Extracellular Vesicles as Immunomodulatory Mediators in Angiogenic-Osteogenic Coupling: Mechanistic Insights and Therapeutic Potential.

Angiogenic-osteogenic coupling is the temporal and spatial interplay between osteogenesis and angiogenesis, profoundly influenced by the immune microenvironment. Extracellular vesicles (EVs), regarded as crucial signaling mediators in bone development, are widely present in immune networks. However, their critical immunomodulatory roles in the coordinated angiogenic-osteogenic coupling process remain insufficiently elaborated. This article reviews their immunomodulatory mechanisms in physiological and pathological angiogenic-osteogenic coupling and summarizes their clinical translation potential. It systemically reveals the sophisticated regulatory network through which EVs orchestrate angiogenic-osteogenic coupling via immune organs, cells, and factors, specifically highlighting the underlying molecular mechanisms. The immunomodulatory mechanism and clinical translational potential of EVs in bone disorders are further examined. Notably, pioneering breakthroughs in engineering exosomes to enhance angiogenesis and osteogenesis are introduced, bridging fundamental research and clinical application. Understanding the interactions between EVs' immunomodulatory effects and angiogenic-osteogenic coupling provide significant insights into future research directions and novel therapeutic strategies for bone regeneration.