The Role of Extracellular Vesicles in Musculoskeletal Diseases

ABSTRACT Extracellular Vesicles (EVs), nanoscale membrane‐bound cell‐released structures, are vital for intercellular communication and material transport. Their role in musculoskeletal health and diseases has recently drawn significant attention. This review focuses on the latest EV research in musculoskeletal diseases, including their roles in disease progression and potential as biomarkers and therapies. Musculoskeletal disorders are the third‐leading cause of global disability‐adjusted life‐years among adolescents and young adults. Current treatments face issues like limited tissue regeneration and poor drug targeting. With their natural messenger function and low immunogenicity, EVs have become a research focus. However, their action mechanisms in the musculoskeletal system remain un‐systematically understood. This paper reviews EVs’ role in musculoskeletal diseases. It covers classification, biogenesis, release, internalization, cargo and their involvement in muscle cell processes, joint diseases, bone metabolism and disc degeneration. It also explores EVs’ role in musculoskeletal crosstalk and their potential as therapeutic agents and drug carriers through engineering with biomaterials. Future research should delve deeper into EV action mechanisms for better treatments. Overall, while EVs offer new treatment strategies for musculoskeletal diseases, more research is needed to overcome technical and clinical barriers.