Extracellular vesicles and their engineering strategies, delivery systems, and biomedical applications.

Extracellular vesicles are nanoscale vesicles that can be secreted by all cell types, are intracellular in origin and have the same composition as their parent cells, play a key role in intercellular communication in organismal health and disease, and are now often used as biomarkers of disease and therapeutic agents in biomedical research. When injected locally or systemically, they have the ability to provide a variety of therapeutic effects, for example, regeneration of skin damage or restoration of cardiac function. However, direct injection of extracellular vesicles may result in their rapid clearance from the injection site.In order to maintain the biological activity of extracellular vesicles and to control the release of effective concentrations for better therapeutic efficacy during long-term disease treatment, the design of an optimized drug delivery system is necessary and different systems for the continuous delivery of extracellular vesicles have been developed. This paper first provides an overview of the biogenesis, composition and physiological function of extracellular vesicles, followed by a review of different strategies for extracellular vesicle isolation and methods for engineering extracellular vesicles. In addition, this paper reviews the latest extracellular vesicle delivery platforms such as micro-nanoparticles, injectable hydrogels, microneedles and scaffold patches. At the same time, the research progress and key cases of extracellular vesicle delivery systems in the field of biomedical therapeutics are described. Finally, the challenges and future trends of extracellular vesicle delivery are discussed.