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

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 <i>in situ</i> 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 (<i>E. coli</i> and <i>S. aureus).</i> The injectable hydrogels also exhibit sustained release of TA and AgNPs. The <i>in vitro</i> cytotoxicity reveals the excellent cytocompatibility of the hydrogel with HDF-N fibroblast cells and red blood cells. <i>In vivo</i> 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 <i>in vivo</i> 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.