Sustained Endogenous Nitric Oxide Catalytic System Endows Skin Scaffolds with Antibiofilm and Antibacterial Activities

Abstract

Infection is the main obstacle to wound repair and usually requires clinical intervention to kill bacteria, while the formed bacterial biofilms protect bacteria against antibacterial treatments. Nitric oxide (NO) therapy is a potential strategy for disrupting biofilms, which encounters a major challenge in the sustainable supply of NO at the wound site. Herein, a nitric oxide catalytic system (Cu@ZIF-8) is constructed by doping Cu 2+ ions on zeolitic imidazolate framework-8 (ZIF-8) via coordination between Cu 2+ ions and dimethylimidazole groups on ZIF-8. Cu@ZIF-8 is then incorporated into poly(p-dioxanone) (PPDO) to prepare a porous skin scaffold, which allows the slow-controlled release of Cu 2+ ions. In this case, the control-released Cu 2+ ions catalyze S-nitrosothiols (RSNOs) enriched at the wound site to continuously supply endogenous NO. NO then reacts with oxygen and free radical superoxide to form reactive nitrogen species to eliminate bacterial biofilms and trigger nitrosative and oxidative stress to kill bacteria. Results showed that the scaffold could continuously release Cu 2+ and catalyze RSNOs to produce NO for more than 28 days, demonstrating the sustainable release ability of NO. The biofilms of Escherichia coli and Staphylococcus aureus cocultured with the scaffold were eliminated by 79.8 and 79.3%, respectively. Moreover, the scaffold showed robust antibacterial activity against E. coli and S. aureus. This study provided an efficient therapy on infection-impaired skin by catalyzing the endogenous donor to produce NO for eliminating biofilms and improving antibacterial activities.