A dynamically crosslinked, self-adapting, injectable gelatin-chondroitin sulfate hydrogel with antibacterial and antioxidant properties for treatment of deep and irregular wounds

Abstract

Chronic, deep, and irregularly shaped wounds often infected with bacteria are considered a major clinical concern. The overproduction of reactive oxygen species (ROS) and disruption of the balance between pro-inflammatory and anti-inflammatory cytokines delay the healing process. Traditionally used dressings are unable to address these multiple issues. We present a multifunctional, self-adaptable, injectable hydrogel composed of gelatin (G) and chondroitin sulfate (CS) containing borate-crosslinked tannic acid (TA), enriched with in situ synthesized silver nanoparticles (AgNPs), which eliminates the necessity of any secondary dressing. The dynamically crosslinked hydrogel demonstrates efficient self-healing, adhesiveness, antioxidant properties, and potential antibacterial activity (E. coli and S. aureus). The injectable hydrogels also exhibit sustained release of TA and AgNPs. The in vitro cytotoxicity reveals the excellent cytocompatibility of the hydrogel with HDF-N fibroblast cells and red blood cells. In vivo studies confirm that the injectable hydrogel demonstrates self-adaptability in irregularly shaped wounds and accelerates the healing process in terms of healing percentage, fibroblast generation, neovascularization, and hair follicle development. Additionally, the in vivo application of the fabricated hydrogels does not produce any significant systemic toxicity. This study demonstrates that the dynamically crosslinked, multifunctional, injectable hydrogel is a promising candidate for treating irregular deep penetrating wounds.