Copper metal-organic framework embedded carboxymethyl chitosan-g-glutathione/polyacrylamide hydrogels for killing bacteria and promoting wound healing

Abstract

Bacterial infection and its induced oxidative stress as major clinical challenge during wound healing call for an urgent response for the development of medical dressings with multi-functions, such as antioxidant and antibacterial. To meet this demand, copper metal organic framework nanoparticles (HKUST NPs) and carboxymethyl chitosan-g-glutathione (CMCs-GSH) were synthesized and characterized. By embedding HKUST NPs into PAM/CMCs-GSH hydrogel (AOH), we developed a novel hydrogel dressing (HKUST-Hs) with dual effects of antibacterial and antioxidant. The morphology, swelling behavior, oxidation resistance and antibacterial properties of HKUST-Hs were investigated as well as the slow-release behavior of copper ions. Full-thickness cutaneous wound model of rats was created to assess the promoting effect of HKUST-Hs on wound healing. We found that HKUST NPs could be well dispersed in HKUST-Hs by shielding the positive charge of copper ions, and thus copper ions released were uniformly distributed and chelated with CMCs-GSH to promote the swelling stability of HKUST-Hs. Also, HKUST-Hs exhibited good free radical scavenging ability in vitro antioxidant assay. Meanwhile, a gradient sustained-release system of copper ions was formed in HKUST-Hs owing to the inhibition of HKUST NPs to copper release and the chelation of CMCs-GSH, which effectively inhibited the explosive release of copper ions and prolonged the release period, thereby reducing cytotoxicity. In vitro antibacterial test demonstrated there was synergistic antibacterial effect between the slow-released copper ions and CMCs-GSH, which improved the antibacterial activity and antibacterial persistence of HKUST-Hs. Finally, HKUST-Hs accelerated wound healing in vivo by continuously killing bacteria and inhibiting oxidative stress.