Bacterial extracellular vesicles in osteoarthritis: a new bridge of the gut-joint axis.

Osteoarthritis (OA) is a degenerative joint disease primarily characterized by cartilage degeneration. Increasing evidence suggests that there is an interplay between the gut microbiota (GM) and joint health, known as the gut-joint axis. In recent years, with the advancement of bacterial extracellular vesicles (BEVs) research, its role in the gut-joint axis has attracted increasing attention. BEVs are phospholipid bilayer nanocarriers with sizes ranging from 20 to 400 nm, which can deliver various bioactive molecules to modulate the intestinal and joint microenvironments. Due to nanoscale structure, low toxicity, high drug loading capacity, good biocompatibility, easy modification, and industrialization, BEVs are promising for OA treatment. Here, we reviewed the research status of BEVs including biogenies, classification, structures, and composition, and summarized the cargo within BEVs that is associated with OA. The application of natural BEVs in the treatment of OA is the core, and the separation, purification, and modification strategies for engineered BEVs are summarized. Finally, we provide an overview and prospects of the role of BEVs in the clinical diagnosis and treatment of OA. We hope that a comprehensive understanding of BEVs will provide new solutions for OA treatment.