Hypoxia, excessive reactive oxygen species (ROS), impaired angiogenesis, lasting inflammation, and bacterial infection, are key problems impeding diabetic wound healing. Particularly, controllable oxygen release and ROS scavenging capacities are critical during the wound healing process. Here, an injectable hydrogel based on hyaluronic acid-graft-dopamine (HA-DA) and polydopamine (PDA) coated Ti3C2 MXene nanosheets is developed catalytically cross-linked by an oxyhemoglobin/hydrogen (HbO2/H2O2) system combined with mild photothermal stimulation for diabetic wound healing. HbO2 not only acts as a horseradish peroxidase-like to catalyze the hydrogel formation but also as an oxygen carrier to controllably release oxygen when activated by the mild heat produced from near-infrared (NIR) irradiation. Specifically, HbO2 can provide oxygen repeatedly by binding oxygen in the air when the NIR is off. The stable photoresponsive heating behavior of MXene ensures the repeatable oxygen release. Additionally, artificial nonenzymatic antioxidant MXene nanosheets are proposed to scavenge excessive reactive nitrogen species and ROS including H2O2, O2 •–, and •OH, keeping the intracellular redox homeostasis and alleviating oxidative stress, and eradicate bacteria to avoid infection. The antioxidant and antibacterial abilities of MXene are further improved by PDA coating, which also promotes the MXene nanosheets cross-linking into the network of the hydrogel. HA-DA molecules endow the hydrogel with the capacity to regulate macrophage polarization from M1 to M2 to achieve anti-inflammation. More importantly, the MXene-anchored hydrogel with multifunctions including tissue adhesion, self-healing, injectability, and hemostasis, combined with mild photothermal stimulation, greatly promotes human umbilical vein endothelial cell proliferation and migration and notably facilitates infected diabetic wound healing.

Bacterial infection, tissue hypoxia and inflammatory response can hinder the infected wound repair process. To mitigate the above issues, tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets (MoS 2 @TA/Fe NSs) with dual enzyme activities were developed and anchored to a multifunctional hydrogel. The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy (PTT), glutathione (GSH) loss, and the peroxidase (POD)-like activity (catalyse H 2 O 2 into ·OH under acid condition) of MoS 2 @TA/Fe NSs. Benefitting from the catalase (CAT)-like activity, the hydrogel could decompose H 2 O 2 into O 2 at neutral pH to relieve hypoxia and supply adequate O 2 . POD-like activity was mainly attributed to MoS 2 NSs, while CAT-like activity was primarily due to TA/Fe complex. Moreover, MoS 2 @TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species (ROS) and reactive nitrogen species (RNS) under neutral environment to maintain the balance of antioxidant systems and prevent inflammation. In addition, the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA. TA retained partial phenolic hydroxyl groups, which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels. Due to the dynamic boron ester bonds between polyvinyl alcohol (PVA), dextran (Dex), MoS 2 @TA/Fe, and borax, the hydrogel demonstrated fast self-healing and rapid shape adaptability. This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound, ensuring that it achieved its functions with maximum efficiency. The MoS 2 @TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.

Diabetic wound healing remains challenging owing to the risk for bacterial infection, hypoxia, excessive glucose levels, and oxidative stress. Glucose‐activated cascade reactions can consume glucose and eradicate bacteria, avoiding the direct use of hydrogen peroxide (H2O2) and wound pH restriction on peroxidase‐like activity. However, the anoxic microenvironment in diabetic wounds impedes the cascade reaction due to the oxygen (O2) dependence of glucose oxidation. Herein, defect‐rich molybdenum disulfide nanosheets loaded with bovine serum albumin‐modified gold nanoparticle (MoS2@Au@BSA NSs) heterostructures are designed and anchored onto injectable hydrogels to promote diabetic wound healing through an O2 self‐supplying cascade reaction. BSA decoration decreases the particle size of Au, increasing the activity of multiple enzymes. Glucose oxidase‐like Au catalyzes the oxidation of glucose into gluconic acid and H2O2, which is transformed into a hydroxyl radical (•OH) catalyzed by peroxidase‐like MoS2@Au@BSA to eradicate bacteria. When the wound pH reaches an alkalescent condition, MoS2@Au@BSA mimicks superoxide dismutase to transform superoxide anions into O2 and H2O2, and decomposes endogenous and exogenous H2O2 into O2 via catalase‐like mechanisms, reducing oxidative stress, alleviating hypoxia, and facilitating glucose oxidation. The MoS2@Au@BSA nanozyme‐anchored injectable hydrogel, composed of oxidized dextran and glycol chitosan crosslinked through a Schiff base, significantly accelerates diabetic wound healing.

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