Exosome-Functionalized Hydrogels Improve Cartilage Repair by Modulating BMSCs Migration and Differentiation

Articular cartilage exhibits inherently poor self-repair capacity, and conventional therapeutic strategies often yield suboptimal long-term functional restoration due to inadequate tissue remodeling and mechanical instability. To address this challenge, we developed a biomimetic hydrogel scaffold integrating bone marrow mesenchymal stem cell (BMSC)-derived exosomes within a cartilage-mimetic matrix composed of gelatin methacrylate (GelMA), chondroitin sulfate methacrylate (CSMA), and hyaluronic acid methacrylate (HAMA). In vitro analyses demonstrated the composite hydrogel's robust capacity to drive chondrogenic differentiation of BMSCs, as evidenced by upregulated expression of collagen II and aggrecan. Crucially, exosome incorporation enhanced cellular internalization efficiency and induced chemotactic migration of BMSCs toward exosome-enriched hydrogel regions, creating a self-reinforcing regenerative niche. The sustained release profile of exosomes from the hydrogel matrix preserved their bioactivity and synergistically amplified chondroinductive signaling. In a rat osteochondral defect model, the GelMA/CSMA/HAMA@Exo scaffold significantly accelerated hyaline-like cartilage regeneration with improved structural integration and biomechanical properties compared to exosome-free controls. This engineered platform exemplifies a spatiotemporally coordinated strategy for recapitulating native cartilage repair cascades, offering a promising therapeutic paradigm for functional cartilage restoration.