Regenerative effects of engineered extracellular vesicles on repairing bone defects

Zhou Yang; Liu Kexin; Wang Deli; Sun Zhang

doi:10.12307/2025.749

Abstract：BACKGROUND:Extracellular vesicles have received extensive attention in the field of bone defect regeneration and repair in recent years.However,natural extracellular vesicles have deficiencies in sustained controlled release,tissue targeting,and drug loading capacity.Therefore,the introduction of engineering strategies to modify extracellular vesicles to enhance their therapeutic efficacy has become a research hotspot. OBJECTIVE:To review the role and application progress of engineered extracellular vesicles in the regeneration and repair of bone defects. METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched for relevant articles published in the past fifteen years.The search terms were"engineering,extracellular vesicles,exosomes,bone defect,bone regeneration,bone repair"in Chinese and English.After removal of poorly related,outdated,and duplicate studies by screening,93 articles were finally included for review according to inclusion criteria. RESULTS AND CONCLUSION:(1)Extracellular vesicles are primarily isolated based on their density,size,immunoaffinity,and surface charge.After isolation,extracellular vesicles are characterized using imaging techniques,size-and counting-based techniques,and flow cytometry.(2)Extracellular vesicles stimulate bone regeneration by regulating immunity,angiogenesis,and proliferation and differentiation of target cells.(3)The engineering strategies of extracellular vesicles include surface modification and cargo loading.(4)The introduction of bone morphogenetic protein 2,mutant hypoxia-inducible factor-1α,vascular endothelial growth factor,miRNA and other bioactive factors into extracellular vesicles through engineering strategies can enhance their regenerative repair ability for bone defects.