Tunicate-mimetic antibacterial hydrogel based on metal ion crosslinking and chitosan functionalization for wound healing

Abstract

With the increasing prevalence of drug-resistant bacterial infections and frequent occurrences of slow wound healing, the development of novel antibacterial wound dressings has become a serious challenge. Hydrogel dressings have attracted extensive attention on wound healing due to their unique three-dimensional network structures and properties. However, it is a challenge to develop natural long-acting antibacterial hydrogels with multiple functions such as excellent cell affinity, wet adhesion and mechanical properties. Inspired by the wound healing mechanism and adhesion characteristics of tunicates, a series of biomimetic antibacterial hydrogels were prepared by utilizing pyrogallol-modified chitosan (GACS) and polyvinyl alcohol (PVA) as matrix, zinc ions (Zn²⁺) as crosslinking and antibacterial agents, and ethyl N-lauroyl l-arginate hydrochloride (LAE) as the antibacterial active ingredient. The morphology, swelling, water retention, degradability, wet adhesion, biocompatibility, mechanical and rheological properties of PVA/GACS/Zn²⁺/LAE hydrogels were evaluated. And the adhesion ability conferred by the pyrogallol structures enabled the hydrogel with enhanced antibacterial effect and hemostatic ability. Moreover, the in vivo experiments on rat models with full-thickness infected wounds confirmed that PVA/GACS/Zn²⁺/LAE hydrogels could efficiently kill bacteria, significantly improve the wound microenvironment, greatly promote fibroblast proliferation and collagen deposition and ultimately accelerate wound healing. In a word, this study provided a feasible and simple way for the development of biomimetic antibacterial hydrogel dressings applied in infected wounds, which could not only seal wounds with various shapes and provide a moist and antibacterial environment for wounds, but also have certain mechanical strength, excellent wound adhesion, good biocompatibility and hemostatic performance.

Keywords: Antibacterial hydrogels; Ethyl N-lauroyl l-arginate hydrochloride; Polyvinyl alcohol; Pyrogallol-modified chitosan; Wound healing; Zinc ion.