Enzymatic one-pot preparation of carboxylmethyl chitosan-based hydrogel with inherent antioxidant and antibacterial properties for accelerating wound healing

Abstract

Facile preparation of multifunctional hydrogel wound dressings with inherent versatile properties is highly desirable in practical healthcare. Here, a biocompatible hydrogel was designed and fabricated via mild enzymatic crosslinking and polymerization. We first designed an enzymatic system containing horseradish peroxidase (HRP), H₂O₂, and the macromolecular initiator-acetoacetyl polyvinyl alcohol (PVA-ACAC), which can generate active PVA-ACAC carbon radicals via HRP-mediated oxidation by H₂O₂. Trimethylammonium chloride (Q), methacryloyl (MA) and phenol (Ph)-grafted carboxymethyl chitosan (Ph-QCMCS-MA) was then synthesized. HRP catalyzes the oxidation of phenol groups to achieve the fast phenol crosslinking, and PVA-ACAC carbon radicals initiate the polymerization of MA groups simultaneously, finally obtaining the target PPQM gel. The quaternary ammonium and phenol groups endow the PPQM gel with excellent antibacterial and antioxidant properties, respectively. This multifunctional hydrogel, which has additional adhesive and hemostatic properties, could promote wound healing processes in an in vivo full-thickness skin defect experiment by reducing the generation of pro-inflammatory cytokines (IL-6) and upregulating anti-inflammatory factors (IL-10) and angiogenesis-related cytokines (VEGF and α-SMA). As a result, it could be used as competitive wound dressings.

Keywords: Carboxylmethyl chitosan; Enzymatic crosslinking and polymerization; Wound dressing.