title: The use of plasma-activated covalent attachment of early domains of tropoelastin to enhance vascular compatibility of surfaces.
abstract: All current metallic vascular prostheses, including stents, exhibit suboptimal biocompatibility. Improving the re-endothelialization and reducing the thrombogenicity of these devices would substantially improve their clinical efficacy. Tropoelastin (TE), the soluble precursor of elastin, mediates favorable endothelial cell interactions while having low thrombogenicity. Here we show that constructs of TE corresponding to the first 10 ("N10") and first 18 ("N18") N-terminal domains of the molecule facilitate endothelial cell attachment and proliferation equivalent to the performance of full-length TE. This N-terminal ability contrasts with the known role of the C-terminus of TE in facilitating cell attachment, particularly of fibroblasts. When immobilized on a plasma-activated coating ("PAC"), N10 and N18 retained their bioactivity and endothelial cell interactive properties, demonstrating attachment and proliferation equivalent to full-length TE. In whole blood assays, both N10 and N18 maintained the low thrombogenicity of PAC. Furthermore, these N-terminal constructs displayed far greater resistance to protease degradation by blood serine proteases kallikrein and thrombin than did full-length TE. When immobilized onto a PAC surface, these shorter constructs form a modified metal interface to establish a platform technology for biologically compatible, implantable cardiovascular devices.
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Matti A
authors.initials: MA
authors.lastname: Hiob
authors.forename: Steven G
authors.initials: SG
authors.lastname: Wise
authors.forename: Alexey
authors.initials: A
authors.lastname: Kondyurin
authors.forename: Anna
authors.initials: A
authors.lastname: Waterhouse
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Bilek
authors.forename: Martin K C
authors.initials: MK
authors.lastname: Ng
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Weiss
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D017550:Spectroscopy, Fourier Transform Infrared; D014333:Tropoelastin / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D014333:Tropoelastin
keywords: Covalent immobilization; Endothelial cell; N-terminus; Plasma surface modification; Stent; Tropoelastin