Xiong Yuan, Wu Qipeng, Zhang Peng, Liao Jiewen, Hu Hui, Shahbazi Mohammad-Ali, Zhao Yanli, Mi Bobin
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Small Methods. 2025 Jul;9(7):e2500391. doi: 10.1002/smtd.202500391. Epub 2025 May 13.
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.
感染性糖尿病伤口带来了严峻的治疗挑战，主要原因在于持续感染、免疫反应受损以及血管化不足。嗜中性粒细胞胞外诱捕网（NETs）的过度分泌日益被认为是糖尿病伤口炎症的关键驱动因素。对临床标本的单细胞测序分析显示，伤口组织中醛脱氢酶2（ALDH2）缺乏，而该酶在维持炎症和阻碍血管再生方面起关键作用。与专注于感染控制或血管修复的传统治疗方法不同，开发了一种具有双重功能策略的光动力水凝胶，独特地将ALDH2激活与免疫 - 血管调节相结合，以应对这些多方面的挑战。水凝胶介导的ALDH2激活有效减少NET形成并减轻慢性炎症，同时促进巨噬细胞从促炎M1表型向修复性M2表型极化。这种转变促进了抗炎微环境的形成，不仅有利于组织修复，还通过刺激内皮细胞活性增强血管生成，改善伤口部位的血管化。与现有疗法相比，该方法直接针对免疫调节与血管再生之间的相互作用，提供了一种协同机制来提高伤口愈合效果。这些发现引入了一种基于免疫 - 血管协同作用的治疗策略，强调了这种水凝胶技术在慢性伤口管理中的转化潜力。
