Wang Zhiwei, Sun Lingshun, Wang Weixing, Wang Zheng, Shi Ge, Dai Honglian, Yu Aixi
Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430070, China.
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China.
Regen Biomater. 2024 Mar 12;11:rbae024. doi: 10.1093/rb/rbae024. eCollection 2024.
Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsion (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit MMPs, increase angiogenesis and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both and studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance and excellent mechanical properties.
糖尿病伤口是一项棘手的医学难题。糖尿病伤口中基质金属蛋白酶-9(MMP-9)的过度分泌会进一步降解细胞外基质和生长因子,并导致严重的血管损伤,这严重阻碍了糖尿病伤口的愈合。为了解决这些问题,通过高内相乳液(HIPE)技术构建了一种由聚(甲基丙烯酸甲酯-共-丙烯酰胺)(p(MMA-共-AM))和聚乙烯醇(PVA)组成的双网络多孔水凝胶,用于递送蔗糖八硫酸酯钾(PSO),这是一种能够抑制MMPs、促进血管生成并改善微循环的药物。该水凝胶具有典型的聚HIPE分级微观结构,具有相互连通的多孔形态、高孔隙率、高比表面积、优异的机械性能和合适的溶胀性能。同时,p(MMA-共-AM)/PVA@PSO水凝胶表现出高载药性能和PSO的有效释放。此外,体外和体内研究均表明,p(MMA-共-AM)/PVA@PSO水凝胶具有良好的生物相容性,通过抑制糖尿病伤口中过量的MMP-9、增加生长因子分泌、改善血管化、增加胶原蛋白沉积和促进再上皮化,显著加速了糖尿病伤口的愈合。因此,本研究为糖尿病伤口愈合提供了一种可靠的治疗策略,为合理设计和制备具有高孔隙率、高载药性能和优异机械性能的伤口水凝胶敷料提供了一些理论依据和新的见解。