Click-crosslinked in-situ hydrogel improves the therapeutic effect in wound infections through antibacterial, antioxidant and anti-inflammatory activities

Abstract

Bacterial infection, free radical accumulation and excessive inflammation are major factors leading to delayed wound healing. The rapid and effective elimination of wound bacteria and excess free radicals, and modulation of the wound immune microenvironment to accelerate infected wound healing is one of the pressing clinical issues. Common wound dressing or drugs are single-functional and risk of developing drug resistance. Therefore, multifunctional biomaterials with accelerated wound healing are urgently desired. Herein, we reported a click-crosslinked hydrogel with antibacterial, antioxidant and anti-inflammatory properties for infected wound repair. The hydrogel gelated from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl chitosan based on “click” chemistry and Schiff base reaction possess short gelation time, good biocompatibility, broad-spectrum antibacterial activity, appropriate antioxidant and anti-inflammatory ability. Hydrogels effectively activate macrophage polarization toward the M2 phenotype and significantly promote the migration of repair-related cells (fibroblasts, epithelial cells and endothelial cells) and angiogenesis in vitro through paracrine mechanism. The in vivo results from a full-thickness infected wound model demonstrated that hydrogels can promote wound repair and regeneration by promoting angiogenesis and re-epithelialization through antibacterial, antioxidant and M2-type macrophage polarization. The bioactive hydrogels designed with antibacterial, antioxidant and M2 polarization promoting properties provide an efficient strategy for infected wound repair.