title: Effects of base material, plasma proteins and FGF2 on endothelial cell adhesion and growth.
abstract: Blood-contacting materials rapidly acquire a coating of plasma proteins which can lead to local platelet activation and thrombus formation. This phenomenon seriously limits the usefulness of small diameter synthetic vascular grafts. One solution to this problem is to pre-seed or encourage in situ colonisation of the material with endothelial cells to maintain a non-thrombogenic surface. We have investigated the effect of contact with plasma and serum on the subsequent ability of human endothelial cells to adhere to model hydrophobic and hydrophylic plastic surfaces, and the effect of surface bound fibroblast growth factor 2 (FGF2) on endothelial cell proliferation. Cell adhesion was mainly dependent on adsorbed fibrinogen or vitronectin, depending on the polymer surface, and correlated with antibody binding to these molecules rather than quantitative surface concentrations. Cell proliferation was directly correlated with surface bound FGF2. Surface binding of the latter was controlled both by the chemical nature of the polymer surface and by the presence of FGF-binding molecules adsorbed on the surface. FGF2 bound specifically to surface-adsorbed fibrinogen, fibronectin and vitronectin as well as to pre-coated heparan sulphate proteoglycan, perlecan. Binding was significantly inhibited by plasma and serum which contained high levels of FGF2 binding proteins. To be effective in supporting endothelialisation of vascular grafts in vivo, surface-bound FGF2 would need to be protected from surface dissociation into the circulating blood.
authors.affiliation: CSIRO Molecular Science, Sydney, NSW, Australia. anne.underwood@csiro.au
authors.forename: P Anne
authors.initials: PA
authors.lastname: Underwood
authors.forename: John M
authors.initials: JM
authors.lastname: Whitelock
authors.forename: Penny A
authors.initials: PA
authors.lastname: Bean
authors.forename: John G
authors.initials: JG
authors.lastname: Steele
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D005340:Fibrinogen / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans / Q000494:pharmacology; D006801:Humans; D011137:Polystyrenes / Q000494:pharmacology; D014469:Umbilical Arteries / Q000166:cytology; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D001798:Blood Proteins; D020099:Coated Materials, Biocompatible; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D011137:Polystyrenes; D019096:Vitronectin; D016222:Fibroblast Growth Factor 2; C071927:perlecan; D005340:Fibrinogen