Tailored Extracellular Vesicles: Novel Tool for Tissue Regeneration.

Extracellular vesicles (EVs) play an essential part in multiple pathophysiological processes including tissue injury and regeneration because of their inherent characteristics of small size, low immunogenicity and toxicity, and capability of carrying a variety of bioactive molecules and mediating intercellular communication. Nevertheless, accumulating studies have shown that the application of EVs faces many challenges such as insufficient therapeutic efficacy, a lack of targeting capability, low yield, and rapid clearance from the body. It is known that EVs can be engineered, modified, and designed to encapsulate therapeutic cargos like proteins, peptides, nucleic acids, and drugs to improve their therapeutic efficacy. Targeted peptides, antibodies, aptamers, magnetic nanoparticles, and proteins are introduced to modify various cell-derived EVs for increasing targeting ability. In addition, extracellular vesicle mimetics (EMs) and self-assembly EV-mimicking nanocomplex are applied to improve production and simplify EV purification process. The combination of EVs with biomaterials like hydrogel, and scaffolds dressing endows EVs with long-term therapeutic efficacy and synergistically enhanced regenerative outcome. Thus, we will summarize recent developments of EV modification strategies for more extraordinary regenerative effect in various tissue injury repair. Subsequently, opportunities and challenges of promoting the clinical application of engineered EVs will be discussed.