Therapeutic potential of stem cell-derived small extracellular vesicles for mandibular cartilage repair

The temporomandibular joint (TMJ) is a complex ginglymoarthrodial synovial joint that endures various mechanical forces during daily use, but its fibrocartilage exhibits limited self-repair capacity due to its avascular nature. This study aims to bridge critical gaps in TMJ fibrocartilage biology and regenerative therapy by focusing on the therapeutic potential of bone marrow stem cell-derived small extracellular vesicles (BMSC-sEV). Using a comprehensive approach, we fully characterize Fibrocartilage stem cells (FCSC) in rabbit mandibular cartilage and compare these with condylar chondrocytes (CCs) and BMSCs. Proteomic and transcriptomic analyses of sEV from all those cell types are performed to elucidate their roles in fibrocartilage maintenance and to identify selective miRNA packaging mechanisms. Furthermore, in vitro studies assess the effects of BMSC-sEV on FCSC functions such as cell migration, apoptosis resistance, and inflammation modulation. In addition, an in vivo rabbit TMJ disc perforation model is developed to mimic degenerative changes observed in human TMDs. The study also compares miRNA landscapes between rabbit and human BMSC-derived small extracellular vesicles to validate the translational relevance of the rabbit model. Collectively, these investigations are expected to advance our understanding of TMJ fibrocartilage regeneration and small extracellular vesicle–based therapies for TMJ disorders and related pathologies.