R01AI177531

Plasma-Initiated Cross-Linked Nanocoatings as Anti-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.

Fairleigh Dickinson University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Teaneck, New Jersey 076661938 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 239% from $257,191 to $870,721.