Artificial\nNonenzymatic Antioxidant MXene Nanosheet-Anchored\nInjectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release\nPlatform for Diabetic Wound Healing

Abstract

Hypoxia,\nexcessive reactive oxygen species (ROS), impaired angiogenesis,\nlasting inflammation, and bacterial infection, are key problems impeding\ndiabetic wound healing. Particularly, controllable oxygen release\nand ROS scavenging capacities are critical during the wound healing\nprocess. Here, an injectable hydrogel based on hyaluronic acid-<i>graft</i>-dopamine (HA-DA) and polydopamine (PDA) coated Ti₃C₂ MXene nanosheets is developed catalytically\ncross-linked by an oxyhemoglobin/hydrogen (HbO₂/H₂O₂) system combined with mild photothermal stimulation\nfor diabetic wound healing. HbO₂ not only acts as a horseradish\nperoxidase-like to catalyze the hydrogel formation but also as an\noxygen carrier to controllably release oxygen when activated by the\nmild heat produced from near-infrared (NIR) irradiation. Specifically,\nHbO₂ can provide oxygen repeatedly by binding oxygen in\nthe air when the NIR is off. The stable photoresponsive heating behavior\nof MXene ensures the repeatable oxygen release. Additionally, artificial\nnonenzymatic antioxidant MXene nanosheets are proposed to scavenge\nexcessive reactive nitrogen species and ROS including H₂O₂, O₂^•–, and ^•OH, keeping the intracellular redox homeostasis and\nalleviating oxidative stress, and eradicate bacteria to avoid infection.\nThe antioxidant and antibacterial abilities of MXene are further improved\nby PDA coating, which also promotes the MXene nanosheets cross-linking\ninto the network of the hydrogel. HA-DA molecules endow the hydrogel\nwith the capacity to regulate macrophage polarization from M1 to M2\nto achieve anti-inflammation. More importantly, the MXene-anchored\nhydrogel with multifunctions including tissue adhesion, self-healing,\ninjectability, and hemostasis, combined with mild photothermal stimulation,\ngreatly promotes human umbilical vein endothelial cell proliferation\nand migration and notably facilitates infected diabetic wound healing.