Restoring Endothelial Mitochondrial Homeostasis With a Bioactive Nanoshield Promotes Vascular Regeneration on...

Defective endothelial regeneration constitutes a fundamental barrier to durable vascular repair. By integrating single cell RNA-sequencing data from rat carotid balloon injury with ultrastructural and histological evidence from rabbit stented arteries, we identified mitochondrial disorganization and dysfunction as common features of injured endothelial cells. Guided by these findings, we developed a poly(citrate-polyglycol-procyanidin) (PCGP) nanoshield to couple mitochondrial protection with anticoagulant and immunoregulatory functions for cardiovascular devices. PCGP preserved mitochondrial integrity, restored endothelial metabolic homeostasis, and rescued the regenerative phenotype of endothelial cells under oxidative stress. In rabbit arterial stent models, this intervention reactivated the PI3K/AKT/eNOS-nitric oxide axis, accelerated functional re-endothelialization, and markedly suppressed neointimal hyperplasia. Collectively, these findings support restoration of endothelial mitochondrial homeostasis as an important mechanistic axis associated with vascular repair.