Each year there are over two million healthcare-associated infections as a result of indwelling device infections in the United States alone, from which approximately 99,000 people die. Antibiotic-resistant biofilms thus create numerous problems in both medical and biomedical applications and have profound negative implications for public health. To tackle this problem, ?smart?, antibiotic-free, anti-infection polymer brush biocoatings (sPBBs), designed specifically for catheters have been developed. In this study, we have utilized the innovative plasma-assisted free radical graft polymerization technique for the construction of sPBBs. These smart biocoatings consist of ammonium polymer brushes that sense bacteria and biofilms and effectively target the infectious organisms discriminately, while promoting tissue cell growth. Mechanistic studies involving sPBBs demonstrate a complex activity, triggered by adherent bacteria. We propose that our anti-infection biocoatings may be the future for the prevention of medical and biomedical implant contaminations. Preliminary data suggest that sPBBs 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, in vitro. Several possible advantages of sPBBs in comparison to traditional anti-bacterial surfaces loaded with antibiotics or antibacterial agents are (1) their broad spectrum of activity against antibiotic resistant bacteria, (2) the unlikelihood of bacterial resistance, (3) specificity, (4) stability, and (5) longevity. Three integrated specific aims are proposed to test the hypothesis that sPBBs can be fabricated using the plasma-initiated surface graft polymerization technique and are efficacious at preventing infections in a medically relevant environment.
In Specific Aim 1, experimental variables will be explored to construct stable sPBBs with increased sensitivity to biofilm formation.
In Specific Aim 2, the anti-infection efficacy of sPBBs will be evaluated against several different gram-positive and gram-negative biofilm-forming strains of bacteria in vitro, as well as in a microfluidic cultivation system, designed 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 different viability assays.
Specific Aim 3, will facilitate the other two aims and evaluate the in vitro specificity of sPBBs against human tissue cells in co-culture. This research seeks to improve upon existing techniques for the eradication of infections associated with medical and biomedical devices. This work and AREA program funding will also enhance the undergraduate research program at Saint Peter?s University by providing students with opportunities to apply theoretical knowledge to practical, hands-on scientific applications.
Infections associated with biomedical devices are extremely challenging to treat because the adherent, pathogenic bacteria that provoke infection develop into biofilms to protect themselves against the host immune system response and antibiotic attack. The smart carbon nanoparticles developed in this study are a viable alternative to treating contaminated medical devices with antibiotics and have the potential to significantly improve the quality of life of patients by drastically reducing the number of health-related complications associated with medical device contaminations.
