title: Poly(dimethylsiloxane)-poly(ethylene oxide)-heparin block copolymers. II: Surface characterization and in vitro assessments.
abstract: Amphiphilic block copolymers containing poly(dimethylsiloxane), poly(ethylene oxide), as well as heparin-coated glass beads and tubes were evaluated for the amounts and activities of surface-immobilized heparin. Because the amphiphilic copolymer system is thermodynamically predicted to demonstrate low-energy phase enrichment on the surfaces of air-cast films, studies were also undertaken to understand the in vitro results. Solvent-cast copolymer films have a heterogeneous microphase-separated structure according to transmission electron micrographs. Wilhelmy plate contact angle analysis indicates significant surface restructuring occurs upon hydration. Attenuated total reflectance infrared spectroscopy studies of the desiccated and hydrated films at two different sampling depths show compositional heterogeneity as a function of depth, as well as near surface restructuring allowing surface enrichment of the high-energy segments following contact with water. Significant concentrations of heparin are detected on the surface of these coatings by toluidine blue assays. In addition, a portion of the surface-bound heparin maintains its original bioactivity as determined by recalcification times, thrombin times, and Factor Xa assays. These substrates were also tested for platelet adhesion and activation reactions in vitro using polymer-coated beads in rabbit platelet-rich plasma. Heparinized polymers promoted low levels of platelet adhesion and serotonin release. Surface concentrations of heparin from bioactivity assays were then correlated with platelet adhesion and the extent of platelet release to assess the efficacy of this heparin-immobilized copolymer as a blood-compatible material or coating.
authors.affiliation: Department of Pharmaceutics, University of Utah, Salt Lake City 84112.
authors.forename: D W
authors.initials: DW
authors.lastname: Grainger
authors.forename: K
authors.initials: K
authors.lastname: Knutson
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Feijen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001681:Biological Assay / Q000379:methods; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004129:Dimethylpolysiloxanes; D006493:Heparin / Q000032:analysis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008422:Materials Testing; D008854:Microscopy, Electron; D011817:Rabbits; D012828:Silicones / Q000494:pharmacology*; D012833:Siloxanes / Q000032:analysis / Q000494:pharmacology*; D013053:Spectrophotometry; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D004129:Dimethylpolysiloxanes; D012828:Silicones; D012833:Siloxanes; C055740:poly(dimethylsiloxane)-(polyethylene oxide)-heparin copolymer; D006493:Heparin