Adipose-derived stem cell exosomes promote critical-sized bone defect repair by enhancing the homing of bone marrow mesenchymal stem cells

The repair of critical-sized bone defects remains a significant clinical challenge. As a cell-free alternative, exosomes derived from adipose-derived stem cells (ADSCs-Exos) hold promise, yet their precise mechanism in endogenous repair is unclear. This study investigated whether ADSCs-Exos enhance bone repair by promoting the homing and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). ADSCs-Exos were isolated and co-cultured with BMSCs to assess proliferation, migration, and osteogenic differentiation in vitro. Key gene expression (e.g., Cxcr4, Runx2) was analyzed. A highly elastic hydrogel was used for sustained exosome delivery in a rat calvarial defect model. mouse bone marrow-derived mesenchymal stem cells (mBMSCs) homing was monitored via live imaging, and bone regeneration was evaluated by micro-CT and histology. Results showed that ADSCs-Exos promoted BMSC migration and osteogenesis, rapidly upregulating homing-related genes (Ccr7, Cxcr4) and subsequently activating osteogenic genes (Runx2, OPN). In vivo, the ADSCs-Exo/hydrogel complex significantly enhanced BMSC recruitment to the defect site, leading to markedly improved new bone formation. This study elucidates a novel, cell-free strategy wherein ADSCs-Exos orchestrate endogenous bone repair by enhancing BMSC homing and differentiation, providing a potential therapeutic approach.