Near-infrared light-responsive multifunctional hydrogel for synergistic photothermal/photodynamic/gas therapy to treat MRSA infections and accelerate wound healing

Conventional wound dressings exhibit limited functionality and bacterial-infected wounds may contribute to the development of drug resistance. Consequently, there is a critical demand for multifunctional nanocomposite hydrogels with enhanced antibacterial efficacy to facilitate rapid healing of infected wounds. Here, we developed a cascade reactor hydrogel (APT/OC) for releasing nitric oxide (NO) to achieve near-infrared (1064 nm) light-activated photothermal/photodynamic/gas synergistic therapy for drug-resistant bacteria-infected wounds. APT/OC hydrogel is prepared by inducing with polyphenolic amino acids and reversible crosslinking, using hyaluronic acid (HA), carboxymethyl chitosan (CMCS), L-arginine (L-Arg), polydopamine (PDA) and mesoporous titanium dioxide (m-TiO 2 ). In vitro and in vivo analyses revealed that the synergistic therapeutic effects triggered by near-infrared irradiation significantly inhibited the proliferation and biofilm formation of E. coli and MRSA ，and markedly accelerated the healing of drug-resistant wounds. Overall, the proposed hydrogel shows great potential in meeting the complex repair requirements arising from antibiotic-resistant bacterial infections of wounds.