Impaired mitophagy and the accumulation of damaged mitochondria are key drivers of endothelial cell (EC) dysfunction in diabetic wounds. While mitochondrial transplantation (MT) has demonstrated therapeuticpotential in such mitochondrial damage-related diseases, its application is still thwarted by elusive mechanisms and practical hurdles such as poor targeting specificity and low delivery efficiency. Here, wereveal that MT acts by reactivating mitophagy to selectively eliminate dysfunctional mitochondria, therebyrestoring mitochondrial homeostasis and rescuing EC functionality. To exploit this discovery, we engineer abiomimetic MT strategy through coating EC-derived apoptotic vesicle membrane (AVM) onto the surfaceof isolated mitochondria. The resulting mitochondria–AVM complex (Mito-AVM) leverages homologoustargeting and phosphatidylserine-mediated “eat-me” signaling, achieving a remarkable 150% increasein delivery efficiency to ECs in diabetic wounds. Furthermore, we construct a 3-aminophenylboric acid-modified hyaluronic acid/polyvinyl alcohol hydrogel for the diabetic wound microenvironment, enablingreactive oxygen species/glucose-triggered sustained release of encapsulated Mito-AVM at the wound site. In summary, our work elucidates a fundamental mechanism of MT and provides an efficient and targetedstrategy for MT therapy, offering fresh perspectives for diabetic wound treatment.
The research findings have been published in Research under the title "Apoptotic Vesicle Membrane-Mediated Targeted Endothelial Mitochondrial Transplantation-Clearance Therapy for Diabetic Wound Healing."
