{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:02:55Z","timestamp":1790661775884,"version":"4.1.0"},"reference-count":16,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shandong Province medical health science and technology project","award":["202404070285"],"award-info":[{"award-number":["202404070285"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Anterior cruciate ligament (ACL) reconstruction is widely performed, yet insufficient tendon-bone healing remains a key contributor to graft failure. Stem cell-based interventions, including mesenchymal stem cells (MSCs) and stem cell-derived products (e.g., exosomes\/extracellular vesicles), have shown potential to enhance tendon-bone integration in preclinical models. However, findings across animal studies are heterogeneous and have not been comprehensively synthesized. This review aims to evaluate the effects of stem cell-based therapies on tendon-bone healing after ACL reconstruction in animal models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This protocol follows PRISMA-P. We will search PubMed, Embase, Scopus, SPORTDiscus, Web of Science, and the Cochrane Library from inception to the final search date. Controlled animal studies comparing ACL reconstruction with stem cell-based interventions versus controls will be included. Primary outcomes are biomechanical properties (ultimate failure load and stiffness). Secondary outcomes include micro-CT measures of bone integration (e.g., bone volume fraction, bone mineral density) and histological outcomes (e.g., interface maturation or validated scoring systems). Risk of bias will be assessed using SYRCLE\u2019s tool. Random-effects meta-analyses will be performed, with prespecified subgroup analyses by stem cell type, delivery method, animal species, and follow-up time. Sensitivity analyses and publication-bias assessments will be conducted where appropriate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>PROSPERO registration<\/jats:title>\n                    <jats:p>CRD420251137985.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0341859","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:37:42Z","timestamp":1770230262000},"page":"e0341859","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of stem cell therapies on tendon-bone healing after anterior cruciate ligament reconstruction in animal models: Protocol for a systematic review and meta-analysis"],"prefix":"10.1371","volume":"21","author":[{"given":"Shibo","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3947-2569","authenticated-orcid":true,"given":"Congcong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"issue":"4","key":"pone.0341859.ref001","article-title":"Rupture of the anterior cruciate ligament","volume":"8","author":"MAS Mowbray","year":"2022","journal-title":"BMJ Open Sport Exerc Med"},{"key":"pone.0341859.ref002","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1093\/milmed\/usac093","article-title":"Anterior Cruciate Ligament Reconstruction Surgery: Creating a Permissive Healing Phenotype in Military Personnel and Civilians for Faster Recovery","volume":"187","author":"JL Morris","year":"2022","journal-title":"Mil Med"},{"issue":"4","key":"pone.0341859.ref003","article-title":"Failure Rates of Autograft and Allograft ACL Reconstruction in Patients 19 Years of Age and Younger: A Systematic Review and Meta-Analysis","volume":"5","author":"AI Cruz","year":"2020","journal-title":"JB JS Open Access"},{"issue":"1","key":"pone.0341859.ref004","first-page":"134","article-title":"Tunnel widening after anterior cruciate ligament reconstruction: a narrative review of etiology, evaluation, and management","volume":"14","author":"A de Beus","year":"2017","journal-title":"J Orthop"},{"key":"pone.0341859.ref005","first-page":"1180199","article-title":"Current strategies to promote tendon-bone healing with stem cells and extracellular vesicles","volume":"11","author":"J Tian","year":"2023","journal-title":"Front Bioeng 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Egger","year":"1997","journal-title":"BMJ"},{"issue":"3","key":"pone.0341859.ref013","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.3390\/app12031593","article-title":"The Effects of Resistance Training on Architecture and Volume of the Upper Extremity Muscles: A Systematic Review of Randomised Controlled Trials and Meta-Analyses","volume":"12","author":"G Yagiz","year":"2022","journal-title":"Appl Sci"},{"issue":"9","key":"pone.0341859.ref014","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1002\/sctm.18-0132","article-title":"Anterior Cruciate Ligament Reconstruction in a Rabbit Model Using a Decellularized Allogenic Semitendinous Tendon Combined with Autologous Bone Marrow-Derived Mesenchymal Stem Cells","volume":"8","author":"W Lu","year":"2019","journal-title":"Stem Cells Transl Med"},{"issue":"13","key":"pone.0341859.ref015","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1177\/03635465211041582","article-title":"Adipose-Derived Stem Cell Sheets Improve Early Biomechanical Graft Strength in Rabbits After Anterior Cruciate Ligament Reconstruction","volume":"49","author":"T Matsumoto","year":"2021","journal-title":"Am J Sports Med"},{"issue":"1","key":"pone.0341859.ref016","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1177\/03635465221135770","article-title":"Bioactive Decellularized Tendon-Derived Stem Cell Sheet for Promoting Graft Healing After Anterior Cruciate Ligament Reconstruction","volume":"51","author":"S Yao","year":"2023","journal-title":"Am J Sports Med"}],"container-title":["PLOS 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