ABSTRACT: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutic strategies for musculoskeletal regeneration. MSC-EVs, which are enriched with diverse cargos, exert multifaceted biological effects, including the modulation of inflammation, the promotion of angiogenesis, and the regulation of immune responses. They also activate key regenerative signaling pathways, such as the PI3K/Akt, Wnt/β-catenin, TGF-β/Smad, and NF-κB pathways, thereby promoting osteogenesis, chondrogenesis, tenogenesis, and muscle repair to support the repair of bone, cartilage, tendon, and muscle tissues. In addition to their intrinsic activity, advances in bioengineering, including surface modification, cargo engineering, and integration with biomaterial scaffolds, have
