Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis

Abstract

BACKGROUND Bone healing is a complex process involving early inflammatory immune regulation, angiogenesis, osteogenic differentiation, and biomineralization. Fracture repair poses challenges for orthopedic surgeons, necessitating the search for efficient healing methods. AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells (BMSCs) facilitate the process of fracture healing. METHODS Hydrogels and loaded BMSC-derived exosome (BMSC-exo) gels were characterized to validate their properties. In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process. Hydrogels could recruit macrophages and inhibit inflammatory responses, enhance of human umbilical vein endothelial cell angiogenesis, and promote the osteogenic differentiation of primary cranial osteoblasts. Furthermore, the effect of hydrogel on fracture healing was confirmed using a mouse fracture model. RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration, promoted the formation of large vessels, and enabled functional vascularization during bone repair. These effects were further validated in fracture models. CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.