Plasma-initiated Cross-linked Nanocoatings asAnti-infection Agents

PROJECT SUMMARY Last year in the United States there were more than 1.9 million medical-device-associated infections resulting in approximately 98,000 deaths. Antibiotic-resistant biofilm-forming bacteria create many problems in medicine and have detrimental implications for public health. To tackle this problem, “smart” antibiotic-free, anti-infection cross-linked nanocoatings (sCLNs) designed specifically for catheters have been developed. We have used argon plasma technology for the construction of sCLNs. These smart nanocoatings consist of acrylic acid polymer brushes that are cross-linked to silver nanoparticles (AgNPs) in a layer-by-layer fashion with an AgNP concentration of 2.46 µg/cm2. This was achieved by using a plasma-initiated “grafting-from” approach, coupled with in situ argon plasma-assisted reduction. These biocompatible anti-infection nanocoatings can sense and target bacteria and biofilms effectively and specifically. Mechanistic studies involving sCLNs demonstrate complex activity, triggered by adherent bacteria and biofilms, rather than mere sustained antimicrobial release. We propose that our sCLNs may be the future for the prevention of medical implant contaminations. Preliminary data suggest that sCLNs are efficacious for eradicating antibiotic-resistant, biofilm-forming bacteria including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli on biomaterials used to make catheters. Several potential advantages of sCLNs, compared to traditional surfaces loaded with antibacterial agents, are their (1) broad activity against antibiotic-resistant bacteria, (2) ability to reduce bacterial adhesion, (3) rare provocation of bacterial resistance, (4) longevity, (5) specificity, (6) biocompatibility, and (7) stability. Three integrated specific aims are proposed to test the hypothesis that sCLNs can be constructed using plasma technology and are effective at preventing bacterial biofilms in a medically relevant environment. In Specific Aim 1, experimental variables will be explored to construct stable sCLNs with increased sensitivity to biofilm formation. In Specific Aim 2, the anti-infective efficacy of sCLNs will be evaluated against several different gram-positive and gram-negative biofilm-forming strains of bacteria in vitro, under both stationary and microfluidic cultivation conditions, specifically to model the actual environment of catheters. An exploration of the mechanism of action with a focus on the induction of bacterial cell lysis in complex biological systems will be studied by using various viability assays. In Specific Aim 3, the first two aims will be augmented by evaluating the in vitro safety of sCLNs for human tissue cells in bacterial co-culture. This research seeks to improve upon existing techniques for the eradication of infections associated with medical and biomedical devices. This work and program funding will also enhance the research program at Fairleigh Dickinson University by providing students with opportunities to apply theoretical knowledge to practical, real-world scientific applications.