A self-oxygenating polyphenol-nanozyme hydrogel remodels the inflammatory microenvironment for diabetic wound healing

Abstract Diabetic wounds are characterized by prolonged hyperglycemia and associated hypoxia, induce oxidative stress and sustained inflammation, which collectively impair angiogenesis and hinder the healing process. Conventional oxygen‑supplying hydrogel dressings are often limited by inefficient oxygen release, poor stability, and insufficient multifunctionality. To overcome these limitations, we have designed a GelMA–MnPZC multifunctional nanocomposite hydrogel dressing capable of stable and prolonged oxygen release. This hydrogel remodels the hypoxic and inflammatory wound microenvironment through sustained oxygen generation and polyphenol‑mediated activity, thereby creating favorable conditions for angiogenesis and tissue regeneration. The hydrogel was fabricated by embedding polydopamine–manganese (PDA–Mn) nanozyme‑modified, ZIF‑8‑encapsulated CaO2 nanoparticles into a gelatin-methacryloyl (GelMA) network. The ZIF‑8 shell enhances the stability of CaO2, while the PDA‑Mn nanozyme exhibits catalase‑like activity, together ensuring a stable and efficient self‑oxygenating capability under hypoxic conditions. Furthermore, the hydrogel’s excellent tissue adhesion ensures long-term stable wound management. Additionally, sustained release of Zn2+ and Mn2+ ions provide potent antibacterial activity, reducing the risk of wound infection. In summary, the GelMA–MnPZC hydrogel accelerates diabetic wound healing through a coordinated multifunctional mechanism, including antibacterial action, oxidative stress mitigation, hypoxia alleviation, and immunomodulation. This innovative self‑oxygenating hydrogel represents a promising clinical strategy for the comprehensive treatment of diabetic wounds.