Fabrication of Mixed-Charge Polypeptide Coating for Enhanced Hemocompatibility and Anti-Infective Effect.

Abstract

Medical catheters are prone to fouling by protein adsorption and platelet adhesion/activation due to their hydrophobic surface, resulting in bacterial adhesion/biofilm formation, associated infection, and thrombosis. Hence, an ultralow-fouling and exceptional infection-resistant coating on devices is urgently needed. Herein, we synthesized mussel-inspired cationic polypeptide (cPep) and mixed-charge polypeptide (mPep) via an N-carboxyanhydride ring opening polymerization method. In the view of the chemical structure, in addition to the catechol group of levodopa, the cationic group of l-lysine (K), and the hydrophobic group of l-phenylalanine (F), the mPep, comparing with cPep, contains the anionic group of l-glutamic acid (E) since the negatively charge amino acid sequence is newly introduced, so as to guarantee its bactericidal ability, low toxicity, and surface self-deposition. Both cPep and mPep coatings are conveniently obtained by a dopamine-assisted codeposition technique. Compared with the cPep coating, the mPep coating has a similar antibacterial activity level (>99%) against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Meanwhile, it is demonstrated that the mPep coating has most effective antibiofilm activity (>3 days) and protein/platelet-resistant ability in vitro, as well as improving hemocompatibility. Furthermore, the mPep-coated silicone catheter induces no inflammatory response and significantly lowers the bacterial cell number with 6 log reduction in a mouse model of infection. Consequently, the rationally designed mPep with a simple coating technique has great potential in combating against medical catheter-related clinical infections.