Ferrous iron-induced formation of glycyrrhizic acid hydrogels for Staphylococcus aureus-infected wound healing

Severe skin wound healing is mainly hindered by bacterial infection and uncontrolled inflammatory reaction. As a wound dressing, multifunctional hydrogel is expected to offer the potential possibility for overcoming current barriers in wound therapeutics. Herein, a natural drug molecule (glycyrrhizic acid, GA) and metal ion (Fe2+) were used to achieve the metal coordination-induced gelation. This as-prepared Fe2+-induced GA hydrogel showed excellent injectability, self-healing property, and sustained release behavior at a relatively lower concentration of GA, thereby reducing the high dose-caused cytotoxicity. In addition to acting as an inducer of gelation, Fe2+ promoted the antibacterial performance of hydrogel against Escherichia coli and Staphylococcus aureus through causing lipid peroxidation, membrane damage, and DNA degradation. Moreover, the released GA from hydrogel significantly accelerated cell migration and inhibited the inflammatory reaction by mediation of NF-κB signaling pathway to downregulate levels of important inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells. Using a mouse skin infected model, we revealed that the Fe2+/GA hydrogel applied to the wound resulted in the rapid wound healing. It is believed that the construction of natural drug molecule-derived hydrogel with antibacterial and anti-inflammatory capabilities may shed a new light to serve as a promising dressing for managing the severe skin wounds.