Li Zhen, Guan Shiyao, Duan Xiao, Wang Liying, Zhang Zhen, Wu Jun
Changzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Changzhi, Changzhi 046000, China; School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou 511400, China.
Int J Biol Macromol. 2025 Jul;318(Pt 2):144944. doi: 10.1016/j.ijbiomac.2025.144944. Epub 2025 Jun 3.
Diabetic wounds present significant challenges due to persistent inflammation and impaired angiogenesis, often resulting in delayed healing or, in severe cases, amputation. Hence, there is an urgent need for innovative wound dressings tailored to the specific needs of diabetic wounds. Deferoxamine (DFO) and metformin (Met) offer promising properties for promoting angiogenesis and modulating the immune-inflammatory response, respectively, but their burst release limits their further application in wound management. Based on this, we developed a novel multifunctional diabetic wound dressing composed of DFO-grafted hyaluronic acid methacrylate (HAMA) hydrogel loaded with Met (Met/DMA hydrogel). In vitro studies demonstrated that the Met/DMA hydrogel enhances fibroblast proliferation and migration, reduces intracellular reactive oxygen species, and accelerates endothelial cell angiogenesis and macrophage polarization to an anti-inflammatory phenotype. Animal experiments further revealed that the hydrogel significantly accelerated wound healing in diabetic rats (41.6±8.7 % improvement vs. control group) by promoting neovascularization, collagen maturation, and regulation of the inflammatory microenvironment at the wound site. In conclusion, this study successfully developed a Met/DMA hydrogel platform that effectively treats diabetic wounds through synergistic promotion of angiogenesis and modulation of the immune-inflammatory response.
糖尿病伤口由于持续的炎症和血管生成受损而面临重大挑战，常常导致愈合延迟，严重时甚至需要截肢。因此，迫切需要针对糖尿病伤口的特定需求定制创新的伤口敷料。去铁胺（DFO）和二甲双胍（Met）分别具有促进血管生成和调节免疫炎症反应的良好特性，但它们的突释限制了它们在伤口处理中的进一步应用。基于此，我们开发了一种新型多功能糖尿病伤口敷料，它由负载Met的DFO接枝甲基丙烯酸透明质酸（HAMA）水凝胶组成（Met/DMA水凝胶）。体外研究表明，Met/DMA水凝胶可增强成纤维细胞的增殖和迁移，减少细胞内活性氧，并加速内皮细胞血管生成和巨噬细胞向抗炎表型的极化。动物实验进一步表明，该水凝胶通过促进新血管形成、胶原蛋白成熟以及调节伤口部位的炎症微环境，显著加速了糖尿病大鼠的伤口愈合（与对照组相比提高了41.6±8.7%）。总之，本研究成功开发了一种Met/DMA水凝胶平台，通过协同促进血管生成和调节免疫炎症反应有效治疗糖尿病伤口。
