Platelet-related extracellular vesicles: Therapeutic roles in musculoskeletal disorders

Musculoskeletal disorders are a major cause of pain, disability, and loss of function. Platelet-rich plasma (PRP) has been widely investigated for musculoskeletal repair, and interest has increasingly extended to extracellular vesicle (EV) preparations obtained from platelet-related starting materials. These include EV-enriched preparations collected from isolated platelets or defined platelet concentrates (P-EVs), from PRP (PRP-EVs), and from platelet lysate (PL-EVs). They do not represent the same biological product. Their cellular contributors, co-isolated soluble components, and molecular composition can differ substantially, and the name of the starting material does not prove the origin of every vesicle in the preparation. Preclinical studies nevertheless suggest that these EV preparations can influence inflammatory responses, cartilage metabolism, tendon-cell behavior, and the local repair environment. The strength of this evidence varies with the source material, separation and characterization methods, experimental model, and delivery strategy. This review examines the therapeutic evidence for platelet-related EV preparations in musculoskeletal disorders, while keeping P-EVs, PRP-EVs, PL-EVs, and plasma-derived EVs distinct and considering the methodological limitations that currently restrict comparison and clinical translation.