{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:50:31Z","timestamp":1791449431559,"version":"4.3.3"},"reference-count":99,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F30AG084163"],"award-info":[{"award-number":["F30AG084163"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM144300"],"award-info":[{"award-number":["T32GM144300"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tendinopathies comprise half of musculoskeletal injuries, yet medical treatments are lacking. Orthobiologics are novel therapeutics developed to address this gap, with extracellular vesicles (EVs) being a promising prospect. However, we lack a complete understanding of how EVs affect regeneration, both endogenously and as a tool for augmenting tendon healing. Therefore, the purpose of this review was to compile the literature focused on understanding the impact of EV treatment on tendon healing using animal models. We performed a literature search in accordance with PRISMA reporting guidelines. Title, abstract, and full\u2010text screening were performed by two authors. We assessed transparency and risk\u2010of\u2010bias using the ARRIVE, MISEV, and SYRCLE Guidelines, and meta\u2010analyses were performed on overlapping outcome variables. After screening, 46 articles were included. Most studies utilized young male Achilles tendons, with a diversity of EV cell sources, injury types, dosage schemes, and biomaterials. Several ARRIVE (e.g., blinding) and MISEV (e.g., seeding density) recommendations remain poorly reported in this literature, and the risk of bias per SYRCLE guidelines is relatively high. Despite high heterogeneity, EV treatment was associated with improved histological tendon healing scores and increased load to failure, tendon stiffness, and Young's modulus. Further meta\u2010analyses revealed EV treatment was associated with increased type I collagen protein and type III collagen transcript expression, and decreased protein expression of IL\u20106 and markers of senescence. We recommend that future studies include different ages, sexes, and more systematically protocolized EV delivery scheme.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Statement of Clinical Significance:<\/jats:bold>\n                    This systematic review identifies gaps in the tendon and EV literature while also unveiling unexplored mechanisms by which EVs may promote tendon healing. This improved understanding and call for rigor in studies enhances the translational potential of EVs as a future treatment for tendon injuries.\n                  <\/jats:p>","DOI":"10.1002\/jor.70289","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:58:02Z","timestamp":1791446282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles Are Associated With Biological, Mechanical, and Structural Tendon Healing Metrics in Preclinical Models: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9039-4183","authenticated-orcid":false,"given":"Gabrielle","family":"Gilmer","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7604-2669","authenticated-orcid":false,"given":"Kariman","family":"Shama","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Klingensmith","sequence":"additional","affiliation":[{"name":"Bethel Musculoskeletal Research Center University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bethel Musculoskeletal Research Center University of Pittsburgh Pittsburgh Pennsylvania USA"},{"name":"Department of Bioengineering Swanson School of Engineering, University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1886-2261","authenticated-orcid":false,"given":"Brittany","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Florida Gainesville Florida USA"},{"name":"Department of Pharmacology and Therapeutics University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0133-9316","authenticated-orcid":false,"given":"Allison C.","family":"Bean","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Swanson School of Engineering, University of Pittsburgh Pittsburgh Pennsylvania USA"},{"name":"Department of Physical Medicine and Rehabilitation University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"McGowan Institute for Regenerative Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.664909","article-title":"Basic Research on Tendon Repair: Strategies, Evaluation, and Development","volume":"8","author":"Li Z. J.","year":"2021","journal-title":"Frontiers in Medicine"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1055\/s-0041-1731632","article-title":"Tendon: Principles of Healing and Repair","volume":"35","author":"Chartier C.","year":"2021","journal-title":"Seminars in Plastic Surgery"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","DOI":"10.1177\/23259671251360402","article-title":"Epidemiology of Acute Primary Tendon Ruptures Presenting to Emergency Departments in the United States","volume":"13","author":"Whitmore J. A.","year":"2025","journal-title":"Orthopaedic Journal of Sports Medicine"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jor.2013.01.008","article-title":"Prevalence of Symptomatic and Asymptomatic Rotator Cuff Tears in the General Population: From Mass\u2010Screening in One Village","volume":"10","author":"Minagawa H.","year":"2013","journal-title":"Journal of Orthopaedics"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-bioeng-071811-150122","article-title":"Tendon Healing: Repair and Regeneration","volume":"14","author":"Voleti P. B.","year":"2012","journal-title":"Annual Review of Biomedical Engineering"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s11999-008-0260-1","article-title":"Treatment of Tendinopathy: What Works, What Does Not, and What Is on the Horizon","volume":"466","author":"Andres B. M.","year":"2008","journal-title":"Clinical Orthopaedics & Related Research"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.jseint.2021.01.013","article-title":"Predictive Factors for Failure of Conservative Management in the Treatment of Calcific Tendinitis of the Shoulder","volume":"5","author":"Drummond Junior M.","year":"2021","journal-title":"JSES International"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1016\/j.arthro.2022.04.002","article-title":"Editorial Commentary: Rotator Cuff Repairs Fail at an Alarmingly High Rate During Long\u2010Term Follow\u2010Up: Graft Augmentation and Biologics May Improve Future Outcomes","volume":"38","author":"Trasolini N. A.","year":"2022","journal-title":"Arthroscopy: The Journal of Arthroscopic & Related Surgery: Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jcot.2021.05.019","article-title":"Re\u2010Tears after Rotator Cuff Repair: Current Concepts Review","volume":"19","author":"Mandaleson A.","year":"2021","journal-title":"Journal of Clinical Orthopaedics and Trauma"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmjsem-2021-001297","article-title":"Nearly Half of Patients With Chronic Tendinopathy May Have a Neuropathic Pain Component, With Significant Differences Seen Between Different Tendon Sites: A Prospective Cohort of More Than 300 Patients","volume":"8","author":"Wheeler P. C.","year":"2022","journal-title":"BMJ Open Sport & Exercise Medicine"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","DOI":"10.1177\/1759720X211037530","article-title":"Comparative Effectiveness of Treatment Options for Subacromial Shoulder Conditions: A Systematic Review and Network Meta\u2010Analysis","volume":"13","author":"Babatunde O. O.","year":"2021","journal-title":"Therapeutic Advances in Musculoskeletal Disease"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1177\/0269215520934147","article-title":"Effectiveness of Progressive and Resisted and Non\u2010Progressive or Non\u2010Resisted Exercise in Rotator Cuff Related Shoulder Pain: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials","volume":"34","author":"Naunton J.","year":"2020","journal-title":"Clinical Rehabilitation"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1177\/0363546517743746","article-title":"The Efficacy of Platelet\u2010Rich Plasma on Tendon and Ligament Healing: A Systematic Review and Meta\u2010Analysis With Bias Assessment","volume":"46","author":"Chen X.","year":"2018","journal-title":"American Journal of Sports Medicine"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/5620286","article-title":"Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an In Vitro Model of Tendon Cell Inflammation","volume":"2019","author":"Vigano M.","year":"2019","journal-title":"Stem Cells International"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.csm.2024.10.006","article-title":"Orthobiologics for Tendon Injuries","volume":"44","author":"Eliasberg C. D.","year":"2025","journal-title":"Clinics in Sports Medicine"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12964-023-01103-6","article-title":"A Review of the Regulatory Mechanisms of Extracellular Vesicles\u2010Mediated Intercellular Communication","volume":"21","author":"Liu Y. J.","year":"2023","journal-title":"Cell Communication and Signaling"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2021.04.013","article-title":"Extracellular Vesicles for Tissue Repair and Regeneration: Evidence, Challenges and Opportunities","volume":"175","author":"Nagelkerke A.","year":"2021","journal-title":"Advanced Drug Delivery Reviews"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13123","article-title":"Platelet\u2010Rich Plasma\u2010Derived Extracellular Vesicles: A Superior Alternative in Regenerative Medicine?","volume":"54","author":"Wu J.","year":"2021","journal-title":"Cell Proliferation"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241713043","article-title":"Advances in Platelet Rich Plasma\u2010Derived Extracellular Vesicles for Regenerative Medicine: A Systematic\u2010Narrative Review","volume":"24","author":"Anitua E.","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bioactmat.2024.02.021","article-title":"Extracellular Vesicles in Nanomedicine and Regenerative Medicine: A Review Over the Last Decade","volume":"36","author":"Moghassemi S.","year":"2024","journal-title":"Bioactive Materials"},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","DOI":"10.3390\/jfb14060299","article-title":"Therapeutic Potential of Exosomes in Tendon and Tendon\u2010Bone Healing: A Systematic Review of Preclinical Studies","volume":"14","author":"Zou M.","year":"2023","journal-title":"Journal of Functional Biomaterials"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines12050942","article-title":"The Use of Extracellular Vesicles in Achilles Tendon Repair: A Systematic Review","volume":"12","author":"Kasula V.","year":"2024","journal-title":"Biomedicines"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cej.2024.156489","article-title":"The Role of Extracellular Vesicles in the Treatment of Tendinopathy by Regulating the Pathological Immune Microenvironment","volume":"499","author":"Liu H.\u2010M.","year":"2024","journal-title":"Chemical Engineering Journal"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells10102553","article-title":"Mesenchymal Stem Cell\u2010Derived Extracellular Vesicles in Tendon and Ligament Repair\u2014A Systematic Review of In Vivo Studies","volume":"10","author":"Lu V.","year":"2021","journal-title":"Cells"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12404","article-title":"Minimal Information for Studies of Extracellular Vesicles (MISEV2023): From Basic to Advanced Approaches","volume":"13","author":"Welsh J. A.","year":"2024","journal-title":"Journal of Extracellular Vesicles"},{"key":"e_1_2_10_27_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page M. J.","year":"2021","journal-title":"BMJ"},{"key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta\u2010Analysis of Observational Studies in Epidemiology: A Proposal for Reporting. Meta\u2010Analysis Of Observational Studies in Epidemiology (MOOSE) Group","volume":"283","author":"Stroup D. F.","year":"2000","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_10_29_1","unstructured":"J. P. T. T. J.Higgins J.Chandler M.Cumpston T.Li M. J.Page et al.2022. Cochrane Handbook for Systematic Reviews of Interventions 6.3 ed."},{"key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jneumeth.2013.09.010","article-title":"Meta\u2010Analysis of Data From Animal Studies: A Practical Guide","volume":"221","author":"Vesterinen H. M.","year":"2014","journal-title":"Journal of Neuroscience Methods"},{"key":"e_1_2_10_31_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13643-018-0699-4","article-title":"Registration of Systematic Reviews in PROSPERO: 30,000 Records and Counting","volume":"7","author":"Page M. J.","year":"2018","journal-title":"Systematic Reviews"},{"key":"e_1_2_10_32_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12913-014-0579-0","article-title":"PICO, PICOS and SPIDER: A Comparison Study of Specificity and Sensitivity in Three Search Tools for Qualitative Systematic Reviews","volume":"14","author":"Methley A. M.","year":"2014","journal-title":"BMC Health Services Research"},{"key":"e_1_2_10_33_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1177\/0145445516673998","article-title":"Intercoder Reliability and Validity of WebPlotDigitizer in Extracting Graphed Data","volume":"41","author":"Drevon D.","year":"2017","journal-title":"Behavior Modification"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.joca.2022.12.009","article-title":"Uncovering the \u2018Riddle of Femininity\u2019 in Osteoarthritis: A Systematic Review and Meta\u2010Analysis of Menopausal Animal Models and Mathematical Modeling of Estrogen Treatment","volume":"31","author":"Gilmer G.","year":"2023","journal-title":"Osteoarthritis and Cartilage"},{"key":"e_1_2_10_35_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research","volume":"18","author":"Percie du Sert N.","year":"2020","journal-title":"PLoS Biology"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal Experimental Requirements for Definition of Extracellular Vesicles and Their Functions: A Position Statement From the International Society for Extracellular Vesicles","volume":"3","author":"Lotvall J.","year":"2014","journal-title":"Journal of Extracellular Vesicles"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018): A Position Statement of the International Society for Extracellular Vesicles and Update of the MISEV2014 Guidelines","volume":"7","author":"Thery C.","year":"2018","journal-title":"Journal of Extracellular Vesicles"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2288-14-43","article-title":"SYRCLE's Risk of Bias Tool for Animal Studies","volume":"14","author":"Hooijmans C. R.","year":"2014","journal-title":"BMC Medical Research Methodology"},{"key":"e_1_2_10_39_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta\u2010Analysis in Clinical Trials","volume":"7","author":"DerSimonian R.","year":"1986","journal-title":"Controlled Clinical Trials"},{"key":"e_1_2_10_40_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12951-022-01763-5","article-title":"NAMPT Encapsulated by Extracellular Vesicles From Young Adipose\u2010Derived Mesenchymal Stem Cells Treated Tendinopathy in a \u2018One\u2010Stone\u2010Two\u2010Birds\u2019 Manner","volume":"21","author":"Wu G.","year":"2023","journal-title":"Journal of Nanobiotechnology"},{"key":"e_1_2_10_41_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13018-024-04869-8","article-title":"Platelet\u2010Derived Exosomes Alleviate Tendon Stem\/Progenitor Cell Senescence and Ferroptosis by Regulating AMPK\/Nrf2\/GPX4 Signaling and Improve Tendon\u2010Bone Junction Regeneration in Rats","volume":"19","author":"Chen D.","year":"2024","journal-title":"Journal of Orthopaedic Surgery and Research"},{"key":"e_1_2_10_42_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-021-00906-4","article-title":"MicroRNA Engineered Umbilical Cord Stem Cell\u2010Derived Exosomes Direct Tendon Regeneration by mTOR Signaling","volume":"19","author":"Yao Z.","year":"2021","journal-title":"Journal of Nanobiotechnology"},{"key":"e_1_2_10_43_1","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/1455226","article-title":"Anti\u2010Inflammatory and Tendon\u2010Protective Effects of Adipose Stem Cell\u2010Derived Exosomes With Concomitant Use of Glucocorticoids","volume":"2022","author":"Zhang X.","year":"2022","journal-title":"Stem Cells International"},{"key":"e_1_2_10_44_1","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/stmcls\/sxad032","article-title":"Extracellular Vesicles From Primed Adipose\u2010Derived Stem Cells Enhance Achilles Tendon Repair by Reducing Inflammation and Promoting Intrinsic Healing","volume":"41","author":"Shen H.","year":"2023","journal-title":"Stem Cells"},{"key":"e_1_2_10_45_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13287-021-02410-w","article-title":"Adipose\u2010Derived Mesenchymal Stromal Cell\u2010Derived Exosomes Promote Tendon Healing by Activating Both SMAD1\/5\/9 and SMAD2\/3","volume":"12","author":"Liu H.","year":"2021","journal-title":"Stem Cell Research & Therapy"},{"key":"e_1_2_10_46_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/jor.24406","article-title":"Stem Cell\u2010Derived Extracellular Vesicles Attenuate the Early Inflammatory Response After Tendon Injury and Repair","volume":"38","author":"Shen H.","year":"2020","journal-title":"Journal of Orthopaedic Research"},{"key":"e_1_2_10_47_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13287-020-01918-x","article-title":"Tendon Stem Cell\u2010Derived Exosomes Regulate Inflammation and Promote the High\u2010Quality Healing of Injured Tendon","volume":"11","author":"Zhang M.","year":"2020","journal-title":"Stem Cell Research & Therapy"},{"key":"e_1_2_10_48_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1177\/03635465231155927","article-title":"Exosomes Derived From Kartogenin\u2010Preconditioned Mesenchymal Stem Cells Promote Cartilage Formation and Collagen Maturation for Enthesis Regeneration in a Rat Model of Chronic Rotator Cuff Tear","volume":"51","author":"Cai J.","year":"2023","journal-title":"American Journal of Sports Medicine"},{"key":"e_1_2_10_49_1","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/3945195","article-title":"Eugenol\u2010Preconditioned Mesenchymal Stem Cell\u2010Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells In Vitro and In Vivo","volume":"2022","author":"Li X.","year":"2022","journal-title":"Oxidative Medicine and Cellular Longevity"},{"key":"e_1_2_10_50_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2147\/JIR.S254879","article-title":"MicroRNA\u201021\u20103p Engineered Umbilical Cord Stem Cell\u2010Derived Exosomes Inhibit Tendon Adhesion","volume":"13","author":"Yao Z.","year":"2020","journal-title":"Journal of Inflammation Research"},{"key":"e_1_2_10_51_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jot.2023.02.002","article-title":"Exosomes from CD133(+) Human Urine\u2010Derived Stem Cells Combined Adhesive Hydrogel Facilitate Rotator Cuff Healing by Mediating Bone Marrow Mesenchymal Stem Cells","volume":"39","author":"Tong X.","year":"2023","journal-title":"Journal of Orthopaedic Translation"},{"key":"e_1_2_10_52_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-019-1960-x","article-title":"Extracellular Vesicles From Bone Marrow\u2010Derived Multipotent Mesenchymal Stromal Cells Regulate Inflammation and Enhance Tendon Healing","volume":"17","author":"Shi Z.","year":"2019","journal-title":"Journal of Translational Medicine"},{"key":"e_1_2_10_53_1","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1177\/03635465221096490","article-title":"Loading Mesenchymal Stem Cell\u2010Derived Exosomes Into a Traditionally Designed Rotator Cuff Patch: A Potential Strategy to Enhance the Repair of Chronic Rotator Cuff Tear Associated With Degenerative Changes","volume":"50","author":"Zhang X.","year":"2022","journal-title":"American Journal of Sports Medicine"},{"key":"e_1_2_10_54_1","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1177\/03635465241296141","article-title":"Kartogenin\u2010Loaded Exosomes Derived From Bone Marrow Mesenchymal Stem Cells Enhance Chondrogenesis and Expedite Tendon Enthesis Healing in a Rat Model of Rotator Cuff Injury","volume":"52","author":"Wang Y.","year":"2024","journal-title":"American Journal of Sports Medicine"},{"key":"e_1_2_10_55_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222212373","article-title":"Extracellular Vesicles of Adipose\u2010Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons","volume":"22","author":"Chen S. H.","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_10_56_1","doi-asserted-by":"crossref","DOI":"10.1177\/23259671211062929","article-title":"Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study","volume":"9","author":"Wellings E. P.","year":"2021","journal-title":"Orthopaedic Journal of Sports Medicine"},{"key":"e_1_2_10_57_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0229914","article-title":"Extracellular Vesicles From Rat\u2010Bone\u2010Marrow Mesenchymal Stromal\/Stem Cells Improve Tendon Repair in Rat Achilles Tendon Injury Model in Dose\u2010Dependent Manner: A Pilot Study","volume":"15","author":"Gissi C.","year":"2020","journal-title":"PLoS One"},{"key":"e_1_2_10_58_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.omtn.2018.11.006","article-title":"Macrophage\u2010Derived miRNA\u2010Containing Exosomes Induce Peritendinous FibrosisAfter Tendon Injury Through the miR\u201021\u20105p\/Smad7 Pathway","volume":"14","author":"Cui H.","year":"2019","journal-title":"Molecular Therapy\u2013Nucleic Acids"},{"key":"e_1_2_10_59_1","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.2147\/JIR.S345517","article-title":"The Therapeutic Effect of iMSC\u2010Derived Small Extracellular Vesicles on Tendinopathy Related Pain Through Alleviating Inflammation: An In Vivo and In Vitro Study","volume":"15","author":"Zhu Z.","year":"2022","journal-title":"Journal of Inflammation Research"},{"key":"e_1_2_10_60_1","doi-asserted-by":"crossref","first-page":"5475","DOI":"10.1111\/jcmm.14430","article-title":"Exosomes From Tendon Stem Cells Promote Injury Tendon Healing Through Balancing Synthesis and Degradation of the Tendon Extracellular Matrix","volume":"23","author":"Wang Y.","year":"2019","journal-title":"Journal of Cellular and Molecular Medicine"},{"key":"e_1_2_10_61_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2021.102200","article-title":"Small Extracellular Vesicles With LncRNA H19 \u2018Overload\u2019: YAP Regulation as a Tendon Repair Therapeutic Tactic","volume":"24","author":"Tao S. C.","year":"2021","journal-title":"iScience"},{"key":"e_1_2_10_62_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13287-020-02016-8","article-title":"Extracellular Vesicles From Hydroxycamptothecin Primed Umbilical Cord Stem Cells Enhance Anti\u2010Adhesion Potential for Treatment of Tendon Injury","volume":"11","author":"Li J.","year":"2020","journal-title":"Stem Cell Research & Therapy"},{"key":"e_1_2_10_63_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.595911","article-title":"Exosomes From M2 Macrophage Promote Peritendinous Fibrosis Posterior Tendon Injury via the MiR\u201015b\u20105p\/FGF\u20101\/7\/9 Pathway by Delivery of circRNA\u2010Ep400","volume":"9","author":"Yu Y.","year":"2021","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"e_1_2_10_64_1","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3724\/abbs.2021026","article-title":"Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Reduce Tendon Injuries via the miR\u201027b\u20103p\/ARHGAP5\/RhoA Signaling Pathway","volume":"54","author":"Han Q.","year":"2022","journal-title":"Acta Biochimica et Biophysica Sinica"},{"key":"e_1_2_10_65_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13287-022-02723-4","article-title":"Exosomes From Tendon Derived Stem Cells Promote Tendon Repair Through miR\u2010144\u20103p\u2010regulated Tenocyte Proliferation and Migration","volume":"13","author":"Song K.","year":"2022","journal-title":"Stem Cell Research & Therapy"},{"key":"e_1_2_10_66_1","doi-asserted-by":"crossref","first-page":"11701","DOI":"10.2147\/IJN.S466363","article-title":"Dendritic Cell\u2010Derived Exosomes Promote Tendon Healing and Regulate Macrophage Polarization in Preventing Tendinopathy","volume":"19","author":"Chen R.","year":"2024","journal-title":"International Journal of Nanomedicine"},{"key":"e_1_2_10_67_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bioactmat.2025.01.016","article-title":"Restoring Tendon Microenvironment in Tendinopathy: Macrophage Modulation and Tendon Regeneration With Injectable Tendon Hydrogel and Tendon\u2010Derived Stem Cells Exosomes","volume":"47","author":"Li D.","year":"2025","journal-title":"Bioactive Materials"},{"key":"e_1_2_10_68_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13018-025-06352-4","article-title":"Exosomes Derived From Schwann Cells (SCDE) Promote Tendon Repair Through the PTEN\/PI3K\/Akt Signaling Pathway","volume":"20","author":"Chunbo L.","year":"2025","journal-title":"Journal of Orthopaedic Surgery and Research"},{"key":"e_1_2_10_69_1","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1016\/j.arthro.2025.03.033","article-title":"Mitochondria\u2010Rich Extracellular Vesicles From Bone Marrow Stem Cells Mitigate Muscle Degeneration in Rotator Cuff Tears in a Rat Model Through Macrophage M2 Phenotype Conversion","volume":"41","author":"Gao X.","year":"2025","journal-title":"Arthroscopy"},{"key":"e_1_2_10_70_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-026-04364-8","article-title":"Bee Sting\u2010Shaped Microneedles for Accelerating Achilles Tendinopathy Healing via Enhanced Regulating Macrophage Polarization","volume":"24","author":"Hao M.","year":"2026","journal-title":"Journal of Nanobiotechnology"},{"key":"e_1_2_10_71_1","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1177\/03635465261421555","article-title":"Regenerative Effect of Injectable Collagen Loaded With Mesenchymal Stem Cell\u2010Derived Extracellular Vesicles in a Collagenase\u2010Induced Tendinopathy Rat Model","volume":"54","author":"Jeon Y. D.","year":"2026","journal-title":"American Journal of Sports Medicine"},{"key":"e_1_2_10_72_1","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1021\/acsabm.4c01429","article-title":"Biodegradable Cryo\u2010Self\u2010Assembled Silk Fibroin Sponge for Enzyme\u2010Responsive Exosome Delivery to Enhance Tendon Regeneration","volume":"8","author":"Kong S.","year":"2025","journal-title":"ACS Applied Bio Materials"},{"key":"e_1_2_10_73_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2026.112515","article-title":"Bone Marrow Mesenchymal Stem Cell\u2010Derived Exosomes Enhance Tendon Regeneration and Promote TDSC Migration and Differentiation","volume":"144","author":"Lin J.","year":"2026","journal-title":"Cellular Signalling"},{"key":"e_1_2_10_74_1","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-025-09210-5","article-title":"Exosomal miR\u2010212\u20105p Promotes Tendon Repair via Targeting FOXO1 to Activate PP1A\/YAP1 Signaling","volume":"8","author":"Lin K.","year":"2025","journal-title":"Communications Biology"},{"key":"e_1_2_10_75_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13287-025-04789-2","article-title":"The Treatment of Acute Tendon Injury With Small Extracellular Vesicles Originating From TNFAIP6(\u2010) ADSCs Subpopoulation Both In Vitro and In Vivo","volume":"17","author":"Liu H.","year":"2025","journal-title":"Stem Cell Research & Therapy"},{"key":"e_1_2_10_76_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.reth.2025.101050","article-title":"NSUN2\u2010Engineered Human Umbilical Cord Mesenchymal Stem Cell\u2010Derived Exosomes Ameliorate Tendon Injury by Promoting DNM2 Expression","volume":"31","author":"Liu Y.","year":"2026","journal-title":"Regenerative Therapy"},{"key":"e_1_2_10_77_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-026-44967-7","article-title":"Mesenchymal Stem Cell Derived Exosomes and Injectable Platelet\u2010Rich Fibrin Enhance SDFT Healing in a Donkey Tendonitis Model","volume":"16","author":"Najeb M.","year":"2026","journal-title":"Scientific Reports"},{"key":"e_1_2_10_78_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-026-40392-y","article-title":"BMSCs Loaded Exosome Hydrogel Promotes the Repair of Rotator Cuff Injury in Rats In Vivo","volume":"16","author":"Peng K.","year":"2026","journal-title":"Scientific Reports"},{"key":"e_1_2_10_79_1","doi-asserted-by":"crossref","first-page":"42637","DOI":"10.1021\/acsami.5c05369","article-title":"Hypoxia Induces HIF\u20101\u03b1 Activation in Tendon Stem Cells to Enhance Extracellular Vesicle\u2010Mediated Tendon Repair","volume":"17","author":"Wu Y.","year":"2025","journal-title":"ACS Applied Materials & Interfaces"},{"key":"e_1_2_10_80_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.mtbio.2025.101790","article-title":"CBD\u2010Conjugated BMP\u2010Inhibiting Exosomes on Collagen Scaffold Dual\u2010Target Achilles Tendon Repair: Synergistic Regeneration and Heterotopic Ossification Prevention","volume":"32","author":"Xu Y.","year":"2025","journal-title":"Materials Today Bio"},{"key":"e_1_2_10_81_1","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1021\/acsnano.5c16275","article-title":"Exosome\u2010Infused DTM\u2010MPs Hydrogel Scaffold: A Smart Platform for Tendon Repair With Sustained Bioactivity and Anti\u2010Inflammatory Benefits","volume":"20","author":"Xu Y.","year":"2026","journal-title":"ACS Nano"},{"key":"e_1_2_10_82_1","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1177\/03635465251358465","article-title":"ADSC\u2010EVs Activate Autophagy via the AKT\/FOXO1 Pathway to Inhibit Tendon Fibrosis","volume":"53","author":"Zhang A. D.","year":"2025","journal-title":"American Journal of Sports Medicine"},{"key":"e_1_2_10_83_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioadv.2025.214272","article-title":"Platelet\u2010Rich Plasma\u2010Derived Exosomes Have the Novel Ability to Alleviate Insertional Achilles Tendinopathy by Promoting Tenogenesis in Tendon Stem\/Progenitor Cells","volume":"173","author":"Zhang A.","year":"2025","journal-title":"Biomaterials Advances"},{"key":"e_1_2_10_84_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.mtbio.2025.102590","article-title":"Turmeric\u2010Derived Extracellular Vesicles Loaded Microneedle System Attenuates Rotator Cuff Degeneration by Orchestrating Energetic Metabolism","volume":"35","author":"Zhang R.","year":"2025","journal-title":"Materials Today Bio"},{"key":"e_1_2_10_85_1","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2025.1615650","article-title":"Restoration of Tendon Repair Microenvironment by Grapefruit Exosome\u2010Loaded Microneedle System for Tendinopathy Therapy","volume":"13","author":"Zhang Y.","year":"2025","journal-title":"Frontiers in Bioengineering and Biotechnology"},{"key":"e_1_2_10_86_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242015183","article-title":"Effect of Aging on Tendon Biology, Biomechanics and Implications for Treatment Approaches","volume":"24","author":"Kwan K. Y. C.","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_10_87_1","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1002\/jor.23580","article-title":"Aging Does Not Alter Tendon Mechanical Properties During Homeostasis, but Does Impair Flexor Tendon Healing","volume":"35","author":"Ackerman J. E.","year":"2017","journal-title":"Journal of Orthopaedic Research"},{"key":"e_1_2_10_88_1","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1002\/jor.23516","article-title":"Sex Differences in Tendon Structure and Function","volume":"35","author":"Sarver D. C.","year":"2017","journal-title":"Journal of Orthopaedic Research"},{"key":"e_1_2_10_89_1","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1002\/jor.25562","article-title":"Regenerative MRL\/MpJ Tendon Cells Exhibit Sex Differences in Morphology, Proliferation, Mechanosensitivity, and Cell\u2010ECM Organization","volume":"41","author":"Marvin J. C.","year":"2023","journal-title":"Journal of Orthopaedic Research"},{"key":"e_1_2_10_90_1","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.7150\/thno.72676","article-title":"Influences of Age, Race, and Sex on Extracellular Vesicle Characteristics","volume":"12","author":"Noren Hooten N.","year":"2022","journal-title":"Theranostics"},{"key":"e_1_2_10_91_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41514-024-00189-7","article-title":"Age\u2010 and Sex\u2010Related Variations in Extracellular Vesicle Profiling for the Assessment of Cardiovascular Risk: The EVaging Index","volume":"10","author":"Burrello J.","year":"2024","journal-title":"NPJ Aging"},{"key":"e_1_2_10_92_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/GME.0b013e31829638e3","article-title":"Prevalence of and Risk Factors for Asymptomatic Rotator Cuff Tears in Postmenopausal Women","volume":"21","author":"Abate M.","year":"2014","journal-title":"Menopause"},{"key":"e_1_2_10_93_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s13224-019-01213-7","article-title":"Musculoskeletal Disorders and Menopause","volume":"69","author":"Khadilkar S. S.","year":"2019","journal-title":"Journal of Obstetrics and Gynecology of India"},{"key":"e_1_2_10_94_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.32098\/mltj.03.2014.11","article-title":"Impact of Oestrogen Deficiency and Aging on Tendon: Concise Review","volume":"4","author":"Frizziero A.","year":"2014","journal-title":"Muscles, Ligaments and Tendons Journal"},{"key":"e_1_2_10_95_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jsbmb.2017.06.008","article-title":"The Effect of Estrogen on Tendon and Ligament Metabolism and Function","volume":"172","author":"Leblanc D. R.","year":"2017","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"e_1_2_10_96_1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1161\/CIRCRESAHA.118.313251","article-title":"New Paradigms in Cell Therapy: Repeated Dosing, Intravenous Delivery, Immunomodulatory Actions, and New Cell Types","volume":"123","author":"Wysoczynki M.","year":"2018","journal-title":"Circulation Research"},{"key":"e_1_2_10_97_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.tcm.2020.08.003","article-title":"Experimental Limitations of Extracellular Vesicle\u2010Based Therapies for the Treatment of Myocardial Infarction","volume":"31","author":"Kennedy T. L.","year":"2021","journal-title":"Trends in Cardiovascular Medicine"},{"key":"e_1_2_10_98_1","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adh1168","article-title":"The Cellular Response to Extracellular Vesicles Is Dependent on Their Cell Source and Dose","volume":"9","author":"Hagey D. W.","year":"2023","journal-title":"Science Advances"},{"key":"e_1_2_10_99_1","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1113\/jphysiol.2007.127639","article-title":"Expression of Collagen and Related Growth Factors in Rat Tendon and Skeletal Muscle in Response to Specific Contraction Types","volume":"582","author":"Heinemeier K. M.","year":"2007","journal-title":"Journal of Physiology"},{"key":"e_1_2_10_100_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2460\/ajvr.2005.66.266","article-title":"Cloning and Expression of Type III Collagen in Normal and Injured Tendons of Horses","volume":"66","author":"Dahlgren L. A.","year":"2005","journal-title":"American Journal of Veterinary Research"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70289","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.70289","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:58:16Z","timestamp":1791446296000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.70289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":99,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jor.70289"],"URL":"https:\/\/doi.org\/10.1002\/jor.70289","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70289"}}