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

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.