Our proposed studies are directed toward obtaining a better understanding of the mechanisms of infection of implanted cardiovascular biomaterials. Our hypothesis is that material surface interactions with flowing blood lead to alteration of basic pathophysiologic mechanisms that increase the probability of bacterial interaction and infection. The studies emphasize the use of clinically derived human materials, i.e., blood and bacteria, and clinically relevant cardiovascular materials coupled with controlled in vitro systems to systematically and comprehensively elucidate infection mechanisms with cardiovascular biomaterials. The overall goals of the project are to: 1) understand how blood protein adsorption and shear stress mediate genotypic and phenotypic aspects of initial Staphylococcus epidermidis adhesion and biofilm formation, 2) examine the role of biomaterial surface chemistry of clinically relevant and model cardiovascular biomaterials in modulating genotypic and phenotypic aspects of biofilm formation, 3) evaluate the bactericidal capacity of leukocytes in the presence of a Staphylococcus epidermidis biofilm formed on cardiovascular biomaterials, 4) develop a treatment for infection by using the fibrinogen-Fbe binding mechanism by which Staphylococcus epidermidis specifically adheres to thrombus formations on cardiovascular biomaterials, and 5) utilize an in vivo biomaterial infection model in rabbits for in vivo-in vitro correlations. Genotypic variations in S. epidermidis adhesion and biofilm will focus on identifying changes in gene expression of the Atle autolysin, capsular polysaccharide adhesin, polysaccharide intercellular adhesin, accumulation associated protein and accessory gene regulator. Corresponding phenotypic studies will quantify S. epidermidis adhesion, aggregation and viability, as well as slime production and biofilm thickness on the various cardiovascular biomaterials. Leukocyte bactericidal capacity in the presence of biofilm on biomaterials will be characterized by leukocyte adhesion, chemotaxis, reactive oxygen and nitrogen species production, phagocytosis, and apoptosis. A fibrinogen-based peptide sequence based on fibrinogen/Fbe (S. epidermidis) will be used as a blocking ligand to investigate adhesion blocking mechanisms to prevent bacterial aggregation and biofilm formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000279-16
Application #
7797433
Study Section
Special Emphasis Panel (ZRG1-SBIB-E (03))
Program Officer
Hunziker, Rosemarie
Project Start
1991-08-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2012-03-31
Support Year
16
Fiscal Year
2010
Total Cost
$371,554
Indirect Cost
Name
Case Western Reserve University
Department
Pathology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Hofmann, Christopher M; Anderson, James M; Marchant, Roger E (2012) Targeted delivery of vancomycin to Staphylococcus epidermidis biofilms using a fibrinogen-derived peptide. J Biomed Mater Res A 100:2517-25
Hofmann, Christopher M; Bednar, Kyle J; Anderson, James M et al. (2012) Disruption of Staphylococcus epidermidis biofilm formation using a targeted cationic peptide. J Biomed Mater Res A 100:1061-7
Mukherjee, Pranab K; Chand, David V; Chandra, Jyotsna et al. (2009) Shear stress modulates the thickness and architecture of Candida albicans biofilms in a phase-dependent manner. Mycoses 52:440-6
Anderson, James M; Jones, Jacqueline A (2007) Phenotypic dichotomies in the foreign body reaction. Biomaterials 28:5114-20
Patel, Jasmine D; Krupka, Tianyi; Anderson, James M (2007) iNOS-mediated generation of reactive oxygen and nitrogen species by biomaterial-adherent neutrophils. J Biomed Mater Res A 80:381-90
MacKintosh, Erin E; Patel, Jasmine D; Marchant, Roger E et al. (2006) Effects of biomaterial surface chemistry on the adhesion and biofilm formation of Staphylococcus epidermidis in vitro. J Biomed Mater Res A 78:836-42
Chandra, Jyotsna; Patel, Jasmine D; Li, Jian et al. (2005) Modification of surface properties of biomaterials influences the ability of Candida albicans to form biofilms. Appl Environ Microbiol 71:8795-801
Maeyama, Ryo; Kwon, Il Keun; Mizunoe, Yoshimitsu et al. (2005) Novel bactericidal surface: Catechin-loaded surface-erodible polymer prevents biofilm formation. J Biomed Mater Res A 75:146-55
Jones, Jacqueline A; Dadsetan, Mahrokh; Collier, Terry O et al. (2004) Macrophage behavior on surface-modified polyurethanes. J Biomater Sci Polym Ed 15:567-84
Maeyama, Ryo; Mizunoe, Yoshimitsu; Anderson, James M et al. (2004) Confocal imaging of biofilm formation process using fluoroprobed Escherichia coli and fluoro-stained exopolysaccharide. J Biomed Mater Res A 70:274-82

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