Adipose-Derived Orthobiologics and Extracellular Vesicles in Foot and Ankle Surgery: Current Evidence and Clinical Limitations

Interest in adipose-derived orthobiologics and extracellular vesicles (EVs) has expanded as clinicians seek minimally invasive treatments for musculoskeletal disorders. However, culture-expanded adipose-derived stromal cells, stromal vascular fraction, microfragmented adipose tissue (MFAT), and isolated EVs are biologically and regulatorily distinct products. This narrative review summarizes their biological rationale, processing, clinical evidence, regulatory considerations, and potential application in foot and ankle surgery. Randomized studies in knee osteoarthritis suggest that MFAT may provide symptomatic improvement, but it has not consistently demonstrated superiority over other orthobiologic injections, and the certainty of evidence remains low. Preclinical EV studies provide biological plausibility for effects on tendon healing, tendon-to-bone integration, and cartilage repair. However, substantial heterogeneity in cellular source, preparation, dose, and experimental model limits translation. Human orthopaedic EV evidence remains confined to early studies in knee osteoarthritis using placental or umbilical cord derived products, with limited and conflicting evidence of efficacy and no completed studies specific to the foot and ankle. No adipose-derived regenerative medicine or EV product is Food and Drug Administration-approved for an orthopaedic indication. Current evidence therefore does not support routine clinical use or claims of tissue regeneration. Standardized product characterization and well-designed comparative trials are required to establish safety, efficacy, and appropriate clinical applications.