Immune‐Vascular Synergy: A Photodynamic Hydrogel Activating ALDH2 to Combat Inflammation and Enhance Angiogenesis in Diabetic Wound Healing

Abstract Infected diabetic wounds present serious therapeutic challenges, primarily due to persistent infections, impaired immune responses, and insufficient vascularization. Excessive secretion of neutrophil extracellular traps (NETs) is increasingly recognized as a key driver of inflammation in diabetic wounds. Single‐cell sequencing analysis of clinical specimens reveals a deficiency in aldehyde dehydrogenase 2 (ALDH2) within wound tissues, which plays a critical role in sustaining inflammation and hindering vascular regeneration. Unlike conventional treatments that focus on either infection control or vascular repair, a photodynamic hydrogel with a dual‐function strategy is developed, uniquely integrating ALDH2 activation with immune‐vascular modulation to address these multifaceted challenges. The hydrogel‐mediated activation of ALDH2 effectively reduces NET formation and mitigates chronic inflammation, while promoting macrophage polarization from the pro‐inflammatory M1 phenotype to the reparative M2 phenotype. This transition fosters an anti‐inflammatory microenvironment that not only facilitates tissue repair but also enhances angiogenesis by stimulating endothelial cell activity, improving vascularization at the wound site. In contrast to existing therapeutics, the approach directly targets the interplay between immune regulation and vascular regeneration, offering a synergistic mechanism to enhance wound healing outcomes. The findings introduce an immune‐vascular synergy‐based therapeutic strategy, emphasizing the translational potential of this hydrogel technology for chronic wound management.