Extracellular vesicles in osteoarthritis: pathological mechanisms, regenerative therapies and clinical translation.

Osteoarthritis (OA) is a common chronic degenerative joint disease that has severe impacts on quality of life and creates a substantial socioeconomic burden. Conventional therapeutic strategies primarily focused on alleviating symptoms such as pain and functional impairment, with limited efficacy and an inability to reverse the disease process. Over the past two decades, regenerative medicine has been developed rapidly. Extracellular vesicles (EVs) have garnered widespread attention and there has been an upsurge of research interest in their immunomodulatory and regenerative potential in OA. However, there remains a lack of up-to-date systematic elaboration on EVs in the pathogenesis, regenerative therapy, and clinical translation of OA. Therefore, this paper focuses on a search of the relevant literature in the past five years, revealing that EVs of multiple tissue origins in individuals work together to drive OA pathological process and various sources-derived EVs demonstrate obvious effects in ameliorating OA, with the related molecular mechanisms becoming increasingly in-depth and comprehensive. Although naturally sourced EVs have limitations in yield, cargo loading, bioavailability and so on, the application of engineering technology is expected to improve these defects, positioning minimally invasive, cell-free, targeted EV-based therapies as a promising approach. In this regard, breaking through the technical bottlenecks in EV manufacturing and establishing unified industry standards have raised stringent requirements for the further clinical translation of EVs.