Extracellular vesicle-based therapeutics for the regeneration of chronic wounds: current knowledge and future perspectives.

Chronic wounds are still an intractable medical problem for both clinicians and researchers and cause a substantial social and medical burden. Current clinical approaches can only manage wounds but have limited capacity to promote the regeneration of chronic wounds. As a type of natural nanovesicle, extracellular vesicles (EVs) from multiple cell types (e.g., stem cells, immune cells, and skin cells) have been shown to participate in all stages of skin wound healing including inflammation, proliferation, and remodeling, and display beneficial roles in promoting wound repair. Moreover, EVs can be further re-engineered with genetic/chemical or scaffold material-based strategies for enhanced skin regeneration. In this review, we provide an overview of EV biology and discuss the current findings regarding the roles of EVs in chronic wound healing, particularly in immune regulation, cell proliferation and migration, angiogenesis, and extracellular matrix remodeling, as well as the therapeutic effects of EVs on chronic wounds by genetic modification, in combination with functionalized biomaterials, and as drug carriers. We also discuss the challenges and perspectives of translating EV-based therapies into clinical wound care in the future.