This competing renewal application proposes to define the interactions between bacterial cell surfaces and biomaterial substrata. Staphylococcus epidermidis and Staphylococcus aureus are principal pathogens in polymer- and metal alloy-based biomaterial infections respectively. Bacteria-to- biomaterial interactions are mediated by extracapsular polysaccharides, bacterial receptors, host derived conditioning films and by the physical and chemical nature of the biomaterial surface. The role of bacterial extracapsular polysaccharide (slime) as well as that of two significant components of conditioning films (fibronectin and collagen) for which certain strains of bacteria have defined receptors will be examined. Primary (initial) adhesion rates to biomaterials, rather than colonization (in situ growth) of S. aureus and exopolysaccharide- and nonexopolysaccharide-producing strains of S. epidermidis will be evaluated as reference values for subsequent aims. The role of slime in primary adhesion will be determined and validated by antibody inhibition studies. S. aureus has been shown to possess receptors for collagen and fibronectin. Host derived conditioning films are in part composed of fibronectin and collagen. The role of single components of conditioning films may in part be defined by studies of those protein molecules for which bacteria are known to have receptors. Adhesion and inhibition studies of surfaces conditioned with collagen and fibronectin will define the role of these proteins and their corresponding specific bacterial receptors. The degree to which those receptors function in initial adhesion will be contrasted with preliminary adhesion for slime producing and non-slime producing strains.
The aims of this investigation are: 1) determine the comparative primary adhesion binding rates of S. aureus and S. epidermidis for polyurethane, ultra high molecular weight polyethylene, polymethylmethacrylate, titanium alloy (Ti6A14V) and silicon dioxide (model, defect-free surface), 2) determine the role of the exopolysaccharide of S. epidermidis in primary adhesion to biomaterials; exopolysaccharide antibodies will be used in competitive inhibition experiments, and 3) determine the binding rates of S. aureus and S. epidermidis for the biomaterials in Aim 1 which have been coated with fibronectin or collagen; epitope competitive inhibition studies will be included to determine the specific epitopes involved and to determine whether slime producing or non-slime producing strains of S. epidermidis have functional receptors for fibronectin or collagen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
7R01AR026957-05
Application #
3155482
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1981-09-30
Project End
1992-08-31
Budget Start
1990-04-15
Budget End
1991-08-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Medical Sciences Research Institute
Department
Type
DUNS #
City
Herndon
State
VA
Country
United States
Zip Code
Grainger, David W (2004) Controlled-release and local delivery of therapeutic antibodies. Expert Opin Biol Ther 4:1029-44
Poelstra, Kornelis A; Barekzi, Nazir A; Rediske, Andrea M et al. (2002) Prophylactic treatment of gram-positive and gram-negative abdominal implant infections using locally delivered polyclonal antibodies. J Biomed Mater Res 60:206-15
Barekzi, Nazir A; Felts, Adrian G; Poelstra, Kornelis A et al. (2002) Locally delivered polyclonal antibodies potentiate intravenous antibiotic efficacy against gram-negative infections. Pharm Res 19:1801-7
Poelstra, K A; van der Mei, H C; Gottenbos, B et al. (2000) Pooled human immunoglobulins reduce adhesion of Pseudomonas aeruginosa in a parallel plate flow chamber. J Biomed Mater Res 51:224-32
Felts, A G; Grainger, D W; Slunt, J B (2000) Locally delivered antibodies combined with systemic antibiotics confer synergistic protection against antibiotic-resistant burn wound infection. J Trauma 49:873-8
Rojas, I A; Slunt, J B; Grainger, D W (2000) Polyurethane coatings release bioactive antibodies to reduce bacterial adhesion. J Control Release 63:175-89
Poelstra, K A; Barekzi, N A; Slunt, J B et al. (2000) Surgical irrigation with pooled human immunoglobulin G to reduce post-operative spinal implant infection. Tissue Eng 6:401-11
Felts, A G; Giridhar, G; Grainger, D W et al. (1999) Efficacy of locally delivered polyclonal immunoglobulin against Pseudomonas aeruginosa infection in a murine burn wound model. Burns 25:415-23
Barekzi, N A; Poelstra, K A; Felts, A G et al. (1999) Efficacy of locally delivered polyclonal immunoglobulin against Pseudomonas aeruginosa peritonitis in a murine model. Antimicrob Agents Chemother 43:1609-15
Azizsoltani, E; Myrvik, Q N; Foster, L A et al. (1995) Simple technique for the preparation of silicone gel particles: the effect of silicone gel particles on oxidative responses of macrophages. J Biomed Mater Res 29:101-5

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