Extracellular vesicle-functionalized bioactive scaffolds for bone regeneration.

The clinical need for effective bone regeneration in compromised conditions continues to drive demand for innovative solutions. Among emerging strategies, extracellular vesicles (EVs) have shown promise as an acellular approach for bone regeneration. However, their efficacy is hindered by rapid sequestration and clearance when administered via bolus injection. To address this challenge, EV-functionalized scaffolds have recently been proposed as an alternative delivery strategy to enhance EV retention and subsequent healing efficacy. This review aims to consolidate recent advancements in the development of EV-functionalized scaffolds for augmenting bone regeneration. It explores various sources of EVs and different strategies for integrating them into biomaterials. Furthermore, the mechanisms underlying their therapeutic effects in bone regeneration are elucidated. Current limitations in clinical translation and perspectives on the design of more efficient EVs for improved therapeutic efficacy are also presented. Overall, this review can provide inspiration for the development of novel EV-assisted grafts with superior bone regeneration potential.