The objective of this work is to develop dual function antibacterial coatings that prevent biofilm formation and thrombus. A key feature of this technology is that it will prevent biofilm formation without an associated risk of creating antibiotic resistant bacteria. The coating combines a novel protein resistant polymer with an antibacterial peptide. The peptide kills bacteria through a multi- tiered mechanism that is fundamentally different from that of clinical antibiotics and is therefore unlikely to promote resistance. Coatings will be produced by binding the peptide to surfaces in two modes: via a flexible tether and entrapment. A layer of the antibacterial peptide prepared in this way should be safe, functional, and long-lasting. This Phase II SBIR plan focuses on meeting requirements for short term central venous catheters. First, coating constituents will be selected to maximize activity. Activity and mode of action will be characterized with a close look at covalently tethered versus physically bound peptides. As a part of this process, structural and functional relationships of surface bound antimicrobials will be examined. Second, methods will be developed to ensure robust performance of coatings under physiological conditions. Efficacy over time under these conditions will be measured, where efficacy criteria include biofilm inhibition as well as nonthrombogenicity. Prototype catheters coated with this technology will then be produced and tested against clinically relevant bacteria including methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. The plan will be completed with an in vivo evaluation of prototypes using a model of central venous catheter infection in rats. Commercial applications include catheters, medical, optical and dental devices. ? ? ?
