Therapeutic potential of early-stage mesenchymal stem cell-derived exosomes and injectable platelet-rich fibrin in a donkey model of superficial digital flexor tendonitis

Therapeutic potential of early-stage mesenchymal stem cell-derived exosomes and injectable platelet-rich fibrin in a donkey model of superficial digital flexor tendonitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Therapeutic potential of early-stage mesenchymal stem cell-derived exosomes and injectable platelet-rich fibrin in a donkey model of superficial digital flexor tendonitis Mahmoud Najeb, Alaa Samy, Awad Rizk, Esam Mosbah, Iman Ibrahim, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7502308/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Tendon injuries remain a major clinical challenge in equine practice due to the limited regenerative capacity of tendons and the high risk of reinjury. Injectable platelet-rich fibrin (I-PRF) and mesenchymal stem cell (MSC) derived exosomes have emerged as promising regenerative therapies with immunomodulatory and matrix-restorative potential. This study aimed to evaluate the therapeutic efficacy of I-PRF alone and in combination with MSC-derived exosomes in a donkey model of collagenase-induced superficial digital flexor (SDF) tendonitis. Twenty-seven donkeys were allocated into three groups: placebo (saline), I-PRF, and I-PRF/exosome. Tendon healing was assessed clinically, ultrasonographically, histologically, immunohistochemically, and biomechanically over 20 weeks. At the endpoint, the PRF/exosome group showed significantly improved tendon shape and weight-bearing scores compared to the placebo group (P < 0.001). Ultrasonographic parameters were significantly enhanced in the PRF/exosome group regardless of changes in tendon cross-sectional area (T-CSA). T-CSA remained elevated in all treated groups, while it significantly decreased in the placebo group. Immunohistochemistry revealed the highest collagen type I and lowest type III expression in the PRF/exosome group. Biomechanically, failure stress and strain percentage were also significantly greater in the PRF/exosome group than in the placebo group. These findings highlight the synergistic potential of combining I-PRF with MSC-derived exosomes in enhancing tendon repair. However, further long-term studies in naturally occurring cases are needed to validate these findings and assess their translational relevance. Health sciences/Diseases Health sciences/Medical research Health sciences/Rheumatology Biological sciences/Stem cells Injectable platelet-rich fibrin MSC-derived exosomes tendon healing superficial digital flexor tendonitis donkey model Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementerytables.docx Cite Share Download PDF Status: Published Journal Publication published 10 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 16 Feb, 2026 Reviews received at journal 15 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers agreed at journal 08 Feb, 2026 Reviews received at journal 23 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers agreed at journal 19 Jan, 2026 Reviewers invited by journal 11 Sep, 2025 Editor assigned by journal 11 Sep, 2025 Editor invited by journal 09 Sep, 2025 Submission checks completed at journal 05 Sep, 2025 First submitted to journal 05 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7502308","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":514764101,"identity":"8c5983b1-24ee-4b10-8ca9-0f97622eaead","order_by":0,"name":"Mahmoud Najeb","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Najeb","suffix":""},{"id":514764102,"identity":"e3de90a0-55a7-4b95-80f6-b986330132b1","order_by":1,"name":"Alaa Samy","email":"","orcid":"","institution":"Mansoura 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Injectable platelet-rich fibrin (I-PRF) and mesenchymal stem cell (MSC) derived exosomes have emerged as promising regenerative therapies with immunomodulatory and matrix-restorative potential. This study aimed to evaluate the therapeutic efficacy of I-PRF alone and in combination with MSC-derived exosomes in a donkey model of collagenase-induced superficial digital flexor (SDF) tendonitis. Twenty-seven donkeys were allocated into three groups: placebo (saline), I-PRF, and I-PRF/exosome. Tendon healing was assessed clinically, ultrasonographically, histologically, immunohistochemically, and biomechanically over 20 weeks. At the endpoint, the PRF/exosome group showed significantly improved tendon shape and weight-bearing scores compared to the placebo group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Ultrasonographic parameters were significantly enhanced in the PRF/exosome group regardless of changes in tendon cross-sectional area (T-CSA). 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