Post-modified biosynthesis strategy to achieve a heme-mimicking bacterial cellulose hydrogel with synergistic antibacterial functions for infected skin defect therapy.

The emergence of global multi-drug-resistant (MDR) bacteria has occurred due to the excessive abuse of antibiotics. Multiple antibacterial technologies have been explored to prevent MDR bacteria. Here, we developed a post-modified biosynthesis strategy to achieve a heme-mimicking bacterial cellulose hydrogel integrating a quaternary ammonium compound (i.e., [VPIM]Br) with a heme-mimicking gallium porphyrin (i.e., Ga-CHP) with synergistic antibacterial functions for infected skin defect therapy. The obtained hydrogel exhibited high in vitro antibacterial activity (99.9%) against both Escherichia coli and Staphylococcus aureus. Its antibacterial action was multimodal and multistep, including (i) positively charged [VPIM]Br and Ga-CHP electrostatically attracting negatively charged bacteria, leading to cell membrane disruption, (ii) Ga-CHP replacing heme in bacteria cells to disrupt bacterial iron metabolism, and (iii) reactive oxygen species (ROS) under light irradiation showing oxidative stress against bacterial cells. The hydrogel accelerated S. aureus-infected wound healing, eradicated wound infection, and improved epithelial regeneration. This strategy offered a promising antibacterial approach for combating bacterial infections.