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

Abstract

An in situ forming hydrogel has emerged as a promising wound dressing recently. As physically crosslinked hydrogels are normally unstable, most in situ 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 in situ forming hydrogel composed of poly(Nisopropylacrylamide 166 -co-n-butyl acrylate 9 )-poly(ethylene glycol)-poly(N-isopropylacrylamide 166 -co-n-butyl acrylate 9 ) copolymer (P(NIPAM 166 -co-nBA 9 )-PEG-P(NIPAM 166 -co-nBA 9 ), 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 Staphylococcus aureus (MRSA) of this PEP-AG hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected skin defect.

Antibacterial Hybrid Hydrogels

“…[157] In another case, Yan et al fabricated Ag NPs decorated rGO nanosheets to trigger temperature-sensitive polymer P(NIPAM 166 -co-nBA 9 )-PEG-P(NIPAM 166 -co-nBA 9 ) in situ gelation for the treatment of MRSA-infected skin wounds. [259] Another aloeemodin and PEG-modified hollow carbon nanoparticles coembedded poly-2-dimethylaminoethyl methacrylate (PDMAA) hybrid hydrogel (AE/PEG-HCNPs) was fabricated by Gao and co-workers, which exhibited the excellent synergistic antibacterial efficacy from photothermal effect, photodynamic effect, and antibiotics ( Figure 13F). [260]…”

Hydrogel Properties and Their Impact on Regenerative Medicine and Tissue Engineering

“…An interesting example of an antibacterial HG was synthesized from poly(N-isopropylacrylamide 166co-n-butyl acrylate 9 ), poly(ethylene glycol), and poly(N-isopropyl-acryl-amide 166 -co-n-butyl acrylate 9 ) (PEP, Figure 5A), which was additionally doped with Ag nanoparticles (PEP-AG, Figure 5B) decorated with reduced graphene oxide nanosheets [102]. The studies showed that the HG solidified at human body temperature, and after cooling, it did not return to its initial state ( Figure 5).…”

“…Illustration of the thermoresponsive mechanism of (A) PEP and (B) PEP-AG HGs. Adapted with permission from[102]. Copyright (2020) American Chemical Society.…”

A fast UV-curable PU-PAAm hydrogel with mechanical flexibility and self-adhesion for wound healing

“…PAAm can be synthesized by free radical polymerization of acrylamide (AAm) monomer with the aid of photo-initiators under UV-irradiation. [17][18][19] Polyurethane (PU) possesses excellent mechanical properties, biocompatibility, anti-thrombosis properties, and has been widely used in biomedical applications. [20][21][22] Waterborne PU contains a large number of functional groups (-COONH-and -COO À ), which make it easily functionalized when interacting with other chemicals.…”