title: Immobilization of bioactive plasmin reduces the thrombogenicity of metal surfaces.
abstract: Components of many vascular prostheses including endovascular stents, heart valves and ventricular assist devices are made using metal alloys. In these blood contacting applications, metallic devices promote blood clotting, which is managed clinically by profound platelet suppression and/or anticoagulation. Here it is proposed that the localized immobilization of bioactive plasmin, a critical mediator of blood clot stability, may attenuate metallic prosthesis-induced thrombus formation. Previously described approaches to covalently immobilize biomolecules on implantable materials have relied on complex chemical linker chemistry, increasing the possibility of toxic side effects and reducing bioactivity. We utilize a plasma deposited thin film platform to covalently immobilize biologically active plasmin on stainless steel substrates, including stents. A range of in vitro whole blood assays demonstrate striking reductions in thrombus formation. This approach has profound potential to improve the efficacy of a wide range of metallic vascular implants.
authors.affiliation: The Heart Research Institute, Sydney, NSW 2042, Australia; Sydney Medical School, University of Sydney, NSW 2006, Australia; School of Molecular Bioscience, University of Sydney, NSW 2006, Australia.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Wise
authors.affiliation: The Heart Research Institute, Sydney, NSW 2042, Australia; Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Praveesuda L
authors.initials: PL
authors.lastname: Michael
authors.affiliation: Wyss Institute of Biologically Inspired Engineering of Harvard University, Boston, MA 02115, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Waterhouse
authors.affiliation: The Heart Research Institute, Sydney, NSW 2042, Australia; Sydney Medical School, University of Sydney, NSW 2006, Australia; School of Physics, University of Sydney, NSW 2006, Australia.
authors.forename: Miguel
authors.initials: M
authors.lastname: Santos
authors.affiliation: The Heart Research Institute, Sydney, NSW 2042, Australia; Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Elysse
authors.initials: E
authors.lastname: Filipe
authors.affiliation: The Heart Research Institute, Sydney, NSW 2042, Australia; Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Juichien
authors.initials: J
authors.lastname: Hung
authors.affiliation: School of Physics, University of Sydney, NSW 2006, Australia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kondyurin
authors.affiliation: School of Physics, University of Sydney, NSW 2006, Australia. Electronic address: marcela.bilek@sydney.edu.au.
authors.forename: Marcela M M
authors.initials: MM
authors.lastname: Bilek
authors.affiliation: The Heart Research Institute, Sydney, NSW 2042, Australia; Sydney Medical School, University of Sydney, NSW 2006, Australia; Department of Cardiology, Royal Prince Alfred Hospital, NSW 2050, Australia. Electronic address: mkcng@med.usyd.edu.au.
authors.forename: Martin K C
authors.initials: MK
authors.lastname: Ng
mesh_terms: D005341:Fibrinolysin / Q000737:chemistry*; D006801:Humans; D008297:Male; D013499:Surface Properties; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D005341:Fibrinolysin
keywords: Covalent immobilization; Plasmin; Stent; Thrombosis