Engineered extracellular vesicles for precision renal therapy: Bioengineering strategies and clinical translation

Abstract Extracellular vesicles (EVs) have emerged as promising nanotherapeutics for kidney diseases due to their innate biocompatibility, barrier penetration, and regenerative cargo delivery. However, native EVs face critical limitations including low drug‐loading efficiency, poor renal targeting, and batch heterogeneity, hampering their clinical utility. Recent advances in EV bioengineering—encompassing cargo loading (electroporation, transfection), membrane modification (ligand conjugation, biomimetic vesicles), and donor cell preconditioning (hypoxia, pharmacological priming)—have significantly enhanced therapeutic precision and efficacy. Integration with biomaterials (e.g., responsive hydrogels, scaffolds) further enables sustained release and targeted delivery, improving outcomes in kidney injury models. This review systematically analyzes these innovative strategies, highlighting mechanistic insights, comparative advantages, and unresolved challenges. We critically evaluate ongoing clinical trials and propose scalable manufacturing solutions and regulatory frameworks to accelerate translation. Engineered EVs represent a next‐generation platform for personalized renal nanomedicine, poised to bridge the regenerative potential with clinical reality.