Plant-derived extracellular vesicles in diabetic wound healing: mechanisms, therapeutic implications and future perspectives

Diabetic wound healing remains a significant clinical challenge, characterized by a protracted and uncertain prognosis. Extracellular vesicles (EVs), functioning as natural carriers released by living cells, play a pivotal role in intercellular communications by delivering diverse bioactive cargo. In recent years, plant-derived extracellular vesicles (PDEVs) have garnered increasing attention due to their inherent biocompatibility, safety, low immunogenicity, and abundant source availability. PDEVs are regarded as a highly promising cell-free therapeutic strategy for diabetic wound healing. This review systematically summarizes the research progress on PDEVs biogenesis, physiological functions and their underlying mechanisms, and isolation/characterization methodologies. Specifically, we explore the potential of PDEVs as drug delivery vehicles and discuss engineering strategies for their modification. Finally, we provide a critical analysis of the potential challenges associated with translating PDEVs into cell-free therapeutics for diabetic wounds and offer perspectives on future research directions.