Antibacterial brush polypeptide coatings with anionic backbones

Preventing initial colonization of bacteria on biomaterial surfaces is crucial to address the medical device-associated infection issues. Antimicrobial peptide (AMP) or cationic polymer modified surfaces have shown promising potentials to inhibit the initial colonization of bacteria by contact killing. However, their development has been impeded because of bacterial adhesion and high cytotoxicity. Herein, we report a series of brush polypeptide coatings with anionic backbones and cationic AMP mimetic side-chains that displayed superior bactericidal activity, antibacterial adhesion property, and biocompatibility. The cationic side-chain density played an important role in the bioactivities of the brush polypeptide modified surfaces. Brush polypeptide coating with low side-chain density exhibited improved bactericidal activity and antibacterial adhesion property, ascribing to the cooperative effects of adjacent side-chains and backbones/side-chains, respectively. It also showed negligible hemolysis/cytotoxicity in vitro and potent anti-infection property (≥99.9% bactericidal efficacy) in vivo. Brush polymers with anionic backbones and cationic side-chains can be used as a promising design motif to potentiate both antibacterial property and biocompatibility of coatings for combating device-associated infections. STATEMENT OF SIGNIFICANCE: Device-associated infections (DAIs) have led to increased medical cost, pain, and even mortality of patients. Antimicrobial peptide and cationic polymer coatings provide an important strategy to combat DAIs by preventing initial colonization of bacteria on biomaterial surfaces. Nevertheless, they have suffered bacterial adhesion and cytotoxicity issues. Herein, we developed a brush polypeptide coating with anionic backbones and cationic side-chains. The brush polypeptide coating showed superior bactericidal and antibacterial adhesion properties outperforming conventional antibacterial coatings based on antimicrobial peptide (i.e., melittin), lysozyme (i.e., lysostaphin), cationic polymer, anionic polymer, and the blends of cationic/anionic polymers. It also showed good biocompatibility and potent anti-infection property, making it a promising candidate to combat the DAIs.