Gold nanoclusters-loaded hydrogel formed by dimeric hydrogen bonds crosslinking: A novel strategy for multidrug-resistant bacteria-infected wound healing

Restoring skin integrity after wound infection remains a tougher health challenge due to the uncontrolled antibiotic-resistant pathogens caused by antibiotic abuse. Herein, an injectable hydrogel with dual antibacterial and anti-inflammatory activities composed of gold nanoclusters (GNCs) and carbomer (CBM) is developed for wound dressing to overcome multidrug-resistant infection. Firstly, both experimental investigations and molecular dynamics simulation validate the protonation state of 6-mercaptohexanoic acid (MHA) ligands play an important role in its antibacterial action of GNCs. The self-organizing GNCs-CBM composite hydrogel is then spontaneously cross-linked by the dimeric hydrogen bonds (H-bonds) between the MHA ligands and the acrylic acid groups of CBM. Benefitting from the dimeric H-bonds, the hydrogel becomes thickening enough as an ideal wound dressing and the GNCs exist in the hydrogel with a high protonation level that contributes to the enhanced bactericidal function. In all, by combining bactericidal and immunomodulatory actions, the GNCs-CBM hydrogel demonstrated excellent synergy in accelerating wound healing in animal infection models. Hence, the dimeric H-bonds strengthening strategy makes the GNCs-CBM hydrogel hold great potential as a safe and effective dressing for treating infected wounds. Image 1 • Keeping the MHA ligands of GNCs at a high protonation level contributes to exerting the bactericidal effects. • The GNCs-CBM hydrogel was spontaneously cross-linked by the dimeric hydrogen bonds between the GNCs and the CBM. • The GNCs-CBM hydrogel possessed enhanced antibacterial activities and immunomodulatory function in vitro and in vivo. • The GNCs-CBM hydrogel exhibited outstanding biocompatibility and promising prospect as a dressing for infected wound healing.