A novel pH/ROS dual responsive engineering hydrogels based on poly(tannic acid)-assisted surface deposition of nano-enzymes with efficient antibacterial and antioxidant activity for diabetic wound healing

Oxygen deficiency, reduced angiogenesis, increased oxidative stress, and infection are critical clinical features contributing to the non-healing of chronic diabetic wounds. Engineered hydrogels capable of exerting both antioxidant stress and promoting angiogenesis may offer improved clinical efficacy for the healing of diabetic wounds in such adverse conditions. This study introduces a unique and intelligent composite hydrogel designed to address the harsh microenvironment of diabetic wounds. The basic framework of the hydrogel network is formed through Schiff's base reaction between hydrazide-modified hyaluronic acid and aldehyde-modified pectin. The hydrogel, containing polydopamine and a metal–organic framework-derived catalytic enzyme mimic (ε-polylysine-coated mesoporous manganese cobalt oxide), efficiently exhibits antioxidant activity, clearing excessive reactive oxygen species (ROS) from the wound. Additionally, it can synergistically perform oxygen generation through ROS-driven catalytic oxygenation. This biomaterial demonstrates outstanding hemostatic activity, biocompatibility, and antioxidant properties, protecting skin cells from ROS and hypoxia-induced death and proliferation inhibition. It effectively accelerates the healing of full-thickness skin wounds in diabetic rats. Further mechanistic studies indicate its ability to promote the polarization of macrophages towards an anti-inflammatory phenotype, alleviating chronic wound inflammation, and significantly improving epithelial regeneration, angiogenesis, and collagen deposition. This work proposes an effective strategy based on antioxidant and nanozyme-enhanced hydrogels, positioning them as ROS-driven oxygenators with the potential to treat diabetic wounds.