Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing

Abstract

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.