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.

Efficiency of Multifunctional Antibacterial Hydrogels for Chronic Wound Healing in Diabetes: A Comprehensive Review

“…Photodynamic and photothermal are also widely used in wound antibacterial applications by combining with hydrogels. 88 , 89 Effective antibacterial hydrogels can help to heal patients’ wounds and reduce the pain from chronic diabetic wounds as well as reduce the healthcare burden.…”

A Narrative Review on Means to Promote Oxygenation and Angiogenesis in Oral Wound Healing

“…Many different types of hydrogel dressings have been investigated, with the aim of enhancing wound healing by promoting angiogenesis while at the same time scavenging ROS. They include alginate, paramylon, fibrinogen, hyaluronic acid, silk fibroin, and carboxymethyl cellulose, among others [ 67 , 68 , 69 , 70 , 71 ]. A different approach is the administration of tOT to the affected areas in patients with peripheral arterial disease (PAD) using a local boot that delivers 100% oxygen to the wound at 1.03 atm [ 72 ].…”

A Wound-Friendly Antibacterial Hyaluronic Acid Dressing with On-Demand Removability for Infected Wound Healing

“…This further indicated that the stability of 8% HA-EPL was better than 4% and 6% HA-EPL. Besides, dressings with the injectable property have various advantages such as ease of operation and matching with the wound perfectly (Figure S3) [34]. As shown in Fig.…”