Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

Abstract

AbstractStem cell‐derived small extracellular vesicles (sEVs) have shown tremendous potential in regenerative medicine in recent years. These sEVs exert multiple therapeutic effects comparable or superior to their parental stem cells while avoiding the limitations of stem cell‐based therapy. The two routine modalities of sEV administration are systemic injection and local delivery. Various biomaterials are developed to assist their local delivery to improve the targeting of organs, minimize nonspecific accumulation in vital organs, and ensure the protection and release of sEVs. This comprehensive, up‐to‐date, specialty‐specific, disease‐oriented, and preclinical review is presented to expound on the surgical application and potential of stem cell‐derived sEVs. The local delivery of stem cell‐derived sEVscan treat numerous diseases encountered in orthopedic surgery, neurosurgery, plastic surgery, cardiothoracic surgery, general surgery, urology, otorhinolaryngology, ophthalmology, obstetrics and gynecology, and dental surgery. In addition, the biomaterials utilized encompass a wide range of sources (e.g., natural, synthetic, and hybrid polymers), format (e.g., scaffold, patch, spray, microneedle), and responsiveness (e.g., temperature, pH, and protein), which enables customized sEV therapy tailored to specific diseases. This review demonstrates biomaterial‐facilitated local delivery of stem cell‐derived sEVs as a viable alternative or even a superior option to systemic sEV therapy.