A self-healing and injectable hydrogel for sustained delivery of BMSC-derived exosomes to promote osteogenesis and inhibit osteoclastogenesis in vitro

The repair of osteoporotic bone defects remains highly challenging due to the pathological local microenvironment. Exosomes have shown potential as a cell-free therapeutic approach, but their rapid clearance in vivo limits their efficacy. In this study, we developed an injectable oxidized starch/gelatin composite hydrogel (GEL) based on dynamic Schiff base bonds as an intelligent sustained-release carrier for bone marrow mesenchymal stem cell-derived exosomes (Exos), aiming to provide a potential in vitro strategy for modulating bone metabolism. The hydrogel exhibits rapid gelation, notable shear-thinning, and self-healing properties. In vitro release studies demonstrated that the hydrogel enables sustained release of Exos for over 14 days. The exosome-loaded composite significantly enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells and effectively suppressed RANKL-induced osteoclastogenesis. In summary, the GEL-Exos composite system constructed in this study provides a local and long-term bidirectional regulatory microenvironment for bone metabolism. Although in vivo validation is still needed, this system shows promise for future osteoporotic bone defect repair.