Biomaterial-based extracellular vesicle delivery systems for wound healing: From fabrication to applications

Skin damage, especially chronic wounds, imposes a significant clinical burden due to the associated risks of disability and death. Extracellular vesicles (EVs) have received extensive attention due to their potential in wound healing. However, the rapid clearance and short retention time of EVs at wound sites hinder the optimal therapeutic effects. The latest advancements in biomaterial delivery systems have spurred the rapid development of engineered EV delivery systems. These biomaterials can not only prolong the localization and stability of EVs in wounds, but also provide structural and biochemical support for cell growth and tissue regeneration. This review provides a comprehensive overview of EVs and the fabrication strategies of EV delivery systems with diverse application forms. The release mechanisms, release profiles, mathematical kinetic models of EVs from biomaterials are also discussed. The application of these EV-loaded biomaterials in treating various types of wounds is also summarized and discussed. Finally, current challenges and future directions in EV-based wound treatment are proposed. Unlike previous reviews that focused separately on the biology of EVs or biomaterials as wound dressings, this review presents a comprehensive summary of the fabrication strategies and applications of advanced biomaterial-based EV delivery platforms for wound healing.