Lu Daoqiang, Yu Wenchong, Zhao Danni, Qi Fei, Wang Xiu, Fu Qiang, Li Jie, Yang Fang, Li Riwang, Wang Xiaoxiao, Lan Haotian, Wang Jieyan, Zhang Honglin, Liu Dahai, Wang Jun, Zhao Xiaodong
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510280, Guangdong Province, China; Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Animal Science and Technology, Foshan University, Foshan 528231, Guangdong Province, China.
Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan 528031, Guangdong Province, China.
Int J Biol Macromol. 2025 Aug;319(Pt 4):145615. doi: 10.1016/j.ijbiomac.2025.145615. Epub 2025 Jun 27.
Hydrogel wound dressings have shown promising potential for treating diabetic wounds, but their efficacy is limited by the complex wound microenvironment and the lack of integrated treatment strategies. In this study, a series of multifunctional hydrogel adhesives with anti-inflammatory, antibacterial, and angiogenesis-promoting properties was synthesized using free radical polymerization. The raw materials included methacrylated hyaluronic acid (HAMA), 3-(bis(pyridin-2-ylmethyl)amino)propyl methacrylate (DPAMA), and N-[tris(hydroxymethyl)methyl]acrylamide (THMA). Cu ions were incorporated into the hydrogels through their strong affinity for dipicolylamine and carboxylic acid groups. Adhesion strength of the hydrogel ranged from 8 to 14 kPa, and tensile strength was 14.9 kPa. The inhibition zones against Escherichia coli and Staphylococcus aureus were 16.16 mm and 14.5 mm, respectively. ELISA results showed that the HTDC2 hydrogel (containing 3 mg/mL Cu) significantly reduced TNF-α and IL-1β expression. The HTDC2 hydrogel significantly promoted full-thickness skin wound healing in diabetic mice, achieving over 85 % closure by day 14. Western blot data showed that TNF-α and IL-1β protein levels in HTDC2 group decreased 3.5-fold on day 10 compared with control. Angiogenesis, immunofluorescence, and immunohistochemistry results confirmed that HTDC2 promoted angiogenesis and reduced pro-inflammatory factor expression. In summary, the proposed supramolecular polymer/hyaluronic acid hydrogel is promising as a diabetic wound dressing.
水凝胶伤口敷料在治疗糖尿病伤口方面已显示出有前景的潜力，但其疗效受到复杂的伤口微环境和缺乏综合治疗策略的限制。在本研究中，使用自由基聚合合成了一系列具有抗炎、抗菌和促血管生成特性的多功能水凝胶粘合剂。原料包括甲基丙烯酸化透明质酸（HAMA）、甲基丙烯酸3-(双(吡啶-2-基甲基)氨基)丙酯（DPAMA）和N-[三(羟甲基)甲基]丙烯酰胺（THMA）。通过铜离子与二吡啶甲胺和羧酸基团的强亲和力将其引入水凝胶中。水凝胶的粘附强度范围为8至14 kPa，拉伸强度为14.9 kPa。对大肠杆菌和金黄色葡萄球菌的抑菌圈分别为16.16 mm和14.5 mm。ELISA结果表明，HTDC2水凝胶（含3 mg/mL铜）显著降低了TNF-α和IL-1β的表达。HTDC2水凝胶显著促进了糖尿病小鼠全层皮肤伤口的愈合，在第14天时伤口闭合率超过85%。蛋白质印迹数据显示，与对照组相比，HTDC2组在第10天时TNF-α和IL-1β蛋白水平下降了3.5倍。血管生成、免疫荧光和免疫组织化学结果证实，HTDC2促进了血管生成并降低了促炎因子的表达。总之，所提出的超分子聚合物/透明质酸水凝胶有望成为一种糖尿病伤口敷料。
