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


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.


To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells (BMSCs) facilitate the process of fracture healing.


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.


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.


We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.

Key Words: Hydrogel, Bone marrow mesenchymal stem cells, Macrophage polarization, Angiogenesis, Bone regeneration


Core Tip: We adopted a new method to enhance tissue repair and promote bone regeneration through hydrogels loaded with mesenchymal stem cell (MSC) exosomes. This experiment demonstrated that bone marrow-derived MSC (BMSC)-derived exosome (BMSC-exo) hydrogel significantly promoted the proliferation, migration and osteogenesis of mouse osteoblast progenitor cells, and at the same time enhanced the M2 polarization of macrophages in bone marrow, thus translating into accelerated fracture healing and angiogenesis in vivo. In addition, BMSC-exo hydrogels successfully enhance the strength and toughness of regenerated bone, with higher maximum load, stiffness and damage absorption energy.

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