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

Abstract

Stem cell‐derived small extracellular vesicles that are either naturally produced or pharmacogenetically engineered 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, such as infusion toxicity, immunogenicity, tumorigenic potential, and ethical issues. The two routine modalities of sEV administration are systemic injection and local delivery, each presenting distinct benefits and drawbacks. Various biomaterials have been developed to assist their local delivery to improve the targeting of organs, minimize non‐specific accumulation in vital organs, and ensure the protection and release of sEVs. Based on a thorough search and meticulous dissection of relevant literature from the past five years, we present this comprehensive, up‐to‐date, specialty‐specific, disease‐oriented, and preclinical review to expound on the surgical application and potential of stem cell‐derived sEVs. The local delivery of stem cell‐derived sEVs, which possess similar indications as systemic transfer, could 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. Future collaboration among surgeons, biomaterial scientists, and stem cell researchers is essential to advance this research area.This article is protected by copyright. All rights reserved