Fabrication of antimicrobial cationic hydrogels driven by physically and chemically crosslinking for wound healing

Abstract

The wound therapy based on antibiotic delivery inevitably leads to the emergence of drug resistance. Hydrogel biomaterials with inherent antibacterial activities have emerged as promising candidates for addressing this issue. However, developing an inherently antibacterial hydrogel through simple and facile strategies to promote localized wound infection healing remains a challenge. In this study, we successfully constructed antimicrobial cationic hydrogels with self-healing and injectable properties through physically and chemically dual-crosslinked networks. The networks were formed by the copolymers poly[(di(ethylene glycol) methyl ether methacrylate)-co-(4-formylphenyl methacrylate)-co-(2-(methacryloyloxy)ethyl]trimethylammonium chloride solution)] (PDFM) and poly[(di(ethylene glycol) methyl ether methacrylate)-co-(2-aminoethyl methacrylate hydrochloride)-co-(2-(((6-(6-methyl-4[1H]pyrimidionylureido) hexyl)carbamoyl)oxy)ethyl methacrylate)] (PDAU). The hydrogel systems effectively facilitate the regeneration and healing of infected wounds through the contact bactericidal feature of quaternary ammonium cations. The presence of Schiff base bonds in the injectable hydrogels imparts remarkable pH responsiveness and self-healing properties. In vitro experiments verified their intrinsic antibacterial activities along with their favorable cytocompatibility and hemocompatibility in both in vitro and in vivo. In addition, the hydrogel significantly accelerated the healing of bacterially infected in a full-thickness skin wound. This facilely prepared dual-crosslinked hydrogel, without antibiotics loading, holds significant prospects for treating infected wounds.