Four-in-one pH/glucose-responsive engineered hydrogel for diabetes wound healing

The healing of diabetic wounds persists as a significant clinical challenge globally, attributed to factors involving microbial colonization, disrupted redox homeostasis, persistent inflammatory responses, and compromised vascular regeneration. Currently, therapeutic strategies that are clinically effective are not available. In this research, we developed a four-in-one multifunctional hydrogel, PPy&L-arg@PVA-TSPBA (PLPT), with self-healing, adhesive, and microenvironment-responsive properties by reacting phenylboronic acid groups with the hydroxyl groups of polyvinyl alcohol. The hydrogel was loaded with the antioxidant polypyrrole (PPy) and the angiogenesis-promoting compound L-arginine (L-arg). The borate ester bonds in the hydrogel respond to the high glucose and low pH microenvironment characteristic of infected diabetic wounds, thereby triggering the controlled release of therapeutic agents. Additionally, PPy imparts excellent photothermal properties to the hydrogel and kills bacteria through localized high temperatures. The PLPT hydrogel demonstrated pronounced anti-inflammatory efficacy and enhanced neovascularization capacity through suppression of IL-6/TNF-α pro-inflammatory factors coupled with up-regulation of VEGF and CD31. Cytotoxicity and hemolysis tests demonstrate that the hydrogel exhibits favorable biocompatibility. In vivo experiments show that PLPT accelerates wound healing in diabetic SD rats through a synergistic effect of bacterial eradication, oxidative stress mitigation, inflammation suppression, and angiogenesis promotion, which together facilitate extracellular matrix reconstruction and collagen deposition. In summary, the PLPT hydrogel have a significantly potential clinical application in the treatment of infected wounds in diabetes.