Mesenchymal stem cell derived exosomes and injectable platelet-rich fibrin enhance SDFT healing in a donkey tendonitis model

Abstract

Abstract Tendon injuries pose a significant challenge in equine medicine due to the inherently limited regenerative capacity of tendon tissue and the high likelihood of reinjury. Recently, injectable platelet-rich fibrin (I-PRF) and exosomes derived from mesenchymal stem cells (MSCs) have shown promise as regenerative treatments, offering potential benefits in matrix restoration and modulation of inflammatory responses. This study investigated the effects of I-PRF alone and in combination with MSC-derived exosomes on collagenase-induced superficial digital flexor (SDF) tendonitis in donkeys. Twenty-seven donkeys were randomly assigned to three treatment groups: saline (placebo), I-PRF, and PRF/exosome. Tendon healing was monitored over a 20-week period using clinical evaluation, ultrasonography, histology, immunohistochemistry, and biomechanical testing. At the study endpoint, the combined PRF/exosome group exhibited the greatest improvement in tendon consistency and weight-bearing ability compared to placebo (P < 0.001). Ultrasonographic findings were markedly better in the PRF/exosome group, even though tendon cross-sectional area (T-CSA) remained elevated across all treated groups, while it decreased significantly in the placebo group. Immunohistochemical analysis revealed the highest collagen type I and lowest type III levels in tendons treated with PRF/exosome. Biomechanical testing further demonstrated superior failure stress and strain in this group relative to placebo. Overall, these results indicate a potential synergistic effect of combining I-PRF with MSC-derived exosomes in promoting tendon repair. Nevertheless, additional long-term studies in naturally occurring tendon injuries are required to confirm these findings and assess their clinical relevance.