title: Fluorinated surface-modifying macromolecules: modulating adhesive protein and platelet interactions on a polyether-urethane.
abstract: Polyether-urethanes (PEUs) have been the materials of choice for the manufacture of conventional blood-contacting devices. Nevertheless, biostability and blood compatibility are still among the principal limitations in their long-term application. Studies investigating the development of protective coatings for PEUs have shown that degradation can be reduced with the use of fluorinated surface-modifying macromolecules (SMMs). It has also been hypothesized that SMM-modified PEU surfaces may exhibit improved blood compatibility because other studies have shown a modulation in fibrinogen adsorption onto these surfaces. To determine the blood compatibility of a PEU-containing fluorinated SMMs, a series of in vitro experiments were designed to study the pattern of protein adsorption from plasma and then to assess the nature of platelet adhesion and activation on each substrate. Western blot analysis as well as single protein studies revealed that the dominant "adhesive proteins" [fibrinogen (Fg), fibronectin (Fnc), and vitronectin (Vnc)] were adsorbed on two of the SMM-containing PEUs in lower amounts relative to unmodified base. Platelet adhesion and activation data further highlighted the differences among the various substrates. It was shown that the unmodified base had a higher number of adhered platelets relative to the SMM-modified surfaces, and that of the SMM-containing substrates, which showed the lowest levels of adhesive proteins also, exhibited significantly lower platelet densities. Close morphological examination further revealed that platelets residing on these latter substrates were not appreciably activated. Based on the current evidence, it is believed that the fluorinated SMMs demonstrate good potential for the development of surfaces with minimal thrombogenic character in in vivo applications.
authors.affiliation: Department of Biological and Diagnostic Sciences, Faculty of Dentistry, University of Toronto, Toronto, Canada.
authors.forename: A R
authors.initials: AR
authors.lastname: Jahangir
authors.forename: W G
authors.initials: WG
authors.lastname: McClung
authors.forename: R M
authors.initials: RM
authors.lastname: Cornelius
authors.forename: C B
authors.initials: CB
authors.lastname: McCloskey
authors.forename: J L
authors.initials: JL
authors.lastname: Brash
authors.forename: J P
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D000327:Adsorption; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000737:chemistry*; D015153:Blotting, Western; D002860:Chromium Radioisotopes; D005340:Fibrinogen / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry; D005465:Fluorocarbon Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007118:Immunoassay; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011140:Polyurethanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D013499:Surface Properties; D013927:Thrombosis / Q000517:prevention & control; D019096:Vitronectin / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D001798:Blood Proteins; D002860:Chromium Radioisotopes; D005353:Fibronectins; D005465:Fluorocarbon Polymers; D011140:Polyurethanes; D019096:Vitronectin; D005340:Fibrinogen; C044690:polyetherurethane urea