
21 1 19 text The current clinical treatments for repair of OCD are only palliative rather than curative [7]. The common goal of [611.0, 1436.0, 1106.0, 1484.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
22 2 0 number 2 [98.0, 86.0, 114.0, 105.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
23 2 1 header Biochemistry Research International [801.0, 85.0, 1102.0, 108.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
24 2 2 text successful treatments is to relieve pain, repair damaged tissue, and improve joint function [8]. Current methods for treatment of cartilage lesions mainly include medical treatments (nonsteroid anti-i [96.0, 142.0, 586.0, 603.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
25 2 3 text In this review, we summarize the benefits and limitations of each species for reproducing specific defects, analyze and compare the similarities between animal models and human clinical conditions, an [95.0, 603.0, 587.0, 719.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
26 2 4 paragraph_title 2. Selection Criteria and Critical Size [96.0, 746.0, 484.0, 772.0] section_heading 0.85 ["paragraph_title label with numbering: 2. Selection Criteria and Critical Size"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
27 2 5 text 2.1. General Selection Criteria. The ideal animal model should be as close to the clinical setting as possible, have biological similarity, and be a suitable model for cartilage physiology [11, 12]. A [96.0, 788.0, 587.0, 1228.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
28 2 6 text 2.2. Critical Size of OCD. The critical size defect is defined as the smallest defect size (in diameter) the animal cannot self-repair without intervention [19]. In animal experiments, the understandi [95.0, 1265.0, 587.0, 1499.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
29 2 7 text [611.0, 141.0, 1104.0, 673.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
30 2 8 paragraph_title 3. Small Animal Models [613.0, 694.0, 866.0, 720.0] section_heading 0.85 ["paragraph_title label with numbering: 3. Small Animal Models"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
31 2 9 text Small animal models are crucial in “proof-of-concept” studies, especially for testing biosafety. In these studies, concepts are validated and in vitro results are first translated in vivo. Small anima [611.0, 735.0, 1103.0, 990.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
32 2 10 text 3.1. Rats. The rat models used for OCD regeneration have several advantages, as rats are inexpensive, easy to handle and house, and clinically more relevant than mice. The skeletal maturity of rats is [611.0, 1024.0, 1104.0, 1417.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
33 2 11 text 3.1.1. Experimental Protocol of Animal Surgeries. In typical procedures, animals were anaesthetized and shaved and the [611.0, 1449.0, 1104.0, 1498.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
34 2 12 aside_text 9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile [1162.0, 31.0, 1181.0, 1576.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
35 3 0 header Biochemistry Research International [98.0, 86.0, 399.0, 109.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
36 3 1 number 3 [1087.0, 87.0, 1101.0, 106.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
37 3 2 figure_title TABLE 1: Comparison of age, cartilage, and defect size in different species. [319.0, 142.0, 878.0, 165.0] table_caption 0.9 ["table prefix matched: TABLE 1: Comparison of age, cartilage, and defect size in di"] table_caption 0.9 display_zone table_caption_like table_number True True
38 3 3 table <table><tr><td>Species</td><td>Age of skeletal maturity</td><td>Cartilage thickness</td><td>Cartilage volume</td><td>Critical-sized defect</td><td>Common defect depth</td></tr><tr><td>Rat</td><td>7 mo [98.0, 171.0, 1103.0, 393.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
39 3 4 figure_title TABLE 2: Examples of studies using rat osteochondral defect models. [341.0, 432.0, 857.0, 454.0] table_caption 0.9 ["table prefix matched: TABLE 2: Examples of studies using rat osteochondral defect "] table_caption 0.9 display_zone table_caption_like table_number True True
40 3 5 table <table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Lee and Im [35]</td><td>12 weeks</td><td> [99.0, 461.0, 1101.0, 704.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
41 3 6 text knee was disinfected. A medial temporal medial longitudinal incision was made to expose the synovium of the knee joint, and then the trochlear groove was further exposed after the lateral patellar lux [96.0, 740.0, 588.0, 927.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
42 3 7 text 3.1.2. Applications of Rat OCD Model for Testing of Osteochondral Repair Materials. Using a 12-week-old rat model, Lee and Im [35] found that SOX trio-co-transduced adipose tissue derived stem cells ( [95.0, 968.0, 588.0, 1499.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
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44 3 9 text 3.2. Rabbit. The rabbit model provides a suitable small animal model for assessing the repair of OCD, as rabbits have larger joints for surgical procedures [41]. The age of skeletal maturity in rabbit [611.0, 946.0, 1105.0, 1497.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
45 3 10 aside_text 9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile [1163.0, 32.0, 1181.0, 1577.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
46 4 0 number 4 [99.0, 88.0, 115.0, 107.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
47 4 1 header Biochemistry Research International [801.0, 86.0, 1102.0, 110.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
48 4 2 figure_title TABLE 3: Examples of studies using rabbit osteochondral defect models. [330.0, 142.0, 868.0, 166.0] table_caption 0.9 ["table prefix matched: TABLE 3: Examples of studies using rabbit osteochondral defe"] table_caption 0.9 display_zone table_caption_like table_number True True
49 4 3 table <table><tr><td>Authors</td><td>Age/ weight</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Liao et al. [42]</td><td>2-2.5 kg [98.0, 171.0, 1101.0, 435.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
50 4 4 text 3.2.1. Experimental Protocol of Animal Surgeries. In most studies, the creation of an OCD was based on the following protocol. The rabbits were anaesthetized; then, a medial peripatellar incision was [95.0, 473.0, 587.0, 705.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
51 4 5 text 3.2.2. Applications of Rabbit OCD Models for Testing of Osteochondral Repair Materials. Liao et al. [42] prepared a novel hybrid scaffold composed of methacrylated chondroitin sulfate (CSMA), poly(eth [95.0, 738.0, 588.0, 1498.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
52 4 6 paragraph_title 4. Large Animal Models [612.0, 474.0, 866.0, 501.0] section_heading 0.85 ["paragraph_title label with numbering: 4. Large Animal Models"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
53 4 7 text The large animals, such as goats, sheep, pigs, dogs, and horses, have the advantages of joint size and cartilage thickness and also have the most similar clinical lesions to humans [55]. Although larg [610.0, 516.0, 1104.0, 863.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
54 4 8 text 4.1. Dog. The dog is considered to be a very friendly and loving partner over the world. The social and ethical issues associated with the use of dogs as preclinical and translational animal models ar [611.0, 902.0, 1104.0, 1295.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
55 4 9 text 4.1.1. Experimental Protocol of Animal Surgeries. Dogs were anaesthetized intravenously. The dog was fixed on the operating table in a supine position and the hair was shaved over the knee joint. The [610.0, 1335.0, 1104.0, 1498.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
56 4 10 aside_text 9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile [1162.0, 30.0, 1181.0, 1576.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
57 5 0 header Biochemistry Research International [98.0, 86.0, 399.0, 109.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
58 5 1 number 5 [1087.0, 87.0, 1102.0, 107.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
59 5 2 image [256.0, 144.0, 942.0, 356.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
60 5 3 figure_title FIGURE 1: The process of the OCD regeneration in rabbits. A: the OCD were generated by electric drill in the femoral patellar groove; B: a 3.2 mm in diameter and 3.0 mm deep OCD was obtained; C: the b [97.0, 366.0, 1103.0, 411.0] figure_caption 0.92 ["figure_title label: FIGURE 1: The process of the OCD regeneration in rabbits. A:"] figure_caption 0.92 display_zone legend_like figure_number True True
61 5 4 figure_title TABLE 4: Examples of studies using dog osteochondral defect models. [337.0, 443.0, 860.0, 465.0] table_caption 0.9 ["table prefix matched: TABLE 4: Examples of studies using dog osteochondral defect "] table_caption 0.9 display_zone table_caption_like table_number True True
62 5 5 table <table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Lv and Yu [59]</td><td>12 months</td><td> [98.0, 469.0, 1100.0, 694.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
63 5 6 text concurrently and medial tibial plateau. Scaffolds were implanted, and the wound layer was sutured [59]. [96.0, 731.0, 587.0, 780.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
64 5 7 text 4.1.2. Applications of Dog OCD Models for Testing of Osteochondral Repair Materials. Lv and Yu [59] investigated the articular OCD (6 mm diameter and 12 mm depth) repair using a composite lamellar sca [96.0, 813.0, 588.0, 1254.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
65 5 8 text 4.2. Pig. Pigs are considered to be a suitable animal model for mimicking human diseases and have widely been used in biomedical research [63, 64]. The pig joint size, weight requirements, and cartila [95.0, 1289.0, 587.0, 1499.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
66 5 9 text [610.0, 731.0, 1103.0, 986.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
67 5 10 text 4.2.1. Experimental Protocol of Animal Surgeries. After animals were anaesthetized, a 5 cm incision was created in the skin to expose the medial condyle. A cylindrical OCD was created in the knee join [611.0, 1021.0, 1103.0, 1186.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
68 5 11 text 4.2.2. Applications of Pig OCD Models for Testing of Osteochondral Repair Materials. Several studies on cartilage and cartilage defects have been reported using min-pig. Christensen and coauthors [68] [610.0, 1219.0, 1105.0, 1498.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
69 5 12 aside_text 9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile [1163.0, 31.0, 1181.0, 1576.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
70 6 0 number 6 [99.0, 88.0, 115.0, 107.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
71 6 1 header Biochemistry Research International [801.0, 86.0, 1102.0, 110.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
72 6 2 figure_title TABLE 5: Examples of studies using pig osteochondral defect models. [340.0, 142.0, 857.0, 166.0] table_caption 0.9 ["table prefix matched: TABLE 5: Examples of studies using pig osteochondral defect "] table_caption 0.9 display_zone table_caption_like table_number True True
73 6 3 table <table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Christensen et al. [68]</td><td>19.8 mont [98.0, 172.0, 1101.0, 371.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
74 6 4 text enhance the mechanical properties and histological appearance of cartilage regenerates in mini-pig OCD models. [95.0, 404.0, 586.0, 453.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
75 6 5 text 4.3. Sheep. Sheep is one of the commonly used animal models in orthopaedic research. The anatomy of the knee is similar to humans. However, due to the thinness of the cartilage, most of the defects ar [96.0, 485.0, 587.0, 877.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
76 6 6 text 4.3.1. Experimental Protocol of Animal Surgeries. The sheep were anaesthetized; then, sheep were placed in dorsal recumbency. The skin on the right knee was sterilized and was ready for sterile surger [95.0, 909.0, 587.0, 1120.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
77 6 7 text 4.3.2. Applications of Sheep OCD Models for Testing of Osteochondral Repair Materials. Schlichting et al. [70] created an 8 mm in diameter and 15 mm deep OCD in the femoral condyles of 24 sheep to pro [95.0, 1150.0, 588.0, 1499.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
78 6 8 text [611.0, 402.0, 1104.0, 569.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
79 6 9 text 4.4. Goat. Goats are similar to sheep and are easy to raise and manage. The skeletal maturity of goats is similar to that of sheep, namely, about 2 to 3 years [11]. Goats aged between 2 and 4 years ha [611.0, 600.0, 1104.0, 1061.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
80 6 10 text 4.4.1. Experimental Protocol of Animal Surgeries. Surgery was performed under general anesthesia via joint surgery. Using retractors with the limb placed at maximal flexion, the implantation site was [611.0, 1093.0, 1104.0, 1278.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
81 6 11 text 4.4.2. Applications of Goat OCD Models for Testing of Osteochondral Repair Materials. Goat has been successfully used as a model for OCD to evaluate new implants. Zhang et al. [76] fabricated BMSC-int [611.0, 1309.0, 1105.0, 1499.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
82 6 12 aside_text 9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile [1162.0, 31.0, 1182.0, 1576.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
83 7 0 header Biochemistry Research International [98.0, 86.0, 400.0, 110.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
84 7 1 number 7 [1086.0, 86.0, 1102.0, 107.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
85 7 2 figure_title TABLE 6: Examples of studies using sheep osteochondral defect models. [330.0, 142.0, 867.0, 166.0] table_caption 0.9 ["table prefix matched: TABLE 6: Examples of studies using sheep osteochondral defec"] table_caption 0.9 display_zone table_caption_like table_number True True
86 7 3 table <table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Schlichting et al. [70]</td><td>2 and 3 y [99.0, 170.0, 1099.0, 413.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
87 7 4 figure_title TABLE 7: Examples of studies using goat osteochondral defect models. [336.0, 452.0, 863.0, 476.0] table_caption 0.9 ["table prefix matched: TABLE 7: Examples of studies using goat osteochondral defect"] table_caption 0.9 display_zone table_caption_like table_number True True
88 7 5 table <table><tr><td>Authors</td><td>Age/ weight</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Zhang et al. [76]</td><td>12 mont [97.0, 482.0, 1100.0, 743.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
89 7 6 text found that PRP would further enhance the regenerative capacity of DBM. Kon et al. [78] created critical-sized defects of 6 mm diameter and 10 mm depth in the medial femoral condyle of the knee joint. [95.0, 782.0, 588.0, 1130.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
90 7 7 text 4.5. Horse. As horses are robust and long-lived animals, they are suitable models for assessing the repair of superficial cartilage and subchondral bone in chronic injuries in weight-bearing condition [95.0, 1174.0, 588.0, 1499.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
91 7 8 text [611.0, 781.0, 1104.0, 1015.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
92 7 9 text 4.5.1. Experimental Protocol of Animal Surgeries. Horse was positioned in dorsal recumbence. General anesthesia was maintained and a 5 cm incision made between the middle and medial patellar ligaments [611.0, 1047.0, 1104.0, 1278.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
93 7 10 text 4.5.2. Applications of Horse OCD Models for Testing of Osteochondral Repair Materials. Bolanos et al. [84] used a horse model to investigate the effect of decellularized cartilage-derived matrix (CDM) [611.0, 1310.0, 1104.0, 1499.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like heading_numbered True True
94 7 11 aside_text 9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile [1162.0, 31.0, 1181.0, 1577.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
95 8 0 number 8 [99.0, 87.0, 115.0, 106.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
96 8 1 header Biochemistry Research International [801.0, 86.0, 1102.0, 109.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
97 8 2 figure_title TABLE 8: Examples of studies using horse osteochondral defect models. [331.0, 142.0, 867.0, 165.0] table_caption 0.9 ["table prefix matched: TABLE 8: Examples of studies using horse osteochondral defec"] table_caption 0.9 display_zone table_caption_like table_number True True
98 8 3 table <table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Material tested</td></tr><tr><td>Seo et al. [83]</td><td>3.6 $ \pm $ 2.3 [98.0, 171.0, 1099.0, 394.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
99 8 4 figure_title TABLE 9: Examples of studies using monkey cartilage or osteochondral defect models. [277.0, 438.0, 920.0, 462.0] table_caption 0.9 ["table prefix matched: TABLE 9: Examples of studies using monkey cartilage or osteo"] table_caption 0.9 display_zone table_caption_like table_number True True
100 8 5 table <table><tr><td>Authors</td><td>Age</td><td>Defect size (diameter $ \times $ depth)</td><td>Location</td><td>Endpoint</td><td>Treatment</td></tr><tr><td>Buckwalter et al. [90]</td><td>—</td><td>3.2 mm [98.0, 468.0, 1101.0, 649.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
101 8 6 text and platelet-rich plasma (PRP) for repairing of OCD in horses. The results showed that the GT/MSCs/BMP-2/PRP implantation promoted osteochondral regeneration in the equine model. McCarrel et al. [85] [95.0, 684.0, 588.0, 963.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
102 8 7 paragraph_title 5. Nonhuman Primate Model [97.0, 993.0, 406.0, 1018.0] section_heading 0.85 ["paragraph_title label with numbering: 5. Nonhuman Primate Model"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
103 8 8 text Most animal models differ in biomechanical functions and/or physiological responses from human, limiting the ability to extrapolate data to clinical practice. The nonhuman primate (NHP) models overcom [96.0, 1035.0, 588.0, 1497.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
104 8 9 text [609.0, 685.0, 1104.0, 1054.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
105 8 10 paragraph_title 6. Selecting an Appropriate Animal Model Based on Multiple Factors [612.0, 1083.0, 1052.0, 1136.0] section_heading 0.85 ["paragraph_title label with numbering: 6. Selecting an Appropriate Animal Model Based on Multiple F"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
106 8 11 text The selection of animal models is critical to promote translational research to the clinical application of biomaterials. Generally, small animal models including rats and rabbits are beneficial for e [609.0, 1151.0, 1105.0, 1500.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
107 8 12 aside_text 9353, 2020, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1155/2020/9659412 by CochraneChina, Wiley Online Library on [25/02/2026]. See the Terms and Conditions (https://onlinelibrary.wile [1162.0, 31.0, 1181.0, 1576.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
108 9 0 header Biochemistry Research International [99.0, 86.0, 398.0, 109.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
109 9 1 number 9 [1087.0, 88.0, 1101.0, 105.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
110 9 2 text should be considered for selecting the appropriate animal models to achieve specific study objectives, such as the size and location of the defect, age, study duration, and surgical considerations. Be [97.0, 143.0, 586.0, 283.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
111 9 3 paragraph_title 7. Conclusion [98.0, 304.0, 244.0, 328.0] section_heading 0.85 ["paragraph_title label with numbering: 7. Conclusion"] section_heading 0.85 body_zone heading_like heading_numbered True True
112 9 4 text In this review, we summarize the benefits and limitations of each species for reproducing specific defects, analyze and compare the similarities between animal models and human clinical situations, an [96.0, 345.0, 586.0, 531.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
113 9 5 paragraph_title Conflicts of Interest [98.0, 552.0, 312.0, 576.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Conflicts of Interest"] subsection_heading 0.6 body_zone heading_like none True True
114 9 6 text The authors declare that they have no conflicts of interest. [97.0, 593.0, 583.0, 617.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
115 9 7 paragraph_title Acknowledgments [98.0, 639.0, 292.0, 664.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgments"] sub_subsection_heading 0.6 body_zone heading_like short_fragment True True
116 9 8 text This work was supported by the National Natural Science Foundation of China (81773964), Sino-Swiss collaborative project from Ministry of Science and Technology (2015DFG32200), the Swiss National Scie [96.0, 681.0, 587.0, 887.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
117 9 9 paragraph_title References [99.0, 909.0, 216.0, 934.0] reference_heading 0.9 ["references heading: References"] reference_heading 0.9 reference_zone heading_like short_fragment True True
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@ -0,0 +1,951 @@
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536
audit/37LK5T97/audit_report.json Normal file
View file

@ -0,0 +1,536 @@
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"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:5"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:6"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:7"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:8"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:9"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
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"block_ids": [
"p17:10"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
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"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
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},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:12"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:13"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:14"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:15"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:16"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:17"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_016.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_020.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
"p1:0",
"p1:1",
"p1:2",
"p1:8",
"p1:9",
"p1:10",
"p1:11",
"p2:0",
"p2:1",
"p2:3",
"p2:4",
"p2:7",
"p2:8",
"p2:10",
"p3:0",
"p3:1",
"p4:1",
"p4:2",
"p5:1",
"p5:3"
],
"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
"annotated_page": null,
"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

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# OCR Truth Audit Report - 37LK5T97
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 2, 3, 5, 6, 7, 8, 9, 12, 16, 20]
- Reviewed blocks: 109
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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{
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1,0,header,"TISSUE ENGINEERING: Part B
Volume 21, Number 3, 2015
© Mary Ann Liebert, Inc.
DOI: 10.1089/ten.teb.2014.0419","[114.0, 66.0, 352.0, 142.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,1,doc_title,Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo,"[116.0, 208.0, 1101.0, 331.0]",paper_title,0.8,"[""page-1 zone title_zone: Endochondral Ossification for Enhancing Bone Regeneration: C""]",paper_title,0.8,frontmatter_main_zone,support_like,none,True,True
1,2,text,"S. Connor Dennis, BS, $ ^{1,2} $ Cory J. Berkland, PhD, $ ^{1-3} $ Lynda F. Bonewald, PhD, $ ^{4} $ and Michael S. Detamore, PhD $ ^{1,2} $","[334.0, 382.0, 883.0, 436.0]",authors,0.8,"[""page-1 zone author_zone: S. Connor Dennis, BS, $ ^{1,2} $ Cory J. Berkland, PhD, $ ^{""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
1,3,abstract,"Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focus","[112.0, 515.0, 1106.0, 1072.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,frontmatter_main_zone,support_like,none,True,True
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1,5,text,THE HUMAN BODY HAS AN EXTENSIVE capacity to regenerate bone tissue after trauma. Disruption of the surrounding vasculature and bone marrow resulting from a bone fracture initially facilitates a cascad,"[111.0, 1166.0, 601.0, 1367.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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1,7,text,"Clinically, however, ABG remains the gold standard of treatment due to its inherent osteoconductivity, osteoinductivity,","[615.0, 1320.0, 1106.0, 1366.0]",frontmatter_noise,0.7,"[""keyword-like block: Clinically, however, ABG remains the gold standard of treatm""]",frontmatter_noise,0.7,body_zone,body_like,none,False,False
1,8,footnote," $ ^{1} $Bioengineering Program, University of Kansas, Lawrence, Kansas.","[131.0, 1400.0, 629.0, 1423.0]",footnote,0.7,"[""footnote label: $ ^{1} $Bioengineering Program, University of Kansas, Lawren""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
1,9,footnote,"²Chemical and Petroleum Engineering Department, University of Kansas, Lawrence, Kansas.","[133.0, 1420.0, 810.0, 1439.0]",footnote,0.7,"[""footnote label: \u00b2Chemical and Petroleum Engineering Department, University o""]",footnote,0.7,body_zone,body_like,none,True,True
1,10,footnote," $ ^{3} $Pharmaceutical Chemistry Department, University of Kansas, Lawrence, Kansas.","[133.0, 1439.0, 732.0, 1458.0]",footnote,0.7,"[""footnote label: $ ^{3} $Pharmaceutical Chemistry Department, University of K""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
1,11,footnote," $ ^{4} $Department of Oral Biology, University of Missouri-Kansas City, Kansas City, Missouri.","[133.0, 1456.0, 789.0, 1477.0]",footnote,0.7,"[""footnote label: $ ^{4} $Department of Oral Biology, University of Missouri-K""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
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2,1,header,DENNIS ET AL.,"[970.0, 68.0, 1105.0, 89.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,2,text,"FIG. 1. Both IM and EC ossification occurs during the bone-healing process in three overlapping regeneration phases. Critical-sized bone defects favor EC ossification over direct IM ossification, prim","[118.0, 135.0, 364.0, 640.0]",body_paragraph,0.9,"[""figure caption candidate (body narrative): FIG. 1. Both IM and EC ossification occurs during the bone-h""]",figure_caption_candidate,0.9,display_zone,legend_like,figure_number,True,True
2,3,paragraph_title,Phase I: Inflammatory 1. Hematoma Week (0-1),"[379.0, 118.0, 575.0, 179.0]",unknown_structural,0.6,"[""page-1 frontmatter title guard: Phase I: Inflammatory 1. Hematoma Week (0-1)""]",paper_title,0.6,body_zone,unknown_like,none,False,True
2,4,text,Damaged vasculature and marrow facilitate hematoma formation along with influx of inflammatory cells and BMSCs. Initial progenitor cells likely fail to survive early inflammatory phase. IM and EC ossi,"[394.0, 186.0, 553.0, 292.0]",non_body_insert,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,False,False
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2,7,text,"Phase III: Remodeling
3. Remodeled Bone
Week ( $ \geq $ 8)","[915.0, 118.0, 1106.0, 180.0]",non_body_insert,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,False,False
2,8,text,Resorption of excess callus and replacement of woven bone with stronger lamellar bone. Dictated often by external mechanical load conditions and results in restoring healthy bone architecture.,"[931.0, 185.0, 1089.0, 305.0]",non_body_insert,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,False,False
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2,10,text,"and thus osteogenic capabilities. $ ^{6,12-14} $ Despite these advantages, ABG has key clinical limitations, including donor site morbidity and pain, increased risk of infection, limited handling capa","[118.0, 706.0, 606.0, 1060.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,11,text,"To date, acellular biomaterial-based products have dominated the alternative bone implant market at the commercial level. $ ^{11,15,16} $ A major characteristic of these products is the ability to mim","[117.0, 1060.0, 606.0, 1388.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,12,text,"Addressing this avenue of research is the emerging paradigm of “developmental engineering” first introduced in 2009 in two reviews by Lenas et al., $ ^{22,23} $ which offer an innovative approach to e","[117.0, 1389.0, 608.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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2,14,text,"The incorporation of donor cells via SCBT strategies may provide advantageous osteo- and chondrogenic capabilities to acellular bone implants, which rely solely on recruited cells from the peripheral ","[619.0, 1103.0, 1109.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,0,header,ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING,"[115.0, 67.0, 922.0, 90.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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3,2,text,"in vitro cell expansion. Critical-sized bone defects often require surgical intervention within hours as opposed to weeks, because delayed bone healing leads to a higher risk of nonunion. $ ^{9} $ The","[111.0, 117.0, 602.0, 446.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,3,text,"An alternative strategy to reduce or remove the cell expansion step may reside in extending developmental engineering principles to in vivo designs (i.e., within the graft or implant), thus removing i","[111.0, 447.0, 602.0, 752.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,4,text,This review will highlight essential design criteria involved in the underexplored regenerative area of developmentally engineering bone in vivo (Fig. 2). Traditional strategies have approached tissue,"[112.0, 753.0, 602.0, 843.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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3,6,paragraph_title,Overview of the Natural Bone-Healing Process,"[616.0, 522.0, 1026.0, 544.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Overview of the Natural Bone-Healing Process""]",subsection_heading,0.6,body_zone,body_like,none,True,True
3,7,text,"As mentioned earlier, the human body has an extensive capacity to regenerate bone tissue after trauma and fracture. The cellular and molecular processes involved in developmental skeletogenesis are cl","[614.0, 555.0, 1105.0, 753.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,8,text,"In general, the fracture-healing process is most often described in three overlapping phases: Inflammatory, Reparative, and Remodeling (Fig. 1), where each phase represents a complex spatiotemporal di","[614.0, 753.0, 1105.0, 843.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,9,image,,"[183.0, 881.0, 1036.0, 1333.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
3,10,figure_title,FIG. 2. Current landscape of EC ossification strategies (blue boxes) along with underexplored design space (dashed outlines) highlighted in this review. Some combined cell and material strategies are ,"[113.0, 1354.0, 1105.0, 1478.0]",figure_caption,0.92,"[""figure_title label: FIG. 2. Current landscape of EC ossification strategies (blu""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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4,2,text,"and bioactive signals. $ ^{1-9} $ Initially, disrupted vasculature and bone marrow during the inflammatory phase facilitates a coagulation cascade along with an influx of progenitor cells, including b","[117.0, 114.0, 606.0, 621.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,3,text,"In contrast, chondrogenesis predominantly occurs in avascular environments where oxygen tension is low. $ ^{39-43} $ The main consequence of this difference is that IM and EC ossification is manifeste","[117.0, 621.0, 606.0, 950.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,4,text,"While the process mentioned earlier describes successful bone regeneration within the body, it is well understood that large defects above a “critical-size” are incapable of completely restoring nativ","[117.0, 950.0, 606.0, 1239.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,5,paragraph_title,Strategies to Enhance EC Ossification Harnessing the potential of developmental engineering,"[118.0, 1255.0, 560.0, 1313.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Strategies to Enhance EC Ossification Harnessing the potenti""]",subsection_heading,0.6,body_zone,body_like,none,True,True
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4,7,text,"Developmental engineering, a term first introduced into the tissue engineering community with two reviews in 2009 by Lenas et al., $ ^{22,23} $ involves the engineering of developmental “processes” an","[116.0, 1321.0, 606.0, 1480.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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4,9,text,(1) Path dependence: successive developmental tissue relies on previous tissue formation,"[640.0, 170.0, 1108.0, 215.0]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_parenthesis,True,True
4,10,text,(2) Robustness: tissue developmental process resistant to unintended external perturbation,"[639.0, 216.0, 1108.0, 259.0]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_parenthesis,True,True
4,11,text,(3) Semi-autonomy: partially self-governed tissue development,"[640.0, 260.0, 1106.0, 305.0]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_parenthesis,True,True
4,12,text,"EC ossification is a feasible route to utilize these guiding principles of developmental engineering, and the current review will cover advances made over the past decade in engineering EC ossificatio","[619.0, 313.0, 1108.0, 403.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,13,text,"While the Lenas reviews only covered replicating in vivo developmental processes in an in vitro environment, $ ^{22,23} $ the current review aims to expand their previous concept further to include re","[618.0, 404.0, 1110.0, 690.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,14,paragraph_title,Coupling in vivo developmental engineering with native ECM biomaterials,"[621.0, 718.0, 980.0, 765.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Coupling in vivo developmental engineering with native ECM b""]",subsection_heading,0.6,body_zone,body_like,none,True,True
4,15,text,Characterizing the influence of DBM on ossification pathway. Inspiration for in vivo developmental designs already exists in the form of native ECM biomaterials. There is significant evidence that EC ,"[618.0, 773.0, 1110.0, 1213.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,16,text,"Regardless of this, the DBM composition containing conductive and inductive biological agents likely influences developmental pathways during bone healing. $ ^{26-29} $ DBM composition, however, is no","[618.0, 1213.0, 1110.0, 1480.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,0,figure_title,TABLE 1. PRIMING IN VITRO CHONDROGENESIS WITH BONE MESENCHYMAL STEM CELLS FOR IN VIVO ENDOCHONDRAL OSSIFICATION,"[116.0, 225.0, 140.0, 1315.0]",table_caption,0.9,"[""table prefix matched: TABLE 1. PRIMING IN VITRO CHONDROGENESIS WITH BONE MESENCHYM""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
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7,3,vision_footnote,"ACs, articular chondrocytes; BMSC, bone mesenchymal stem cell; beta-TCP, beta tricalcium phosphate; EC, endochondral; GAG, glycosaminoglycan; hAC, human AC; hBMSC, human BMSC; IM, intramembranous; pBM","[975.0, 70.0, 1017.0, 1471.0]",footnote,0.7,"[""vision_footnote label: ACs, articular chondrocytes; BMSC, bone mesenchymal stem cel""]",footnote,0.7,body_zone,body_like,none,True,True
8,0,figure_title,"TABLE 2. PRIMING IN VITRO CHONDROGENESIS WITH EMBRYONIC STEM CELLS, SYNOVIUM-DERIVED STEM CELLS, ARTICULAR CHONDROCYTE AND INDICATED PITRIPOTENT STEM CELLS FOR IN VIVO ENDOCHONDRAL OSSIFICATION","[147.0, 197.0, 189.0, 1358.0]",table_caption,0.9,"[""table prefix matched: TABLE 2. PRIMING IN VITRO CHONDROGENESIS WITH EMBRYONIC STEM""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
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8,2,number,254,"[597.0, 1498.0, 632.0, 1521.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
8,3,vision_footnote,"ADSC, adipose-derived stem cell; ESC, embryonic stem cell; hADSC, human ADSC; hFB, human fibroblast; PBS, phosphate-buffered saline; PGA, polyglycolic acid; SVF, stromal vascular","[1037.0, 72.0, 1066.0, 1481.0]",footnote,0.7,"[""vision_footnote label: ADSC, adipose-derived stem cell; ESC, embryonic stem cell; h""]",footnote,0.7,body_zone,body_like,none,True,True
9,0,figure_title,TABLE 3. COMPARING IN VITRO CHONDROGENICALLY PRIMED CELL SOURCES FOR IN VIVO ENDOCHONDRAL OSSIFICATION,"[116.0, 276.0, 139.0, 1270.0]",table_caption,0.9,"[""table prefix matched: TABLE 3. COMPARING IN VITRO CHONDROGENICALLY PRIMED CELL SOU""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
9,1,table,<table><tr><td>Reference(s)</td><td>Year</td><td>Cell source</td><td>Additional materials</td><td>In vitro priming method</td><td>Animal moea</td><td>Chondrogenic priming led to similar collagen type ,"[130.0, 61.0, 1127.0, 1482.0]",media_asset,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
9,2,number,255,"[592.0, 1498.0, 627.0, 1520.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
9,3,vision_footnote,"ALP, alkaline phosphatase; BCP, biphasic calcium phosphate; FPSCs, fat-pad derived stem cells; OB, osteoblast; rOB, human OB; SDSC, synovium-derived stem cell.","[1104.0, 246.0, 1128.0, 1469.0]",footnote,0.7,"[""vision_footnote label: ALP, alkaline phosphatase; BCP, biphasic calcium phosphate; ""]",footnote,0.7,body_zone,body_like,none,True,True
10,0,number,256,"[120.0, 68.0, 157.0, 89.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
10,1,header,DENNIS ET AL.,"[968.0, 67.0, 1106.0, 89.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
10,2,text,"suggesting that only implants directed toward IM ossification will possess regenerative potential. However, evidence from Rabie et al. $ ^{28,30,31} $ showed that IM and EC ossification pathways can b","[117.0, 117.0, 606.0, 534.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,3,text,"The differences in regenerative potential and developmental pathways seen in the Rabie studies were attributed to varying inductive and conductive ECM factors within DBM. $ ^{28,30-32} $ Inductive fac","[117.0, 533.0, 606.0, 1015.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,4,text,"Collectively, there is significant evidence to suggest that EC ossification can occur within native ECM biomaterials in the form of acellular DBM implants. While there has been extensive research into","[117.0, 1014.0, 606.0, 1261.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,5,text,"Exploring EC ossification potential in ECM biomaterials. In general, native ECM refers to both soluble and insoluble biomolecules that may be utilized as cell scaffolding and bioactive signaling. In a","[117.0, 1277.0, 606.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,6,text,,"[618.0, 116.0, 1108.0, 203.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
10,7,text,"Traditional bone ECM strategies: ABG intrinsically involves the grafting of native bone ECM tissue with associated autologous cells into bone defects, and it remains the gold standard of treatment in ","[618.0, 205.0, 1110.0, 774.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,8,text,"It is important to note, however, that the functional and structural properties of ECM during the bone-healing process are spatiotemporally dynamic and do not resemble healthy native bone until well i","[619.0, 774.0, 1110.0, 972.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,9,text,"Alternative ECM biomaterial strategies for EC ossification: By instead leveraging the concepts of both developmental engineering and the spatiotemporal dynamics of ECM in bone healing, there may be po","[618.0, 972.0, 1110.0, 1258.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,10,text,"Characterization of the complex cascade of signaling events and ECM changes involved in bone healing and EC ossification has been the focus of several recent reviews, $ ^{6,9,33,34} $ and readers inte","[618.0, 1256.0, 1110.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,0,header,ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING,"[114.0, 67.0, 922.0, 90.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
11,1,number,257,"[1067.0, 69.0, 1102.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
11,2,text,ECM biomaterials that correspond to the early and intermediate stages of native bone healing.,"[112.0, 117.0, 601.0, 162.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,3,text,"Native ECM biomaterials possess both conductive and inductive potential that are difficult to match with synthetic designs (e.g., non-native polymers). $ ^{17-20} $ In addition, it is increasingly evi","[111.0, 161.0, 602.0, 511.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,4,text,"To date, a few studies have attempted to coordinate developmental bone engineering strategies with acellular native ECM biomaterials (Figs. 1 and 2). Subsequent sections will address key features of e","[112.0, 511.0, 602.0, 666.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,5,text,"Inflammatory stage ECM strategies for EC ossification: Since most tissues primarily rely on broken vasculature to supply damaged areas with inflammatory signals and cells, modulating the body's initia","[111.0, 665.0, 602.0, 1038.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,6,text,"One strategy to enhance the regenerative response in inflammatory stage ECM strategies has been to supply the fracture space with stem cells from bone marrow aspirate, as fractured bone is supplied wi","[111.0, 1038.0, 603.0, 1481.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,7,text,,"[614.0, 117.0, 1105.0, 249.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
11,8,text,Coupling the evidence of low progenitor count with poor cell survival rate observed in hypoxic bone defects suggests the importance of spatiotemporal cellular recruitment strategies for bone regenerat,"[614.0, 248.0, 1105.0, 665.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,9,text,"Collectively, the evidence surrounding the use of inflammatory stage ECM scaffolds, signals, and recruited cells indicates that current designs remain insufficient in regenerating bone in critical-siz","[614.0, 665.0, 1105.0, 863.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,10,text,"Procallus stage ECM strategies for EC ossification: An intuitive source for enhancing stimulation of EC ossification is the procallus ECM, as natural bone healing progresses to this stage early in the","[614.0, 863.0, 1105.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,0,number,258,"[120.0, 69.0, 157.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
12,1,header,DENNIS ET AL.,"[969.0, 67.0, 1106.0, 89.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
12,2,figure_title,TABLE 4. MODULATORS OF CHONDROCYTE HYPERTROPHY,"[373.0, 117.0, 852.0, 140.0]",table_caption,0.9,"[""table prefix matched: TABLE 4. MODULATORS OF CHONDROCYTE HYPERTROPHY""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
12,3,table,"<table><tr><td>Differentiation pathway</td><td>Chemical</td><td>Physical</td><td>Mechanical</td></tr><tr><td>Chondrogenesis</td><td>TGF- $ \beta $, BMPs, Dexamethasone</td><td>Low oxygen tension</td><","[117.0, 146.0, 1104.0, 337.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
12,4,vision_footnote,"BMPs, bone morphogenic proteins; MMP, matrix metalloproteinase; TGF, transforming growth factor; IL-1β, interleukin-1β.","[135.0, 348.0, 1042.0, 371.0]",footnote,0.7,"[""vision_footnote label: BMPs, bone morphogenic proteins; MMP, matrix metalloproteina""]",footnote,0.7,body_zone,body_like,none,True,True
12,5,text,"that external chemical, $ ^{9,33,38,41,73,80-85,89,90} $ physical, $ ^{39-42} $ and mechanical cues $ ^{41,45} $ stimulated BMSCs to stay locked in a stable cartilage state or progress into a hypertro","[117.0, 399.0, 606.0, 533.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,6,text,"In summary, the success of in vivo developmental engineering designs for EC ossification will likely depend on the incorporation of physiologically relevant bioactive chemical mediators along with phy","[117.0, 533.0, 607.0, 843.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,7,paragraph_title,"Isolating, identifying, and delivering native ECM for EC ossification","[118.0, 873.0, 510.0, 918.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Isolating, identifying, and delivering native ECM for EC oss""]",subsection_heading,0.6,body_zone,body_like,none,True,True
12,8,text,Utilizing step-wise ECM strategies. Strategies to design scaffolds with incorporated native ECM components can be divided into two main categories: (1) Bottom-up approach or (2) Top-down approach (i.e,"[117.0, 929.0, 606.0, 1477.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,9,text,,"[618.0, 402.0, 1110.0, 713.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
12,10,image,,"[656.0, 752.0, 1076.0, 1353.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
12,11,figure_title,"FIG. 3. Top-down approaches to mimic native ECM tissue require less processing before implantation and retain more of the ECM's physicochemical composition, structure, and function compared with botto","[619.0, 1373.0, 1108.0, 1478.0]",figure_caption,0.92,"[""figure_title label: FIG. 3. Top-down approaches to mimic native ECM tissue requi""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
13,0,header,ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING,"[115.0, 67.0, 923.0, 90.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
13,1,number,259,"[1067.0, 69.0, 1102.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
13,2,text,"“raw” biomaterial re-synthesis, however, is that designs can be modular, which means that separate elements of the design can be tested independently. As a result, each component can be characterized ","[112.0, 120.0, 602.0, 751.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,3,text,"Step-wise designs from both allogeneic and xenogeneic tissue sources have been utilized clinically for cartilage and bone tissue engineering along with dermal, vascular, nerve, and urogenital tissue. ","[112.0, 752.0, 602.0, 1041.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,4,text,"Decellularized cartilage for enhancing EC ossification. Intuitively, it follows that designs mimicking the native bone or cartilage ECM hold vast potential for eliciting ossification and chondrogenesi","[112.0, 1059.0, 602.0, 1480.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,5,text,,"[614.0, 117.0, 1105.0, 381.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
13,6,text,"DCC, from both allogeneic and xenogeneic sources, is a poorly explored native ECM biomaterial. Recently, it has emerged as a source that is rich in both chondroinductive and chondroconductive potentia","[614.0, 381.0, 1106.0, 1171.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,7,text,Delivery strategies for decellularized tissues. Crucial to the future success of these ECM materials will be the strategies used to incorporate and deliver them within engineered implants. If maximum ,"[614.0, 1191.0, 1106.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,0,number,260,"[120.0, 69.0, 157.0, 89.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
14,1,header,DENNIS ET AL.,"[968.0, 67.0, 1106.0, 89.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
14,2,text,particle size on regenerative capacity of these materials remains unclear. A recent review of DBM clinical products and procurement by Gruskin et al. $ ^{15} $ indicated that larger particles of DBM (,"[116.0, 117.0, 606.0, 358.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,3,text,"While morselization strategies most often include some form of mechanical breakdown (e.g., pulverization or cyro-grinding), solubilization uses chemical and enzymatic methods (e.g., demineralization a","[116.0, 359.0, 606.0, 622.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,4,text,"In summary, the extent of native ECM processing required to enhance the regenerative capacity of a bone implant will be application specific. These specifications will include issues such as load-bear","[116.0, 622.0, 607.0, 931.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,5,paragraph_title,Incorporating SCBTs into the design,"[120.0, 961.0, 421.0, 983.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Incorporating SCBTs into the design""]",subsection_heading,0.6,body_zone,body_like,none,True,True
14,6,text,"Priming chondrogenesis in vitro for EC ossification. While acellular ECM design strategies possess great conductive and inductive potential for eliciting in vivo EC ossification, SCBTs may provide adv","[117.0, 992.0, 606.0, 1410.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,7,text,"The bone regeneration community has attempted to harness the advantages of SCBT strategies, either as exclusive therapies or combined and encapsulated within biomaterial implants, to overcome cell rec","[116.0, 1410.0, 606.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,8,text,,"[618.0, 117.0, 1109.0, 447.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
14,9,text,"Within the realm of SCBTs for bone regeneration, a majority of strategies have focused on stimulating cell populations to undergo direct osteogenesis rather than chondrogenesis. However, as previously","[618.0, 448.0, 1110.0, 1039.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,10,text,"While the majority of the tissue priming research aimed at establishing feasibility from a particular cell population (Tables 2 and 3), several studies compared various cell sources to elucidate diffe","[618.0, 1039.0, 1111.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,0,header,ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING,"[115.0, 67.0, 922.0, 90.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
15,1,number,261,"[1067.0, 69.0, 1101.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
15,2,text,and could be a worthwhile focus of future investigation in enhancing EC ossification and bone regeneration designs.,"[113.0, 117.0, 601.0, 162.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,3,text,"Regardless of the cell source used for priming EC ossification, several generalized conclusions from the reviewed primed in vitro stem cell studies (Tables 2–4) can be summarized as follows:","[113.0, 161.0, 601.0, 251.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,4,text,(1) Chondrogenic cell priming in vitro was required to elicit EC ossification in vivo.,"[132.0, 259.0, 601.0, 302.0]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_parenthesis,True,True
15,5,text,"(2) Cartilage templates were necessary, but not sufficient to elicit EC ossification in vivo.","[133.0, 303.0, 601.0, 346.0]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_parenthesis,True,True
15,6,text,(a) Stable or permanent AC templates progressed through EC ossification.,"[133.0, 348.0, 600.0, 390.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
15,7,text,(3) Osteogenic priming alternatively favored IM over EC ossification.,"[133.0, 391.0, 601.0, 434.0]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_parenthesis,True,True
15,8,text,(4) Hypertrophic chondrocyte priming elicited the most extensive EC ossification.,"[133.0, 435.0, 601.0, 479.0]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_parenthesis,True,True
15,9,text,"While the collective evidence from these studies suggested that EC ossification remains necessarily tethered to the burden of in vitro cell priming and expansion, previous evidence was already present","[111.0, 489.0, 601.0, 688.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,10,text,"Consequently, this contradictory evidence suggests that an intermediate and underexplored strategy for bone regeneration may exist which incorporates advantages exhibited by both DBM biomaterials and ","[111.0, 688.0, 601.0, 976.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,11,text,"Intraoperative SCBT strategies with native ECM biomaterials. An emerging strategy to streamline SCBTs is to consolidate necessary cell protocols, including the harvesting, isolation, stimulation, and ","[112.0, 992.0, 602.0, 1300.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
15,12,text,"To date, however, no intraoperative SCBT approaches using either BMSCs or ADSCs derived from the stromal vascular fraction (SVF) have been able to regenerate bone in critical-sized defects without the","[112.0, 1300.0, 602.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
15,13,text,,"[614.0, 118.0, 1105.0, 489.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
15,14,text,"Emerging evidence in this area suggests that quick stimulation of isolated stem cells (e.g., minutes to hours) may improve differentiation and gene expression outcomes compared with untreated cells. $","[614.0, 490.0, 1105.0, 730.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
15,15,text,"Meanwhile, it should be reiterated and emphasized that native ECM biomaterials from allogeneic and xenogeneic sources possess both conductive and inductive biomolecules. $ ^{17,18,20,21} $ These bioma","[614.0, 730.0, 1104.0, 1017.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
15,16,text,"In summary, establishing the regenerative potential of acellular ECM biomaterial designs will help elucidate the additional benefits of incorporating either SCBTs or other purified inductive and condu","[614.0, 1015.0, 1105.0, 1237.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
15,17,paragraph_title,Discussion: Converging Framework of EC Ossification in the Future of Bone Regeneration,"[615.0, 1267.0, 1039.0, 1313.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Discussion: Converging Framework of EC Ossification in the F""]",subsection_heading,0.6,body_zone,unknown_like,none,True,True
15,18,text,"EC ossification, a process that naturally occurs in almost all bone-healing events, $ ^{1-9} $ can be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascula","[614.0, 1322.0, 1105.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
16,0,number,262,"[120.0, 69.0, 157.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
16,1,header,DENNIS ET AL.,"[969.0, 67.0, 1105.0, 89.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
16,2,text,intervention but can potentially be enhanced by combining in vivo developmental engineering strategies with biomimetic ECM biomaterials. Evidence to support this claim of utility resides in two evolvi,"[117.0, 117.0, 606.0, 402.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,3,text,"Currently, however, both in vitro priming and DBM strategies face formidable technical, business, and regulatory challenges that limit their feasibility as commercially competitive alternatives to the","[117.0, 402.0, 606.0, 600.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,4,text,"In addition, regulatory challenges exist for both strategies. $ ^{118} $ The in vitro expansion of autologous stem cells inherently involves a high level of manufacturing risk that should meet stringe","[117.0, 601.0, 606.0, 1170.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,5,text,"An alternative, and underexplored, developmental engineering strategy integrates the advantages of these two EC ossification approaches with a new class of ECM biomaterials that instead resemble the e","[117.0, 1169.0, 607.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
16,6,text,,"[618.0, 117.0, 1108.0, 270.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
16,7,text,"Although significant focus was given to acellular ECM strategies, critical perspectives on SCBTs were also discussed. While the reviewed chondrogenic priming studies collectively concluded that in vit","[619.0, 269.0, 1110.0, 930.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,8,text,"In summary, native ECM biomaterials inherently possessing ideal conductive, inductive, and mechanical properties have yet to be considered with regard to EC ossification and developmental engineering ","[619.0, 929.0, 1109.0, 1194.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,9,paragraph_title,Acknowledgments,"[622.0, 1211.0, 789.0, 1233.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgments""]",sub_subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
16,10,text,The authors are grateful for the support from the NIH (R01 DE022472 and R01 AR056347) and the NIGMS Predoctoral Biotechnology Training Grant Program (T32 GM-08359).,"[619.0, 1243.0, 1107.0, 1311.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,11,paragraph_title,Disclosure Statement,"[622.0, 1328.0, 815.0, 1350.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Disclosure Statement""]",subsection_heading,0.6,body_zone,body_like,none,True,True
16,12,text,No competing financial interests exist.,"[640.0, 1360.0, 958.0, 1384.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,13,paragraph_title,References,"[623.0, 1401.0, 726.0, 1423.0]",reference_heading,0.9,"[""references heading: References""]",reference_heading,0.9,reference_zone,unknown_like,short_fragment,True,True
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20,0,number,266,"[120.0, 69.0, 157.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
20,1,header,DENNIS ET AL.,"[969.0, 68.0, 1105.0, 89.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False
20,2,reference_content,"100. Lin, Y., Boker, A., He, J., Sill, K., Xiang, H., Abetz, C., et al. Self-directed self-assembly of nanoparticle/copolymer mixtures. Nature 434, 55, 2005.","[123.0, 118.0, 604.0, 180.0]",reference_item,0.85,"[""reference content label: 100. Lin, Y., Boker, A., He, J., Sill, K., Xiang, H., Abetz,""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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20,16,reference_content,"114. Muller, A.M., Mehrkens, A., Schafer, D.J., Jaquiery, C., Guven, S., Lehmicke, M., et al. Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular frac","[626.0, 370.0, 1107.0, 471.0]",reference_item,0.85,"[""reference content label: 114. Muller, A.M., Mehrkens, A., Schafer, D.J., Jaquiery, C.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
20,17,reference_content,"115. Mehrkens, A., Saxer, F., Guven, S., Hoffmann, W., Muller, A.M., Jakob, M., et al. Intraoperative engineering of osteogenic grafts combining freshly harvested, human adipose-derived cells and phys","[626.0, 474.0, 1107.0, 577.0]",reference_item,0.85,"[""reference content label: 115. Mehrkens, A., Saxer, F., Guven, S., Hoffmann, W., Mulle""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
20,18,reference_content,"116. Evans, C.H., Palmer, G.D., Pascher, A., Porter, R., Kwong, F.N., Gouze, E., et al. Facilitated endogenous repair: making tissue engineering simple, practical, and economical. Tissue Eng 13, 1987,","[625.0, 579.0, 1107.0, 661.0]",reference_item,0.85,"[""reference content label: 116. Evans, C.H., Palmer, G.D., Pascher, A., Porter, R., Kwo""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
20,19,reference_content,"117. Kitamura, S., Ohgushi, H., Hirose, M., Funaoka, H., Takakura, Y., and Ito, H. Osteogenic differentiation of human bone marrow-derived mesenchymal cells cultured on alumina ceramics. Artif Organs ","[626.0, 664.0, 1106.0, 743.0]",reference_item,0.85,"[""reference content label: 117. Kitamura, S., Ohgushi, H., Hirose, M., Funaoka, H., Tak""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
20,20,reference_content,"118. Lee, M.H., Arcidiacono, J.A., Bilek, A.M., Wille, J.J., Hamill, C.A., Wonnacott, K.M., et al. Considerations for tissue-engineered and regenerative medicine product development prior to clinical ","[627.0, 746.0, 1107.0, 849.0]",reference_item,0.85,"[""reference content label: 118. Lee, M.H., Arcidiacono, J.A., Bilek, A.M., Wille, J.J.,""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
20,21,text,"Address correspondence to:
Michael S. Detamore, PhD
Chemical and Petroleum Engineering Department
University of Kansas
4163 Learned Hall
1530 West 15th Street
Lawrence, KS 66045-7618","[693.0, 866.0, 1110.0, 1022.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
20,22,text,E-mail: detamore@ku.edu,"[889.0, 1025.0, 1108.0, 1047.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
20,23,text,"Received: July 14, 2014
Accepted: October 20, 2014
Online Publication Date: December 3, 2014","[741.0, 1057.0, 1110.0, 1124.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
1 page block_id raw_label content_preview bbox role role_confidence evidence seed_role seed_confidence zone style_family marker_type render_default index_default
2 1 0 header TISSUE ENGINEERING: Part B Volume 21, Number 3, 2015 © Mary Ann Liebert, Inc. DOI: 10.1089/ten.teb.2014.0419 [114.0, 66.0, 352.0, 142.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
3 1 1 doc_title Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo [116.0, 208.0, 1101.0, 331.0] paper_title 0.8 ["page-1 zone title_zone: Endochondral Ossification for Enhancing Bone Regeneration: C"] paper_title 0.8 frontmatter_main_zone support_like none True True
4 1 2 text S. Connor Dennis, BS, $ ^{1,2} $ Cory J. Berkland, PhD, $ ^{1-3} $ Lynda F. Bonewald, PhD, $ ^{4} $ and Michael S. Detamore, PhD $ ^{1,2} $ [334.0, 382.0, 883.0, 436.0] authors 0.8 ["page-1 zone author_zone: S. Connor Dennis, BS, $ ^{1,2} $ Cory J. Berkland, PhD, $ ^{"] authors 0.8 frontmatter_main_zone support_like none True True
5 1 3 abstract Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focus [112.0, 515.0, 1106.0, 1072.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 frontmatter_main_zone support_like none True True
6 1 4 paragraph_title Introduction [114.0, 1123.0, 229.0, 1145.0] section_heading 0.9 ["explicit scholarly heading: Introduction"] section_heading 0.9 body_zone heading_like canonical_section_name True True
7 1 5 text THE HUMAN BODY HAS AN EXTENSIVE capacity to regenerate bone tissue after trauma. Disruption of the surrounding vasculature and bone marrow resulting from a bone fracture initially facilitates a cascad [111.0, 1166.0, 601.0, 1367.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
8 1 6 text [613.0, 1122.0, 1105.0, 1319.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 frontmatter_main_zone support_like empty True True
9 1 7 text Clinically, however, ABG remains the gold standard of treatment due to its inherent osteoconductivity, osteoinductivity, [615.0, 1320.0, 1106.0, 1366.0] frontmatter_noise 0.7 ["keyword-like block: Clinically, however, ABG remains the gold standard of treatm"] frontmatter_noise 0.7 body_zone body_like none False False
10 1 8 footnote $ ^{1} $Bioengineering Program, University of Kansas, Lawrence, Kansas. [131.0, 1400.0, 629.0, 1423.0] footnote 0.7 ["footnote label: $ ^{1} $Bioengineering Program, University of Kansas, Lawren"] footnote 0.7 body_zone body_like affiliation_marker True True
11 1 9 footnote ²Chemical and Petroleum Engineering Department, University of Kansas, Lawrence, Kansas. [133.0, 1420.0, 810.0, 1439.0] footnote 0.7 ["footnote label: \u00b2Chemical and Petroleum Engineering Department, University o"] footnote 0.7 body_zone body_like none True True
12 1 10 footnote $ ^{3} $Pharmaceutical Chemistry Department, University of Kansas, Lawrence, Kansas. [133.0, 1439.0, 732.0, 1458.0] footnote 0.7 ["footnote label: $ ^{3} $Pharmaceutical Chemistry Department, University of K"] footnote 0.7 body_zone body_like affiliation_marker True True
13 1 11 footnote $ ^{4} $Department of Oral Biology, University of Missouri-Kansas City, Kansas City, Missouri. [133.0, 1456.0, 789.0, 1477.0] footnote 0.7 ["footnote label: $ ^{4} $Department of Oral Biology, University of Missouri-K"] footnote 0.7 body_zone body_like affiliation_marker True True
14 1 12 number 247 [592.0, 1500.0, 627.0, 1520.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
15 2 0 number 248 [120.0, 69.0, 157.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
16 2 1 header DENNIS ET AL. [970.0, 68.0, 1105.0, 89.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
17 2 2 text FIG. 1. Both IM and EC ossification occurs during the bone-healing process in three overlapping regeneration phases. Critical-sized bone defects favor EC ossification over direct IM ossification, prim [118.0, 135.0, 364.0, 640.0] body_paragraph 0.9 ["figure caption candidate (body narrative): FIG. 1. Both IM and EC ossification occurs during the bone-h"] figure_caption_candidate 0.9 display_zone legend_like figure_number True True
18 2 3 paragraph_title Phase I: Inflammatory 1. Hematoma Week (0-1) [379.0, 118.0, 575.0, 179.0] unknown_structural 0.6 ["page-1 frontmatter title guard: Phase I: Inflammatory 1. Hematoma Week (0-1)"] paper_title 0.6 body_zone unknown_like none False True
19 2 4 text Damaged vasculature and marrow facilitate hematoma formation along with influx of inflammatory cells and BMSCs. Initial progenitor cells likely fail to survive early inflammatory phase. IM and EC ossi [394.0, 186.0, 553.0, 292.0] non_body_insert 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none False False
20 2 5 text [586.0, 186.0, 741.0, 305.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone unknown_like empty True True
21 2 6 text [762.0, 186.0, 916.0, 305.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone unknown_like empty True True
22 2 7 text Phase III: Remodeling 3. Remodeled Bone Week ( $ \geq $ 8) [915.0, 118.0, 1106.0, 180.0] non_body_insert 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none False False
23 2 8 text Resorption of excess callus and replacement of woven bone with stronger lamellar bone. Dictated often by external mechanical load conditions and results in restoring healthy bone architecture. [931.0, 185.0, 1089.0, 305.0] non_body_insert 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none False False
24 2 9 image [398.0, 306.0, 1091.0, 645.0] media_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
25 2 10 text and thus osteogenic capabilities. $ ^{6,12-14} $ Despite these advantages, ABG has key clinical limitations, including donor site morbidity and pain, increased risk of infection, limited handling capa [118.0, 706.0, 606.0, 1060.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
26 2 11 text To date, acellular biomaterial-based products have dominated the alternative bone implant market at the commercial level. $ ^{11,15,16} $ A major characteristic of these products is the ability to mim [117.0, 1060.0, 606.0, 1388.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
27 2 12 text Addressing this avenue of research is the emerging paradigm of “developmental engineering” first introduced in 2009 in two reviews by Lenas et al., $ ^{22,23} $ which offer an innovative approach to e [117.0, 1389.0, 608.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
28 2 13 text [618.0, 706.0, 1109.0, 1104.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
29 2 14 text The incorporation of donor cells via SCBT strategies may provide advantageous osteo- and chondrogenic capabilities to acellular bone implants, which rely solely on recruited cells from the peripheral [619.0, 1103.0, 1109.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
30 3 0 header ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING [115.0, 67.0, 922.0, 90.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
31 3 1 number 249 [1067.0, 69.0, 1103.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
32 3 2 text in vitro cell expansion. Critical-sized bone defects often require surgical intervention within hours as opposed to weeks, because delayed bone healing leads to a higher risk of nonunion. $ ^{9} $ The [111.0, 117.0, 602.0, 446.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
33 3 3 text An alternative strategy to reduce or remove the cell expansion step may reside in extending developmental engineering principles to in vivo designs (i.e., within the graft or implant), thus removing i [111.0, 447.0, 602.0, 752.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
34 3 4 text This review will highlight essential design criteria involved in the underexplored regenerative area of developmentally engineering bone in vivo (Fig. 2). Traditional strategies have approached tissue [112.0, 753.0, 602.0, 843.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
35 3 5 text [614.0, 116.0, 1105.0, 492.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
36 3 6 paragraph_title Overview of the Natural Bone-Healing Process [616.0, 522.0, 1026.0, 544.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Overview of the Natural Bone-Healing Process"] subsection_heading 0.6 body_zone body_like none True True
37 3 7 text As mentioned earlier, the human body has an extensive capacity to regenerate bone tissue after trauma and fracture. The cellular and molecular processes involved in developmental skeletogenesis are cl [614.0, 555.0, 1105.0, 753.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
38 3 8 text In general, the fracture-healing process is most often described in three overlapping phases: Inflammatory, Reparative, and Remodeling (Fig. 1), where each phase represents a complex spatiotemporal di [614.0, 753.0, 1105.0, 843.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
39 3 9 image [183.0, 881.0, 1036.0, 1333.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
40 3 10 figure_title FIG. 2. Current landscape of EC ossification strategies (blue boxes) along with underexplored design space (dashed outlines) highlighted in this review. Some combined cell and material strategies are [113.0, 1354.0, 1105.0, 1478.0] figure_caption 0.92 ["figure_title label: FIG. 2. Current landscape of EC ossification strategies (blu"] figure_caption 0.92 display_zone legend_like figure_number True True
41 4 0 number 250 [120.0, 68.0, 158.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
42 4 1 header DENNIS ET AL. [969.0, 67.0, 1106.0, 89.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
43 4 2 text and bioactive signals. $ ^{1-9} $ Initially, disrupted vasculature and bone marrow during the inflammatory phase facilitates a coagulation cascade along with an influx of progenitor cells, including b [117.0, 114.0, 606.0, 621.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
44 4 3 text In contrast, chondrogenesis predominantly occurs in avascular environments where oxygen tension is low. $ ^{39-43} $ The main consequence of this difference is that IM and EC ossification is manifeste [117.0, 621.0, 606.0, 950.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
45 4 4 text While the process mentioned earlier describes successful bone regeneration within the body, it is well understood that large defects above a “critical-size” are incapable of completely restoring nativ [117.0, 950.0, 606.0, 1239.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
46 4 5 paragraph_title Strategies to Enhance EC Ossification Harnessing the potential of developmental engineering [118.0, 1255.0, 560.0, 1313.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Strategies to Enhance EC Ossification Harnessing the potenti"] subsection_heading 0.6 body_zone body_like none True True
47 4 6 footer [119.0, 1288.0, 560.0, 1313.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like empty False False
48 4 7 text Developmental engineering, a term first introduced into the tissue engineering community with two reviews in 2009 by Lenas et al., $ ^{22,23} $ involves the engineering of developmental “processes” an [116.0, 1321.0, 606.0, 1480.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
49 4 8 text [619.0, 116.0, 1108.0, 163.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
50 4 9 text (1) Path dependence: successive developmental tissue relies on previous tissue formation [640.0, 170.0, 1108.0, 215.0] body_paragraph 0.78 ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] body_paragraph 0.6 reference_like reference_numeric_parenthesis True True
51 4 10 text (2) Robustness: tissue developmental process resistant to unintended external perturbation [639.0, 216.0, 1108.0, 259.0] body_paragraph 0.78 ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] body_paragraph 0.6 reference_like reference_numeric_parenthesis True True
52 4 11 text (3) Semi-autonomy: partially self-governed tissue development [640.0, 260.0, 1106.0, 305.0] body_paragraph 0.78 ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] body_paragraph 0.6 reference_like reference_numeric_parenthesis True True
53 4 12 text EC ossification is a feasible route to utilize these guiding principles of developmental engineering, and the current review will cover advances made over the past decade in engineering EC ossificatio [619.0, 313.0, 1108.0, 403.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
54 4 13 text While the Lenas reviews only covered replicating in vivo developmental processes in an in vitro environment, $ ^{22,23} $ the current review aims to expand their previous concept further to include re [618.0, 404.0, 1110.0, 690.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
55 4 14 paragraph_title Coupling in vivo developmental engineering with native ECM biomaterials [621.0, 718.0, 980.0, 765.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Coupling in vivo developmental engineering with native ECM b"] subsection_heading 0.6 body_zone body_like none True True
56 4 15 text Characterizing the influence of DBM on ossification pathway. Inspiration for in vivo developmental designs already exists in the form of native ECM biomaterials. There is significant evidence that EC [618.0, 773.0, 1110.0, 1213.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
57 4 16 text Regardless of this, the DBM composition containing conductive and inductive biological agents likely influences developmental pathways during bone healing. $ ^{26-29} $ DBM composition, however, is no [618.0, 1213.0, 1110.0, 1480.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
58 5 0 figure_title TABLE 1. PRIMING IN VITRO CHONDROGENESIS WITH BONE MESENCHYMAL STEM CELLS FOR IN VIVO ENDOCHONDRAL OSSIFICATION [116.0, 225.0, 140.0, 1315.0] table_caption 0.9 ["table prefix matched: TABLE 1. PRIMING IN VITRO CHONDROGENESIS WITH BONE MESENCHYM"] table_caption 0.9 display_zone table_caption_like table_number True True
59 5 1 table <table><tr><td>Reference(s)</td><td>Year</td><td>Cell source</td><td>Additional materials</td><td>In vitro priming method</td><td>Animal model</td><td>Highlighted results</td></tr><tr><td>Yamada et al [132.0, 58.0, 1070.0, 1487.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
60 5 2 number 251 [592.0, 1499.0, 625.0, 1521.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
61 5 3 vision_footnote (continued) [1071.0, 69.0, 1093.0, 167.0] footnote 0.7 ["vision_footnote label: (continued)"] footnote 0.7 body_zone body_like short_fragment True True
62 6 0 figure_title TABLE 1. (CONTINUED) [195.0, 669.0, 217.0, 872.0] table_caption 0.9 ["table prefix matched: TABLE 1. (CONTINUED)"] table_caption 0.9 display_zone table_caption_like table_number True True
63 6 1 table <table><tr><td>Reference(s)</td><td>Year</td><td>Cell source</td><td>Additional materials</td><td>In vitro priming method</td><td>Animal model</td><td>Highlighted results</td></tr><tr><td>Farrell et a [225.0, 61.0, 1053.0, 1486.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
64 6 2 number 252 [597.0, 1499.0, 631.0, 1520.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
65 7 0 figure_title TABLE 1. (CONTINUED) [174.0, 669.0, 195.0, 872.0] table_caption 0.9 ["table prefix matched: TABLE 1. (CONTINUED)"] table_caption 0.9 display_zone table_caption_like table_number True True
66 7 1 table <table><tr><td>Reference(s)</td><td>Year</td><td>Cell source</td><td>Additional materials</td><td>In vitro priming method</td><td>Animal model</td><td>Highlighted results</td></tr><tr><td>Bahney et al [198.0, 68.0, 998.0, 1488.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
67 7 2 number 253 [593.0, 1499.0, 626.0, 1520.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
68 7 3 vision_footnote ACs, articular chondrocytes; BMSC, bone mesenchymal stem cell; beta-TCP, beta tricalcium phosphate; EC, endochondral; GAG, glycosaminoglycan; hAC, human AC; hBMSC, human BMSC; IM, intramembranous; pBM [975.0, 70.0, 1017.0, 1471.0] footnote 0.7 ["vision_footnote label: ACs, articular chondrocytes; BMSC, bone mesenchymal stem cel"] footnote 0.7 body_zone body_like none True True
69 8 0 figure_title TABLE 2. PRIMING IN VITRO CHONDROGENESIS WITH EMBRYONIC STEM CELLS, SYNOVIUM-DERIVED STEM CELLS, ARTICULAR CHONDROCYTE AND INDICATED PITRIPOTENT STEM CELLS FOR IN VIVO ENDOCHONDRAL OSSIFICATION [147.0, 197.0, 189.0, 1358.0] table_caption 0.9 ["table prefix matched: TABLE 2. PRIMING IN VITRO CHONDROGENESIS WITH EMBRYONIC STEM"] table_caption 0.9 display_zone table_caption_like table_number True True
70 8 1 table <table><tr><td>Reference(s)</td><td>Year</td><td>Cell source</td><td>Additional materials</td><td>In vitro priming method</td><td>Animal model</td><td>Highlighted results</td></tr><tr><td>Montufar-Sol [176.0, 62.0, 1068.0, 1495.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
71 8 2 number 254 [597.0, 1498.0, 632.0, 1521.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
72 8 3 vision_footnote ADSC, adipose-derived stem cell; ESC, embryonic stem cell; hADSC, human ADSC; hFB, human fibroblast; PBS, phosphate-buffered saline; PGA, polyglycolic acid; SVF, stromal vascular [1037.0, 72.0, 1066.0, 1481.0] footnote 0.7 ["vision_footnote label: ADSC, adipose-derived stem cell; ESC, embryonic stem cell; h"] footnote 0.7 body_zone body_like none True True
73 9 0 figure_title TABLE 3. COMPARING IN VITRO CHONDROGENICALLY PRIMED CELL SOURCES FOR IN VIVO ENDOCHONDRAL OSSIFICATION [116.0, 276.0, 139.0, 1270.0] table_caption 0.9 ["table prefix matched: TABLE 3. COMPARING IN VITRO CHONDROGENICALLY PRIMED CELL SOU"] table_caption 0.9 display_zone table_caption_like table_number True True
74 9 1 table <table><tr><td>Reference(s)</td><td>Year</td><td>Cell source</td><td>Additional materials</td><td>In vitro priming method</td><td>Animal moea</td><td>Chondrogenic priming led to similar collagen type [130.0, 61.0, 1127.0, 1482.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
75 9 2 number 255 [592.0, 1498.0, 627.0, 1520.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
76 9 3 vision_footnote ALP, alkaline phosphatase; BCP, biphasic calcium phosphate; FPSCs, fat-pad derived stem cells; OB, osteoblast; rOB, human OB; SDSC, synovium-derived stem cell. [1104.0, 246.0, 1128.0, 1469.0] footnote 0.7 ["vision_footnote label: ALP, alkaline phosphatase; BCP, biphasic calcium phosphate; "] footnote 0.7 body_zone body_like none True True
77 10 0 number 256 [120.0, 68.0, 157.0, 89.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
78 10 1 header DENNIS ET AL. [968.0, 67.0, 1106.0, 89.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
79 10 2 text suggesting that only implants directed toward IM ossification will possess regenerative potential. However, evidence from Rabie et al. $ ^{28,30,31} $ showed that IM and EC ossification pathways can b [117.0, 117.0, 606.0, 534.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
80 10 3 text The differences in regenerative potential and developmental pathways seen in the Rabie studies were attributed to varying inductive and conductive ECM factors within DBM. $ ^{28,30-32} $ Inductive fac [117.0, 533.0, 606.0, 1015.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
81 10 4 text Collectively, there is significant evidence to suggest that EC ossification can occur within native ECM biomaterials in the form of acellular DBM implants. While there has been extensive research into [117.0, 1014.0, 606.0, 1261.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
82 10 5 text Exploring EC ossification potential in ECM biomaterials. In general, native ECM refers to both soluble and insoluble biomolecules that may be utilized as cell scaffolding and bioactive signaling. In a [117.0, 1277.0, 606.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
83 10 6 text [618.0, 116.0, 1108.0, 203.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
84 10 7 text Traditional bone ECM strategies: ABG intrinsically involves the grafting of native bone ECM tissue with associated autologous cells into bone defects, and it remains the gold standard of treatment in [618.0, 205.0, 1110.0, 774.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
85 10 8 text It is important to note, however, that the functional and structural properties of ECM during the bone-healing process are spatiotemporally dynamic and do not resemble healthy native bone until well i [619.0, 774.0, 1110.0, 972.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
86 10 9 text Alternative ECM biomaterial strategies for EC ossification: By instead leveraging the concepts of both developmental engineering and the spatiotemporal dynamics of ECM in bone healing, there may be po [618.0, 972.0, 1110.0, 1258.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
87 10 10 text Characterization of the complex cascade of signaling events and ECM changes involved in bone healing and EC ossification has been the focus of several recent reviews, $ ^{6,9,33,34} $ and readers inte [618.0, 1256.0, 1110.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
88 11 0 header ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING [114.0, 67.0, 922.0, 90.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
89 11 1 number 257 [1067.0, 69.0, 1102.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
90 11 2 text ECM biomaterials that correspond to the early and intermediate stages of native bone healing. [112.0, 117.0, 601.0, 162.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
91 11 3 text Native ECM biomaterials possess both conductive and inductive potential that are difficult to match with synthetic designs (e.g., non-native polymers). $ ^{17-20} $ In addition, it is increasingly evi [111.0, 161.0, 602.0, 511.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
92 11 4 text To date, a few studies have attempted to coordinate developmental bone engineering strategies with acellular native ECM biomaterials (Figs. 1 and 2). Subsequent sections will address key features of e [112.0, 511.0, 602.0, 666.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
93 11 5 text Inflammatory stage ECM strategies for EC ossification: Since most tissues primarily rely on broken vasculature to supply damaged areas with inflammatory signals and cells, modulating the body's initia [111.0, 665.0, 602.0, 1038.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
94 11 6 text One strategy to enhance the regenerative response in inflammatory stage ECM strategies has been to supply the fracture space with stem cells from bone marrow aspirate, as fractured bone is supplied wi [111.0, 1038.0, 603.0, 1481.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
95 11 7 text [614.0, 117.0, 1105.0, 249.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
96 11 8 text Coupling the evidence of low progenitor count with poor cell survival rate observed in hypoxic bone defects suggests the importance of spatiotemporal cellular recruitment strategies for bone regenerat [614.0, 248.0, 1105.0, 665.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
97 11 9 text Collectively, the evidence surrounding the use of inflammatory stage ECM scaffolds, signals, and recruited cells indicates that current designs remain insufficient in regenerating bone in critical-siz [614.0, 665.0, 1105.0, 863.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
98 11 10 text Procallus stage ECM strategies for EC ossification: An intuitive source for enhancing stimulation of EC ossification is the procallus ECM, as natural bone healing progresses to this stage early in the [614.0, 863.0, 1105.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
99 12 0 number 258 [120.0, 69.0, 157.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
100 12 1 header DENNIS ET AL. [969.0, 67.0, 1106.0, 89.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
101 12 2 figure_title TABLE 4. MODULATORS OF CHONDROCYTE HYPERTROPHY [373.0, 117.0, 852.0, 140.0] table_caption 0.9 ["table prefix matched: TABLE 4. MODULATORS OF CHONDROCYTE HYPERTROPHY"] table_caption 0.9 display_zone table_caption_like table_number True True
102 12 3 table <table><tr><td>Differentiation pathway</td><td>Chemical</td><td>Physical</td><td>Mechanical</td></tr><tr><td>Chondrogenesis</td><td>TGF- $ \beta $, BMPs, Dexamethasone</td><td>Low oxygen tension</td>< [117.0, 146.0, 1104.0, 337.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
103 12 4 vision_footnote BMPs, bone morphogenic proteins; MMP, matrix metalloproteinase; TGF, transforming growth factor; IL-1β, interleukin-1β. [135.0, 348.0, 1042.0, 371.0] footnote 0.7 ["vision_footnote label: BMPs, bone morphogenic proteins; MMP, matrix metalloproteina"] footnote 0.7 body_zone body_like none True True
104 12 5 text that external chemical, $ ^{9,33,38,41,73,80-85,89,90} $ physical, $ ^{39-42} $ and mechanical cues $ ^{41,45} $ stimulated BMSCs to stay locked in a stable cartilage state or progress into a hypertro [117.0, 399.0, 606.0, 533.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
105 12 6 text In summary, the success of in vivo developmental engineering designs for EC ossification will likely depend on the incorporation of physiologically relevant bioactive chemical mediators along with phy [117.0, 533.0, 607.0, 843.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
106 12 7 paragraph_title Isolating, identifying, and delivering native ECM for EC ossification [118.0, 873.0, 510.0, 918.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Isolating, identifying, and delivering native ECM for EC oss"] subsection_heading 0.6 body_zone body_like none True True
107 12 8 text Utilizing step-wise ECM strategies. Strategies to design scaffolds with incorporated native ECM components can be divided into two main categories: (1) Bottom-up approach or (2) Top-down approach (i.e [117.0, 929.0, 606.0, 1477.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
108 12 9 text [618.0, 402.0, 1110.0, 713.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
109 12 10 image [656.0, 752.0, 1076.0, 1353.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
110 12 11 figure_title FIG. 3. Top-down approaches to mimic native ECM tissue require less processing before implantation and retain more of the ECM's physicochemical composition, structure, and function compared with botto [619.0, 1373.0, 1108.0, 1478.0] figure_caption 0.92 ["figure_title label: FIG. 3. Top-down approaches to mimic native ECM tissue requi"] figure_caption 0.92 display_zone legend_like figure_number True True
111 13 0 header ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING [115.0, 67.0, 923.0, 90.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
112 13 1 number 259 [1067.0, 69.0, 1102.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
113 13 2 text “raw” biomaterial re-synthesis, however, is that designs can be modular, which means that separate elements of the design can be tested independently. As a result, each component can be characterized [112.0, 120.0, 602.0, 751.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
114 13 3 text Step-wise designs from both allogeneic and xenogeneic tissue sources have been utilized clinically for cartilage and bone tissue engineering along with dermal, vascular, nerve, and urogenital tissue. [112.0, 752.0, 602.0, 1041.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
115 13 4 text Decellularized cartilage for enhancing EC ossification. Intuitively, it follows that designs mimicking the native bone or cartilage ECM hold vast potential for eliciting ossification and chondrogenesi [112.0, 1059.0, 602.0, 1480.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
116 13 5 text [614.0, 117.0, 1105.0, 381.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
117 13 6 text DCC, from both allogeneic and xenogeneic sources, is a poorly explored native ECM biomaterial. Recently, it has emerged as a source that is rich in both chondroinductive and chondroconductive potentia [614.0, 381.0, 1106.0, 1171.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
118 13 7 text Delivery strategies for decellularized tissues. Crucial to the future success of these ECM materials will be the strategies used to incorporate and deliver them within engineered implants. If maximum [614.0, 1191.0, 1106.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
119 14 0 number 260 [120.0, 69.0, 157.0, 89.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
120 14 1 header DENNIS ET AL. [968.0, 67.0, 1106.0, 89.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
121 14 2 text particle size on regenerative capacity of these materials remains unclear. A recent review of DBM clinical products and procurement by Gruskin et al. $ ^{15} $ indicated that larger particles of DBM ( [116.0, 117.0, 606.0, 358.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
122 14 3 text While morselization strategies most often include some form of mechanical breakdown (e.g., pulverization or cyro-grinding), solubilization uses chemical and enzymatic methods (e.g., demineralization a [116.0, 359.0, 606.0, 622.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
123 14 4 text In summary, the extent of native ECM processing required to enhance the regenerative capacity of a bone implant will be application specific. These specifications will include issues such as load-bear [116.0, 622.0, 607.0, 931.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
124 14 5 paragraph_title Incorporating SCBTs into the design [120.0, 961.0, 421.0, 983.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Incorporating SCBTs into the design"] subsection_heading 0.6 body_zone body_like none True True
125 14 6 text Priming chondrogenesis in vitro for EC ossification. While acellular ECM design strategies possess great conductive and inductive potential for eliciting in vivo EC ossification, SCBTs may provide adv [117.0, 992.0, 606.0, 1410.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
126 14 7 text The bone regeneration community has attempted to harness the advantages of SCBT strategies, either as exclusive therapies or combined and encapsulated within biomaterial implants, to overcome cell rec [116.0, 1410.0, 606.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
127 14 8 text [618.0, 117.0, 1109.0, 447.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
128 14 9 text Within the realm of SCBTs for bone regeneration, a majority of strategies have focused on stimulating cell populations to undergo direct osteogenesis rather than chondrogenesis. However, as previously [618.0, 448.0, 1110.0, 1039.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
129 14 10 text While the majority of the tissue priming research aimed at establishing feasibility from a particular cell population (Tables 2 and 3), several studies compared various cell sources to elucidate diffe [618.0, 1039.0, 1111.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
130 15 0 header ENDOCHONDRAL OSSIFICATION WITH NATIVE ECM AND DEVELOPMENTAL ENGINEERING [115.0, 67.0, 922.0, 90.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
131 15 1 number 261 [1067.0, 69.0, 1101.0, 88.0] noise 0.9 ["page number label"] noise 0.9 unknown_like short_fragment False False
132 15 2 text and could be a worthwhile focus of future investigation in enhancing EC ossification and bone regeneration designs. [113.0, 117.0, 601.0, 162.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
133 15 3 text Regardless of the cell source used for priming EC ossification, several generalized conclusions from the reviewed primed in vitro stem cell studies (Tables 2–4) can be summarized as follows: [113.0, 161.0, 601.0, 251.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
134 15 4 text (1) Chondrogenic cell priming in vitro was required to elicit EC ossification in vivo. [132.0, 259.0, 601.0, 302.0] body_paragraph 0.78 ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] body_paragraph 0.6 reference_like reference_numeric_parenthesis True True
135 15 5 text (2) Cartilage templates were necessary, but not sufficient to elicit EC ossification in vivo. [133.0, 303.0, 601.0, 346.0] body_paragraph 0.78 ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] body_paragraph 0.6 reference_like reference_numeric_parenthesis True True
136 15 6 text (a) Stable or permanent AC templates progressed through EC ossification. [133.0, 348.0, 600.0, 390.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
137 15 7 text (3) Osteogenic priming alternatively favored IM over EC ossification. [133.0, 391.0, 601.0, 434.0] body_paragraph 0.78 ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] body_paragraph 0.6 reference_like reference_numeric_parenthesis True True
138 15 8 text (4) Hypertrophic chondrocyte priming elicited the most extensive EC ossification. [133.0, 435.0, 601.0, 479.0] body_paragraph 0.78 ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] body_paragraph 0.6 reference_like reference_numeric_parenthesis True True
139 15 9 text While the collective evidence from these studies suggested that EC ossification remains necessarily tethered to the burden of in vitro cell priming and expansion, previous evidence was already present [111.0, 489.0, 601.0, 688.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
140 15 10 text Consequently, this contradictory evidence suggests that an intermediate and underexplored strategy for bone regeneration may exist which incorporates advantages exhibited by both DBM biomaterials and [111.0, 688.0, 601.0, 976.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
141 15 11 text Intraoperative SCBT strategies with native ECM biomaterials. An emerging strategy to streamline SCBTs is to consolidate necessary cell protocols, including the harvesting, isolation, stimulation, and [112.0, 992.0, 602.0, 1300.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
142 15 12 text To date, however, no intraoperative SCBT approaches using either BMSCs or ADSCs derived from the stromal vascular fraction (SVF) have been able to regenerate bone in critical-sized defects without the [112.0, 1300.0, 602.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
143 15 13 text [614.0, 118.0, 1105.0, 489.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
144 15 14 text Emerging evidence in this area suggests that quick stimulation of isolated stem cells (e.g., minutes to hours) may improve differentiation and gene expression outcomes compared with untreated cells. $ [614.0, 490.0, 1105.0, 730.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
145 15 15 text Meanwhile, it should be reiterated and emphasized that native ECM biomaterials from allogeneic and xenogeneic sources possess both conductive and inductive biomolecules. $ ^{17,18,20,21} $ These bioma [614.0, 730.0, 1104.0, 1017.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
146 15 16 text In summary, establishing the regenerative potential of acellular ECM biomaterial designs will help elucidate the additional benefits of incorporating either SCBTs or other purified inductive and condu [614.0, 1015.0, 1105.0, 1237.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
147 15 17 paragraph_title Discussion: Converging Framework of EC Ossification in the Future of Bone Regeneration [615.0, 1267.0, 1039.0, 1313.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Discussion: Converging Framework of EC Ossification in the F"] subsection_heading 0.6 body_zone unknown_like none True True
148 15 18 text EC ossification, a process that naturally occurs in almost all bone-healing events, $ ^{1-9} $ can be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascula [614.0, 1322.0, 1105.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
149 16 0 number 262 [120.0, 69.0, 157.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
150 16 1 header DENNIS ET AL. [969.0, 67.0, 1105.0, 89.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
151 16 2 text intervention but can potentially be enhanced by combining in vivo developmental engineering strategies with biomimetic ECM biomaterials. Evidence to support this claim of utility resides in two evolvi [117.0, 117.0, 606.0, 402.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
152 16 3 text Currently, however, both in vitro priming and DBM strategies face formidable technical, business, and regulatory challenges that limit their feasibility as commercially competitive alternatives to the [117.0, 402.0, 606.0, 600.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
153 16 4 text In addition, regulatory challenges exist for both strategies. $ ^{118} $ The in vitro expansion of autologous stem cells inherently involves a high level of manufacturing risk that should meet stringe [117.0, 601.0, 606.0, 1170.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
154 16 5 text An alternative, and underexplored, developmental engineering strategy integrates the advantages of these two EC ossification approaches with a new class of ECM biomaterials that instead resemble the e [117.0, 1169.0, 607.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone body_like none True True
155 16 6 text [618.0, 117.0, 1108.0, 270.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
156 16 7 text Although significant focus was given to acellular ECM strategies, critical perspectives on SCBTs were also discussed. While the reviewed chondrogenic priming studies collectively concluded that in vit [619.0, 269.0, 1110.0, 930.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
157 16 8 text In summary, native ECM biomaterials inherently possessing ideal conductive, inductive, and mechanical properties have yet to be considered with regard to EC ossification and developmental engineering [619.0, 929.0, 1109.0, 1194.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
158 16 9 paragraph_title Acknowledgments [622.0, 1211.0, 789.0, 1233.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgments"] sub_subsection_heading 0.6 body_zone body_like short_fragment True True
159 16 10 text The authors are grateful for the support from the NIH (R01 DE022472 and R01 AR056347) and the NIGMS Predoctoral Biotechnology Training Grant Program (T32 GM-08359). [619.0, 1243.0, 1107.0, 1311.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
160 16 11 paragraph_title Disclosure Statement [622.0, 1328.0, 815.0, 1350.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Disclosure Statement"] subsection_heading 0.6 body_zone body_like none True True
161 16 12 text No competing financial interests exist. [640.0, 1360.0, 958.0, 1384.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
162 16 13 paragraph_title References [623.0, 1401.0, 726.0, 1423.0] reference_heading 0.9 ["references heading: References"] reference_heading 0.9 reference_zone unknown_like short_fragment True True
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291 20 21 text Address correspondence to: Michael S. Detamore, PhD Chemical and Petroleum Engineering Department University of Kansas 4163 Learned Hall 1530 West 15th Street Lawrence, KS 66045-7618 [693.0, 866.0, 1110.0, 1022.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
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293 20 23 text Received: July 14, 2014 Accepted: October 20, 2014 Online Publication Date: December 3, 2014 [741.0, 1057.0, 1110.0, 1124.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True

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"findings": [
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:0"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:1"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:2"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
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"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:3"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
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"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:4"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:5"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:6"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:7"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
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"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:8"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
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"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:9"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:10"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:11"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:12"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:13"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:14"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:15"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:16"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:17"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:18"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p10:19"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_010.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
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"p1:6",
"p1:7",
"p1:8",
"p1:9",
"p1:10",
"p1:11",
"p1:15",
"p1:25",
"p1:26",
"p1:27",
"p2:10",
"p4:3",
"p6:6",
"p7:3",
"p7:4",
"p9:2",
"p10:3",
"p10:5",
"p10:8"
],
"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
"annotated_page": null,
"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

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# OCR Truth Audit Report - 49NUE2G7
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 3, 4, 5, 6, 7, 8, 10]
- Reviewed blocks: 151
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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page,block_id,raw_label,content_preview,bbox,role,role_confidence,evidence,seed_role,seed_confidence,zone,style_family,marker_type,render_default,index_default
1,0,header,Osteoarthritis and Cartilage 34 (2026) 28–38,"[445.0, 68.0, 721.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,1,header,"Osteoarthritis
and Cartilage","[55.0, 151.0, 328.0, 243.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,2,header_image,,"[796.0, 125.0, 1110.0, 241.0]",unknown_structural,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,frontmatter_main_zone,support_like,empty,False,True
1,3,doc_title,Osteoarthritis year in review 2025: Imaging,"[56.0, 329.0, 618.0, 363.0]",paper_title,0.6,"[""page-1 frontmatter title guard: Osteoarthritis year in review 2025: Imaging""]",paper_title,0.6,frontmatter_main_zone,support_like,none,True,True
1,4,text,"Matthew S. Harkey $ {}^{a} $, Anthony A. Gatti $ {}^{b} $, Mylène P. Jansen $ {}^{c} $, McKenzie S. White $ {}^{b} $, Jessica Tolzman $ {}^{a} $, Arjun Parmar $ {}^{a} $, Ian Frederick $ {}^{a}","[55.0, 378.0, 909.0, 433.0]",authors,0.8,"[""page-1 zone author_zone: Matthew S. Harkey $ {}^{a} $, Anthony A. Gatti $ {}^{b} $,""]",authors,0.8,body_zone,reference_like,citation_line,True,True
1,5,image,,"[1049.0, 334.0, 1105.0, 389.0]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,frontmatter_main_zone,support_like,empty,True,True
1,6,text," $ ^{a} $ Department of Kinesiology, Michigan State University, East Lansing, MI, USA","[57.0, 441.0, 509.0, 459.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{a} $ Department of Kinesiology, Michigan State Universit""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,7,text," $ ^{b} $ Department of Radiology, Stanford University, Stanford, CA, USA","[57.0, 459.0, 442.0, 476.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{b} $ Department of Radiology, Stanford University, Stanf""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,8,text," $ ^{c} $ Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands","[57.0, 474.0, 725.0, 492.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{c} $ Department of Rheumatology & Clinical Immunology, U""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,9,text," $ ^{d} $ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA","[57.0, 492.0, 637.0, 509.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{d} $ Department of Radiology and Biomedical Imaging, Uni""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,10,text," $ ^{e} $ La Trobe Sport and Exercise Medicine Research Centre, La Trobe University, Melbourne, VIC, Australia","[57.0, 508.0, 652.0, 525.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{e} $ La Trobe Sport and Exercise Medicine Research Centr""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,11,text,"School of Physical Therapy, Western University, London, ONT, Canada","[57.0, 527.0, 468.0, 544.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: School of Physical Therapy, Western University, London, ONT,""]",affiliation,0.8,frontmatter_main_zone,support_like,none,True,True
1,12,paragraph_title,ARTICLE INFO,"[57.0, 590.0, 255.0, 610.0]",frontmatter_noise,0.5,"[""unnumbered paragraph_title on page 1 outside title zone: ARTICLE INFO""]",section_heading,0.5,frontmatter_main_zone,support_like,short_fragment,False,False
1,13,text,"Article history:
Received 19 June 2025
Received in revised form 10 October 2025
Accepted 6 November 2025","[57.0, 630.0, 316.0, 700.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Article history:\nReceived 19 June 2025\nReceived in revised f""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
1,14,text,"Keywords:
Ultrasound
Computer Tomography
Magnetic resonance imaging
Radiography","[57.0, 721.0, 236.0, 810.0]",frontmatter_noise,0.7,"[""frontmatter noise text: Keywords:\nUltrasound\nComputer Tomography\nMagnetic resonance ""]",frontmatter_noise,0.7,body_zone,body_like,none,False,False
1,15,paragraph_title,A B S T R A C T,"[390.0, 590.0, 538.0, 610.0]",section_heading,0.5,"[""unnumbered paragraph_title on page 1 outside title zone: A B S T R A C T""]",section_heading,0.5,body_zone,body_like,short_fragment,True,True
1,16,abstract,"on how emerging methods and multi-tissue assessments are contributing to disease characterization, early detection, and intervention strategies.
Design: We conducted a comprehensive search strategy of","[388.0, 657.0, 1111.0, 818.0]",body_paragraph,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,body_zone,body_like,none,True,True
1,17,abstract,"Results: A total of 26 studies were included. Collectively, the studies reinforce the importance of viewing osteoarthritis as a condition involving multiple joint structures, with inflammation as a re","[389.0, 822.0, 1111.0, 955.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,body_zone,body_like,none,True,True
1,18,abstract,Conclusions: Imaging research in the osteoarthritis continues to broaden in scope and application. The studies highlighted in this review illustrate how advances in methods and metrics are improving o,"[389.0, 954.0, 1109.0, 1030.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,body_zone,body_like,none,True,True
1,19,text,"© 2025 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","[408.0, 1030.0, 1109.0, 1071.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: \u00a9 2025 Osteoarthritis Research Society International. Publis""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
1,20,paragraph_title,Introduction,"[58.0, 1134.0, 163.0, 1154.0]",section_heading,0.9,"[""explicit scholarly heading: Introduction""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
1,21,text,"Osteoarthritis (OA) is a heterogeneous, multi-tissue disease characterized by structural changes, inflammation, and altered joint function $ [1] $. Medical imaging plays a critical role in the assess","[56.0, 1176.0, 569.0, 1219.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,22,text,,"[595.0, 1133.0, 1111.0, 1367.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
1,23,footnote," $ ^{*} $ Correspondence to: Department of Kinesiology, Michigan State University, 308 W. Circle Drive #112, East Lansing MI, 48824.","[57.0, 1261.0, 569.0, 1298.0]",footnote,0.7,"[""footnote label: $ ^{*} $ Correspondence to: Department of Kinesiology, Michi""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
1,24,footnote,"E-mail addresses: harkeym1@msu.edu (M. Harkey),","[72.0, 1297.0, 393.0, 1314.0]",footnote,0.7,"[""footnote label: E-mail addresses: harkeym1@msu.edu (M. Harkey),""]",footnote,0.7,body_zone,body_like,none,True,True
1,25,footnote,"aagatti@stanford.edu (A. Gatti), m.p.jansen-36@umcutrecht.nl (M. Jansen), kenziew@stanford.edu (M. White), tolzmanj@msu.edu (J. Tolzman), parmarar@msu.edu (A. Parmar), frede220@msu.edu (I. Frederick),","[57.0, 1304.0, 509.0, 1386.0]",footnote,0.7,"[""footnote label: aagatti@stanford.edu (A. Gatti), m.p.jansen-36@umcutrecht.nl""]",footnote,0.7,body_zone,body_like,none,True,True
1,26,footer,https://doi.org/10.1016/j.joca.2025.11.004,"[58.0, 1402.0, 307.0, 1419.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
1,27,footer,"1063-4584/© 2025 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","[55.0, 1417.0, 1111.0, 1455.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,0,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[416.0, 70.0, 797.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
2,1,number,29,"[1112.0, 70.0, 1132.0, 86.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,2,text,"identify imaging features of early disease, defined as changes preceding radiographic OA (Kellgren Lawrence [KL] grade > 1), and to better characterize distinct OA subgroups [3–5].","[78.0, 107.0, 593.0, 170.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,3,text,"This narrative review aimed to identify a select number of imaging studies from the past year that highlight emerging trends, novel approaches, and clinical relevance in OA. We acknowledge that many o","[79.0, 171.0, 594.0, 424.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,4,paragraph_title,Methods,"[81.0, 443.0, 156.0, 463.0]",section_heading,0.9,"[""explicit scholarly heading: Methods""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
2,5,text,"To ensure a comprehensive and unbiased selection of studies, we performed a systematic search of PubMed, Embase via EBSCO, and CINAHL via EBSCO for studies on imaging and OA with an initial search on ","[78.0, 484.0, 594.0, 1012.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,paragraph_title,Search results and thematic organization,"[80.0, 1032.0, 411.0, 1053.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Search results and thematic organization""]",subsection_heading,0.6,body_zone,body_like,none,True,True
2,7,text,"The initial search yielded 4842 records. After removing duplicates, we screened 3852 titles and abstracts, and 262 full-text studies met the inclusion criteria (Fig. 1). Each full-text article was ind","[78.0, 1073.0, 594.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,8,text,,"[618.0, 107.0, 1135.0, 256.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
2,9,paragraph_title,Major themes,"[620.0, 275.0, 738.0, 297.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Major themes""]",subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
2,10,text,Theme #1: effusion-synovitis imaging,"[620.0, 317.0, 896.0, 340.0]",unknown_structural,0.8,"[""page-1 zone author_zone: Theme #1: effusion-synovitis imaging""]",authors,0.8,body_zone,body_like,none,False,True
2,11,text,Highlighted study: [11C]-PBR28 PET as a novel marker of synovial inflammation,"[618.0, 358.0, 1133.0, 401.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,12,text,Sandström et al. [6] conducted the first in vivo study using [11 C]-PBR28 PET/MRI in knee osteoarthritis (OA) to measure joint inflammation (Fig. 2). The technique targets the 18-kDa translocator prot,"[619.0, 401.0, 1135.0, 737.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,13,text,Additional Key Studies,"[644.0, 737.0, 822.0, 758.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,14,text,"• Ultrasound Effusion-Synovitis and Gait Asymmetry: Harkey et al. [7] found that 87% of individuals 1–5 years post-ACL reconstruction had ultrasound-detected effusion-synovitis, with higher effusion g","[628.0, 778.0, 1134.0, 926.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,15,text,• Early Knee OA Effusion and Symptoms: Mizuno et al. [8] used ultrasound to evaluate joint effusion and reported that even mild effusion in participants with early knee OA was associated with worse sy,"[628.0, 926.0, 1134.0, 1073.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,16,text,• Synovitis Mediates OA Progression: Deng et al. [9] used longitudinal MRI and mediation modeling to show that synovitis mediates the relationship between medial meniscus extrusion and knee OA progres,"[628.0, 1074.0, 1133.0, 1179.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,17,text,"- AI-Based Effusion Detection on Radiographs: Won et al. [10] developed an AI model to classify knee joint effusion on radiographs, using MRI-defined effusion as the reference standard. The model outp","[628.0, 1179.0, 1134.0, 1307.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,18,text,Theme summary: advancing the detection and interpretation of synovial inflammation,"[620.0, 1326.0, 1085.0, 1369.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,19,text,"The past year's work reinforces that effusion-synovitis is not merely an incidental finding but a clinically meaningful feature across the OA spectrum, from post-traumatic populations to early and est","[618.0, 1389.0, 1135.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,0,number,30,"[58.0, 70.0, 79.0, 86.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,1,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[392.0, 69.0, 774.0, 89.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
3,2,image,,"[141.0, 136.0, 1018.0, 1261.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
3,3,figure_title,Fig. 1,"[77.0, 1306.0, 138.0, 1330.0]",figure_caption,0.92,"[""figure_title label: Fig. 1""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
3,4,figure_title,"Flow diagram outlining the study selection process for the narrative review. A total of 4842 records were identified through database searches, with 990 duplicates removed and 262 studies assessed as ","[67.0, 1345.0, 1099.0, 1411.0]",figure_caption,0.85,"[""figure_title label: Flow diagram outlining the study selection process for the n""]",figure_caption,0.85,body_zone,legend_like,none,True,True
4,0,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[416.0, 69.0, 797.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
4,1,number,31,"[1111.0, 70.0, 1131.0, 87.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,2,image,,"[87.0, 121.0, 1120.0, 649.0]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,True,True
4,3,vision_footnote,"PET/MRI as a Marker of Synovial Inflammation in Knee Osteoarthritis. Representative $ [^{11}C] $-PBR28 PET/MRI images showing tracer uptake of $ [^{11}C] $-PBR28, which binds to the 18-kDa transloca","[88.0, 681.0, 1122.0, 828.0]",footnote,0.7,"[""vision_footnote label: PET/MRI as a Marker of Synovial Inflammation in Knee Osteoar""]",footnote,0.7,,unknown_like,none,True,True
4,4,text,"AI-enhanced radiography demonstrate progress in improving detection, quantification, and interpretation of synovial inflammation. Importantly, these imaging features correlate with pain and function m","[78.0, 862.0, 593.0, 1033.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,5,paragraph_title,Theme #2: infrapatellar fat pad,"[81.0, 1073.0, 313.0, 1096.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Theme #2: infrapatellar fat pad""]",subsection_heading,0.6,body_zone,body_like,none,True,True
4,6,text,Highlighted study: dynamic ultrasound evaluation of the infrapatellar fat pad,"[78.0, 1115.0, 592.0, 1158.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,7,text,Sugimoto et al. [11] advanced the field by assessing real-time morphological changes of the infrapatellar fat pad (IFP) during walking using synchronized ultrasound and 3D motion capture (Fig. 3). In ,"[77.0, 1159.0, 594.0, 1476.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,8,text,,"[619.0, 862.0, 1131.0, 906.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
4,9,text,Additional Key Studies,"[644.0, 906.0, 822.0, 927.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,10,text,• Sex- and BMI-Specific Associations Between Infrapatellar Fat Pad and Symptoms: Wagner et al. [12] found that infrapatellar fat pad abnormalities on MRI were associated with worse self-reported sympt,"[628.0, 946.0, 1133.0, 1115.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,11,text,• Infrapatellar Fat Pad Injury and Cartilage Degeneration: Harris et al. [13] showed that more severe baseline infrapatellar fat pad injury on MRI predicted greater progression of patellofemoral carti,"[627.0, 1115.0, 1134.0, 1242.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,12,text,- Radiomic Infrapatellar Fat Pad Features Predict OA and Symptoms: Khan et al. [14] used radiomics and machine learning on MRIs 10 years post-ACL reconstruction to identify infrapatellar fat pad featu,"[628.0, 1242.0, 1134.0, 1368.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,13,text,• Ultrasound Echo Intensity as a Marker of Symptom Burden: Nakayama et al. [15] reported that higher ultrasound echo intensity in the superficial medial infrapatellar fat pad was linked to knee sympto,"[628.0, 1368.0, 1134.0, 1476.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,0,number,32,"[58.0, 70.0, 79.0, 86.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,1,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[393.0, 69.0, 773.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
5,2,image,,"[255.0, 141.0, 910.0, 755.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
5,3,vision_footnote,Osteoarthritis and Cartilage,"[836.0, 791.0, 1100.0, 824.0]",footnote,0.7,"[""vision_footnote label: Osteoarthritis and Cartilage""]",footnote,0.7,body_zone,unknown_like,none,True,True
5,4,figure_title,Fig. 3,"[76.0, 798.0, 139.0, 822.0]",figure_caption,0.92,"[""figure_title label: Fig. 3""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
5,5,figure_title,Ultrasound-Based Measurement of Infrapatellar Fat Pad Morphology. Schematic representation (left) highlighting the anatomical location of the infrapatellar fat pad relative to the patellar tendon and ,"[66.0, 838.0, 1100.0, 965.0]",figure_caption,0.85,"[""figure_title label: Ultrasound-Based Measurement of Infrapatellar Fat Pad Morpho""]",figure_caption,0.85,body_zone,legend_like,none,True,True
5,6,text,"Theme summary: fat pad imaging links inflammation, mechanics, and clinical symptoms","[56.0, 989.0, 569.0, 1030.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,7,text,This year's studies highlight the multifaceted role of the infrapatellar fat pad in OA as both a biomechanical buffer and an inflammatory organ. By applying novel techniques such as dynamic ultrasound,"[55.0, 1032.0, 571.0, 1307.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,8,paragraph_title,Theme #3: muscle,"[58.0, 1327.0, 193.0, 1346.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Theme #3: muscle""]",subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
5,9,text,Highlighted study: AI-based CT muscle composition and function,"[57.0, 1368.0, 526.0, 1388.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,10,text,Kono et al. [16] used an AI-based approach to analyze CT-derived muscle composition and its relationship to patient-reported outcomes in 43 patients with end-stage knee OA undergoing total knee arthro,"[56.0, 1390.0, 570.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,11,text,,"[595.0, 989.0, 1110.0, 1219.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
5,12,paragraph_title,Additional Key Studies,"[621.0, 1221.0, 798.0, 1241.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Additional Key Studies""]",backmatter_boundary_candidate,0.5,body_zone,body_like,none,True,True
5,13,text,"• Intramuscular Fat and Cartilage Quality: Okada et al. [17] used two-point Dixon MRI to assess intramuscular fat infiltration in the quadriceps and found that greater fat infiltration, particularly i","[604.0, 1263.0, 1110.0, 1410.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,14,text,"• Intramuscular Fat and Muscle Weakness: Gorski et al. [18] used Dixon MRI to show that greater fat infiltration in the gluteus minimus was associated with fiber type shifts, increased collagen","[605.0, 1411.0, 1111.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,0,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[416.0, 69.0, 797.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
6,1,number,33,"[1112.0, 70.0, 1132.0, 87.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,2,figure_title,a,"[111.0, 139.0, 130.0, 160.0]",figure_inner_text,0.9,"[""panel label / figure inner text: a""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
6,3,image,,"[95.0, 170.0, 1113.0, 846.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
6,4,figure_title,b,"[650.0, 134.0, 670.0, 161.0]",figure_inner_text,0.9,"[""panel label / figure inner text: b""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
6,5,figure_title,Fig. 4,"[100.0, 883.0, 162.0, 907.0]",figure_caption,0.92,"[""figure_title label: Fig. 4""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
6,6,figure_title,"Al-Based CT Segmentation and 3D Reconstruction of Lower Limb Muscles. (A) Cross-sectional CT image at the mid-thigh level with AI-based segmentation of individual muscle groups, allowing for quantific","[90.0, 923.0, 1123.0, 1029.0]",figure_caption_candidate,0.85,"[""figure_title label: Al-Based CT Segmentation and 3D Reconstruction of Lower Limb""]",figure_caption,0.85,body_zone,legend_like,none,False,False
6,7,text,"deposition, reduced vastus lateralis activation, and lower knee extensor strength in patients with hip OA.","[101.0, 1049.0, 591.0, 1091.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,8,text,"• Normative Trends in Intramuscular Fat: Joseph et al. [19] used axial MRI data from the Osteoarthritis Initiative to establish normative intramuscular fat values using the Goutallier classification, ","[87.0, 1091.0, 593.0, 1259.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,9,text,"• Ultrasound as a Marker of Muscle Quality: Li et al. [20] showed that quadriceps ultrasound markers (e.g., echo intensity, stiffness) were elevated in knee OA-affected limbs and correlated with radio","[88.0, 1259.0, 592.0, 1367.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,10,text,Theme summary: muscle quality over size as a marker of OA risk and progression,"[80.0, 1389.0, 592.0, 1431.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,11,text,"Across modalities including CT, MRI, and ultrasound, the emerging consensus is that muscle quality, particularly intramuscular fat, is a stronger indicator of OA risk and functional decline than muscl","[79.0, 1432.0, 592.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,12,text,,"[618.0, 1049.0, 1134.0, 1282.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
6,13,paragraph_title,Theme #4: subchondral bone,"[621.0, 1305.0, 834.0, 1327.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Theme #4: subchondral bone""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,14,text,Highlighted study: ShapeMed-knee neural shape model benchmark,"[620.0, 1346.0, 1106.0, 1368.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,15,text,"A key advancement this year was the introduction of the ShapeMed-Knee dataset and benchmark by Gatti et al., $ [21] $ which includes over 9300 femur and cartilage meshes derived from MRI scans. This ","[618.0, 1368.0, 1133.0, 1476.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,0,number,34,"[58.0, 70.0, 79.0, 86.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
7,1,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[393.0, 69.0, 773.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
7,2,image,,"[70.0, 138.0, 1098.0, 435.0]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,True,True
7,3,vision_footnote,Overview of the ShapeMed-Knee Dataset and Neural Shape Model Benchmark Workflow. Orange Box (ShapeMed-Knee Dataset): 9376 knee MRI scans were segmented to generate bone and cartilage anatomical shapes,"[66.0, 446.0, 1098.0, 557.0]",footnote,0.7,"[""vision_footnote label: Overview of the ShapeMed-Knee Dataset and Neural Shape Model""]",footnote,0.7,body_zone,body_like,none,True,True
7,4,vision_footnote,"With permission from: Gatti et al., 2025, IEEE Transactions on Medical Imaging, ©2025 IEEE [21]. No changes were made to the original figure.","[65.0, 554.0, 1096.0, 575.0]",footnote,0.7,"[""vision_footnote label: With permission from: Gatti et al., 2025, IEEE Transactions ""]",footnote,0.7,body_zone,body_like,none,True,True
7,5,text,"reconstruction accuracy compared to traditional statistical shape models (Fig. 5). Specifically, the hybrid model reduced average surface distance errors by over 40% and showed enhanced performance in","[56.0, 611.0, 570.0, 822.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,6,paragraph_title,Additional Key Studies,"[80.0, 822.0, 258.0, 842.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Additional Key Studies""]",backmatter_boundary_candidate,0.5,body_zone,body_like,none,True,True
7,7,text,- CT-Based Subchondral Bone Shape Modeling: Burlison et al. [22] validated the use of CT-based modeling as a reliable alternative to MRI for quantifying distal femoral bone shape. CT-derived subchondr,"[65.0, 863.0, 569.0, 989.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,8,text,- Ultrasound-Based Statistical Shape Modeling: Parmar et al. [23] developed and validated a statistical shape model using ultrasound images of the femoral trochlea to identify shape changes associated,"[64.0, 989.0, 570.0, 1180.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,9,text,• Patellofemoral Subchondral Bone Shape and Malalignment: Demirjian et al. [24] demonstrated that ACL reconstruction patients exhibit altered patellofemoral alignment and femoral trochlear shape using,"[65.0, 1179.0, 569.0, 1284.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,10,text,- Longitudinal Predictive Value of Subchondral Bone Shape: Saxer et al. [25] demonstrated that MRI-derived subchondral bone shape metrics were independently associated with the risk of knee replacemen,"[65.0, 1284.0, 570.0, 1455.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,11,text,,"[605.0, 611.0, 1110.0, 718.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
7,12,text,Theme summary: subchondral bone shape modeling across modalities and clinical contexts,"[595.0, 744.0, 1109.0, 786.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,13,text,"Across modalities including MRI, CT, and ultrasound, recent studies converge on the clinical utility of shape modeling to quantify subchondral bone morphology, track disease progression, and stratify ","[595.0, 787.0, 1111.0, 1061.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,14,paragraph_title,Theme #5: subcutaneous fat,"[597.0, 1094.0, 805.0, 1115.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Theme #5: subcutaneous fat""]",subsection_heading,0.6,body_zone,body_like,none,True,True
7,15,text,Highlighted study: knee-adjacent subcutaneous fat and structural decline,"[596.0, 1137.0, 1109.0, 1178.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,16,text,"Joseph et al., [27] conducted a large-scale cross-sectional analysis using the full Osteoarthritis Initiative baseline MRI dataset (n = 4796) to evaluate whether local subcutaneous fat—defined as adip","[595.0, 1180.0, 1110.0, 1455.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,0,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[416.0, 69.0, 797.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
8,1,number,35,"[1112.0, 70.0, 1132.0, 87.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
8,2,image,,"[249.0, 139.0, 965.0, 556.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True
8,3,figure_title,"MRI-Based Measurement of Knee Subcutaneous Fat Thickness. A coronal reformation of the DESS sequence showing subcutaneous fat thickness measurements at the medial femur, medial tibia, lateral femur, a","[91.0, 635.0, 1122.0, 742.0]",figure_caption,0.85,"[""figure_title label: MRI-Based Measurement of Knee Subcutaneous Fat Thickness. A ""]",figure_caption,0.85,,legend_like,none,True,True
8,4,paragraph_title,Additional Key Studies,"[104.0, 779.0, 280.0, 801.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Additional Key Studies""]",backmatter_boundary_candidate,0.5,,unknown_like,none,True,True
8,5,text,• Subcutaneous Fat and Cartilage Lesions: Hart et al. [28] found that greater subcutaneous fat thickness on knee MRI at one-year post-ACL reconstruction predicted worsening tibiofemoral and patellofem,"[89.0, 820.0, 593.0, 946.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
8,6,text,"• Subcutaneous Fat and Long-Term Symptoms: Michaud et al. [29] found that subcutaneous knee fat thickness decreased on average from one to five years post-ACL reconstruction, while BMI and waist circu","[88.0, 947.0, 593.0, 1094.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
8,7,text,• Subcutaneous Fat Changes Linked to Radiographic Progression: Lee et al. [30] conducted a case-control study of individuals with baseline KL grades 0–3 and found greater two-year increases in thigh s,"[89.0, 1095.0, 592.0, 1242.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
8,8,text,"• Ultrasound Estimation of Body Fat: Tolzman et al. [31] validated a method for estimating body fat using ultrasound-measured thigh fat thickness, accurately predicting DXA-derived body fat in collegi","[87.0, 1242.0, 593.0, 1349.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
8,9,text,Theme summary: local subcutaneous fat as a distinct and actionable imaging marker,"[80.0, 1368.0, 591.0, 1409.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
8,10,text,"Emerging evidence consistently supports that regional subcutaneous fat surrounding the knee, rather than BMI alone, relates to early OA risk, cartilage deterioration, and potentially functional declin","[79.0, 1411.0, 594.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,11,text,,"[618.0, 778.0, 1134.0, 970.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
8,12,paragraph_title,Cross-cutting themes in Oa imaging,"[620.0, 990.0, 910.0, 1011.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Cross-cutting themes in Oa imaging""]",subsection_heading,0.6,body_zone,unknown_like,none,True,True
8,13,text,Recent research in OA imaging has underscored that disease processes extend across multiple joint structures and can be understood through several recurring themes. Building on the studies highlighted,"[618.0, 1031.0, 1134.0, 1287.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
8,14,text,"1. OA affects multiple joint structures. The past year's work reinforces that OA is a condition involving the whole joint, with meaningful imaging findings reported across subchondral bone, effusion-s","[623.0, 1304.0, 1134.0, 1476.0]",body_paragraph,0.6,"[""reference-like pattern: 1. OA affects multiple joint structures. The past year's wor""]",reference_item,0.6,,reference_like,reference_numeric_dot,True,True
9,0,number,36,"[59.0, 71.0, 79.0, 86.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
9,1,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[393.0, 70.0, 773.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
9,2,text,"was linked to symptom burden and radiographic progression $ [6,8,9] $, fat pad changes to altered mechanics and inflammation $ [11–13] $, and muscle quality and local adiposity to structural alterat","[79.0, 107.0, 569.0, 254.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
9,3,text,"2. Inflammation is a unifying OA feature. Inflammatory processes were consistently observed across diverse joint structures using modalities such as PET, ultrasound, and radiography. Over the past yea","[59.0, 254.0, 570.0, 485.0]",body_paragraph,0.6,"[""reference-like pattern: 2. Inflammation is a unifying OA feature. Inflammatory proce""]",reference_item,0.6,,reference_like,reference_numeric_dot,True,True
9,4,text,"3. Accessible tools broaden OA imaging. The use of ultrasound and automated, AI-based image analysis highlights how OA imaging is becoming more scalable and clinically applicable. Quantitative ultraso","[60.0, 485.0, 570.0, 715.0]",body_paragraph,0.6,"[""reference-like pattern: 3. Accessible tools broaden OA imaging. The use of ultrasoun""]",reference_item,0.6,,unknown_like,heading_numbered,True,True
9,5,text,4. Structure and biomechanics are becoming more integrated. A growing number of studies are pairing imaging biomarkers with biomechanical data to examine how tissue-level pathology affects movement an,"[59.0, 716.0, 570.0, 950.0]",body_paragraph,0.6,"[""reference-like pattern: 4. Structure and biomechanics are becoming more integrated. ""]",reference_item,0.6,,reference_like,reference_numeric_dot,True,True
9,6,paragraph_title,Future directions in Oa imaging research,"[57.0, 968.0, 386.0, 990.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Future directions in Oa imaging research""]",subsection_heading,0.6,body_zone,unknown_like,none,True,True
9,7,text,"Building on the insights from recent studies, future directions in OA imaging are focused on translating research advancements into more scalable, predictive, and patient-centered applications. Across","[54.0, 1010.0, 570.0, 1243.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
9,8,text,"1. Clinical integration of AI-driven imaging biomarkers. AI has opened new frontiers in OA imaging by enabling large-scale, automated quantification of structural and compositional features across div","[60.0, 1262.0, 570.0, 1475.0]",body_paragraph,0.6,"[""reference-like pattern: 1. Clinical integration of AI-driven imaging biomarkers. AI ""]",reference_item,0.6,,reference_like,reference_numeric_dot,True,True
9,9,text,,"[618.0, 107.0, 1110.0, 274.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
9,10,text,"2. Track biomechanical drivers of imaging changes. As structural imaging becomes more sensitive and quantitative, there is increasing recognition that biomechanics must be more fully integrated with i","[596.0, 276.0, 1111.0, 632.0]",body_paragraph,0.6,"[""reference-like pattern: 2. Track biomechanical drivers of imaging changes. As struct""]",reference_item,0.6,,reference_like,reference_numeric_dot,True,True
9,11,text,"3. Standardize imaging protocols across modalities. The field of OA imaging is rapidly diversifying, but methodological inconsistency remains a major barrier to synthesis and scalability. For ultrasou","[596.0, 632.0, 1111.0, 1011.0]",body_paragraph,0.6,"[""reference-like pattern: 3. Standardize imaging protocols across modalities. The fiel""]",reference_item,0.6,,reference_like,reference_numeric_dot,True,True
9,12,text,"4. Post-injury imaging to guide precision prevention. Post-traumatic OA remains a major research priority [47], yet a persistent challenge is the heterogeneity in how individuals respond to joint inju","[596.0, 1010.0, 1111.0, 1370.0]",body_paragraph,0.6,"[""reference-like pattern: 4. Post-injury imaging to guide precision prevention. Post-t""]",reference_item,0.6,,reference_like,reference_numeric_dot,True,True
9,13,paragraph_title,Conclusion,"[597.0, 1389.0, 691.0, 1410.0]",section_heading,0.9,"[""explicit scholarly heading: Conclusion""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
9,14,text,"Imaging in the OA field has long recognized OA as a condition involving the whole joint, but recent work highlights rapid advances","[595.0, 1431.0, 1110.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
10,0,header,M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38,"[416.0, 70.0, 796.0, 88.0]",reference_item,0.9,"[""header label""]",noise,0.9,reference_zone,unknown_like,none,True,True
10,1,number,37,"[1112.0, 71.0, 1132.0, 87.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
10,2,text,"in imaging across multiple tissues, underscoring a more comprehensive, systems-level approach to joint assessment. This review highlights recent advances across subchondral bone, muscle, fat pads, syn","[79.0, 107.0, 594.0, 424.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
10,3,paragraph_title,Author contribution,"[80.0, 444.0, 246.0, 465.0]",unknown_structural,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Author contribution""]",subsection_heading,0.6,tail_nonref_hold_zone,unknown_like,short_fragment,False,True
10,4,text,All authors meet the four ICMJE authorship criteria. Each has made substantial contributions to the manuscript and accepts accountability for the accuracy and integrity of the work.,"[80.0, 487.0, 592.0, 551.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
10,5,table,"<table><tr><td>Contribution</td><td>Authors (initials)</td></tr><tr><td>Conception &amp; design of the review</td><td>MH, AG, MJ, MW, HH, JT, AP, IF, TL</td></tr><tr><td>Abstract &amp; title screening","[91.0, 572.0, 581.0, 796.0]",media_asset,0.85,"[""media label: table""]",media_asset,0.85,,reference_like,none,True,True
10,6,text,Osteoarthritis and Cartilage,"[320.0, 827.0, 584.0, 853.0]",structured_insert_candidate,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,False,False
10,7,text,Guarantors of the work:,"[106.0, 925.0, 291.0, 946.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
10,8,paragraph_title,"• Matthew S. Harkey, PhD, ATC (harkeym1@msu.edu)","[89.0, 967.0, 497.0, 989.0]",unknown_structural,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: \u2022 Matthew S. Harkey, PhD, ATC (harkeym1@msu.edu)""]",subsection_heading,0.6,tail_nonref_hold_zone,heading_like,none,False,True
10,9,paragraph_title,Appendix A. Supporting information,"[620.0, 107.0, 916.0, 129.0]",reference_item,0.5,"[""backmatter boundary candidate: Appendix A. Supporting information""]",backmatter_boundary_candidate,0.5,reference_zone,reference_like,citation_line,True,True
10,10,text,"Dr. Harkey takes overall responsibility for the integrity of the work, from inception to published article, and will address any questions regarding its accuracy or integrity.","[80.0, 1009.0, 592.0, 1074.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
10,11,paragraph_title,Declaration of Generative AI and AI-assisted technologies in the writing process,"[80.0, 1093.0, 587.0, 1136.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Declaration of Generative AI and AI-assisted technologies in""]",backmatter_boundary_candidate,0.5,,unknown_like,none,True,True
10,12,text,"During the preparation of this work the author used ChatGPT (OpenAI) to assist with editing and improving the clarity of the manuscript text. After using this tool, the author reviewed and edited the ","[79.0, 1155.0, 593.0, 1263.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
10,13,paragraph_title,Disclosures,"[81.0, 1283.0, 177.0, 1304.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Disclosures""]",sub_subsection_heading,0.6,tail_nonref_hold_zone,unknown_like,short_fragment,True,True
10,14,text,"MSH was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant number: K01 AR081389). AAG is a shareholder of NeuralSeg, GeminiOV, and NodeAI.","[79.0, 1325.0, 591.0, 1390.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
10,15,paragraph_title,Acknowledgements,"[81.0, 1411.0, 240.0, 1431.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements""]",sub_subsection_heading,0.6,tail_nonref_hold_zone,unknown_like,short_fragment,True,True
10,16,text,None.,"[105.0, 1453.0, 155.0, 1473.0]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,,unknown_like,short_fragment,False,True
10,17,text,Supplementary data associated with this article can be found in the online version at doi:10.1016/j.joca.2025.11.004.,"[619.0, 149.0, 1132.0, 192.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,18,paragraph_title,References,"[622.0, 212.0, 713.0, 233.0]",reference_heading,0.9,"[""references heading: References""]",reference_heading,0.9,reference_zone,unknown_like,short_fragment,True,True
10,19,reference_content,"[1] Sa Tang, C. Zhang, W.M. Oo, et al., Osteoarthritis, Nat. Rev. Dis. Prim. 11 (1) (2025) 10, https://doi.org/10.1038/s41572-025-00594-6","[629.0, 252.0, 1132.0, 284.0]",reference_item,0.85,"[""reference content label: [1] Sa Tang, C. Zhang, W.M. Oo, et al., Osteoarthritis, Nat.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
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1 page block_id raw_label content_preview bbox role role_confidence evidence seed_role seed_confidence zone style_family marker_type render_default index_default
2 1 0 header Osteoarthritis and Cartilage 34 (2026) 28–38 [445.0, 68.0, 721.0, 88.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
3 1 1 header Osteoarthritis and Cartilage [55.0, 151.0, 328.0, 243.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
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5 1 3 doc_title Osteoarthritis year in review 2025: Imaging [56.0, 329.0, 618.0, 363.0] paper_title 0.6 ["page-1 frontmatter title guard: Osteoarthritis year in review 2025: Imaging"] paper_title 0.6 frontmatter_main_zone support_like none True True
6 1 4 text Matthew S. Harkey $ {}^{a} $, Anthony A. Gatti $ {}^{b} $, Mylène P. Jansen $ {}^{c} $, McKenzie S. White $ {}^{b} $, Jessica Tolzman $ {}^{a} $, Arjun Parmar $ {}^{a} $, Ian Frederick $ {}^{a} [55.0, 378.0, 909.0, 433.0] authors 0.8 ["page-1 zone author_zone: Matthew S. Harkey $ {}^{a} $, Anthony A. Gatti $ {}^{b} $,"] authors 0.8 body_zone reference_like citation_line True True
7 1 5 image [1049.0, 334.0, 1105.0, 389.0] media_asset 0.85 ["media label: image"] media_asset 0.85 frontmatter_main_zone support_like empty True True
8 1 6 text $ ^{a} $ Department of Kinesiology, Michigan State University, East Lansing, MI, USA [57.0, 441.0, 509.0, 459.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{a} $ Department of Kinesiology, Michigan State Universit"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
9 1 7 text $ ^{b} $ Department of Radiology, Stanford University, Stanford, CA, USA [57.0, 459.0, 442.0, 476.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{b} $ Department of Radiology, Stanford University, Stanf"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
10 1 8 text $ ^{c} $ Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands [57.0, 474.0, 725.0, 492.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{c} $ Department of Rheumatology & Clinical Immunology, U"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
11 1 9 text $ ^{d} $ Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA [57.0, 492.0, 637.0, 509.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{d} $ Department of Radiology and Biomedical Imaging, Uni"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
12 1 10 text $ ^{e} $ La Trobe Sport and Exercise Medicine Research Centre, La Trobe University, Melbourne, VIC, Australia [57.0, 508.0, 652.0, 525.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{e} $ La Trobe Sport and Exercise Medicine Research Centr"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
13 1 11 text School of Physical Therapy, Western University, London, ONT, Canada [57.0, 527.0, 468.0, 544.0] affiliation 0.8 ["page-1 zone affiliation_zone: School of Physical Therapy, Western University, London, ONT,"] affiliation 0.8 frontmatter_main_zone support_like none True True
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15 1 13 text Article history: Received 19 June 2025 Received in revised form 10 October 2025 Accepted 6 November 2025 [57.0, 630.0, 316.0, 700.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Article history:\nReceived 19 June 2025\nReceived in revised f"] frontmatter_noise 0.8 body_zone body_like none False False
16 1 14 text Keywords: Ultrasound Computer Tomography Magnetic resonance imaging Radiography [57.0, 721.0, 236.0, 810.0] frontmatter_noise 0.7 ["frontmatter noise text: Keywords:\nUltrasound\nComputer Tomography\nMagnetic resonance "] frontmatter_noise 0.7 body_zone body_like none False False
17 1 15 paragraph_title A B S T R A C T [390.0, 590.0, 538.0, 610.0] section_heading 0.5 ["unnumbered paragraph_title on page 1 outside title zone: A B S T R A C T"] section_heading 0.5 body_zone body_like short_fragment True True
18 1 16 abstract on how emerging methods and multi-tissue assessments are contributing to disease characterization, early detection, and intervention strategies. Design: We conducted a comprehensive search strategy of [388.0, 657.0, 1111.0, 818.0] body_paragraph 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 body_zone body_like none True True
19 1 17 abstract Results: A total of 26 studies were included. Collectively, the studies reinforce the importance of viewing osteoarthritis as a condition involving multiple joint structures, with inflammation as a re [389.0, 822.0, 1111.0, 955.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 body_zone body_like none True True
20 1 18 abstract Conclusions: Imaging research in the osteoarthritis continues to broaden in scope and application. The studies highlighted in this review illustrate how advances in methods and metrics are improving o [389.0, 954.0, 1109.0, 1030.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 body_zone body_like none True True
21 1 19 text © 2025 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. [408.0, 1030.0, 1109.0, 1071.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: \u00a9 2025 Osteoarthritis Research Society International. Publis"] frontmatter_noise 0.8 body_zone body_like none False False
22 1 20 paragraph_title Introduction [58.0, 1134.0, 163.0, 1154.0] section_heading 0.9 ["explicit scholarly heading: Introduction"] section_heading 0.9 body_zone heading_like canonical_section_name True True
23 1 21 text Osteoarthritis (OA) is a heterogeneous, multi-tissue disease characterized by structural changes, inflammation, and altered joint function $ [1] $. Medical imaging plays a critical role in the assess [56.0, 1176.0, 569.0, 1219.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
24 1 22 text [595.0, 1133.0, 1111.0, 1367.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
25 1 23 footnote $ ^{*} $ Correspondence to: Department of Kinesiology, Michigan State University, 308 W. Circle Drive #112, East Lansing MI, 48824. [57.0, 1261.0, 569.0, 1298.0] footnote 0.7 ["footnote label: $ ^{*} $ Correspondence to: Department of Kinesiology, Michi"] footnote 0.7 body_zone body_like affiliation_marker True True
26 1 24 footnote E-mail addresses: harkeym1@msu.edu (M. Harkey), [72.0, 1297.0, 393.0, 1314.0] footnote 0.7 ["footnote label: E-mail addresses: harkeym1@msu.edu (M. Harkey),"] footnote 0.7 body_zone body_like none True True
27 1 25 footnote aagatti@stanford.edu (A. Gatti), m.p.jansen-36@umcutrecht.nl (M. Jansen), kenziew@stanford.edu (M. White), tolzmanj@msu.edu (J. Tolzman), parmarar@msu.edu (A. Parmar), frede220@msu.edu (I. Frederick), [57.0, 1304.0, 509.0, 1386.0] footnote 0.7 ["footnote label: aagatti@stanford.edu (A. Gatti), m.p.jansen-36@umcutrecht.nl"] footnote 0.7 body_zone body_like none True True
28 1 26 footer https://doi.org/10.1016/j.joca.2025.11.004 [58.0, 1402.0, 307.0, 1419.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
29 1 27 footer 1063-4584/© 2025 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. [55.0, 1417.0, 1111.0, 1455.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
30 2 0 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [416.0, 70.0, 797.0, 88.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
31 2 1 number 29 [1112.0, 70.0, 1132.0, 86.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
32 2 2 text identify imaging features of early disease, defined as changes preceding radiographic OA (Kellgren Lawrence [KL] grade > 1), and to better characterize distinct OA subgroups [3–5]. [78.0, 107.0, 593.0, 170.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
33 2 3 text This narrative review aimed to identify a select number of imaging studies from the past year that highlight emerging trends, novel approaches, and clinical relevance in OA. We acknowledge that many o [79.0, 171.0, 594.0, 424.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
34 2 4 paragraph_title Methods [81.0, 443.0, 156.0, 463.0] section_heading 0.9 ["explicit scholarly heading: Methods"] section_heading 0.9 body_zone heading_like canonical_section_name True True
35 2 5 text To ensure a comprehensive and unbiased selection of studies, we performed a systematic search of PubMed, Embase via EBSCO, and CINAHL via EBSCO for studies on imaging and OA with an initial search on [78.0, 484.0, 594.0, 1012.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
36 2 6 paragraph_title Search results and thematic organization [80.0, 1032.0, 411.0, 1053.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Search results and thematic organization"] subsection_heading 0.6 body_zone body_like none True True
37 2 7 text The initial search yielded 4842 records. After removing duplicates, we screened 3852 titles and abstracts, and 262 full-text studies met the inclusion criteria (Fig. 1). Each full-text article was ind [78.0, 1073.0, 594.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
38 2 8 text [618.0, 107.0, 1135.0, 256.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
39 2 9 paragraph_title Major themes [620.0, 275.0, 738.0, 297.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Major themes"] subsection_heading 0.6 body_zone body_like short_fragment True True
40 2 10 text Theme #1: effusion-synovitis imaging [620.0, 317.0, 896.0, 340.0] unknown_structural 0.8 ["page-1 zone author_zone: Theme #1: effusion-synovitis imaging"] authors 0.8 body_zone body_like none False True
41 2 11 text Highlighted study: [11C]-PBR28 PET as a novel marker of synovial inflammation [618.0, 358.0, 1133.0, 401.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
42 2 12 text Sandström et al. [6] conducted the first in vivo study using [11 C]-PBR28 PET/MRI in knee osteoarthritis (OA) to measure joint inflammation (Fig. 2). The technique targets the 18-kDa translocator prot [619.0, 401.0, 1135.0, 737.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
43 2 13 text Additional Key Studies [644.0, 737.0, 822.0, 758.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
44 2 14 text • Ultrasound Effusion-Synovitis and Gait Asymmetry: Harkey et al. [7] found that 87% of individuals 1–5 years post-ACL reconstruction had ultrasound-detected effusion-synovitis, with higher effusion g [628.0, 778.0, 1134.0, 926.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
45 2 15 text • Early Knee OA Effusion and Symptoms: Mizuno et al. [8] used ultrasound to evaluate joint effusion and reported that even mild effusion in participants with early knee OA was associated with worse sy [628.0, 926.0, 1134.0, 1073.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
46 2 16 text • Synovitis Mediates OA Progression: Deng et al. [9] used longitudinal MRI and mediation modeling to show that synovitis mediates the relationship between medial meniscus extrusion and knee OA progres [628.0, 1074.0, 1133.0, 1179.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
47 2 17 text - AI-Based Effusion Detection on Radiographs: Won et al. [10] developed an AI model to classify knee joint effusion on radiographs, using MRI-defined effusion as the reference standard. The model outp [628.0, 1179.0, 1134.0, 1307.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
48 2 18 text Theme summary: advancing the detection and interpretation of synovial inflammation [620.0, 1326.0, 1085.0, 1369.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
49 2 19 text The past year's work reinforces that effusion-synovitis is not merely an incidental finding but a clinically meaningful feature across the OA spectrum, from post-traumatic populations to early and est [618.0, 1389.0, 1135.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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51 3 1 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [392.0, 69.0, 774.0, 89.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
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53 3 3 figure_title Fig. 1 [77.0, 1306.0, 138.0, 1330.0] figure_caption 0.92 ["figure_title label: Fig. 1"] figure_caption 0.92 display_zone legend_like figure_number True True
54 3 4 figure_title Flow diagram outlining the study selection process for the narrative review. A total of 4842 records were identified through database searches, with 990 duplicates removed and 262 studies assessed as [67.0, 1345.0, 1099.0, 1411.0] figure_caption 0.85 ["figure_title label: Flow diagram outlining the study selection process for the n"] figure_caption 0.85 body_zone legend_like none True True
55 4 0 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [416.0, 69.0, 797.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
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58 4 3 vision_footnote PET/MRI as a Marker of Synovial Inflammation in Knee Osteoarthritis. Representative $ [^{11}C] $-PBR28 PET/MRI images showing tracer uptake of $ [^{11}C] $-PBR28, which binds to the 18-kDa transloca [88.0, 681.0, 1122.0, 828.0] footnote 0.7 ["vision_footnote label: PET/MRI as a Marker of Synovial Inflammation in Knee Osteoar"] footnote 0.7 unknown_like none True True
59 4 4 text AI-enhanced radiography demonstrate progress in improving detection, quantification, and interpretation of synovial inflammation. Importantly, these imaging features correlate with pain and function m [78.0, 862.0, 593.0, 1033.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
60 4 5 paragraph_title Theme #2: infrapatellar fat pad [81.0, 1073.0, 313.0, 1096.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Theme #2: infrapatellar fat pad"] subsection_heading 0.6 body_zone body_like none True True
61 4 6 text Highlighted study: dynamic ultrasound evaluation of the infrapatellar fat pad [78.0, 1115.0, 592.0, 1158.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
62 4 7 text Sugimoto et al. [11] advanced the field by assessing real-time morphological changes of the infrapatellar fat pad (IFP) during walking using synchronized ultrasound and 3D motion capture (Fig. 3). In [77.0, 1159.0, 594.0, 1476.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
63 4 8 text [619.0, 862.0, 1131.0, 906.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
64 4 9 text Additional Key Studies [644.0, 906.0, 822.0, 927.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
65 4 10 text • Sex- and BMI-Specific Associations Between Infrapatellar Fat Pad and Symptoms: Wagner et al. [12] found that infrapatellar fat pad abnormalities on MRI were associated with worse self-reported sympt [628.0, 946.0, 1133.0, 1115.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
66 4 11 text • Infrapatellar Fat Pad Injury and Cartilage Degeneration: Harris et al. [13] showed that more severe baseline infrapatellar fat pad injury on MRI predicted greater progression of patellofemoral carti [627.0, 1115.0, 1134.0, 1242.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
67 4 12 text - Radiomic Infrapatellar Fat Pad Features Predict OA and Symptoms: Khan et al. [14] used radiomics and machine learning on MRIs 10 years post-ACL reconstruction to identify infrapatellar fat pad featu [628.0, 1242.0, 1134.0, 1368.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
68 4 13 text • Ultrasound Echo Intensity as a Marker of Symptom Burden: Nakayama et al. [15] reported that higher ultrasound echo intensity in the superficial medial infrapatellar fat pad was linked to knee sympto [628.0, 1368.0, 1134.0, 1476.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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70 5 1 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [393.0, 69.0, 773.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
71 5 2 image [255.0, 141.0, 910.0, 755.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
72 5 3 vision_footnote Osteoarthritis and Cartilage [836.0, 791.0, 1100.0, 824.0] footnote 0.7 ["vision_footnote label: Osteoarthritis and Cartilage"] footnote 0.7 body_zone unknown_like none True True
73 5 4 figure_title Fig. 3 [76.0, 798.0, 139.0, 822.0] figure_caption 0.92 ["figure_title label: Fig. 3"] figure_caption 0.92 display_zone legend_like figure_number True True
74 5 5 figure_title Ultrasound-Based Measurement of Infrapatellar Fat Pad Morphology. Schematic representation (left) highlighting the anatomical location of the infrapatellar fat pad relative to the patellar tendon and [66.0, 838.0, 1100.0, 965.0] figure_caption 0.85 ["figure_title label: Ultrasound-Based Measurement of Infrapatellar Fat Pad Morpho"] figure_caption 0.85 body_zone legend_like none True True
75 5 6 text Theme summary: fat pad imaging links inflammation, mechanics, and clinical symptoms [56.0, 989.0, 569.0, 1030.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
76 5 7 text This year's studies highlight the multifaceted role of the infrapatellar fat pad in OA as both a biomechanical buffer and an inflammatory organ. By applying novel techniques such as dynamic ultrasound [55.0, 1032.0, 571.0, 1307.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
77 5 8 paragraph_title Theme #3: muscle [58.0, 1327.0, 193.0, 1346.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Theme #3: muscle"] subsection_heading 0.6 body_zone body_like short_fragment True True
78 5 9 text Highlighted study: AI-based CT muscle composition and function [57.0, 1368.0, 526.0, 1388.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
79 5 10 text Kono et al. [16] used an AI-based approach to analyze CT-derived muscle composition and its relationship to patient-reported outcomes in 43 patients with end-stage knee OA undergoing total knee arthro [56.0, 1390.0, 570.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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81 5 12 paragraph_title Additional Key Studies [621.0, 1221.0, 798.0, 1241.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Additional Key Studies"] backmatter_boundary_candidate 0.5 body_zone body_like none True True
82 5 13 text • Intramuscular Fat and Cartilage Quality: Okada et al. [17] used two-point Dixon MRI to assess intramuscular fat infiltration in the quadriceps and found that greater fat infiltration, particularly i [604.0, 1263.0, 1110.0, 1410.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
83 5 14 text • Intramuscular Fat and Muscle Weakness: Gorski et al. [18] used Dixon MRI to show that greater fat infiltration in the gluteus minimus was associated with fiber type shifts, increased collagen [605.0, 1411.0, 1111.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
84 6 0 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [416.0, 69.0, 797.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
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86 6 2 figure_title a [111.0, 139.0, 130.0, 160.0] figure_inner_text 0.9 ["panel label / figure inner text: a"] figure_inner_text 0.9 display_zone legend_like panel_label True True
87 6 3 image [95.0, 170.0, 1113.0, 846.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
88 6 4 figure_title b [650.0, 134.0, 670.0, 161.0] figure_inner_text 0.9 ["panel label / figure inner text: b"] figure_inner_text 0.9 display_zone legend_like panel_label True True
89 6 5 figure_title Fig. 4 [100.0, 883.0, 162.0, 907.0] figure_caption 0.92 ["figure_title label: Fig. 4"] figure_caption 0.92 display_zone legend_like figure_number True True
90 6 6 figure_title Al-Based CT Segmentation and 3D Reconstruction of Lower Limb Muscles. (A) Cross-sectional CT image at the mid-thigh level with AI-based segmentation of individual muscle groups, allowing for quantific [90.0, 923.0, 1123.0, 1029.0] figure_caption_candidate 0.85 ["figure_title label: Al-Based CT Segmentation and 3D Reconstruction of Lower Limb"] figure_caption 0.85 body_zone legend_like none False False
91 6 7 text deposition, reduced vastus lateralis activation, and lower knee extensor strength in patients with hip OA. [101.0, 1049.0, 591.0, 1091.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
92 6 8 text • Normative Trends in Intramuscular Fat: Joseph et al. [19] used axial MRI data from the Osteoarthritis Initiative to establish normative intramuscular fat values using the Goutallier classification, [87.0, 1091.0, 593.0, 1259.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
93 6 9 text • Ultrasound as a Marker of Muscle Quality: Li et al. [20] showed that quadriceps ultrasound markers (e.g., echo intensity, stiffness) were elevated in knee OA-affected limbs and correlated with radio [88.0, 1259.0, 592.0, 1367.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
94 6 10 text Theme summary: muscle quality over size as a marker of OA risk and progression [80.0, 1389.0, 592.0, 1431.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
95 6 11 text Across modalities including CT, MRI, and ultrasound, the emerging consensus is that muscle quality, particularly intramuscular fat, is a stronger indicator of OA risk and functional decline than muscl [79.0, 1432.0, 592.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
96 6 12 text [618.0, 1049.0, 1134.0, 1282.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
97 6 13 paragraph_title Theme #4: subchondral bone [621.0, 1305.0, 834.0, 1327.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Theme #4: subchondral bone"] subsection_heading 0.6 body_zone body_like none True True
98 6 14 text Highlighted study: ShapeMed-knee neural shape model benchmark [620.0, 1346.0, 1106.0, 1368.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
99 6 15 text A key advancement this year was the introduction of the ShapeMed-Knee dataset and benchmark by Gatti et al., $ [21] $ which includes over 9300 femur and cartilage meshes derived from MRI scans. This [618.0, 1368.0, 1133.0, 1476.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
100 7 0 number 34 [58.0, 70.0, 79.0, 86.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
101 7 1 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [393.0, 69.0, 773.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
102 7 2 image [70.0, 138.0, 1098.0, 435.0] media_asset 0.85 ["media label: image"] media_asset 0.85 body_zone body_like empty True True
103 7 3 vision_footnote Overview of the ShapeMed-Knee Dataset and Neural Shape Model Benchmark Workflow. Orange Box (ShapeMed-Knee Dataset): 9376 knee MRI scans were segmented to generate bone and cartilage anatomical shapes [66.0, 446.0, 1098.0, 557.0] footnote 0.7 ["vision_footnote label: Overview of the ShapeMed-Knee Dataset and Neural Shape Model"] footnote 0.7 body_zone body_like none True True
104 7 4 vision_footnote With permission from: Gatti et al., 2025, IEEE Transactions on Medical Imaging, ©2025 IEEE [21]. No changes were made to the original figure. [65.0, 554.0, 1096.0, 575.0] footnote 0.7 ["vision_footnote label: With permission from: Gatti et al., 2025, IEEE Transactions "] footnote 0.7 body_zone body_like none True True
105 7 5 text reconstruction accuracy compared to traditional statistical shape models (Fig. 5). Specifically, the hybrid model reduced average surface distance errors by over 40% and showed enhanced performance in [56.0, 611.0, 570.0, 822.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
106 7 6 paragraph_title Additional Key Studies [80.0, 822.0, 258.0, 842.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Additional Key Studies"] backmatter_boundary_candidate 0.5 body_zone body_like none True True
107 7 7 text - CT-Based Subchondral Bone Shape Modeling: Burlison et al. [22] validated the use of CT-based modeling as a reliable alternative to MRI for quantifying distal femoral bone shape. CT-derived subchondr [65.0, 863.0, 569.0, 989.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
108 7 8 text - Ultrasound-Based Statistical Shape Modeling: Parmar et al. [23] developed and validated a statistical shape model using ultrasound images of the femoral trochlea to identify shape changes associated [64.0, 989.0, 570.0, 1180.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
109 7 9 text • Patellofemoral Subchondral Bone Shape and Malalignment: Demirjian et al. [24] demonstrated that ACL reconstruction patients exhibit altered patellofemoral alignment and femoral trochlear shape using [65.0, 1179.0, 569.0, 1284.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
110 7 10 text - Longitudinal Predictive Value of Subchondral Bone Shape: Saxer et al. [25] demonstrated that MRI-derived subchondral bone shape metrics were independently associated with the risk of knee replacemen [65.0, 1284.0, 570.0, 1455.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
111 7 11 text [605.0, 611.0, 1110.0, 718.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
112 7 12 text Theme summary: subchondral bone shape modeling across modalities and clinical contexts [595.0, 744.0, 1109.0, 786.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
113 7 13 text Across modalities including MRI, CT, and ultrasound, recent studies converge on the clinical utility of shape modeling to quantify subchondral bone morphology, track disease progression, and stratify [595.0, 787.0, 1111.0, 1061.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
114 7 14 paragraph_title Theme #5: subcutaneous fat [597.0, 1094.0, 805.0, 1115.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Theme #5: subcutaneous fat"] subsection_heading 0.6 body_zone body_like none True True
115 7 15 text Highlighted study: knee-adjacent subcutaneous fat and structural decline [596.0, 1137.0, 1109.0, 1178.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
116 7 16 text Joseph et al., [27] conducted a large-scale cross-sectional analysis using the full Osteoarthritis Initiative baseline MRI dataset (n = 4796) to evaluate whether local subcutaneous fat—defined as adip [595.0, 1180.0, 1110.0, 1455.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
117 8 0 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [416.0, 69.0, 797.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
118 8 1 number 35 [1112.0, 70.0, 1132.0, 87.0] noise 0.9 ["page number label"] noise 0.9 unknown_like short_fragment False False
119 8 2 image [249.0, 139.0, 965.0, 556.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 unknown_like empty True True
120 8 3 figure_title MRI-Based Measurement of Knee Subcutaneous Fat Thickness. A coronal reformation of the DESS sequence showing subcutaneous fat thickness measurements at the medial femur, medial tibia, lateral femur, a [91.0, 635.0, 1122.0, 742.0] figure_caption 0.85 ["figure_title label: MRI-Based Measurement of Knee Subcutaneous Fat Thickness. A "] figure_caption 0.85 legend_like none True True
121 8 4 paragraph_title Additional Key Studies [104.0, 779.0, 280.0, 801.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Additional Key Studies"] backmatter_boundary_candidate 0.5 unknown_like none True True
122 8 5 text • Subcutaneous Fat and Cartilage Lesions: Hart et al. [28] found that greater subcutaneous fat thickness on knee MRI at one-year post-ACL reconstruction predicted worsening tibiofemoral and patellofem [89.0, 820.0, 593.0, 946.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
123 8 6 text • Subcutaneous Fat and Long-Term Symptoms: Michaud et al. [29] found that subcutaneous knee fat thickness decreased on average from one to five years post-ACL reconstruction, while BMI and waist circu [88.0, 947.0, 593.0, 1094.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
124 8 7 text • Subcutaneous Fat Changes Linked to Radiographic Progression: Lee et al. [30] conducted a case-control study of individuals with baseline KL grades 0–3 and found greater two-year increases in thigh s [89.0, 1095.0, 592.0, 1242.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
125 8 8 text • Ultrasound Estimation of Body Fat: Tolzman et al. [31] validated a method for estimating body fat using ultrasound-measured thigh fat thickness, accurately predicting DXA-derived body fat in collegi [87.0, 1242.0, 593.0, 1349.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
126 8 9 text Theme summary: local subcutaneous fat as a distinct and actionable imaging marker [80.0, 1368.0, 591.0, 1409.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
127 8 10 text Emerging evidence consistently supports that regional subcutaneous fat surrounding the knee, rather than BMI alone, relates to early OA risk, cartilage deterioration, and potentially functional declin [79.0, 1411.0, 594.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
128 8 11 text [618.0, 778.0, 1134.0, 970.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
129 8 12 paragraph_title Cross-cutting themes in Oa imaging [620.0, 990.0, 910.0, 1011.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Cross-cutting themes in Oa imaging"] subsection_heading 0.6 body_zone unknown_like none True True
130 8 13 text Recent research in OA imaging has underscored that disease processes extend across multiple joint structures and can be understood through several recurring themes. Building on the studies highlighted [618.0, 1031.0, 1134.0, 1287.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
131 8 14 text 1. OA affects multiple joint structures. The past year's work reinforces that OA is a condition involving the whole joint, with meaningful imaging findings reported across subchondral bone, effusion-s [623.0, 1304.0, 1134.0, 1476.0] body_paragraph 0.6 ["reference-like pattern: 1. OA affects multiple joint structures. The past year's wor"] reference_item 0.6 reference_like reference_numeric_dot True True
132 9 0 number 36 [59.0, 71.0, 79.0, 86.0] noise 0.9 ["page number label"] noise 0.9 unknown_like short_fragment False False
133 9 1 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [393.0, 70.0, 773.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
134 9 2 text was linked to symptom burden and radiographic progression $ [6,8,9] $, fat pad changes to altered mechanics and inflammation $ [11–13] $, and muscle quality and local adiposity to structural alterat [79.0, 107.0, 569.0, 254.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
135 9 3 text 2. Inflammation is a unifying OA feature. Inflammatory processes were consistently observed across diverse joint structures using modalities such as PET, ultrasound, and radiography. Over the past yea [59.0, 254.0, 570.0, 485.0] body_paragraph 0.6 ["reference-like pattern: 2. Inflammation is a unifying OA feature. Inflammatory proce"] reference_item 0.6 reference_like reference_numeric_dot True True
136 9 4 text 3. Accessible tools broaden OA imaging. The use of ultrasound and automated, AI-based image analysis highlights how OA imaging is becoming more scalable and clinically applicable. Quantitative ultraso [60.0, 485.0, 570.0, 715.0] body_paragraph 0.6 ["reference-like pattern: 3. Accessible tools broaden OA imaging. The use of ultrasoun"] reference_item 0.6 unknown_like heading_numbered True True
137 9 5 text 4. Structure and biomechanics are becoming more integrated. A growing number of studies are pairing imaging biomarkers with biomechanical data to examine how tissue-level pathology affects movement an [59.0, 716.0, 570.0, 950.0] body_paragraph 0.6 ["reference-like pattern: 4. Structure and biomechanics are becoming more integrated. "] reference_item 0.6 reference_like reference_numeric_dot True True
138 9 6 paragraph_title Future directions in Oa imaging research [57.0, 968.0, 386.0, 990.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Future directions in Oa imaging research"] subsection_heading 0.6 body_zone unknown_like none True True
139 9 7 text Building on the insights from recent studies, future directions in OA imaging are focused on translating research advancements into more scalable, predictive, and patient-centered applications. Across [54.0, 1010.0, 570.0, 1243.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
140 9 8 text 1. Clinical integration of AI-driven imaging biomarkers. AI has opened new frontiers in OA imaging by enabling large-scale, automated quantification of structural and compositional features across div [60.0, 1262.0, 570.0, 1475.0] body_paragraph 0.6 ["reference-like pattern: 1. Clinical integration of AI-driven imaging biomarkers. AI "] reference_item 0.6 reference_like reference_numeric_dot True True
141 9 9 text [618.0, 107.0, 1110.0, 274.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
142 9 10 text 2. Track biomechanical drivers of imaging changes. As structural imaging becomes more sensitive and quantitative, there is increasing recognition that biomechanics must be more fully integrated with i [596.0, 276.0, 1111.0, 632.0] body_paragraph 0.6 ["reference-like pattern: 2. Track biomechanical drivers of imaging changes. As struct"] reference_item 0.6 reference_like reference_numeric_dot True True
143 9 11 text 3. Standardize imaging protocols across modalities. The field of OA imaging is rapidly diversifying, but methodological inconsistency remains a major barrier to synthesis and scalability. For ultrasou [596.0, 632.0, 1111.0, 1011.0] body_paragraph 0.6 ["reference-like pattern: 3. Standardize imaging protocols across modalities. The fiel"] reference_item 0.6 reference_like reference_numeric_dot True True
144 9 12 text 4. Post-injury imaging to guide precision prevention. Post-traumatic OA remains a major research priority [47], yet a persistent challenge is the heterogeneity in how individuals respond to joint inju [596.0, 1010.0, 1111.0, 1370.0] body_paragraph 0.6 ["reference-like pattern: 4. Post-injury imaging to guide precision prevention. Post-t"] reference_item 0.6 reference_like reference_numeric_dot True True
145 9 13 paragraph_title Conclusion [597.0, 1389.0, 691.0, 1410.0] section_heading 0.9 ["explicit scholarly heading: Conclusion"] section_heading 0.9 body_zone heading_like canonical_section_name True True
146 9 14 text Imaging in the OA field has long recognized OA as a condition involving the whole joint, but recent work highlights rapid advances [595.0, 1431.0, 1110.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
147 10 0 header M.S. Harkey et al. / Osteoarthritis and Cartilage 34 (2026) 28–38 [416.0, 70.0, 796.0, 88.0] reference_item 0.9 ["header label"] noise 0.9 reference_zone unknown_like none True True
148 10 1 number 37 [1112.0, 71.0, 1132.0, 87.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
149 10 2 text in imaging across multiple tissues, underscoring a more comprehensive, systems-level approach to joint assessment. This review highlights recent advances across subchondral bone, muscle, fat pads, syn [79.0, 107.0, 594.0, 424.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone body_like none True True
150 10 3 paragraph_title Author contribution [80.0, 444.0, 246.0, 465.0] unknown_structural 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Author contribution"] subsection_heading 0.6 tail_nonref_hold_zone unknown_like short_fragment False True
151 10 4 text All authors meet the four ICMJE authorship criteria. Each has made substantial contributions to the manuscript and accepts accountability for the accuracy and integrity of the work. [80.0, 487.0, 592.0, 551.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
152 10 5 table <table><tr><td>Contribution</td><td>Authors (initials)</td></tr><tr><td>Conception &amp; design of the review</td><td>MH, AG, MJ, MW, HH, JT, AP, IF, TL</td></tr><tr><td>Abstract &amp; title screening [91.0, 572.0, 581.0, 796.0] media_asset 0.85 ["media label: table"] media_asset 0.85 reference_like none True True
153 10 6 text Osteoarthritis and Cartilage [320.0, 827.0, 584.0, 853.0] structured_insert_candidate 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none False False
154 10 7 text Guarantors of the work: [106.0, 925.0, 291.0, 946.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
155 10 8 paragraph_title • Matthew S. Harkey, PhD, ATC (harkeym1@msu.edu) [89.0, 967.0, 497.0, 989.0] unknown_structural 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: \u2022 Matthew S. Harkey, PhD, ATC (harkeym1@msu.edu)"] subsection_heading 0.6 tail_nonref_hold_zone heading_like none False True
156 10 9 paragraph_title Appendix A. Supporting information [620.0, 107.0, 916.0, 129.0] reference_item 0.5 ["backmatter boundary candidate: Appendix A. Supporting information"] backmatter_boundary_candidate 0.5 reference_zone reference_like citation_line True True
157 10 10 text Dr. Harkey takes overall responsibility for the integrity of the work, from inception to published article, and will address any questions regarding its accuracy or integrity. [80.0, 1009.0, 592.0, 1074.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
158 10 11 paragraph_title Declaration of Generative AI and AI-assisted technologies in the writing process [80.0, 1093.0, 587.0, 1136.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Declaration of Generative AI and AI-assisted technologies in"] backmatter_boundary_candidate 0.5 unknown_like none True True
159 10 12 text During the preparation of this work the author used ChatGPT (OpenAI) to assist with editing and improving the clarity of the manuscript text. After using this tool, the author reviewed and edited the [79.0, 1155.0, 593.0, 1263.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone body_like none True True
160 10 13 paragraph_title Disclosures [81.0, 1283.0, 177.0, 1304.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Disclosures"] sub_subsection_heading 0.6 tail_nonref_hold_zone unknown_like short_fragment True True
161 10 14 text MSH was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant number: K01 AR081389). AAG is a shareholder of NeuralSeg, GeminiOV, and NodeAI. [79.0, 1325.0, 591.0, 1390.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
162 10 15 paragraph_title Acknowledgements [81.0, 1411.0, 240.0, 1431.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements"] sub_subsection_heading 0.6 tail_nonref_hold_zone unknown_like short_fragment True True
163 10 16 text None. [105.0, 1453.0, 155.0, 1473.0] unknown_structural 0.3 ["short text, uncertain role"] unknown_structural 0.3 unknown_like short_fragment False True
164 10 17 text Supplementary data associated with this article can be found in the online version at doi:10.1016/j.joca.2025.11.004. [619.0, 149.0, 1132.0, 192.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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audit/49NUE2G7/reference_span_audit.json Normal file
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@ -0,0 +1,604 @@
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547
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@ -0,0 +1,547 @@
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}
}
]
}

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# OCR Truth Audit Report - 53B47JM8
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 2, 6, 7, 8, 9, 11]
- Reviewed blocks: 154
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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page,block_id,raw_label,content_preview,bbox,role,role_confidence,evidence,seed_role,seed_confidence,zone,style_family,marker_type,render_default,index_default
1,0,header_image,,"[73.0, 121.0, 193.0, 228.0]",non_body_insert,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,frontmatter_main_zone,support_like,empty,False,False
1,1,header,Nano Energy 76 (2020) 105028,"[488.0, 68.0, 700.0, 90.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,2,header,ELSEVIER,"[73.0, 233.0, 194.0, 258.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,short_fragment,False,False
1,3,header,Contents lists available at ScienceDirect,"[453.0, 122.0, 742.0, 144.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,4,header,Nano Energy,"[514.0, 171.0, 680.0, 202.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,short_fragment,False,False
1,5,header,journal homepage: http://www.elsevier.com/locate/nanoen,"[372.0, 233.0, 822.0, 256.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,6,header_image,,"[1000.0, 108.0, 1116.0, 253.0]",non_body_insert,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,frontmatter_main_zone,support_like,empty,False,False
1,7,doc_title,Biodegradable nanofiber bone-tissue scaffold as remotely-controlled and self-powering electrical stimulator,"[70.0, 329.0, 947.0, 397.0]",paper_title,0.6,"[""page-1 frontmatter title guard: Biodegradable nanofiber bone-tissue scaffold as remotely-con""]",paper_title,0.6,frontmatter_main_zone,support_like,none,True,True
1,8,image,,"[1001.0, 297.0, 1059.0, 354.0]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,frontmatter_main_zone,support_like,empty,True,True
1,9,text,"Ritopa Das $ ^{a} $, Eli J. Curry $ ^{a,1} $, Thinh T. Le $ ^{b,1} $, Guleid Awale $ ^{c} $, Yang Liu $ ^{b} $, Shunyi Li $ ^{a} $, Joemart Contreras $ ^{a} $, Casey Bednarz $ ^{d} $, Jayla Millender ","[69.0, 417.0, 882.0, 496.0]",authors,0.8,"[""page-1 zone author_zone: Ritopa Das $ ^{a} $, Eli J. Curry $ ^{a,1} $, Thinh T. Le $ ""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
1,10,text," $ ^{a} $ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA","[70.0, 509.0, 576.0, 528.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{a} $ Department of Biomedical Engineering, University of""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,11,text," $ ^{b} $ Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA","[70.0, 527.0, 577.0, 545.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{b} $ Department of Mechanical Engineering, University of""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,12,text," $ ^{c} $ Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA","[70.0, 544.0, 660.0, 562.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{c} $ Department of Chemical and Biomolecular Engineering""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,13,text," $ ^{d} $ Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, 06269, USA","[70.0, 563.0, 608.0, 582.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{d} $ Department of Physiology and Neurobiology, Universi""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,14,text," $ ^{e} $ Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, 06030, USA","[70.0, 577.0, 944.0, 595.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{e} $ Center for Regenerative Medicine and Skeletal Devel""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,15,text," $ ^{1} $ The Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center, Farmington, CT, 06030, USA","[67.0, 594.0, 912.0, 615.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{1} $ The Connecticut Convergence Institute for Translati""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,16,text," $ ^{8} $ Department of Medicine, University of Connecticut Health Center, Farmington, CT, 06030, USA","[71.0, 613.0, 606.0, 629.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{8} $ Department of Medicine, University of Connecticut H""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,17,text," $ ^{h} $ Institute of Materials Science, University of Connecticut, Storrs, CT, 06269, USA","[71.0, 629.0, 525.0, 648.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{h} $ Institute of Materials Science, University of Conne""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,18,paragraph_title,ARTICLE INFO,"[72.0, 695.0, 234.0, 713.0]",section_heading,0.5,"[""unnumbered paragraph_title on page 1 outside title zone: ARTICLE INFO""]",section_heading,0.5,body_zone,body_like,short_fragment,True,True
1,19,text,"Keywords:
Biodegradable piezoelectric nanofibers
Ultrasound
Electrical stimulation
Bone regeneration
Tissue engineering","[71.0, 732.0, 300.0, 839.0]",frontmatter_noise,0.7,"[""frontmatter noise text: Keywords:\nBiodegradable piezoelectric nanofibers\nUltrasound\n""]",frontmatter_noise,0.7,body_zone,body_like,none,False,False
1,20,paragraph_title,A B S T R A C T,"[400.0, 694.0, 522.0, 713.0]",section_heading,0.5,"[""unnumbered paragraph_title on page 1 outside title zone: A B S T R A C T""]",section_heading,0.5,body_zone,body_like,short_fragment,True,True
1,21,abstract,Electrical stimulation (ES) has been shown to induce and enhance bone regeneration. By combining this treatment with tissue-engineering approaches (which rely on biomaterial scaffolds to construct art,"[397.0, 733.0, 1120.0, 966.0]",body_paragraph,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,body_zone,body_like,none,True,True
1,22,paragraph_title,1. Introduction,"[72.0, 1023.0, 198.0, 1043.0]",section_heading,0.85,"[""paragraph_title label with numbering: 1. Introduction""]",section_heading,0.85,body_zone,body_like,heading_numbered,True,True
1,23,text,"Reconstruction of large/major bone defects remains a significant challenge in modern medicine $ [1,2] $. Until now, the gold standard has been to use auto- or allo-grafts, which suffer from problems ","[69.0, 1065.0, 581.0, 1232.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,24,text,"Several biomaterials including hydrogels, naturally-derived biomaterials, synthetic polymers (e.g. poly(lactic-co-glycolic acid), poly(lactic acid), polycaprolactone, etc.) [7–9] in combination with c","[70.0, 1233.0, 581.0, 1276.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,25,text,,"[605.0, 1022.0, 1120.0, 1276.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
1,26,footnote,"* Corresponding author. Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA.","[80.0, 1322.0, 835.0, 1345.0]",footnote,0.7,"[""footnote label: * Corresponding author. Department of Mechanical Engineering""]",footnote,0.7,body_zone,body_like,none,True,True
1,27,footnote,E-mail address: nguyentd@uconn.edu (T.D. Nguyen).,"[81.0, 1342.0, 442.0, 1363.0]",footnote,0.7,"[""footnote label: E-mail address: nguyentd@uconn.edu (T.D. Nguyen).""]",footnote,0.7,body_zone,body_like,none,True,True
1,28,footnote, $ ^{1} $ Denotes equally contributed Authors.,"[81.0, 1361.0, 344.0, 1380.0]",footnote,0.7,"[""footnote label: $ ^{1} $ Denotes equally contributed Authors.""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
1,29,footnote,https://doi.org/10.1016/j.nanoen.2020.105028,"[71.0, 1394.0, 384.0, 1413.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: https://doi.org/10.1016/j.nanoen.2020.105028""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
1,30,footer,"Received 26 March 2020; Received in revised form 6 May 2020; Accepted 27 May 2020
Available online 27 June 2020
2211-2855/© 2020 Elsevier Ltd. All rights reserved.","[70.0, 1405.0, 648.0, 1469.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,0,header,R. Das et al.,"[71.0, 70.0, 146.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,1,header,Nano Energy 76 (2020) 105028,"[937.0, 70.0, 1120.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
2,2,text,render ES limited in clinical applications and combination with tissue engineering approaches.,"[70.0, 107.0, 581.0, 148.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,3,text,"Piezoelectric materials, a group of “smart” materials which produce electricity under applied force, can be used as a self-powered scaffold that can utilize body movements or external mechanical vibra","[68.0, 151.0, 582.0, 609.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,4,text,"Consequently, the development of biodegradable piezoelectric materials becomes important to offer novel biomaterials that can generate electrical charges to promote bone regeneration and safely degrad","[68.0, 610.0, 582.0, 944.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,5,text,"The nanofibers not only offer an extracellular matrix (ECM)-like environment [35–37] but are also biodegradable to avoid the need for any removal procedures and facilitate tissue in-growth, an advance","[68.0, 944.0, 582.0, 1155.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,text,,"[606.0, 107.0, 1120.0, 190.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
2,7,paragraph_title,2. Experimental section,"[607.0, 211.0, 802.0, 232.0]",section_heading,0.85,"[""paragraph_title label with numbering: 2. Experimental section""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
2,8,paragraph_title,2.1. Preparation of PLLA nanofiber mat,"[608.0, 253.0, 893.0, 274.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.1. Preparation of PLLA nanofiber mat""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
2,9,text,"The poly(L-lactic acid) (PLLA) nanofiber mat was fabricated by electrospinning as described in our previous work [32]. PLLA (PUR-ASORB PL38) was purchased from Corbion Purac (Amsterdam, Netherlands). ","[606.0, 295.0, 1120.0, 819.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,10,paragraph_title,2.2. Characterization of PLLA film,"[609.0, 840.0, 857.0, 861.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2. Characterization of PLLA film""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
2,11,text,SEM: Scanning Electron Microscopy (SEM) was performed on mats prepared to observe the orientation of the PLLA fibers and the microstructure of the mats. Square shaped PLLA films with a dimension of 7m,"[606.0, 882.0, 1120.0, 1111.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,12,text,Measurement of the piezoelectric property and ultrasound receiving capability of the PLLA films: A force sensor was fabricated to test the,"[606.0, 1113.0, 1121.0, 1155.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,13,image,,"[74.0, 1184.0, 815.0, 1463.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
2,14,figure_title,"Fig. 1. The use of biodegradable piezoelectric PLLA nanofibers in combination with non-invasive ultrasound (US) to produce well-controlled, on-demand and stable surface charge (i.e. electrical stimula","[826.0, 1179.0, 1119.0, 1466.0]",figure_caption,0.92,"[""figure_title label: Fig. 1. The use of biodegradable piezoelectric PLLA nanofibe""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
2,15,number,2,"[589.0, 1513.0, 603.0, 1528.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,0,header,R. Das et al.,"[71.0, 70.0, 145.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,1,header,Nano Energy 76 (2020) 105028,"[938.0, 70.0, 1120.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,2,text,"piezoelectric property of the PLLA film. The treated PLLA films were cut at a 45° angle with the fiber direction films with a dimension of 1.27 cm long, 1.27 cm wide to maximize the shear force under ","[69.0, 108.0, 582.0, 441.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,3,text,Film degradation study: This study was designed to determine the functional lifetime of the piezoelectric PLLA nanofiber mat. The objective of this experiment is to determine how long the PLLA mat ret,"[69.0, 444.0, 582.0, 1028.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,4,paragraph_title,2.2.1. Preparation of PLLA scaffolds for ADSC culture,"[71.0, 1050.0, 453.0, 1068.0]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.1. Preparation of PLLA scaffolds for ADSC culture""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
3,5,text,The scaffolds were prepared by electrospinning as previously described. The scaffolds used as the experimental group were spun at 3000-rpm and 1000-rpm (i.e. piezoelectric samples and less-piezoelectr,"[69.0, 1070.0, 581.0, 1237.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,6,paragraph_title,2.3. Sterilization of the PLLA scaffolds and preparation of the cell culture plates to seed ADSCs,"[69.0, 1259.0, 569.0, 1300.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3. Sterilization of the PLLA scaffolds and preparation of ""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
3,7,text,"The scaffolds prepared were sterilized using ethanol and UV treatment. The entire process was carried out under a laminar flow cell culture hood. First, the scaffolds were soaked in 70% ethanol for 30","[68.0, 1322.0, 581.0, 1466.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,8,text,"Once the whole process of sterilization was completed, the scaffolds are fixed onto 6-well culture plates (purchased from Thermo Scientific) using biocompatible silicone glue (KWIK-SIL produced by Wor","[92.0, 1468.0, 581.0, 1488.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,9,text,,"[607.0, 107.0, 1120.0, 338.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
3,10,paragraph_title,2.4. ADSC culture,"[609.0, 359.0, 745.0, 379.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4. ADSC culture""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
3,11,text,Cells were seeded onto the PLLA scaffolds after they were sterilized and glued to the well plates. The cells used for this purpose were adipose derived stem cells (ADSCs) that were purchased from iXCe,"[607.0, 399.0, 1119.0, 926.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,12,paragraph_title,2.5. Ultrasonic (US) treatment on the ADSCs,"[608.0, 945.0, 927.0, 965.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.5. Ultrasonic (US) treatment on the ADSCs""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
3,13,text,The US treatment on the cells was started a day after the cells were put in osteogenic media. The treatment was performed using a sonication cleaning bath (Branson 2800 CPX series). The ultrasound pro,"[606.0, 988.0, 1120.0, 1195.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,14,text,"First, we taped the lid onto 4 sides of the plate using labelling tape. Then we removed the plate from the cell hood and encapsulated it in two layers of plastic wrap (Kirkland Signature Stretch-Tite ","[606.0, 1197.0, 1120.0, 1489.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,15,number,3,"[589.0, 1514.0, 603.0, 1528.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,0,header,R. Das et al.,"[72.0, 70.0, 145.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,1,header,Nano Energy 76 (2020) 105028,"[938.0, 70.0, 1120.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
4,2,text,"laboratory clamp, stand apparatus and an alligator clip. The plate was suspended so that it was submerged halfway into the water and horizontally level. The plate was sonicated for 20 min. When the 20","[70.0, 107.0, 581.0, 295.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,3,text,"After 10 days of treatment, the cultures were terminated and analyzed for osteogenic differentiation activity. The assays performed are Alkaline phosphatase (ALP) enzyme quantification, polymerase cha","[69.0, 358.0, 582.0, 527.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,4,paragraph_title,2.6. Bone regeneration assays,"[71.0, 317.0, 284.0, 337.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.6. Bone regeneration assays""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,5,paragraph_title,2.7. BCA assay,"[71.0, 547.0, 188.0, 567.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.7. BCA assay""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,6,text,BCA assay was used to quantify the total protein content of the cultures and this quantity was used to normalize the results of ALP and Alizarin red quantification. Protein was extracted from the cult,"[69.0, 589.0, 582.0, 757.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,7,paragraph_title,2.8. ALP quantification assay,"[71.0, 777.0, 283.0, 798.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.8. ALP quantification assay""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,8,text,The Alkaline phosphatase quantification was carried out using a kit purchased from Biorad (cat no-172-1063). The kit has a p-Nitrophenyl Phosphate (pNPP) based quantification technique. The protein so,"[69.0, 819.0, 582.0, 1051.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,9,paragraph_title,2.9. Alizarin red assay,"[71.0, 1071.0, 237.0, 1091.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.9. Alizarin red assay""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,10,text,"For the Alizarin red assay, the cultures (after removing the media) were fixed in 70% ethanol at 4 °C for 1 h. Following this, the ethanol was removed, the wells were rinsed and the Alizarin red dye (","[69.0, 1112.0, 581.0, 1343.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,11,paragraph_title,2.10. PCR quantification,"[70.0, 1364.0, 251.0, 1385.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.10. PCR quantification""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,12,text,PCR (polymerase chain reaction) quantification was performed using the universal sybr green master mix manufactured by Bio-rad. The primers used were osterix (forward sequence of 5'-GGA AAG GAG GCA CA,"[68.0, 1406.0, 581.0, 1488.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,13,text,,"[607.0, 108.0, 1120.0, 419.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
4,14,paragraph_title,2.11. BMSC reporter cell usage,"[609.0, 442.0, 832.0, 463.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.11. BMSC reporter cell usage""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,15,text,"Apart from our ADSC cultures, we also used a fluorescent reporter cell system to confirm the osteogenic properties of our materials which allowed us to monitor the proliferation and differentiation of","[606.0, 484.0, 1120.0, 736.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,16,paragraph_title,2.12. Preparation of PLLA scaffolds for BMSCs,"[609.0, 756.0, 942.0, 777.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.12. Preparation of PLLA scaffolds for BMSCs""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,17,text,The groups used were the same as those for the ADSC cultures. The scaffolds were prepared by electrospinning as previously described. The scaffolds used as the experimental group were spun at 3000-rpm,"[607.0, 798.0, 1120.0, 925.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,18,paragraph_title,2.13. Sterilization of the PLLA scaffolds and preparation of the cell culture plates to seed BMSCs,"[608.0, 945.0, 1075.0, 987.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.13. Sterilization of the PLLA scaffolds and preparation of""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,19,text,The scaffolds prepared were sterilized using 70% ethanol and UV and attached to 6 well plates using biocompatible silicone glue in the same way as described previously for the ADSC cultures and in viv,"[607.0, 1007.0, 1119.0, 1092.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,20,paragraph_title,2.14. BMSC culture,"[609.0, 1113.0, 756.0, 1133.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.14. BMSC culture""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
4,21,text,Primary BMSCs were harvested from the bone marrow of 3-4-week-old dual transgenic mice containing BSP-GFP-topaz and DMP1-RFP-mCherry fluorescent reporter genes. The hind legs of the mice were harveste,"[607.0, 1154.0, 1120.0, 1490.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,22,number,4,"[590.0, 1514.0, 602.0, 1528.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,0,header,R. Das et al.,"[71.0, 70.0, 145.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,1,header,Nano Energy 76 (2020) 105028,"[937.0, 70.0, 1120.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
5,2,text,"cells were allowed to attach for one day under proliferation media. After that, the proliferation medium was replaced with osteogenic differentiation medium that was prepared by adding 50 $ \mu $g/ml","[70.0, 106.0, 581.0, 233.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,3,paragraph_title,2.15. Ultrasonic (US) treatment on the BMSCs,"[70.0, 253.0, 400.0, 273.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.15. Ultrasonic (US) treatment on the BMSCs""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,4,text,The US treatment was done on the reporter cell seeded scaffolds in the same manner as the ADSC seeded scaffolds. The culture plate was sealed using plastic wrap and duct tape and half suspended into t,"[69.0, 295.0, 582.0, 422.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,5,paragraph_title,2.16. Fluorescence microscopy and image processing,"[70.0, 442.0, 436.0, 463.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.16. Fluorescence microscopy and image processing""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,6,text,"At days 0 (pre-seeding), 1, 2 and 3 of US treatment, reporter cell fluorescence (N = 3) was captured using the Zeiss Axio Observer Z.1 inverted fluorescence microscope. The fluorescence of the cells w","[69.0, 483.0, 582.0, 736.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,7,paragraph_title,2.17. Preparation of PLLA scaffolds for the in vivo experiment on mice,"[71.0, 757.0, 562.0, 777.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.17. Preparation of PLLA scaffolds for the in vivo experime""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,8,text,"The scaffolds used were prepared by electrospinning and then cutting out squares from the electro spun films at the dimensions of $ 4 \, mm \times 4 \, mm $. The scaffolds that were used as the exper","[68.0, 798.0, 581.0, 946.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,9,paragraph_title,2.18. Sterilization of the PLLA scaffolds for the implantation,"[71.0, 966.0, 492.0, 987.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.18. Sterilization of the PLLA scaffolds for the implantati""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,10,text,"The scaffolds prepared were cut into $ 4 \, mm \times 4 \, mm $ pieces and sterilized using 70% ethanol and UV in the same way as described previously for the ADSC cultures.","[69.0, 1008.0, 581.0, 1072.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,11,paragraph_title,2.19. Implantation surgery to demonstrate the osteoinductive property of the PLLA nanofiber film,"[70.0, 1092.0, 571.0, 1133.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.19. Implantation surgery to demonstrate the osteoinductive""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,12,text,The surgical procedure has been approved by the institutional Animal Use Committee (Protocol # 101815-0421). Six transgenic NSG mice containing Collagen 3.6 -GFP-topaz fluorescent genes (Charlse River,"[68.0, 1154.0, 583.0, 1490.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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5,14,paragraph_title,2.20. US treatment on the animals,"[609.0, 295.0, 855.0, 315.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.20. US treatment on the animals""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,15,text,"The US treatment was received by the animals for 30 min a day, 5 days a week, 4 weeks in total. The US transducer used for this experiment was a bolt clamped langevin transducer that operated at 40 kH","[607.0, 337.0, 1120.0, 694.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,16,paragraph_title,2.21. Sample collection,"[609.0, 714.0, 779.0, 734.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.21. Sample collection""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,17,text,"Two weeks after the termination of the US treatment, the animals were euthanized and their calvarial bone (Fig. S2) was harvested to look for evidence of bone regeneration inside the defect.","[607.0, 756.0, 1119.0, 819.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,18,paragraph_title,2.22. Histology,"[609.0, 840.0, 725.0, 861.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.22. Histology""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,19,text,"The harvested calvaria bone was fixed in 10% neutral neutral-buffered formalin (Sigma) at 4 °C overnight, rinsed with PBS (1X) three times, and then soaked in 30% sucrose (Sigma) in deionized water at","[606.0, 882.0, 1120.0, 1238.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,20,paragraph_title,3. Results and discussions,"[609.0, 1259.0, 822.0, 1279.0]",section_heading,0.85,"[""paragraph_title label with numbering: 3. Results and discussions""]",section_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,21,text,"We used electrospinning to create the piezoelectric PLLA nanofiber mats and post-process the films by annealing and cutting at $ 45^{\circ} $ to achieve piezoelectric PLLA nanofibers, following our p","[606.0, 1301.0, 1120.0, 1490.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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6,1,header,Nano Energy 76 (2020) 105028,"[937.0, 70.0, 1120.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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6,6,figure_title,Fig. 2. Characterization of the microstructure and piezoelectric performance of the PLLA nanofiber mats under applied ultrasound (US). a. Schematic of the electrospinning setup used to fabricate the P,"[69.0, 1083.0, 582.0, 1315.0]",figure_caption,0.92,"[""figure_title label: Fig. 2. Characterization of the microstructure and piezoelec""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
6,7,text,"significantly higher output voltage than the ones produced at 1000 rpm while the signal is smallest for the samples made at 300 rpm under the same applied US (see Fig. 2b and c, and S1). Therefore, we","[69.0, 1337.0, 583.0, 1486.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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6,9,text,"Importantly, we carried out in vitro experiments to study osteogenesis of stem cells grown on the scaffolds. Fig. 3a and Fig. S3 describes our in vitro experiment in which we apply US (40 KHz, 20 min/","[607.0, 463.0, 1120.0, 632.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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6,17,figure_title,"Fig. 3. Osteogenic differentiation of stem cells, grown on the piezoelectric PLLA nanofiber scaffold under applied US in vitro. a. A simple schematic demonstrates our setup for seeding adipose stem ce","[606.0, 1241.0, 1120.0, 1488.0]",figure_caption,0.92,"[""figure_title label: Fig. 3. Osteogenic differentiation of stem cells, grown on t""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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7,2,text,"of stem cells for combination with our PLLA nanofibers (if needed in the future) to construct a tissue scaffold. We used three nanofiber films of 3000-rpm (piezo. sample), 1000-rpm (less-piezo. sample","[68.0, 106.0, 583.0, 652.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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7,4,text,"In addition to ADSCs, we also confirmed the ability of our piezoelectric nanofiber scaffold under applied US to induce osteogenesis from bone marrow stem cells (BMSCs) with reporter genes in vitro, as","[606.0, 483.0, 1120.0, 653.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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7,8,figure_title,Fig. 4. Osteogenic activity of reporter bone marrow stem cells (BMSCs) when grown on the electrospun PLLA scaffolds with US treatment. a. Schematic to demonstrate the progressive expression from BSP t,"[799.0, 678.0, 1119.0, 1025.0]",figure_caption,0.92,"[""figure_title label: Fig. 4. Osteogenic activity of reporter bone marrow stem cel""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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8,2,text,electrospun scaffolds (same groups as for the ADSC cultures). Fig. 4a demonstrates schematically the progressive expression from BSP to DMP for the BMSCs that undergo osteogenic differentiation and ch,"[68.0, 106.0, 583.0, 610.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,3,text,"To further demonstrate the osteo-inductive property of the surface charge produced by our biodegradable piezoelectric nanofibers, we performed an in vivo proof of concept experiment, as seen in Fig. 5","[68.0, 609.0, 582.0, 758.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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8,14,figure_title,Fig. 5. Representative histology sections of the mouse calvarial bone showing details of bone formation and cell migration into the defects for the groups of piezo-scaffold (3000 rpm) and non-piezo. s,"[69.0, 1317.0, 1121.0, 1490.0]",figure_caption,0.92,"[""figure_title label: Fig. 5. Representative histology sections of the mouse calva""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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9,0,header,R. Das et al.,"[71.0, 70.0, 145.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
9,1,header,Nano Energy 76 (2020) 105028,"[937.0, 70.0, 1120.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
9,2,text,"osteoblast activity in a region [63,64]. Therefore, the green Collagen 3.6 fluorescent signals allow us to visualize the number of osteoblast-like cells at the defect site. Fig. 5c (iii) clearly shows","[69.0, 107.0, 582.0, 420.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,3,text,"In brief, the in vivo results clearly illustrate that the group 1 with the piezoelectric scaffold and ultrasound (US) strongly induce mineral/bone formation, ALP release and osteoblast migration. Thes","[69.0, 421.0, 581.0, 547.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,4,paragraph_title,4. Conclusions,"[71.0, 567.0, 195.0, 587.0]",section_heading,0.85,"[""paragraph_title label with numbering: 4. Conclusions""]",section_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,5,text,"We have presented a novel tissue electrical-stimulation approach, using the biodegradable piezoelectric PLLA nanofiber scaffold with non-invasive US to generate controllable surface charges, consequen","[68.0, 608.0, 583.0, 985.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
9,6,text,"Despite such a significant advantage, further studies and optimizations of the presented tissue-stimulation approach are still required. First, an optimal amount of piezoelectric charge for osteogenes","[68.0, 986.0, 583.0, 1447.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
9,7,paragraph_title,Data statement,"[609.0, 108.0, 733.0, 127.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Data statement""]",subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
9,8,text,"The experimental data, presented herein, are available for sharing upon a reasonable request.","[607.0, 149.0, 1118.0, 191.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,9,paragraph_title,Declaration of competing interest,"[608.0, 211.0, 875.0, 232.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Declaration of competing interest""]",backmatter_boundary_candidate,0.5,body_zone,body_like,none,True,True
9,10,text,Authors declare no competing interests.,"[632.0, 253.0, 921.0, 273.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,11,paragraph_title,CRediT authorship contribution statement,"[608.0, 294.0, 942.0, 315.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: CRediT authorship contribution statement""]",subsection_heading,0.6,body_zone,body_like,none,True,True
9,12,text,"Ritopa Das: Conceptualization, Methodology, Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Eli J. Curry: Data curation, Formal analysis, Writing - review & editi","[606.0, 337.0, 1120.0, 632.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,13,paragraph_title,Acknowledgements,"[609.0, 651.0, 765.0, 672.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements""]",sub_subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
9,14,text,The work is supported by the NIH (Grant # 1R21AR075196 and # 1R21AR075133). Guleid Awale is supported by NIH (supplementary grant #R21EB024787-02S1). The authors thank Allison Taylor and Jessica Horny,"[607.0, 692.0, 1120.0, 799.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,15,paragraph_title,Appendix A. Supplementary data,"[608.0, 818.0, 875.0, 839.0]",reference_item,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Appendix A. Supplementary data""]",subsection_heading,0.6,reference_zone,reference_like,citation_line,True,True
9,16,text,Supplementary data to this article can be found online at https://doi.org/10.1016/j.nanoen.2020.105028.,"[607.0, 860.0, 1116.0, 902.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,17,paragraph_title,References,"[610.0, 923.0, 700.0, 943.0]",reference_heading,0.9,"[""references heading: References""]",reference_heading,0.9,reference_zone,unknown_like,short_fragment,True,True
9,18,reference_content,"[1] A.R. Amini, C.T. Laurencin, S.P. Nukavarapu, Crit. Rev. Biomed. Eng. 40 (2012) 363–408.","[617.0, 962.0, 1106.0, 993.0]",reference_item,0.85,"[""reference content label: [1] A.R. Amini, C.T. Laurencin, S.P. Nukavarapu, Crit. Rev. ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
9,19,reference_content,"[2] T.W. Bauer, G.F. Muschler, Clin. Orthop. Relat. Res. 371 (2000) 10–27.","[617.0, 996.0, 1059.0, 1013.0]",reference_item,0.85,"[""reference content label: [2] T.W. Bauer, G.F. Muschler, Clin. Orthop. Relat. Res. 371""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
9,20,reference_content,"[3] C. Laurencin, Y. Khan, S.F. El-Amin, Expet Rev. Med. Dev. 3 (2006) 49–57.","[618.0, 1013.0, 1082.0, 1027.0]",reference_item,0.85,"[""reference content label: [3] C. Laurencin, Y. Khan, S.F. El-Amin, Expet Rev. Med. Dev""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
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9,22,reference_content,"[5] C.T. Laurencin, Y. Khan, Regenerative Engineering, American Association for the Advancement of Science, 2012.","[619.0, 1058.0, 1111.0, 1089.0]",reference_item,0.85,"[""reference content label: [5] C.T. Laurencin, Y. Khan, Regenerative Engineering, Ameri""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
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10,38,reference_content,"[58] M. Kharaziha, M.H. Fathi, H. Edris, J. Mech. Behav. Biomed. Mater. 24 (2013) 9–20.","[74.0, 1240.0, 561.0, 1271.0]",reference_item,0.85,"[""reference content label: [58] M. Kharaziha, M.H. Fathi, H. Edris, J. Mech. Behav. Bio""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,39,reference_content,"[59] U. Stachewicz, T. Qiao, S.C.F. Rawlinson, F.V. Almeida, W.-Q. Li, M. Cattell, A. H. Barber, Acta Biomater. 27 (2015) 88–100.","[74.0, 1272.0, 563.0, 1305.0]",reference_item,0.85,"[""reference content label: [59] U. Stachewicz, T. Qiao, S.C.F. Rawlinson, F.V. Almeida,""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,40,reference_content,"[60] T.L. Arinzeh, J. Moy, G.P. Huang, Am. Sci. 105 (2017) 298+.","[74.0, 1304.0, 464.0, 1320.0]",reference_item,0.85,"[""reference content label: [60] T.L. Arinzeh, J. Moy, G.P. Huang, Am. Sci. 105 (2017) 2""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,41,reference_content,"[61] S.M. Damaraju, Y. Shen, E. Elele, B. Khusid, A. Eshghinejad, J. Li, M. Jaffe, T. L. Arinzeh, Biomaterials 149 (2017) 51–62.","[73.0, 1320.0, 559.0, 1350.0]",reference_item,0.85,"[""reference content label: [61] S.M. Damaraju, Y. Shen, E. Elele, B. Khusid, A. Eshghin""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,42,reference_content,"[62] M. Aghajanpoor, S. Hashemi-Najafabadi, M. Baghaban-Eslaminejad, F. Bagheri, S. Mohammad Mousavi, F. Azam Sayyahpour, J. Biomed. Mater. Res. 105 (2017) 1887–1899.","[74.0, 1351.0, 574.0, 1398.0]",reference_item,0.85,"[""reference content label: [62] M. Aghajanpoor, S. Hashemi-Najafabadi, M. Baghaban-Esla""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,43,reference_content,"[63] S. Cremers, P. Garnero, M.J. Seibel, Chapter 87 - biochemical markers of bone metabolism, in: J.P. Bilezikian, L.G. Raisz, T.J. Martin (Eds.), Principles of Bone Biology, third ed., Academic Pres","[74.0, 1399.0, 568.0, 1446.0]",reference_item,0.85,"[""reference content label: [63] S. Cremers, P. Garnero, M.J. Seibel, Chapter 87 - bioch""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,44,reference_content,"[64] J.A. Gordon, C.E. Tye, A.V. Sampaio, T.M. Underhill, G.K. Hunter, H.A. Goldberg, Bone 41 (2007) 462–473.","[73.0, 1447.0, 575.0, 1478.0]",reference_item,0.85,"[""reference content label: [64] J.A. Gordon, C.E. Tye, A.V. Sampaio, T.M. Underhill, G.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,45,reference_content,"[65] J. Jacob, N. More, K. Kalia, G. Kapusetti, Inflamm. Regen. 38 (2018), 2-2.","[612.0, 108.0, 1071.0, 125.0]",reference_item,0.85,"[""reference content label: [65] J. Jacob, N. More, K. Kalia, G. Kapusetti, Inflamm. Reg""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,46,reference_content,"[66] Y. Zhang, T.R. Nayak, H. Hong, W. Cai, Curr. Mol. Med. 13 (2013) 1633–1645.","[612.0, 127.0, 1104.0, 141.0]",reference_item,0.85,"[""reference content label: [66] Y. Zhang, T.R. Nayak, H. Hong, W. Cai, Curr. Mol. Med. ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
10,47,reference_content,"[67] Z.Y. Zhang, Y.D. Xu, Y.Y. Ma, L.L. Qiu, Y. Wang, J.L. Kong, H.M. Xiong, Angew. Chem. Int. Ed. 52 (2013) 4127–4131.","[613.0, 141.0, 1106.0, 170.0]",reference_item,0.85,"[""reference content label: [67] Z.Y. Zhang, Y.D. Xu, Y.Y. Ma, L.L. Qiu, Y. Wang, J.L. K""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
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10,51,figure_title,Eli J. Curry is currently pursuing his Ph.D. in Biomedical Engineering at the University of Connecticut. He also received his B.S. in Biomedical Engineering at the University of Connecticut (2016). Hi,"[759.0, 470.0, 1119.0, 570.0]",reference_item,0.85,"[""figure_title label: Eli J. Curry is currently pursuing his Ph.D. in Biomedical E""]",figure_caption,0.85,reference_zone,reference_like,citation_line,True,True
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10,53,figure_title,"Thinh T. Le received his M.S. degree of mechanical engineering from the Catholic University of America, US in 2017. He is currently pursuing Ph.D. degree in Mechanical Engineering Department, Universi","[759.0, 729.0, 1119.0, 828.0]",reference_item,0.85,"[""figure_title label: Thinh T. Le received his M.S. degree of mechanical engineeri""]",figure_caption,0.85,reference_zone,reference_like,citation_line,True,True
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10,55,vision_footnote,Guleid Awale received his B.S. degree and M.S. degree in Chemical Engineering from the University of Connecticut in 2014 and 2019 respectively. He is currently a Ph.D. candidate in Chemical Engineerin,"[759.0, 987.0, 1120.0, 1102.0]",footnote,0.7,"[""vision_footnote label: Guleid Awale received his B.S. degree and M.S. degree in Che""]",footnote,0.7,,unknown_like,none,True,True
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11,1,header,Nano Energy 76 (2020) 105028,"[937.0, 70.0, 1120.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
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11,3,figure_title,"Yang Liu received his Ph.D degree from Peking University in 2018. He is now a postdoc researcher in the Department of Mechanical Engineering, University of Connecticut. His research interest focuses o","[219.0, 101.0, 584.0, 186.0]",figure_caption_candidate,0.85,"[""figure_title label: Yang Liu received his Ph.D degree from Peking University in ""]",figure_caption,0.85,,legend_like,none,False,False
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11,6,figure_title,"Xiaonan Xin, MD, Ph.D, Currently, an Assistant Research Professor at University of Connecticut Health. She has worked in the field of skeletal biology and regeneration. In her studies, she has establi","[757.0, 103.0, 1120.0, 264.0]",figure_caption,0.85,"[""figure_title label: Xiaonan Xin, MD, Ph.D, Currently, an Assistant Research Prof""]",figure_caption,0.85,,legend_like,none,True,True
11,7,figure_title,"Shunyi Li received her B.S.E. degree in Biomedical Engineering with a Materials Science and Engineering minor from the University of Connecticut in 2020. Currently, she is entering the medical device ","[220.0, 360.0, 582.0, 443.0]",reference_item,0.85,"[""figure_title label: Shunyi Li received her B.S.E. degree in Biomedical Engineeri""]",figure_caption,0.85,reference_zone,legend_like,none,True,True
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11,12,figure_title,Joemart Ian Contreras has a degree in biomedical engineering with a concentration in bioinstrumentation from the University of Connecticut. He is currently pursuing a master's degree in biomedical eng,"[220.0, 617.0, 582.0, 718.0]",figure_caption_candidate,0.85,"[""figure_title label: Joemart Ian Contreras has a degree in biomedical engineering""]",figure_caption,0.85,,legend_like,none,False,False
11,13,figure_title,Dr. David Rowe received his MD from the University of Vermont. Currently he is a Professor of Reconstructive Sciences at UConn Health and the Director of the Center for Regenerative Medicine and Skele,"[758.0, 360.0, 1120.0, 490.0]",figure_caption_candidate,0.85,"[""figure_title label: Dr. David Rowe received his MD from the University of Vermon""]",figure_caption,0.85,,legend_like,none,False,False
11,14,image,,"[613.0, 620.0, 755.0, 821.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True
11,15,figure_title,"Dr. Sharareh Emadi finished her Ph.D. at the Pasteur Institute in France, specializing in Cardiovascular Pharmacology. She is currently an Assistant Professor-In-Residence in the department of Biomedi","[757.0, 618.0, 1120.0, 733.0]",figure_caption_candidate,0.85,"[""figure_title label: Dr. Sharareh Emadi finished her Ph.D. at the Pasteur Institu""]",figure_caption,0.85,,legend_like,none,False,False
11,16,figure_title,Casey E. Bednarz received her B.S. degree in Physiology and Neurobiology from the University of Connecticut in 2019. She is currently working full time and planning to go back and to school to pursue ,"[220.0, 876.0, 582.0, 945.0]",reference_item,0.85,"[""figure_title label: Casey E. Bednarz received her B.S. degree in Physiology and ""]",figure_caption,0.85,reference_zone,reference_like,citation_line,True,True
11,17,figure_title,Dr. Kevin Lo is an Assistant Professor of Medicine at UConn Health. He has held editorial positions on several prestigious journals including PLoS ONE. His research programs include musculoskeletal re,"[758.0, 876.0, 1120.0, 1071.0]",figure_caption,0.85,"[""figure_title label: Dr. Kevin Lo is an Assistant Professor of Medicine at UConn ""]",figure_caption,0.85,,legend_like,none,True,True
11,18,image,,"[611.0, 877.0, 756.0, 1078.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True
11,19,figure_title,Jayla Millender is an honors undergraduate student at the University of Connecticut pursuing degrees in Africana Studies and Molecular and Cellular Biology. Her research focuses on the development of ,"[220.0, 1133.0, 582.0, 1218.0]",figure_caption_candidate,0.85,"[""figure_title label: Jayla Millender is an honors undergraduate student at the Un""]",figure_caption,0.85,,legend_like,none,False,False
11,20,image,,"[613.0, 1136.0, 756.0, 1337.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True
11,21,figure_title,"Dr. Thanh Duc Nguyen received his PhD from Princeton University (2013) and completed his postdoctoral training from Massachusetts Institute of Technology (MIT, 2015). Currently, he is an Assistant Pro","[758.0, 1134.0, 1120.0, 1329.0]",backmatter_body,0.85,"[""figure_title label: Dr. Thanh Duc Nguyen received his PhD from Princeton Univers""]",figure_caption,0.85,,legend_like,none,True,True
11,22,number,11,"[587.0, 1513.0, 604.0, 1529.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
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3 1 1 header Nano Energy 76 (2020) 105028 [488.0, 68.0, 700.0, 90.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
4 1 2 header ELSEVIER [73.0, 233.0, 194.0, 258.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like short_fragment False False
5 1 3 header Contents lists available at ScienceDirect [453.0, 122.0, 742.0, 144.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
6 1 4 header Nano Energy [514.0, 171.0, 680.0, 202.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like short_fragment False False
7 1 5 header journal homepage: http://www.elsevier.com/locate/nanoen [372.0, 233.0, 822.0, 256.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
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9 1 7 doc_title Biodegradable nanofiber bone-tissue scaffold as remotely-controlled and self-powering electrical stimulator [70.0, 329.0, 947.0, 397.0] paper_title 0.6 ["page-1 frontmatter title guard: Biodegradable nanofiber bone-tissue scaffold as remotely-con"] paper_title 0.6 frontmatter_main_zone support_like none True True
10 1 8 image [1001.0, 297.0, 1059.0, 354.0] media_asset 0.85 ["media label: image"] media_asset 0.85 frontmatter_main_zone support_like empty True True
11 1 9 text Ritopa Das $ ^{a} $, Eli J. Curry $ ^{a,1} $, Thinh T. Le $ ^{b,1} $, Guleid Awale $ ^{c} $, Yang Liu $ ^{b} $, Shunyi Li $ ^{a} $, Joemart Contreras $ ^{a} $, Casey Bednarz $ ^{d} $, Jayla Millender [69.0, 417.0, 882.0, 496.0] authors 0.8 ["page-1 zone author_zone: Ritopa Das $ ^{a} $, Eli J. Curry $ ^{a,1} $, Thinh T. Le $ "] authors 0.8 frontmatter_main_zone support_like none True True
12 1 10 text $ ^{a} $ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA [70.0, 509.0, 576.0, 528.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{a} $ Department of Biomedical Engineering, University of"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
13 1 11 text $ ^{b} $ Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA [70.0, 527.0, 577.0, 545.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{b} $ Department of Mechanical Engineering, University of"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
14 1 12 text $ ^{c} $ Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA [70.0, 544.0, 660.0, 562.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{c} $ Department of Chemical and Biomolecular Engineering"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
15 1 13 text $ ^{d} $ Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, 06269, USA [70.0, 563.0, 608.0, 582.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{d} $ Department of Physiology and Neurobiology, Universi"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
16 1 14 text $ ^{e} $ Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, 06030, USA [70.0, 577.0, 944.0, 595.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{e} $ Center for Regenerative Medicine and Skeletal Devel"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
17 1 15 text $ ^{1} $ The Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center, Farmington, CT, 06030, USA [67.0, 594.0, 912.0, 615.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{1} $ The Connecticut Convergence Institute for Translati"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
18 1 16 text $ ^{8} $ Department of Medicine, University of Connecticut Health Center, Farmington, CT, 06030, USA [71.0, 613.0, 606.0, 629.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{8} $ Department of Medicine, University of Connecticut H"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
19 1 17 text $ ^{h} $ Institute of Materials Science, University of Connecticut, Storrs, CT, 06269, USA [71.0, 629.0, 525.0, 648.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{h} $ Institute of Materials Science, University of Conne"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
20 1 18 paragraph_title ARTICLE INFO [72.0, 695.0, 234.0, 713.0] section_heading 0.5 ["unnumbered paragraph_title on page 1 outside title zone: ARTICLE INFO"] section_heading 0.5 body_zone body_like short_fragment True True
21 1 19 text Keywords: Biodegradable piezoelectric nanofibers Ultrasound Electrical stimulation Bone regeneration Tissue engineering [71.0, 732.0, 300.0, 839.0] frontmatter_noise 0.7 ["frontmatter noise text: Keywords:\nBiodegradable piezoelectric nanofibers\nUltrasound\n"] frontmatter_noise 0.7 body_zone body_like none False False
22 1 20 paragraph_title A B S T R A C T [400.0, 694.0, 522.0, 713.0] section_heading 0.5 ["unnumbered paragraph_title on page 1 outside title zone: A B S T R A C T"] section_heading 0.5 body_zone body_like short_fragment True True
23 1 21 abstract Electrical stimulation (ES) has been shown to induce and enhance bone regeneration. By combining this treatment with tissue-engineering approaches (which rely on biomaterial scaffolds to construct art [397.0, 733.0, 1120.0, 966.0] body_paragraph 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 body_zone body_like none True True
24 1 22 paragraph_title 1. Introduction [72.0, 1023.0, 198.0, 1043.0] section_heading 0.85 ["paragraph_title label with numbering: 1. Introduction"] section_heading 0.85 body_zone body_like heading_numbered True True
25 1 23 text Reconstruction of large/major bone defects remains a significant challenge in modern medicine $ [1,2] $. Until now, the gold standard has been to use auto- or allo-grafts, which suffer from problems [69.0, 1065.0, 581.0, 1232.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
26 1 24 text Several biomaterials including hydrogels, naturally-derived biomaterials, synthetic polymers (e.g. poly(lactic-co-glycolic acid), poly(lactic acid), polycaprolactone, etc.) [7–9] in combination with c [70.0, 1233.0, 581.0, 1276.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
27 1 25 text [605.0, 1022.0, 1120.0, 1276.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
28 1 26 footnote * Corresponding author. Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA. [80.0, 1322.0, 835.0, 1345.0] footnote 0.7 ["footnote label: * Corresponding author. Department of Mechanical Engineering"] footnote 0.7 body_zone body_like none True True
29 1 27 footnote E-mail address: nguyentd@uconn.edu (T.D. Nguyen). [81.0, 1342.0, 442.0, 1363.0] footnote 0.7 ["footnote label: E-mail address: nguyentd@uconn.edu (T.D. Nguyen)."] footnote 0.7 body_zone body_like none True True
30 1 28 footnote $ ^{1} $ Denotes equally contributed Authors. [81.0, 1361.0, 344.0, 1380.0] footnote 0.7 ["footnote label: $ ^{1} $ Denotes equally contributed Authors."] footnote 0.7 body_zone body_like affiliation_marker True True
31 1 29 footnote https://doi.org/10.1016/j.nanoen.2020.105028 [71.0, 1394.0, 384.0, 1413.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: https://doi.org/10.1016/j.nanoen.2020.105028"] frontmatter_noise 0.8 body_zone body_like none False False
32 1 30 footer Received 26 March 2020; Received in revised form 6 May 2020; Accepted 27 May 2020 Available online 27 June 2020 2211-2855/© 2020 Elsevier Ltd. All rights reserved. [70.0, 1405.0, 648.0, 1469.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
33 2 0 header R. Das et al. [71.0, 70.0, 146.0, 87.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
34 2 1 header Nano Energy 76 (2020) 105028 [937.0, 70.0, 1120.0, 88.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
35 2 2 text render ES limited in clinical applications and combination with tissue engineering approaches. [70.0, 107.0, 581.0, 148.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
36 2 3 text Piezoelectric materials, a group of “smart” materials which produce electricity under applied force, can be used as a self-powered scaffold that can utilize body movements or external mechanical vibra [68.0, 151.0, 582.0, 609.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
37 2 4 text Consequently, the development of biodegradable piezoelectric materials becomes important to offer novel biomaterials that can generate electrical charges to promote bone regeneration and safely degrad [68.0, 610.0, 582.0, 944.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
38 2 5 text The nanofibers not only offer an extracellular matrix (ECM)-like environment [35–37] but are also biodegradable to avoid the need for any removal procedures and facilitate tissue in-growth, an advance [68.0, 944.0, 582.0, 1155.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
39 2 6 text [606.0, 107.0, 1120.0, 190.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
40 2 7 paragraph_title 2. Experimental section [607.0, 211.0, 802.0, 232.0] section_heading 0.85 ["paragraph_title label with numbering: 2. Experimental section"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
41 2 8 paragraph_title 2.1. Preparation of PLLA nanofiber mat [608.0, 253.0, 893.0, 274.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.1. Preparation of PLLA nanofiber mat"] subsection_heading 0.85 body_zone body_like heading_numbered True True
42 2 9 text The poly(L-lactic acid) (PLLA) nanofiber mat was fabricated by electrospinning as described in our previous work [32]. PLLA (PUR-ASORB PL38) was purchased from Corbion Purac (Amsterdam, Netherlands). [606.0, 295.0, 1120.0, 819.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
43 2 10 paragraph_title 2.2. Characterization of PLLA film [609.0, 840.0, 857.0, 861.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.2. Characterization of PLLA film"] subsection_heading 0.85 body_zone body_like heading_numbered True True
44 2 11 text SEM: Scanning Electron Microscopy (SEM) was performed on mats prepared to observe the orientation of the PLLA fibers and the microstructure of the mats. Square shaped PLLA films with a dimension of 7m [606.0, 882.0, 1120.0, 1111.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
45 2 12 text Measurement of the piezoelectric property and ultrasound receiving capability of the PLLA films: A force sensor was fabricated to test the [606.0, 1113.0, 1121.0, 1155.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
46 2 13 image [74.0, 1184.0, 815.0, 1463.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
47 2 14 figure_title Fig. 1. The use of biodegradable piezoelectric PLLA nanofibers in combination with non-invasive ultrasound (US) to produce well-controlled, on-demand and stable surface charge (i.e. electrical stimula [826.0, 1179.0, 1119.0, 1466.0] figure_caption 0.92 ["figure_title label: Fig. 1. The use of biodegradable piezoelectric PLLA nanofibe"] figure_caption 0.92 display_zone legend_like figure_number True True
48 2 15 number 2 [589.0, 1513.0, 603.0, 1528.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
49 3 0 header R. Das et al. [71.0, 70.0, 145.0, 87.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
50 3 1 header Nano Energy 76 (2020) 105028 [938.0, 70.0, 1120.0, 88.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
51 3 2 text piezoelectric property of the PLLA film. The treated PLLA films were cut at a 45° angle with the fiber direction films with a dimension of 1.27 cm long, 1.27 cm wide to maximize the shear force under [69.0, 108.0, 582.0, 441.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
52 3 3 text Film degradation study: This study was designed to determine the functional lifetime of the piezoelectric PLLA nanofiber mat. The objective of this experiment is to determine how long the PLLA mat ret [69.0, 444.0, 582.0, 1028.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
53 3 4 paragraph_title 2.2.1. Preparation of PLLA scaffolds for ADSC culture [71.0, 1050.0, 453.0, 1068.0] sub_subsection_heading 0.85 ["paragraph_title label with numbering: 2.2.1. Preparation of PLLA scaffolds for ADSC culture"] sub_subsection_heading 0.85 body_zone body_like heading_numbered True True
54 3 5 text The scaffolds were prepared by electrospinning as previously described. The scaffolds used as the experimental group were spun at 3000-rpm and 1000-rpm (i.e. piezoelectric samples and less-piezoelectr [69.0, 1070.0, 581.0, 1237.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
55 3 6 paragraph_title 2.3. Sterilization of the PLLA scaffolds and preparation of the cell culture plates to seed ADSCs [69.0, 1259.0, 569.0, 1300.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.3. Sterilization of the PLLA scaffolds and preparation of "] subsection_heading 0.85 body_zone body_like heading_numbered True True
56 3 7 text The scaffolds prepared were sterilized using ethanol and UV treatment. The entire process was carried out under a laminar flow cell culture hood. First, the scaffolds were soaked in 70% ethanol for 30 [68.0, 1322.0, 581.0, 1466.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
57 3 8 text Once the whole process of sterilization was completed, the scaffolds are fixed onto 6-well culture plates (purchased from Thermo Scientific) using biocompatible silicone glue (KWIK-SIL produced by Wor [92.0, 1468.0, 581.0, 1488.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
58 3 9 text [607.0, 107.0, 1120.0, 338.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
59 3 10 paragraph_title 2.4. ADSC culture [609.0, 359.0, 745.0, 379.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.4. ADSC culture"] subsection_heading 0.85 body_zone body_like heading_numbered True True
60 3 11 text Cells were seeded onto the PLLA scaffolds after they were sterilized and glued to the well plates. The cells used for this purpose were adipose derived stem cells (ADSCs) that were purchased from iXCe [607.0, 399.0, 1119.0, 926.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
61 3 12 paragraph_title 2.5. Ultrasonic (US) treatment on the ADSCs [608.0, 945.0, 927.0, 965.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.5. Ultrasonic (US) treatment on the ADSCs"] subsection_heading 0.85 body_zone body_like heading_numbered True True
62 3 13 text The US treatment on the cells was started a day after the cells were put in osteogenic media. The treatment was performed using a sonication cleaning bath (Branson 2800 CPX series). The ultrasound pro [606.0, 988.0, 1120.0, 1195.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
63 3 14 text First, we taped the lid onto 4 sides of the plate using labelling tape. Then we removed the plate from the cell hood and encapsulated it in two layers of plastic wrap (Kirkland Signature Stretch-Tite [606.0, 1197.0, 1120.0, 1489.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
64 3 15 number 3 [589.0, 1514.0, 603.0, 1528.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
65 4 0 header R. Das et al. [72.0, 70.0, 145.0, 87.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
66 4 1 header Nano Energy 76 (2020) 105028 [938.0, 70.0, 1120.0, 87.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
67 4 2 text laboratory clamp, stand apparatus and an alligator clip. The plate was suspended so that it was submerged halfway into the water and horizontally level. The plate was sonicated for 20 min. When the 20 [70.0, 107.0, 581.0, 295.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
68 4 3 text After 10 days of treatment, the cultures were terminated and analyzed for osteogenic differentiation activity. The assays performed are Alkaline phosphatase (ALP) enzyme quantification, polymerase cha [69.0, 358.0, 582.0, 527.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
69 4 4 paragraph_title 2.6. Bone regeneration assays [71.0, 317.0, 284.0, 337.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.6. Bone regeneration assays"] subsection_heading 0.85 body_zone body_like heading_numbered True True
70 4 5 paragraph_title 2.7. BCA assay [71.0, 547.0, 188.0, 567.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.7. BCA assay"] subsection_heading 0.85 body_zone body_like heading_numbered True True
71 4 6 text BCA assay was used to quantify the total protein content of the cultures and this quantity was used to normalize the results of ALP and Alizarin red quantification. Protein was extracted from the cult [69.0, 589.0, 582.0, 757.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
72 4 7 paragraph_title 2.8. ALP quantification assay [71.0, 777.0, 283.0, 798.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.8. ALP quantification assay"] subsection_heading 0.85 body_zone body_like heading_numbered True True
73 4 8 text The Alkaline phosphatase quantification was carried out using a kit purchased from Biorad (cat no-172-1063). The kit has a p-Nitrophenyl Phosphate (pNPP) based quantification technique. The protein so [69.0, 819.0, 582.0, 1051.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
74 4 9 paragraph_title 2.9. Alizarin red assay [71.0, 1071.0, 237.0, 1091.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.9. Alizarin red assay"] subsection_heading 0.85 body_zone body_like heading_numbered True True
75 4 10 text For the Alizarin red assay, the cultures (after removing the media) were fixed in 70% ethanol at 4 °C for 1 h. Following this, the ethanol was removed, the wells were rinsed and the Alizarin red dye ( [69.0, 1112.0, 581.0, 1343.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
76 4 11 paragraph_title 2.10. PCR quantification [70.0, 1364.0, 251.0, 1385.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.10. PCR quantification"] subsection_heading 0.85 body_zone body_like heading_numbered True True
77 4 12 text PCR (polymerase chain reaction) quantification was performed using the universal sybr green master mix manufactured by Bio-rad. The primers used were osterix (forward sequence of 5'-GGA AAG GAG GCA CA [68.0, 1406.0, 581.0, 1488.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
78 4 13 text [607.0, 108.0, 1120.0, 419.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
79 4 14 paragraph_title 2.11. BMSC reporter cell usage [609.0, 442.0, 832.0, 463.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.11. BMSC reporter cell usage"] subsection_heading 0.85 body_zone body_like heading_numbered True True
80 4 15 text Apart from our ADSC cultures, we also used a fluorescent reporter cell system to confirm the osteogenic properties of our materials which allowed us to monitor the proliferation and differentiation of [606.0, 484.0, 1120.0, 736.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
81 4 16 paragraph_title 2.12. Preparation of PLLA scaffolds for BMSCs [609.0, 756.0, 942.0, 777.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.12. Preparation of PLLA scaffolds for BMSCs"] subsection_heading 0.85 body_zone body_like heading_numbered True True
82 4 17 text The groups used were the same as those for the ADSC cultures. The scaffolds were prepared by electrospinning as previously described. The scaffolds used as the experimental group were spun at 3000-rpm [607.0, 798.0, 1120.0, 925.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
83 4 18 paragraph_title 2.13. Sterilization of the PLLA scaffolds and preparation of the cell culture plates to seed BMSCs [608.0, 945.0, 1075.0, 987.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.13. Sterilization of the PLLA scaffolds and preparation of"] subsection_heading 0.85 body_zone body_like heading_numbered True True
84 4 19 text The scaffolds prepared were sterilized using 70% ethanol and UV and attached to 6 well plates using biocompatible silicone glue in the same way as described previously for the ADSC cultures and in viv [607.0, 1007.0, 1119.0, 1092.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
85 4 20 paragraph_title 2.14. BMSC culture [609.0, 1113.0, 756.0, 1133.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.14. BMSC culture"] subsection_heading 0.85 body_zone body_like heading_numbered True True
86 4 21 text Primary BMSCs were harvested from the bone marrow of 3-4-week-old dual transgenic mice containing BSP-GFP-topaz and DMP1-RFP-mCherry fluorescent reporter genes. The hind legs of the mice were harveste [607.0, 1154.0, 1120.0, 1490.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
87 4 22 number 4 [590.0, 1514.0, 602.0, 1528.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
88 5 0 header R. Das et al. [71.0, 70.0, 145.0, 87.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
89 5 1 header Nano Energy 76 (2020) 105028 [937.0, 70.0, 1120.0, 88.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
90 5 2 text cells were allowed to attach for one day under proliferation media. After that, the proliferation medium was replaced with osteogenic differentiation medium that was prepared by adding 50 $ \mu $g/ml [70.0, 106.0, 581.0, 233.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
91 5 3 paragraph_title 2.15. Ultrasonic (US) treatment on the BMSCs [70.0, 253.0, 400.0, 273.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.15. Ultrasonic (US) treatment on the BMSCs"] subsection_heading 0.85 body_zone body_like heading_numbered True True
92 5 4 text The US treatment was done on the reporter cell seeded scaffolds in the same manner as the ADSC seeded scaffolds. The culture plate was sealed using plastic wrap and duct tape and half suspended into t [69.0, 295.0, 582.0, 422.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
93 5 5 paragraph_title 2.16. Fluorescence microscopy and image processing [70.0, 442.0, 436.0, 463.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.16. Fluorescence microscopy and image processing"] subsection_heading 0.85 body_zone body_like heading_numbered True True
94 5 6 text At days 0 (pre-seeding), 1, 2 and 3 of US treatment, reporter cell fluorescence (N = 3) was captured using the Zeiss Axio Observer Z.1 inverted fluorescence microscope. The fluorescence of the cells w [69.0, 483.0, 582.0, 736.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
95 5 7 paragraph_title 2.17. Preparation of PLLA scaffolds for the in vivo experiment on mice [71.0, 757.0, 562.0, 777.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.17. Preparation of PLLA scaffolds for the in vivo experime"] subsection_heading 0.85 body_zone body_like heading_numbered True True
96 5 8 text The scaffolds used were prepared by electrospinning and then cutting out squares from the electro spun films at the dimensions of $ 4 \, mm \times 4 \, mm $. The scaffolds that were used as the exper [68.0, 798.0, 581.0, 946.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
97 5 9 paragraph_title 2.18. Sterilization of the PLLA scaffolds for the implantation [71.0, 966.0, 492.0, 987.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.18. Sterilization of the PLLA scaffolds for the implantati"] subsection_heading 0.85 body_zone body_like heading_numbered True True
98 5 10 text The scaffolds prepared were cut into $ 4 \, mm \times 4 \, mm $ pieces and sterilized using 70% ethanol and UV in the same way as described previously for the ADSC cultures. [69.0, 1008.0, 581.0, 1072.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
99 5 11 paragraph_title 2.19. Implantation surgery to demonstrate the osteoinductive property of the PLLA nanofiber film [70.0, 1092.0, 571.0, 1133.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.19. Implantation surgery to demonstrate the osteoinductive"] subsection_heading 0.85 body_zone body_like heading_numbered True True
100 5 12 text The surgical procedure has been approved by the institutional Animal Use Committee (Protocol # 101815-0421). Six transgenic NSG mice containing Collagen 3.6 -GFP-topaz fluorescent genes (Charlse River [68.0, 1154.0, 583.0, 1490.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
101 5 13 text [607.0, 108.0, 1120.0, 275.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
102 5 14 paragraph_title 2.20. US treatment on the animals [609.0, 295.0, 855.0, 315.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.20. US treatment on the animals"] subsection_heading 0.85 body_zone body_like heading_numbered True True
103 5 15 text The US treatment was received by the animals for 30 min a day, 5 days a week, 4 weeks in total. The US transducer used for this experiment was a bolt clamped langevin transducer that operated at 40 kH [607.0, 337.0, 1120.0, 694.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
104 5 16 paragraph_title 2.21. Sample collection [609.0, 714.0, 779.0, 734.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.21. Sample collection"] subsection_heading 0.85 body_zone body_like heading_numbered True True
105 5 17 text Two weeks after the termination of the US treatment, the animals were euthanized and their calvarial bone (Fig. S2) was harvested to look for evidence of bone regeneration inside the defect. [607.0, 756.0, 1119.0, 819.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
106 5 18 paragraph_title 2.22. Histology [609.0, 840.0, 725.0, 861.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.22. Histology"] subsection_heading 0.85 body_zone body_like heading_numbered True True
107 5 19 text The harvested calvaria bone was fixed in 10% neutral neutral-buffered formalin (Sigma) at 4 °C overnight, rinsed with PBS (1X) three times, and then soaked in 30% sucrose (Sigma) in deionized water at [606.0, 882.0, 1120.0, 1238.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
108 5 20 paragraph_title 3. Results and discussions [609.0, 1259.0, 822.0, 1279.0] section_heading 0.85 ["paragraph_title label with numbering: 3. Results and discussions"] section_heading 0.85 body_zone body_like heading_numbered True True
109 5 21 text We used electrospinning to create the piezoelectric PLLA nanofiber mats and post-process the films by annealing and cutting at $ 45^{\circ} $ to achieve piezoelectric PLLA nanofibers, following our p [606.0, 1301.0, 1120.0, 1490.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
110 5 22 number 5 [589.0, 1515.0, 602.0, 1528.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
111 6 0 header R. Das et al. [71.0, 70.0, 145.0, 88.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
112 6 1 header Nano Energy 76 (2020) 105028 [937.0, 70.0, 1120.0, 88.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
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116 6 5 chart [157.0, 819.0, 491.0, 1068.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
117 6 6 figure_title Fig. 2. Characterization of the microstructure and piezoelectric performance of the PLLA nanofiber mats under applied ultrasound (US). a. Schematic of the electrospinning setup used to fabricate the P [69.0, 1083.0, 582.0, 1315.0] figure_caption 0.92 ["figure_title label: Fig. 2. Characterization of the microstructure and piezoelec"] figure_caption 0.92 display_zone legend_like figure_number True True
118 6 7 text significantly higher output voltage than the ones produced at 1000 rpm while the signal is smallest for the samples made at 300 rpm under the same applied US (see Fig. 2b and c, and S1). Therefore, we [69.0, 1337.0, 583.0, 1486.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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120 6 9 text Importantly, we carried out in vitro experiments to study osteogenesis of stem cells grown on the scaffolds. Fig. 3a and Fig. S3 describes our in vitro experiment in which we apply US (40 KHz, 20 min/ [607.0, 463.0, 1120.0, 632.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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128 6 17 figure_title Fig. 3. Osteogenic differentiation of stem cells, grown on the piezoelectric PLLA nanofiber scaffold under applied US in vitro. a. A simple schematic demonstrates our setup for seeding adipose stem ce [606.0, 1241.0, 1120.0, 1488.0] figure_caption 0.92 ["figure_title label: Fig. 3. Osteogenic differentiation of stem cells, grown on t"] figure_caption 0.92 display_zone legend_like figure_number True True
129 6 18 number 6 [589.0, 1515.0, 602.0, 1529.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
130 7 0 header R. Das et al. [71.0, 70.0, 145.0, 87.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
131 7 1 header Nano Energy 76 (2020) 105028 [937.0, 70.0, 1120.0, 88.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
132 7 2 text of stem cells for combination with our PLLA nanofibers (if needed in the future) to construct a tissue scaffold. We used three nanofiber films of 3000-rpm (piezo. sample), 1000-rpm (less-piezo. sample [68.0, 106.0, 583.0, 652.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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134 7 4 text In addition to ADSCs, we also confirmed the ability of our piezoelectric nanofiber scaffold under applied US to induce osteogenesis from bone marrow stem cells (BMSCs) with reporter genes in vitro, as [606.0, 483.0, 1120.0, 653.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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137 7 7 chart [425.0, 1133.0, 784.0, 1466.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
138 7 8 figure_title Fig. 4. Osteogenic activity of reporter bone marrow stem cells (BMSCs) when grown on the electrospun PLLA scaffolds with US treatment. a. Schematic to demonstrate the progressive expression from BSP t [799.0, 678.0, 1119.0, 1025.0] figure_caption 0.92 ["figure_title label: Fig. 4. Osteogenic activity of reporter bone marrow stem cel"] figure_caption 0.92 display_zone legend_like figure_number True True
139 7 9 number 7 [589.0, 1514.0, 602.0, 1528.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
140 8 0 header R. Das et al. [71.0, 70.0, 146.0, 87.0] noise 0.9 ["header label"] noise 0.9 unknown_like short_fragment False False
141 8 1 header Nano Energy 76 (2020) 105028 [937.0, 70.0, 1120.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
142 8 2 text electrospun scaffolds (same groups as for the ADSC cultures). Fig. 4a demonstrates schematically the progressive expression from BSP to DMP for the BMSCs that undergo osteogenic differentiation and ch [68.0, 106.0, 583.0, 610.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
143 8 3 text To further demonstrate the osteo-inductive property of the surface charge produced by our biodegradable piezoelectric nanofibers, we performed an in vivo proof of concept experiment, as seen in Fig. 5 [68.0, 609.0, 582.0, 758.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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154 8 14 figure_title Fig. 5. Representative histology sections of the mouse calvarial bone showing details of bone formation and cell migration into the defects for the groups of piezo-scaffold (3000 rpm) and non-piezo. s [69.0, 1317.0, 1121.0, 1490.0] figure_caption 0.92 ["figure_title label: Fig. 5. Representative histology sections of the mouse calva"] figure_caption 0.92 display_zone legend_like figure_number True True
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156 9 0 header R. Das et al. [71.0, 70.0, 145.0, 87.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
157 9 1 header Nano Energy 76 (2020) 105028 [937.0, 70.0, 1120.0, 88.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
158 9 2 text osteoblast activity in a region [63,64]. Therefore, the green Collagen 3.6 fluorescent signals allow us to visualize the number of osteoblast-like cells at the defect site. Fig. 5c (iii) clearly shows [69.0, 107.0, 582.0, 420.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
159 9 3 text In brief, the in vivo results clearly illustrate that the group 1 with the piezoelectric scaffold and ultrasound (US) strongly induce mineral/bone formation, ALP release and osteoblast migration. Thes [69.0, 421.0, 581.0, 547.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
160 9 4 paragraph_title 4. Conclusions [71.0, 567.0, 195.0, 587.0] section_heading 0.85 ["paragraph_title label with numbering: 4. Conclusions"] section_heading 0.85 body_zone body_like heading_numbered True True
161 9 5 text We have presented a novel tissue electrical-stimulation approach, using the biodegradable piezoelectric PLLA nanofiber scaffold with non-invasive US to generate controllable surface charges, consequen [68.0, 608.0, 583.0, 985.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone body_like none True True
162 9 6 text Despite such a significant advantage, further studies and optimizations of the presented tissue-stimulation approach are still required. First, an optimal amount of piezoelectric charge for osteogenes [68.0, 986.0, 583.0, 1447.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone body_like none True True
163 9 7 paragraph_title Data statement [609.0, 108.0, 733.0, 127.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Data statement"] subsection_heading 0.6 body_zone body_like short_fragment True True
164 9 8 text The experimental data, presented herein, are available for sharing upon a reasonable request. [607.0, 149.0, 1118.0, 191.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
165 9 9 paragraph_title Declaration of competing interest [608.0, 211.0, 875.0, 232.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Declaration of competing interest"] backmatter_boundary_candidate 0.5 body_zone body_like none True True
166 9 10 text Authors declare no competing interests. [632.0, 253.0, 921.0, 273.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
167 9 11 paragraph_title CRediT authorship contribution statement [608.0, 294.0, 942.0, 315.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: CRediT authorship contribution statement"] subsection_heading 0.6 body_zone body_like none True True
168 9 12 text Ritopa Das: Conceptualization, Methodology, Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Eli J. Curry: Data curation, Formal analysis, Writing - review & editi [606.0, 337.0, 1120.0, 632.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
169 9 13 paragraph_title Acknowledgements [609.0, 651.0, 765.0, 672.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements"] sub_subsection_heading 0.6 body_zone body_like short_fragment True True
170 9 14 text The work is supported by the NIH (Grant # 1R21AR075196 and # 1R21AR075133). Guleid Awale is supported by NIH (supplementary grant #R21EB024787-02S1). The authors thank Allison Taylor and Jessica Horny [607.0, 692.0, 1120.0, 799.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
171 9 15 paragraph_title Appendix A. Supplementary data [608.0, 818.0, 875.0, 839.0] reference_item 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Appendix A. Supplementary data"] subsection_heading 0.6 reference_zone reference_like citation_line True True
172 9 16 text Supplementary data to this article can be found online at https://doi.org/10.1016/j.nanoen.2020.105028. [607.0, 860.0, 1116.0, 902.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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258 11 6 figure_title Xiaonan Xin, MD, Ph.D, Currently, an Assistant Research Professor at University of Connecticut Health. She has worked in the field of skeletal biology and regeneration. In her studies, she has establi [757.0, 103.0, 1120.0, 264.0] figure_caption 0.85 ["figure_title label: Xiaonan Xin, MD, Ph.D, Currently, an Assistant Research Prof"] figure_caption 0.85 legend_like none True True
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502
audit/62LTMCI8/audit_report.json Normal file
View file

@ -0,0 +1,502 @@
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"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p13:15"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p13:16"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p13:17"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p13:18"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p13:19"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p13:20"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
"p1:4",
"p1:5",
"p1:6",
"p1:11",
"p1:19",
"p1:20",
"p2:0",
"p2:1",
"p3:0",
"p4:0",
"p4:4",
"p5:0",
"p5:2",
"p6:0",
"p7:0",
"p7:5",
"p8:0",
"p8:5",
"p9:0",
"p9:1"
],
"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
"annotated_page": null,
"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

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# OCR Truth Audit Report - 62LTMCI8
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 4, 5, 6, 7, 8, 9, 11, 13]
- Reviewed blocks: 105
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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page,block_id,raw_label,content_preview,bbox,role,role_confidence,evidence,seed_role,seed_confidence,zone,style_family,marker_type,render_default,index_default
1,0,header_image,,"[70.0, 98.0, 237.0, 168.0]",non_body_insert,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,frontmatter_main_zone,support_like,empty,False,False
1,1,header_image,,"[1030.0, 109.0, 1120.0, 169.0]",non_body_insert,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,frontmatter_main_zone,support_like,empty,False,False
1,2,text,Review,"[67.0, 207.0, 134.0, 231.0]",non_body_insert,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,frontmatter_main_zone,support_like,short_fragment,False,False
1,3,doc_title,Electrically Conductive Hydrogels for Articular Cartilage Tissue Engineering,"[66.0, 232.0, 1007.0, 313.0]",paper_title,0.8,"[""page-1 zone title_zone: Electrically Conductive Hydrogels for Articular Cartilage Ti""]",paper_title,0.8,frontmatter_main_zone,support_like,none,True,True
1,4,text,"Filipe Miguel $ ^{1,2} $, Frederico Barbosa $ ^{1,2} $, Frederico Castelo Ferreira $ ^{1,2,*} $ and João Carlos Silva $ ^{1,2,*} $","[66.0, 334.0, 969.0, 362.0]",authors,0.8,"[""page-1 zone author_zone: Filipe Miguel $ ^{1,2} $, Frederico Barbosa $ ^{1,2} $, Fr""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
1,5,text,"iBB—Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa,","[326.0, 402.0, 977.0, 446.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: iBB\u2014Institute for Bioengineering and Biosciences and Departm""]",affiliation,0.8,frontmatter_main_zone,support_like,none,True,True
1,6,text,"2 Associate Laboratory i4HB—Institute for Health and Bioeconomy, Instituto Superior Técnico,","[327.0, 448.0, 1026.0, 476.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: 2 Associate Laboratory i4HB\u2014Institute for Health and Bioecon""]",affiliation,0.8,body_zone,reference_like,reference_numeric_dot,True,True
1,7,text,"check for updates
* Correspondence: frederico.ferreira@tecnico.ulisboa.pt (F.C.F.); joao.f.da.silva@tecnico.ulisboa.pt (J.C.S.)","[70.0, 853.0, 179.0, 889.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: check for updates\n* Correspondence: frederico.ferreira@tecni""]",frontmatter_noise,0.8,frontmatter_main_zone,support_like,none,False,False
1,8,text,,"[327.0, 491.0, 1087.0, 514.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,frontmatter_main_zone,support_like,empty,True,True
1,9,text,"Citation: Miguel, F.; Barbosa, F.; Ferreira, F.C.; Silva, J.C. Electrically Conductive Hydrogels for Articular Cartilage Tissue Engineering. Gels 2022, 8, 710. https://doi.org/10.3390/gels8110710","[66.0, 897.0, 296.0, 1039.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Citation: Miguel, F.; Barbosa, F.; Ferreira, F.C.; Silva, J.""]",frontmatter_noise,0.8,frontmatter_main_zone,support_like,none,False,False
1,10,text,"Received: 4 October 2022
Accepted: 1 November 2022
Published: 3 November 2022","[67.0, 1114.0, 252.0, 1183.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Received: 4 October 2022\nAccepted: 1 November 2022\nPublished""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
1,11,text,Academic Editors: Junfeng Shi and Fei Xu,"[67.0, 1052.0, 291.0, 1097.0]",frontmatter_support,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,12,text,Publisher's Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.,"[66.0, 1197.0, 307.0, 1289.0]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,body_zone,support_like,none,False,False
1,13,image,,"[69.0, 1313.0, 185.0, 1354.0]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
1,14,abstract,"Abstract: Articular cartilage is a highly specialized tissue found in diarthrodial joints, which is crucial for healthy articular motion. Despite its importance, articular cartilage has limited regene","[327.0, 540.0, 1124.0, 878.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,frontmatter_main_zone,support_like,none,True,True
1,15,text,"Copyright: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licen","[66.0, 1363.0, 309.0, 1551.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Copyright: \u00a9 2022 by the authors.\nLicensee MDPI, Basel, Swit""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
1,16,text,,"[326.0, 901.0, 1124.0, 951.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,frontmatter_main_zone,support_like,empty,True,True
1,17,paragraph_title,1. Introduction,"[329.0, 1028.0, 473.0, 1050.0]",section_heading,0.85,"[""paragraph_title label with numbering: 1. Introduction""]",section_heading,0.85,body_zone,heading_like,heading_numbered,True,True
1,18,text,"Articular cartilage (AC) is a highly complex and specialized connective tissue present in diarthrodial joints and is paramount for joint mobility and health. Regarding cell populations, AC is composed","[325.0, 1056.0, 1125.0, 1538.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,19,footer,"Gels 2022, 8, 710. https://doi.org/10.3390/gels8110710","[67.0, 1625.0, 460.0, 1647.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
1,20,footer,https://www.mdpi.com/journal/gels,"[843.0, 1625.0, 1121.0, 1648.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,0,header,"Gels 2022, 8, 710","[67.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,1,header,2 of 18,"[1068.0, 111.0, 1121.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,reference_like,reference_numeric_dot,False,False
2,2,text,"AC has a complex, multilayered structure, with each zone having different densities of chondrocytes, ECM composition and organization, and water content. The superficial zone makes up to 10–20% of tot","[324.0, 192.0, 1124.0, 393.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,3,text,"The intrafibrillar water present within the tissue is able to move through the ECM when the tissue experiences compression, despite existing a high frictional resistance to this flow within the tissue","[324.0, 394.0, 1124.0, 669.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,4,text,"Osteoarthritis (OA) is the most common degenerative joint disorder, characterized by a progressive loss of AC and severe joint pain and stiffness $ [10] $. In fact, it is a leading cause of disabilit","[325.0, 670.0, 1124.0, 870.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,5,text,"Pharmaceutical therapy is the most common option for OA treatment, and largely consists of acetaminophen, non-steroidal anti-inflammatory drugs, opioid analgesics, and serotonin-norepinephrine re-upta","[325.0, 870.0, 1124.0, 1096.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,text,"Considering the unmet medical need for the effective treatment of OA, cartilage tissue engineering (CTE) has emerged as a promising alternative to treat AC defects [17]. CTE employs the use of a bioco","[325.0, 1097.0, 1124.0, 1347.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,7,text,"Concerning the main cell sources used in CTE strategies, mesenchymal stem/stromal cells (MSCs) have been widely explored as an alternative to chondrocytes due to their ready availability from differen","[325.0, 1347.0, 1125.0, 1549.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,1,header,3 of 18,"[1068.0, 111.0, 1121.0, 132.0]",noise,0.9,"[""header label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
3,2,text,"when compared to MSCs isolated from non-joint tissues [21–23]. Moreover, in recent years, alternative cell sources including articular cartilage progenitor cells (ACPCs) and induced pluripotent stem c","[323.0, 192.0, 1124.0, 293.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,3,text,"Various growth factors and other bioactive molecules have been used as candidates to promote cartilage regeneration. For example, TGF- $ \beta $3 has been demonstrated to enhance the chondrogenesis of","[323.0, 294.0, 1125.0, 619.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,4,text,"Hydrogels are highly absorbent polymer networks swollen in large quantities of water, yet maintaining well-defined structures [30]. Biomedical applications of hydrogels started about 60 years ago, and","[323.0, 620.0, 1125.0, 1324.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,5,text,"Hydrogels for CTE strategies have been fabricated using both natural and synthetic polymers. Hydrogels produced from natural polymers (e.g., alginate, gelatin, collagen, hyaluronic acid, chondroitin s","[324.0, 1323.0, 1125.0, 1526.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,1,number,4 of 18,"[1069.0, 111.0, 1121.0, 131.0]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
4,2,text,"mechanical loading), batch-to-batch variability, and difficult processability and control over structural properties and degradation rate [38–40].","[325.0, 192.0, 1123.0, 242.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,3,text,"These extensive customizable features alongside their native-like swelling properties, have allowed the widespread use of hydrogels in CTE strategies [41]. Hydrogels can be designed to be structurally","[324.0, 240.0, 1125.0, 951.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,4,figure_title,Table 1. Examples of hydrogels materials used as injectable systems for CTE applications.,"[327.0, 970.0, 1046.0, 994.0]",table_caption,0.9,"[""table prefix matched: Table 1. Examples of hydrogels materials used as injectable ""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
4,5,table,<table><tr><td>Injectable Hydrogel Material</td><td>Advantages</td><td>Disadvantages</td><td>Refs</td></tr><tr><td>Heparin</td><td>Naturally occurring negatively charged GAG able to interact with ECM ,"[329.0, 1003.0, 1120.0, 1410.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
5,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,1,number,5 of 18,"[1069.0, 111.0, 1121.0, 132.0]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
5,2,figure_title,Table 1. Cont.,"[329.0, 191.0, 443.0, 214.0]",table_caption,0.9,"[""table prefix matched: Table 1. Cont.""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
5,3,table,<table><tr><td>Injectable Hydrogel Material</td><td>Advantages</td><td>Disadvantages</td><td>Refs</td></tr><tr><td>Alginate</td><td>Fast gelationCost-effectiveNon-immunogenicNon-toxic</td><td>Lack of ,"[329.0, 223.0, 1119.0, 799.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
5,4,text,"One of the abovementioned biophysical cues is electrical stimulation, which has been shown to increase the proliferation of chondrocytes and secretion of ECM molecules, accelerating the repair of cart","[325.0, 830.0, 1125.0, 1081.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,5,text,"In this review, a summary of the conductive biomaterials that have been utilized in conjunction with hydrogels is presented. The current state of development of electrically conductive hydrogels for A","[326.0, 1081.0, 1125.0, 1183.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,1,number,6 of 18,"[1069.0, 111.0, 1122.0, 132.0]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
6,2,image,,"[164.0, 184.0, 1023.0, 1031.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
6,3,figure_title,Figure 1. Electrically conductive hydrogels as a promising tool for the repair of articular cartilage defects caused by trauma or debilitating diseases such as osteoarthritis (top). These functional c,"[325.0, 1054.0, 1123.0, 1133.0]",figure_caption,0.92,"[""figure_title label: Figure 1. Electrically conductive hydrogels as a promising t""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
6,4,paragraph_title,2. Electrical Properties of Articular Cartilage Tissue,"[327.0, 1146.0, 803.0, 1171.0]",section_heading,0.85,"[""paragraph_title label with numbering: 2. Electrical Properties of Articular Cartilage Tissue""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
6,5,text,"AC has intrinsic electrical/electrochemical properties, derived from the flow of free electrolytes (K⁺, Ca²⁺, Na⁺) through the fixed negative charges of carboxyl and sulfate groups attached to the GAG","[325.0, 1178.0, 1125.0, 1455.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,6,paragraph_title,3. Conductive Materials for Tissue Engineering,"[327.0, 1473.0, 768.0, 1498.0]",section_heading,0.85,"[""paragraph_title label with numbering: 3. Conductive Materials for Tissue Engineering""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
6,7,text,A great variety of conductive materials can be implemented with hydrogels in order to create electrically conductive scaffolds. These platforms are invaluable for CTE as they can,"[326.0, 1505.0, 1124.0, 1555.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
7,1,number,7 of 18,"[1068.0, 110.0, 1121.0, 132.0]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
7,2,text,"provide not only native-like physical properties, but are responsive to relevant biophysical cues such as electrical stimulation, simulating a more physiological environment. Despite some combinations","[324.0, 192.0, 1124.0, 368.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,3,paragraph_title,3.1. Metallic Nanoparticles,"[329.0, 387.0, 558.0, 411.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.1. Metallic Nanoparticles""]",subsection_heading,0.85,body_zone,heading_like,heading_numbered,True,True
7,4,text,"Metallic nanoparticles are electrically conductive nanosized particles, with a metal core shelled by an inorganic or organic metal or metal oxide, behaving differently according to their size, shape, ","[324.0, 417.0, 1125.0, 1125.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,5,figure_title,Table 2. Properties and applications of metallic nanoparticles.,"[327.0, 1147.0, 824.0, 1171.0]",table_caption,0.9,"[""table prefix matched: Table 2. Properties and applications of metallic nanoparticl""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
7,6,table,<table><tr><td>Nanoparticle Material</td><td>Advantages</td><td>Disadvantages</td><td>Applications</td><td>References</td></tr><tr><td>Gold nanoparticles (Au NPs)</td><td>Low initial cytotoxicityHigh ,"[67.0, 1184.0, 1118.0, 1521.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
8,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
8,1,number,8 of 18,"[1069.0, 111.0, 1121.0, 131.0]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
8,2,paragraph_title,3.2. Graphene-Based Materials and Carbon Nanotubes,"[327.0, 192.0, 778.0, 217.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2. Graphene-Based Materials and Carbon Nanotubes""]",subsection_heading,0.85,body_zone,heading_like,heading_numbered,True,True
8,3,text,Both graphene and carbon nanotubes (CNTs) are conductive materials with high tensile strengths that can be employed to reinforce and provide conductivity to hydrogel biomatrices with a broad range of ,"[324.0, 223.0, 1125.0, 500.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,4,text,"CNTs are cylindrical shaped tubes with nanosized diameters. Due to their high tensile strength, excellent electric and thermal conductivity, their coupling with hydrogel matrices has seen a widespread","[324.0, 499.0, 1126.0, 905.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,5,figure_title,Table 3. Properties and applications of graphene and carbon nanotubes.,"[326.0, 927.0, 907.0, 950.0]",table_caption,0.9,"[""table prefix matched: Table 3. Properties and applications of graphene and carbon ""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
8,6,table,"<table><tr><td>Carbon Type</td><td>Advantages</td><td>Disadvantages</td><td>Applications</td><td>References</td></tr><tr><td rowspan=""3"">Graphene</td><td>High mechanical strength</td><td>Oxidative str","[67.0, 964.0, 1119.0, 1149.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
8,7,paragraph_title,3.3. Conductive Polymers,"[328.0, 1180.0, 546.0, 1205.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.3. Conductive Polymers""]",subsection_heading,0.85,body_zone,heading_like,heading_numbered,True,True
8,8,text,Conductive polymers are organic polymers with unique mechanical and optical properties. They have characteristics similar to some metals and inorganic semiconductors while maintaining characteristic p,"[324.0, 1210.0, 1127.0, 1566.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,0,header,"Gels 2022, 8, 710","[67.0, 111.0, 187.0, 132.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
9,1,number,9 of 18,"[1068.0, 111.0, 1122.0, 131.0]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
9,2,text,gies both as coating material and mixed with other biomaterials [123–126]. Our group has recently showed that PEDOT:PSS coated polybenzimidazole nanofibers were able to promote the adhesion and prolif,"[324.0, 192.0, 1126.0, 446.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,3,figure_title,Table 4. Properties and applications of main conductive polymers.,"[326.0, 467.0, 863.0, 491.0]",table_caption,0.9,"[""table prefix matched: Table 4. Properties and applications of main conductive poly""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
9,4,table,<table><tr><td>Conductive Polymer Type</td><td>Advantages</td><td>Disadvantages</td><td>Applications</td><td>References</td></tr><tr><td>Polyaniline (PANi)</td><td>High stabilityHigh conductivity</td>,"[68.0, 506.0, 1119.0, 805.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
9,5,paragraph_title,4. Electrically Conductive Hydrogels for Articular Cartilage Tissue Engineering,"[327.0, 835.0, 1059.0, 860.0]",section_heading,0.85,"[""paragraph_title label with numbering: 4. Electrically Conductive Hydrogels for Articular Cartilage""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
9,6,text,"The fabrication of hydrogels with different materials and properties as cartilage-healing constructs is well documented. However, recently there has been an emergence of a few research studies trying ","[323.0, 866.0, 1125.0, 1092.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,7,text,"The underlying mechanisms through which endogenous or external electrical stimuli influence cell behavior are still poorly described. However, the alteration of cell membrane resting potential by elec","[324.0, 1093.0, 1126.0, 1494.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,8,text,"When designing conductive hydrogel scaffolds as cartilage substitutes, some parameters are necessary to consider in order to correctly recapitulating the native environment, including the mechanical s","[326.0, 1495.0, 1127.0, 1572.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
10,1,header,10 of 18,"[1062.0, 111.0, 1122.0, 132.0]",noise,0.9,"[""header label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
10,2,text,"ibility. Despite literature on this topic being scarce, the existing results are highly promising, highlighting the potential of electrically conductive hydrogels for improved CTE strategies (Table 5)","[325.0, 192.0, 1123.0, 266.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,3,text,"Zhang et al., produced a poly(vinyl alcohol) (PVA) hydrogel combined with sodium phytate (PANa), which conferred conductivity and excellent mechanical properties to the hydrogel [141]. The mechanical ","[323.0, 269.0, 1124.0, 645.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,4,text,"In a different study, Shen and colleagues investigated the chondrogenic inducing potential of a graphene oxide (GO) containing poly-D,L-lactic acid/polyethylene glycol (PDLLA) nanocomposite hydrogel [","[325.0, 644.0, 1124.0, 1071.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,5,text,3D printing allows layer-by-layer development of 3D structures and the fabrication of complex scaffolds in a fast and reproducible manner. Given that this technique enables a precise control over the ,"[325.0, 1071.0, 1126.0, 1525.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,0,header,"Gels 2022, 8, 710","[67.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
11,1,header,11 of 18,"[1061.0, 111.0, 1122.0, 132.0]",noise,0.9,"[""header label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
11,2,figure_title,Table 5. Summary of research studies on electrically conductive hydrogels for AC tissue engineering.,"[326.0, 192.0, 1122.0, 216.0]",table_caption,0.9,"[""table prefix matched: Table 5. Summary of research studies on electrically conduct""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
11,3,table,<table><tr><td>Hydrogel</td><td>Conductive Filler</td><td>Main Outcomes</td><td>References</td></tr><tr><td>Poly(vinyl alcohol) (PVA)</td><td>Sodium phytate (PANa)</td><td>Easy to produce and cost-eff,"[328.0, 223.0, 1119.0, 844.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
11,4,paragraph_title,5. Challenges and Future Perspectives,"[328.0, 874.0, 683.0, 897.0]",section_heading,0.85,"[""paragraph_title label with numbering: 5. Challenges and Future Perspectives""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
11,5,text,The promising results observed in the few studies developing electrically conductive hydrogels for AC regeneration highlight its potential as a suitable culture platform for improved CTE strategies. H,"[324.0, 903.0, 1125.0, 1382.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,6,text,"Another challenge limiting the application of conductive hydrogels in regenerative medicine is their low processability by 3D additive manufacturing techniques. In fact, the fabrication of complex str","[325.0, 1381.0, 1126.0, 1535.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,0,header,"Gels 2022, 8, 710","[68.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
12,1,number,12 of 18,"[1062.0, 111.0, 1122.0, 132.0]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
12,2,text,structures should be explored with high potential for introducing major advances in AC and osteochondral tissue engineering.,"[326.0, 192.0, 1122.0, 241.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,3,text,"Furthermore, a deeper understanding of the tissue's electrical properties is necessary in order to successfully mimic the AC's native niche and achieve proper regeneration outcomes. Novel methods to d","[325.0, 243.0, 1125.0, 721.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,4,paragraph_title,6. Conclusions,"[329.0, 740.0, 471.0, 763.0]",section_heading,0.85,"[""paragraph_title label with numbering: 6. Conclusions""]",section_heading,0.85,body_zone,heading_like,heading_numbered,True,True
12,5,text,"CTE has emerged as an exciting alternative to the current ineffective treatments for cartilage damage and degeneration, as in cases of OA. In particular, the development of electrically conductive hyd","[326.0, 770.0, 1124.0, 895.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,6,text,"In summary, this review provides an overview of the most common conductive materials that have been combined with hydrogels for tissue engineering and other biomedical applications. Conductive materia","[325.0, 896.0, 1125.0, 1201.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,7,text,"Author Contributions: Conceptualization: F.M., F.C.F. and J.C.S.; investigation: F.M. and J.C.S.; writing—original draft preparation: F.M., F.B. and J.C.S.; writing—review and editing: F.M., F.B., F.C","[326.0, 1220.0, 1124.0, 1316.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,support_like,none,True,True
12,8,text,"Funding: The authors acknowledge funding from FCT—Portuguese Foundation for Science and Technology (FCT/MCTES), with dedicated funding from InSilico4OCReg (PTDC/EME-SIS/0838/2021) and OptiBioScaffold ","[326.0, 1326.0, 1124.0, 1444.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,9,text,Data Availability Statement: Not applicable.,"[328.0, 1454.0, 696.0, 1479.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,10,text,Conflicts of Interest: The authors declare no conflict of interest.,"[328.0, 1490.0, 840.0, 1513.0]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,body_zone,support_like,none,False,False
13,0,header,"Gels 2022, 8, 710","[67.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
13,1,number,13 of 18,"[1061.0, 111.0, 1122.0, 131.0]",reference_item,0.9,"[""page number label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True
13,2,paragraph_title,References,"[67.0, 192.0, 176.0, 215.0]",reference_heading,0.9,"[""references heading: References""]",reference_heading,0.9,reference_zone,heading_like,short_fragment,True,True
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13,14,reference_content,"12. Gu, Y.-T.; Chen, J.; Meng, Z.-L.; Ge, W.-Y.; Bian, Y.-Y.; Cheng, S.-W.; Xing, C.-K.; Yao, J.-L.; Fu, J.; Peng, L. Research progress on osteoarthritis treatment mechanisms. Biomed. Pharmacother. 20","[68.0, 683.0, 1122.0, 727.0]",reference_item,0.85,"[""reference content label: 12. Gu, Y.-T.; Chen, J.; Meng, Z.-L.; Ge, W.-Y.; Bian, Y.-Y.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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13,31,reference_content,"29. Van Beuningen, H.M.; Glansbeek, H.L.; van der Kraan, P.M.; van den Berg, W.B. Osteoarthritis-like changes in the murine knee joint resulting from intra-articular transforming growth factor- $ \bet","[67.0, 1512.0, 1120.0, 1557.0]",reference_item,0.85,"[""reference content label: 29. Van Beuningen, H.M.; Glansbeek, H.L.; van der Kraan, P.M""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,0,header,"Gels 2022, 8, 710","[67.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False
14,1,number,14 of 18,"[1061.0, 111.0, 1122.0, 131.0]",reference_item,0.9,"[""page number label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True
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14,5,reference_content,"33. Cukierman, E.; Pankov, R.; Stevens, D.R.; Yamada, K.M. Taking cell-matrix adhesions to the third dimension. Science 2001, 294, 1708–1712. [CrossRef]","[67.0, 286.0, 1123.0, 328.0]",reference_item,0.85,"[""reference content label: 33. Cukierman, E.; Pankov, R.; Stevens, D.R.; Yamada, K.M. T""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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14,7,reference_content,"35. Mow, V.C.; Guo, X. Mechano-electrical properties of articular cartilage: Their inhomogeneities and anisotropies. Annu. Rev. Biomed. Eng. 2004, 4, 175–209. [CrossRef]","[67.0, 377.0, 1123.0, 421.0]",reference_item,0.85,"[""reference content label: 35. Mow, V.C.; Guo, X. Mechano-electrical properties of arti""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,8,reference_content,"36. Lien, S.M.; Ko, L.Y.; Huang, T.J. Effect of pore size on ECM secretion and cell growth in gelatin scaffold for articular cartilage tissue engineering. Acta Biomater. 2009, 5, 670–679. [CrossRef]","[67.0, 423.0, 1123.0, 468.0]",reference_item,0.85,"[""reference content label: 36. Lien, S.M.; Ko, L.Y.; Huang, T.J. Effect of pore size on""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,9,reference_content,"37. Nava, M.M.; Draghi, L.; Giordano, C.; Pietrabissa, R. The effect of scaffold pore size in cartilage tissue engineering. J. Appl. Biomater. Funct. Mater. 2016, 14, e223–e229. [CrossRef]","[67.0, 470.0, 1122.0, 513.0]",reference_item,0.85,"[""reference content label: 37. Nava, M.M.; Draghi, L.; Giordano, C.; Pietrabissa, R. Th""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,10,reference_content,"38. Bao, W.; Li, M.; Yang, Y.; Wan, Y.; Wang, X.; Bi, N.; Li, C.J. Advancements and Frontiers in the High Performance of Natural Hydrogels for Cartilage Tissue Engineering. Front. Chem. 2020, 8, 53. [","[67.0, 516.0, 1121.0, 560.0]",reference_item,0.85,"[""reference content label: 38. Bao, W.; Li, M.; Yang, Y.; Wan, Y.; Wang, X.; Bi, N.; Li""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,11,reference_content,"39. Sivashanmugam, A.; Kumar, R.A.; Priya, M.V.; Nair, S.V.; Jayakumar, R. An overview of injectable polymeric hydrogels for tissue engineering. Eur. Polym. J. 2015, 72, 543–565. [CrossRef]","[68.0, 562.0, 1120.0, 606.0]",reference_item,0.85,"[""reference content label: 39. Sivashanmugam, A.; Kumar, R.A.; Priya, M.V.; Nair, S.V.;""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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14,14,reference_content,"42. Bidarra, S.J.; Barrias, C.C.; Granja, P.L. Injectable alginate hydrogels for cell delivery in tissue engineering. Acta Biomater. 2014, 10, 1646–1662. [CrossRef]","[67.0, 676.0, 1123.0, 720.0]",reference_item,0.85,"[""reference content label: 42. Bidarra, S.J.; Barrias, C.C.; Granja, P.L. Injectable al""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,15,reference_content,"43. Fedorovich, N.E.; Swennen, I.; Girones, J.; Moroni, L.; van Blitterswijk, C.A.; Schacht, E.; Alblas, J.; Dhert, W.J.A. Evaluation of photocrosslinked lutrol hydrogel for tissue printing applicatio","[66.0, 722.0, 1123.0, 767.0]",reference_item,0.85,"[""reference content label: 43. Fedorovich, N.E.; Swennen, I.; Girones, J.; Moroni, L.; ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,16,reference_content,"44. Huang, Y.; Ma, Y.; Chen, Y.; Wu, X.; Fang, L.; Zhu, Z.; Yang, C.J. Target-responsive DNAzyme cross-linked hydrogel for visual quantitative detection of lead. Anal. Chem. 2014, 86, 11434–11439. [Cr","[66.0, 770.0, 1123.0, 813.0]",reference_item,0.85,"[""reference content label: 44. Huang, Y.; Ma, Y.; Chen, Y.; Wu, X.; Fang, L.; Zhu, Z.; ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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14,18,reference_content,"46. Konieczynska, M.D.; Grinstaff, M.W. On-Demand Dissolution of Chemically Cross-Linked Hydrogels. Acc. Chem. Res. 2017, 50, 151–160. [CrossRef]","[67.0, 837.0, 1122.0, 881.0]",reference_item,0.85,"[""reference content label: 46. Konieczynska, M.D.; Grinstaff, M.W. On-Demand Dissolutio""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,19,reference_content,"47. Atala, A.; Cima, L.G.; Kim, W.; Paige, K.T.; Vacanti, J.P.; Retik, A.B.; Vacanti, C.A. Injectable Alginate Seeded with Chondrocytes as a Potential Treatment for Vesicouretal Reflux. J. Urol. 1993,","[66.0, 884.0, 1122.0, 928.0]",reference_item,0.85,"[""reference content label: 47. Atala, A.; Cima, L.G.; Kim, W.; Paige, K.T.; Vacanti, J.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,20,reference_content,"48. Shu, X.Z.; Liu, Y.; Luo, Y.; Roberts, M.C.; Prestwich, G.D. Disulfide cross-linked hyaluronan hydrogels. Biomacromolecules 2002, 3, 1304–1311. [CrossRef]","[67.0, 930.0, 1124.0, 973.0]",reference_item,0.85,"[""reference content label: 48. Shu, X.Z.; Liu, Y.; Luo, Y.; Roberts, M.C.; Prestwich, G""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,21,reference_content,"49. Skrabania, K.; Kristen, J.; Laschewsky, A.; Akdemir, O.; Hoth, A.; Lutz, J.F. Design, synthesis and aqueous aggregation behavior of nonionic single and multiple thermoresponsive polymers. Langmuir","[66.0, 975.0, 1122.0, 1020.0]",reference_item,0.85,"[""reference content label: 49. Skrabania, K.; Kristen, J.; Laschewsky, A.; Akdemir, O.;""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,22,reference_content,"50. Wu, J.; Su, Z.-G.; Ma, G.-H. A thermo-and pH-sensitive hydrogel composed of quaternized chitosan/glycerophosphate. Int. J. Pharm. 2006, 315, 1–11. [CrossRef]","[66.0, 1022.0, 1123.0, 1065.0]",reference_item,0.85,"[""reference content label: 50. Wu, J.; Su, Z.-G.; Ma, G.-H. A thermo-and pH-sensitive h""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,23,reference_content,"51. Chiu, Y.-L.; Chen, S.-C.; Su, C.-J.; Hsiao, C.-W.; Chen, Y.-M.; Chen, H.-L.; Sung, H.-W. pH-triggered injectable hydrogels prepared from aqueous N-palmitoyl chitosan: In vitro characteristics and ","[66.0, 1068.0, 1123.0, 1135.0]",reference_item,0.85,"[""reference content label: 51. Chiu, Y.-L.; Chen, S.-C.; Su, C.-J.; Hsiao, C.-W.; Chen,""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,24,reference_content,"52. Jin, R.; Moreira Teixeira, L.S.; Dijkstra, P.J.; van Blitterswijk, C.A.; Karperien, M.; Feijen, J. Chondrogenesis in injectable enzymatically crosslinked heparin/dextran hydrogels. J. Control. Rel","[66.0, 1137.0, 1122.0, 1182.0]",reference_item,0.85,"[""reference content label: 52. Jin, R.; Moreira Teixeira, L.S.; Dijkstra, P.J.; van Bli""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,25,reference_content,"53. Kim, M.; Shin, Y.; Hong, B.-H.; Kim, Y.-J.; Chun, J.-S.; Kim, Y.H. In vitro Chondrocyte Culture in a Heparin-Based Hydrogel for Cartilage Regeneration. Tissue Eng. C Methods 2009, 16, 1–10. [Cross","[66.0, 1183.0, 1124.0, 1227.0]",reference_item,0.85,"[""reference content label: 53. Kim, M.; Shin, Y.; Hong, B.-H.; Kim, Y.-J.; Chun, J.-S.;""]",reference_item,0.85,reference_zone,unknown_like,heading_numbered,True,True
14,26,reference_content,"54. Funayama, A.; Niki, Y.; Matsumoto, H.; Maeno, S.; Yatabe, T.; Morioka, H.; Yanagimoto, S.; Taguchi, T.; Tanaka, J.; Toyama, Y. Repair of full-thickness articular cartilage defects using injectable","[67.0, 1228.0, 1123.0, 1295.0]",reference_item,0.85,"[""reference content label: 54. Funayama, A.; Niki, Y.; Matsumoto, H.; Maeno, S.; Yatabe""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,27,reference_content,"55. Rigogliuso, S.; Salamone, M.; Barbarino, E.; Barbarino, M.; Nicosia, A.; Ghersi, G. Production of Injectable Marine Collagen-Based Hydrogel for the Maintenance of Differentiated Chondrocytes in Ti","[68.0, 1297.0, 1123.0, 1365.0]",reference_item,0.85,"[""reference content label: 55. Rigogliuso, S.; Salamone, M.; Barbarino, E.; Barbarino, ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,28,reference_content,"56. Gu, L.; Li, T.; Song, X.; Yang, X.; Li, S.; Chen, L.; Liu, P.; Gong, X.; Chen, C.; Sun, L. Preparation and characterization of methacrylated gelatin/bacterial cellulose composite hydrogels cartila","[67.0, 1368.0, 1122.0, 1433.0]",reference_item,0.85,"[""reference content label: 56. Gu, L.; Li, T.; Song, X.; Yang, X.; Li, S.; Chen, L.; Li""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,29,reference_content,"57. Balakrishnan, B.; Joshi, N.; Jayakrishnan, A.; Banerjee, R. Self-crosslinked oxidized alginate/gelatin hydrogel as injectable, adhesive biomimetic scaffolds for cartilage regeneration. Acta Biomat","[67.0, 1436.0, 1123.0, 1481.0]",reference_item,0.85,"[""reference content label: 57. Balakrishnan, B.; Joshi, N.; Jayakrishnan, A.; Banerjee,""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
14,30,reference_content,"58. Zhang, Y.; Cao, Y.; Zhang, L.; Zhao, H.; Ni, T.; Liu, Y.; An, Z.; Liu, M.; Pei, R. Fabrication of an injectable BMSC-laden double network hydrogel based on silk fibroin/PEG for cartilage repair. J","[67.0, 1483.0, 1122.0, 1527.0]",reference_item,0.85,"[""reference content label: 58. Zhang, Y.; Cao, Y.; Zhang, L.; Zhao, H.; Ni, T.; Liu, Y.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,0,header,"Gels 2022, 8, 710","[67.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False
15,1,number,15 of 18,"[1061.0, 111.0, 1122.0, 131.0]",reference_item,0.9,"[""page number label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True
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15,3,reference_content,"60. Li, X.; Xu, Q.; Johnson, M.; Wang, X.; Lyu, J.; Li, Y.; McMahon, S.; Greiser, U.; Sigen, A.; Wang, W. A chondroitin sulfate based injectable hydrogel for delivery of stem cells in cartilage regene","[67.0, 240.0, 1121.0, 284.0]",reference_item,0.85,"[""reference content label: 60. Li, X.; Xu, Q.; Johnson, M.; Wang, X.; Lyu, J.; Li, Y.; ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,4,reference_content,"61. Wang, G.; Cao, X.; Dong, H.; Zeng, L.; Yu, C.; Chen, X. A Hyaluronic Acid Based Injectable Hydrogel Formed via Photo-Crosslinking Reaction and Thermal-Induced Diels-Alder Reaction for Cartilage Ti","[67.0, 285.0, 1124.0, 352.0]",reference_item,0.85,"[""reference content label: 61. Wang, G.; Cao, X.; Dong, H.; Zeng, L.; Yu, C.; Chen, X. ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,5,reference_content,"62. Chen, J.; Yang, J.; Wang, L.; Zhang, X.; Heng, B.C.; Wang, D.-A.; Ge, Z. Modified hyaluronic acid hydrogels with chemical groups that facilitate adhesion to host tissues enhance cartilage regenera","[66.0, 354.0, 1122.0, 398.0]",reference_item,0.85,"[""reference content label: 62. Chen, J.; Yang, J.; Wang, L.; Zhang, X.; Heng, B.C.; Wan""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,6,reference_content,"63. Shen, Z.-S.; Cui, X.; Hou, R.-X.; Li, Q.; Deng, H.-X.; Fu, J. Tough biodegradable chitosan–gelatin hydrogels via in situ precipitation for potential cartilage tissue engineering. RSC Adv. 2015, 5,","[67.0, 401.0, 1120.0, 445.0]",reference_item,0.85,"[""reference content label: 63. Shen, Z.-S.; Cui, X.; Hou, R.-X.; Li, Q.; Deng, H.-X.; F""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,7,reference_content,"64. Jin, R.; Teixeira, L.S.M.; Dijkstra, P.J.; Karperien, M.; van Blitterswijk, C.A.; Zhong, Z.Y.; Feijen, J. Injectable chitosan-based hydrogels for cartilage tissue engineering. Biomaterials 2009, 3","[67.0, 447.0, 1122.0, 491.0]",reference_item,0.85,"[""reference content label: 64. Jin, R.; Teixeira, L.S.M.; Dijkstra, P.J.; Karperien, M.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,8,reference_content,"65. Yu, Y.; Brouillette, M.J.; Seol, D.; Zheng, H.; Buckwalter, J.A.; Martin, J.A. Use of Recombinant Human Stromal Cell-Derived Factor 1α-Loaded Fibrin/Hyaluronic Acid Hydrogel Networks to Achieve Fu","[67.0, 493.0, 1123.0, 560.0]",reference_item,0.85,"[""reference content label: 65. Yu, Y.; Brouillette, M.J.; Seol, D.; Zheng, H.; Buckwalt""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,9,reference_content,"66. Lim, S.M.; Oh, S.H.; Lee, H.H.; Yuk, S.H.; Im, G.I.; Lee, J.H. Dual growth factor-releasing nanoparticle/hydrogel system for cartilage tissue engineering. J. Mater. Sci. Mater. Med. 2010, 21, 2593","[68.0, 562.0, 1122.0, 606.0]",reference_item,0.85,"[""reference content label: 66. Lim, S.M.; Oh, S.H.; Lee, H.H.; Yuk, S.H.; Im, G.I.; Lee""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,10,reference_content,"67. Dehghan-Baniani, D.; Chen, Y.; Wang, D.; Bagheri, R.; Solouk, A.; Wu, H. Injectable in situ forming kartogenin-loaded chitosan hydrogel with tunable rheological properties for cartilage tissue eng","[67.0, 608.0, 1123.0, 673.0]",reference_item,0.85,"[""reference content label: 67. Dehghan-Baniani, D.; Chen, Y.; Wang, D.; Bagheri, R.; So""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
15,11,reference_content,"68. Zuzzi, D.C.; Ciccone, C.C.; Neves, L.M.G.; Mendonça, J.S.; Joazeiro, P.P.; Esquisatto, M.A.M. Evaluation of the effects of electrical stimulation on cartilage repair in adult male rats. Tissue Cel","[67.0, 676.0, 1123.0, 721.0]",reference_item,0.85,"[""reference content label: 68. Zuzzi, D.C.; Ciccone, C.C.; Neves, L.M.G.; Mendon\u00e7a, J.S""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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15,20,reference_content,"77. Deng, Y.; Zhang, H. The synergistic effect and mechanism of doxorubicin-ZnO nanocomplexes as a multimodal agent integrating diverse anticancer therapeutics. Int. J. Nanomed. 2013, 8, 1835.","[67.0, 1114.0, 1122.0, 1158.0]",reference_item,0.85,"[""reference content label: 77. Deng, Y.; Zhang, H. The synergistic effect and mechanism""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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15,23,reference_content,"80. Baei, P.; Jalili-Firoozinezhad, S.; Rajabi-Zeleti, S.; Tafazzoli-Shadpour, M.; Baharvand, H.; Aghdami, N. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac t","[67.0, 1228.0, 1123.0, 1295.0]",reference_item,0.85,"[""reference content label: 80. Baei, P.; Jalili-Firoozinezhad, S.; Rajabi-Zeleti, S.; T""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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15,28,reference_content,"85. Zimmermann, J.; Distler, T.; Boccaccini, A.R.; van Rienen, U. Numerical Simulations as Means for Tailoring Electrically Conductive Hydrogels towards Cartilage Tissue Engineering by Electrical Stim","[67.0, 1483.0, 1119.0, 1528.0]",reference_item,0.85,"[""reference content label: 85. Zimmermann, J.; Distler, T.; Boccaccini, A.R.; van Riene""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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16,2,reference_content,"86. Alarcon, E.I.; Udekwu, K.I.; Noel, C.W.; Gagnon, L.B.-P.; Taylor, P.K.; Vulesevic, B.; Simpson, M.J.; Gkotzis, S.; Islam, M.M.; Lee, C.-J.; et al. Safety and efficacy of composite collagen-silver ","[65.0, 193.0, 1122.0, 261.0]",reference_item,0.85,"[""reference content label: 86. Alarcon, E.I.; Udekwu, K.I.; Noel, C.W.; Gagnon, L.B.-P.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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16,4,reference_content,"88. Narang, J.; Malhotra, N.; Singh, G.; Pundir, C.S. Electrochemical impediometric detection of anti-HIV drug taking gold nanorods as a sensing interface. Biosens. Bioelectron. 2015, 66, 332–337. [Cr","[67.0, 309.0, 1123.0, 353.0]",reference_item,0.85,"[""reference content label: 88. Narang, J.; Malhotra, N.; Singh, G.; Pundir, C.S. Electr""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,5,reference_content,"89. Yin, D.; Li, X.; Ma, Y.; Liu, Z. Targeted cancer imaging and photothermal therapy via monosaccharide-imprinted gold nanorods. Chem. Commun. 2017, 53, 6716–6719. [CrossRef]","[67.0, 354.0, 1123.0, 398.0]",reference_item,0.85,"[""reference content label: 89. Yin, D.; Li, X.; Ma, Y.; Liu, Z. Targeted cancer imaging""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,6,reference_content,"90. Bharti, A.; Singh, S.; Meena, V.K.; Goyal, N. Structural Characterization of Silver-Hydroxyapatite Nanocomposite: A Bone Repair Biomaterial. Mater. Today Proc. 2016, 3, 2113–2120. [CrossRef]","[67.0, 400.0, 1123.0, 444.0]",reference_item,0.85,"[""reference content label: 90. Bharti, A.; Singh, S.; Meena, V.K.; Goyal, N. Structural""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,7,reference_content,"91. Yang, H.; Zhang, J.; Tian, Q.; Hu, H.; Fang, Y.; Wu, H.; Yang, S. One-pot synthesis of amphiphilic superparamagnetic FePt nanoparticles and magnetic resonance imaging in vitro. J. Magn. Magn. Mate","[67.0, 447.0, 1123.0, 491.0]",reference_item,0.85,"[""reference content label: 91. Yang, H.; Zhang, J.; Tian, Q.; Hu, H.; Fang, Y.; Wu, H.;""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,8,reference_content,"92. Fuchigami, T.; Kawamura, R.; Kitamoto, Y.; Nakagawa, M.; Namiki, Y. A magnetically guided anti-cancer drug delivery system using porous FePt capsules. Biomaterials 2012, 33, 1682–1687. [CrossRef]","[67.0, 493.0, 1124.0, 537.0]",reference_item,0.85,"[""reference content label: 92. Fuchigami, T.; Kawamura, R.; Kitamoto, Y.; Nakagawa, M.;""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,9,reference_content,"93. Chen, C.-L.; Kuo, L.-R.; Lee, S.-Y.; Hwu, Y.-K.; Chou, S.-W.; Chen, C.-C.; Chang, F.-H.; Lin, K.-H.; Tsai, D.-H.; Chen, Y.-Y. Photothermal cancer therapy via femtosecond-laser-excited FePt nanopar","[67.0, 538.0, 1123.0, 587.0]",reference_item,0.85,"[""reference content label: 93. Chen, C.-L.; Kuo, L.-R.; Lee, S.-Y.; Hwu, Y.-K.; Chou, S""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,10,reference_content,"94. Xiong, H.M. ZnO Nanoparticles Applied to Bioimaging and Drug Delivery. Adv. Mater. 2013, 25, 5329–5335. [CrossRef]","[65.0, 585.0, 1064.0, 607.0]",reference_item,0.85,"[""reference content label: 94. Xiong, H.M. ZnO Nanoparticles Applied to Bioimaging and ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,11,reference_content,"95. Ilves, M.; Palomäki, J.; Vippola, M.; Lehto, M.; Savolainen, K.; Savinko, T.; Alenius, H. Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE pr","[67.0, 609.0, 1123.0, 673.0]",reference_item,0.85,"[""reference content label: 95. Ilves, M.; Palom\u00e4ki, J.; Vippola, M.; Lehto, M.; Savolai""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,12,reference_content,"96. Nazarizadeh, A.; Asri-Rezaie, S. Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats. AAPS Pharm. Sci. Tech. 2016,","[66.0, 676.0, 1123.0, 721.0]",reference_item,0.85,"[""reference content label: 96. Nazarizadeh, A.; Asri-Rezaie, S. Comparative Study of An""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,13,reference_content,"97. Moghaddam, A.B.; Moniri, M.; Azizi, S.; Rahim, R.A.; Ariff, A.B.; Navaderi, M.; Mohamad, R. Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest and Apoptosis in the MC","[66.0, 723.0, 1124.0, 767.0]",reference_item,0.85,"[""reference content label: 97. Moghaddam, A.B.; Moniri, M.; Azizi, S.; Rahim, R.A.; Ari""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,14,reference_content,"98. Fan, Z.; Liu, B.; Wang, J.; Zhang, S.; Lin, Q.; Gong, P.; Ma, L.; Yang, S. A Novel Wound Dressing Based on Ag/Graphene Polymer Hydrogel: Effectively Kill Bacteria and Accelerate Wound Healing. Adv","[66.0, 769.0, 1122.0, 813.0]",reference_item,0.85,"[""reference content label: 98. Fan, Z.; Liu, B.; Wang, J.; Zhang, S.; Lin, Q.; Gong, P.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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16,17,reference_content,"101. Lee, W.C.; Lim, C.H.Y.X.; Shi, H.; Tang, L.A.L.; Wang, Y.; Lim, C.T.; Loh, K.P. Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide. ACS Nano 2011, 5, 7334–7341","[66.0, 907.0, 1122.0, 951.0]",reference_item,0.85,"[""reference content label: 101. Lee, W.C.; Lim, C.H.Y.X.; Shi, H.; Tang, L.A.L.; Wang, ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,18,reference_content,"102. Sayyar, S.; Murray, E.; Thompson, B.C.; Chung, J.; Officer, D.L.; Gambhir, S.; Spinks, G.M.; Wallace, G.G. Processable conducting graphene/chitosan hydrogels for tissue engineering. J. Mater. Che","[66.0, 953.0, 1122.0, 998.0]",reference_item,0.85,"[""reference content label: 102. Sayyar, S.; Murray, E.; Thompson, B.C.; Chung, J.; Offi""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,19,reference_content,"103. Comba, F.N.; Romero, M.R.; Garay, F.S.; Baruzzi, A.M. Mucin and carbon nanotube-based biosensor for detection of glucose in human plasma. Anal. Biochem. 2018, 550, 34–40. [CrossRef] [PubMed]","[68.0, 999.0, 1123.0, 1043.0]",reference_item,0.85,"[""reference content label: 103. Comba, F.N.; Romero, M.R.; Garay, F.S.; Baruzzi, A.M. M""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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16,24,reference_content,"108. Sanjuan-Alberte, P.; Whitehead, C.; Jones, J.N.; Silva, J.C.; Carter, N.; Kellaway, S.; Hague, R.J.M.; Cabral, J.M.S.; Ferreira, F.C.; White, L.J.; et al. Printing biohybrid materials for bioelec","[67.0, 1228.0, 1123.0, 1275.0]",reference_item,0.85,"[""reference content label: 108. Sanjuan-Alberte, P.; Whitehead, C.; Jones, J.N.; Silva,""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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17,0,header,"Gels 2022, 8, 710","[67.0, 111.0, 187.0, 131.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False
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5 1 3 doc_title Electrically Conductive Hydrogels for Articular Cartilage Tissue Engineering [66.0, 232.0, 1007.0, 313.0] paper_title 0.8 ["page-1 zone title_zone: Electrically Conductive Hydrogels for Articular Cartilage Ti"] paper_title 0.8 frontmatter_main_zone support_like none True True
6 1 4 text Filipe Miguel $ ^{1,2} $, Frederico Barbosa $ ^{1,2} $, Frederico Castelo Ferreira $ ^{1,2,*} $ and João Carlos Silva $ ^{1,2,*} $ [66.0, 334.0, 969.0, 362.0] authors 0.8 ["page-1 zone author_zone: Filipe Miguel $ ^{1,2} $, Frederico Barbosa $ ^{1,2} $, Fr"] authors 0.8 frontmatter_main_zone support_like none True True
7 1 5 text iBB—Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, [326.0, 402.0, 977.0, 446.0] affiliation 0.8 ["page-1 zone affiliation_zone: iBB\u2014Institute for Bioengineering and Biosciences and Departm"] affiliation 0.8 frontmatter_main_zone support_like none True True
8 1 6 text 2 Associate Laboratory i4HB—Institute for Health and Bioeconomy, Instituto Superior Técnico, [327.0, 448.0, 1026.0, 476.0] affiliation 0.8 ["page-1 zone affiliation_zone: 2 Associate Laboratory i4HB\u2014Institute for Health and Bioecon"] affiliation 0.8 body_zone reference_like reference_numeric_dot True True
9 1 7 text check for updates * Correspondence: frederico.ferreira@tecnico.ulisboa.pt (F.C.F.); joao.f.da.silva@tecnico.ulisboa.pt (J.C.S.) [70.0, 853.0, 179.0, 889.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: check for updates\n* Correspondence: frederico.ferreira@tecni"] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
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11 1 9 text Citation: Miguel, F.; Barbosa, F.; Ferreira, F.C.; Silva, J.C. Electrically Conductive Hydrogels for Articular Cartilage Tissue Engineering. Gels 2022, 8, 710. https://doi.org/10.3390/gels8110710 [66.0, 897.0, 296.0, 1039.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Citation: Miguel, F.; Barbosa, F.; Ferreira, F.C.; Silva, J."] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
12 1 10 text Received: 4 October 2022 Accepted: 1 November 2022 Published: 3 November 2022 [67.0, 1114.0, 252.0, 1183.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Received: 4 October 2022\nAccepted: 1 November 2022\nPublished"] frontmatter_noise 0.8 body_zone body_like none False False
13 1 11 text Academic Editors: Junfeng Shi and Fei Xu [67.0, 1052.0, 291.0, 1097.0] frontmatter_support 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
14 1 12 text Publisher's Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. [66.0, 1197.0, 307.0, 1289.0] frontmatter_noise 0.88 ["default body_paragraph for text label", "late role resolution: editorial phrase cross-validates non-body classification", "zone=body_zone", "style_family=support_like"] body_paragraph 0.6 body_zone support_like none False False
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16 1 14 abstract Abstract: Articular cartilage is a highly specialized tissue found in diarthrodial joints, which is crucial for healthy articular motion. Despite its importance, articular cartilage has limited regene [327.0, 540.0, 1124.0, 878.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 frontmatter_main_zone support_like none True True
17 1 15 text Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licen [66.0, 1363.0, 309.0, 1551.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Copyright: \u00a9 2022 by the authors.\nLicensee MDPI, Basel, Swit"] frontmatter_noise 0.8 body_zone body_like none False False
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19 1 17 paragraph_title 1. Introduction [329.0, 1028.0, 473.0, 1050.0] section_heading 0.85 ["paragraph_title label with numbering: 1. Introduction"] section_heading 0.85 body_zone heading_like heading_numbered True True
20 1 18 text Articular cartilage (AC) is a highly complex and specialized connective tissue present in diarthrodial joints and is paramount for joint mobility and health. Regarding cell populations, AC is composed [325.0, 1056.0, 1125.0, 1538.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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25 2 2 text AC has a complex, multilayered structure, with each zone having different densities of chondrocytes, ECM composition and organization, and water content. The superficial zone makes up to 10–20% of tot [324.0, 192.0, 1124.0, 393.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
26 2 3 text The intrafibrillar water present within the tissue is able to move through the ECM when the tissue experiences compression, despite existing a high frictional resistance to this flow within the tissue [324.0, 394.0, 1124.0, 669.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
27 2 4 text Osteoarthritis (OA) is the most common degenerative joint disorder, characterized by a progressive loss of AC and severe joint pain and stiffness $ [10] $. In fact, it is a leading cause of disabilit [325.0, 670.0, 1124.0, 870.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
28 2 5 text Pharmaceutical therapy is the most common option for OA treatment, and largely consists of acetaminophen, non-steroidal anti-inflammatory drugs, opioid analgesics, and serotonin-norepinephrine re-upta [325.0, 870.0, 1124.0, 1096.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
29 2 6 text Considering the unmet medical need for the effective treatment of OA, cartilage tissue engineering (CTE) has emerged as a promising alternative to treat AC defects [17]. CTE employs the use of a bioco [325.0, 1097.0, 1124.0, 1347.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
30 2 7 text Concerning the main cell sources used in CTE strategies, mesenchymal stem/stromal cells (MSCs) have been widely explored as an alternative to chondrocytes due to their ready availability from differen [325.0, 1347.0, 1125.0, 1549.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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33 3 2 text when compared to MSCs isolated from non-joint tissues [21–23]. Moreover, in recent years, alternative cell sources including articular cartilage progenitor cells (ACPCs) and induced pluripotent stem c [323.0, 192.0, 1124.0, 293.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
34 3 3 text Various growth factors and other bioactive molecules have been used as candidates to promote cartilage regeneration. For example, TGF- $ \beta $3 has been demonstrated to enhance the chondrogenesis of [323.0, 294.0, 1125.0, 619.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
35 3 4 text Hydrogels are highly absorbent polymer networks swollen in large quantities of water, yet maintaining well-defined structures [30]. Biomedical applications of hydrogels started about 60 years ago, and [323.0, 620.0, 1125.0, 1324.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
36 3 5 text Hydrogels for CTE strategies have been fabricated using both natural and synthetic polymers. Hydrogels produced from natural polymers (e.g., alginate, gelatin, collagen, hyaluronic acid, chondroitin s [324.0, 1323.0, 1125.0, 1526.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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39 4 2 text mechanical loading), batch-to-batch variability, and difficult processability and control over structural properties and degradation rate [38–40]. [325.0, 192.0, 1123.0, 242.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
40 4 3 text These extensive customizable features alongside their native-like swelling properties, have allowed the widespread use of hydrogels in CTE strategies [41]. Hydrogels can be designed to be structurally [324.0, 240.0, 1125.0, 951.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
41 4 4 figure_title Table 1. Examples of hydrogels materials used as injectable systems for CTE applications. [327.0, 970.0, 1046.0, 994.0] table_caption 0.9 ["table prefix matched: Table 1. Examples of hydrogels materials used as injectable "] table_caption 0.9 display_zone table_caption_like table_number True True
42 4 5 table <table><tr><td>Injectable Hydrogel Material</td><td>Advantages</td><td>Disadvantages</td><td>Refs</td></tr><tr><td>Heparin</td><td>Naturally occurring negatively charged GAG able to interact with ECM [329.0, 1003.0, 1120.0, 1410.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
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45 5 2 figure_title Table 1. Cont. [329.0, 191.0, 443.0, 214.0] table_caption 0.9 ["table prefix matched: Table 1. Cont."] table_caption 0.9 display_zone table_caption_like table_number True True
46 5 3 table <table><tr><td>Injectable Hydrogel Material</td><td>Advantages</td><td>Disadvantages</td><td>Refs</td></tr><tr><td>Alginate</td><td>Fast gelationCost-effectiveNon-immunogenicNon-toxic</td><td>Lack of [329.0, 223.0, 1119.0, 799.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
47 5 4 text One of the abovementioned biophysical cues is electrical stimulation, which has been shown to increase the proliferation of chondrocytes and secretion of ECM molecules, accelerating the repair of cart [325.0, 830.0, 1125.0, 1081.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
48 5 5 text In this review, a summary of the conductive biomaterials that have been utilized in conjunction with hydrogels is presented. The current state of development of electrically conductive hydrogels for A [326.0, 1081.0, 1125.0, 1183.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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52 6 3 figure_title Figure 1. Electrically conductive hydrogels as a promising tool for the repair of articular cartilage defects caused by trauma or debilitating diseases such as osteoarthritis (top). These functional c [325.0, 1054.0, 1123.0, 1133.0] figure_caption 0.92 ["figure_title label: Figure 1. Electrically conductive hydrogels as a promising t"] figure_caption 0.92 display_zone legend_like figure_number True True
53 6 4 paragraph_title 2. Electrical Properties of Articular Cartilage Tissue [327.0, 1146.0, 803.0, 1171.0] section_heading 0.85 ["paragraph_title label with numbering: 2. Electrical Properties of Articular Cartilage Tissue"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
54 6 5 text AC has intrinsic electrical/electrochemical properties, derived from the flow of free electrolytes (K⁺, Ca²⁺, Na⁺) through the fixed negative charges of carboxyl and sulfate groups attached to the GAG [325.0, 1178.0, 1125.0, 1455.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
55 6 6 paragraph_title 3. Conductive Materials for Tissue Engineering [327.0, 1473.0, 768.0, 1498.0] section_heading 0.85 ["paragraph_title label with numbering: 3. Conductive Materials for Tissue Engineering"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
56 6 7 text A great variety of conductive materials can be implemented with hydrogels in order to create electrically conductive scaffolds. These platforms are invaluable for CTE as they can [326.0, 1505.0, 1124.0, 1555.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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59 7 2 text provide not only native-like physical properties, but are responsive to relevant biophysical cues such as electrical stimulation, simulating a more physiological environment. Despite some combinations [324.0, 192.0, 1124.0, 368.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
60 7 3 paragraph_title 3.1. Metallic Nanoparticles [329.0, 387.0, 558.0, 411.0] subsection_heading 0.85 ["paragraph_title label with numbering: 3.1. Metallic Nanoparticles"] subsection_heading 0.85 body_zone heading_like heading_numbered True True
61 7 4 text Metallic nanoparticles are electrically conductive nanosized particles, with a metal core shelled by an inorganic or organic metal or metal oxide, behaving differently according to their size, shape, [324.0, 417.0, 1125.0, 1125.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
62 7 5 figure_title Table 2. Properties and applications of metallic nanoparticles. [327.0, 1147.0, 824.0, 1171.0] table_caption 0.9 ["table prefix matched: Table 2. Properties and applications of metallic nanoparticl"] table_caption 0.9 display_zone table_caption_like table_number True True
63 7 6 table <table><tr><td>Nanoparticle Material</td><td>Advantages</td><td>Disadvantages</td><td>Applications</td><td>References</td></tr><tr><td>Gold nanoparticles (Au NPs)</td><td>Low initial cytotoxicityHigh [67.0, 1184.0, 1118.0, 1521.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
64 8 0 header Gels 2022, 8, 710 [68.0, 111.0, 187.0, 131.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
65 8 1 number 8 of 18 [1069.0, 111.0, 1121.0, 131.0] noise 0.9 ["page number label"] noise 0.9 reference_like reference_numeric_dot False False
66 8 2 paragraph_title 3.2. Graphene-Based Materials and Carbon Nanotubes [327.0, 192.0, 778.0, 217.0] subsection_heading 0.85 ["paragraph_title label with numbering: 3.2. Graphene-Based Materials and Carbon Nanotubes"] subsection_heading 0.85 body_zone heading_like heading_numbered True True
67 8 3 text Both graphene and carbon nanotubes (CNTs) are conductive materials with high tensile strengths that can be employed to reinforce and provide conductivity to hydrogel biomatrices with a broad range of [324.0, 223.0, 1125.0, 500.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
68 8 4 text CNTs are cylindrical shaped tubes with nanosized diameters. Due to their high tensile strength, excellent electric and thermal conductivity, their coupling with hydrogel matrices has seen a widespread [324.0, 499.0, 1126.0, 905.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
69 8 5 figure_title Table 3. Properties and applications of graphene and carbon nanotubes. [326.0, 927.0, 907.0, 950.0] table_caption 0.9 ["table prefix matched: Table 3. Properties and applications of graphene and carbon "] table_caption 0.9 display_zone table_caption_like table_number True True
70 8 6 table <table><tr><td>Carbon Type</td><td>Advantages</td><td>Disadvantages</td><td>Applications</td><td>References</td></tr><tr><td rowspan="3">Graphene</td><td>High mechanical strength</td><td>Oxidative str [67.0, 964.0, 1119.0, 1149.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
71 8 7 paragraph_title 3.3. Conductive Polymers [328.0, 1180.0, 546.0, 1205.0] subsection_heading 0.85 ["paragraph_title label with numbering: 3.3. Conductive Polymers"] subsection_heading 0.85 body_zone heading_like heading_numbered True True
72 8 8 text Conductive polymers are organic polymers with unique mechanical and optical properties. They have characteristics similar to some metals and inorganic semiconductors while maintaining characteristic p [324.0, 1210.0, 1127.0, 1566.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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75 9 2 text gies both as coating material and mixed with other biomaterials [123–126]. Our group has recently showed that PEDOT:PSS coated polybenzimidazole nanofibers were able to promote the adhesion and prolif [324.0, 192.0, 1126.0, 446.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
76 9 3 figure_title Table 4. Properties and applications of main conductive polymers. [326.0, 467.0, 863.0, 491.0] table_caption 0.9 ["table prefix matched: Table 4. Properties and applications of main conductive poly"] table_caption 0.9 display_zone table_caption_like table_number True True
77 9 4 table <table><tr><td>Conductive Polymer Type</td><td>Advantages</td><td>Disadvantages</td><td>Applications</td><td>References</td></tr><tr><td>Polyaniline (PANi)</td><td>High stabilityHigh conductivity</td> [68.0, 506.0, 1119.0, 805.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
78 9 5 paragraph_title 4. Electrically Conductive Hydrogels for Articular Cartilage Tissue Engineering [327.0, 835.0, 1059.0, 860.0] section_heading 0.85 ["paragraph_title label with numbering: 4. Electrically Conductive Hydrogels for Articular Cartilage"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
79 9 6 text The fabrication of hydrogels with different materials and properties as cartilage-healing constructs is well documented. However, recently there has been an emergence of a few research studies trying [323.0, 866.0, 1125.0, 1092.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
80 9 7 text The underlying mechanisms through which endogenous or external electrical stimuli influence cell behavior are still poorly described. However, the alteration of cell membrane resting potential by elec [324.0, 1093.0, 1126.0, 1494.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
81 9 8 text When designing conductive hydrogel scaffolds as cartilage substitutes, some parameters are necessary to consider in order to correctly recapitulating the native environment, including the mechanical s [326.0, 1495.0, 1127.0, 1572.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
82 10 0 header Gels 2022, 8, 710 [68.0, 111.0, 187.0, 131.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
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84 10 2 text ibility. Despite literature on this topic being scarce, the existing results are highly promising, highlighting the potential of electrically conductive hydrogels for improved CTE strategies (Table 5) [325.0, 192.0, 1123.0, 266.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
85 10 3 text Zhang et al., produced a poly(vinyl alcohol) (PVA) hydrogel combined with sodium phytate (PANa), which conferred conductivity and excellent mechanical properties to the hydrogel [141]. The mechanical [323.0, 269.0, 1124.0, 645.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
86 10 4 text In a different study, Shen and colleagues investigated the chondrogenic inducing potential of a graphene oxide (GO) containing poly-D,L-lactic acid/polyethylene glycol (PDLLA) nanocomposite hydrogel [ [325.0, 644.0, 1124.0, 1071.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
87 10 5 text 3D printing allows layer-by-layer development of 3D structures and the fabrication of complex scaffolds in a fast and reproducible manner. Given that this technique enables a precise control over the [325.0, 1071.0, 1126.0, 1525.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
88 11 0 header Gels 2022, 8, 710 [67.0, 111.0, 187.0, 131.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
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90 11 2 figure_title Table 5. Summary of research studies on electrically conductive hydrogels for AC tissue engineering. [326.0, 192.0, 1122.0, 216.0] table_caption 0.9 ["table prefix matched: Table 5. Summary of research studies on electrically conduct"] table_caption 0.9 display_zone table_caption_like table_number True True
91 11 3 table <table><tr><td>Hydrogel</td><td>Conductive Filler</td><td>Main Outcomes</td><td>References</td></tr><tr><td>Poly(vinyl alcohol) (PVA)</td><td>Sodium phytate (PANa)</td><td>Easy to produce and cost-eff [328.0, 223.0, 1119.0, 844.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
92 11 4 paragraph_title 5. Challenges and Future Perspectives [328.0, 874.0, 683.0, 897.0] section_heading 0.85 ["paragraph_title label with numbering: 5. Challenges and Future Perspectives"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
93 11 5 text The promising results observed in the few studies developing electrically conductive hydrogels for AC regeneration highlight its potential as a suitable culture platform for improved CTE strategies. H [324.0, 903.0, 1125.0, 1382.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
94 11 6 text Another challenge limiting the application of conductive hydrogels in regenerative medicine is their low processability by 3D additive manufacturing techniques. In fact, the fabrication of complex str [325.0, 1381.0, 1126.0, 1535.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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97 12 2 text structures should be explored with high potential for introducing major advances in AC and osteochondral tissue engineering. [326.0, 192.0, 1122.0, 241.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
98 12 3 text Furthermore, a deeper understanding of the tissue's electrical properties is necessary in order to successfully mimic the AC's native niche and achieve proper regeneration outcomes. Novel methods to d [325.0, 243.0, 1125.0, 721.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
99 12 4 paragraph_title 6. Conclusions [329.0, 740.0, 471.0, 763.0] section_heading 0.85 ["paragraph_title label with numbering: 6. Conclusions"] section_heading 0.85 body_zone heading_like heading_numbered True True
100 12 5 text CTE has emerged as an exciting alternative to the current ineffective treatments for cartilage damage and degeneration, as in cases of OA. In particular, the development of electrically conductive hyd [326.0, 770.0, 1124.0, 895.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
101 12 6 text In summary, this review provides an overview of the most common conductive materials that have been combined with hydrogels for tissue engineering and other biomedical applications. Conductive materia [325.0, 896.0, 1125.0, 1201.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
102 12 7 text Author Contributions: Conceptualization: F.M., F.C.F. and J.C.S.; investigation: F.M. and J.C.S.; writing—original draft preparation: F.M., F.B. and J.C.S.; writing—review and editing: F.M., F.B., F.C [326.0, 1220.0, 1124.0, 1316.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone support_like none True True
103 12 8 text Funding: The authors acknowledge funding from FCT—Portuguese Foundation for Science and Technology (FCT/MCTES), with dedicated funding from InSilico4OCReg (PTDC/EME-SIS/0838/2021) and OptiBioScaffold [326.0, 1326.0, 1124.0, 1444.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
104 12 9 text Data Availability Statement: Not applicable. [328.0, 1454.0, 696.0, 1479.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
105 12 10 text Conflicts of Interest: The authors declare no conflict of interest. [328.0, 1490.0, 840.0, 1513.0] frontmatter_noise 0.88 ["default body_paragraph for text label", "late role resolution: editorial phrase cross-validates non-body classification", "zone=body_zone", "style_family=support_like"] body_paragraph 0.6 body_zone support_like none False False
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108 13 2 paragraph_title References [67.0, 192.0, 176.0, 215.0] reference_heading 0.9 ["references heading: References"] reference_heading 0.9 reference_zone heading_like short_fragment True True
109 13 3 reference_content 1. Bhosale, A.M.; Richardson, J.B. Articular cartilage: Structure, injuries and review of management. Br. Med. Bull. 2020, 87, 77–95. [CrossRef] [PubMed] [65.0, 221.0, 1122.0, 266.0] reference_item 0.85 ["reference content label: 1. Bhosale, A.M.; Richardson, J.B. Articular cartilage: Stru"] reference_item 0.85 reference_zone reference_like reference_numeric_dot True True
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{
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{
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{
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{
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{
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{
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{
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{
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{
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{
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"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
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"artifact": "reference_span_audit.json"
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{
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"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
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{
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"block_ids": [
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],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
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"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p8:8"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_008.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_007.png",
"artifact": "page_risk_summary.json"
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{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
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"p1:3",
"p1:11",
"p1:12",
"p2:0",
"p3:1",
"p3:13",
"p4:0",
"p4:10",
"p5:1",
"p5:4",
"p6:0",
"p6:1",
"p6:6",
"p7:0",
"p7:1",
"p8:0"
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"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
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"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

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# OCR Truth Audit Report - 72D4YXEB
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 2, 3, 4, 5, 6, 7]
- Reviewed blocks: 92
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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{
"mode": "high-risk",
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1,1,doc_title,Electromechanical Assessment of Human Knee Articular Cartilage with Compression-Induced Streaming Potentials,"[90.0, 138.0, 835.0, 258.0]",paper_title,0.8,"[""page-1 zone title_zone: Electromechanical Assessment of Human Knee Articular Cartila""]",paper_title,0.8,frontmatter_main_zone,support_like,none,True,True
1,2,text,"Cartilage
2016, Vol. 7(1) 62–69
© The Author(s) 2015
Reprints and permissions:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1947603515599191
cart.sagepub.com
SAGE","[858.0, 119.0, 1079.0, 268.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Cartilage\n2016, Vol. 7(1) 62\u201369\n\u00a9 The Author(s) 2015\nReprint""]",frontmatter_noise,0.8,frontmatter_main_zone,support_like,none,False,False
1,3,text,"Christoph Becher $ ^{1} $, Marcel Ricklefs $ ^{1} $, Elmar Willbold $ ^{2} $, Christof Hurschler $ ^{2} $, and Reza Abedian $ ^{2} $","[89.0, 325.0, 927.0, 384.0]",authors,0.8,"[""page-1 zone author_zone: Christoph Becher $ ^{1} $, Marcel Ricklefs $ ^{1} $, Elmar W""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
1,4,paragraph_title,Abstract,"[91.0, 454.0, 183.0, 477.0]",abstract_heading,0.95,"[""abstract heading""]",abstract_heading,0.95,frontmatter_main_zone,heading_like,short_fragment,True,True
1,5,abstract,Purpose: To assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation with macroscopic and his,"[87.0, 479.0, 1085.0, 842.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,frontmatter_main_zone,support_like,none,True,True
1,6,paragraph_title,Keywords,"[91.0, 873.0, 193.0, 896.0]",structured_insert,0.9,"[""frontmatter noise: Keywords""]",frontmatter_noise,0.9,frontmatter_main_zone,heading_like,short_fragment,False,False
1,7,text,"streaming potential integrals (SPI), articular cartilage, osteoarthritis, ICRS/Mankin score","[90.0, 898.0, 805.0, 923.0]",frontmatter_noise,0.7,"[""keyword-like block: streaming potential integrals (SPI), articular cartilage, os""]",frontmatter_noise,0.7,frontmatter_main_zone,support_like,none,False,False
1,8,paragraph_title,Introduction,"[92.0, 983.0, 241.0, 1007.0]",section_heading,0.9,"[""explicit scholarly heading: Introduction""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
1,9,text,"Articular cartilage defects are common findings at arthroscopic surgery of the knee joint. $ ^{1-3} $ These defects may be the cause of a variety of symptoms, such as swelling, pain, or joint stiffnes","[89.0, 1021.0, 575.0, 1431.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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1,11,footnote," $ ^{1} $Department of Orthopedic Surgery, Hannover Medical School, Hannover, Germany
$ ^{2} $Laboratory for Biomechanics and Biomaterials, Hannover Medical School, Hannover, Germany","[600.0, 1233.0, 1042.0, 1316.0]",footnote,0.7,"[""footnote label: $ ^{1} $Department of Orthopedic Surgery, Hannover Medical S""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
1,12,footnote,"Corresponding Author:
Christoph Becher, Department of Orthopedic Surgery, Hannover Medical School, 1-7 Anna-von-Borries-Straße, 30625 Hannover, Germany.
Email: becher.chris@web.de","[599.0, 1325.0, 1039.0, 1428.0]",frontmatter_support,0.75,"[""page-1 correspondence footnote: Corresponding Author:\nChristoph Becher, Department of Orthop""]",frontmatter_support,0.75,body_zone,body_like,none,True,True
2,0,header,Becher et al.,"[123.0, 81.0, 223.0, 103.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,1,number,63,"[1087.0, 81.0, 1112.0, 102.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
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2,3,figure_title,Figure 1. (a) Principle of the technique for the measurement of compression-induced streaming potentials of articular cartilage according to the user manual. $ ^{16} $ As a result of compression loadi,"[120.0, 449.0, 1107.0, 558.0]",figure_caption,0.92,"[""figure_title label: Figure 1. (a) Principle of the technique for the measurement""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
2,4,text,"and healing grafts, more reliable and sensitive measurement techniques are necessary.","[119.0, 594.0, 603.0, 640.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,5,text,"In recent years, several diagnostic tools capable of objective evaluation of the cartilage properties in the early and potentially reversible stages of the disease have been developed to assess the st","[120.0, 641.0, 605.0, 1026.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,text,The device investigated herein relies on the fact that streaming potentials are induced in cartilage in response to loading. The extracellular matrix is loaded with negatively charged proteoglycans th,"[119.0, 1026.0, 606.0, 1435.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,7,text,,"[628.0, 592.0, 1114.0, 906.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
2,8,text,"In this study, multiuser repeating measurements were performed to assess the learning phase for different users in 10 human knee cadaver specimens in vitro and under benchtop measurement configuration","[628.0, 907.0, 1115.0, 1171.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,9,paragraph_title,Materials and Methods Specimen Preparation and SPI Measurements,"[629.0, 1211.0, 1052.0, 1278.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Materials and Methods Specimen Preparation and SPI Measureme""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
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2,11,text,"After approval of the local ethics committee (IRB No. 1182-2011), femoral condyles of 10 fresh human cadaver knee specimen (2 male, 3 female, mean age 58 [43-65] years) were dissected and distal femur","[628.0, 1288.0, 1115.0, 1435.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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3,1,header,Cartilage 7(1),"[972.0, 80.0, 1083.0, 104.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
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3,3,figure_title,"Figure 2. (a) Location scheme for distal femur with measurement points marked on the anatomical locations for SPI measurement (L, lateral; M, medial). (b) Tip of the Arthro-BST hemispherical indentati","[90.0, 414.0, 1066.0, 481.0]",figure_caption,0.92,"[""figure_title label: Figure 2. (a) Location scheme for distal femur with measurem""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
3,4,text,ink-marked on the trochlea (2-3) and medial/lateral condyles (14) according to a standardized location scheme (Fig. 2). The thus defined measurement locations were evaluated by an experienced board-ce,"[89.0, 514.0, 575.0, 779.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,5,text,The testing chamber was filled with phosphate-buffered saline (pH 7.4) and a minimum of 15 minutes was allowed for equilibration prior to electromechanical mapping. Streaming potentials were measured ,"[88.0, 779.0, 576.0, 1116.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,6,paragraph_title,Histological and Biochemical Evaluation,"[91.0, 1148.0, 454.0, 1175.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Histological and Biochemical Evaluation""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
3,7,text,"A total of 162 equal osteochondral cylinders of 6-mm diameter and 8-mm height were harvested from the marked locations with orthopedic tissue punches (Osteochondral Autograft Transfer System [OATS], A","[89.0, 1186.0, 574.0, 1356.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,8,text,"General Histology. The cylinders were first fixed in commercial 3.5% formalin for 5 days at room temperature. Then, the cylinders were washed, dehydrated in a graded series of ethanol, embedded in met","[89.0, 1378.0, 575.0, 1452.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,9,text,,"[599.0, 514.0, 1085.0, 756.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
3,10,text,"Hematoxylin–Eosin Staining. Rehydrated sections were first rinsed in distilled water for 2 minutes, then stained for 6 minutes with Mayer's hematoxylin (Merck), rinsed in tap water for 10 minutes, the","[599.0, 778.0, 1085.0, 924.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,11,text,"Safranin-O Staining. Rehydrated sections were incubated for 4 minutes in a solution of 0.1% safranin-O (Sigma, Taufkirchen, Germany), then washed in distilled water, dehydrated in a graded series of e","[599.0, 945.0, 1085.0, 1044.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,12,text,"Mankin Score. Mankin scores were determined for the histological evaluation. Values range from 0 (healthy cartilage) to 14 (severe cartilage destruction), distributed in 4 categories: structure (range","[600.0, 1066.0, 1084.0, 1284.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,13,text,"Biochemical Evaluation. The content of sGAG (reported in $ \mu $g/mL, normalized to a standardized sample surface area of 28.3 mm $ ^{2} $) was determined using the commercially available Blyscan Ass","[599.0, 1305.0, 1086.0, 1452.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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4,3,figure_title,Figure 3. Box plots displaying the SPI measurements of the 3 observers. The interclass correlation coefficient (ICC) was 0.77 (0.70-0.83) indicating good to excellent linear agreement of streaming pot,"[120.0, 659.0, 1102.0, 706.0]",figure_caption,0.92,"[""figure_title label: Figure 3. Box plots displaying the SPI measurements of the 3""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
4,4,text,"the cartilage cylinders, each specimen was dissolved in 1.5-mL microcentrifuge tubes in a papain extraction reagent, containing 100 mL of 0.2 M sodium phosphate buffer (pH 6.4) with 0.82 g of sodium a","[119.0, 739.0, 605.0, 1245.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,5,paragraph_title,Data Evaluation and Statistical Methods,"[121.0, 1278.0, 492.0, 1303.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Data Evaluation and Statistical Methods""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
4,6,text,"To validate the methodologies of the measurements, 3 of the authors (observer 1, board-certified orthopedic surgeon; observer 2, engineering student trained in the use of the device $ ^{17} $; observe","[119.0, 1316.0, 605.0, 1438.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,7,text,,"[626.0, 739.0, 1115.0, 1054.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
4,8,paragraph_title,Results,"[631.0, 1085.0, 720.0, 1111.0]",section_heading,0.9,"[""explicit scholarly heading: Results""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
4,9,text,"The computed ICC was 0.77 (0.70-0.83), indicating good to excellent linear agreement of SPI values among the 3 users (Fig. 3). However, unsuccessful measurements occurred at several locations for all ","[628.0, 1123.0, 1113.0, 1340.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,10,text,"The mean ICRS score was $ 0.8 \pm 0.7 $ (range 0-3), and the mean Mankin score was $ 2.8 \pm 1.5 $ (range 0-7). Significant negative correlations between SPI and both ICRS and Mankin scores were obs","[628.0, 1341.0, 1115.0, 1437.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,0,number,66,"[94.0, 81.0, 119.0, 102.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,1,header,Cartilage 7(1),"[972.0, 80.0, 1083.0, 105.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,2,chart,,"[274.0, 149.0, 906.0, 752.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
5,3,figure_title,Figure 4. Linear regression between learning index and number of evaluated knees.,"[90.0, 785.0, 720.0, 807.0]",figure_caption,0.92,"[""figure_title label: Figure 4. Linear regression between learning index and numbe""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
5,4,text,"$r = 0.255$, $P = 0.02$, respectively; Fig. 5a and b) together with a significant positive linear correlation between the ICRS and Mankin scores ($r = 0.334$, $P = 0.002$). No significant correlations","[90.0, 845.0, 574.0, 967.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,5,paragraph_title,Discussion,"[92.0, 999.0, 216.0, 1024.0]",section_heading,0.9,"[""explicit scholarly heading: Discussion""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
5,6,text,The purpose of this study was to assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation wit,"[89.0, 1037.0, 574.0, 1348.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,7,text,"Standardized methods for evaluating of cartilage defects, cartilage repair tissue, and clinical outcomes of cartilage resurfacing are crucial in both the clinical and research contexts. However, the d","[89.0, 1350.0, 574.0, 1422.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,8,text,,"[598.0, 846.0, 1086.0, 1424.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
6,0,header,Becher et al.,"[123.0, 81.0, 223.0, 103.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,1,number,67,"[1087.0, 81.0, 1113.0, 102.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,2,chart,,"[138.0, 163.0, 621.0, 543.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
6,3,chart,,"[626.0, 164.0, 1087.0, 534.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
6,4,chart,,"[390.0, 554.0, 850.0, 921.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
6,5,figure_title,"Figure 5. Correlations between streaming potential integral (SPI) values and (a) International Cartilage Repair Society (ICRS) score, (b) Mankin score, and (c) sulfated glycosaminoglycan (sGAG) conten","[120.0, 966.0, 1102.0, 1012.0]",figure_caption,0.92,"[""figure_title label: Figure 5. Correlations between streaming potential integral ""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
6,6,text,"from one pilot study from our group published by Abedian et al. $ ^{17} $, the available literature about the Arthro-BST is somewhat related to the inventers of the device. $ ^{10,14,18-20} $","[120.0, 1046.0, 604.0, 1116.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,7,text,"In the present study, we demonstrated good to excellent linear agreement of SPI values with an ICC of 0.77 (0.70-0.83), which confirms the reliability of the streaming potential measurements among dif","[119.0, 1119.0, 605.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,8,text,,"[628.0, 1045.0, 1115.0, 1262.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
6,9,text,"The present study revealed statistically significant negative correlations between SPI and both ICRS (r = 0.502) and Mankin scores (r = 0.255). Although the correlation coefficient was not high, these","[629.0, 1263.0, 1115.0, 1432.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,0,number,68,"[93.0, 81.0, 120.0, 102.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
7,1,header,Cartilage 7(1),"[972.0, 80.0, 1083.0, 105.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
7,2,text,demonstrated comparable findings when correlating the characteristic value (CV) calculated from NIR with a handheld probe to ICRS scores (r = 0.47) $ ^{29} $ and Mankin score (r = 0.55). $ ^{30} $ A g,"[89.0, 134.0, 575.0, 710.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
7,3,text,"Although the decrease of glycosaminoglycan content is typical for severe cartilage lesions, $ ^{31,32} $ we could not detect a correlation of SPI values to the sGAG content per wet weight. This observ","[89.0, 712.0, 576.0, 1165.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
7,4,text,"In conclusion, the findings of this study confirm the agreement between the SPI and clinically relevant cartilage scores ex vivo under benchtop conditions substantiating that the SPI values may be use","[89.0, 1167.0, 575.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
7,5,text,,"[599.0, 134.0, 1085.0, 232.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
7,6,paragraph_title,Acknowledgment and Funding,"[600.0, 259.0, 895.0, 282.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Acknowledgment and Funding""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
7,7,text,"The author(s) received no financial support for the research, authorship, and/or publication of this article.","[599.0, 290.0, 1083.0, 336.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,8,paragraph_title,Declaration of Conflicting Interests,"[601.0, 362.0, 940.0, 386.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Declaration of Conflicting Interests""]",backmatter_boundary_candidate,0.5,body_zone,heading_like,none,True,True
7,9,text,"The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.","[599.0, 393.0, 1084.0, 460.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,10,paragraph_title,Ethical Approval,"[601.0, 486.0, 766.0, 510.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Ethical Approval""]",subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
7,11,text,The local ethics committee provide ethical approval (IRB No. 1182-2011).,"[600.0, 518.0, 1082.0, 561.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,12,paragraph_title,References,"[602.0, 586.0, 713.0, 609.0]",reference_heading,0.9,"[""references heading: References""]",reference_heading,0.9,reference_zone,heading_like,short_fragment,True,True
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8,0,header,Becher et al.,"[124.0, 82.0, 222.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False
8,1,number,69,"[1088.0, 82.0, 1112.0, 101.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
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8,20,reference_content,"28. Changoor A, Quenneville E, Garon M, Cloutier L, Hurtig MB, Buschmann MD. Streaming potential-based arthroscopic device discerns topographical differences in cartilage covered and uncovered by meni","[634.0, 509.0, 1112.0, 616.0]",reference_item,0.85,"[""reference content label: 28. Changoor A, Quenneville E, Garon M, Cloutier L, Hurtig M""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
8,21,reference_content,"29. Marticke JK, Hosselbarth A, Hoffmeier KL, Marintschev I, Otto S, Lange M, et al. How do visual, spectroscopic and biomechanical changes of cartilage correlate in osteoarthritic knee joints? Clin B","[634.0, 620.0, 1112.0, 704.0]",reference_item,0.85,"[""reference content label: 29. Marticke JK, Hosselbarth A, Hoffmeier KL, Marintschev I,""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
8,22,reference_content,"30. Pester JK, Stumpfe ST, Steinert S, Marintschev I, Plettenberg HK, Aurich M, et al. Histological, biochemical and spectroscopic changes of articular cartilage in osteoarthritis: is there a chance f","[634.0, 708.0, 1112.0, 814.0]",reference_item,0.85,"[""reference content label: 30. Pester JK, Stumpfe ST, Steinert S, Marintschev I, Plette""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
8,23,reference_content,"31. Bonassar LJ, Jeffries KA, Paguio CG, Grodzinsky AJ. Cartilage degradation and associated changes in biochemical and electromechanical properties. Acta Orthop Scand Suppl. 1995;266:38-44.","[634.0, 818.0, 1111.0, 901.0]",reference_item,0.85,"[""reference content label: 31. Bonassar LJ, Jeffries KA, Paguio CG, Grodzinsky AJ. Cart""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
8,24,reference_content,"32. Franz T, Hasler EM, Hagg R, Weiler C, Jakob RP, Mainil-Varlet P. In situ compressive stiffness, biochemical composition, and structural integrity of articular cartilage of the human knee joint. Os","[634.0, 906.0, 1113.0, 1011.0]",reference_item,0.85,"[""reference content label: 32. Franz T, Hasler EM, Hagg R, Weiler C, Jakob RP, Mainil-V""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
8,25,reference_content,"33. Stumpfe ST, Pester JK, Steinert S, Marintschev I, Plettenberg H, Aurich M, Hofmann GO. Is there a correlation between biophotonical, biochemical, histological, and visual changes in the cartilage ","[635.0, 1016.0, 1114.0, 1121.0]",reference_item,0.85,"[""reference content label: 33. Stumpfe ST, Pester JK, Steinert S, Marintschev I, Plette""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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2 1 0 header Article [92.0, 76.0, 146.0, 99.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like short_fragment False False
3 1 1 doc_title Electromechanical Assessment of Human Knee Articular Cartilage with Compression-Induced Streaming Potentials [90.0, 138.0, 835.0, 258.0] paper_title 0.8 ["page-1 zone title_zone: Electromechanical Assessment of Human Knee Articular Cartila"] paper_title 0.8 frontmatter_main_zone support_like none True True
4 1 2 text Cartilage 2016, Vol. 7(1) 62–69 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1947603515599191 cart.sagepub.com SAGE [858.0, 119.0, 1079.0, 268.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Cartilage\n2016, Vol. 7(1) 62\u201369\n\u00a9 The Author(s) 2015\nReprint"] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
5 1 3 text Christoph Becher $ ^{1} $, Marcel Ricklefs $ ^{1} $, Elmar Willbold $ ^{2} $, Christof Hurschler $ ^{2} $, and Reza Abedian $ ^{2} $ [89.0, 325.0, 927.0, 384.0] authors 0.8 ["page-1 zone author_zone: Christoph Becher $ ^{1} $, Marcel Ricklefs $ ^{1} $, Elmar W"] authors 0.8 frontmatter_main_zone support_like none True True
6 1 4 paragraph_title Abstract [91.0, 454.0, 183.0, 477.0] abstract_heading 0.95 ["abstract heading"] abstract_heading 0.95 frontmatter_main_zone heading_like short_fragment True True
7 1 5 abstract Purpose: To assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation with macroscopic and his [87.0, 479.0, 1085.0, 842.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 frontmatter_main_zone support_like none True True
8 1 6 paragraph_title Keywords [91.0, 873.0, 193.0, 896.0] structured_insert 0.9 ["frontmatter noise: Keywords"] frontmatter_noise 0.9 frontmatter_main_zone heading_like short_fragment False False
9 1 7 text streaming potential integrals (SPI), articular cartilage, osteoarthritis, ICRS/Mankin score [90.0, 898.0, 805.0, 923.0] frontmatter_noise 0.7 ["keyword-like block: streaming potential integrals (SPI), articular cartilage, os"] frontmatter_noise 0.7 frontmatter_main_zone support_like none False False
10 1 8 paragraph_title Introduction [92.0, 983.0, 241.0, 1007.0] section_heading 0.9 ["explicit scholarly heading: Introduction"] section_heading 0.9 body_zone heading_like canonical_section_name True True
11 1 9 text Articular cartilage defects are common findings at arthroscopic surgery of the knee joint. $ ^{1-3} $ These defects may be the cause of a variety of symptoms, such as swelling, pain, or joint stiffnes [89.0, 1021.0, 575.0, 1431.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
12 1 10 text [598.0, 982.0, 1085.0, 1177.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 frontmatter_main_zone support_like empty True True
13 1 11 footnote $ ^{1} $Department of Orthopedic Surgery, Hannover Medical School, Hannover, Germany $ ^{2} $Laboratory for Biomechanics and Biomaterials, Hannover Medical School, Hannover, Germany [600.0, 1233.0, 1042.0, 1316.0] footnote 0.7 ["footnote label: $ ^{1} $Department of Orthopedic Surgery, Hannover Medical S"] footnote 0.7 body_zone body_like affiliation_marker True True
14 1 12 footnote Corresponding Author: Christoph Becher, Department of Orthopedic Surgery, Hannover Medical School, 1-7 Anna-von-Borries-Straße, 30625 Hannover, Germany. Email: becher.chris@web.de [599.0, 1325.0, 1039.0, 1428.0] frontmatter_support 0.75 ["page-1 correspondence footnote: Corresponding Author:\nChristoph Becher, Department of Orthop"] frontmatter_support 0.75 body_zone body_like none True True
15 2 0 header Becher et al. [123.0, 81.0, 223.0, 103.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
16 2 1 number 63 [1087.0, 81.0, 1112.0, 102.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
17 2 2 image [307.0, 151.0, 932.0, 418.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
18 2 3 figure_title Figure 1. (a) Principle of the technique for the measurement of compression-induced streaming potentials of articular cartilage according to the user manual. $ ^{16} $ As a result of compression loadi [120.0, 449.0, 1107.0, 558.0] figure_caption 0.92 ["figure_title label: Figure 1. (a) Principle of the technique for the measurement"] figure_caption 0.92 display_zone legend_like figure_number True True
19 2 4 text and healing grafts, more reliable and sensitive measurement techniques are necessary. [119.0, 594.0, 603.0, 640.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
20 2 5 text In recent years, several diagnostic tools capable of objective evaluation of the cartilage properties in the early and potentially reversible stages of the disease have been developed to assess the st [120.0, 641.0, 605.0, 1026.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
21 2 6 text The device investigated herein relies on the fact that streaming potentials are induced in cartilage in response to loading. The extracellular matrix is loaded with negatively charged proteoglycans th [119.0, 1026.0, 606.0, 1435.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
22 2 7 text [628.0, 592.0, 1114.0, 906.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
23 2 8 text In this study, multiuser repeating measurements were performed to assess the learning phase for different users in 10 human knee cadaver specimens in vitro and under benchtop measurement configuration [628.0, 907.0, 1115.0, 1171.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
24 2 9 paragraph_title Materials and Methods Specimen Preparation and SPI Measurements [629.0, 1211.0, 1052.0, 1278.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Materials and Methods Specimen Preparation and SPI Measureme"] subsection_heading 0.6 body_zone heading_like none True True
25 2 10 footer [629.0, 1251.0, 1052.0, 1278.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like empty False False
26 2 11 text After approval of the local ethics committee (IRB No. 1182-2011), femoral condyles of 10 fresh human cadaver knee specimen (2 male, 3 female, mean age 58 [43-65] years) were dissected and distal femur [628.0, 1288.0, 1115.0, 1435.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
27 3 0 number 64 [93.0, 81.0, 120.0, 102.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
28 3 1 header Cartilage 7(1) [972.0, 80.0, 1083.0, 104.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
29 3 2 image [240.0, 158.0, 921.0, 383.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
30 3 3 figure_title Figure 2. (a) Location scheme for distal femur with measurement points marked on the anatomical locations for SPI measurement (L, lateral; M, medial). (b) Tip of the Arthro-BST hemispherical indentati [90.0, 414.0, 1066.0, 481.0] figure_caption 0.92 ["figure_title label: Figure 2. (a) Location scheme for distal femur with measurem"] figure_caption 0.92 display_zone legend_like figure_number True True
31 3 4 text ink-marked on the trochlea (2-3) and medial/lateral condyles (14) according to a standardized location scheme (Fig. 2). The thus defined measurement locations were evaluated by an experienced board-ce [89.0, 514.0, 575.0, 779.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
32 3 5 text The testing chamber was filled with phosphate-buffered saline (pH 7.4) and a minimum of 15 minutes was allowed for equilibration prior to electromechanical mapping. Streaming potentials were measured [88.0, 779.0, 576.0, 1116.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
33 3 6 paragraph_title Histological and Biochemical Evaluation [91.0, 1148.0, 454.0, 1175.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Histological and Biochemical Evaluation"] subsection_heading 0.6 body_zone heading_like none True True
34 3 7 text A total of 162 equal osteochondral cylinders of 6-mm diameter and 8-mm height were harvested from the marked locations with orthopedic tissue punches (Osteochondral Autograft Transfer System [OATS], A [89.0, 1186.0, 574.0, 1356.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
35 3 8 text General Histology. The cylinders were first fixed in commercial 3.5% formalin for 5 days at room temperature. Then, the cylinders were washed, dehydrated in a graded series of ethanol, embedded in met [89.0, 1378.0, 575.0, 1452.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
36 3 9 text [599.0, 514.0, 1085.0, 756.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
37 3 10 text Hematoxylin–Eosin Staining. Rehydrated sections were first rinsed in distilled water for 2 minutes, then stained for 6 minutes with Mayer's hematoxylin (Merck), rinsed in tap water for 10 minutes, the [599.0, 778.0, 1085.0, 924.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
38 3 11 text Safranin-O Staining. Rehydrated sections were incubated for 4 minutes in a solution of 0.1% safranin-O (Sigma, Taufkirchen, Germany), then washed in distilled water, dehydrated in a graded series of e [599.0, 945.0, 1085.0, 1044.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
39 3 12 text Mankin Score. Mankin scores were determined for the histological evaluation. Values range from 0 (healthy cartilage) to 14 (severe cartilage destruction), distributed in 4 categories: structure (range [600.0, 1066.0, 1084.0, 1284.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
40 3 13 text Biochemical Evaluation. The content of sGAG (reported in $ \mu $g/mL, normalized to a standardized sample surface area of 28.3 mm $ ^{2} $) was determined using the commercially available Blyscan Ass [599.0, 1305.0, 1086.0, 1452.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
41 4 0 header Becher et al. [123.0, 81.0, 223.0, 103.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
42 4 1 number 65 [1087.0, 81.0, 1113.0, 102.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
43 4 2 chart [302.0, 150.0, 934.0, 633.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
44 4 3 figure_title Figure 3. Box plots displaying the SPI measurements of the 3 observers. The interclass correlation coefficient (ICC) was 0.77 (0.70-0.83) indicating good to excellent linear agreement of streaming pot [120.0, 659.0, 1102.0, 706.0] figure_caption 0.92 ["figure_title label: Figure 3. Box plots displaying the SPI measurements of the 3"] figure_caption 0.92 display_zone legend_like figure_number True True
45 4 4 text the cartilage cylinders, each specimen was dissolved in 1.5-mL microcentrifuge tubes in a papain extraction reagent, containing 100 mL of 0.2 M sodium phosphate buffer (pH 6.4) with 0.82 g of sodium a [119.0, 739.0, 605.0, 1245.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
46 4 5 paragraph_title Data Evaluation and Statistical Methods [121.0, 1278.0, 492.0, 1303.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Data Evaluation and Statistical Methods"] subsection_heading 0.6 body_zone heading_like none True True
47 4 6 text To validate the methodologies of the measurements, 3 of the authors (observer 1, board-certified orthopedic surgeon; observer 2, engineering student trained in the use of the device $ ^{17} $; observe [119.0, 1316.0, 605.0, 1438.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
48 4 7 text [626.0, 739.0, 1115.0, 1054.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
49 4 8 paragraph_title Results [631.0, 1085.0, 720.0, 1111.0] section_heading 0.9 ["explicit scholarly heading: Results"] section_heading 0.9 body_zone heading_like canonical_section_name True True
50 4 9 text The computed ICC was 0.77 (0.70-0.83), indicating good to excellent linear agreement of SPI values among the 3 users (Fig. 3). However, unsuccessful measurements occurred at several locations for all [628.0, 1123.0, 1113.0, 1340.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
51 4 10 text The mean ICRS score was $ 0.8 \pm 0.7 $ (range 0-3), and the mean Mankin score was $ 2.8 \pm 1.5 $ (range 0-7). Significant negative correlations between SPI and both ICRS and Mankin scores were obs [628.0, 1341.0, 1115.0, 1437.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
52 5 0 number 66 [94.0, 81.0, 119.0, 102.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
53 5 1 header Cartilage 7(1) [972.0, 80.0, 1083.0, 105.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
54 5 2 chart [274.0, 149.0, 906.0, 752.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
55 5 3 figure_title Figure 4. Linear regression between learning index and number of evaluated knees. [90.0, 785.0, 720.0, 807.0] figure_caption 0.92 ["figure_title label: Figure 4. Linear regression between learning index and numbe"] figure_caption 0.92 display_zone legend_like figure_number True True
56 5 4 text $r = 0.255$, $P = 0.02$, respectively; Fig. 5a and b) together with a significant positive linear correlation between the ICRS and Mankin scores ($r = 0.334$, $P = 0.002$). No significant correlations [90.0, 845.0, 574.0, 967.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
57 5 5 paragraph_title Discussion [92.0, 999.0, 216.0, 1024.0] section_heading 0.9 ["explicit scholarly heading: Discussion"] section_heading 0.9 body_zone heading_like canonical_section_name True True
58 5 6 text The purpose of this study was to assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation wit [89.0, 1037.0, 574.0, 1348.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
59 5 7 text Standardized methods for evaluating of cartilage defects, cartilage repair tissue, and clinical outcomes of cartilage resurfacing are crucial in both the clinical and research contexts. However, the d [89.0, 1350.0, 574.0, 1422.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
60 5 8 text [598.0, 846.0, 1086.0, 1424.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
61 6 0 header Becher et al. [123.0, 81.0, 223.0, 103.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
62 6 1 number 67 [1087.0, 81.0, 1113.0, 102.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
63 6 2 chart [138.0, 163.0, 621.0, 543.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
64 6 3 chart [626.0, 164.0, 1087.0, 534.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
65 6 4 chart [390.0, 554.0, 850.0, 921.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
66 6 5 figure_title Figure 5. Correlations between streaming potential integral (SPI) values and (a) International Cartilage Repair Society (ICRS) score, (b) Mankin score, and (c) sulfated glycosaminoglycan (sGAG) conten [120.0, 966.0, 1102.0, 1012.0] figure_caption 0.92 ["figure_title label: Figure 5. Correlations between streaming potential integral "] figure_caption 0.92 display_zone legend_like figure_number True True
67 6 6 text from one pilot study from our group published by Abedian et al. $ ^{17} $, the available literature about the Arthro-BST is somewhat related to the inventers of the device. $ ^{10,14,18-20} $ [120.0, 1046.0, 604.0, 1116.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
68 6 7 text In the present study, we demonstrated good to excellent linear agreement of SPI values with an ICC of 0.77 (0.70-0.83), which confirms the reliability of the streaming potential measurements among dif [119.0, 1119.0, 605.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
69 6 8 text [628.0, 1045.0, 1115.0, 1262.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
70 6 9 text The present study revealed statistically significant negative correlations between SPI and both ICRS (r = 0.502) and Mankin scores (r = 0.255). Although the correlation coefficient was not high, these [629.0, 1263.0, 1115.0, 1432.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
71 7 0 number 68 [93.0, 81.0, 120.0, 102.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
72 7 1 header Cartilage 7(1) [972.0, 80.0, 1083.0, 105.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
73 7 2 text demonstrated comparable findings when correlating the characteristic value (CV) calculated from NIR with a handheld probe to ICRS scores (r = 0.47) $ ^{29} $ and Mankin score (r = 0.55). $ ^{30} $ A g [89.0, 134.0, 575.0, 710.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
74 7 3 text Although the decrease of glycosaminoglycan content is typical for severe cartilage lesions, $ ^{31,32} $ we could not detect a correlation of SPI values to the sGAG content per wet weight. This observ [89.0, 712.0, 576.0, 1165.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
75 7 4 text In conclusion, the findings of this study confirm the agreement between the SPI and clinically relevant cartilage scores ex vivo under benchtop conditions substantiating that the SPI values may be use [89.0, 1167.0, 575.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone body_like none True True
76 7 5 text [599.0, 134.0, 1085.0, 232.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
77 7 6 paragraph_title Acknowledgment and Funding [600.0, 259.0, 895.0, 282.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Acknowledgment and Funding"] subsection_heading 0.6 body_zone heading_like none True True
78 7 7 text The author(s) received no financial support for the research, authorship, and/or publication of this article. [599.0, 290.0, 1083.0, 336.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
79 7 8 paragraph_title Declaration of Conflicting Interests [601.0, 362.0, 940.0, 386.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Declaration of Conflicting Interests"] backmatter_boundary_candidate 0.5 body_zone heading_like none True True
80 7 9 text The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. [599.0, 393.0, 1084.0, 460.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
81 7 10 paragraph_title Ethical Approval [601.0, 486.0, 766.0, 510.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Ethical Approval"] subsection_heading 0.6 body_zone heading_like short_fragment True True
82 7 11 text The local ethics committee provide ethical approval (IRB No. 1182-2011). [600.0, 518.0, 1082.0, 561.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
83 7 12 paragraph_title References [602.0, 586.0, 713.0, 609.0] reference_heading 0.9 ["references heading: References"] reference_heading 0.9 reference_zone heading_like short_fragment True True
84 7 13 reference_content 1. Brittberg M, Winalski CS. Evaluation of cartilage injuries and repair. J Bone Joint Surg Am. 2003;85-A(Suppl 2):58-69. [611.0, 618.0, 1082.0, 661.0] reference_item 0.85 ["reference content label: 1. Brittberg M, Winalski CS. Evaluation of cartilage injurie"] reference_item 0.85 reference_zone reference_like reference_numeric_dot True True
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87 7 16 reference_content 4. Brittberg M. Cell carriers as the next generation of cell therapy for cartilage repair: a review of the matrix-induced autologous chondrocyte implantation procedure. Am J Sports Med. 2010;38(6):125 [611.0, 817.0, 1083.0, 902.0] reference_item 0.85 ["reference content label: 4. Brittberg M. Cell carriers as the next generation of cell"] reference_item 0.85 reference_zone reference_like reference_numeric_dot True True
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"p15:20",
"p15:21",
"p15:22",
"p15:23",
"p15:24",
"p15:25",
"p15:26",
"p15:27",
"p15:28",
"p15:29",
"p15:30"
],
"findings": [
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_013.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_015.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
"p1:0",
"p1:2",
"p1:4",
"p1:8",
"p1:9",
"p1:11",
"p1:12",
"p1:13",
"p1:15",
"p1:17",
"p1:18",
"p1:19",
"p1:20",
"p1:21",
"p1:22",
"p1:23",
"p2:0",
"p2:12",
"p2:13",
"p2:14"
],
"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
"annotated_page": null,
"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

18
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@ -0,0 +1,18 @@
# OCR Truth Audit Report - 82W2IJIP
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 3, 4, 6, 8, 10, 12, 13, 14, 15]
- Reviewed blocks: 211
## Findings
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

1736
audit/82W2IJIP/audit_scope.json Normal file
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7264
audit/82W2IJIP/block_coverage_summary.json Normal file
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417
audit/82W2IJIP/block_trace.csv Normal file
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@ -0,0 +1,417 @@
page,block_id,raw_label,content_preview,bbox,role,role_confidence,evidence,seed_role,seed_confidence,zone,style_family,marker_type,render_default,index_default
1,0,header,RESEARCH ARTICLE,"[98.0, 53.0, 358.0, 82.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,short_fragment,False,False
1,1,header_image,,"[1037.0, 1.0, 1191.0, 28.0]",unknown_structural,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,frontmatter_main_zone,support_like,empty,False,True
1,2,header,"ADVANCED MATERIALS
www.advmat.de","[942.0, 44.0, 1098.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,3,doc_title,Mechano-Iontronic Hydrogels Generating Biomimetic Endogenous Bioelectricity for Promoting Cartilage Regeneration,"[96.0, 147.0, 992.0, 284.0]",paper_title,0.8,"[""page-1 zone title_zone: Mechano-Iontronic Hydrogels Generating Biomimetic Endogenous""]",paper_title,0.8,frontmatter_main_zone,support_like,none,True,True
1,4,text,"Longwei Li, Zheng Li,* Muxin Yue, Yangshi Shao, Jing Wang, Yutong Song, Zhong Lin Wang,* Yongsheng Zhou,* and Xiong Pu*","[96.0, 314.0, 923.0, 386.0]",authors,0.8,"[""page-1 zone author_zone: Longwei Li, Zheng Li,* Muxin Yue, Yangshi Shao, Jing Wang, Y""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
1,5,abstract,"Articular cartilage regeneration has long been a formidable challenge because of its avascular and aneural nature. Traditional approaches, using exogenous electrical stimulation or electroactive mater","[96.0, 447.0, 739.0, 893.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,body_zone,body_like,none,True,True
1,6,paragraph_title,1. Introduction,"[97.0, 964.0, 246.0, 989.0]",section_heading,0.85,"[""paragraph_title label with numbering: 1. Introduction""]",section_heading,0.85,body_zone,heading_like,heading_numbered,True,True
1,7,text,"Articular cartilage injuries often result in chronic pain and impaired functionality, posing a significant challenge to patients' physical and mental well-being. $ ^{[1]} $ The limited repair capacity","[95.0, 1002.0, 588.0, 1094.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,8,text,"avascular and anneal nature, presenting substantial clinical challenges. $ ^{[2,3]} $ Consequently, it is of paramount importance to develop biomimetic scaffold materials with superior biocompatibilit","[763.0, 434.0, 1099.0, 960.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,9,text,relevant ion channels on the cell membrane (such as calcium ion channels). $ ^{[15-19]} $,"[605.0, 962.0, 1097.0, 1003.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,10,text,"In fact, bioelectricity is majorly in the form of iontronic electricity, that is, the electric field of unscreened ions or the electric current of ion flux. $ ^{[20,21]} $ For example, the bioelectric","[605.0, 1005.0, 1099.0, 1093.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,11,footnote,"L. Li, Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu
Beijing Key Laboratory of High-Entropy Energy Materials and Devices
Beijing Institute of Nanoenergy and Nanosystems
Chinese Academy of Sciences
Beij","[96.0, 1125.0, 564.0, 1236.0]",footnote,0.7,"[""footnote label: L. Li, Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu\nBeijing ""]",footnote,0.7,body_zone,body_like,none,True,True
1,12,footnote,"Z. Li, M. Yue, Y. Zhou
Department of Prosthodontics
Peking University School and Hospital of Stomatology
Beijing 100081, P. R. China
E-mail: prostho_lizheng@hsc.pku.edu.cn; kqzhouysh@hsc.pku.edu.cn","[97.0, 1240.0, 574.0, 1332.0]",footnote,0.7,"[""footnote label: Z. Li, M. Yue, Y. Zhou\nDepartment of Prosthodontics\nPeking U""]",footnote,0.7,body_zone,body_like,none,True,True
1,13,footnote,"Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu
School of Nanoscience and Engineering
University of Chinese Academy of Sciences
Beijing 100049, P. R. China","[606.0, 1122.0, 902.0, 1198.0]",footnote,0.7,"[""footnote label: Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu \nSchool of Nan""]",footnote,0.7,body_zone,body_like,none,True,True
1,14,footnote,"Z. Li, Y. Zhou","[607.0, 1198.0, 705.0, 1219.0]",footnote,0.7,"[""footnote label: Z. Li, Y. Zhou""]",footnote,0.7,body_zone,body_like,short_fragment,True,True
1,15,footnote,National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory o,"[607.0, 1214.0, 1092.0, 1295.0]",footnote,0.7,"[""footnote label: National Center for Stomatology & National Clinical Research""]",footnote,0.7,body_zone,body_like,none,True,True
1,16,footnote,The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202514604,"[97.0, 1374.0, 588.0, 1415.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: The ORCID identification number(s) for the author(s) of this""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
1,17,footnote,"Haidian District, Beijing 100081, P. R. China","[608.0, 1290.0, 907.0, 1310.0]",footnote,0.7,"[""footnote label: Haidian District, Beijing 100081, P. R. China""]",footnote,0.7,body_zone,body_like,none,True,True
1,18,footnote,"M. Yue, Y. Zhou
Institute of Medical Technology
Peking University Health Science Center
Haidian District, Beijing 100191, P. R. China","[608.0, 1312.0, 909.0, 1386.0]",footnote,0.7,"[""footnote label: M. Yue, Y. Zhou\nInstitute of Medical Technology\nPeking Unive""]",footnote,0.7,body_zone,body_like,none,True,True
1,19,footer,DOI: 10.1002/adma.202514604,"[97.0, 1420.0, 341.0, 1443.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
1,20,footnote,"Z. L. Wang
Guangzhou Institute of Blue Energy
Knowledge City, Guangzhou 510555, P. R. China","[607.0, 1389.0, 935.0, 1444.0]",footnote,0.7,"[""footnote label: Z. L. Wang\nGuangzhou Institute of Blue Energy\nKnowledge City""]",footnote,0.7,body_zone,body_like,none,True,True
1,21,footer,"Adv. Mater. 2026, 38, e14604","[98.0, 1487.0, 270.0, 1505.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
1,22,number,e14604 (1 of 17),"[535.0, 1484.0, 659.0, 1508.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
1,23,footer,© 2025 Wiley-VCH GmbH,"[937.0, 1487.0, 1096.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[92.0, 46.0, 339.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
2,1,header_image,,"[936.0, 45.0, 1091.0, 116.0]",unknown_structural,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,body_zone,body_like,empty,False,True
2,2,text,"membrane is the foundation of life activities.[22] For cartilage, it has also been demonstrated that iontronic electric-potential could be generated under pressure deformation, resulting from the ion ","[89.0, 148.0, 582.0, 522.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,3,text,"Herein, we designed a mechano-iontronic hydrogel (MI-hydrogel) for promoting cartilage repair by mimicking the iontronic bioelectricity generation of natural cartilage. The MI-hydrogel, implanted in t","[89.0, 522.0, 582.0, 917.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,4,text,"Our MI-hydrogel presented obvious advantages for cartilage repair, including low infection risk, freedom from secondary surgery, superior convenience, and outstanding repair effect, compared with prev","[89.0, 916.0, 582.0, 1160.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,5,paragraph_title,2. Results and Discussion,"[91.0, 1185.0, 345.0, 1209.0]",section_heading,0.85,"[""paragraph_title label with numbering: 2. Results and Discussion""]",section_heading,0.85,body_zone,heading_like,heading_numbered,True,True
2,6,paragraph_title,2.1. Iontronic Electricity Generation in Cartilage and MI-Hydrogel,"[90.0, 1223.0, 581.0, 1247.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.1. Iontronic Electricity Generation in Cartilage and MI-Hy""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
2,7,text,"The iontronic electricity generation mechanisms of natural cartilage and our MI-hydrogel are compared schematically in Figure 2a. Generally, the cartilage or MI-hydrogel is a porous medium soaked with","[89.0, 1267.0, 582.0, 1444.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,8,text,,"[600.0, 149.0, 1093.0, 434.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
2,9,text,"To measure the iontronic electricity, cartilage or hydrogel samples were immersed in culture solution, and two gold electrodes were arranged at both ends of the bottom. An indenter was used to compres","[599.0, 433.0, 1093.0, 719.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,10,text,"For better understanding, finite-element simulations were conducted by combining Poroelastic mechanics and Poisson–Nernst–Planck equations to calculate the distribution of internal pore pressure, ion ","[599.0, 719.0, 1092.0, 1048.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,11,text,"For the MI-hydrogel, three samples were investigated, namely 7.5 wt.% PNAGA, 15 wt.% PNAGA + 0.9 wt.% NaCl, and 30 wt.% PNAGA + 0.9 wt.% NaCl. According to previous studies, the iontronic electricity ","[598.0, 1049.0, 1093.0, 1445.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,12,footer,"Adv. Mater. 2026, 38, e14604","[93.0, 1487.0, 264.0, 1505.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,13,number,e14604 (2 of 17),"[529.0, 1484.0, 654.0, 1508.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,14,footer,© 2025 Wiley-VCH GmbH,"[931.0, 1486.0, 1090.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,15,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1533.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
3,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98.0, 45.0, 345.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,1,header_image,,"[942.0, 44.0, 1097.0, 116.0]",unknown_structural,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,body_zone,body_like,empty,False,True
3,2,image,,"[160.0, 144.0, 1036.0, 1123.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
3,3,figure_title,Figure 1. Mechano-iontronic effect for promoting cartilage regeneration. a) MI-hydrogel implanted in an articular cartilage defect. b) Mechano-iontronic conversion in MI-hydrogel. c) Comparison betwee,"[95.0, 1134.0, 1100.0, 1233.0]",figure_caption,0.92,"[""figure_title label: Figure 1. Mechano-iontronic effect for promoting cartilage r""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
3,4,text,"and 120 nA at 30% compression strain, significantly higher than 0.6 mV and 26.4 nA of 7.5 wt.% PNAGA hydrogel, respectively (summarized data in Figure 2f and profiles in Figure S5, Supporting Informat","[96.0, 1266.0, 588.0, 1445.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,5,text,,"[604.0, 1266.0, 1099.0, 1446.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
3,6,footer,"Adv. Mater. 2026, 38, e14604","[98.0, 1487.0, 270.0, 1505.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
3,7,number,e14604 (3 of 17),"[535.0, 1484.0, 659.0, 1508.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,8,footer,© 2025 Wiley-VCH GmbH,"[937.0, 1486.0, 1096.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
3,9,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1535.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
4,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[92.0, 45.0, 340.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
4,1,header,"ADVANCED MATERIALS
www.advmat.de","[936.0, 45.0, 1092.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
4,2,figure_title,a,"[99.0, 151.0, 119.0, 171.0]",figure_inner_text,0.9,"[""panel label / figure inner text: a""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
4,3,figure_title,Mechano-iontronic conversion in cartilage,"[109.0, 180.0, 456.0, 201.0]",figure_caption,0.85,"[""figure_title label: Mechano-iontronic conversion in cartilage""]",figure_caption,0.85,body_zone,legend_like,none,True,True
4,4,image,,"[143.0, 208.0, 444.0, 347.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,5,image,,"[135.0, 357.0, 435.0, 415.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,6,image,,"[468.0, 185.0, 747.0, 347.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,7,image,,"[473.0, 356.0, 758.0, 412.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,8,figure_title,b,"[768.0, 150.0, 789.0, 175.0]",figure_inner_text,0.9,"[""panel label / figure inner text: b""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
4,9,image,,"[786.0, 156.0, 1087.0, 293.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,10,image,,"[800.0, 304.0, 1075.0, 405.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,11,figure_title,C,"[104.0, 463.0, 124.0, 483.0]",figure_inner_text,0.9,"[""panel label / figure inner text: C""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
4,12,chart,,"[112.0, 468.0, 418.0, 706.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,13,image,,"[466.0, 456.0, 693.0, 678.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,14,chart,,"[778.0, 448.0, 1084.0, 703.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,15,figure_title,f,"[106.0, 709.0, 122.0, 734.0]",figure_inner_text,0.9,"[""panel label / figure inner text: f""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
4,16,chart,,"[112.0, 712.0, 461.0, 994.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,17,image,,"[465.0, 711.0, 770.0, 923.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,18,chart,,"[778.0, 709.0, 1084.0, 960.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,19,chart,,"[118.0, 988.0, 426.0, 1231.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,20,chart,,"[491.0, 1000.0, 1052.0, 1232.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,21,figure_title,Figure 2. Mechano-iontronic conversion in cartilage and MI-hydrogel. a) Schematic illustration of the mechano-iontronic conversion in cartilage (left) and MI-hydrogel (right). b) Electrical signal tes,"[90.0, 1243.0, 1093.0, 1341.0]",figure_caption,0.92,"[""figure_title label: Figure 2. Mechano-iontronic conversion in cartilage and MI-h""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
4,22,footer,"Adv. Mater. 2026, 38, e14604","[93.0, 1487.0, 264.0, 1504.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
4,23,number,e14604 (4 of 17),"[529.0, 1485.0, 654.0, 1508.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,24,footer,© 2025 Wiley-VCH GmbH,"[931.0, 1487.0, 1090.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
4,25,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1534.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
5,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98.0, 46.0, 345.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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5,2,text,the MI-hydrogel was tested and its output remained stable for 5000 s ( $ \approx $1000 cycles) (Figure 2j). The rheological properties of the MI-hydrogel were also tested. Under room temperature condi,"[95.0, 149.0, 588.0, 303.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,3,text,"We also tested the degradation and swelling of the MI-hydrogel in the PBS (phosphate-buffered saline) solution in vitro, as well as the electrical properties under different periods (Figure S7, Suppor","[96.0, 303.0, 587.0, 501.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,4,paragraph_title,2.2. MI-Hydrogels Promote Chondrogenic Differentiation In Vitro,"[96.0, 543.0, 587.0, 566.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2. MI-Hydrogels Promote Chondrogenic Differentiation In Vi""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,5,text,"We proposed that our MI-hydrogels, under physical stress, can generate endogenous bioelectricity-like electrical signals to promote chondrogenic differentiation of stem cells. In this context, bone ma","[96.0, 588.0, 588.0, 1268.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,6,text,Four control experiments were compared. The two hydrogels with the highest (30 wt.% PNAGA + 0.9 wt.% NaCl) and lowest (7.5 wt.% PNAGA) iontronic electrical outputs were defined as I+ and I− (iontronic,"[95.0, 1268.0, 588.0, 1445.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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5,8,text,"At the gene and protein dimensions, SKY-box transcription factor 9 (SOX9), collagen type 11 alpha 1 chain (COL2A1), and aggrecan (ACAN) were selected as biomarkers to evaluate chondrogenic differentia","[605.0, 301.0, 1098.0, 1050.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,9,text,"Mechanically sensitive ion channels, namely Piezo proteins, are indispensable for mechano-transduction across diverse cellular contexts. Prior studies have emphasized the pivotal role of Piezo1 in med","[604.0, 1048.0, 1098.0, 1445.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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6,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[92.0, 45.0, 339.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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6,12,figure_title,Figure 3. Chondrogenic differentiation of BMSCs in MI-hydrogel under an applied pressure. a) Schematic representation of the mechanical stimulation on BMSCs in MI-hydrogel. The MI-hydrogel is compress,"[90.0, 1238.0, 1094.0, 1428.0]",figure_caption,0.92,"[""figure_title label: Figure 3. Chondrogenic differentiation of BMSCs in MI-hydrog""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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7,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98.0, 46.0, 345.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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7,2,text,"seventh and 14th day after chondrogenic induction. Clearly, the expression of Piezo1 in the iontronic hydrogel under the mechanical force group (I+ M+) was significantly higher than the other three gr","[95.0, 149.0, 587.0, 302.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,3,text,"To further validate the applicability of our findings, we conducted additional experiments using human adipose-derived mesenchymal stem cells (hADSCs). As shown in Figure S12 (Supporting Information),","[95.0, 303.0, 588.0, 525.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,4,paragraph_title,2.3. MI-Hydrogels Reinforce Cartilage Regeneration in Rats,"[95.0, 566.0, 541.0, 589.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3. MI-Hydrogels Reinforce Cartilage Regeneration in Rats""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
7,5,text,"We performed in vivo investigations to assess the influence of our MI-hydrogel within rat knee joints, harnessing exercise-facilitated joint mobility as a means to expedite cartilage repair. For 4 and","[95.0, 609.0, 587.0, 1290.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,6,text,Histological examination of major organs was performed to assess systemic biocompatibility and long-term safety following implantation of the MI-hydrogel constructs. Hematoxylin and eosin (H&E) staini,"[95.0, 1290.0, 588.0, 1446.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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7,8,text,"After 4 and 8 weeks of exercise, the knees were collected and analyzed using various methods, including macroscopic evaluation, new subchondral bone quantification, and histological evaluation. Overal","[606.0, 215.0, 1098.0, 655.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,9,text,"To further evaluate the regeneration of subchondral bone, we employed micro-computed tomography (micro-CT), demonstrating enhanced recovery of subchondral bone in iontronic hydrogel combined with the ","[605.0, 654.0, 1098.0, 1070.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,10,text,"Histological assessment including H&E staining, Safranin O/fast green staining (SOFG), and immunofluorescence staining of Col2a1 revealed the improved regeneration of hyaline cartilage within cartilag","[606.0, 1071.0, 1098.0, 1445.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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8,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[91.0, 45.0, 339.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
8,1,header,"ADVANCED MATERIALS
www.advmat.de","[936.0, 45.0, 1092.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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8,12,figure_title,Figure 4. Promoted cartilage regeneration in vivo with MI-hydrogel implantation. a) Schematic representation and timeline of the experimentation on rats. Defects were created in the femoral knee joint,"[90.0, 1246.0, 1093.0, 1435.0]",figure_caption,0.92,"[""figure_title label: Figure 4. Promoted cartilage regeneration in vivo with MI-hy""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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8,16,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1533.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
9,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98.0, 46.0, 345.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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9,2,text,"exercise, the iontronic hydrogel group demonstrated enhancement in cartilage regeneration (Figure 4b,f), potentially attributable to the spontaneous or passive movements of rats, which may have also p","[95.0, 149.0, 588.0, 564.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,3,text,"Gait analysis at 4 weeks revealed that rats in the I+M+ group exhibited markedly improved paw contact patterns, with larger and more uniform footprints compared to other defect groups (Figure S15a, Su","[95.0, 566.0, 588.0, 851.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,4,text,"Across in vivo outcomes, the omnibus one-way ANOVAs were overwhelmingly powered, with achieved power >0.95 for each outcome (noncentral F method; $ \lambda = \hat{f} \times N $, $ df_1 = 6 $, $ df_","[95.0, 851.0, 587.0, 1051.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,5,paragraph_title,2.4. Metabolic Rewiring Induced by MI-Hydrogel in Cartilage Repair,"[96.0, 1092.0, 553.0, 1137.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4. Metabolic Rewiring Induced by MI-Hydrogel in Cartilage ""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,6,text,"Piezo1 channels are activated in response to mechanical stimuli generated by movement, and their downstream signaling pathways are mainly regulated by activation of calcium channels within the cell me","[95.0, 1157.0, 587.0, 1376.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,7,text,"To unravel the metabolic events in the coupled mechano-iontronic effect contributing to cartilage repair, the articular cartilage was isolated from rats 4 and 8 weeks with or without exercise treatmen","[95.0, 1377.0, 588.0, 1444.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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9,9,text,"Next, to detect the overlap of significantly differentially expressed metabolites in the four groups of I+ M+, I− M+, I+M−, and I− M−, the Venn diagram analysis on the fourth and eighth week was condu","[606.0, 566.0, 1098.0, 786.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,10,text,"A synergistic or exclusive interplay exists among diverse metabolites, and correlation analysis serves as a tool to quantify the metabolic proximities among notably distinct metabolites. This approach","[605.0, 785.0, 1098.0, 1444.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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9,14,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1154.0, 31.0, 1171.0, 1532.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
10,0,header,"ADVANCED
SCIENCE NEWS
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10,5,table,"<table><tr><td colspan=""2"">Metabolites</td><td>Class II</td></tr><tr><td>Pos</td><td>2468</td><td>1783</td></tr><tr><td>Neg</td><td>1746</td><td>1418</td></tr><tr><td>Total</td><td>4214</td><td>3201</","[169.0, 598.0, 403.0, 761.0]",media_asset,0.85,"[""media label: table""]",media_asset,0.85,body_zone,unknown_like,none,True,True
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10,19,figure_title,Figure 5. Overview of metabolic profile analyses of MI-hydrogel in cartilage. a) Schematic representation of the experimentation on cartilage of rats for metabolomic analysis. b) Statistical table of ,"[90.0, 1281.0, 1094.0, 1437.0]",figure_caption,0.92,"[""figure_title label: Figure 5. Overview of metabolic profile analyses of MI-hydro""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
10,20,footer,"Adv. Mater. 2026, 38, e14604","[93.0, 1488.0, 264.0, 1504.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
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10,23,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1535.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
11,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98.0, 46.0, 345.0, 117.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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11,2,paragraph_title,2.5. Improved Cartilage Regeneration via Glutamine Metabolism Remodeling,"[95.0, 149.0, 581.0, 195.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.5. Improved Cartilage Regeneration via Glutamine Metabolis""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
11,3,text,"Subsequently, we conducted an in-depth analysis to identify the specific metabolic signatures that comprise the metabolic pools modulated by the mechano-iontronic coupling effect, thereby elucidating ","[96.0, 214.0, 588.0, 654.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,4,text,We then analyzed the correlation of metabolic proximities to reveal the complex and tightly interaction signaling networks of metabolite categories between I+ M+ and I− M− on weeks 4 and 8. The correl,"[96.0, 654.0, 588.0, 984.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,5,text,"To further validate the enhancement of glutamine metabolism and TCA cycle activity, we performed targeted biochemical assays to quantify key metabolites and enzyme activities. As shown in Figure S19a–","[95.0, 982.0, 587.0, 1399.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,6,text,"Glutamine, the prevalent circulating amino acid, fulfills diverse metabolic functions in cells. A recent investigation elucidated the significance of glutamine metabolism in growth plate chondrocytes ","[96.0, 1399.0, 587.0, 1443.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,7,text,,"[606.0, 149.0, 1098.0, 785.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
11,8,text,"To further validate the role of Piezo1 in mediating the mechano-responsive chondrogenic effects of the M1-hydrogel, we conducted both in vitro and in vivo pharmacological inhibition experiments. Inhib","[605.0, 786.0, 1098.0, 1179.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,9,text,"To confirm the physiological relevance of this pathway, we further performed in vivo experiments by administering intraarticular injections of GsMTx4 or the GLS1 inhibitor BPTES in a rat cartilage def","[605.0, 1181.0, 1099.0, 1445.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,10,footer,"Adv. Mater. 2026, 38, e14604","[98.0, 1487.0, 269.0, 1505.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
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11,12,footer,© 2025 Wiley-VCH GmbH,"[937.0, 1486.0, 1096.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
11,13,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1533.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
12,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[90.0, 45.0, 338.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
12,1,header,"ADVANCED MATERIALS
www.advmat.de","[937.0, 45.0, 1092.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
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12,19,figure_title,"Figure 6. Promoted cartilage regeneration via glutamine metabolism. a–d) Heatmap and volcano plots of DEGs showing that key metabolites in the main metabolic pathways in (a,c) 1+ M+ group versus 1– M−","[91.0, 1282.0, 1093.0, 1436.0]",figure_caption,0.92,"[""figure_title label: Figure 6. Promoted cartilage regeneration via glutamine meta""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
12,20,footer,"Adv. Mater. 2026, 38, e14604","[94.0, 1487.0, 264.0, 1504.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
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12,22,footer,© 2025 Wiley-VCH GmbH,"[932.0, 1487.0, 1090.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
12,23,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1534.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
13,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98.0, 46.0, 345.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
13,1,header_image,,"[942.0, 46.0, 1097.0, 115.0]",unknown_structural,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,,unknown_like,empty,False,True
13,2,text,"metabolism are critical mediators of the MI-hydrogel–induced re-
generative effect.","[95.0, 149.0, 586.0, 192.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,3,text,Our results establish a mechanistic framework in which the MI-hydrogel promotes cartilage repair through a Piezo1–Ca $ ^{2+} $–CaMKII–GLS1 signaling axis. Mechanical stimulation via the hydrogel activ,"[96.0, 194.0, 587.0, 412.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,4,text,These findings provide strong functional evidence for the electro-metabolic coupling mechanism underlying MI-hydrogel-mediated tissue regeneration. While prior studies have highlighted the importance ,"[95.0, 413.0, 587.0, 590.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,5,paragraph_title,3. Conclusion,"[97.0, 625.0, 234.0, 649.0]",section_heading,0.85,"[""paragraph_title label with numbering: 3. Conclusion""]",section_heading,0.85,body_zone,heading_like,heading_numbered,True,True
13,6,text,We biomimetically designed a mechano-iontronic hydrogel exhibiting iontronic electricity under mechanical deformation for promoting cartilage repair. The iontronic electricity generation mechanism was,"[96.0, 663.0, 588.0, 1170.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,7,paragraph_title,4. Experimental Section,"[97.0, 1215.0, 329.0, 1240.0]",reference_item,0.85,"[""paragraph_title label with numbering: 4. Experimental Section""]",section_heading,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
13,8,text,"Materials: N-acryloyl-glycinamide (NAGA), N, N-Methylenebisacrylamide Bis-acrylamide (MBAA), and NaCl were purchased from MACKLIN, China. Photo-initiator 1173 was purchased from Aladdin, China. The α-","[96.0, 1252.0, 586.0, 1385.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
13,9,text,"Iontronic Hydrogel Preparation: The iontronic hydrogels were prepared by mixing 7.5–30 wt.% NAGA (monomer), 0.5 wt.% crosslinker MBAA (mass ratio to monomer), 0.5 wt.% photo-initiator 1173 in 0 or 0.9","[96.0, 1385.0, 587.0, 1443.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
13,10,text,,"[606.0, 151.0, 1098.0, 285.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
13,11,text,"Measurement of Mechano-Iontronic: First, the pork cartilage or hydrogel was cut into long strips (50 × 5 × 3 mm). Placed two 5 × 5 mm gold electrodes at the bottom of the rectangular groove, with a sp","[607.0, 285.0, 1097.0, 416.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
13,12,text,"Characterizations: The mechanical properties of the hydrogel were tested through a universal mechanical machine YLS-71. The hydrogel samples were cylinders with 10 mm in height and 10 mm in diameter, ","[606.0, 417.0, 1098.0, 625.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
13,13,text,"Cell Culture: The human bone marrow-derived mesenchymal stem cells (hBMSCs) used in this study were commercially purchased from ScienCell Research Laboratories (USA, Catalog #7500). BMSCs were collect","[606.0, 625.0, 1098.0, 890.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
13,14,text,"Chondrogenic Induction: Cylindrical molds with a height of 9 mm and a radius of 5 mm were used to create hydrogel samples for the I+ and I− groups, which were then placed centrally on the surface of t","[606.0, 891.0, 1098.0, 1060.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
13,15,text,"Live/Dead Cell Staining: After 14 days of chondrogenic induction, GelMA-encapsulated BMSCs from the different treatment groups were subjected to live/dead fluorescence double staining. A commercial ca","[606.0, 1060.0, 1097.0, 1230.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
13,16,text,"Alcian Blue Staining and Quantification: The compressed hydrogels and culture medium were removed from the wells, and the GelMA blocks were washed three times with PBS, followed by fixation in 95% eth","[606.0, 1231.0, 1098.0, 1401.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
13,17,text,"Quantification of GAG Content by DMMB Assay: To evaluate the synthesis of GAGs by BMSCs under different conditions, cell-laden GelMA","[606.0, 1401.0, 1098.0, 1439.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
13,18,footer,"Adv. Mater. 2026, 38, e14604","[99.0, 1488.0, 269.0, 1504.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
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13,20,footer,© 2025 Wiley-VCH GmbH,"[937.0, 1487.0, 1096.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
13,21,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 29.0, 1171.0, 1533.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
14,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[92.0, 46.0, 338.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
14,1,header_image,,"[936.0, 45.0, 1091.0, 116.0]",unknown_structural,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,,unknown_like,empty,False,True
14,2,text,"constructs were harvested after 14 days of chondrogenic induction. Samples were first digested at 37 °C in a GelMA lysis solution (EFL-Tech Co., Ltd, China) for 2 h. The GAG content in the digested sa","[89.0, 150.0, 582.0, 341.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,3,text,"Confocal Microscopy: The blocks of GelMA-hBMMSCs mixture were collected and washed three times with PBS. The samples were processed using an immunofluorescence (IF) kit (Beyotime, China). The GelMA bl","[89.0, 342.0, 581.0, 795.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,4,text,"Intracellular Calcium Staining by Fluo-4 AM: To assess intracellular calcium levels, GelMA-encapsulated BMSCs after 14 days of chondrogenic induction under different treatment conditions were incubate","[89.0, 795.0, 581.0, 1021.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,5,text,"qRT-PCR: GelMA blocks containing 3D cultured BMSCs were collected and immersed in a 0.3 mg mL⁻¹ GelMA lysis solution (EFL-Tech Co., Ltd, China). The blocks were subjected to repeated pipetting to ensu","[91.0, 1022.0, 581.0, 1361.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,6,text,Western Blot Analysis: Proteins were extracted from GelMA-encapsulated BMSCs using RIPA lysis buffer supplemented with protease and phosphatase inhibitors. Equal amounts of protein were separated by S,"[91.0, 1363.0, 581.0, 1440.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,7,figure_title,Table 1. Primers used in qRT-PCR.,"[602.0, 148.0, 834.0, 168.0]",table_caption,0.9,"[""table prefix matched: Table 1. Primers used in qRT-PCR.""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
14,8,table,<table><tr><td>Gene</td><td>Forward primer(5′-3′)</td><td>Reverse primer(5′-3′)</td></tr><tr><td>GAPDH</td><td>GGTCACCAGGGCTGCTTTT</td><td>GGATCTCGCTCCTGGAAGATG</td></tr><tr><td>SOX9</td><td>CCCTTCAAC,"[602.0, 187.0, 1087.0, 340.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,,unknown_like,none,True,True
14,9,text,"were blocked with 10% non-fat milk and incubated overnight at 4 °C with primary antibodies against COL2A1, p-CaMKII, CaMKII, GLS1, and $ \beta $-actin (internal control). After incubation with HRP-co","[600.0, 400.0, 1092.0, 552.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,10,text,"Animal Experiments: Hydrogel precursor was placed into cylindrical molds with a diameter of 2 mm and a height of 1.5 mm, followed by UV light curing at a wavelength of 365 nm to prepare hydrogel sampl","[601.0, 552.0, 1092.0, 704.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,11,text,"To establish a model of knee cartilage defects, SD rats were anesthetized via intraperitoneal injection of 1% pentobarbital and fixed in a supine position. The fur at the surgical site was shaved. Aft","[600.0, 705.0, 1092.0, 1444.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
14,12,footer,"Adv. Mater. 2026, 38, e14604","[93.0, 1487.0, 264.0, 1504.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
14,13,number,e14604 (14 of 17),"[525.0, 1484.0, 658.0, 1507.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
14,14,footer,© 2025 Wiley-VCH GmbH,"[931.0, 1487.0, 1090.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
14,15,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1534.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
15,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98.0, 46.0, 345.0, 116.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
15,1,header_image,,"[942.0, 46.0, 1097.0, 116.0]",unknown_structural,0.2,"[""unrecognized label 'header_image'""]",unknown_structural,0.2,,unknown_like,empty,False,True
15,2,text,"S.O.-Fast Green Staining: Dehydrated paraffin sections by sequentially immersing them in xylene I for 20 min, xylene II for 20 min, absolute ethanol I for 5 min, absolute ethanol II for 5 min, and 75%","[96.0, 150.0, 587.0, 341.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,3,text,"Micro-CT Analysis and Histomorphometry Analysis: Utilizing an Inveon system (Siemens, Germany), Micro-CT imaging was conducted to assess new bone formation within the defect site. Subsequently, the co","[96.0, 342.0, 587.0, 605.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,4,text,"Gait Analysis: To evaluate the functional recovery of the operated limbs, gait analysis was performed. Rats from each group were allowed to walk freely across a transparent walkway equipped with an au","[97.0, 605.0, 587.0, 776.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,5,text,"Metabolic Analysis: The cartilage of rats in the iontronic hydrogel and exercise group (M+ 1+), non-iontronic hydrogel and exercise group (M+ 1-), iontronic hydrogel and no exercise group (M− 1+), and","[96.0, 776.0, 588.0, 1117.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,6,text,"Quantification of Glu, Gln, and $ \alpha $-KG Contents: The contents of glutamate (Glu), glutamine (Gln), and $ \alpha $-KG in the samples were measured using commercial assay kits (Elabscience, Chi","[96.0, 1117.0, 587.0, 1306.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
15,7,text,Enzyme Activity Assays: The activities of CS and $ \alpha $-KGDH were measured using commercial kits purchased from Sangon Biotech (China) following the manufacturers' protocols. GelMA-encapsulated c,"[96.0, 1306.0, 587.0, 1440.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
15,8,text,,"[606.0, 151.0, 1097.0, 265.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
15,9,text,"Statistical Analysis: Statistical analysis of the data was conducted using GraphPad Prism 8.2.1 software (GraphPad Software Inc., USA), with results presented as mean ± SD. For comparisons involving m","[606.0, 265.0, 1097.0, 437.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,10,paragraph_title,Supporting Information,"[607.0, 476.0, 839.0, 503.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Supporting Information""]",backmatter_boundary_candidate,0.5,,heading_like,none,True,True
15,11,text,Supporting Information is available from the Wiley Online Library or from the author.,"[606.0, 514.0, 1096.0, 553.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,12,paragraph_title,Acknowledgements,"[608.0, 594.0, 800.0, 620.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements""]",sub_subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
15,13,text,"L.L., Z.L., and M.Y. contributed equally to this work. The authors acknowledge support from the grants of the National Natural Science Foundation of China (52173274, 82201023, 82270954), Hainan Provin","[606.0, 632.0, 1098.0, 786.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,14,paragraph_title,Conflict of Interest,"[608.0, 825.0, 792.0, 850.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Conflict of Interest""]",subsection_heading,0.6,body_zone,support_like,none,True,True
15,15,text,The authors declare no conflict of interest.,"[608.0, 862.0, 894.0, 884.0]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,,support_like,none,False,False
15,16,paragraph_title,Data Availability Statement,"[608.0, 925.0, 872.0, 950.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Data Availability Statement""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
15,17,text,The data that support the findings of this study are available from the corresponding author upon reasonable request.,"[606.0, 962.0, 1097.0, 1003.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,18,paragraph_title,Keywords,"[608.0, 1042.0, 707.0, 1068.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Keywords""]",sub_subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
15,19,text,"cartilage repair, endogenous bioelectricity, mechano-iontronic effect, metabolic reprogramming","[606.0, 1080.0, 1096.0, 1121.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,20,text,"Received: July 29, 2025","[941.0, 1142.0, 1096.0, 1160.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,21,text,"Revised: September 7, 2025
Published online: September 18, 2025","[841.0, 1157.0, 1096.0, 1195.0]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,,support_like,none,False,False
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15,27,footer,"Adv. Mater. 2026, 38, e14604","[99.0, 1488.0, 270.0, 1505.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
15,28,footer,e14604 (15 of 17),"[530.0, 1485.0, 664.0, 1507.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,short_fragment,False,False
15,29,footer,© 2025 Wiley-VCH GmbH,"[937.0, 1487.0, 1096.0, 1506.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False
15,30,aside_text,"15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition","[1155.0, 30.0, 1171.0, 1534.0]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
16,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenew","[93.0, 46.0, 295.0, 115.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
16,1,header,"ADVANCED MATERIALS
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1 page block_id raw_label content_preview bbox role role_confidence evidence seed_role seed_confidence zone style_family marker_type render_default index_default
2 1 0 header RESEARCH ARTICLE [98.0, 53.0, 358.0, 82.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like short_fragment False False
3 1 1 header_image [1037.0, 1.0, 1191.0, 28.0] unknown_structural 0.2 ["unrecognized label 'header_image'"] unknown_structural 0.2 frontmatter_main_zone support_like empty False True
4 1 2 header ADVANCED MATERIALS www.advmat.de [942.0, 44.0, 1098.0, 116.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
5 1 3 doc_title Mechano-Iontronic Hydrogels Generating Biomimetic Endogenous Bioelectricity for Promoting Cartilage Regeneration [96.0, 147.0, 992.0, 284.0] paper_title 0.8 ["page-1 zone title_zone: Mechano-Iontronic Hydrogels Generating Biomimetic Endogenous"] paper_title 0.8 frontmatter_main_zone support_like none True True
6 1 4 text Longwei Li, Zheng Li,* Muxin Yue, Yangshi Shao, Jing Wang, Yutong Song, Zhong Lin Wang,* Yongsheng Zhou,* and Xiong Pu* [96.0, 314.0, 923.0, 386.0] authors 0.8 ["page-1 zone author_zone: Longwei Li, Zheng Li,* Muxin Yue, Yangshi Shao, Jing Wang, Y"] authors 0.8 frontmatter_main_zone support_like none True True
7 1 5 abstract Articular cartilage regeneration has long been a formidable challenge because of its avascular and aneural nature. Traditional approaches, using exogenous electrical stimulation or electroactive mater [96.0, 447.0, 739.0, 893.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 body_zone body_like none True True
8 1 6 paragraph_title 1. Introduction [97.0, 964.0, 246.0, 989.0] section_heading 0.85 ["paragraph_title label with numbering: 1. Introduction"] section_heading 0.85 body_zone heading_like heading_numbered True True
9 1 7 text Articular cartilage injuries often result in chronic pain and impaired functionality, posing a significant challenge to patients' physical and mental well-being. $ ^{[1]} $ The limited repair capacity [95.0, 1002.0, 588.0, 1094.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
10 1 8 text avascular and anneal nature, presenting substantial clinical challenges. $ ^{[2,3]} $ Consequently, it is of paramount importance to develop biomimetic scaffold materials with superior biocompatibilit [763.0, 434.0, 1099.0, 960.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
11 1 9 text relevant ion channels on the cell membrane (such as calcium ion channels). $ ^{[15-19]} $ [605.0, 962.0, 1097.0, 1003.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
12 1 10 text In fact, bioelectricity is majorly in the form of iontronic electricity, that is, the electric field of unscreened ions or the electric current of ion flux. $ ^{[20,21]} $ For example, the bioelectric [605.0, 1005.0, 1099.0, 1093.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
13 1 11 footnote L. Li, Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu Beijing Key Laboratory of High-Entropy Energy Materials and Devices Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beij [96.0, 1125.0, 564.0, 1236.0] footnote 0.7 ["footnote label: L. Li, Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu\nBeijing "] footnote 0.7 body_zone body_like none True True
14 1 12 footnote Z. Li, M. Yue, Y. Zhou Department of Prosthodontics Peking University School and Hospital of Stomatology Beijing 100081, P. R. China E-mail: prostho_lizheng@hsc.pku.edu.cn; kqzhouysh@hsc.pku.edu.cn [97.0, 1240.0, 574.0, 1332.0] footnote 0.7 ["footnote label: Z. Li, M. Yue, Y. Zhou\nDepartment of Prosthodontics\nPeking U"] footnote 0.7 body_zone body_like none True True
15 1 13 footnote Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu School of Nanoscience and Engineering University of Chinese Academy of Sciences Beijing 100049, P. R. China [606.0, 1122.0, 902.0, 1198.0] footnote 0.7 ["footnote label: Y. Shao, J. Wang, Y. Song, Z. L. Wang, X. Pu \nSchool of Nan"] footnote 0.7 body_zone body_like none True True
16 1 14 footnote Z. Li, Y. Zhou [607.0, 1198.0, 705.0, 1219.0] footnote 0.7 ["footnote label: Z. Li, Y. Zhou"] footnote 0.7 body_zone body_like short_fragment True True
17 1 15 footnote National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory o [607.0, 1214.0, 1092.0, 1295.0] footnote 0.7 ["footnote label: National Center for Stomatology & National Clinical Research"] footnote 0.7 body_zone body_like none True True
18 1 16 footnote The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202514604 [97.0, 1374.0, 588.0, 1415.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: The ORCID identification number(s) for the author(s) of this"] frontmatter_noise 0.8 body_zone body_like none False False
19 1 17 footnote Haidian District, Beijing 100081, P. R. China [608.0, 1290.0, 907.0, 1310.0] footnote 0.7 ["footnote label: Haidian District, Beijing 100081, P. R. China"] footnote 0.7 body_zone body_like none True True
20 1 18 footnote M. Yue, Y. Zhou Institute of Medical Technology Peking University Health Science Center Haidian District, Beijing 100191, P. R. China [608.0, 1312.0, 909.0, 1386.0] footnote 0.7 ["footnote label: M. Yue, Y. Zhou\nInstitute of Medical Technology\nPeking Unive"] footnote 0.7 body_zone body_like none True True
21 1 19 footer DOI: 10.1002/adma.202514604 [97.0, 1420.0, 341.0, 1443.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
22 1 20 footnote Z. L. Wang Guangzhou Institute of Blue Energy Knowledge City, Guangzhou 510555, P. R. China [607.0, 1389.0, 935.0, 1444.0] footnote 0.7 ["footnote label: Z. L. Wang\nGuangzhou Institute of Blue Energy\nKnowledge City"] footnote 0.7 body_zone body_like none True True
23 1 21 footer Adv. Mater. 2026, 38, e14604 [98.0, 1487.0, 270.0, 1505.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
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25 1 23 footer © 2025 Wiley-VCH GmbH [937.0, 1487.0, 1096.0, 1506.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
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28 2 2 text membrane is the foundation of life activities.[22] For cartilage, it has also been demonstrated that iontronic electric-potential could be generated under pressure deformation, resulting from the ion [89.0, 148.0, 582.0, 522.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
29 2 3 text Herein, we designed a mechano-iontronic hydrogel (MI-hydrogel) for promoting cartilage repair by mimicking the iontronic bioelectricity generation of natural cartilage. The MI-hydrogel, implanted in t [89.0, 522.0, 582.0, 917.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
30 2 4 text Our MI-hydrogel presented obvious advantages for cartilage repair, including low infection risk, freedom from secondary surgery, superior convenience, and outstanding repair effect, compared with prev [89.0, 916.0, 582.0, 1160.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
31 2 5 paragraph_title 2. Results and Discussion [91.0, 1185.0, 345.0, 1209.0] section_heading 0.85 ["paragraph_title label with numbering: 2. Results and Discussion"] section_heading 0.85 body_zone heading_like heading_numbered True True
32 2 6 paragraph_title 2.1. Iontronic Electricity Generation in Cartilage and MI-Hydrogel [90.0, 1223.0, 581.0, 1247.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.1. Iontronic Electricity Generation in Cartilage and MI-Hy"] subsection_heading 0.85 body_zone body_like heading_numbered True True
33 2 7 text The iontronic electricity generation mechanisms of natural cartilage and our MI-hydrogel are compared schematically in Figure 2a. Generally, the cartilage or MI-hydrogel is a porous medium soaked with [89.0, 1267.0, 582.0, 1444.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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35 2 9 text To measure the iontronic electricity, cartilage or hydrogel samples were immersed in culture solution, and two gold electrodes were arranged at both ends of the bottom. An indenter was used to compres [599.0, 433.0, 1093.0, 719.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
36 2 10 text For better understanding, finite-element simulations were conducted by combining Poroelastic mechanics and Poisson–Nernst–Planck equations to calculate the distribution of internal pore pressure, ion [599.0, 719.0, 1092.0, 1048.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
37 2 11 text For the MI-hydrogel, three samples were investigated, namely 7.5 wt.% PNAGA, 15 wt.% PNAGA + 0.9 wt.% NaCl, and 30 wt.% PNAGA + 0.9 wt.% NaCl. According to previous studies, the iontronic electricity [598.0, 1049.0, 1093.0, 1445.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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45 3 3 figure_title Figure 1. Mechano-iontronic effect for promoting cartilage regeneration. a) MI-hydrogel implanted in an articular cartilage defect. b) Mechano-iontronic conversion in MI-hydrogel. c) Comparison betwee [95.0, 1134.0, 1100.0, 1233.0] figure_caption 0.92 ["figure_title label: Figure 1. Mechano-iontronic effect for promoting cartilage r"] figure_caption 0.92 display_zone legend_like figure_number True True
46 3 4 text and 120 nA at 30% compression strain, significantly higher than 0.6 mV and 26.4 nA of 7.5 wt.% PNAGA hydrogel, respectively (summarized data in Figure 2f and profiles in Figure S5, Supporting Informat [96.0, 1266.0, 588.0, 1445.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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73 4 21 figure_title Figure 2. Mechano-iontronic conversion in cartilage and MI-hydrogel. a) Schematic illustration of the mechano-iontronic conversion in cartilage (left) and MI-hydrogel (right). b) Electrical signal tes [90.0, 1243.0, 1093.0, 1341.0] figure_caption 0.92 ["figure_title label: Figure 2. Mechano-iontronic conversion in cartilage and MI-h"] figure_caption 0.92 display_zone legend_like figure_number True True
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77 4 25 aside_text 15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition [1155.0, 30.0, 1171.0, 1534.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
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80 5 2 text the MI-hydrogel was tested and its output remained stable for 5000 s ( $ \approx $1000 cycles) (Figure 2j). The rheological properties of the MI-hydrogel were also tested. Under room temperature condi [95.0, 149.0, 588.0, 303.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
81 5 3 text We also tested the degradation and swelling of the MI-hydrogel in the PBS (phosphate-buffered saline) solution in vitro, as well as the electrical properties under different periods (Figure S7, Suppor [96.0, 303.0, 587.0, 501.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
82 5 4 paragraph_title 2.2. MI-Hydrogels Promote Chondrogenic Differentiation In Vitro [96.0, 543.0, 587.0, 566.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.2. MI-Hydrogels Promote Chondrogenic Differentiation In Vi"] subsection_heading 0.85 body_zone body_like heading_numbered True True
83 5 5 text We proposed that our MI-hydrogels, under physical stress, can generate endogenous bioelectricity-like electrical signals to promote chondrogenic differentiation of stem cells. In this context, bone ma [96.0, 588.0, 588.0, 1268.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
84 5 6 text Four control experiments were compared. The two hydrogels with the highest (30 wt.% PNAGA + 0.9 wt.% NaCl) and lowest (7.5 wt.% PNAGA) iontronic electrical outputs were defined as I+ and I− (iontronic [95.0, 1268.0, 588.0, 1445.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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86 5 8 text At the gene and protein dimensions, SKY-box transcription factor 9 (SOX9), collagen type 11 alpha 1 chain (COL2A1), and aggrecan (ACAN) were selected as biomarkers to evaluate chondrogenic differentia [605.0, 301.0, 1098.0, 1050.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
87 5 9 text Mechanically sensitive ion channels, namely Piezo proteins, are indispensable for mechano-transduction across diverse cellular contexts. Prior studies have emphasized the pivotal role of Piezo1 in med [604.0, 1048.0, 1098.0, 1445.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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104 6 12 figure_title Figure 3. Chondrogenic differentiation of BMSCs in MI-hydrogel under an applied pressure. a) Schematic representation of the mechanical stimulation on BMSCs in MI-hydrogel. The MI-hydrogel is compress [90.0, 1238.0, 1094.0, 1428.0] figure_caption 0.92 ["figure_title label: Figure 3. Chondrogenic differentiation of BMSCs in MI-hydrog"] figure_caption 0.92 display_zone legend_like figure_number True True
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111 7 2 text seventh and 14th day after chondrogenic induction. Clearly, the expression of Piezo1 in the iontronic hydrogel under the mechanical force group (I+ M+) was significantly higher than the other three gr [95.0, 149.0, 587.0, 302.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
112 7 3 text To further validate the applicability of our findings, we conducted additional experiments using human adipose-derived mesenchymal stem cells (hADSCs). As shown in Figure S12 (Supporting Information), [95.0, 303.0, 588.0, 525.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
113 7 4 paragraph_title 2.3. MI-Hydrogels Reinforce Cartilage Regeneration in Rats [95.0, 566.0, 541.0, 589.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.3. MI-Hydrogels Reinforce Cartilage Regeneration in Rats"] subsection_heading 0.85 body_zone body_like heading_numbered True True
114 7 5 text We performed in vivo investigations to assess the influence of our MI-hydrogel within rat knee joints, harnessing exercise-facilitated joint mobility as a means to expedite cartilage repair. For 4 and [95.0, 609.0, 587.0, 1290.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
115 7 6 text Histological examination of major organs was performed to assess systemic biocompatibility and long-term safety following implantation of the MI-hydrogel constructs. Hematoxylin and eosin (H&E) staini [95.0, 1290.0, 588.0, 1446.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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117 7 8 text After 4 and 8 weeks of exercise, the knees were collected and analyzed using various methods, including macroscopic evaluation, new subchondral bone quantification, and histological evaluation. Overal [606.0, 215.0, 1098.0, 655.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
118 7 9 text To further evaluate the regeneration of subchondral bone, we employed micro-computed tomography (micro-CT), demonstrating enhanced recovery of subchondral bone in iontronic hydrogel combined with the [605.0, 654.0, 1098.0, 1070.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
119 7 10 text Histological assessment including H&E staining, Safranin O/fast green staining (SOFG), and immunofluorescence staining of Col2a1 revealed the improved regeneration of hyaline cartilage within cartilag [606.0, 1071.0, 1098.0, 1445.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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136 8 12 figure_title Figure 4. Promoted cartilage regeneration in vivo with MI-hydrogel implantation. a) Schematic representation and timeline of the experimentation on rats. Defects were created in the femoral knee joint [90.0, 1246.0, 1093.0, 1435.0] figure_caption 0.92 ["figure_title label: Figure 4. Promoted cartilage regeneration in vivo with MI-hy"] figure_caption 0.92 display_zone legend_like figure_number True True
137 8 13 footer Adv. Mater. 2026, 38, e14604 [93.0, 1488.0, 264.0, 1504.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
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143 9 2 text exercise, the iontronic hydrogel group demonstrated enhancement in cartilage regeneration (Figure 4b,f), potentially attributable to the spontaneous or passive movements of rats, which may have also p [95.0, 149.0, 588.0, 564.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
144 9 3 text Gait analysis at 4 weeks revealed that rats in the I+M+ group exhibited markedly improved paw contact patterns, with larger and more uniform footprints compared to other defect groups (Figure S15a, Su [95.0, 566.0, 588.0, 851.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
145 9 4 text Across in vivo outcomes, the omnibus one-way ANOVAs were overwhelmingly powered, with achieved power >0.95 for each outcome (noncentral F method; $ \lambda = \hat{f} \times N $, $ df_1 = 6 $, $ df_ [95.0, 851.0, 587.0, 1051.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
146 9 5 paragraph_title 2.4. Metabolic Rewiring Induced by MI-Hydrogel in Cartilage Repair [96.0, 1092.0, 553.0, 1137.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.4. Metabolic Rewiring Induced by MI-Hydrogel in Cartilage "] subsection_heading 0.85 body_zone body_like heading_numbered True True
147 9 6 text Piezo1 channels are activated in response to mechanical stimuli generated by movement, and their downstream signaling pathways are mainly regulated by activation of calcium channels within the cell me [95.0, 1157.0, 587.0, 1376.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
148 9 7 text To unravel the metabolic events in the coupled mechano-iontronic effect contributing to cartilage repair, the articular cartilage was isolated from rats 4 and 8 weeks with or without exercise treatmen [95.0, 1377.0, 588.0, 1444.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
149 9 8 text [605.0, 150.0, 1098.0, 566.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
150 9 9 text Next, to detect the overlap of significantly differentially expressed metabolites in the four groups of I+ M+, I− M+, I+M−, and I− M−, the Venn diagram analysis on the fourth and eighth week was condu [606.0, 566.0, 1098.0, 786.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
151 9 10 text A synergistic or exclusive interplay exists among diverse metabolites, and correlation analysis serves as a tool to quantify the metabolic proximities among notably distinct metabolites. This approach [605.0, 785.0, 1098.0, 1444.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
152 9 11 footer Adv. Mater. 2026, 38, e14604 [98.0, 1487.0, 269.0, 1505.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
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161 10 5 table <table><tr><td colspan="2">Metabolites</td><td>Class II</td></tr><tr><td>Pos</td><td>2468</td><td>1783</td></tr><tr><td>Neg</td><td>1746</td><td>1418</td></tr><tr><td>Total</td><td>4214</td><td>3201</ [169.0, 598.0, 403.0, 761.0] media_asset 0.85 ["media label: table"] media_asset 0.85 body_zone unknown_like none True True
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175 10 19 figure_title Figure 5. Overview of metabolic profile analyses of MI-hydrogel in cartilage. a) Schematic representation of the experimentation on cartilage of rats for metabolomic analysis. b) Statistical table of [90.0, 1281.0, 1094.0, 1437.0] figure_caption 0.92 ["figure_title label: Figure 5. Overview of metabolic profile analyses of MI-hydro"] figure_caption 0.92 display_zone legend_like figure_number True True
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179 10 23 aside_text 15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition [1155.0, 30.0, 1171.0, 1535.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 body_zone body_like none False False
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182 11 2 paragraph_title 2.5. Improved Cartilage Regeneration via Glutamine Metabolism Remodeling [95.0, 149.0, 581.0, 195.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.5. Improved Cartilage Regeneration via Glutamine Metabolis"] subsection_heading 0.85 body_zone body_like heading_numbered True True
183 11 3 text Subsequently, we conducted an in-depth analysis to identify the specific metabolic signatures that comprise the metabolic pools modulated by the mechano-iontronic coupling effect, thereby elucidating [96.0, 214.0, 588.0, 654.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
184 11 4 text We then analyzed the correlation of metabolic proximities to reveal the complex and tightly interaction signaling networks of metabolite categories between I+ M+ and I− M− on weeks 4 and 8. The correl [96.0, 654.0, 588.0, 984.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
185 11 5 text To further validate the enhancement of glutamine metabolism and TCA cycle activity, we performed targeted biochemical assays to quantify key metabolites and enzyme activities. As shown in Figure S19a– [95.0, 982.0, 587.0, 1399.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
186 11 6 text Glutamine, the prevalent circulating amino acid, fulfills diverse metabolic functions in cells. A recent investigation elucidated the significance of glutamine metabolism in growth plate chondrocytes [96.0, 1399.0, 587.0, 1443.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
187 11 7 text [606.0, 149.0, 1098.0, 785.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
188 11 8 text To further validate the role of Piezo1 in mediating the mechano-responsive chondrogenic effects of the M1-hydrogel, we conducted both in vitro and in vivo pharmacological inhibition experiments. Inhib [605.0, 786.0, 1098.0, 1179.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
189 11 9 text To confirm the physiological relevance of this pathway, we further performed in vivo experiments by administering intraarticular injections of GsMTx4 or the GLS1 inhibitor BPTES in a rat cartilage def [605.0, 1181.0, 1099.0, 1445.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
190 11 10 footer Adv. Mater. 2026, 38, e14604 [98.0, 1487.0, 269.0, 1505.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
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213 12 19 figure_title Figure 6. Promoted cartilage regeneration via glutamine metabolism. a–d) Heatmap and volcano plots of DEGs showing that key metabolites in the main metabolic pathways in (a,c) 1+ M+ group versus 1– M− [91.0, 1282.0, 1093.0, 1436.0] figure_caption 0.92 ["figure_title label: Figure 6. Promoted cartilage regeneration via glutamine meta"] figure_caption 0.92 display_zone legend_like figure_number True True
214 12 20 footer Adv. Mater. 2026, 38, e14604 [94.0, 1487.0, 264.0, 1504.0] noise 0.9 ["footer label"] noise 0.9 unknown_like none False False
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217 12 23 aside_text 15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition [1155.0, 30.0, 1171.0, 1534.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 unknown_like none False False
218 13 0 header ADVANCED SCIENCE NEWS www.advancedsciencenews.com [98.0, 46.0, 345.0, 116.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
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220 13 2 text metabolism are critical mediators of the MI-hydrogel–induced re- generative effect. [95.0, 149.0, 586.0, 192.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
221 13 3 text Our results establish a mechanistic framework in which the MI-hydrogel promotes cartilage repair through a Piezo1–Ca $ ^{2+} $–CaMKII–GLS1 signaling axis. Mechanical stimulation via the hydrogel activ [96.0, 194.0, 587.0, 412.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
222 13 4 text These findings provide strong functional evidence for the electro-metabolic coupling mechanism underlying MI-hydrogel-mediated tissue regeneration. While prior studies have highlighted the importance [95.0, 413.0, 587.0, 590.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
223 13 5 paragraph_title 3. Conclusion [97.0, 625.0, 234.0, 649.0] section_heading 0.85 ["paragraph_title label with numbering: 3. Conclusion"] section_heading 0.85 body_zone heading_like heading_numbered True True
224 13 6 text We biomimetically designed a mechano-iontronic hydrogel exhibiting iontronic electricity under mechanical deformation for promoting cartilage repair. The iontronic electricity generation mechanism was [96.0, 663.0, 588.0, 1170.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
225 13 7 paragraph_title 4. Experimental Section [97.0, 1215.0, 329.0, 1240.0] reference_item 0.85 ["paragraph_title label with numbering: 4. Experimental Section"] section_heading 0.85 reference_zone reference_like reference_numeric_dot True True
226 13 8 text Materials: N-acryloyl-glycinamide (NAGA), N, N-Methylenebisacrylamide Bis-acrylamide (MBAA), and NaCl were purchased from MACKLIN, China. Photo-initiator 1173 was purchased from Aladdin, China. The α- [96.0, 1252.0, 586.0, 1385.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
227 13 9 text Iontronic Hydrogel Preparation: The iontronic hydrogels were prepared by mixing 7.5–30 wt.% NAGA (monomer), 0.5 wt.% crosslinker MBAA (mass ratio to monomer), 0.5 wt.% photo-initiator 1173 in 0 or 0.9 [96.0, 1385.0, 587.0, 1443.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
228 13 10 text [606.0, 151.0, 1098.0, 285.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
229 13 11 text Measurement of Mechano-Iontronic: First, the pork cartilage or hydrogel was cut into long strips (50 × 5 × 3 mm). Placed two 5 × 5 mm gold electrodes at the bottom of the rectangular groove, with a sp [607.0, 285.0, 1097.0, 416.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
230 13 12 text Characterizations: The mechanical properties of the hydrogel were tested through a universal mechanical machine YLS-71. The hydrogel samples were cylinders with 10 mm in height and 10 mm in diameter, [606.0, 417.0, 1098.0, 625.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
231 13 13 text Cell Culture: The human bone marrow-derived mesenchymal stem cells (hBMSCs) used in this study were commercially purchased from ScienCell Research Laboratories (USA, Catalog #7500). BMSCs were collect [606.0, 625.0, 1098.0, 890.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
232 13 14 text Chondrogenic Induction: Cylindrical molds with a height of 9 mm and a radius of 5 mm were used to create hydrogel samples for the I+ and I− groups, which were then placed centrally on the surface of t [606.0, 891.0, 1098.0, 1060.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
233 13 15 text Live/Dead Cell Staining: After 14 days of chondrogenic induction, GelMA-encapsulated BMSCs from the different treatment groups were subjected to live/dead fluorescence double staining. A commercial ca [606.0, 1060.0, 1097.0, 1230.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
234 13 16 text Alcian Blue Staining and Quantification: The compressed hydrogels and culture medium were removed from the wells, and the GelMA blocks were washed three times with PBS, followed by fixation in 95% eth [606.0, 1231.0, 1098.0, 1401.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
235 13 17 text Quantification of GAG Content by DMMB Assay: To evaluate the synthesis of GAGs by BMSCs under different conditions, cell-laden GelMA [606.0, 1401.0, 1098.0, 1439.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
236 13 18 footer Adv. Mater. 2026, 38, e14604 [99.0, 1488.0, 269.0, 1504.0] noise 0.9 ["footer label"] noise 0.9 unknown_like none False False
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238 13 20 footer © 2025 Wiley-VCH GmbH [937.0, 1487.0, 1096.0, 1506.0] noise 0.9 ["footer label"] noise 0.9 unknown_like none False False
239 13 21 aside_text 15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition [1155.0, 29.0, 1171.0, 1533.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 unknown_like none False False
240 14 0 header ADVANCED SCIENCE NEWS www.advancedsciencenews.com [92.0, 46.0, 338.0, 116.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
241 14 1 header_image [936.0, 45.0, 1091.0, 116.0] unknown_structural 0.2 ["unrecognized label 'header_image'"] unknown_structural 0.2 unknown_like empty False True
242 14 2 text constructs were harvested after 14 days of chondrogenic induction. Samples were first digested at 37 °C in a GelMA lysis solution (EFL-Tech Co., Ltd, China) for 2 h. The GAG content in the digested sa [89.0, 150.0, 582.0, 341.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
243 14 3 text Confocal Microscopy: The blocks of GelMA-hBMMSCs mixture were collected and washed three times with PBS. The samples were processed using an immunofluorescence (IF) kit (Beyotime, China). The GelMA bl [89.0, 342.0, 581.0, 795.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
244 14 4 text Intracellular Calcium Staining by Fluo-4 AM: To assess intracellular calcium levels, GelMA-encapsulated BMSCs after 14 days of chondrogenic induction under different treatment conditions were incubate [89.0, 795.0, 581.0, 1021.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
245 14 5 text qRT-PCR: GelMA blocks containing 3D cultured BMSCs were collected and immersed in a 0.3 mg mL⁻¹ GelMA lysis solution (EFL-Tech Co., Ltd, China). The blocks were subjected to repeated pipetting to ensu [91.0, 1022.0, 581.0, 1361.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
246 14 6 text Western Blot Analysis: Proteins were extracted from GelMA-encapsulated BMSCs using RIPA lysis buffer supplemented with protease and phosphatase inhibitors. Equal amounts of protein were separated by S [91.0, 1363.0, 581.0, 1440.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
247 14 7 figure_title Table 1. Primers used in qRT-PCR. [602.0, 148.0, 834.0, 168.0] table_caption 0.9 ["table prefix matched: Table 1. Primers used in qRT-PCR."] table_caption 0.9 display_zone table_caption_like table_number True True
248 14 8 table <table><tr><td>Gene</td><td>Forward primer(5′-3′)</td><td>Reverse primer(5′-3′)</td></tr><tr><td>GAPDH</td><td>GGTCACCAGGGCTGCTTTT</td><td>GGATCTCGCTCCTGGAAGATG</td></tr><tr><td>SOX9</td><td>CCCTTCAAC [602.0, 187.0, 1087.0, 340.0] table_html 0.85 ["media label: table"] media_asset 0.85 unknown_like none True True
249 14 9 text were blocked with 10% non-fat milk and incubated overnight at 4 °C with primary antibodies against COL2A1, p-CaMKII, CaMKII, GLS1, and $ \beta $-actin (internal control). After incubation with HRP-co [600.0, 400.0, 1092.0, 552.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
250 14 10 text Animal Experiments: Hydrogel precursor was placed into cylindrical molds with a diameter of 2 mm and a height of 1.5 mm, followed by UV light curing at a wavelength of 365 nm to prepare hydrogel sampl [601.0, 552.0, 1092.0, 704.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
251 14 11 text To establish a model of knee cartilage defects, SD rats were anesthetized via intraperitoneal injection of 1% pentobarbital and fixed in a supine position. The fur at the surgical site was shaved. Aft [600.0, 705.0, 1092.0, 1444.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
252 14 12 footer Adv. Mater. 2026, 38, e14604 [93.0, 1487.0, 264.0, 1504.0] noise 0.9 ["footer label"] noise 0.9 unknown_like none False False
253 14 13 number e14604 (14 of 17) [525.0, 1484.0, 658.0, 1507.0] noise 0.9 ["page number label"] noise 0.9 unknown_like short_fragment False False
254 14 14 footer © 2025 Wiley-VCH GmbH [931.0, 1487.0, 1090.0, 1506.0] noise 0.9 ["footer label"] noise 0.9 unknown_like none False False
255 14 15 aside_text 15214095, 2026, 2, Downloaded from https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202514604 by Shandong University Library, Wiley Online Library on [05/04/2026]. See the Terms and Condition [1155.0, 30.0, 1171.0, 1534.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 unknown_like none False False
256 15 0 header ADVANCED SCIENCE NEWS www.advancedsciencenews.com [98.0, 46.0, 345.0, 116.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
257 15 1 header_image [942.0, 46.0, 1097.0, 116.0] unknown_structural 0.2 ["unrecognized label 'header_image'"] unknown_structural 0.2 unknown_like empty False True
258 15 2 text S.O.-Fast Green Staining: Dehydrated paraffin sections by sequentially immersing them in xylene I for 20 min, xylene II for 20 min, absolute ethanol I for 5 min, absolute ethanol II for 5 min, and 75% [96.0, 150.0, 587.0, 341.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
259 15 3 text Micro-CT Analysis and Histomorphometry Analysis: Utilizing an Inveon system (Siemens, Germany), Micro-CT imaging was conducted to assess new bone formation within the defect site. Subsequently, the co [96.0, 342.0, 587.0, 605.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
260 15 4 text Gait Analysis: To evaluate the functional recovery of the operated limbs, gait analysis was performed. Rats from each group were allowed to walk freely across a transparent walkway equipped with an au [97.0, 605.0, 587.0, 776.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
261 15 5 text Metabolic Analysis: The cartilage of rats in the iontronic hydrogel and exercise group (M+ 1+), non-iontronic hydrogel and exercise group (M+ 1-), iontronic hydrogel and no exercise group (M− 1+), and [96.0, 776.0, 588.0, 1117.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
262 15 6 text Quantification of Glu, Gln, and $ \alpha $-KG Contents: The contents of glutamate (Glu), glutamine (Gln), and $ \alpha $-KG in the samples were measured using commercial assay kits (Elabscience, Chi [96.0, 1117.0, 587.0, 1306.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
263 15 7 text Enzyme Activity Assays: The activities of CS and $ \alpha $-KGDH were measured using commercial kits purchased from Sangon Biotech (China) following the manufacturers' protocols. GelMA-encapsulated c [96.0, 1306.0, 587.0, 1440.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
264 15 8 text [606.0, 151.0, 1097.0, 265.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
265 15 9 text Statistical Analysis: Statistical analysis of the data was conducted using GraphPad Prism 8.2.1 software (GraphPad Software Inc., USA), with results presented as mean ± SD. For comparisons involving m [606.0, 265.0, 1097.0, 437.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
266 15 10 paragraph_title Supporting Information [607.0, 476.0, 839.0, 503.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Supporting Information"] backmatter_boundary_candidate 0.5 heading_like none True True
267 15 11 text Supporting Information is available from the Wiley Online Library or from the author. [606.0, 514.0, 1096.0, 553.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
268 15 12 paragraph_title Acknowledgements [608.0, 594.0, 800.0, 620.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements"] sub_subsection_heading 0.6 body_zone heading_like short_fragment True True
269 15 13 text L.L., Z.L., and M.Y. contributed equally to this work. The authors acknowledge support from the grants of the National Natural Science Foundation of China (52173274, 82201023, 82270954), Hainan Provin [606.0, 632.0, 1098.0, 786.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
270 15 14 paragraph_title Conflict of Interest [608.0, 825.0, 792.0, 850.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Conflict of Interest"] subsection_heading 0.6 body_zone support_like none True True
271 15 15 text The authors declare no conflict of interest. [608.0, 862.0, 894.0, 884.0] frontmatter_noise 0.88 ["default body_paragraph for text label", "late role resolution: editorial phrase cross-validates non-body classification", "zone=body_zone", "style_family=support_like"] body_paragraph 0.6 support_like none False False
272 15 16 paragraph_title Data Availability Statement [608.0, 925.0, 872.0, 950.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Data Availability Statement"] subsection_heading 0.6 body_zone heading_like none True True
273 15 17 text The data that support the findings of this study are available from the corresponding author upon reasonable request. [606.0, 962.0, 1097.0, 1003.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
274 15 18 paragraph_title Keywords [608.0, 1042.0, 707.0, 1068.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Keywords"] sub_subsection_heading 0.6 body_zone heading_like short_fragment True True
275 15 19 text cartilage repair, endogenous bioelectricity, mechano-iontronic effect, metabolic reprogramming [606.0, 1080.0, 1096.0, 1121.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
276 15 20 text Received: July 29, 2025 [941.0, 1142.0, 1096.0, 1160.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
277 15 21 text Revised: September 7, 2025 Published online: September 18, 2025 [841.0, 1157.0, 1096.0, 1195.0] frontmatter_noise 0.88 ["default body_paragraph for text label", "late role resolution: editorial phrase cross-validates non-body classification", "zone=body_zone", "style_family=support_like"] body_paragraph 0.6 support_like none False False
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283 15 27 footer Adv. Mater. 2026, 38, e14604 [99.0, 1488.0, 270.0, 1505.0] noise 0.9 ["footer label"] noise 0.9 unknown_like none False False
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285 15 29 footer © 2025 Wiley-VCH GmbH [937.0, 1487.0, 1096.0, 1506.0] noise 0.9 ["footer label"] noise 0.9 unknown_like none False False
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3
audit/82W2IJIP/reference_intrusion_candidates.json Normal file
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@ -0,0 +1,3 @@
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12
audit/82W2IJIP/reference_span_audit.json Normal file
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609
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"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:3"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:4"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:5"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:6"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p17:7"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_017.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_016.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
"p1:0",
"p1:1",
"p1:2",
"p1:3",
"p1:4",
"p1:5",
"p1:14",
"p1:16",
"p1:17",
"p1:19",
"p2:0",
"p2:1",
"p2:2",
"p2:6",
"p2:7",
"p2:8",
"p2:9",
"p2:10",
"p2:11",
"p2:12"
],
"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
"annotated_page": null,
"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

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# OCR Truth Audit Report - 95FDVE4W
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 4, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]
- Reviewed blocks: 199
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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page,block_id,raw_label,content_preview,bbox,role,role_confidence,evidence,seed_role,seed_confidence,zone,style_family,marker_type,render_default,index_default
1,0,header,"Clin Orthop Relat Res (2024) 482:2239-2255
DOI 10.1097/CORR.0000000000003218","[99.0, 79.0, 433.0, 123.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,1,header,"Clinical Orthopaedics and Related Research $ ^{®} $
A Publication of The Association of Bone and Joint Surgeons $ ^{*} $","[794.0, 52.0, 1070.0, 124.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,2,text,Basic Research,"[113.0, 144.0, 262.0, 168.0]",non_body_insert,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,frontmatter_main_zone,support_like,short_fragment,False,False
1,3,text,OPEN,"[995.0, 143.0, 1065.0, 171.0]",non_body_insert,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,frontmatter_main_zone,support_like,short_fragment,False,False
1,4,doc_title,Tissue-engineered Bicipital Autologous Tendon Patch Enhances Massive Rotator Cuff Defect Repair in a Rabbit Infraspinatus Tendon Defect Model,"[99.0, 221.0, 1067.0, 333.0]",paper_title,0.8,"[""page-1 zone title_zone: Tissue-engineered Bicipital Autologous Tendon Patch Enhances""]",paper_title,0.8,frontmatter_main_zone,support_like,none,True,True
1,5,text,"Youguo Liao MD $ ^{1,2,3,4,5,6} $, Hengzhi Liu MM $ ^{1,2,3,4,5,6} $, Jiayun Huang MD $ ^{1,2,3,4,5,6} $, Zetao Wang MM $ ^{1,2,3,4,5,6,7} $, Tao Zhang MD $ ^{1,2,3,4,5,6} $, Xiangjun Hu MM $ ^{1,8} $","[97.0, 368.0, 1059.0, 490.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,6,text,Received: 15 February 2024 / Accepted: 18 July 2024 / Published online: 17 September 2024,"[99.0, 586.0, 706.0, 607.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Received: 15 February 2024 / Accepted: 18 July 2024 / Publis""]",frontmatter_noise,0.8,body_zone,support_like,none,False,False
1,7,text,"Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons","[99.0, 605.0, 957.0, 628.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Copyright \u00a9 2024 The Author(s). Published by Wolters Kluwer ""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
1,8,paragraph_title,Abstract,"[98.0, 664.0, 184.0, 686.0]",abstract_heading,0.95,"[""abstract heading""]",abstract_heading,0.95,body_zone,heading_like,short_fragment,True,True
1,9,abstract,"Background Massive rotator cuff defects represent an important source of shoulder pain and functional debilitation, substantially diminishing patients' quality of life. The primary treatment of massiv","[97.0, 688.0, 570.0, 927.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,body_zone,body_like,none,True,True
1,10,abstract,"Questions/purposes Using an in vitro analysis, we first asked: (1) What is the biocompatibility and collagen synthesis ability of fibrin glue, and what is the cell growth of tissue-engineered bicipita","[98.0, 928.0, 572.0, 1026.0]",body_paragraph,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,body_zone,body_like,none,True,True
1,11,text,"comprised of fibrin glue and biceps tendon tissue particles? Then, using an in vivo animal model of full-thickness defects in the infraspinatus tendon in New Zealand White rabbits, we asked: (2) What ","[598.0, 664.0, 1072.0, 808.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,12,text,"Methods In vitro experiments were conducted to assess the survival, proliferation, and collagen synthesis ability of tendon stem/progenitor cells cultured in fibrin glue. This was achieved through an ","[598.0, 809.0, 1073.0, 1026.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,13,footnote,The first three authors contributed equally to this manuscript. The last three authors contributed equally to this manuscript.,"[99.0, 1089.0, 984.0, 1113.0]",footnote,0.7,"[""footnote label: The first three authors contributed equally to this manuscri""]",footnote,0.7,body_zone,body_like,none,True,True
1,14,footnote,"The institution of one or more of the authors (WS) has received, during the study period, funding from the NSFC grants (82372376), the Medical Health Science and Technology Project of Zhejiang Provinc","[98.0, 1109.0, 1072.0, 1211.0]",footnote,0.7,"[""footnote label: The institution of one or more of the authors (WS) has recei""]",footnote,0.7,body_zone,body_like,none,True,True
1,15,footnote,"Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest","[98.0, 1210.0, 1071.0, 1271.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Each author certifies that there are no funding or commercia""]",frontmatter_noise,0.8,body_zone,support_like,none,False,False
1,16,footnote,All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research $ ^{\circledR} $ editors and board members are on file with the publication and can be viewed on request,"[98.0, 1270.0, 1070.0, 1310.0]",footnote,0.7,"[""footnote label: All ICMJE Conflict of Interest Forms for authors and Clinica""]",footnote,0.7,body_zone,support_like,none,True,True
1,17,footnote,"Clinical Orthopaedics and Related Research $ ^{\circledR} $ neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, incl","[98.0, 1310.0, 1025.0, 1353.0]",footnote,0.7,"[""footnote label: Clinical Orthopaedics and Related Research $ ^{\\circledR} $ ""]",footnote,0.7,body_zone,body_like,none,True,True
1,18,footnote,Ethical approval for this study was obtained from the Laboratory Animal Welfare and Ethics Committee of Zhejiang University (ZJU20230297).,"[97.0, 1347.0, 1005.0, 1389.0]",footnote,0.7,"[""footnote label: Ethical approval for this study was obtained from the Labora""]",footnote,0.7,body_zone,body_like,none,True,True
1,19,footnote,"This work was performed at Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.","[98.0, 1389.0, 1064.0, 1432.0]",footnote,0.7,"[""footnote label: This work was performed at Department of Orthopedic Surgery,""]",footnote,0.7,body_zone,body_like,none,True,True
1,20,footer_image,,"[904.0, 1470.0, 1070.0, 1502.0]",non_body_insert,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,body_zone,unknown_like,empty,False,False
2,0,number,2240,"[101.0, 80.0, 143.0, 100.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,1,header,Liao et al.,"[172.0, 80.0, 250.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,2,header,Clinical Orthopaedics and Related Research $ ^{\circledR} $,"[737.0, 79.0, 1070.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
2,3,text,control group and 15 rabbits each in the gel and patch groups. Six rabbits were allocated to each of the three groups at the 1- and 3-month time points and three rabbits each were in the gel and patch,"[96.0, 142.0, 571.0, 714.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,4,text,,"[597.0, 141.0, 1072.0, 593.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
2,5,text,"Conclusion This animal study demonstrates that the tissue-engineered bicipital autologous tendon patch effectively modulates an immune response and collagen fibril organization, leading to the promoti","[599.0, 595.0, 1072.0, 717.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,footnote," $ ^{1} $Dr. Li Dak Sum-Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of The Second Affiliated Hospital, Zhejiang University School of Medicine, Han","[98.0, 789.0, 1069.0, 836.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{1} $Dr. Li Dak Sum-Yip Yio Chin Center for Stem Cells an""]",affiliation,0.8,body_zone,body_like,affiliation_marker,True,True
2,7,footnote," $ ^{2} $Institute of Sports Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China","[97.0, 848.0, 672.0, 876.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{2} $Institute of Sports Medicine, Zhejiang University, H""]",affiliation,0.8,body_zone,body_like,affiliation_marker,True,True
2,8,footnote," $ ^{3} $Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, PR China","[97.0, 887.0, 705.0, 916.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{3} $Orthopedics Research Institute of Zhejiang Universit""]",affiliation,0.8,body_zone,body_like,affiliation_marker,True,True
2,9,footnote," $ ^{4} $Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, PR China","[97.0, 927.0, 990.0, 956.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{4} $Key Laboratory of Motor System Disease Research and ""]",affiliation,0.8,body_zone,body_like,affiliation_marker,True,True
2,10,footnote," $ ^{5} $Clinical Research Center of Motor System Disease of Zhejiang Province, Zhejiang, PR China","[97.0, 967.0, 753.0, 996.0]",footnote,0.7,"[""footnote label: $ ^{5} $Clinical Research Center of Motor System Disease of ""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,11,footnote," $ ^{6} $Department of Sports Medicine and Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China","[95.0, 1007.0, 1070.0, 1056.0]",footnote,0.7,"[""footnote label: $ ^{6} $Department of Sports Medicine and Orthopedic Surgery""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,12,footnote," $ ^{7} $Department of Orthopedics, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, Zhejiang, PR China","[95.0, 1067.0, 1071.0, 1116.0]",footnote,0.7,"[""footnote label: $ ^{7} $Department of Orthopedics, Huzhou Central Hospital, ""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,13,footnote," $ ^{8} $School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China","[97.0, 1127.0, 777.0, 1155.0]",footnote,0.7,"[""footnote label: $ ^{8} $School of Stomatology, Zhejiang University School of""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,14,footnote," $ ^{9} $Hangzhou Single-Clean Medical Products Co Ltd, Hangzhou, Zhejiang, PR China","[97.0, 1167.0, 655.0, 1195.0]",footnote,0.7,"[""footnote label: $ ^{9} $Hangzhou Single-Clean Medical Products Co Ltd, Hangz""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,15,footnote," $ ^{10} $Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China","[98.0, 1206.0, 958.0, 1235.0]",footnote,0.7,"[""footnote label: $ ^{10} $Department of Plastic Surgery, Sir Run Run Shaw Hos""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,16,footnote," $ ^{11} $China Orthopedic Regenerative Medicine Group, CORMed, Hangzhou, Zhejiang, PR China","[98.0, 1246.0, 750.0, 1275.0]",footnote,0.7,"[""footnote label: $ ^{11} $China Orthopedic Regenerative Medicine Group, CORMe""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,17,footnote," $ ^{12} $Ningbo No.2 Hospital, Ningbo, Zhejiang, PR China","[98.0, 1286.0, 478.0, 1314.0]",footnote,0.7,"[""footnote label: $ ^{12} $Ningbo No.2 Hospital, Ningbo, Zhejiang, PR China""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,18,footnote," $ ^{13} $Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejia","[98.0, 1327.0, 1070.0, 1373.0]",footnote,0.7,"[""footnote label: $ ^{13} $Zhejiang University-University of Edinburgh Institu""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
2,19,footnote,"W. Shen $ \otimes $, Department of Sports Medicine and Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China, Email: wlshen@zju.edu.","[98.0, 1389.0, 1070.0, 1433.0]",footnote,0.7,"[""footnote label: W. Shen $ \\otimes $, Department of Sports Medicine and Orth""]",footnote,0.7,body_zone,body_like,none,True,True
2,20,footer_image,,"[100.0, 1471.0, 267.0, 1501.0]",unknown_structural,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,body_zone,unknown_like,empty,False,True
3,0,header,"Volume 482, Number 12","[100.0, 80.0, 287.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,1,header,Tissue-engineered Tendon Patch Enhances Tendon Repair,"[573.0, 80.0, 999.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,2,number,2241,"[1029.0, 80.0, 1067.0, 100.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,3,text,"Clinical Relevance The tissue-engineered bicipital autologous tendon patch represents a promising strategy for tendon regeneration, offering potential in the repair of massive rotator cuff defects dur","[98.0, 139.0, 571.0, 333.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,4,paragraph_title,Introduction,"[98.0, 380.0, 219.0, 403.0]",section_heading,0.9,"[""explicit scholarly heading: Introduction""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
3,5,text,"Massive rotator cuff defects are a common shoulder disorder, accounting for 40% of all rotator cuff injuries [2, 12]. Millions of people worldwide are affected by massive rotator cuff defects, which s","[97.0, 427.0, 568.0, 714.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,6,text,"Additionally, massive rotator cuff defects often accompany biceps tendon injury or rupture $ [16] $, frequently necessitating concomitant biceps tenotomy during rotator cuff repair. Therefore, excess","[97.0, 714.0, 570.0, 1120.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,7,text,"Therefore, in this study, we evaluated the use of a tissue-engineered bicipital autologous tendon patch, composed of tendon tissue particles and fibrin glue, for repair of massive rotator cuff defects","[96.0, 1120.0, 571.0, 1434.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,8,paragraph_title,Materials and Methods Overview of Study Design,"[600.0, 140.0, 818.0, 213.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Materials and Methods Overview of Study Design""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
3,9,footer,,"[601.0, 188.0, 818.0, 213.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,empty,False,False
3,10,text,"In this study, we evaluated the biocompatibility and collagen synthesis ability of fibrin glue and the cell growth ability of tissue-engineered tendon patches in vitro, and we assessed tendon regenera","[599.0, 235.0, 1071.0, 548.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,11,paragraph_title,Isolation and Expansion of Cells,"[600.0, 594.0, 872.0, 619.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Isolation and Expansion of Cells""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
3,12,text,"Rabbit tendon stem/progenitor cells were isolated and expanded following established protocols [3]. Briefly, the long head of the biceps tendons were harvested from one male and one female New Zealand","[598.0, 642.0, 1072.0, 1291.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,13,paragraph_title,Assessment of Cell Viability,"[601.0, 1335.0, 833.0, 1359.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Assessment of Cell Viability""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
3,14,text,"The tendon stem/progenitor cells were suspended in the fibrinogen solution of fibrin glue (Fibingluraas $ ^{\textregistered} $, Shanghai","[599.0, 1382.0, 1071.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,15,footer_image,,"[904.0, 1471.0, 1070.0, 1502.0]",unknown_structural,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,body_zone,unknown_like,empty,False,True
4,0,number,2242,"[101.0, 80.0, 143.0, 100.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,1,header,Liao et al.,"[173.0, 80.0, 249.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,2,header,Clinical Orthopaedics and Related Research $ ^{\textregistered} $,"[738.0, 79.0, 1069.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
4,3,image,,"[114.0, 146.0, 1052.0, 622.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,4,figure_title,Fig. 1 This schematic illustration shows the experimental design of the study.,"[109.0, 644.0, 704.0, 666.0]",figure_caption,0.92,"[""figure_title label: Fig. 1 This schematic illustration shows the experimental de""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
4,5,text,"RAAS) at a density of $ 2.5 \times 10^5 $/mL. Subsequently, an equal volume of thrombin solution of fibrin glue was added using a duplex syringe to prepare a cell-laden hydrogel. The cells were cultu","[97.0, 713.0, 570.0, 978.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,6,paragraph_title,Assessment of Cell Proliferation,"[98.0, 1024.0, 365.0, 1048.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Assessment of Cell Proliferation""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
4,7,text,The leach liquor of fibrin glue was prepared following established procedures outlined by the International Organization for Standardization (ISO 10993-12). The fibrin glue was formed by crosslinking ,"[98.0, 1070.0, 568.0, 1263.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,8,text,"Cell proliferation was evaluated using the cell counting kit-8 (CCK-8, Dojindo) assay. Briefly, tendon stem/progenitor cells were seeded at a density of 1000 cells per well in a 96-well plate (Corning","[97.0, 1264.0, 569.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,9,text,,"[599.0, 713.0, 1072.0, 858.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
4,10,paragraph_title,Assessment of Collagen Synthesis Ability,"[601.0, 905.0, 937.0, 929.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Assessment of Collagen Synthesis Ability""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
4,11,text,"We investigated the collagen synthesis ability of tendon stem/progenitor cells in fibrin glue following previously established protocols [24]. Initially, tendon stem/progenitor cells were cultured in ","[599.0, 952.0, 1071.0, 1265.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,12,paragraph_title,Preparation of Autologous Tendon Patch,"[601.0, 1310.0, 941.0, 1335.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Preparation of Autologous Tendon Patch""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
4,13,text,We obtained a small segment of the long head of the biceps tendon tissue of New Zealand White rabbits and washed the tissue with physiological saline during the creation of massive,"[599.0, 1358.0, 1072.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,14,footer,Wolters Kluwer,"[101.0, 1472.0, 266.0, 1501.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,unknown_like,short_fragment,False,False
5,0,header,"Volume 482, Number 12","[100.0, 80.0, 287.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
5,1,header,Tissue-engineered Tendon Patch Enhances Tendon Repair,"[573.0, 80.0, 1000.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
5,2,number,2243,"[1028.0, 80.0, 1069.0, 100.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,3,text,"rotator cuff defects. The tendon tissue was minced while simultaneously adding fibrinogen of fibrin glue. After achieving a paste-like consistency, the tendon tissue was shaped into cuboids measuring ","[97.0, 140.0, 570.0, 310.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,4,paragraph_title,Surgical Procedure of Massive Rotator Cuff Defects and Animal Care,"[97.0, 355.0, 562.0, 404.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Surgical Procedure of Massive Rotator Cuff Defects and Anima""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
5,5,text,"We selected 42 healthy New Zealand White rabbits (provided by the Laboratory Animal Center at Zhejiang University), including 21 male and 21 female rabbits. Their weights ranged from 2.0 to 2.5 kg. Al","[97.0, 426.0, 570.0, 881.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,6,text,"The rabbits were anesthetized with 3% pentobarbital sodium (chemBlink) at a dose of 1.0 mL/kg. A 4-cm incision was made on the left shoulder of the rabbits, followed by layered dissection to expose th","[97.0, 882.0, 570.0, 1335.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,7,text,"All animals survived postoperatively without any adverse reactions, such as infection. At 1 and 3 months after surgery, six rabbits from each of the three groups were euthanized. At 2 months after sur","[97.0, 1335.0, 569.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,8,text,,"[598.0, 141.0, 1072.0, 405.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
5,9,paragraph_title,Histological Analysis,"[601.0, 451.0, 780.0, 476.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Histological Analysis""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
5,10,text,"To evaluate the repair efficacy of the tissue-engineered bicipital autologous tendon patch and the morphology of tendon regeneration, we dehydrated the samples of repaired infraspinatus tendon using a","[598.0, 497.0, 1073.0, 837.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,11,paragraph_title,TEM,"[602.0, 880.0, 652.0, 903.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: TEM""]",sub_subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
5,12,text,"To assess the repair effectiveness of the tissue-engineered bicipital autologous tendon patches on the rotator cuff, particularly in quantitatively analyzing the diameter of regenerated collagen fibri","[599.0, 928.0, 1071.0, 1292.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,13,paragraph_title,Bulk RNA-seq,"[602.0, 1335.0, 722.0, 1359.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Bulk RNA-seq""]",subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
5,14,text,To explore the potential mechanisms underlying tendon regeneration facilitated by tissue-engineered autologous tendon,"[599.0, 1383.0, 1072.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,15,footer_image,,"[903.0, 1471.0, 1070.0, 1502.0]",unknown_structural,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,body_zone,unknown_like,empty,False,True
6,0,number,2244,"[101.0, 80.0, 143.0, 100.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,1,header,Liao et al.,"[172.0, 80.0, 249.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,2,header,Clinical Orthopaedics and Related Research $ ^{\circledR} $,"[738.0, 79.0, 1070.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
6,3,text,"patches, we conducted bulk RNA-seq analysis. The tendon samples were collected at 1, 2, and 3 months after transplantation. After we extracted the tissue RNA, we assessed the RNA quality. The RNA was ","[97.0, 141.0, 569.0, 572.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,4,paragraph_title,Ethical Approval,"[99.0, 606.0, 245.0, 631.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Ethical Approval""]",subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
6,5,text,Ethical approval for this study was obtained from the Laboratory Animal Welfare and Ethics Committee of Zhejiang University (ZJU20230297). The surgical procedures were authorized by the Laboratory Ani,"[98.0, 654.0, 570.0, 777.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,6,paragraph_title,Statistical Analysis,"[99.0, 813.0, 259.0, 837.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Statistical Analysis""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
6,7,text,"The data on cell proliferation with the CCK-8 assay, collagen synthesis ability by Sirius red staining, and the infraspinatus tendon width of the repaired tendon are presented as mean ± SD. Statistica","[97.0, 861.0, 569.0, 1175.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,8,paragraph_title,Results In Vitro Study,"[98.0, 1219.0, 220.0, 1292.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Results In Vitro Study""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
6,9,footer,,"[98.0, 1268.0, 220.0, 1292.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,empty,False,False
6,10,paragraph_title,Evaluation of Biocompatibility and Collagen Synthesis Ability of Fibrin Glue,"[99.0, 1314.0, 522.0, 1360.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Evaluation of Biocompatibility and Collagen Synthesis Abilit""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,11,text,"Fibrin glue did not substantially influence the viability and enduring proliferation of tendon stem/progenitor cells. Live/dead cell viability assay after 1, 4, and 7 days showed that the viability of","[97.0, 1382.0, 569.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,12,text,,"[598.0, 140.0, 1071.0, 331.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
6,13,text,"Fibrin glue effectively enhanced the collagen synthesis ability of tendon stem/progenitor cells, as evidenced by deeper Sirius red staining compared with cells cultured without fibrin glue (Fig. 2D). ","[599.0, 332.0, 1071.0, 548.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,14,paragraph_title,Cell Growth and Collagen Deposition Capacity of Tissue-engineered Bicipital Tendon Patches,"[599.0, 593.0, 990.0, 638.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Cell Growth and Collagen Deposition Capacity of Tissue-engin""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,15,text,"With prolonged cultivation, the number of cells increased (Fig. 3A-B). The cell growth area of tissue-engineered bicipital tendon patches showed a notable increase after culturing for 14 days (78.13% ","[598.0, 662.0, 1073.0, 1263.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,16,paragraph_title,In Vivo Evaluation of Tendon Regeneration in Tissue-engineered Bicipital Autologous Tendon Patches,"[599.0, 1311.0, 1059.0, 1360.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: In Vivo Evaluation of Tendon Regeneration in Tissue-engineer""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
6,17,text,The regenerated tissue in the defect site of the patch group closely approximates the characteristics of natural tendon,"[599.0, 1383.0, 1071.0, 1433.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,18,footer_image,,"[100.0, 1472.0, 266.0, 1501.0]",unknown_structural,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,body_zone,unknown_like,empty,False,True
7,0,header,"Volume 482, Number 12","[101.0, 80.0, 286.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
7,1,header,Tissue-engineered Tendon Patch Enhances Tendon Repair,"[573.0, 81.0, 999.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
7,2,number,2245,"[1029.0, 81.0, 1069.0, 99.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
7,3,image,,"[133.0, 145.0, 298.0, 333.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
7,4,image,,"[297.0, 148.0, 460.0, 311.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
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7,8,figure_title,B,"[642.0, 318.0, 660.0, 338.0]",figure_inner_text,0.9,"[""panel label / figure inner text: B""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
7,9,figure_title,C,"[850.0, 319.0, 870.0, 339.0]",figure_inner_text,0.9,"[""panel label / figure inner text: C""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
7,10,image,,"[134.0, 367.0, 382.0, 536.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
7,11,figure_title,D,"[116.0, 547.0, 138.0, 567.0]",figure_inner_text,0.9,"[""panel label / figure inner text: D""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
7,12,figure_title,Control,"[227.0, 541.0, 290.0, 560.0]",figure_caption_candidate,0.85,"[""figure_title label: Control""]",figure_caption,0.85,body_zone,unknown_like,short_fragment,False,False
7,13,image,,"[381.0, 367.0, 626.0, 544.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
7,14,chart,,"[650.0, 366.0, 840.0, 578.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
7,15,figure_title,Fig. 2 In vitro evaluation of the biocompatibility and collagen synthesis ability of fibrin glue showed that fibrin glue did not influence the viability and enduring proliferation but enhanced the col,"[108.0, 598.0, 1063.0, 820.0]",figure_caption,0.92,"[""figure_title label: Fig. 2 In vitro evaluation of the biocompatibility and colla""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
7,16,text,"tissue, including macroscopic structure, cell nuclear morphology, and collagen fibril arrangement. At 1 month after transplantation, the results of macroscopic observation in a rabbit massive rotator ","[97.0, 851.0, 569.0, 1113.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,17,text,"Histological staining revealed the following observations: In the control group, the tendon defect site exhibited notable voids, characterized by limited regenerated tendon tissue, irregular fiber arr","[98.0, 1114.0, 570.0, 1425.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,18,text,,"[598.0, 851.0, 1071.0, 1185.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
7,19,text,The collagen fibrils in the gel and patch groups had a larger diameter compared with those in the control group (Fig. 6A-E). The cross-sectional examination and quantitative analysis revealed that the,"[599.0, 1186.0, 1071.0, 1426.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,20,footer_image,,"[904.0, 1471.0, 1070.0, 1501.0]",unknown_structural,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,body_zone,unknown_like,empty,False,True
8,0,number,2246,"[101.0, 81.0, 142.0, 99.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
8,1,header,Liao et al.,"[173.0, 81.0, 249.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
8,2,header,Clinical Orthopaedics and Related Research $ ^{\textregistered} $,"[738.0, 79.0, 1069.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
8,3,image,,"[121.0, 138.0, 1047.0, 809.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
8,4,figure_title,"Fig. 3 The cell growth and collagen deposition of tissue-engineered bicipital tendon patches showed ongoing proliferation of cells, resulting in abundant collagen Type I construction. (A) Live cell st","[107.0, 825.0, 1061.0, 959.0]",figure_caption,0.92,"[""figure_title label: Fig. 3 The cell growth and collagen deposition of tissue-eng""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
8,5,text,notably large diameter collagen fibrils were exhibited in the patch group. The collagen fibrils within natural tendons displayed a relatively consistent direction and were closely aligned. Quantitativ,"[97.0, 989.0, 569.0, 1204.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,6,text,"Even 3 months after transplantation, macroscopic observation revealed that in the control group, there was only a small amount of regenerated tissue at the tendon defect site, and the width of the ten","[98.0, 1205.0, 570.0, 1421.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,7,text,,"[598.0, 989.0, 1071.0, 1107.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
8,8,text,"H&E and Masson trichrome staining sections revealed the microstructural characteristics of regenerated tissue (Fig. 7E). In the control group, the defect site displayed scarce dispersed fibrous tissue","[599.0, 1108.0, 1073.0, 1420.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,9,footer,Wolters Kluwer,"[101.0, 1472.0, 266.0, 1501.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,unknown_like,short_fragment,False,False
9,0,header,"Volume 482, Number 12","[101.0, 80.0, 286.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
9,1,header,Tissue-engineered Tendon Patch Enhances Tendon Repair,"[573.0, 81.0, 999.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
9,2,number,2247,"[1029.0, 81.0, 1069.0, 99.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
9,3,image,,"[120.0, 151.0, 1055.0, 951.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
9,4,figure_title,Fig. 4 Macroscopic and histological evaluation of regenerated tendon at 1 month in vivo. (A) This schematic illustration shows the surgical procedure for tissue-engineered bicipital autologous tendon ,"[107.0, 972.0, 1062.0, 1170.0]",figure_caption,0.92,"[""figure_title label: Fig. 4 Macroscopic and histological evaluation of regenerate""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
9,5,text,"both the control and gel groups. Histological scoring also demonstrated that the patch group exhibited the lowest score among three groups (Fig. 8). At 3 months after transplantation, the histological","[97.0, 1218.0, 568.0, 1409.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,6,text,,"[599.0, 1217.0, 1072.0, 1409.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
9,7,footer_image,,"[904.0, 1471.0, 1070.0, 1501.0]",unknown_structural,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,body_zone,unknown_like,empty,False,True
10,0,number,2248,"[101.0, 80.0, 143.0, 100.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
10,1,header,Liao et al.,"[172.0, 80.0, 249.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
10,2,header,Clinical Orthopaedics and Related Research $ ^{\textregistered} $,"[738.0, 79.0, 1069.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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10,7,figure_title,"Fig. 5 (A) The total histological scoring and (B) histological scoring of six separate parameters of regenerated tendon at 1 month in the control group, gel group, and patch group demonstrated the low","[239.0, 494.0, 930.0, 584.0]",figure_caption,0.92,"[""figure_title label: Fig. 5 (A) The total histological scoring and (B) histologic""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
10,8,text,"diameter of collagen fibrils in the three groups were $ 53.34 \pm 6.64 $ nm in the control group, $ 57.11 \pm 7.80 $ nm in the gel group (mean difference 3.77 [95% CI 2.02 to 5.52]; p < 0.001), and ","[97.0, 623.0, 570.0, 908.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,9,text,"The tissue-engineered bicipital autologous tendon patch suppressed immune and inflammatory response while promoting fibril organization, cell adhesion, and differentiation, thereby enhancing tendon re","[97.0, 910.0, 569.0, 1412.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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10,12,text,"Massive rotator cuff defects present a substantive challenge to the patients' daily lives, with a high risk of recurrence after surgical intervention because of the limited regeneration capacity of te","[598.0, 908.0, 1073.0, 1413.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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11,14,figure_title,Fig. 6 (A) This image shows transmission electron microscopy analysis of the regenerated tendon tissues at 1 month. Longitudinal and transverse cross-sections of collagen fibrils showed that the colla,"[106.0, 1038.0, 1060.0, 1236.0]",figure_caption,0.92,"[""figure_title label: Fig. 6 (A) This image shows transmission electron microscopy""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
11,15,text,"alternative for the repair of massive rotator cuff defects by facilitating tendon regeneration. Moreover, the preparation and implantation of the tissue-engineered bicipital autologous tendon patch co","[97.0, 1262.0, 569.0, 1431.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,16,paragraph_title,Limitations,"[603.0, 1263.0, 700.0, 1285.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Limitations""]",sub_subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
11,17,text,"This study has several limitations that warrant consideration. First, in our in vitro experiments we observed substantial cell growth on the surface of the tissue-engineered bicipital tendon patch, wh","[599.0, 1309.0, 1071.0, 1431.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
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12,15,figure_title,Gel,"[582.0, 1100.0, 611.0, 1119.0]",figure_caption,0.85,"[""figure_title label: Gel""]",figure_caption,0.85,,unknown_like,short_fragment,True,True
12,16,figure_title,"Fig. 7 Macroscopic and histological evaluation of tendon regeneration at 3 months in vivo. (A) The macroscopic view of regenerated tendon in the control, gel, and patch groups indicated better repair ","[240.0, 1151.0, 930.0, 1373.0]",figure_caption,0.92,"[""figure_title label: Fig. 7 Macroscopic and histological evaluation of tendon reg""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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13,0,header,"Volume 482, Number 12","[100.0, 80.0, 287.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
13,1,header,Tissue-engineered Tendon Patch Enhances Tendon Repair,"[573.0, 81.0, 1000.0, 102.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
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13,5,figure_title,"Fig. 8 (A) The total histological scoring and (B) histological scoring of six separate parameters of regenerated tendon at 3 months in the control, gel, and patch groups demonstrated the lowest scores","[240.0, 490.0, 930.0, 580.0]",figure_caption,0.92,"[""figure_title label: Fig. 8 (A) The total histological scoring and (B) histologic""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
13,6,text,tendon patch. This discrepancy in cell distribution might result from potential nutrient deficiencies within the tissue-engineered bicipital tendon patch that were caused by in vitro culture. The in v,"[98.0, 621.0, 569.0, 860.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,7,text,"The process of tendon injury regeneration is a complex and lengthy process, including initial inflammatory cell infiltration, subsequent migration and proliferation of tendon cells, collagen Type III ","[98.0, 861.0, 569.0, 1100.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,8,text,"The size and shape of the bones, muscles, and tendons in the shoulder complex can vary greatly from species to species, which can affect the biomechanics and function of the rotator cuff $ [11] $. Ra","[97.0, 1100.0, 570.0, 1314.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,9,text,"In addition, the influence of extrinsic factors (especially muscle mass) on repair also needs to be considered in subsequent studies [1]. Muscle atrophy is considered to be an independent predictor of","[96.0, 1315.0, 569.0, 1412.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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13,11,paragraph_title,Discussion of Key Findings,"[601.0, 957.0, 830.0, 981.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Discussion of Key Findings""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
13,12,text,"In this study, we observed that the patch group exhibited a higher density of robust collagen fibrils with better alignment compared with both the gel and control groups 3 months after in vivo transpl","[599.0, 1004.0, 1073.0, 1413.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
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14,12,figure_title,Orientation in degrees,"[603.0, 1011.0, 781.0, 1031.0]",figure_caption_candidate,0.85,"[""figure_title label: Orientation in degrees""]",figure_caption,0.85,,unknown_like,none,False,False
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14,14,figure_title,Fig. 9 (A) This image shows TEM analysis of the regenerated tendon tissues at 3 months. Longitudinal and transverse cross-sections of collagen fibrils showed that the collagen fibrils in the patch gro,"[107.0, 1051.0, 1059.0, 1229.0]",figure_caption,0.92,"[""figure_title label: Fig. 9 (A) This image shows TEM analysis of the regenerated ""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
14,15,text,"Additionally, the tissue-engineered bicipital autologous tendon patches contain tendon stem/progenitor cells, which accelerate tendon regeneration through mechanisms involving proliferation, different","[98.0, 1262.0, 569.0, 1432.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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14,17,footer,Wolters Kluwer,"[101.0, 1472.0, 266.0, 1501.0]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,short_fragment,False,False
15,0,header,"Volume 482, Number 12","[101.0, 80.0, 286.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
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15,9,figure_title,"Fig. 10 Transcriptional analysis of regenerated tendons from 1 month to 3 months. (A) In the repair process of the patch group and gel group at different points (1, 2, and 3 months) after transplantat","[205.0, 1096.0, 965.0, 1469.0]",figure_caption,0.92,"[""figure_title label: Fig. 10 Transcriptional analysis of regenerated tendons from""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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16,2,header,Clinical Orthopaedics and Related Research $ ^{\textregistered} $,"[738.0, 80.0, 1069.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
16,3,text,"have been discarded during previous massive rotator cuff repair procedures, actually possesses the potential to promote tendon regeneration and serves as a high-quality source for tissue-engineered bi","[97.0, 141.0, 569.0, 284.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,4,text,"Although the mechanisms of tendon regeneration were not the primary focus of this study, through bulk RNA sequencing techniques, we were able to clarify the potential of tissue-engineered bicipital au","[98.0, 285.0, 568.0, 452.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,5,paragraph_title,Conclusion,"[101.0, 499.0, 197.0, 521.0]",section_heading,0.9,"[""explicit scholarly heading: Conclusion""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
16,6,text,"In this in vivo rabbit study, we propose a clinically feasible novel therapy for repairing massive rotator cuff defects. We validated the regenerative potential of tissue-engineered bicipital autologo","[98.0, 547.0, 570.0, 1049.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,7,text,"This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the","[98.0, 1071.0, 568.0, 1193.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,8,text,Acknowledgments We thank the Core Facilities of Zhejiang University School of Medicine for their technical assistance. We thank Mrs. Shuangshuang Liu for her assistance with the confocal laser scannin,"[99.0, 1225.0, 568.0, 1327.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,9,paragraph_title,References,"[100.0, 1345.0, 204.0, 1367.0]",reference_heading,0.9,"[""references heading: References""]",reference_heading,0.9,reference_zone,heading_like,short_fragment,True,True
16,10,reference_content,"1. Bedi A, Bishop J, Keener J, et al. Rotator cuff tears. Nat Rev Dis Primers. 2024;10:8.","[110.0, 1377.0, 566.0, 1416.0]",reference_item,0.85,"[""reference content label: 1. Bedi A, Bishop J, Keener J, et al. Rotator cuff tears. Na""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
16,11,reference_content,"2. Bedi A, Dines J, Warren RF, Dines DM. Massive tears of the rotator cuff. J Bone Joint Surg Am. 2010;92:1894-1908.","[611.0, 142.0, 1069.0, 180.0]",reference_item,0.85,"[""reference content label: 2. Bedi A, Dines J, Warren RF, Dines DM. Massive tears of th""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
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17,1,header,Tissue-engineered Tendon Patch Enhances Tendon Repair,"[574.0, 82.0, 999.0, 101.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
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1 page block_id raw_label content_preview bbox role role_confidence evidence seed_role seed_confidence zone style_family marker_type render_default index_default
2 1 0 header Clin Orthop Relat Res (2024) 482:2239-2255 DOI 10.1097/CORR.0000000000003218 [99.0, 79.0, 433.0, 123.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
3 1 1 header Clinical Orthopaedics and Related Research $ ^{®} $ A Publication of The Association of Bone and Joint Surgeons $ ^{*} $ [794.0, 52.0, 1070.0, 124.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
4 1 2 text Basic Research [113.0, 144.0, 262.0, 168.0] non_body_insert 0.3 ["short text, uncertain role"] unknown_structural 0.3 frontmatter_main_zone support_like short_fragment False False
5 1 3 text OPEN [995.0, 143.0, 1065.0, 171.0] non_body_insert 0.3 ["short text, uncertain role"] unknown_structural 0.3 frontmatter_main_zone support_like short_fragment False False
6 1 4 doc_title Tissue-engineered Bicipital Autologous Tendon Patch Enhances Massive Rotator Cuff Defect Repair in a Rabbit Infraspinatus Tendon Defect Model [99.0, 221.0, 1067.0, 333.0] paper_title 0.8 ["page-1 zone title_zone: Tissue-engineered Bicipital Autologous Tendon Patch Enhances"] paper_title 0.8 frontmatter_main_zone support_like none True True
7 1 5 text Youguo Liao MD $ ^{1,2,3,4,5,6} $, Hengzhi Liu MM $ ^{1,2,3,4,5,6} $, Jiayun Huang MD $ ^{1,2,3,4,5,6} $, Zetao Wang MM $ ^{1,2,3,4,5,6,7} $, Tao Zhang MD $ ^{1,2,3,4,5,6} $, Xiangjun Hu MM $ ^{1,8} $ [97.0, 368.0, 1059.0, 490.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
8 1 6 text Received: 15 February 2024 / Accepted: 18 July 2024 / Published online: 17 September 2024 [99.0, 586.0, 706.0, 607.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Received: 15 February 2024 / Accepted: 18 July 2024 / Publis"] frontmatter_noise 0.8 body_zone support_like none False False
9 1 7 text Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons [99.0, 605.0, 957.0, 628.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Copyright \u00a9 2024 The Author(s). Published by Wolters Kluwer "] frontmatter_noise 0.8 body_zone body_like none False False
10 1 8 paragraph_title Abstract [98.0, 664.0, 184.0, 686.0] abstract_heading 0.95 ["abstract heading"] abstract_heading 0.95 body_zone heading_like short_fragment True True
11 1 9 abstract Background Massive rotator cuff defects represent an important source of shoulder pain and functional debilitation, substantially diminishing patients' quality of life. The primary treatment of massiv [97.0, 688.0, 570.0, 927.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 body_zone body_like none True True
12 1 10 abstract Questions/purposes Using an in vitro analysis, we first asked: (1) What is the biocompatibility and collagen synthesis ability of fibrin glue, and what is the cell growth of tissue-engineered bicipita [98.0, 928.0, 572.0, 1026.0] body_paragraph 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 body_zone body_like none True True
13 1 11 text comprised of fibrin glue and biceps tendon tissue particles? Then, using an in vivo animal model of full-thickness defects in the infraspinatus tendon in New Zealand White rabbits, we asked: (2) What [598.0, 664.0, 1072.0, 808.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
14 1 12 text Methods In vitro experiments were conducted to assess the survival, proliferation, and collagen synthesis ability of tendon stem/progenitor cells cultured in fibrin glue. This was achieved through an [598.0, 809.0, 1073.0, 1026.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
15 1 13 footnote The first three authors contributed equally to this manuscript. The last three authors contributed equally to this manuscript. [99.0, 1089.0, 984.0, 1113.0] footnote 0.7 ["footnote label: The first three authors contributed equally to this manuscri"] footnote 0.7 body_zone body_like none True True
16 1 14 footnote The institution of one or more of the authors (WS) has received, during the study period, funding from the NSFC grants (82372376), the Medical Health Science and Technology Project of Zhejiang Provinc [98.0, 1109.0, 1072.0, 1211.0] footnote 0.7 ["footnote label: The institution of one or more of the authors (WS) has recei"] footnote 0.7 body_zone body_like none True True
17 1 15 footnote Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest [98.0, 1210.0, 1071.0, 1271.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Each author certifies that there are no funding or commercia"] frontmatter_noise 0.8 body_zone support_like none False False
18 1 16 footnote All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research $ ^{\circledR} $ editors and board members are on file with the publication and can be viewed on request [98.0, 1270.0, 1070.0, 1310.0] footnote 0.7 ["footnote label: All ICMJE Conflict of Interest Forms for authors and Clinica"] footnote 0.7 body_zone support_like none True True
19 1 17 footnote Clinical Orthopaedics and Related Research $ ^{\circledR} $ neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, incl [98.0, 1310.0, 1025.0, 1353.0] footnote 0.7 ["footnote label: Clinical Orthopaedics and Related Research $ ^{\\circledR} $ "] footnote 0.7 body_zone body_like none True True
20 1 18 footnote Ethical approval for this study was obtained from the Laboratory Animal Welfare and Ethics Committee of Zhejiang University (ZJU20230297). [97.0, 1347.0, 1005.0, 1389.0] footnote 0.7 ["footnote label: Ethical approval for this study was obtained from the Labora"] footnote 0.7 body_zone body_like none True True
21 1 19 footnote This work was performed at Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China. [98.0, 1389.0, 1064.0, 1432.0] footnote 0.7 ["footnote label: This work was performed at Department of Orthopedic Surgery,"] footnote 0.7 body_zone body_like none True True
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24 2 1 header Liao et al. [172.0, 80.0, 250.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
25 2 2 header Clinical Orthopaedics and Related Research $ ^{\circledR} $ [737.0, 79.0, 1070.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
26 2 3 text control group and 15 rabbits each in the gel and patch groups. Six rabbits were allocated to each of the three groups at the 1- and 3-month time points and three rabbits each were in the gel and patch [96.0, 142.0, 571.0, 714.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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28 2 5 text Conclusion This animal study demonstrates that the tissue-engineered bicipital autologous tendon patch effectively modulates an immune response and collagen fibril organization, leading to the promoti [599.0, 595.0, 1072.0, 717.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
29 2 6 footnote $ ^{1} $Dr. Li Dak Sum-Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of The Second Affiliated Hospital, Zhejiang University School of Medicine, Han [98.0, 789.0, 1069.0, 836.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{1} $Dr. Li Dak Sum-Yip Yio Chin Center for Stem Cells an"] affiliation 0.8 body_zone body_like affiliation_marker True True
30 2 7 footnote $ ^{2} $Institute of Sports Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China [97.0, 848.0, 672.0, 876.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{2} $Institute of Sports Medicine, Zhejiang University, H"] affiliation 0.8 body_zone body_like affiliation_marker True True
31 2 8 footnote $ ^{3} $Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, PR China [97.0, 887.0, 705.0, 916.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{3} $Orthopedics Research Institute of Zhejiang Universit"] affiliation 0.8 body_zone body_like affiliation_marker True True
32 2 9 footnote $ ^{4} $Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, PR China [97.0, 927.0, 990.0, 956.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{4} $Key Laboratory of Motor System Disease Research and "] affiliation 0.8 body_zone body_like affiliation_marker True True
33 2 10 footnote $ ^{5} $Clinical Research Center of Motor System Disease of Zhejiang Province, Zhejiang, PR China [97.0, 967.0, 753.0, 996.0] footnote 0.7 ["footnote label: $ ^{5} $Clinical Research Center of Motor System Disease of "] footnote 0.7 body_zone body_like affiliation_marker True True
34 2 11 footnote $ ^{6} $Department of Sports Medicine and Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China [95.0, 1007.0, 1070.0, 1056.0] footnote 0.7 ["footnote label: $ ^{6} $Department of Sports Medicine and Orthopedic Surgery"] footnote 0.7 body_zone body_like affiliation_marker True True
35 2 12 footnote $ ^{7} $Department of Orthopedics, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, Zhejiang, PR China [95.0, 1067.0, 1071.0, 1116.0] footnote 0.7 ["footnote label: $ ^{7} $Department of Orthopedics, Huzhou Central Hospital, "] footnote 0.7 body_zone body_like affiliation_marker True True
36 2 13 footnote $ ^{8} $School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China [97.0, 1127.0, 777.0, 1155.0] footnote 0.7 ["footnote label: $ ^{8} $School of Stomatology, Zhejiang University School of"] footnote 0.7 body_zone body_like affiliation_marker True True
37 2 14 footnote $ ^{9} $Hangzhou Single-Clean Medical Products Co Ltd, Hangzhou, Zhejiang, PR China [97.0, 1167.0, 655.0, 1195.0] footnote 0.7 ["footnote label: $ ^{9} $Hangzhou Single-Clean Medical Products Co Ltd, Hangz"] footnote 0.7 body_zone body_like affiliation_marker True True
38 2 15 footnote $ ^{10} $Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China [98.0, 1206.0, 958.0, 1235.0] footnote 0.7 ["footnote label: $ ^{10} $Department of Plastic Surgery, Sir Run Run Shaw Hos"] footnote 0.7 body_zone body_like affiliation_marker True True
39 2 16 footnote $ ^{11} $China Orthopedic Regenerative Medicine Group, CORMed, Hangzhou, Zhejiang, PR China [98.0, 1246.0, 750.0, 1275.0] footnote 0.7 ["footnote label: $ ^{11} $China Orthopedic Regenerative Medicine Group, CORMe"] footnote 0.7 body_zone body_like affiliation_marker True True
40 2 17 footnote $ ^{12} $Ningbo No.2 Hospital, Ningbo, Zhejiang, PR China [98.0, 1286.0, 478.0, 1314.0] footnote 0.7 ["footnote label: $ ^{12} $Ningbo No.2 Hospital, Ningbo, Zhejiang, PR China"] footnote 0.7 body_zone body_like affiliation_marker True True
41 2 18 footnote $ ^{13} $Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejia [98.0, 1327.0, 1070.0, 1373.0] footnote 0.7 ["footnote label: $ ^{13} $Zhejiang University-University of Edinburgh Institu"] footnote 0.7 body_zone body_like affiliation_marker True True
42 2 19 footnote W. Shen $ \otimes $, Department of Sports Medicine and Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China, Email: wlshen@zju.edu. [98.0, 1389.0, 1070.0, 1433.0] footnote 0.7 ["footnote label: W. Shen $ \\otimes $, Department of Sports Medicine and Orth"] footnote 0.7 body_zone body_like none True True
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44 3 0 header Volume 482, Number 12 [100.0, 80.0, 287.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
45 3 1 header Tissue-engineered Tendon Patch Enhances Tendon Repair [573.0, 80.0, 999.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
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47 3 3 text Clinical Relevance The tissue-engineered bicipital autologous tendon patch represents a promising strategy for tendon regeneration, offering potential in the repair of massive rotator cuff defects dur [98.0, 139.0, 571.0, 333.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
48 3 4 paragraph_title Introduction [98.0, 380.0, 219.0, 403.0] section_heading 0.9 ["explicit scholarly heading: Introduction"] section_heading 0.9 body_zone heading_like canonical_section_name True True
49 3 5 text Massive rotator cuff defects are a common shoulder disorder, accounting for 40% of all rotator cuff injuries [2, 12]. Millions of people worldwide are affected by massive rotator cuff defects, which s [97.0, 427.0, 568.0, 714.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
50 3 6 text Additionally, massive rotator cuff defects often accompany biceps tendon injury or rupture $ [16] $, frequently necessitating concomitant biceps tenotomy during rotator cuff repair. Therefore, excess [97.0, 714.0, 570.0, 1120.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
51 3 7 text Therefore, in this study, we evaluated the use of a tissue-engineered bicipital autologous tendon patch, composed of tendon tissue particles and fibrin glue, for repair of massive rotator cuff defects [96.0, 1120.0, 571.0, 1434.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
52 3 8 paragraph_title Materials and Methods Overview of Study Design [600.0, 140.0, 818.0, 213.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Materials and Methods Overview of Study Design"] subsection_heading 0.6 body_zone heading_like none True True
53 3 9 footer [601.0, 188.0, 818.0, 213.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like empty False False
54 3 10 text In this study, we evaluated the biocompatibility and collagen synthesis ability of fibrin glue and the cell growth ability of tissue-engineered tendon patches in vitro, and we assessed tendon regenera [599.0, 235.0, 1071.0, 548.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
55 3 11 paragraph_title Isolation and Expansion of Cells [600.0, 594.0, 872.0, 619.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Isolation and Expansion of Cells"] subsection_heading 0.6 body_zone heading_like none True True
56 3 12 text Rabbit tendon stem/progenitor cells were isolated and expanded following established protocols [3]. Briefly, the long head of the biceps tendons were harvested from one male and one female New Zealand [598.0, 642.0, 1072.0, 1291.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
57 3 13 paragraph_title Assessment of Cell Viability [601.0, 1335.0, 833.0, 1359.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Assessment of Cell Viability"] subsection_heading 0.6 body_zone heading_like none True True
58 3 14 text The tendon stem/progenitor cells were suspended in the fibrinogen solution of fibrin glue (Fibingluraas $ ^{\textregistered} $, Shanghai [599.0, 1382.0, 1071.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
59 3 15 footer_image [904.0, 1471.0, 1070.0, 1502.0] unknown_structural 0.2 ["unrecognized label 'footer_image'"] unknown_structural 0.2 body_zone unknown_like empty False True
60 4 0 number 2242 [101.0, 80.0, 143.0, 100.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
61 4 1 header Liao et al. [173.0, 80.0, 249.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
62 4 2 header Clinical Orthopaedics and Related Research $ ^{\textregistered} $ [738.0, 79.0, 1069.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
63 4 3 image [114.0, 146.0, 1052.0, 622.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
64 4 4 figure_title Fig. 1 This schematic illustration shows the experimental design of the study. [109.0, 644.0, 704.0, 666.0] figure_caption 0.92 ["figure_title label: Fig. 1 This schematic illustration shows the experimental de"] figure_caption 0.92 display_zone legend_like figure_number True True
65 4 5 text RAAS) at a density of $ 2.5 \times 10^5 $/mL. Subsequently, an equal volume of thrombin solution of fibrin glue was added using a duplex syringe to prepare a cell-laden hydrogel. The cells were cultu [97.0, 713.0, 570.0, 978.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
66 4 6 paragraph_title Assessment of Cell Proliferation [98.0, 1024.0, 365.0, 1048.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Assessment of Cell Proliferation"] subsection_heading 0.6 body_zone heading_like none True True
67 4 7 text The leach liquor of fibrin glue was prepared following established procedures outlined by the International Organization for Standardization (ISO 10993-12). The fibrin glue was formed by crosslinking [98.0, 1070.0, 568.0, 1263.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
68 4 8 text Cell proliferation was evaluated using the cell counting kit-8 (CCK-8, Dojindo) assay. Briefly, tendon stem/progenitor cells were seeded at a density of 1000 cells per well in a 96-well plate (Corning [97.0, 1264.0, 569.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
69 4 9 text [599.0, 713.0, 1072.0, 858.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
70 4 10 paragraph_title Assessment of Collagen Synthesis Ability [601.0, 905.0, 937.0, 929.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Assessment of Collagen Synthesis Ability"] subsection_heading 0.6 body_zone heading_like none True True
71 4 11 text We investigated the collagen synthesis ability of tendon stem/progenitor cells in fibrin glue following previously established protocols [24]. Initially, tendon stem/progenitor cells were cultured in [599.0, 952.0, 1071.0, 1265.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
72 4 12 paragraph_title Preparation of Autologous Tendon Patch [601.0, 1310.0, 941.0, 1335.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Preparation of Autologous Tendon Patch"] subsection_heading 0.6 body_zone heading_like none True True
73 4 13 text We obtained a small segment of the long head of the biceps tendon tissue of New Zealand White rabbits and washed the tissue with physiological saline during the creation of massive [599.0, 1358.0, 1072.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
74 4 14 footer Wolters Kluwer [101.0, 1472.0, 266.0, 1501.0] noise 0.9 ["footer label"] noise 0.9 body_zone unknown_like short_fragment False False
75 5 0 header Volume 482, Number 12 [100.0, 80.0, 287.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
76 5 1 header Tissue-engineered Tendon Patch Enhances Tendon Repair [573.0, 80.0, 1000.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
77 5 2 number 2243 [1028.0, 80.0, 1069.0, 100.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
78 5 3 text rotator cuff defects. The tendon tissue was minced while simultaneously adding fibrinogen of fibrin glue. After achieving a paste-like consistency, the tendon tissue was shaped into cuboids measuring [97.0, 140.0, 570.0, 310.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
79 5 4 paragraph_title Surgical Procedure of Massive Rotator Cuff Defects and Animal Care [97.0, 355.0, 562.0, 404.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Surgical Procedure of Massive Rotator Cuff Defects and Anima"] subsection_heading 0.6 body_zone heading_like none True True
80 5 5 text We selected 42 healthy New Zealand White rabbits (provided by the Laboratory Animal Center at Zhejiang University), including 21 male and 21 female rabbits. Their weights ranged from 2.0 to 2.5 kg. Al [97.0, 426.0, 570.0, 881.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
81 5 6 text The rabbits were anesthetized with 3% pentobarbital sodium (chemBlink) at a dose of 1.0 mL/kg. A 4-cm incision was made on the left shoulder of the rabbits, followed by layered dissection to expose th [97.0, 882.0, 570.0, 1335.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
82 5 7 text All animals survived postoperatively without any adverse reactions, such as infection. At 1 and 3 months after surgery, six rabbits from each of the three groups were euthanized. At 2 months after sur [97.0, 1335.0, 569.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
83 5 8 text [598.0, 141.0, 1072.0, 405.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
84 5 9 paragraph_title Histological Analysis [601.0, 451.0, 780.0, 476.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Histological Analysis"] subsection_heading 0.6 body_zone heading_like none True True
85 5 10 text To evaluate the repair efficacy of the tissue-engineered bicipital autologous tendon patch and the morphology of tendon regeneration, we dehydrated the samples of repaired infraspinatus tendon using a [598.0, 497.0, 1073.0, 837.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
86 5 11 paragraph_title TEM [602.0, 880.0, 652.0, 903.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: TEM"] sub_subsection_heading 0.6 body_zone heading_like short_fragment True True
87 5 12 text To assess the repair effectiveness of the tissue-engineered bicipital autologous tendon patches on the rotator cuff, particularly in quantitatively analyzing the diameter of regenerated collagen fibri [599.0, 928.0, 1071.0, 1292.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
88 5 13 paragraph_title Bulk RNA-seq [602.0, 1335.0, 722.0, 1359.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Bulk RNA-seq"] subsection_heading 0.6 body_zone heading_like short_fragment True True
89 5 14 text To explore the potential mechanisms underlying tendon regeneration facilitated by tissue-engineered autologous tendon [599.0, 1383.0, 1072.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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91 6 0 number 2244 [101.0, 80.0, 143.0, 100.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
92 6 1 header Liao et al. [172.0, 80.0, 249.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
93 6 2 header Clinical Orthopaedics and Related Research $ ^{\circledR} $ [738.0, 79.0, 1070.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
94 6 3 text patches, we conducted bulk RNA-seq analysis. The tendon samples were collected at 1, 2, and 3 months after transplantation. After we extracted the tissue RNA, we assessed the RNA quality. The RNA was [97.0, 141.0, 569.0, 572.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
95 6 4 paragraph_title Ethical Approval [99.0, 606.0, 245.0, 631.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Ethical Approval"] subsection_heading 0.6 body_zone heading_like short_fragment True True
96 6 5 text Ethical approval for this study was obtained from the Laboratory Animal Welfare and Ethics Committee of Zhejiang University (ZJU20230297). The surgical procedures were authorized by the Laboratory Ani [98.0, 654.0, 570.0, 777.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
97 6 6 paragraph_title Statistical Analysis [99.0, 813.0, 259.0, 837.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Statistical Analysis"] subsection_heading 0.6 body_zone heading_like none True True
98 6 7 text The data on cell proliferation with the CCK-8 assay, collagen synthesis ability by Sirius red staining, and the infraspinatus tendon width of the repaired tendon are presented as mean ± SD. Statistica [97.0, 861.0, 569.0, 1175.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
99 6 8 paragraph_title Results In Vitro Study [98.0, 1219.0, 220.0, 1292.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Results In Vitro Study"] subsection_heading 0.6 body_zone heading_like none True True
100 6 9 footer [98.0, 1268.0, 220.0, 1292.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like empty False False
101 6 10 paragraph_title Evaluation of Biocompatibility and Collagen Synthesis Ability of Fibrin Glue [99.0, 1314.0, 522.0, 1360.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Evaluation of Biocompatibility and Collagen Synthesis Abilit"] subsection_heading 0.6 body_zone body_like none True True
102 6 11 text Fibrin glue did not substantially influence the viability and enduring proliferation of tendon stem/progenitor cells. Live/dead cell viability assay after 1, 4, and 7 days showed that the viability of [97.0, 1382.0, 569.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
103 6 12 text [598.0, 140.0, 1071.0, 331.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
104 6 13 text Fibrin glue effectively enhanced the collagen synthesis ability of tendon stem/progenitor cells, as evidenced by deeper Sirius red staining compared with cells cultured without fibrin glue (Fig. 2D). [599.0, 332.0, 1071.0, 548.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
105 6 14 paragraph_title Cell Growth and Collagen Deposition Capacity of Tissue-engineered Bicipital Tendon Patches [599.0, 593.0, 990.0, 638.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Cell Growth and Collagen Deposition Capacity of Tissue-engin"] subsection_heading 0.6 body_zone body_like none True True
106 6 15 text With prolonged cultivation, the number of cells increased (Fig. 3A-B). The cell growth area of tissue-engineered bicipital tendon patches showed a notable increase after culturing for 14 days (78.13% [598.0, 662.0, 1073.0, 1263.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
107 6 16 paragraph_title In Vivo Evaluation of Tendon Regeneration in Tissue-engineered Bicipital Autologous Tendon Patches [599.0, 1311.0, 1059.0, 1360.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: In Vivo Evaluation of Tendon Regeneration in Tissue-engineer"] subsection_heading 0.6 body_zone heading_like none True True
108 6 17 text The regenerated tissue in the defect site of the patch group closely approximates the characteristics of natural tendon [599.0, 1383.0, 1071.0, 1433.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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110 7 0 header Volume 482, Number 12 [101.0, 80.0, 286.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
111 7 1 header Tissue-engineered Tendon Patch Enhances Tendon Repair [573.0, 81.0, 999.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
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115 7 5 image [462.0, 146.0, 625.0, 315.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
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122 7 12 figure_title Control [227.0, 541.0, 290.0, 560.0] figure_caption_candidate 0.85 ["figure_title label: Control"] figure_caption 0.85 body_zone unknown_like short_fragment False False
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124 7 14 chart [650.0, 366.0, 840.0, 578.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 body_zone unknown_like empty True True
125 7 15 figure_title Fig. 2 In vitro evaluation of the biocompatibility and collagen synthesis ability of fibrin glue showed that fibrin glue did not influence the viability and enduring proliferation but enhanced the col [108.0, 598.0, 1063.0, 820.0] figure_caption 0.92 ["figure_title label: Fig. 2 In vitro evaluation of the biocompatibility and colla"] figure_caption 0.92 display_zone legend_like figure_number True True
126 7 16 text tissue, including macroscopic structure, cell nuclear morphology, and collagen fibril arrangement. At 1 month after transplantation, the results of macroscopic observation in a rabbit massive rotator [97.0, 851.0, 569.0, 1113.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
127 7 17 text Histological staining revealed the following observations: In the control group, the tendon defect site exhibited notable voids, characterized by limited regenerated tendon tissue, irregular fiber arr [98.0, 1114.0, 570.0, 1425.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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129 7 19 text The collagen fibrils in the gel and patch groups had a larger diameter compared with those in the control group (Fig. 6A-E). The cross-sectional examination and quantitative analysis revealed that the [599.0, 1186.0, 1071.0, 1426.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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132 8 1 header Liao et al. [173.0, 81.0, 249.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
133 8 2 header Clinical Orthopaedics and Related Research $ ^{\textregistered} $ [738.0, 79.0, 1069.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
134 8 3 image [121.0, 138.0, 1047.0, 809.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
135 8 4 figure_title Fig. 3 The cell growth and collagen deposition of tissue-engineered bicipital tendon patches showed ongoing proliferation of cells, resulting in abundant collagen Type I construction. (A) Live cell st [107.0, 825.0, 1061.0, 959.0] figure_caption 0.92 ["figure_title label: Fig. 3 The cell growth and collagen deposition of tissue-eng"] figure_caption 0.92 display_zone legend_like figure_number True True
136 8 5 text notably large diameter collagen fibrils were exhibited in the patch group. The collagen fibrils within natural tendons displayed a relatively consistent direction and were closely aligned. Quantitativ [97.0, 989.0, 569.0, 1204.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
137 8 6 text Even 3 months after transplantation, macroscopic observation revealed that in the control group, there was only a small amount of regenerated tissue at the tendon defect site, and the width of the ten [98.0, 1205.0, 570.0, 1421.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
138 8 7 text [598.0, 989.0, 1071.0, 1107.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
139 8 8 text H&E and Masson trichrome staining sections revealed the microstructural characteristics of regenerated tissue (Fig. 7E). In the control group, the defect site displayed scarce dispersed fibrous tissue [599.0, 1108.0, 1073.0, 1420.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
140 8 9 footer Wolters Kluwer [101.0, 1472.0, 266.0, 1501.0] noise 0.9 ["footer label"] noise 0.9 body_zone unknown_like short_fragment False False
141 9 0 header Volume 482, Number 12 [101.0, 80.0, 286.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
142 9 1 header Tissue-engineered Tendon Patch Enhances Tendon Repair [573.0, 81.0, 999.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
143 9 2 number 2247 [1029.0, 81.0, 1069.0, 99.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
144 9 3 image [120.0, 151.0, 1055.0, 951.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
145 9 4 figure_title Fig. 4 Macroscopic and histological evaluation of regenerated tendon at 1 month in vivo. (A) This schematic illustration shows the surgical procedure for tissue-engineered bicipital autologous tendon [107.0, 972.0, 1062.0, 1170.0] figure_caption 0.92 ["figure_title label: Fig. 4 Macroscopic and histological evaluation of regenerate"] figure_caption 0.92 display_zone legend_like figure_number True True
146 9 5 text both the control and gel groups. Histological scoring also demonstrated that the patch group exhibited the lowest score among three groups (Fig. 8). At 3 months after transplantation, the histological [97.0, 1218.0, 568.0, 1409.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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150 10 1 header Liao et al. [172.0, 80.0, 249.0, 101.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
151 10 2 header Clinical Orthopaedics and Related Research $ ^{\textregistered} $ [738.0, 79.0, 1069.0, 102.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
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153 10 4 figure_title A [248.0, 450.0, 275.0, 473.0] figure_inner_text 0.9 ["panel label / figure inner text: A"] figure_inner_text 0.9 display_zone legend_like panel_label True True
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155 10 6 figure_title B [584.0, 450.0, 608.0, 472.0] figure_inner_text 0.9 ["panel label / figure inner text: B"] figure_inner_text 0.9 display_zone legend_like panel_label True True
156 10 7 figure_title Fig. 5 (A) The total histological scoring and (B) histological scoring of six separate parameters of regenerated tendon at 1 month in the control group, gel group, and patch group demonstrated the low [239.0, 494.0, 930.0, 584.0] figure_caption 0.92 ["figure_title label: Fig. 5 (A) The total histological scoring and (B) histologic"] figure_caption 0.92 display_zone legend_like figure_number True True
157 10 8 text diameter of collagen fibrils in the three groups were $ 53.34 \pm 6.64 $ nm in the control group, $ 57.11 \pm 7.80 $ nm in the gel group (mean difference 3.77 [95% CI 2.02 to 5.52]; p < 0.001), and [97.0, 623.0, 570.0, 908.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
158 10 9 text The tissue-engineered bicipital autologous tendon patch suppressed immune and inflammatory response while promoting fibril organization, cell adhesion, and differentiation, thereby enhancing tendon re [97.0, 910.0, 569.0, 1412.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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160 10 11 paragraph_title Discussion [601.0, 859.0, 704.0, 883.0] section_heading 0.9 ["explicit scholarly heading: Discussion"] section_heading 0.9 body_zone heading_like canonical_section_name True True
161 10 12 text Massive rotator cuff defects present a substantive challenge to the patients' daily lives, with a high risk of recurrence after surgical intervention because of the limited regeneration capacity of te [598.0, 908.0, 1073.0, 1413.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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177 11 14 figure_title Fig. 6 (A) This image shows transmission electron microscopy analysis of the regenerated tendon tissues at 1 month. Longitudinal and transverse cross-sections of collagen fibrils showed that the colla [106.0, 1038.0, 1060.0, 1236.0] figure_caption 0.92 ["figure_title label: Fig. 6 (A) This image shows transmission electron microscopy"] figure_caption 0.92 display_zone legend_like figure_number True True
178 11 15 text alternative for the repair of massive rotator cuff defects by facilitating tendon regeneration. Moreover, the preparation and implantation of the tissue-engineered bicipital autologous tendon patch co [97.0, 1262.0, 569.0, 1431.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
179 11 16 paragraph_title Limitations [603.0, 1263.0, 700.0, 1285.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Limitations"] sub_subsection_heading 0.6 body_zone heading_like short_fragment True True
180 11 17 text This study has several limitations that warrant consideration. First, in our in vitro experiments we observed substantial cell growth on the surface of the tissue-engineered bicipital tendon patch, wh [599.0, 1309.0, 1071.0, 1431.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
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197 12 15 figure_title Gel [582.0, 1100.0, 611.0, 1119.0] figure_caption 0.85 ["figure_title label: Gel"] figure_caption 0.85 unknown_like short_fragment True True
198 12 16 figure_title Fig. 7 Macroscopic and histological evaluation of tendon regeneration at 3 months in vivo. (A) The macroscopic view of regenerated tendon in the control, gel, and patch groups indicated better repair [240.0, 1151.0, 930.0, 1373.0] figure_caption 0.92 ["figure_title label: Fig. 7 Macroscopic and histological evaluation of tendon reg"] figure_caption 0.92 display_zone legend_like figure_number True True
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205 13 5 figure_title Fig. 8 (A) The total histological scoring and (B) histological scoring of six separate parameters of regenerated tendon at 3 months in the control, gel, and patch groups demonstrated the lowest scores [240.0, 490.0, 930.0, 580.0] figure_caption 0.92 ["figure_title label: Fig. 8 (A) The total histological scoring and (B) histologic"] figure_caption 0.92 display_zone legend_like figure_number True True
206 13 6 text tendon patch. This discrepancy in cell distribution might result from potential nutrient deficiencies within the tissue-engineered bicipital tendon patch that were caused by in vitro culture. The in v [98.0, 621.0, 569.0, 860.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
207 13 7 text The process of tendon injury regeneration is a complex and lengthy process, including initial inflammatory cell infiltration, subsequent migration and proliferation of tendon cells, collagen Type III [98.0, 861.0, 569.0, 1100.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
208 13 8 text The size and shape of the bones, muscles, and tendons in the shoulder complex can vary greatly from species to species, which can affect the biomechanics and function of the rotator cuff $ [11] $. Ra [97.0, 1100.0, 570.0, 1314.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
209 13 9 text In addition, the influence of extrinsic factors (especially muscle mass) on repair also needs to be considered in subsequent studies [1]. Muscle atrophy is considered to be an independent predictor of [96.0, 1315.0, 569.0, 1412.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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211 13 11 paragraph_title Discussion of Key Findings [601.0, 957.0, 830.0, 981.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Discussion of Key Findings"] subsection_heading 0.6 body_zone heading_like none True True
212 13 12 text In this study, we observed that the patch group exhibited a higher density of robust collagen fibrils with better alignment compared with both the gel and control groups 3 months after in vivo transpl [599.0, 1004.0, 1073.0, 1413.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
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228 14 14 figure_title Fig. 9 (A) This image shows TEM analysis of the regenerated tendon tissues at 3 months. Longitudinal and transverse cross-sections of collagen fibrils showed that the collagen fibrils in the patch gro [107.0, 1051.0, 1059.0, 1229.0] figure_caption 0.92 ["figure_title label: Fig. 9 (A) This image shows TEM analysis of the regenerated "] figure_caption 0.92 display_zone legend_like figure_number True True
229 14 15 text Additionally, the tissue-engineered bicipital autologous tendon patches contain tendon stem/progenitor cells, which accelerate tendon regeneration through mechanisms involving proliferation, different [98.0, 1262.0, 569.0, 1432.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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241 15 9 figure_title Fig. 10 Transcriptional analysis of regenerated tendons from 1 month to 3 months. (A) In the repair process of the patch group and gel group at different points (1, 2, and 3 months) after transplantat [205.0, 1096.0, 965.0, 1469.0] figure_caption 0.92 ["figure_title label: Fig. 10 Transcriptional analysis of regenerated tendons from"] figure_caption 0.92 display_zone legend_like figure_number True True
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246 16 3 text have been discarded during previous massive rotator cuff repair procedures, actually possesses the potential to promote tendon regeneration and serves as a high-quality source for tissue-engineered bi [97.0, 141.0, 569.0, 284.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
247 16 4 text Although the mechanisms of tendon regeneration were not the primary focus of this study, through bulk RNA sequencing techniques, we were able to clarify the potential of tissue-engineered bicipital au [98.0, 285.0, 568.0, 452.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
248 16 5 paragraph_title Conclusion [101.0, 499.0, 197.0, 521.0] section_heading 0.9 ["explicit scholarly heading: Conclusion"] section_heading 0.9 body_zone heading_like canonical_section_name True True
249 16 6 text In this in vivo rabbit study, we propose a clinically feasible novel therapy for repairing massive rotator cuff defects. We validated the regenerative potential of tissue-engineered bicipital autologo [98.0, 547.0, 570.0, 1049.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
250 16 7 text This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the [98.0, 1071.0, 568.0, 1193.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
251 16 8 text Acknowledgments We thank the Core Facilities of Zhejiang University School of Medicine for their technical assistance. We thank Mrs. Shuangshuang Liu for her assistance with the confocal laser scannin [99.0, 1225.0, 568.0, 1327.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
252 16 9 paragraph_title References [100.0, 1345.0, 204.0, 1367.0] reference_heading 0.9 ["references heading: References"] reference_heading 0.9 reference_zone heading_like short_fragment True True
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268 16 25 reference_content 16. Nemirov DA, Herman Z, Paul RW, et al. Evaluation of rotator cuff repair with and without concomitant biceps intervention: a retrospective review of patient outcomes. Am J Sports Med. 2022;50:1534- [606.0, 1119.0, 1070.0, 1195.0] reference_item 0.85 ["reference content label: 16. Nemirov DA, Herman Z, Paul RW, et al. Evaluation of rota"] reference_item 0.85 reference_zone reference_like reference_numeric_dot True True
269 16 26 reference_content 17. Osti L, Buda M, Buono AD, Osti R, Massari L. Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid. Muscles Ligaments Tendons J. 2015;5:270-275. [605.0, 1198.0, 1069.0, 1256.0] reference_item 0.85 ["reference content label: 17. Osti L, Buda M, Buono AD, Osti R, Massari L. Clinical ev"] reference_item 0.85 reference_zone reference_like reference_numeric_dot True True
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430
audit/A35UYJBK/audit_report.json Normal file
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@ -0,0 +1,430 @@
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}

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audit/A35UYJBK/audit_report.md Normal file
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# OCR Truth Audit Report - A35UYJBK
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 4]
- Reviewed blocks: 50
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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1,3,header,Send Orders for Reprints to reprints@benthamscience.net,"[769.0, 19.0, 1207.0, 39.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
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1,9,text,"Yawen Chen¹,#, Xinli Ouyang¹,#, Yide Wu¹, Shaojia Guo¹, Yongfang Xie¹,* and Guohui Wang¹,*","[91.0, 324.0, 1023.0, 356.0]",authors,0.8,"[""page-1 zone author_zone: Yawen Chen\u00b9,#, Xinli Ouyang\u00b9,#, Yide Wu\u00b9, Shaojia Guo\u00b9, Yong""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
1,10,text," $ ^{1} $Key Laboratory of Biological Medicines in Universities of Shandong Province, Weifang Medical University, Weifang, 261053, China","[91.0, 402.0, 1065.0, 452.0]",affiliation,0.8,"[""page-1 zone affiliation_zone: $ ^{1} $Key Laboratory of Biological Medicines in Universiti""]",affiliation,0.8,frontmatter_main_zone,support_like,affiliation_marker,True,True
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1,12,abstract,"Abstract: Defects in articular cartilage injury and chronic osteoarthritis are very widespread and common, and the ability of injured cartilage to repair itself is limited. Stem cell-based cartilage t","[316.0, 480.0, 1068.0, 816.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,frontmatter_main_zone,support_like,none,True,True
1,13,text,"Received: August 06, 2019
Revised: September 09, 2019
Accepted: September 18, 2019","[92.0, 649.0, 247.0, 695.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: Received: August 06, 2019 \nRevised: September 09, 2019 \nAc""]",frontmatter_noise,0.8,frontmatter_main_zone,support_like,none,False,False
1,14,text,DOI:10.2174/1574888X14666191029104249,"[91.0, 706.0, 294.0, 737.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,frontmatter_main_zone,support_like,none,True,True
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1,16,text,"Keywords: Mesenchymal stem cells, chondrocytes, cartilage tissue engineering, co-culture, mechanical stimulation, chondrogenic differentiation.","[90.0, 839.0, 1124.0, 885.0]",frontmatter_noise,0.7,"[""keyword-like block: Keywords: Mesenchymal stem cells, chondrocytes, cartilage ti""]",frontmatter_noise,0.7,frontmatter_main_zone,support_like,none,False,False
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1,18,text,Articular cartilage defects caused by trauma and various diseases are becoming common with increased aging. Articular cartilage damage usually causes fibrillation and peripheral articular surface dege,"[88.0, 952.0, 591.0, 1242.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,19,text,"In recent decades, cartilage repair and reconstruction have been mainly performed using tissue engineering methods. The choice of cells is the most important link or prerequisite in tissue engineering","[88.0, 1250.0, 592.0, 1318.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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1,21,text,"In this review, the role of co-culture and mechanical stimulation in supporting cartilage tissue engineering is examined. Moreover, a combination of the advantages of co-culture and mechanical environ","[622.0, 1243.0, 1126.0, 1447.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
1,22,footnote," $ ^{*} $Address correspondence to these authors at the Key Laboratory of Biological Medicines in Universities of Shandong Province, Weifang Medical University, Weifang, 261053, China; Tel: +86-137916","[88.0, 1350.0, 592.0, 1442.0]",footnote,0.7,"[""footnote label: $ ^{*} $Address correspondence to these authors at the Key L""]",footnote,0.7,body_zone,body_like,affiliation_marker,True,True
1,23,footer,2212-3946/20 $65.00+.00 © 2020 Bentham Science Publishers,"[427.0, 1485.0, 873.0, 1504.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,0,header,Co-culture and Mechanical Stimulation on Mesenchymal Stem Cells,"[123.0, 72.0, 584.0, 91.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
2,1,header,"Current Stem Cell Research & Therapy, 2020, Vol. 15, No. 1","[718.0, 72.0, 1125.0, 91.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
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2,4,paragraph_title,2. THE CHONDROCYTES AND MESENCHYMAL STEM CELLS FOR ARTICULAR CARTILAGE TISSUE ENGINEERING,"[121.0, 202.0, 622.0, 270.0]",paper_title,0.8,"[""page-1 zone title_zone: 2. THE CHONDROCYTES AND MESENCHYMAL STEM CELLS FOR ARTICULAR""]",paper_title,0.8,frontmatter_main_zone,reference_like,reference_numeric_dot,True,True
2,5,text,The available cells of good quality are the premise for articular cartilage tissue engineering. Chondrocytes and mesenchymal stem cells can most potentially be used for articular cartilage tissue engi,"[121.0, 281.0, 623.0, 371.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,paragraph_title,2.1. Chondrocytes,"[123.0, 391.0, 286.0, 414.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.1. Chondrocytes""]",subsection_heading,0.85,body_zone,heading_like,heading_numbered,True,True
2,7,text,"In the past, bone marrow stimulation techniques (one of the treatment options for articular cartilage damage) failed to produce tissue with the same functional and mechanical properties as native hyal","[121.0, 424.0, 625.0, 891.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: In the past, bone marrow stimulation techniques (one of the ""]",frontmatter_noise,0.8,body_zone,body_like,none,False,False
2,8,paragraph_title,2.2. Mesenchymal Stem Cells,"[122.0, 909.0, 379.0, 932.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2. Mesenchymal Stem Cells""]",subsection_heading,0.85,body_zone,heading_like,heading_numbered,True,True
2,9,text,"Mesenchymal stem cells are the subpopulations of cells with strong proliferative capacity and multiple differentiation potentials and can differentiate into bone, cartilage, fat, nerves and myoblasts,","[120.0, 941.0, 625.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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2,11,paragraph_title,3. CO-CULTURE OF MESENCHYMAL STEM CELLS WITH CHONDROCYTES,"[655.0, 575.0, 1156.0, 620.0]",section_heading,0.85,"[""paragraph_title label with numbering: 3. CO-CULTURE OF MESENCHYMAL STEM CELLS WITH CHONDROCYTES""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
2,12,text,"Recently, the co-culture of stem cells and mature cells was shown to induce stem cells to differentiate into the target lineage cells. The method of mesenchymal stem cells co-culture with chondrocytes","[654.0, 632.0, 1159.0, 1053.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,13,paragraph_title,3.1. The Effects of Co-Culture on Chondrocytes,"[655.0, 1072.0, 1072.0, 1095.0]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.1. The Effects of Co-Culture on Chondrocytes""]",subsection_heading,0.85,body_zone,heading_like,heading_numbered,True,True
2,14,text,The method of mesenchymal stem cells co-culture with chondrocytes can maintain the chondrocytes' phenotype and promote the proliferative capacity of chondrocytes [45-50] and delay the dedifferentiatio,"[654.0, 1106.0, 1159.0, 1483.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,0,number,56,"[125.0, 72.0, 146.0, 89.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,1,header,"Current Stem Cell Research & Therapy, 2020, Vol. 15, No. 1","[157.0, 72.0, 563.0, 91.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,2,header,Chen et al.,"[1080.0, 71.0, 1157.0, 91.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,3,text,"and cartilaginous extracellular matrix secretion by RhoA/ROCK signaling [48]. The mesenchymal stem cells derived exosomes promoted cartilage repair and chondrocyte proliferation [55]. Moreover, mesenc","[120.0, 113.0, 624.0, 314.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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3,5,text,The method of mesenchymal stem cells co-culture with chondrocytes can induce chondrogenic differentiation of mesenchymal stem cells [46]. Previous studies demonstrated that the co-culture of chondrocy,"[120.0, 389.0, 624.0, 1098.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,6,text,"However, the function of the co-culture system remains controversial. The reasons for the disagreements among the scientists may be related to the differences in cell sources, mixing ratios, cytokine ","[120.0, 1104.0, 624.0, 1327.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,7,paragraph_title,4. THE EFFECT OF MECHANICAL STIMULATION ON CHONDROCYTES AND MESENCHYMAL STEM CELLS,"[122.0, 1345.0, 622.0, 1413.0]",section_heading,0.85,"[""paragraph_title label with numbering: 4. THE EFFECT OF MECHANICAL STIMULATION ON CHONDROCYTES AND ""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
3,8,text,Mechanical stimulation plays a significant factor in the development of articular cartilage and proper mechanical stimulation is a crucial regulatory factor of chondrocyte metabolism and function in v,"[120.0, 1423.0, 624.0, 1470.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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3,10,text,"The mechanical stimulation regulates gene expression, thereby promoting chondrogenic differentiation. The mechanical stimulation can manipulate the senescence and function of mesenchymal stem cells in","[654.0, 762.0, 1158.0, 1007.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,11,text,The specific fluid flows shear mechanical stimulation and stretch stress mechanical stimulation can induce the chondrogenic differentiation of mesenchymal stem cells in two-dimensional culture. For ex,"[654.0, 1014.0, 1159.0, 1391.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,12,text,The different forms of compression mechanical stimulation can induce the chondrogenic differentiation of mesenchymal stem cells in constructed three-dimensional tissue.,"[653.0, 1397.0, 1158.0, 1467.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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4,1,header,"Current Stem Cell Research & Therapy, 2020, Vol. 15, No. 1","[718.0, 72.0, 1127.0, 91.0]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
4,2,number,57,"[1135.0, 72.0, 1156.0, 89.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,3,text,"The mechanical stimulation of cyclic unconfined compressive loading, same as the stimulation of transforming growth factor- $ \beta_1 $, stimulated mesenchymal stem cells in agarose to increase the ex","[121.0, 113.0, 624.0, 688.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,4,paragraph_title,5. COMBINED WITH CO-CULTURE AND MECHANICAL STIMULATION,"[122.0, 708.0, 621.0, 752.0]",reference_item,0.85,"[""paragraph_title label with numbering: 5. COMBINED WITH CO-CULTURE AND MECHANICAL STIMULATION""]",section_heading,0.85,reference_zone,reference_like,reference_numeric_dot,True,True
4,5,text,"As mentioned above, the co-culture of mesenchymal stem cells with chondrocytes can promote cartilage phenotype and proliferation of chondrocytes induce chondrogenic differentiation of mesenchymal stem","[121.0, 762.0, 624.0, 1450.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
4,6,paragraph_title,CONCLUSION,"[658.0, 114.0, 800.0, 135.0]",section_heading,0.9,"[""explicit scholarly heading: CONCLUSION""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
4,7,text,"Articular cartilage has an important bearing capacity, and damaged cartilage has limited self-repairing ability. Mesenchymal stem cells have vast differentiation potential; however, stem cell-based ca","[654.0, 148.0, 1159.0, 524.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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4,11,text,"This study was supported by the National Natural Science Foundation of China (11802209), the Natural Science Foundation of Shandong Province China (ZR2019MA018) and the National innovation and entrepr","[655.0, 655.0, 1157.0, 769.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,12,paragraph_title,CONFLICT OF INTEREST,"[657.0, 787.0, 910.0, 810.0]",section_heading,0.6,"[""unnumbered paragraph_title, inferred level section_heading: CONFLICT OF INTEREST""]",section_heading,0.6,body_zone,support_like,none,True,True
4,13,text,"The authors declare no conflict of interest, financial or otherwise.","[655.0, 822.0, 1156.0, 866.0]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,body_zone,support_like,none,False,False
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4,15,text,Declared none.,"[686.0, 922.0, 814.0, 944.0]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,short_fragment,False,True
4,16,paragraph_title,REFERENCES,"[659.0, 965.0, 799.0, 987.0]",reference_heading,0.9,"[""references heading: REFERENCES""]",reference_heading,0.9,reference_zone,heading_like,short_fragment,True,True
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5,0,number,58,"[126.0, 73.0, 146.0, 89.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
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[74] Szychlinska MA, Stoddart MI, D'Amora U, Ambrosio I, Alini M","[128.0, 278.0, 620.0, 304.0]",reference_item,0.85,"[""reference content label: [http://dx.doi.org/10.1016/j.biopha.2019.109146] [PMID: 3138""]",reference_item,0.85,reference_zone,unknown_like,none,True,True
7,7,reference_content,"[74] Szychlinska MA, Stoddart MJ, D'Amora U, Ambrosio L, Alini M, Musumeci G. Mesenchymal stem cell-based cartilage regeneration approach and cell senescence: Can we manipulate cell aging and function","[126.0, 291.0, 621.0, 381.0]",reference_item,0.85,"[""reference content label: [74] Szychlinska MA, Stoddart MJ, D'Amora U, Ambrosio L, Ali""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,8,reference_content,"[75] Zhong W, Tian K, Zheng X, et al. Mesenchymal stem cell and chondrocyte fates in a multishear microdevice are regulated by Yes-associated protein. Stem Cells Dev 2013; 22(14): 2083-93.","[126.0, 381.0, 621.0, 446.0]",reference_item,0.85,"[""reference content label: [75] Zhong W, Tian K, Zheng X, et al. Mesenchymal stem cell ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,9,reference_content,http://dx.doi.org/10.1089/scd.2012.0685 [PMID: 23442010],"[129.0, 439.0, 585.0, 458.0]",reference_item,0.85,"[""reference content label: http://dx.doi.org/10.1089/scd.2012.0685 [PMID: 23442010]""]",reference_item,0.85,reference_zone,unknown_like,none,True,True
7,10,reference_content,"[76] Hosseini MS, Tafazzoli-Shadpour M, Haghighipour N, Aghdami N, Goodarzi A. The synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchy","[126.0, 457.0, 622.0, 545.0]",reference_item,0.85,"[""reference content label: [76] Hosseini MS, Tafazzoli-Shadpour M, Haghighipour N, Aghd""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,11,reference_content,"[77] Bao X, Li Z, Liu H, et al. Stimulation of chondrocytes and chondroinduced mesenchymal stem cells by osteoinduced mesenchymal stem cells under a fluid flow stimulus on an integrated microfluidic d","[126.0, 547.0, 620.0, 631.0]",reference_item,0.85,"[""reference content label: [77] Bao X, Li Z, Liu H, et al. Stimulation of chondrocytes ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,12,reference_content,"[78] Yang ZQ, Men YX. [Effect of equiaxial tensile strain in early differentiation of mesenchymal stem cells into cartilage cells]. Zhongguo Gu Shang 2018; 31(9): 846-52. [PMID: 30332879]","[126.0, 636.0, 620.0, 708.0]",reference_item,0.85,"[""reference content label: [78] Yang ZQ, Men YX. [Effect of equiaxial tensile strain in""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,13,reference_content,"[79] Huang CY, Hagar KL, Frost LE, Sun Y, Cheung HS. Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells 2004; 22(3): 313-23.","[660.0, 114.0, 1156.0, 186.0]",reference_item,0.85,"[""reference content label: [79] Huang CY, Hagar KL, Frost LE, Sun Y, Cheung HS. Effects""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,14,reference_content,[http://dx.doi.org/10.1634/stemcells.22-3-313][PMID:15153608],"[661.0, 187.0, 1148.0, 209.0]",reference_item,0.85,"[""reference content label: [http://dx.doi.org/10.1634/stemcells.22-3-313][PMID:15153608""]",reference_item,0.85,reference_zone,unknown_like,none,True,True
7,15,reference_content,"[80] Guo T, Yu L, Lim CG, et al. Effect of dynamic culture and periodic compression on human mesenchymal stem cell proliferation and chondrogenesis. Ann Biomed Eng 2016; 44(7): 2103-13. [http://dx.doi","[660.0, 204.0, 1154.0, 276.0]",reference_item,0.85,"[""reference content label: [80] Guo T, Yu L, Lim CG, et al. Effect of dynamic culture a""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,16,reference_content,"[81] Remya NS, Nair PD. Mechanoresponsiveness of human umbilical cord mesenchymal stem cells in in vitro chondrogenesis-A comparative study with growth factor induction. J Biomed Mater Res A 2016; 104","[660.0, 276.0, 1156.0, 353.0]",reference_item,0.85,"[""reference content label: [81] Remya NS, Nair PD. Mechanoresponsiveness of human umbil""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,17,reference_content,[http://dx.doi.org/10.1002/jbm.a.35792] [PMID: 27227673],"[671.0, 349.0, 1103.0, 367.0]",reference_item,0.85,"[""reference content label: [http://dx.doi.org/10.1002/jbm.a.35792] [PMID: 27227673]""]",reference_item,0.85,reference_zone,unknown_like,none,True,True
7,18,reference_content,"[82] Zamanlui S, Amirabad LM, Soleimani M, Faghihi S. Influence of hydrodynamic pressure on chondrogenic differentiation of human bone marrow mesenchymal stem cells cultured in perfusion system. Biolo","[660.0, 366.0, 1156.0, 472.0]",reference_item,0.85,"[""reference content label: [82] Zamanlui S, Amirabad LM, Soleimani M, Faghihi S. Influe""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,19,reference_content,"[83] Vining KH, Mooney DJ. Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol 2017;18(12):728-42.","[660.0, 475.0, 1155.0, 529.0]",reference_item,0.85,"[""reference content label: [83] Vining KH, Mooney DJ. Mechanical forces direct stem cel""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,20,reference_content,[http://dx.doi.org/10.1038/nrm.2017.108] [PMID: 29115301],"[700.0, 529.0, 1114.0, 546.0]",reference_item,0.85,"[""reference content label: [http://dx.doi.org/10.1038/nrm.2017.108] [PMID: 29115301]""]",reference_item,0.85,reference_zone,unknown_like,none,True,True
7,21,reference_content,"[84] Jeong JY, Park SH, Shin JW, Kang YG, Han KH, Shin JW. Effects of intermittent hydrostatic pressure magnitude on the chondrogenesis of MSCs without biochemical agents under 3D co-culture. J Mater ","[660.0, 547.0, 1155.0, 628.0]",reference_item,0.85,"[""reference content label: [84] Jeong JY, Park SH, Shin JW, Kang YG, Han KH, Shin JW. E""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
7,22,reference_content,"[85] Chen CH, Kuo CY, Chen JP. Effect of cyclic dynamic compressive loading on chondrocytes and adipose-derived stem cells cocultured in highly elastic cryogel scaffolds. Int J Mol Sci 2018;19(2):370.","[659.0, 633.0, 1155.0, 727.0]",reference_item,0.85,"[""reference content label: [85] Chen CH, Kuo CY, Chen JP. Effect of cyclic dynamic comp""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
1 page block_id raw_label content_preview bbox role role_confidence evidence seed_role seed_confidence zone style_family marker_type render_default index_default
2 1 0 aside_text Current Stem Cell Research & Therapy [8.0, 563.0, 61.0, 1551.0] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 frontmatter_main_zone support_like none False False
3 1 1 number 54 [14.0, 7.0, 44.0, 30.0] noise 0.9 ["page number label"] noise 0.9 frontmatter_main_zone support_like short_fragment False False
4 1 2 header_image [16.0, 120.0, 170.0, 271.0] unknown_structural 0.2 ["unrecognized label 'header_image'"] unknown_structural 0.2 frontmatter_main_zone support_like empty False True
5 1 3 header Send Orders for Reprints to reprints@benthamscience.net [769.0, 19.0, 1207.0, 39.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
6 1 4 header MINI-REVIEW ARTICLE [179.0, 95.0, 422.0, 117.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like short_fragment False False
7 1 5 header Current Stem Cell Research & Therapy, 2020, 15, 54-60 [505.0, 75.0, 884.0, 95.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
8 1 6 doc_title Co-culture and Mechanical Stimulation on Mesenchymal Stem Cells and Chondrocytes for Cartilage Tissue Engineering [196.0, 160.0, 1055.0, 218.0] paper_title 0.8 ["page-1 zone title_zone: Co-culture and Mechanical Stimulation on Mesenchymal Stem Ce"] paper_title 0.8 frontmatter_main_zone support_like none True True
9 1 7 header Current Stem Cell Research & Therapy [1096.0, 126.0, 1186.0, 167.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
10 1 8 header_image [1092.0, 170.0, 1204.0, 267.0] non_body_insert 0.2 ["unrecognized label 'header_image'"] unknown_structural 0.2 frontmatter_main_zone support_like empty False False
11 1 9 text Yawen Chen¹,#, Xinli Ouyang¹,#, Yide Wu¹, Shaojia Guo¹, Yongfang Xie¹,* and Guohui Wang¹,* [91.0, 324.0, 1023.0, 356.0] authors 0.8 ["page-1 zone author_zone: Yawen Chen\u00b9,#, Xinli Ouyang\u00b9,#, Yide Wu\u00b9, Shaojia Guo\u00b9, Yong"] authors 0.8 frontmatter_main_zone support_like none True True
12 1 10 text $ ^{1} $Key Laboratory of Biological Medicines in Universities of Shandong Province, Weifang Medical University, Weifang, 261053, China [91.0, 402.0, 1065.0, 452.0] affiliation 0.8 ["page-1 zone affiliation_zone: $ ^{1} $Key Laboratory of Biological Medicines in Universiti"] affiliation 0.8 frontmatter_main_zone support_like affiliation_marker True True
13 1 11 paragraph_title ARTICLE HISTORY [106.0, 600.0, 291.0, 619.0] frontmatter_noise 0.5 ["unnumbered paragraph_title on page 1 outside title zone: ARTICLE HISTORY"] section_heading 0.5 frontmatter_main_zone support_like short_fragment False False
14 1 12 abstract Abstract: Defects in articular cartilage injury and chronic osteoarthritis are very widespread and common, and the ability of injured cartilage to repair itself is limited. Stem cell-based cartilage t [316.0, 480.0, 1068.0, 816.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 frontmatter_main_zone support_like none True True
15 1 13 text Received: August 06, 2019 Revised: September 09, 2019 Accepted: September 18, 2019 [92.0, 649.0, 247.0, 695.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: Received: August 06, 2019 \nRevised: September 09, 2019 \nAc"] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
16 1 14 text DOI:10.2174/1574888X14666191029104249 [91.0, 706.0, 294.0, 737.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 frontmatter_main_zone support_like none True True
17 1 15 image [125.0, 741.0, 254.0, 788.0] media_asset 0.85 ["media label: image"] media_asset 0.85 frontmatter_main_zone support_like empty True True
18 1 16 text Keywords: Mesenchymal stem cells, chondrocytes, cartilage tissue engineering, co-culture, mechanical stimulation, chondrogenic differentiation. [90.0, 839.0, 1124.0, 885.0] frontmatter_noise 0.7 ["keyword-like block: Keywords: Mesenchymal stem cells, chondrocytes, cartilage ti"] frontmatter_noise 0.7 frontmatter_main_zone support_like none False False
19 1 17 paragraph_title 1. INTRODUCTION [92.0, 918.0, 278.0, 940.0] section_heading 0.85 ["paragraph_title label with numbering: 1. INTRODUCTION"] section_heading 0.85 body_zone heading_like heading_numbered True True
20 1 18 text Articular cartilage defects caused by trauma and various diseases are becoming common with increased aging. Articular cartilage damage usually causes fibrillation and peripheral articular surface dege [88.0, 952.0, 591.0, 1242.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
21 1 19 text In recent decades, cartilage repair and reconstruction have been mainly performed using tissue engineering methods. The choice of cells is the most important link or prerequisite in tissue engineering [88.0, 1250.0, 592.0, 1318.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
22 1 20 text [622.0, 919.0, 1126.0, 1235.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
23 1 21 text In this review, the role of co-culture and mechanical stimulation in supporting cartilage tissue engineering is examined. Moreover, a combination of the advantages of co-culture and mechanical environ [622.0, 1243.0, 1126.0, 1447.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
24 1 22 footnote $ ^{*} $Address correspondence to these authors at the Key Laboratory of Biological Medicines in Universities of Shandong Province, Weifang Medical University, Weifang, 261053, China; Tel: +86-137916 [88.0, 1350.0, 592.0, 1442.0] footnote 0.7 ["footnote label: $ ^{*} $Address correspondence to these authors at the Key L"] footnote 0.7 body_zone body_like affiliation_marker True True
25 1 23 footer 2212-3946/20 $65.00+.00 © 2020 Bentham Science Publishers [427.0, 1485.0, 873.0, 1504.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
26 2 0 header Co-culture and Mechanical Stimulation on Mesenchymal Stem Cells [123.0, 72.0, 584.0, 91.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
27 2 1 header Current Stem Cell Research & Therapy, 2020, Vol. 15, No. 1 [718.0, 72.0, 1125.0, 91.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
28 2 2 number 55 [1135.0, 72.0, 1156.0, 89.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
29 2 3 text ronment is a potential approach that cannot be ignored in the development of cartilage tissue engineering and repair of cartilage defects. [121.0, 113.0, 625.0, 183.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
30 2 4 paragraph_title 2. THE CHONDROCYTES AND MESENCHYMAL STEM CELLS FOR ARTICULAR CARTILAGE TISSUE ENGINEERING [121.0, 202.0, 622.0, 270.0] paper_title 0.8 ["page-1 zone title_zone: 2. THE CHONDROCYTES AND MESENCHYMAL STEM CELLS FOR ARTICULAR"] paper_title 0.8 frontmatter_main_zone reference_like reference_numeric_dot True True
31 2 5 text The available cells of good quality are the premise for articular cartilage tissue engineering. Chondrocytes and mesenchymal stem cells can most potentially be used for articular cartilage tissue engi [121.0, 281.0, 623.0, 371.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
32 2 6 paragraph_title 2.1. Chondrocytes [123.0, 391.0, 286.0, 414.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.1. Chondrocytes"] subsection_heading 0.85 body_zone heading_like heading_numbered True True
33 2 7 text In the past, bone marrow stimulation techniques (one of the treatment options for articular cartilage damage) failed to produce tissue with the same functional and mechanical properties as native hyal [121.0, 424.0, 625.0, 891.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: In the past, bone marrow stimulation techniques (one of the "] frontmatter_noise 0.8 body_zone body_like none False False
34 2 8 paragraph_title 2.2. Mesenchymal Stem Cells [122.0, 909.0, 379.0, 932.0] subsection_heading 0.85 ["paragraph_title label with numbering: 2.2. Mesenchymal Stem Cells"] subsection_heading 0.85 body_zone heading_like heading_numbered True True
35 2 9 text Mesenchymal stem cells are the subpopulations of cells with strong proliferative capacity and multiple differentiation potentials and can differentiate into bone, cartilage, fat, nerves and myoblasts, [120.0, 941.0, 625.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
36 2 10 text [654.0, 113.0, 1158.0, 555.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
37 2 11 paragraph_title 3. CO-CULTURE OF MESENCHYMAL STEM CELLS WITH CHONDROCYTES [655.0, 575.0, 1156.0, 620.0] section_heading 0.85 ["paragraph_title label with numbering: 3. CO-CULTURE OF MESENCHYMAL STEM CELLS WITH CHONDROCYTES"] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
38 2 12 text Recently, the co-culture of stem cells and mature cells was shown to induce stem cells to differentiate into the target lineage cells. The method of mesenchymal stem cells co-culture with chondrocytes [654.0, 632.0, 1159.0, 1053.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
39 2 13 paragraph_title 3.1. The Effects of Co-Culture on Chondrocytes [655.0, 1072.0, 1072.0, 1095.0] subsection_heading 0.85 ["paragraph_title label with numbering: 3.1. The Effects of Co-Culture on Chondrocytes"] subsection_heading 0.85 body_zone heading_like heading_numbered True True
40 2 14 text The method of mesenchymal stem cells co-culture with chondrocytes can maintain the chondrocytes' phenotype and promote the proliferative capacity of chondrocytes [45-50] and delay the dedifferentiatio [654.0, 1106.0, 1159.0, 1483.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
41 3 0 number 56 [125.0, 72.0, 146.0, 89.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
42 3 1 header Current Stem Cell Research & Therapy, 2020, Vol. 15, No. 1 [157.0, 72.0, 563.0, 91.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
43 3 2 header Chen et al. [1080.0, 71.0, 1157.0, 91.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like short_fragment False False
44 3 3 text and cartilaginous extracellular matrix secretion by RhoA/ROCK signaling [48]. The mesenchymal stem cells derived exosomes promoted cartilage repair and chondrocyte proliferation [55]. Moreover, mesenc [120.0, 113.0, 624.0, 314.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
45 3 4 paragraph_title 3.2. The Effects of Co-Culture on Mesenchymal Stem Cells [121.0, 334.0, 621.0, 378.0] subsection_heading 0.85 ["paragraph_title label with numbering: 3.2. The Effects of Co-Culture on Mesenchymal Stem Cells"] subsection_heading 0.85 body_zone heading_like heading_numbered True True
46 3 5 text The method of mesenchymal stem cells co-culture with chondrocytes can induce chondrogenic differentiation of mesenchymal stem cells [46]. Previous studies demonstrated that the co-culture of chondrocy [120.0, 389.0, 624.0, 1098.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
47 3 6 text However, the function of the co-culture system remains controversial. The reasons for the disagreements among the scientists may be related to the differences in cell sources, mixing ratios, cytokine [120.0, 1104.0, 624.0, 1327.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
48 3 7 paragraph_title 4. THE EFFECT OF MECHANICAL STIMULATION ON CHONDROCYTES AND MESENCHYMAL STEM CELLS [122.0, 1345.0, 622.0, 1413.0] section_heading 0.85 ["paragraph_title label with numbering: 4. THE EFFECT OF MECHANICAL STIMULATION ON CHONDROCYTES AND "] section_heading 0.85 body_zone reference_like reference_numeric_dot True True
49 3 8 text Mechanical stimulation plays a significant factor in the development of articular cartilage and proper mechanical stimulation is a crucial regulatory factor of chondrocyte metabolism and function in v [120.0, 1423.0, 624.0, 1470.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
50 3 9 text [654.0, 112.0, 1159.0, 755.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
51 3 10 text The mechanical stimulation regulates gene expression, thereby promoting chondrogenic differentiation. The mechanical stimulation can manipulate the senescence and function of mesenchymal stem cells in [654.0, 762.0, 1158.0, 1007.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
52 3 11 text The specific fluid flows shear mechanical stimulation and stretch stress mechanical stimulation can induce the chondrogenic differentiation of mesenchymal stem cells in two-dimensional culture. For ex [654.0, 1014.0, 1159.0, 1391.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
53 3 12 text The different forms of compression mechanical stimulation can induce the chondrogenic differentiation of mesenchymal stem cells in constructed three-dimensional tissue. [653.0, 1397.0, 1158.0, 1467.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
54 4 0 header Co-culture and Mechanical Stimulation on Mesenchymal Stem Cells [123.0, 72.0, 584.0, 91.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
55 4 1 header Current Stem Cell Research & Therapy, 2020, Vol. 15, No. 1 [718.0, 72.0, 1127.0, 91.0] noise 0.9 ["header label"] noise 0.9 body_zone body_like none False False
56 4 2 number 57 [1135.0, 72.0, 1156.0, 89.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
57 4 3 text The mechanical stimulation of cyclic unconfined compressive loading, same as the stimulation of transforming growth factor- $ \beta_1 $, stimulated mesenchymal stem cells in agarose to increase the ex [121.0, 113.0, 624.0, 688.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
58 4 4 paragraph_title 5. COMBINED WITH CO-CULTURE AND MECHANICAL STIMULATION [122.0, 708.0, 621.0, 752.0] reference_item 0.85 ["paragraph_title label with numbering: 5. COMBINED WITH CO-CULTURE AND MECHANICAL STIMULATION"] section_heading 0.85 reference_zone reference_like reference_numeric_dot True True
59 4 5 text As mentioned above, the co-culture of mesenchymal stem cells with chondrocytes can promote cartilage phenotype and proliferation of chondrocytes induce chondrogenic differentiation of mesenchymal stem [121.0, 762.0, 624.0, 1450.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone body_like none True True
60 4 6 paragraph_title CONCLUSION [658.0, 114.0, 800.0, 135.0] section_heading 0.9 ["explicit scholarly heading: CONCLUSION"] section_heading 0.9 body_zone heading_like canonical_section_name True True
61 4 7 text Articular cartilage has an important bearing capacity, and damaged cartilage has limited self-repairing ability. Mesenchymal stem cells have vast differentiation potential; however, stem cell-based ca [654.0, 148.0, 1159.0, 524.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
62 4 8 paragraph_title CONSENT FOR PUBLICATION [656.0, 543.0, 954.0, 565.0] section_heading 0.6 ["unnumbered paragraph_title, inferred level section_heading: CONSENT FOR PUBLICATION"] section_heading 0.6 body_zone heading_like none True True
63 4 9 text Not applicable. [685.0, 578.0, 814.0, 601.0] unknown_structural 0.3 ["short text, uncertain role"] unknown_structural 0.3 body_zone body_like short_fragment False True
64 4 10 paragraph_title FUNDING [657.0, 620.0, 759.0, 643.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: FUNDING"] sub_subsection_heading 0.6 body_zone heading_like short_fragment True True
65 4 11 text This study was supported by the National Natural Science Foundation of China (11802209), the Natural Science Foundation of Shandong Province China (ZR2019MA018) and the National innovation and entrepr [655.0, 655.0, 1157.0, 769.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
66 4 12 paragraph_title CONFLICT OF INTEREST [657.0, 787.0, 910.0, 810.0] section_heading 0.6 ["unnumbered paragraph_title, inferred level section_heading: CONFLICT OF INTEREST"] section_heading 0.6 body_zone support_like none True True
67 4 13 text The authors declare no conflict of interest, financial or otherwise. [655.0, 822.0, 1156.0, 866.0] frontmatter_noise 0.88 ["default body_paragraph for text label", "late role resolution: editorial phrase cross-validates non-body classification", "zone=body_zone", "style_family=support_like"] body_paragraph 0.6 body_zone support_like none False False
68 4 14 paragraph_title ACKNOWLEDGEMENTS [658.0, 887.0, 900.0, 910.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: ACKNOWLEDGEMENTS"] sub_subsection_heading 0.6 body_zone heading_like short_fragment True True
69 4 15 text Declared none. [686.0, 922.0, 814.0, 944.0] unknown_structural 0.3 ["short text, uncertain role"] unknown_structural 0.3 body_zone body_like short_fragment False True
70 4 16 paragraph_title REFERENCES [659.0, 965.0, 799.0, 987.0] reference_heading 0.9 ["references heading: REFERENCES"] reference_heading 0.9 reference_zone heading_like short_fragment True True
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"severity": "critical",
"block_ids": [
"p21:15"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_021.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p21:16"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_021.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p21:17"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_021.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p21:18"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_021.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p21:19"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_021.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "reference_span_error",
"severity": "critical",
"block_ids": [
"p21:20"
],
"truth": "block should remain outside the accepted reference span",
"pipeline_behavior": "block appears inside the logical reference reading-order region",
"root_cause_hypothesis": "logical_order_between_reference_members",
"evidence": {
"annotated_page": "annotated_pages/page_021.png",
"artifact": "reference_span_audit.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_021.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "same_page_boundary_error",
"severity": "major",
"block_ids": [],
"truth": "body/reference/backmatter boundaries should be explainable at block level",
"pipeline_behavior": "page contains mixed body/reference/tail signals",
"root_cause_hypothesis": "same-page boundary ambiguity",
"evidence": {
"annotated_page": "annotated_pages/page_022.png",
"artifact": "page_risk_summary.json"
}
},
{
"category": "render_mapping_error",
"severity": "minor",
"block_ids": [
"p1:0",
"p1:2",
"p1:6",
"p1:9",
"p1:11",
"p1:13",
"p2:1",
"p2:2",
"p3:1",
"p4:1",
"p4:8",
"p5:1",
"p5:5",
"p5:9",
"p6:1",
"p6:6",
"p6:10",
"p7:1",
"p7:3",
"p8:1"
],
"truth": "rendered fulltext should be traceable back to source blocks",
"pipeline_behavior": "some render-default blocks are not easily mapped into the current fulltext output",
"root_cause_hypothesis": "render omission or snippet mismatch",
"evidence": {
"annotated_page": null,
"artifact": "fulltext_block_mapping_summary.json"
}
}
]
}

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# OCR Truth Audit Report - B43QSAJP
- Mode: `high-risk`
- Status: `READY`
- Reviewed pages: [1, 4, 5, 6, 9, 10, 13, 14, 15, 17, 19, 21, 22]
- Reviewed blocks: 230
## Findings
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `critical` `reference_span_error`: block appears inside the logical reference reading-order region
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `major` `same_page_boundary_error`: page contains mixed body/reference/tail signals
- `minor` `render_mapping_error`: some render-default blocks are not easily mapped into the current fulltext output
## Disposition Guidance
- Use `repair` when the finding reflects a pipeline defect worth fixing now.
- Use `residual` when the finding is real but intentionally deferred.
- Do not rewrite expected truth to make current output look correct.

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page,block_id,raw_label,content_preview,bbox,role,role_confidence,evidence,seed_role,seed_confidence,zone,style_family,marker_type,render_default,index_default
1,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239 https://doi.org/10.1186/s12951-026-04131-9,"[108.0, 66.0, 492.0, 108.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,1,header,Journal of Nanobiotechnology,"[758.0, 64.0, 1081.0, 96.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
1,2,text,RESEARCH,"[116.0, 183.0, 270.0, 211.0]",non_body_insert,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,frontmatter_main_zone,support_like,short_fragment,False,False
1,3,text,Open Access,"[922.0, 183.0, 1075.0, 212.0]",frontmatter_noise,0.7,"[""frontmatter noise text: Open Access""]",frontmatter_noise,0.7,frontmatter_main_zone,support_like,short_fragment,False,False
1,4,image,,"[1019.0, 226.0, 1076.0, 283.0]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,frontmatter_main_zone,support_like,empty,True,True
1,5,doc_title,Piezoelectric scaffold with enhanced effect drives the healing of osteochondral defects through electromechanical-immune coupling,"[108.0, 245.0, 982.0, 403.0]",paper_title,0.8,"[""page-1 zone title_zone: Piezoelectric scaffold with enhanced effect drives the heali""]",paper_title,0.8,frontmatter_main_zone,support_like,none,True,True
1,6,text,"Xin Liu $ ^{1,2*} $ $ ^{\dagger} $, Congyang Xue $ ^{1,2} $ $ ^{\dagger} $, Jun Guo $ ^{1,2} $ $ ^{\dagger} $, Nan Chen $ ^{1,2} $, Bo Chen $ ^{3} $, Zihan Wang $ ^{4} $, Xuan Han $ ^{5} $, Liping Che","[106.0, 435.0, 999.0, 496.0]",authors,0.8,"[""page-1 zone author_zone: Xin Liu $ ^{1,2*} $ $ ^{\\dagger} $, Congyang Xue $ ^{1,2} $ ""]",authors,0.8,frontmatter_main_zone,support_like,none,True,True
1,7,paragraph_title,Abstract,"[121.0, 546.0, 210.0, 569.0]",abstract_heading,0.95,"[""abstract heading""]",abstract_heading,0.95,frontmatter_main_zone,heading_like,short_fragment,True,True
1,8,abstract,Silk fibroin scaffolds (SFCs) that exploit piezoelectricity for osteochondral repair have been hampered by both insufficient electromechanical output and a pro-inflammatory joint microenvironment that,"[118.0, 569.0, 1067.0, 1030.0]",abstract_body,0.85,"[""abstract label from Paddle OCR""]",abstract_body,0.85,frontmatter_main_zone,support_like,none,True,True
1,9,text," $ ^{\dagger} $Xin Liu, Congyang Xue and Jun Guo contributed equally to this work.","[109.0, 1107.0, 499.0, 1145.0]",frontmatter_support,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,frontmatter_main_zone,support_like,affiliation_marker,True,True
1,10,footnote,"*Correspondence:
Xin Liu
liuxin@njucm.edu.cn
Ding Qu
quding1985@hotmail.com
Ran Kang
kangran126@126.com","[108.0, 1154.0, 279.0, 1280.0]",frontmatter_noise,0.8,"[""page-1 zone journal_furniture_zone: *Correspondence:\nXin Liu\nliuxin@njucm.edu.cn\nDing Qu\nquding1""]",frontmatter_noise,0.8,frontmatter_main_zone,support_like,none,False,False
1,11,footnote,Full list of author information is available at the end of the article,"[108.0, 1288.0, 501.0, 1308.0]",footnote,0.7,"[""footnote label: Full list of author information is available at the end of t""]",footnote,0.7,frontmatter_main_zone,support_like,none,True,True
1,12,footer_image,,"[113.0, 1342.0, 331.0, 1402.0]",non_body_insert,0.2,"[""unrecognized label 'footer_image'""]",unknown_structural,0.2,frontmatter_main_zone,support_like,empty,False,False
1,13,footer,"© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, di","[354.0, 1344.0, 1083.0, 1473.0]",noise,0.9,"[""footer label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
2,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 509.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_main_zone,support_like,none,False,False
2,1,number,Page 2 of 22,"[990.0, 66.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
2,2,text,"Keywords Magnetic nanoparticles, Silk fibroin scaffold, Piezoelectric effect, Osteochondral, Stem cell","[119.0, 177.0, 934.0, 204.0]",unknown_structural,0.8,"[""page-1 zone author_zone: Keywords Magnetic nanoparticles, Silk fibroin scaffold, Piez""]",authors,0.8,body_zone,body_like,none,False,True
2,3,paragraph_title,Introduction,"[107.0, 246.0, 235.0, 268.0]",section_heading,0.9,"[""explicit scholarly heading: Introduction""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
2,4,text,"Osteochondral defects (OCD) are one of the leading causes of pain, disability and osteoarthritis [1], affecting more than 300 million people worldwide. Due to the lack of vascular and nerve innervatio","[107.0, 269.0, 586.0, 872.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,5,text,"At present, a number of naturals or synthetic polymers have been used to develop osteochondral scaffolds [7–9]. Among them, natural polymers are widely used in bone tissue engineering because of their","[106.0, 873.0, 587.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,text,,"[602.0, 246.0, 1083.0, 558.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
2,7,text,"In recent years, piezoelectric materials with force-electric conversion function have attracted the attention of scholars at home and abroad [16], especially natural piezoelectric materials with good ","[602.0, 556.0, 1085.0, 1476.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 509.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
3,1,number,Page 3 of 22,"[990.0, 65.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
3,2,text,crystal units indicates that the silk fibroin has a piezoelectric effect [26]. Previous studies have also shown that negative charge has a more obvious repairing effect on OCD than positive charge [27,"[107.0, 175.0, 587.0, 775.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,3,text,"Based on this, we innovatively propose combining magnetic nanoparticles (MNPs) with SF to construct a smart scaffold (FENS@MF) with enhanced piezoelectric effects. Magnetic nanomaterials (MNPs) are bi","[106.0, 777.0, 586.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
3,4,text,,"[602.0, 175.0, 1084.0, 609.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
3,5,paragraph_title,Materials and materials γ-Fe₂O₃@PSC preparation,"[603.0, 628.0, 829.0, 679.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Materials and materials \u03b3-Fe\u2082O\u2083@PSC preparation""]",subsection_heading,0.6,body_zone,body_like,none,True,True
3,6,text,"First, 168 mg of Polyethylene sorbitol carboxymethyl ether is weighed and added to a 15 mL round-bottomed flask, followed by 2.5 mL of ultra-pure water and fully dissolved. Then, 92 mg of ferric chlor","[602.0, 676.0, 1082.0, 1403.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[109.0, 67.0, 508.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
4,1,number,Page 4 of 22,"[990.0, 66.0, 1080.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
4,2,image,,"[119.0, 164.0, 1073.0, 961.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
4,3,figure_title,"Fig. 1 Schematic diagram of the construction of iron-based nanoparticle enhanced silk fibroin (SF) piezoelectric scaffold, ① γ-Fe₂O₃@PSC covalently binds to a pure silk fibroin scaffold (SFC) to form ","[106.0, 982.0, 1082.0, 1084.0]",figure_caption,0.92,"[""figure_title label: Fig. 1 Schematic diagram of the construction of iron-based n""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
4,4,paragraph_title,Silk fibroin scaffold (SFC) preparation,"[108.0, 1111.0, 412.0, 1132.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Silk fibroin scaffold (SFC) preparation""]",subsection_heading,0.6,body_zone,body_like,none,True,True
4,5,text,"The SF solution was extracted, purified and concentrated according to the previous working method [33]. In brief, the natural mulberry silk (50 g, purchased by Xinyuan Biotechnology Co., Ltd, Hangzhou","[106.0, 1135.0, 586.0, 1472.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,6,text,,"[602.0, 1110.0, 1082.0, 1255.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
4,7,paragraph_title,Preparation of SFC with enhanced piezoelectric effect,"[604.0, 1278.0, 1038.0, 1303.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Preparation of SFC with enhanced piezoelectric effect""]",subsection_heading,0.6,body_zone,body_like,none,True,True
4,8,text,"The $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC (121.4 mg, Jiangsu Key Laboratory of Biomaterials and Devices), EDC (267.4 mg, Sigma-Aldrich, USA) and NHS (118 mg, Sigma-Aldrich, USA) were weighed and mixed","[602.0, 1302.0, 1083.0, 1472.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 508.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
5,1,number,Page 5 of 22,"[990.0, 65.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
5,2,text,"in the mixture for 12 h, forming a stable amide-bonded structure through covalent self-assembly. Finally, an SFC that can exert enhanced piezoelectric effect under MF, called enhanced piezoelectric sc","[106.0, 174.0, 586.0, 368.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,3,paragraph_title,Structural characterization of enhanced SF piezoelectric scaffold,"[106.0, 391.0, 561.0, 437.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Structural characterization of enhanced SF piezoelectric sca""]",subsection_heading,0.6,body_zone,body_like,none,True,True
5,4,text,"The surface morphology of the enhanced piezoelectric scaffold was observed by scanning electron microscopy (SEM, Ultra Plus, Zeiss, Germany), and the elemental composition of the scaffold was analyzed","[106.0, 439.0, 588.0, 1159.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,5,figure_title,Table 1 Composition and abbreviation of each samples,"[107.0, 1175.0, 522.0, 1197.0]",table_caption,0.9,"[""table prefix matched: Table 1 Composition and abbreviation of each samples""]",table_caption,0.9,display_zone,table_caption_like,table_number,True,True
5,6,table,<table><tr><td>Samples</td><td>Abbreviation</td><td>MNPs concentration ( $ \mu $L/mL)</td></tr><tr><td>Silk fibroin</td><td>SF</td><td>0</td></tr><tr><td>Silk fibroin scaffold</td><td>SFC</td><td>0</t,"[106.0, 1200.0, 581.0, 1469.0]",table_html,0.85,"[""media label: table""]",media_asset,0.85,body_zone,body_like,none,True,True
5,7,text,"In addition, XRD patterns of SFC, FENS and FENS@MF were tested by XRD diffractometer at radiation wavelength $ \gamma=0.154 $ A, beam energy 40 kV, current 40 mV and scanning rate 5 $ \sigma $/min ( ","[602.0, 174.0, 1083.0, 320.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,8,paragraph_title,Cytological research of SF enhanced piezoelectric scaffold optimization,"[602.0, 343.0, 1073.0, 388.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Cytological research of SF enhanced piezoelectric scaffold o""]",subsection_heading,0.6,body_zone,body_like,none,True,True
5,9,text,"The $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC, FEN20, FEN50, FEN100 samples were first obtained and sterilized by irradiation for later use. Subsequently, the suspension of cartilage cell line (ATDC5) wit","[602.0, 387.0, 1084.0, 1402.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 508.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
6,1,number,Page 6 of 22,"[989.0, 65.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
6,2,paragraph_title,Mechanical properties,"[108.0, 175.0, 297.0, 197.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Mechanical properties""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,3,text,"An MTS Criterion Test system (MTS, Model 42, USA) was used to test the mechanical strength of SFC and FENS@MF under wet conditions, including longitudinal tensile and compression tests. For both tensi","[106.0, 198.0, 585.0, 417.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,4,paragraph_title,In vitro degradation,"[107.0, 439.0, 275.0, 461.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: In vitro degradation""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,5,text,"Each sample was prepared in 24-well cell culture plates, and 1 mL (8%) sample solution was added to each well. For each group, refer to 2.3 for sample preparation procedures. Each group of dry piezoel","[106.0, 462.0, 586.0, 969.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,6,display_formula, $$ Weight remaining(\%)=W2/W1\times100\% $$ ,"[165.0, 985.0, 528.0, 1012.0]",unknown_structural,0.2,"[""unrecognized label 'display_formula'""]",unknown_structural,0.2,body_zone,body_like,none,False,True
6,7,formula_number,(1),"[557.0, 988.0, 581.0, 1011.0]",unknown_structural,0.2,"[""unrecognized label 'formula_number'""]",unknown_structural,0.2,body_zone,body_like,short_fragment,False,True
6,8,paragraph_title,Swelling behavior,"[108.0, 1062.0, 261.0, 1085.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Swelling behavior""]",subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
6,9,text,"Refer to 2.7 for the preparation model of sample scaffolds for each group. The swelling rate was measured with PBS as a replacement solution. After drying, the scaffolds of each group were weighed and","[106.0, 1086.0, 586.0, 1328.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,10,display_formula, $$ Swelling ratio (\%)=(W2-W1)/W1\times100\% $$ ,"[146.0, 1344.0, 558.0, 1372.0]",unknown_structural,0.2,"[""unrecognized label 'display_formula'""]",unknown_structural,0.2,body_zone,body_like,none,False,True
6,11,formula_number,(2),"[557.0, 1348.0, 582.0, 1370.0]",unknown_structural,0.2,"[""unrecognized label 'formula_number'""]",unknown_structural,0.2,body_zone,body_like,short_fragment,False,True
6,12,paragraph_title,Magnetic responsiveness,"[604.0, 175.0, 815.0, 197.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Magnetic responsiveness""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,13,text,"The magnetic responses of SFC and FENS were evaluated using a vibrating sample magnetometer (VSM, MPMS-3, Quantum Design, USA) in the range of -10000-10000 Oe. The sample was ground into a fine powder","[602.0, 198.0, 1082.0, 367.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,14,paragraph_title,Piezoelectric properties,"[604.0, 391.0, 804.0, 413.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Piezoelectric properties""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,15,text,"The piezoelectric properties of each scaffold were measured by D33 and homemade stepper motors. For the D33, the piezoelectric scaffold was cut into a blocky structure (20×15×2 mm in length, width and","[602.0, 414.0, 1083.0, 1015.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,16,paragraph_title,Cytotoxicity test in vitro,"[603.0, 1039.0, 803.0, 1061.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Cytotoxicity test in vitro""]",subsection_heading,0.6,body_zone,body_like,none,True,True
6,17,text,"The piezoelectric scaffold for each group (SFC, FENS, FENS@MF) was prepared by a 48-well culture plate containing 300 μL SF solution, freeze-dried, and crosslinked with anhydrous ethanol. The enhanced","[602.0, 1064.0, 1083.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 509.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
7,1,number,Page 7 of 22,"[989.0, 65.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
7,2,text,"and cytoskeleton system, respectively. For Edu staining, follow the manufacturer's instructions (S0812, RiboBio, Guangzhou, China) for testing procedures. For cytoskeletal staining, refer to 2.5 for t","[106.0, 174.0, 585.0, 415.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,3,text,"For the BMSCs experiment, the suspension of BMSCs with a density of $ 1 \times 10^5 $ cells/well was seeded into a 24-well culture plate containing 2 mL culture medium and cultured in a humid environ","[106.0, 413.0, 587.0, 991.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,4,paragraph_title,Chondrogenic and osteogenic differentiation,"[107.0, 1015.0, 476.0, 1037.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Chondrogenic and osteogenic differentiation""]",subsection_heading,0.6,body_zone,body_like,none,True,True
7,5,text,"The cell supernatant (2 d) was collected using the 2.11 culture method described above, and GAG and COL2 cytokines were detected using an ELISA kit (MEIMIAN, Wuhan, China) for preliminary evaluation o","[106.0, 1038.0, 586.0, 1302.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,6,text,"Furthermore, BMSCs were co-cultured with different piezoelectric scaffolds (SFC, FENS, FENS@MF) for 3 d, and the supernatant was extracted as the conditioned medium. Among them, FENS@MF samples were s","[106.0, 1302.0, 586.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,7,text,,"[602.0, 174.0, 1083.0, 487.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
7,8,paragraph_title,Angiogenesis,"[604.0, 510.0, 723.0, 533.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Angiogenesis""]",sub_subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
7,9,text,"Rat vascular endothelial cells (ECs) were co-cultured in a 6-well plate with a density of $ 1 \times 10^{5} $ cells/well and cocultured with SFC, FENS, and FENS@MF samples. The cells were cultured fo","[601.0, 532.0, 1083.0, 1256.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,10,paragraph_title,Animal experiment,"[604.0, 1279.0, 768.0, 1301.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Animal experiment""]",subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
7,11,text,Animal model construction and processing: All animal experiments were performed following the guidelines for the care and use of laboratory animals established by the Affiliated Hospital of Integrated,"[602.0, 1301.0, 1084.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 508.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
8,1,number,Page 8 of 22,"[990.0, 65.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
8,2,text,"Hospital (Ethical Lot Number: 2022-LWKYS-046). The experimental procedures were approved by the hospital ethics committee. A total of 36 SD rats (average weight 300–350 g, male) were selected to const","[106.0, 173.0, 586.0, 486.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,3,text,"Macroscopic observation, microscopic computed tomography (Micro-CT), and histological analysis: At 4 w and 8 w, three living specimens were randomly selected from each group for Micro-CT observation (","[106.0, 483.0, 586.0, 1329.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,4,paragraph_title,Statistical analysis,"[108.0, 1351.0, 264.0, 1374.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Statistical analysis""]",subsection_heading,0.6,body_zone,body_like,none,True,True
8,5,text,"All quantitative data are expressed as the mean±standard deviation (SD). Differences between the two groups were inspected using a paired Student’s t-test, and a comparison of multiple groups was perf","[106.0, 1375.0, 587.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,6,text,,"[603.0, 175.0, 1080.0, 245.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
8,7,paragraph_title,Results Optimization analysis of the concentration of f magnetic nanoparticles (MNPs),"[602.0, 269.0, 1061.0, 341.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Results Optimization analysis of the concentration of f magn""]",subsection_heading,0.6,body_zone,heading_like,none,True,True
8,8,footer,,"[602.0, 294.0, 1061.0, 341.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,empty,False,False
8,9,text,screened so that the constructed piezoelectric scaffold can perform the best repair effect in the future. The $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC was first prepared into a suspension with a concentr,"[602.0, 354.0, 1085.0, 1470.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[109.0, 67.0, 508.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
9,1,number,Page 9 of 22,"[990.0, 66.0, 1080.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
9,2,chart,,"[118.0, 164.0, 444.0, 452.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
9,3,figure_title,B,"[470.0, 167.0, 495.0, 198.0]",figure_inner_text,0.9,"[""panel label / figure inner text: B""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
9,4,chart,,"[438.0, 181.0, 737.0, 450.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
9,5,figure_title,C,"[762.0, 169.0, 793.0, 201.0]",figure_inner_text,0.9,"[""panel label / figure inner text: C""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
9,6,chart,,"[748.0, 206.0, 1069.0, 439.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
9,7,image,,"[143.0, 459.0, 1062.0, 916.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
9,8,figure_title,"Fig. 2 (A) The magnetothermal curves FEN20, FEN50, FEN100 at an operating frequency of 1.5 MHz and a current of 15 mA for 1200 s; (B) The XPS spectrum of FEN20, FEN50, FEN100; (C) The CCK-8 assay resu","[108.0, 932.0, 1082.0, 1015.0]",figure_caption,0.92,"[""figure_title label: Fig. 2 (A) The magnetothermal curves FEN20, FEN50, FEN100 at""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
9,9,text,"performed SEM-EDS analysis of the spatial structure of the scaffold. As shown in Fig. 2E, each scaffold presents a continuous network of porous structures, and the pore size decreases with the increas","[107.0, 1038.0, 587.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,10,paragraph_title,Preparation and characterization of silk fibroin enhanced piezoelectric scaffolds,"[602.0, 1038.0, 1064.0, 1085.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Preparation and characterization of silk fibroin enhanced pi""]",subsection_heading,0.6,body_zone,body_like,none,True,True
9,11,text,"The piezoelectric scaffolds were prepared by freeze-drying technology and included pure silk fibroin scaffolds named SFC, MNPs-modified SFC named FENS, and magnetic field-induced FENS named FENS@MF. T","[602.0, 1087.0, 1082.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[110.0, 67.0, 507.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
10,1,number,Page 10 of 22,"[982.0, 66.0, 1080.0, 87.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
10,2,chart,,"[126.0, 168.0, 1066.0, 473.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
10,3,image,,"[117.0, 154.0, 1069.0, 768.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
10,4,figure_title,"Fig. 3 (A) The FTIR spectrum of SFC, $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC, EDC, NHS, and FENS; (B) Representative tensile stress-strain curves of SFC and FENS; (C) Representative compression-stress c","[107.0, 786.0, 1083.0, 950.0]",figure_caption,0.92,"[""figure_title label: Fig. 3 (A) The FTIR spectrum of SFC, $ \\gamma $-Fe $ _{2} $""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
10,5,text,"are consistent with SFC and $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC. After the activation of the carboxyl group by ECD-NHS, it can be seen that the amide covalent bond is significantly shifted to 3293 c","[106.0, 964.0, 587.0, 1472.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,6,text,,"[602.0, 968.0, 1083.0, 1300.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
10,7,text,"The osteochondral repair period is usually longer, generally more than 3 months. Even materials like SFC degrade more slowly than other natural materials, making it difficult to achieve a match betwee","[603.0, 1302.0, 1083.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 509.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
11,1,number,Page 11 of 22,"[981.0, 65.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
11,2,text,of each group of piezoelectric scaffolds was evaluated by immersing them in a control PBS solution and a simulated enzyme solution (protease XIV). The test results showed that all the samples in PBS s,"[106.0, 174.0, 586.0, 897.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,3,paragraph_title,Piezoelectric effect analysis,"[108.0, 919.0, 335.0, 941.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Piezoelectric effect analysis""]",subsection_heading,0.6,body_zone,body_like,none,True,True
11,4,text,"To investigate the enhanced piezoelectricity of FENS@MF, we measured it with a D33 piezoelectric tester and self-made piezoelectric equipment. FENS@MF samples must be subjected to intermittent MF acti","[106.0, 942.0, 587.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,5,text,,"[602.0, 174.0, 1082.0, 273.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
11,6,paragraph_title,In vitro cytotoxicity evaluation analysis,"[603.0, 295.0, 922.0, 317.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: In vitro cytotoxicity evaluation analysis""]",subsection_heading,0.6,body_zone,body_like,none,True,True
11,7,text,"Chondrocytes (ATDC5) and bone marrow mesenchymal stem cells (BMSCs), as important seed cells for bone tissue regeneration, were used to further evaluate the biosafety of piezoelectric scaffolds. First","[602.0, 318.0, 1083.0, 871.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,8,text,"Furthermore, BMSCs cells were used to investigate the toxic effects of piezoelectric scaffolds. The Edu results showed almost the same change trend as ATDC5 cells, but the FENS@MF proliferation was mo","[602.0, 871.0, 1083.0, 1327.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,9,text,"Finally, we further evaluate enhanced piezoelectric scaffolds' safety and potential biomedical value through the CCK-8 experiment. The evaluation results of ATDC5 cells showed that (Fig. S3B), except ","[602.0, 1327.0, 1083.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 509.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
12,1,number,Page 12 of 22,"[981.0, 65.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
12,2,text,"d, the cell proliferation was not obvious, which may be due to the fast growth rate of cells that made the fusion rate reach 100%. The results of BMSCs showed almost the same change trend (Fig. S4D), ","[106.0, 174.0, 586.0, 393.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,3,paragraph_title,Analysis of regulating chondrogenic and osteogenic differentiation of BMSCs through FENS@MF,"[106.0, 414.0, 530.0, 461.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Analysis of regulating chondrogenic and osteogenic different""]",subsection_heading,0.6,body_zone,body_like,none,True,True
12,4,text,"Subsequently, we further investigated the effect of piezoelectric scaffolds on chondrogenic and osteogenic differentiation of BMSCs. BMSCs suspension 2.11 was collected and centrifuged for preliminary","[106.0, 463.0, 588.0, 1424.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,5,text,"Next, the osteogenic differentiation of BMSCs via piezoelectric scaffolds was further investigated. It was evident that the FENS@MF group had more calcium deposition at 21 d by alizarin red staining (","[107.0, 1423.0, 587.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
12,6,text,,"[601.0, 175.0, 1084.0, 920.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
12,7,paragraph_title,Angiogenesis analysis,"[604.0, 943.0, 790.0, 966.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Angiogenesis analysis""]",subsection_heading,0.6,body_zone,body_like,none,True,True
12,8,text,"Bone cartilage consists of hard bone tissue and cartilage tissue, in which the subchondral bone area is rich in capillary tissue, which can provide nutritional support for the growth and development o","[602.0, 968.0, 1082.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[109.0, 67.0, 508.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
13,1,number,Page 13 of 22,"[981.0, 66.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
13,2,figure_title,A,"[135.0, 167.0, 160.0, 193.0]",figure_inner_text,0.9,"[""panel label / figure inner text: A""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
13,3,image,,"[137.0, 167.0, 775.0, 317.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
13,4,figure_title,B,"[775.0, 168.0, 799.0, 194.0]",figure_inner_text,0.9,"[""panel label / figure inner text: B""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
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13,6,chart,,"[126.0, 326.0, 341.0, 526.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
13,7,figure_title,D,"[332.0, 330.0, 355.0, 352.0]",figure_inner_text,0.9,"[""panel label / figure inner text: D""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
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13,11,figure_title,G,"[136.0, 542.0, 163.0, 569.0]",figure_inner_text,0.9,"[""panel label / figure inner text: G""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
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13,15,chart,,"[809.0, 546.0, 1036.0, 719.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
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13,18,chart,,"[558.0, 706.0, 822.0, 909.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
13,19,image,,"[821.0, 720.0, 1059.0, 910.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True
13,20,figure_title,"Fig. 4 Analysis of chondroblast differentiation (A–F). (A) Representative Alcian blue stained images after co-cultivation of BMSCs with piezoelectric scaffolds (SFC, FENS, FENS@MF) for 21 d; (B) The e","[106.0, 936.0, 1084.0, 1138.0]",figure_caption,0.92,"[""figure_title label: Fig. 4 Analysis of chondroblast differentiation (A\u2013F). (A) R""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
13,21,text,"proliferating cell nuclear antigen (PCNA) (Fig. 5H–I) expression is higher than that in SFC and FENS groups, indicating that FENS@MF has better angiogenesis potential.","[107.0, 1158.0, 586.0, 1256.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,22,paragraph_title,Phenotypic analysis of macrophages,"[108.0, 1279.0, 408.0, 1301.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Phenotypic analysis of macrophages""]",subsection_heading,0.6,body_zone,body_like,none,True,True
13,23,text,"OCD are usually accompanied by a sharp deterioration of the inflammatory microenvironment, recruiting more M1-type macrophages, further accelerating the apoptosis of chondrocytes and worsening the mic","[107.0, 1303.0, 586.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,24,text,,"[602.0, 1158.0, 1084.0, 1472.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,body_zone,body_like,empty,True,True
14,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 508.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
14,1,number,Page 14 of 22,"[981.0, 66.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
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14,9,figure_title,I,"[862.0, 916.0, 876.0, 940.0]",figure_inner_text,0.9,"[""panel label / figure inner text: I""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
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14,11,chart,,"[859.0, 939.0, 1062.0, 1108.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,,unknown_like,empty,True,True
14,12,figure_title,"Fig. 5 Angiogenesis analysis. (A) Representative Prussian blue stained images after co-cultivation of ECs with piezoelectric scaffolds (SFC, FENS, FENS@MF) for 2 d; (B) Representative immunofluorescen","[106.0, 1132.0, 1083.0, 1215.0]",figure_caption,0.92,"[""figure_title label: Fig. 5 Angiogenesis analysis. (A) Representative Prussian bl""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
14,13,text,"expression level of TNF- $ \alpha $ decreased in SFC, FENS, and FENS@MF samples, respectively, and was almost the same in IL-4 and FENS@MF groups. On the contrary, VEGF expression showed an increasing","[106.0, 1230.0, 586.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,14,text,,"[602.0, 1230.0, 1083.0, 1450.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
15,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[109.0, 67.0, 507.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
15,1,number,Page 15 of 22,"[982.0, 66.0, 1080.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
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15,7,figure_title,Fig. 6 (A) Silk fibroin piezoelectric scaffolds or silk fibroin-enhanced piezoelectric scaffolds were used to promote the regeneration of OCD in rats. It was inserted into the osteochondral defect of ,"[108.0, 1173.0, 1083.0, 1334.0]",figure_caption,0.92,"[""figure_title label: Fig. 6 (A) Silk fibroin piezoelectric scaffolds or silk fibr""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
15,8,text,"conditions, while sham surgery, models, and autologous transplantation (ATPT) groups were established.","[108.0, 1351.0, 584.0, 1399.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,9,text,"Macroscopic observation In general, at 4 w after the operation, the structure of the sham operation group was complete, while no regenerated tissue was found in the model group (blank control group), ","[108.0, 1401.0, 586.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
15,10,text,,"[603.0, 1351.0, 1082.0, 1473.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
16,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 509.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
16,1,number,Page 16 of 22,"[981.0, 66.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
16,2,text,"non-degradation state of the piezoelectric scaffolds can be observed in the SFC, FENS, and FENS@MF groups, and chondroid tissue growth can be observed in the defect area, but the tissue coverage is li","[106.0, 175.0, 586.0, 486.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,3,text,Micro-CT analyses The 1.5 mm profound osteochondral defect in rats involved the entire cartilage layer and part of the hard bone. Figure 6C shows a Micro-CT view of cartilage regeneration in the defec,"[107.0, 486.0, 587.0, 1477.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
16,4,text,,"[602.0, 174.0, 1082.0, 367.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
16,5,text,"Histological analyses Histological staining (HE, Safranin O&Fast Green, Masson, Alcian Blue, Von Kossa, and Sirius red) was used to evaluate the repair effect of each group of scaffolds. The H&E stain","[602.0, 366.0, 1084.0, 992.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
16,6,text,"At 4 w after the operation, large defect space and less new tissue were still observed in the model group, and the defect was deep into the subchondral bone. At this stage, the tissue growth was mainl","[602.0, 992.0, 1083.0, 1475.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
17,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 67.0, 507.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
17,1,number,Page 17 of 22,"[981.0, 66.0, 1080.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
17,2,image,,"[126.0, 162.0, 1036.0, 1028.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True
17,3,chart,,"[142.0, 1046.0, 1071.0, 1193.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,,unknown_like,empty,True,True
17,4,figure_title,"Fig. 7 Histological analysis. Representative H&E (A), Safranin O&Fast Green (B), Masson (C) and Alcian Blue (D) staining images of the osteochondral regeneration in the defects in different groups 4 a","[107.0, 1214.0, 1083.0, 1298.0]",figure_caption,0.92,"[""figure_title label: Fig. 7 Histological analysis. Representative H&E (A), Safran""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
17,5,text,"obviously observed that a large number of new collagen fibers represent new bone growth, and a small number of areas have highly mature bone tissue. On the contrary, at 8 w, we can see that many new b","[107.0, 1327.0, 586.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
17,6,text,,"[603.0, 1327.0, 1083.0, 1472.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
18,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 508.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
18,1,number,Page 18 of 22,"[982.0, 66.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
18,2,text,"in the SFC and FENS groups (yellow region) than in the other groups (Model, ATPT, FENS@MF), while FENS@MF showed the most type II collagen fibers (red region). At 8 w, FENS@MF showed more type I colla","[107.0, 175.0, 586.0, 1182.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
18,3,text,"Immunohistochemistry analyses Type I and type II collagen immunohistochemical staining were used to further investigate subchondral bone and chondrogenesis. As shown in Fig. 7G, it can be observed tha","[106.0, 1183.0, 586.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
18,4,text,,"[602.0, 174.0, 1083.0, 609.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
18,5,paragraph_title,Discussion,"[605.0, 629.0, 712.0, 652.0]",section_heading,0.9,"[""explicit scholarly heading: Discussion""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
18,6,text,Bone tissue engineering is considered to be one of the most promising therapeutic approaches for treating OCD. The defective osteochondral bone leads to changes in the physiological electrical microen,"[602.0, 654.0, 1083.0, 943.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
18,7,text,"Among the many electroactive materials [42], piezoelectric materials have attracted great attention because they can directly convert mechanical pressure into electrical signals in vivo without additi","[602.0, 944.0, 1083.0, 1375.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
18,8,text,MNPs are widely used in clinical and preclinical experimental studies due to their excellent biocompatibility [45]. Their ability to delay degradation is based on modifiers on the surface of the mater,"[602.0, 1375.0, 1083.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
19,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[109.0, 67.0, 508.0, 87.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
19,1,number,Page 19 of 22,"[982.0, 66.0, 1080.0, 87.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
19,2,figure_title,A,"[141.0, 166.0, 161.0, 186.0]",figure_inner_text,0.9,"[""panel label / figure inner text: A""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
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19,9,figure_title,G,"[789.0, 384.0, 807.0, 405.0]",figure_inner_text,0.9,"[""panel label / figure inner text: G""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
19,10,chart,,"[798.0, 400.0, 1069.0, 615.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,,unknown_like,empty,True,True
19,11,figure_title,C,"[139.0, 633.0, 159.0, 653.0]",figure_inner_text,0.9,"[""panel label / figure inner text: C""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
19,12,chart,,"[144.0, 639.0, 438.0, 879.0]",figure_asset,0.85,"[""media label: chart""]",media_asset,0.85,,unknown_like,empty,True,True
19,13,figure_title,H,"[466.0, 640.0, 487.0, 661.0]",figure_inner_text,0.9,"[""panel label / figure inner text: H""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
19,14,image,,"[556.0, 632.0, 1009.0, 871.0]",figure_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True
19,15,figure_title,"Fig. 8 (A–B) w/s and quantitative analysis or $ \mu $-catenin protein levels in BMs_s culture in piezoelectric scaffold (FENs, FENs@MT) conditioned medium for 21 d (N=3); (C, G) The qPCR detection of","[106.0, 901.0, 1083.0, 1023.0]",figure_caption,0.92,"[""figure_title label: Fig. 8 (A\u2013B) w/s and quantitative analysis or $ \\mu $-caten""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
19,16,text,"the composite scaffold [33]. We successfully constructed FENS@MF scaffolds by mixing MNPs (FEN50) with SF solution under an EDC/NHC environment (Fig. 3A–D). As with the envisaged results, the mechanic","[107.0, 1038.0, 585.0, 1375.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
19,17,text,"The SFC itself have a weak piezoelectric effect, and although many researchers have used SFC to treat osteochondral injuries, few studies have been conducted to enhance the piezoelectric effect of SF ","[107.0, 1376.0, 586.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
19,18,text,,"[602.0, 1040.0, 1083.0, 1474.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
20,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[108.0, 66.0, 508.0, 88.0]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
20,1,number,Page 20 of 22,"[981.0, 66.0, 1081.0, 88.0]",noise,0.9,"[""page number label""]",noise,0.9,,unknown_like,short_fragment,False,False
20,2,text,"form a local electromagnetic field in the magnetic field (MF), which generates a magneto-thermal effect with the external alternating magnetic field (AMF) [47], and the moderate temperature rise gener","[106.0, 175.0, 587.0, 1402.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
20,3,text,"With these methods from in vitro studies, we expected that the FENS@MF scaffold could also achieve good repair results in in vivo experiments. Therefore, we established different experimental groups, ","[107.0, 1400.0, 586.0, 1473.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
20,4,text,,"[602.0, 175.0, 1083.0, 846.0]",ocr_text_missing,0.8,"[""ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available""]",ocr_text_missing,0.8,,unknown_like,empty,True,True
20,5,text,"To the best of our knowledge, this is the first time that the combination of SFC and MNPs has been comprehensively evaluated in in vitro and in vivo experiments to assess the therapeutic efficacy of F","[602.0, 847.0, 1082.0, 1330.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
20,6,paragraph_title,Conclusion,"[604.0, 1350.0, 716.0, 1374.0]",section_heading,0.9,"[""explicit scholarly heading: Conclusion""]",section_heading,0.9,body_zone,heading_like,canonical_section_name,True,True
20,7,text,This study developed a magnetic nanoparticle-enhanced silk fibroin scaffold (FENS@MF) with superior piezoelectric performance for osteochondral repair. By covalently integrating $ \gamma $-Fe $ _{2} ,"[602.0, 1374.0, 1083.0, 1474.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
21,0,header,Liu et al. Journal of Nanobiotechnology (2026) 24:239,"[109.0, 67.0, 507.0, 87.0]",reference_item,0.9,"[""header label""]",noise,0.9,reference_zone,unknown_like,none,True,True
21,1,number,Page 21 of 22,"[982.0, 66.0, 1080.0, 87.0]",noise,0.9,"[""page number label""]",noise,0.9,body_zone,body_like,short_fragment,False,False
21,2,text,"via EDC/NHS crosslinking, FENS@MF achieved a 3-fold increase in tensile strength and 15.65% slower degradation than pristine SFC in vitro. The scaffold exhibited a 8.5-fold enhancement in piezoelectri","[108.0, 175.0, 586.0, 729.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,3,paragraph_title,Supplementary Information,"[109.0, 751.0, 372.0, 772.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Supplementary Information""]",backmatter_boundary_candidate,0.5,body_zone,heading_like,none,True,True
21,4,text,The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04131-9.,"[108.0, 773.0, 578.0, 809.0]",body_paragraph,0.6,"[""default body_paragraph for text label"", ""tail_nonref_hold_zone excluded from body flow""]",backmatter_body,0.6,,unknown_like,none,True,True
21,5,text,Supplementary Material 1,"[121.0, 830.0, 280.0, 851.0]",body_paragraph,0.6,"[""default body_paragraph for text label"", ""tail_nonref_hold_zone excluded from body flow""]",backmatter_body,0.6,,unknown_like,none,True,True
21,6,paragraph_title,Author contributions,"[110.0, 884.0, 252.0, 901.0]",unknown_structural,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Author contributions""]",subsection_heading,0.6,tail_nonref_hold_zone,support_like,none,False,True
21,7,text,"Xin Liu: Experimental procedures included material characterization and cell culture, writing-original draft, revision, etc., Supervision, Funding provision. Congyang Xue: WB and some animal experimen","[108.0, 903.0, 576.0, 1120.0]",body_paragraph,0.6,"[""default body_paragraph for text label"", ""tail_nonref_hold_zone excluded from body flow""]",backmatter_body,0.6,,unknown_like,none,True,True
21,8,paragraph_title,Funding,"[110.0, 1136.0, 170.0, 1154.0]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Funding""]",sub_subsection_heading,0.6,tail_nonref_hold_zone,unknown_like,short_fragment,True,True
21,9,text,"The research was supported by the Natural Science Foundation of Jiangsu Province (BK20220464), the National Natural Science Foundation of China (82302735), the Project of Institute of Chinese Medicine","[108.0, 1155.0, 577.0, 1390.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
21,10,paragraph_title,Data availability,"[110.0, 1406.0, 222.0, 1424.0]",unknown_structural,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Data availability""]",subsection_heading,0.6,tail_nonref_hold_zone,unknown_like,short_fragment,False,True
21,11,text,Data will be made available on request.,"[110.0, 1425.0, 349.0, 1443.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
21,12,paragraph_title,Declarations Ethics approval and consent to participate,"[606.0, 166.0, 885.0, 223.0]",backmatter_boundary_candidate,0.5,"[""backmatter boundary candidate: Declarations Ethics approval and consent to participate""]",backmatter_boundary_candidate,0.5,body_zone,body_like,none,True,True
21,13,footer,,"[606.0, 204.0, 885.0, 223.0]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,empty,False,False
21,14,text,The handling of animals followed the relevant provisions of the Regulations on the Management of Laboratory Animals. The relevant procedures were approved by the Animal Ethics Committee of the Affilia,"[604.0, 223.0, 1062.0, 313.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,15,paragraph_title,Consent for publication,"[606.0, 330.0, 765.0, 348.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Consent for publication""]",subsection_heading,0.6,body_zone,body_like,none,True,True
21,16,text,All authors have provided consent for the manuscript to be published in Journal of Nanobiotechnology.,"[606.0, 348.0, 1043.0, 385.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,17,paragraph_title,Competing interests,"[606.0, 402.0, 744.0, 420.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Competing interests""]",subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
21,18,text,The authors declare no competing interests.,"[606.0, 422.0, 875.0, 439.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,19,paragraph_title,Author details,"[606.0, 456.0, 705.0, 474.0]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Author details""]",subsection_heading,0.6,body_zone,body_like,short_fragment,True,True
21,20,text,"¹The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R. China
²Department of Spine Surgery, Affiliated Hospital of Integrated Traditional ","[604.0, 475.0, 1048.0, 691.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,21,text,Received: 31 July 2025 / Accepted: 31 January 2026,"[605.0, 712.0, 932.0, 731.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,22,text,Published online: 09 February 2026,"[605.0, 734.0, 860.0, 755.0]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,body_zone,support_like,none,False,False
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22,43,paragraph_title,Publisher's note,"[607.0, 1303.0, 759.0, 1323.0]",backmatter_heading,0.8,"[""backmatter heading on page 22: Publisher's note""]",backmatter_heading_candidate,0.8,,support_like,short_fragment,True,True
22,44,text,Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.,"[605.0, 1325.0, 1026.0, 1362.0]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
1 page block_id raw_label content_preview bbox role role_confidence evidence seed_role seed_confidence zone style_family marker_type render_default index_default
2 1 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 https://doi.org/10.1186/s12951-026-04131-9 [108.0, 66.0, 492.0, 108.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
3 1 1 header Journal of Nanobiotechnology [758.0, 64.0, 1081.0, 96.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
4 1 2 text RESEARCH [116.0, 183.0, 270.0, 211.0] non_body_insert 0.3 ["short text, uncertain role"] unknown_structural 0.3 frontmatter_main_zone support_like short_fragment False False
5 1 3 text Open Access [922.0, 183.0, 1075.0, 212.0] frontmatter_noise 0.7 ["frontmatter noise text: Open Access"] frontmatter_noise 0.7 frontmatter_main_zone support_like short_fragment False False
6 1 4 image [1019.0, 226.0, 1076.0, 283.0] media_asset 0.85 ["media label: image"] media_asset 0.85 frontmatter_main_zone support_like empty True True
7 1 5 doc_title Piezoelectric scaffold with enhanced effect drives the healing of osteochondral defects through electromechanical-immune coupling [108.0, 245.0, 982.0, 403.0] paper_title 0.8 ["page-1 zone title_zone: Piezoelectric scaffold with enhanced effect drives the heali"] paper_title 0.8 frontmatter_main_zone support_like none True True
8 1 6 text Xin Liu $ ^{1,2*} $ $ ^{\dagger} $, Congyang Xue $ ^{1,2} $ $ ^{\dagger} $, Jun Guo $ ^{1,2} $ $ ^{\dagger} $, Nan Chen $ ^{1,2} $, Bo Chen $ ^{3} $, Zihan Wang $ ^{4} $, Xuan Han $ ^{5} $, Liping Che [106.0, 435.0, 999.0, 496.0] authors 0.8 ["page-1 zone author_zone: Xin Liu $ ^{1,2*} $ $ ^{\\dagger} $, Congyang Xue $ ^{1,2} $ "] authors 0.8 frontmatter_main_zone support_like none True True
9 1 7 paragraph_title Abstract [121.0, 546.0, 210.0, 569.0] abstract_heading 0.95 ["abstract heading"] abstract_heading 0.95 frontmatter_main_zone heading_like short_fragment True True
10 1 8 abstract Silk fibroin scaffolds (SFCs) that exploit piezoelectricity for osteochondral repair have been hampered by both insufficient electromechanical output and a pro-inflammatory joint microenvironment that [118.0, 569.0, 1067.0, 1030.0] abstract_body 0.85 ["abstract label from Paddle OCR"] abstract_body 0.85 frontmatter_main_zone support_like none True True
11 1 9 text $ ^{\dagger} $Xin Liu, Congyang Xue and Jun Guo contributed equally to this work. [109.0, 1107.0, 499.0, 1145.0] frontmatter_support 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 frontmatter_main_zone support_like affiliation_marker True True
12 1 10 footnote *Correspondence: Xin Liu liuxin@njucm.edu.cn Ding Qu quding1985@hotmail.com Ran Kang kangran126@126.com [108.0, 1154.0, 279.0, 1280.0] frontmatter_noise 0.8 ["page-1 zone journal_furniture_zone: *Correspondence:\nXin Liu\nliuxin@njucm.edu.cn\nDing Qu\nquding1"] frontmatter_noise 0.8 frontmatter_main_zone support_like none False False
13 1 11 footnote Full list of author information is available at the end of the article [108.0, 1288.0, 501.0, 1308.0] footnote 0.7 ["footnote label: Full list of author information is available at the end of t"] footnote 0.7 frontmatter_main_zone support_like none True True
14 1 12 footer_image [113.0, 1342.0, 331.0, 1402.0] non_body_insert 0.2 ["unrecognized label 'footer_image'"] unknown_structural 0.2 frontmatter_main_zone support_like empty False False
15 1 13 footer © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, di [354.0, 1344.0, 1083.0, 1473.0] noise 0.9 ["footer label"] noise 0.9 frontmatter_main_zone support_like none False False
16 2 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 509.0, 88.0] noise 0.9 ["header label"] noise 0.9 frontmatter_main_zone support_like none False False
17 2 1 number Page 2 of 22 [990.0, 66.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
18 2 2 text Keywords Magnetic nanoparticles, Silk fibroin scaffold, Piezoelectric effect, Osteochondral, Stem cell [119.0, 177.0, 934.0, 204.0] unknown_structural 0.8 ["page-1 zone author_zone: Keywords Magnetic nanoparticles, Silk fibroin scaffold, Piez"] authors 0.8 body_zone body_like none False True
19 2 3 paragraph_title Introduction [107.0, 246.0, 235.0, 268.0] section_heading 0.9 ["explicit scholarly heading: Introduction"] section_heading 0.9 body_zone heading_like canonical_section_name True True
20 2 4 text Osteochondral defects (OCD) are one of the leading causes of pain, disability and osteoarthritis [1], affecting more than 300 million people worldwide. Due to the lack of vascular and nerve innervatio [107.0, 269.0, 586.0, 872.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
21 2 5 text At present, a number of naturals or synthetic polymers have been used to develop osteochondral scaffolds [7–9]. Among them, natural polymers are widely used in bone tissue engineering because of their [106.0, 873.0, 587.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
22 2 6 text [602.0, 246.0, 1083.0, 558.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
23 2 7 text In recent years, piezoelectric materials with force-electric conversion function have attracted the attention of scholars at home and abroad [16], especially natural piezoelectric materials with good [602.0, 556.0, 1085.0, 1476.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
24 3 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 509.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
25 3 1 number Page 3 of 22 [990.0, 65.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
26 3 2 text crystal units indicates that the silk fibroin has a piezoelectric effect [26]. Previous studies have also shown that negative charge has a more obvious repairing effect on OCD than positive charge [27 [107.0, 175.0, 587.0, 775.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
27 3 3 text Based on this, we innovatively propose combining magnetic nanoparticles (MNPs) with SF to construct a smart scaffold (FENS@MF) with enhanced piezoelectric effects. Magnetic nanomaterials (MNPs) are bi [106.0, 777.0, 586.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
28 3 4 text [602.0, 175.0, 1084.0, 609.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
29 3 5 paragraph_title Materials and materials γ-Fe₂O₃@PSC preparation [603.0, 628.0, 829.0, 679.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Materials and materials \u03b3-Fe\u2082O\u2083@PSC preparation"] subsection_heading 0.6 body_zone body_like none True True
30 3 6 text First, 168 mg of Polyethylene sorbitol carboxymethyl ether is weighed and added to a 15 mL round-bottomed flask, followed by 2.5 mL of ultra-pure water and fully dissolved. Then, 92 mg of ferric chlor [602.0, 676.0, 1082.0, 1403.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
31 4 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [109.0, 67.0, 508.0, 87.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
32 4 1 number Page 4 of 22 [990.0, 66.0, 1080.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
33 4 2 image [119.0, 164.0, 1073.0, 961.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
34 4 3 figure_title Fig. 1 Schematic diagram of the construction of iron-based nanoparticle enhanced silk fibroin (SF) piezoelectric scaffold, ① γ-Fe₂O₃@PSC covalently binds to a pure silk fibroin scaffold (SFC) to form [106.0, 982.0, 1082.0, 1084.0] figure_caption 0.92 ["figure_title label: Fig. 1 Schematic diagram of the construction of iron-based n"] figure_caption 0.92 display_zone legend_like figure_number True True
35 4 4 paragraph_title Silk fibroin scaffold (SFC) preparation [108.0, 1111.0, 412.0, 1132.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Silk fibroin scaffold (SFC) preparation"] subsection_heading 0.6 body_zone body_like none True True
36 4 5 text The SF solution was extracted, purified and concentrated according to the previous working method [33]. In brief, the natural mulberry silk (50 g, purchased by Xinyuan Biotechnology Co., Ltd, Hangzhou [106.0, 1135.0, 586.0, 1472.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
37 4 6 text [602.0, 1110.0, 1082.0, 1255.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
38 4 7 paragraph_title Preparation of SFC with enhanced piezoelectric effect [604.0, 1278.0, 1038.0, 1303.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Preparation of SFC with enhanced piezoelectric effect"] subsection_heading 0.6 body_zone body_like none True True
39 4 8 text The $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC (121.4 mg, Jiangsu Key Laboratory of Biomaterials and Devices), EDC (267.4 mg, Sigma-Aldrich, USA) and NHS (118 mg, Sigma-Aldrich, USA) were weighed and mixed [602.0, 1302.0, 1083.0, 1472.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
40 5 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 508.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
41 5 1 number Page 5 of 22 [990.0, 65.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
42 5 2 text in the mixture for 12 h, forming a stable amide-bonded structure through covalent self-assembly. Finally, an SFC that can exert enhanced piezoelectric effect under MF, called enhanced piezoelectric sc [106.0, 174.0, 586.0, 368.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
43 5 3 paragraph_title Structural characterization of enhanced SF piezoelectric scaffold [106.0, 391.0, 561.0, 437.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Structural characterization of enhanced SF piezoelectric sca"] subsection_heading 0.6 body_zone body_like none True True
44 5 4 text The surface morphology of the enhanced piezoelectric scaffold was observed by scanning electron microscopy (SEM, Ultra Plus, Zeiss, Germany), and the elemental composition of the scaffold was analyzed [106.0, 439.0, 588.0, 1159.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
45 5 5 figure_title Table 1 Composition and abbreviation of each samples [107.0, 1175.0, 522.0, 1197.0] table_caption 0.9 ["table prefix matched: Table 1 Composition and abbreviation of each samples"] table_caption 0.9 display_zone table_caption_like table_number True True
46 5 6 table <table><tr><td>Samples</td><td>Abbreviation</td><td>MNPs concentration ( $ \mu $L/mL)</td></tr><tr><td>Silk fibroin</td><td>SF</td><td>0</td></tr><tr><td>Silk fibroin scaffold</td><td>SFC</td><td>0</t [106.0, 1200.0, 581.0, 1469.0] table_html 0.85 ["media label: table"] media_asset 0.85 body_zone body_like none True True
47 5 7 text In addition, XRD patterns of SFC, FENS and FENS@MF were tested by XRD diffractometer at radiation wavelength $ \gamma=0.154 $ A, beam energy 40 kV, current 40 mV and scanning rate 5 $ \sigma $/min ( [602.0, 174.0, 1083.0, 320.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
48 5 8 paragraph_title Cytological research of SF enhanced piezoelectric scaffold optimization [602.0, 343.0, 1073.0, 388.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Cytological research of SF enhanced piezoelectric scaffold o"] subsection_heading 0.6 body_zone body_like none True True
49 5 9 text The $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC, FEN20, FEN50, FEN100 samples were first obtained and sterilized by irradiation for later use. Subsequently, the suspension of cartilage cell line (ATDC5) wit [602.0, 387.0, 1084.0, 1402.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
50 6 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 508.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
51 6 1 number Page 6 of 22 [989.0, 65.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
52 6 2 paragraph_title Mechanical properties [108.0, 175.0, 297.0, 197.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Mechanical properties"] subsection_heading 0.6 body_zone body_like none True True
53 6 3 text An MTS Criterion Test system (MTS, Model 42, USA) was used to test the mechanical strength of SFC and FENS@MF under wet conditions, including longitudinal tensile and compression tests. For both tensi [106.0, 198.0, 585.0, 417.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
54 6 4 paragraph_title In vitro degradation [107.0, 439.0, 275.0, 461.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: In vitro degradation"] subsection_heading 0.6 body_zone body_like none True True
55 6 5 text Each sample was prepared in 24-well cell culture plates, and 1 mL (8%) sample solution was added to each well. For each group, refer to 2.3 for sample preparation procedures. Each group of dry piezoel [106.0, 462.0, 586.0, 969.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
56 6 6 display_formula $$ Weight remaining(\%)=W2/W1\times100\% $$ [165.0, 985.0, 528.0, 1012.0] unknown_structural 0.2 ["unrecognized label 'display_formula'"] unknown_structural 0.2 body_zone body_like none False True
57 6 7 formula_number (1) [557.0, 988.0, 581.0, 1011.0] unknown_structural 0.2 ["unrecognized label 'formula_number'"] unknown_structural 0.2 body_zone body_like short_fragment False True
58 6 8 paragraph_title Swelling behavior [108.0, 1062.0, 261.0, 1085.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Swelling behavior"] subsection_heading 0.6 body_zone body_like short_fragment True True
59 6 9 text Refer to 2.7 for the preparation model of sample scaffolds for each group. The swelling rate was measured with PBS as a replacement solution. After drying, the scaffolds of each group were weighed and [106.0, 1086.0, 586.0, 1328.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
60 6 10 display_formula $$ Swelling ratio (\%)=(W2-W1)/W1\times100\% $$ [146.0, 1344.0, 558.0, 1372.0] unknown_structural 0.2 ["unrecognized label 'display_formula'"] unknown_structural 0.2 body_zone body_like none False True
61 6 11 formula_number (2) [557.0, 1348.0, 582.0, 1370.0] unknown_structural 0.2 ["unrecognized label 'formula_number'"] unknown_structural 0.2 body_zone body_like short_fragment False True
62 6 12 paragraph_title Magnetic responsiveness [604.0, 175.0, 815.0, 197.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Magnetic responsiveness"] subsection_heading 0.6 body_zone body_like none True True
63 6 13 text The magnetic responses of SFC and FENS were evaluated using a vibrating sample magnetometer (VSM, MPMS-3, Quantum Design, USA) in the range of -10000-10000 Oe. The sample was ground into a fine powder [602.0, 198.0, 1082.0, 367.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
64 6 14 paragraph_title Piezoelectric properties [604.0, 391.0, 804.0, 413.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Piezoelectric properties"] subsection_heading 0.6 body_zone body_like none True True
65 6 15 text The piezoelectric properties of each scaffold were measured by D33 and homemade stepper motors. For the D33, the piezoelectric scaffold was cut into a blocky structure (20×15×2 mm in length, width and [602.0, 414.0, 1083.0, 1015.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
66 6 16 paragraph_title Cytotoxicity test in vitro [603.0, 1039.0, 803.0, 1061.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Cytotoxicity test in vitro"] subsection_heading 0.6 body_zone body_like none True True
67 6 17 text The piezoelectric scaffold for each group (SFC, FENS, FENS@MF) was prepared by a 48-well culture plate containing 300 μL SF solution, freeze-dried, and crosslinked with anhydrous ethanol. The enhanced [602.0, 1064.0, 1083.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
68 7 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 509.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
69 7 1 number Page 7 of 22 [989.0, 65.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
70 7 2 text and cytoskeleton system, respectively. For Edu staining, follow the manufacturer's instructions (S0812, RiboBio, Guangzhou, China) for testing procedures. For cytoskeletal staining, refer to 2.5 for t [106.0, 174.0, 585.0, 415.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
71 7 3 text For the BMSCs experiment, the suspension of BMSCs with a density of $ 1 \times 10^5 $ cells/well was seeded into a 24-well culture plate containing 2 mL culture medium and cultured in a humid environ [106.0, 413.0, 587.0, 991.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
72 7 4 paragraph_title Chondrogenic and osteogenic differentiation [107.0, 1015.0, 476.0, 1037.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Chondrogenic and osteogenic differentiation"] subsection_heading 0.6 body_zone body_like none True True
73 7 5 text The cell supernatant (2 d) was collected using the 2.11 culture method described above, and GAG and COL2 cytokines were detected using an ELISA kit (MEIMIAN, Wuhan, China) for preliminary evaluation o [106.0, 1038.0, 586.0, 1302.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
74 7 6 text Furthermore, BMSCs were co-cultured with different piezoelectric scaffolds (SFC, FENS, FENS@MF) for 3 d, and the supernatant was extracted as the conditioned medium. Among them, FENS@MF samples were s [106.0, 1302.0, 586.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
75 7 7 text [602.0, 174.0, 1083.0, 487.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
76 7 8 paragraph_title Angiogenesis [604.0, 510.0, 723.0, 533.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Angiogenesis"] sub_subsection_heading 0.6 body_zone body_like short_fragment True True
77 7 9 text Rat vascular endothelial cells (ECs) were co-cultured in a 6-well plate with a density of $ 1 \times 10^{5} $ cells/well and cocultured with SFC, FENS, and FENS@MF samples. The cells were cultured fo [601.0, 532.0, 1083.0, 1256.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
78 7 10 paragraph_title Animal experiment [604.0, 1279.0, 768.0, 1301.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Animal experiment"] subsection_heading 0.6 body_zone body_like short_fragment True True
79 7 11 text Animal model construction and processing: All animal experiments were performed following the guidelines for the care and use of laboratory animals established by the Affiliated Hospital of Integrated [602.0, 1301.0, 1084.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
80 8 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 508.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
81 8 1 number Page 8 of 22 [990.0, 65.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
82 8 2 text Hospital (Ethical Lot Number: 2022-LWKYS-046). The experimental procedures were approved by the hospital ethics committee. A total of 36 SD rats (average weight 300–350 g, male) were selected to const [106.0, 173.0, 586.0, 486.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
83 8 3 text Macroscopic observation, microscopic computed tomography (Micro-CT), and histological analysis: At 4 w and 8 w, three living specimens were randomly selected from each group for Micro-CT observation ( [106.0, 483.0, 586.0, 1329.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
84 8 4 paragraph_title Statistical analysis [108.0, 1351.0, 264.0, 1374.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Statistical analysis"] subsection_heading 0.6 body_zone body_like none True True
85 8 5 text All quantitative data are expressed as the mean±standard deviation (SD). Differences between the two groups were inspected using a paired Student’s t-test, and a comparison of multiple groups was perf [106.0, 1375.0, 587.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
86 8 6 text [603.0, 175.0, 1080.0, 245.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
87 8 7 paragraph_title Results Optimization analysis of the concentration of f magnetic nanoparticles (MNPs) [602.0, 269.0, 1061.0, 341.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Results Optimization analysis of the concentration of f magn"] subsection_heading 0.6 body_zone heading_like none True True
88 8 8 footer [602.0, 294.0, 1061.0, 341.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like empty False False
89 8 9 text screened so that the constructed piezoelectric scaffold can perform the best repair effect in the future. The $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC was first prepared into a suspension with a concentr [602.0, 354.0, 1085.0, 1470.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
90 9 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [109.0, 67.0, 508.0, 87.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
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95 9 5 figure_title C [762.0, 169.0, 793.0, 201.0] figure_inner_text 0.9 ["panel label / figure inner text: C"] figure_inner_text 0.9 display_zone legend_like panel_label True True
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97 9 7 image [143.0, 459.0, 1062.0, 916.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
98 9 8 figure_title Fig. 2 (A) The magnetothermal curves FEN20, FEN50, FEN100 at an operating frequency of 1.5 MHz and a current of 15 mA for 1200 s; (B) The XPS spectrum of FEN20, FEN50, FEN100; (C) The CCK-8 assay resu [108.0, 932.0, 1082.0, 1015.0] figure_caption 0.92 ["figure_title label: Fig. 2 (A) The magnetothermal curves FEN20, FEN50, FEN100 at"] figure_caption 0.92 display_zone legend_like figure_number True True
99 9 9 text performed SEM-EDS analysis of the spatial structure of the scaffold. As shown in Fig. 2E, each scaffold presents a continuous network of porous structures, and the pore size decreases with the increas [107.0, 1038.0, 587.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
100 9 10 paragraph_title Preparation and characterization of silk fibroin enhanced piezoelectric scaffolds [602.0, 1038.0, 1064.0, 1085.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Preparation and characterization of silk fibroin enhanced pi"] subsection_heading 0.6 body_zone body_like none True True
101 9 11 text The piezoelectric scaffolds were prepared by freeze-drying technology and included pure silk fibroin scaffolds named SFC, MNPs-modified SFC named FENS, and magnetic field-induced FENS named FENS@MF. T [602.0, 1087.0, 1082.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
102 10 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [110.0, 67.0, 507.0, 87.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
103 10 1 number Page 10 of 22 [982.0, 66.0, 1080.0, 87.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
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105 10 3 image [117.0, 154.0, 1069.0, 768.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
106 10 4 figure_title Fig. 3 (A) The FTIR spectrum of SFC, $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC, EDC, NHS, and FENS; (B) Representative tensile stress-strain curves of SFC and FENS; (C) Representative compression-stress c [107.0, 786.0, 1083.0, 950.0] figure_caption 0.92 ["figure_title label: Fig. 3 (A) The FTIR spectrum of SFC, $ \\gamma $-Fe $ _{2} $"] figure_caption 0.92 display_zone legend_like figure_number True True
107 10 5 text are consistent with SFC and $ \gamma $-Fe $ _{2} $O $ _{3} $@PSC. After the activation of the carboxyl group by ECD-NHS, it can be seen that the amide covalent bond is significantly shifted to 3293 c [106.0, 964.0, 587.0, 1472.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
108 10 6 text [602.0, 968.0, 1083.0, 1300.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
109 10 7 text The osteochondral repair period is usually longer, generally more than 3 months. Even materials like SFC degrade more slowly than other natural materials, making it difficult to achieve a match betwee [603.0, 1302.0, 1083.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
110 11 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 509.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
111 11 1 number Page 11 of 22 [981.0, 65.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
112 11 2 text of each group of piezoelectric scaffolds was evaluated by immersing them in a control PBS solution and a simulated enzyme solution (protease XIV). The test results showed that all the samples in PBS s [106.0, 174.0, 586.0, 897.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
113 11 3 paragraph_title Piezoelectric effect analysis [108.0, 919.0, 335.0, 941.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Piezoelectric effect analysis"] subsection_heading 0.6 body_zone body_like none True True
114 11 4 text To investigate the enhanced piezoelectricity of FENS@MF, we measured it with a D33 piezoelectric tester and self-made piezoelectric equipment. FENS@MF samples must be subjected to intermittent MF acti [106.0, 942.0, 587.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
115 11 5 text [602.0, 174.0, 1082.0, 273.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 body_zone body_like empty True True
116 11 6 paragraph_title In vitro cytotoxicity evaluation analysis [603.0, 295.0, 922.0, 317.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: In vitro cytotoxicity evaluation analysis"] subsection_heading 0.6 body_zone body_like none True True
117 11 7 text Chondrocytes (ATDC5) and bone marrow mesenchymal stem cells (BMSCs), as important seed cells for bone tissue regeneration, were used to further evaluate the biosafety of piezoelectric scaffolds. First [602.0, 318.0, 1083.0, 871.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
118 11 8 text Furthermore, BMSCs cells were used to investigate the toxic effects of piezoelectric scaffolds. The Edu results showed almost the same change trend as ATDC5 cells, but the FENS@MF proliferation was mo [602.0, 871.0, 1083.0, 1327.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
119 11 9 text Finally, we further evaluate enhanced piezoelectric scaffolds' safety and potential biomedical value through the CCK-8 experiment. The evaluation results of ATDC5 cells showed that (Fig. S3B), except [602.0, 1327.0, 1083.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
120 12 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 509.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
121 12 1 number Page 12 of 22 [981.0, 65.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
122 12 2 text d, the cell proliferation was not obvious, which may be due to the fast growth rate of cells that made the fusion rate reach 100%. The results of BMSCs showed almost the same change trend (Fig. S4D), [106.0, 174.0, 586.0, 393.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
123 12 3 paragraph_title Analysis of regulating chondrogenic and osteogenic differentiation of BMSCs through FENS@MF [106.0, 414.0, 530.0, 461.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Analysis of regulating chondrogenic and osteogenic different"] subsection_heading 0.6 body_zone body_like none True True
124 12 4 text Subsequently, we further investigated the effect of piezoelectric scaffolds on chondrogenic and osteogenic differentiation of BMSCs. BMSCs suspension 2.11 was collected and centrifuged for preliminary [106.0, 463.0, 588.0, 1424.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
125 12 5 text Next, the osteogenic differentiation of BMSCs via piezoelectric scaffolds was further investigated. It was evident that the FENS@MF group had more calcium deposition at 21 d by alizarin red staining ( [107.0, 1423.0, 587.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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127 12 7 paragraph_title Angiogenesis analysis [604.0, 943.0, 790.0, 966.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Angiogenesis analysis"] subsection_heading 0.6 body_zone body_like none True True
128 12 8 text Bone cartilage consists of hard bone tissue and cartilage tissue, in which the subchondral bone area is rich in capillary tissue, which can provide nutritional support for the growth and development o [602.0, 968.0, 1082.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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148 13 19 image [821.0, 720.0, 1059.0, 910.0] figure_asset 0.85 ["media label: image"] media_asset 0.85 body_zone unknown_like empty True True
149 13 20 figure_title Fig. 4 Analysis of chondroblast differentiation (A–F). (A) Representative Alcian blue stained images after co-cultivation of BMSCs with piezoelectric scaffolds (SFC, FENS, FENS@MF) for 21 d; (B) The e [106.0, 936.0, 1084.0, 1138.0] figure_caption 0.92 ["figure_title label: Fig. 4 Analysis of chondroblast differentiation (A\u2013F). (A) R"] figure_caption 0.92 display_zone legend_like figure_number True True
150 13 21 text proliferating cell nuclear antigen (PCNA) (Fig. 5H–I) expression is higher than that in SFC and FENS groups, indicating that FENS@MF has better angiogenesis potential. [107.0, 1158.0, 586.0, 1256.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
151 13 22 paragraph_title Phenotypic analysis of macrophages [108.0, 1279.0, 408.0, 1301.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Phenotypic analysis of macrophages"] subsection_heading 0.6 body_zone body_like none True True
152 13 23 text OCD are usually accompanied by a sharp deterioration of the inflammatory microenvironment, recruiting more M1-type macrophages, further accelerating the apoptosis of chondrocytes and worsening the mic [107.0, 1303.0, 586.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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165 14 11 chart [859.0, 939.0, 1062.0, 1108.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 unknown_like empty True True
166 14 12 figure_title Fig. 5 Angiogenesis analysis. (A) Representative Prussian blue stained images after co-cultivation of ECs with piezoelectric scaffolds (SFC, FENS, FENS@MF) for 2 d; (B) Representative immunofluorescen [106.0, 1132.0, 1083.0, 1215.0] figure_caption 0.92 ["figure_title label: Fig. 5 Angiogenesis analysis. (A) Representative Prussian bl"] figure_caption 0.92 display_zone legend_like figure_number True True
167 14 13 text expression level of TNF- $ \alpha $ decreased in SFC, FENS, and FENS@MF samples, respectively, and was almost the same in IL-4 and FENS@MF groups. On the contrary, VEGF expression showed an increasing [106.0, 1230.0, 586.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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176 15 7 figure_title Fig. 6 (A) Silk fibroin piezoelectric scaffolds or silk fibroin-enhanced piezoelectric scaffolds were used to promote the regeneration of OCD in rats. It was inserted into the osteochondral defect of [108.0, 1173.0, 1083.0, 1334.0] figure_caption 0.92 ["figure_title label: Fig. 6 (A) Silk fibroin piezoelectric scaffolds or silk fibr"] figure_caption 0.92 display_zone legend_like figure_number True True
177 15 8 text conditions, while sham surgery, models, and autologous transplantation (ATPT) groups were established. [108.0, 1351.0, 584.0, 1399.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
178 15 9 text Macroscopic observation In general, at 4 w after the operation, the structure of the sham operation group was complete, while no regenerated tissue was found in the model group (blank control group), [108.0, 1401.0, 586.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
179 15 10 text [603.0, 1351.0, 1082.0, 1473.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
180 16 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 509.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
181 16 1 number Page 16 of 22 [981.0, 66.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 unknown_like short_fragment False False
182 16 2 text non-degradation state of the piezoelectric scaffolds can be observed in the SFC, FENS, and FENS@MF groups, and chondroid tissue growth can be observed in the defect area, but the tissue coverage is li [106.0, 175.0, 586.0, 486.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
183 16 3 text Micro-CT analyses The 1.5 mm profound osteochondral defect in rats involved the entire cartilage layer and part of the hard bone. Figure 6C shows a Micro-CT view of cartilage regeneration in the defec [107.0, 486.0, 587.0, 1477.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
184 16 4 text [602.0, 174.0, 1082.0, 367.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
185 16 5 text Histological analyses Histological staining (HE, Safranin O&Fast Green, Masson, Alcian Blue, Von Kossa, and Sirius red) was used to evaluate the repair effect of each group of scaffolds. The H&E stain [602.0, 366.0, 1084.0, 992.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
186 16 6 text At 4 w after the operation, large defect space and less new tissue were still observed in the model group, and the defect was deep into the subchondral bone. At this stage, the tissue growth was mainl [602.0, 992.0, 1083.0, 1475.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
187 17 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 67.0, 507.0, 87.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
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190 17 3 chart [142.0, 1046.0, 1071.0, 1193.0] figure_asset 0.85 ["media label: chart"] media_asset 0.85 unknown_like empty True True
191 17 4 figure_title Fig. 7 Histological analysis. Representative H&E (A), Safranin O&Fast Green (B), Masson (C) and Alcian Blue (D) staining images of the osteochondral regeneration in the defects in different groups 4 a [107.0, 1214.0, 1083.0, 1298.0] figure_caption 0.92 ["figure_title label: Fig. 7 Histological analysis. Representative H&E (A), Safran"] figure_caption 0.92 display_zone legend_like figure_number True True
192 17 5 text obviously observed that a large number of new collagen fibers represent new bone growth, and a small number of areas have highly mature bone tissue. On the contrary, at 8 w, we can see that many new b [107.0, 1327.0, 586.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
193 17 6 text [603.0, 1327.0, 1083.0, 1472.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
194 18 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 508.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
195 18 1 number Page 18 of 22 [982.0, 66.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 unknown_like short_fragment False False
196 18 2 text in the SFC and FENS groups (yellow region) than in the other groups (Model, ATPT, FENS@MF), while FENS@MF showed the most type II collagen fibers (red region). At 8 w, FENS@MF showed more type I colla [107.0, 175.0, 586.0, 1182.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
197 18 3 text Immunohistochemistry analyses Type I and type II collagen immunohistochemical staining were used to further investigate subchondral bone and chondrogenesis. As shown in Fig. 7G, it can be observed tha [106.0, 1183.0, 586.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
198 18 4 text [602.0, 174.0, 1083.0, 609.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
199 18 5 paragraph_title Discussion [605.0, 629.0, 712.0, 652.0] section_heading 0.9 ["explicit scholarly heading: Discussion"] section_heading 0.9 body_zone heading_like canonical_section_name True True
200 18 6 text Bone tissue engineering is considered to be one of the most promising therapeutic approaches for treating OCD. The defective osteochondral bone leads to changes in the physiological electrical microen [602.0, 654.0, 1083.0, 943.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
201 18 7 text Among the many electroactive materials [42], piezoelectric materials have attracted great attention because they can directly convert mechanical pressure into electrical signals in vivo without additi [602.0, 944.0, 1083.0, 1375.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
202 18 8 text MNPs are widely used in clinical and preclinical experimental studies due to their excellent biocompatibility [45]. Their ability to delay degradation is based on modifiers on the surface of the mater [602.0, 1375.0, 1083.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
203 19 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [109.0, 67.0, 508.0, 87.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
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218 19 15 figure_title Fig. 8 (A–B) w/s and quantitative analysis or $ \mu $-catenin protein levels in BMs_s culture in piezoelectric scaffold (FENs, FENs@MT) conditioned medium for 21 d (N=3); (C, G) The qPCR detection of [106.0, 901.0, 1083.0, 1023.0] figure_caption 0.92 ["figure_title label: Fig. 8 (A\u2013B) w/s and quantitative analysis or $ \\mu $-caten"] figure_caption 0.92 display_zone legend_like figure_number True True
219 19 16 text the composite scaffold [33]. We successfully constructed FENS@MF scaffolds by mixing MNPs (FEN50) with SF solution under an EDC/NHC environment (Fig. 3A–D). As with the envisaged results, the mechanic [107.0, 1038.0, 585.0, 1375.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
220 19 17 text The SFC itself have a weak piezoelectric effect, and although many researchers have used SFC to treat osteochondral injuries, few studies have been conducted to enhance the piezoelectric effect of SF [107.0, 1376.0, 586.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
221 19 18 text [602.0, 1040.0, 1083.0, 1474.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
222 20 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [108.0, 66.0, 508.0, 88.0] noise 0.9 ["header label"] noise 0.9 unknown_like none False False
223 20 1 number Page 20 of 22 [981.0, 66.0, 1081.0, 88.0] noise 0.9 ["page number label"] noise 0.9 unknown_like short_fragment False False
224 20 2 text form a local electromagnetic field in the magnetic field (MF), which generates a magneto-thermal effect with the external alternating magnetic field (AMF) [47], and the moderate temperature rise gener [106.0, 175.0, 587.0, 1402.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
225 20 3 text With these methods from in vitro studies, we expected that the FENS@MF scaffold could also achieve good repair results in in vivo experiments. Therefore, we established different experimental groups, [107.0, 1400.0, 586.0, 1473.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
226 20 4 text [602.0, 175.0, 1083.0, 846.0] ocr_text_missing 0.8 ["ocr detected text region (raw_label=text) but no text extracted; no pdf backfill available"] ocr_text_missing 0.8 unknown_like empty True True
227 20 5 text To the best of our knowledge, this is the first time that the combination of SFC and MNPs has been comprehensively evaluated in in vitro and in vivo experiments to assess the therapeutic efficacy of F [602.0, 847.0, 1082.0, 1330.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
228 20 6 paragraph_title Conclusion [604.0, 1350.0, 716.0, 1374.0] section_heading 0.9 ["explicit scholarly heading: Conclusion"] section_heading 0.9 body_zone heading_like canonical_section_name True True
229 20 7 text This study developed a magnetic nanoparticle-enhanced silk fibroin scaffold (FENS@MF) with superior piezoelectric performance for osteochondral repair. By covalently integrating $ \gamma $-Fe $ _{2} [602.0, 1374.0, 1083.0, 1474.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone unknown_like none True True
230 21 0 header Liu et al. Journal of Nanobiotechnology (2026) 24:239 [109.0, 67.0, 507.0, 87.0] reference_item 0.9 ["header label"] noise 0.9 reference_zone unknown_like none True True
231 21 1 number Page 21 of 22 [982.0, 66.0, 1080.0, 87.0] noise 0.9 ["page number label"] noise 0.9 body_zone body_like short_fragment False False
232 21 2 text via EDC/NHS crosslinking, FENS@MF achieved a 3-fold increase in tensile strength and 15.65% slower degradation than pristine SFC in vitro. The scaffold exhibited a 8.5-fold enhancement in piezoelectri [108.0, 175.0, 586.0, 729.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
233 21 3 paragraph_title Supplementary Information [109.0, 751.0, 372.0, 772.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Supplementary Information"] backmatter_boundary_candidate 0.5 body_zone heading_like none True True
234 21 4 text The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04131-9. [108.0, 773.0, 578.0, 809.0] body_paragraph 0.6 ["default body_paragraph for text label", "tail_nonref_hold_zone excluded from body flow"] backmatter_body 0.6 unknown_like none True True
235 21 5 text Supplementary Material 1 [121.0, 830.0, 280.0, 851.0] body_paragraph 0.6 ["default body_paragraph for text label", "tail_nonref_hold_zone excluded from body flow"] backmatter_body 0.6 unknown_like none True True
236 21 6 paragraph_title Author contributions [110.0, 884.0, 252.0, 901.0] unknown_structural 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Author contributions"] subsection_heading 0.6 tail_nonref_hold_zone support_like none False True
237 21 7 text Xin Liu: Experimental procedures included material characterization and cell culture, writing-original draft, revision, etc., Supervision, Funding provision. Congyang Xue: WB and some animal experimen [108.0, 903.0, 576.0, 1120.0] body_paragraph 0.6 ["default body_paragraph for text label", "tail_nonref_hold_zone excluded from body flow"] backmatter_body 0.6 unknown_like none True True
238 21 8 paragraph_title Funding [110.0, 1136.0, 170.0, 1154.0] sub_subsection_heading 0.6 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Funding"] sub_subsection_heading 0.6 tail_nonref_hold_zone unknown_like short_fragment True True
239 21 9 text The research was supported by the Natural Science Foundation of Jiangsu Province (BK20220464), the National Natural Science Foundation of China (82302735), the Project of Institute of Chinese Medicine [108.0, 1155.0, 577.0, 1390.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
240 21 10 paragraph_title Data availability [110.0, 1406.0, 222.0, 1424.0] unknown_structural 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Data availability"] subsection_heading 0.6 tail_nonref_hold_zone unknown_like short_fragment False True
241 21 11 text Data will be made available on request. [110.0, 1425.0, 349.0, 1443.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 tail_nonref_hold_zone unknown_like none True True
242 21 12 paragraph_title Declarations Ethics approval and consent to participate [606.0, 166.0, 885.0, 223.0] backmatter_boundary_candidate 0.5 ["backmatter boundary candidate: Declarations Ethics approval and consent to participate"] backmatter_boundary_candidate 0.5 body_zone body_like none True True
243 21 13 footer [606.0, 204.0, 885.0, 223.0] noise 0.9 ["footer label"] noise 0.9 body_zone body_like empty False False
244 21 14 text The handling of animals followed the relevant provisions of the Regulations on the Management of Laboratory Animals. The relevant procedures were approved by the Animal Ethics Committee of the Affilia [604.0, 223.0, 1062.0, 313.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
245 21 15 paragraph_title Consent for publication [606.0, 330.0, 765.0, 348.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Consent for publication"] subsection_heading 0.6 body_zone body_like none True True
246 21 16 text All authors have provided consent for the manuscript to be published in Journal of Nanobiotechnology. [606.0, 348.0, 1043.0, 385.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
247 21 17 paragraph_title Competing interests [606.0, 402.0, 744.0, 420.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Competing interests"] subsection_heading 0.6 body_zone body_like short_fragment True True
248 21 18 text The authors declare no competing interests. [606.0, 422.0, 875.0, 439.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
249 21 19 paragraph_title Author details [606.0, 456.0, 705.0, 474.0] subsection_heading 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Author details"] subsection_heading 0.6 body_zone body_like short_fragment True True
250 21 20 text ¹The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R. China ²Department of Spine Surgery, Affiliated Hospital of Integrated Traditional [604.0, 475.0, 1048.0, 691.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
251 21 21 text Received: 31 July 2025 / Accepted: 31 January 2026 [605.0, 712.0, 932.0, 731.0] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
252 21 22 text Published online: 09 February 2026 [605.0, 734.0, 860.0, 755.0] frontmatter_noise 0.88 ["default body_paragraph for text label", "late role resolution: editorial phrase cross-validates non-body classification", "zone=body_zone", "style_family=support_like"] body_paragraph 0.6 body_zone support_like none False False
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515
audit/B43QSAJP/reference_intrusion_candidates.json Normal file
View file

@ -0,0 +1,515 @@
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654
audit/B43QSAJP/reference_span_audit.json Normal file
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@ -0,0 +1,654 @@
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