Precisely Engineering a ROS‐Regulatable Decellularized Matrix to Rejuvenate Endogenous Repair for Heart Valve Remodeling in Diabetic Cohort

The reconstruction of a heart valve through in situ tissue engineering remains a formidable challenge, particularly for patients with diabetes mellitus, because the pathophysiological alterations associated with diabetes substantially impair the cardiovascular system's intrinsic repair capacity. In this study, reactive oxygen species (ROS) regulation are integrated into the fabrication of pro‐endothelialization interfaces to counteract the adverse repair environment. Specifically, a heparin‐mimicking alginate‐derived glycopeptide and the natural ROS scavenger melanin are modified onto the surface of a decellularized extracellular matrix (dECM). This tailored interface significantly enhances endothelial cell (EC) adhesion while reducing platelet adhesion. The incorporation of melanin effectively suppresses ROS elevation in ECs and macrophages under hyperglycemic conditions. Consequently, this intervention promotes EC rejuvenation by enhancing proliferation, migration, and anti‐apoptotic capabilities, while concurrently attenuating the release of inflammatory and pro‐fibrotic factors by macrophages. The dECM is intravascularly implanted in a diabetic rabbit model after being fabricated into a covered stent, demonstrating favorable remodeling characteristics such as enhanced endothelialization and reduced fibrotic deposition. This scaffold design, specifically tailored to the pathological conditions of diabetes, offers a precise biomaterial strategy for in situ heart valve tissue engineering. This study develops a novel heart valve scaffold for in situ tissue engineering that enhances remodeling in diabetic cohorts by integrating reactive oxygen species regulation and a pro‐endothelialization interface. This approach effectively counteracts the comprised intrinsic repair capacity of pathological systems, providing insights into a patient‐specific, environment‐directed scaffold design strategy for in situ tissue engineering.