A double-network porous hydrogel based on high internal phase emulsions as a vehicle for potassium sucrose octasulfate delivery accelerates diabetic wound healing

Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix (ECM) 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 emulsions (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit matrix metalloproteinases (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.