Multi-Stimulus Responsive Multilayer Coating for Treatment of Device-Associated Infections

Abstract

Antibacterial coating with antibiotics is highly effective in avoiding device-associated infections (DAIs) which is an unsolved healthcare problem that causes significant morbidity and mortality rates. However, bacterial drug resistance caused by uncontrolled release of antibiotics seriously restricts clinical efficacy of antibacterial coating. Hence, a local and controlled-release system which can release antibiotics in response to bacterial infected signals is necessary in antibacterial coating. Herein, a multi-stimulus responsive multilayer antibacterial coating was prepared through layer-by-layer (LbL) self-assembly of montmorillonite (MMT), chlorhexidine acetate (CHA) and Poly(protocatechuic acid-polyethylene glycol 1000-bis(phenylboronic acid carbamoyl) cystamine) (PPPB). The coating can be covered on various substrates such as cellulose acetate membrane, polyacrylonitrile membrane, polyvinyl chloride membrane, and polyurethane membrane, proving it is a versatile coating. Under the stimulation of acids, glucose or dithiothreitol, this coating was able to achieve controlled release of CHA and kill more than 99% of Staphylococcus aureus and Escherichia coli (4 × 108 CFU/mL) within 4 h. In the mouse infection model, CHA releasing of the coating was triggered by infected microenvironment to completely kill bacteria, achieving wounds healing within 14 days.