Thermoresponsive <i>in Situ</i> Forming Hydrogel with Sol–Gel Irreversibility for Effective Methicillin-Resistant <i>Staphylococcus aureus</i> Infected Wound Healing

Abstract

An <i>in situ</i> forming hydrogel has emerged as a promising wound dressing recently. As physically cross-linked hydrogels are normally unstable, most <i>in situ</i> forming hydrogels are chemically cross-linked. However, big concerns have remained regarding the slow gelation and the potential toxicity of residual functional groups from cross-linkers or the polymer matrix. Herein, we report a sprayable <i>in situ</i> forming hydrogel composed of poly(<i>N</i>-isopropylacrylamide₁₆₆-<i>co</i>-<i>n</i>-butyl acrylate₉)-poly(ethylene glycol)-poly(<i>N</i>-isopropylacrylamide₁₆₆-<i>co</i>-<i>n</i>-butyl acrylate₉) copolymer (P(NIPAM₁₆₆-<i>co</i>-nBA₉)-PEG-P(NIPAM₁₆₆-<i>co</i>-nBA₉), denoted as PEP) and silver-nanoparticles-decorated reduced graphene oxide nanosheets (Ag@rGO, denoted as AG) in response to skin temperature. This thermoresponsive hydrogel exhibits intriguing sol-gel irreversibility at low temperatures for the stable dressing of a wound, which is attributed to the inorganic/polymeric dual network and abundant coordination interactions between Ag@rGO nanosheets and PNIPAM. The biocompatibility and antibacterial ability against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) of this PEP-AG hydrogel wound dressing are confirmed <i>in vitro</i> and <i>in vivo</i>, which could transparently promote the healing of a MRSA-infected skin defect.