Doping proanthocyanidins into gel/zirconium hybrid hydrogel to reshape the microenvironment of diabetic wounds for healing acceleration

Infection and chronic inflammation caused by oxidative stress are major challenges in chronic wound healing. Preparing a simple, efficient hydrogel with reactive oxygen–scavenging properties for chronic wound repair is a promising strategy. Herein, we report an injectable, self-repairing hydrogel with antioxidant and antibacterial properties that can be used to regenerate diabetic wounds. Hydrogels are prepared by coordination crosslinking of gelatin (Gel), a natural biopolymer derived from collagen, with Zr4+. Because of the dynamic properties of metal ion coordination bonds and the bactericidal effect of Zr4+, the obtained coordination hydrogels exhibit self-healing, injectable, and antibacterial properties. The plant polyphenol "proanthocyanidins," which has reactive oxygen–scavenging and anti-inflammatory effects, was simultaneously loaded into the coordination hydrogel during cross-linking. We obtained a versatile hydrogel that is easy to prepare, resistant to mechanical irritation, and antioxidant, and antibacterial in vitro. We further demonstrated that the injectable self-healing hydrogels could effectively repair diabetic skin wounds and accelerate collagen deposition and wound healing. This study shows that the multifunctional antioxidant hydrogel has great potential in developing multifunctional biomaterials for chronic wound healing.