Nanozyme doped chitosan hydrogel driven by glucose oxidase for dual regulation of ROS homeostasis and macrophage reprogramming in diabetic wound healing

Nov 30, 2025Carbohydrate polymers

Glucose-powered nanozyme hydrogel helps balance harmful molecules and change immune cells to improve healing of diabetic wounds

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

A multifunctional hydrogel delivery system based on tannic acid-Cu chelated CeO nanoparticles significantly accelerated wound re-epithelialization in a diabetic mouse model.

The hydrogel system incorporates glucose oxidase to generate hydrogen peroxide at the wound site, which is then converted to oxygen, alleviating tissue hypoxia.
CeO nanoparticles scavenge reactive oxygen species, reducing oxidative stress and promoting the M2 polarization of macrophages to regulate inflammation.
The pH-responsive release of copper from the tannic acid-Cu complex targets antibacterial action in the acidic environment of infected wounds.
In vitro studies show strong reactive oxygen species-scavenging capacity and favorable pH-dependent release properties of the hydrogel.
The hydrogel improved angiogenesis and tissue oxygenation while reducing bacterial infection in the diabetic mouse model.

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Diabetic wounds are characterized by persistent oxidative stress, dysregulated inflammation, hypoxia due to impaired microcirculation, and heightened susceptibility to infection, posing significant challenges for effective treatment. In this work, a multifunctional hydrogel delivery system based on tannic acid-Cu(TA/Cu) chelated CeOnanocomposites was developed for synergistic diabetic wound repair. The system utilizes a succinyl chitosan-PVA hydrogel matrix incorporating glucose oxidase (GOx), which specifically catalyzes excess glucose at the wound site to generate HO. The CeOnanoparticles then decompose HOinto Othrough their catalase-like activity, effectively alleviating tissue hypoxia. Additionally, CeOscavenges reactive oxygen species (ROS), significantly reducing oxidative stress while promote the polarization of macrophages toward the M2 phenotype to regulate wound inflammation. The TA/Cu complex exhibits pH-responsive release of Cuin the acidic infection microenvironment, enabling targeted antibacterial action. In vitro studies demonstrated the excellent ROS-scavenging capacity of the system, Ogenerating performance, and pH-dependent Curelease properties. In a diabetic mouse model with full-thickness skin defects, the hydrogel significantly accelerated wound re-epithelialization, promoted angiogenesis, reduced bacterial infection, and improved tissue oxygenation. This integrated therapeutic strategy combining "oxidative stress/inflammation regulation and pH-responsive antibacterial activity" offers a novel approach for the treatment of chronic diabetic wounds. 2+ 2+ 2+ 2 2 2 2 2 2 2 2 2

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Nanozyme doped chitosan hydrogel driven by glucose oxidase for dual regulation of ROS homeostasis and macrophage reprogramming in diabetic wound healing

Abstract

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