Exosome-functionalized heterogeneous nanofibrous scaffolds repair bone defects accompanied by muscle injury

Patients with clinical bone defects often experience varying degrees of muscle injury. Due to the high heterogeneity of hard and soft tissue structures, the integrated treatment of muscle injuries associated with bone defects remains a challenge. To address this challenge, this study proposes the construction of a heterogeneous bilayered electrospun nanofibrous scaffold based on the structural heterogeneity of bone and muscle to guide bone-muscle regeneration. The oriented fiber layer of the asymmetric bilayered scaffold promoted myofibroblast orientation and myogenic differentiation, whereas the random fiber layer promoted bone marrow mesenchymal stem cells (BMSCs) differentiation. Furthermore, immobilizing BMSCs-derived exosomes (BMSCs-Exo) on a heterogeneous bilayered scaffold via surface chemical modification of PEI enhances angiogenesis and immunoregulation. The foreign body response and muscle repair effect of the exosome-laden scaffolds were evaluated by subcutaneous implantation and a volumetric muscle loss model in mice. The performance of guided bone regeneration was assessed using a critical-sized cranial bone defect model in rats. BMSCs-Exo-functionalized heterogeneous bilayered electrospun nanofibrous scaffolds have great application potential in repairing bone-muscle injury.