A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing

Hyaluronic acid (HA)-based biopolymer hydrogels are promising therapeutic dressings for various wounds but still underperform in treating diabetic wounds. These wounds are extremely difficult to heal and undergo a prolonged and severe inflammatory process due to bacterial infection, overexpression of reactive oxygen species (ROS), and insufficient synthesis of NO. In this study, a dynamic crosslinked hyaluronic acid (HA) hydrogel dressing (Gel-HAB) loaded with allomelanin (AMNP)-N, N′-dis-sec-butyl-N, N′-dinitroso-1, 4-phenylenediamine (BNN6) nanoparticles (AMNP-BNN6) was developed for healing diabetic wounds. The dynamic acylhydrazone bond formed between hydrazide-modified HA (HA-ADH) and oxidized HA (OHA) makes the hydrogel injectable, self-healing, and biocompatible. The hydrogel, loaded with AMNP-BNN6 nanoparticles, exhibits promising ROS scavenging ability and on-demand release of nitric oxide (NO) under near-infrared (NIR) laser irradiation to achieve mild photothermal antibacterial therapy (PTAT) (∼ 48 °C). Notably, the Gel-HAB hydrogel effectively reduced the oxidative stress level, controlled infections, accelerated vascular regeneration, and promoted angiogenesis, thereby achieving rapid healing of diabetic wounds. The injectable self-healing nanocomposite hydrogel could serve as a mild photothermal-enhanced antibacterial, antioxidant, and nitric oxide release platform for the treatment of diabetic wounds.