Enhancing diabetic wound healing with a pH-responsive nanozyme hydrogel featuring multi-enzyme-like activities and oxygen self-supply.

Diabetic wound treating remains a challenging due to bacterial infections, oxidative stress, tissue hypoxia, and high glucose levels. Herein, a multi-enzyme-like activities nanocomposite (Mo,Fe/Cu,I-Ag@GOx) was designed and anchored to a multifunctional fluorescence hydrogel. The nanozyme gel, loaded with glucose-oxidase (GOx), exhibits intrinsic GOx, peroxidase (POD)-, oxidase (OXD)-, catalase (CAT)- and superoxide dismutase (SOD)-like activities with pH-switchable glucose-initiated cascade reaction for diabetic wound healing. In the first cascade-reaction, initiated by GOx, the nanozyme gel catalyzes glucose and O2 into gluconic acid and H2O2 to further generate superoxide anion radical (O2·-) and hydroxyl radicals (·OH) to eradicate bacteria. In the second cascade-reaction, as the wound pH changes alkalescent microenvironment, the nanozyme gel simulates SOD to transform O2·- into O2 and H2O2, and then decomposes endogenous and exogenous H2O2 into O2 via CAT-like activity to reduce oxidative stress and alleviate hypoxia. The gel by calcium ion (Ca2+) cross-linked sodium alginate (SA) and chitosan (CS) containing nanozyme was constructed with injectability, adhesion and fluorescence properties, as well as beneficial biocompatible. Importantly, the water/alcohol solubility of the nanozyme gel allows it to be used as a dressing without causing secondary injury to the wound. The multifunctional fluorescence hydrogel exhibits efficiently promote pro-angiogenesis and bacteria-infected wound healing.

A multi-enzyme-like activity exhibiting mussel-inspired nanozyme hydrogel for bacteria-infected wound healing.

Bacterial infection, tissue hypoxia, and inflammatory and oxidative stress are several key problems in wound healing of chronic infections. Herein, a multi-enzyme-like activity exhibiting multifunctional hydrogel made up of mussel-inspired carbon dot reduced-Ag (CDs/AgNPs) and Cu/Fe-nitrogen-doped carbon (Cu,Fe-NC) was designed. Due to the loss of glutathione (GSH) and oxidase (OXD)-like activity of the nanozyme (decomposes O2 to generate a superoxide anion radical (O2˙-) and hydroxyl radical production (˙OH)), the multifunctional hydrogel exhibited excellent antibacterial performance. More importantly, during the bacterial elimination within the inflammatory phase of wound healing, the hydrogel could act as a catalase (CAT)-like agent to supply adequate O2 by catalyzing intracellular H2O2 for hypoxia abatement. The catechol groups on the CDs/AgNPs endowed them with the dynamic redox equilibrium properties of phenol-quinones, thus providing the hydrogel with mussel-like adhesion properties. The multifunctional hydrogel was shown to excellently promote bacterial infection wound healing and maximize the efficiency of nanozymes.