Engineered Extracellular Vesicles as Bioinspired Nanoplatforms for Ischemia–Reperfusion Injury Therapy

Abstract Ischemia–reperfusion injury (IRI) is a major cause of tissue damage in patients with myocardial infarction, stroke, acute kidney injury, and intestinal Ischemia. Restoring blood flow is necessary for tissue survival, but injury is often worsened by reperfusion through too much oxidative stress, inflammation without infection, and controlled cell death. As a result, current therapies are limited in their effectiveness. Extracellular vesicles (EVs) are small vesicles with a lipid bilayer, and they are released by most cell types. These EVs have become a possible cell-free treatment for IRI. Their high biocompatibility, intrinsic immunomodulatory properties, and organ-targeting capability enable the efficient delivery of protective and regenerative biomolecules across physiological barriers. This review sums up new progress in treatments that use EVs for IRI in several organ systems, and it also pays attention to three related parts. The first part is about the main ways EVs may work in treatment, and these ways include effects that reduce damage from oxidation, lower inflammation, and help tissues repair. This review discusses these points as well. Second, this review also describes that EVs derived from stem cells, endothelial cells, and immune cells show functional heterogeneity. In other words, the functions of these EVs are not the same, and this point is also discussed here. Third, some recent engineering methods are also stressed,such as surface modification, cargo loading, and biomaterial-assisted delivery, are highlighted. The review also pays attention to these methods.This review does more than sum up the progress that already exists; it also discusses an important gap, that is, how to make more reasonable design plans that link EVs with IRI therapy; in addition, this review addresses some key problems in turning these findings into practical use, and these problems include producing EVs in large amounts, controlling their quality, and checking whether they are safe in the body.