The immunomodulatory and regenerative features of mesenchymal stem cells are regulated in part by extracellular vesicle (EV)-mediated paracrine signaling. EVs are small membrane-enclosed particles that transport bioactive proteins, metabolites, and genetic materials inherited from a parent cell. EVs play a critical role in tissue repair and regeneration by inducing phenotypic and genotypic changes in recipient cells, and thus are a viable cell-free therapy to circumvent issues associated with cell-based therapies. However, a major challenge towards therapeutic utility of EVs is their heterogeneous composition which complicates the design, standardization, and targeted delivery of EVs. Thus, our goal is identifying the EV components that play a critical role throughout musculoskeletal healing and engineering EVs with tailored functional properties for targeted repair.