Extracellular Vesicles and Their Role in Osteogenesis.

Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents for bone regeneration due to their ability to modulate osteogenesis, angiogenesis, and immune responses. This review summarizes the current knowledge on EV biology, including their classification, biogenesis, and molecular cargo, with a particular focus on their role in bone healing. EVs derived from mesenchymal stromal cells and other cell types promote osteoblast differentiation, inhibit osteoclast activity, enhance vascularization, and modulate inflammation through the transfer of bioactive proteins and non-coding RNAs. Recent advances in EV engineering, biomaterial-assisted delivery, and isolation techniques are discussed, together with their translational potential for the treatment of critical bone defects and avascular osteonecrosis. Although preclinical evidence is highly encouraging, clinical evidence remains limited, particularly in orthopedics, and clinical translation is challenged by EV heterogeneity, lack of dose standardization, limited understanding of biodistribution, scalable manufacturing, and regulatory requirements. Overall, EV-based therapies represent a promising future strategy for regenerative orthopedics and bone tissue engineering.