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 dama...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 in vitro and in vivo 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.展开更多
基金supported by the National Key Research and Development Program of China(2022YFB4601402)the National Natural Science Foundation of China(32201109,51772233,82072446)+3 种基金the Guangdong Basic and Applied Basic Research Foundation(2022B1515120052,2021A1515110557)the Key Basic Research Program of Shenzhen(JCYJ20200109150218836)the Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory(HJL202202A002)the Trauma Microsurgery Clinical Medical Research Center of Hubei Province and the Health Commission of Hubei Province Medical Leading Talent Project(LJ20200405).
文摘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 in vitro and in vivo 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.
