Therapeutic application of extracellular vesicles for musculoskeletal repair & regeneration.

Traumatic musculoskeletal injuries are common in both the civilian and combat care settings. Significant barriers exist to repairing these injuries including fracture nonunion, muscle fibrosis, re-innervation, and compartment syndrome, as well as infection and inflammation. Recently, extracellular vesicles (EVs), including exosomes and microvesicles, have attracted attention in the field of musculoskeletal regeneration. These vesicles are released by different cell types and play a vital role in cell communication by delivering functional cargoes such as proteins and RNAs. Many of these cargo molecules can be utilized for repair purposes in skeletal disorders such as osteoporosis, osteogenesis imperfecta, sarcopenia, and fracture healing. There are, however, some challenges to overcome in order to advance the successful application of these vesicles in the therapeutic setting. These include large-scale production and isolation of exosomes, long-term storage, stability, and strategies for tissue-specific targeting and delivery. This paper reviews the general characteristics of exosomes along with their physiological roles and contribution to the pathogenesis of musculoskeletal diseases. We also highlight new findings on the use of synthetic exosomes to overcome the limitations of native exosomes in treating musculoskeletal injuries and disorders.