title: In vitro blood compatibility of polymeric biomaterials through covalent immobilization of an amidine derivative.
abstract: We present a surface coating with anticoagulant characteristics showing significantly reduced coagulation activation. The synthesis of a monomeric conjugate containing a benzamidine moiety was carried out and its inhibitory activity against human thrombin, the key enzyme of the blood coagulation cascade, was determined using a chromogenic assay. Based on that, low-thrombogenic interfaces were prepared by covalent attachment of this low-molecular weight thrombin inhibitor on poly(octadecene-alt-maleic anhydride) copolymer thin films and characterized using ellipsometry, XPS and dynamic contact angle measurements. The in vitro hemocompatibility tests using freshly drawn human whole blood showed, in agreement with the SEM images, that a PO-MA film modified with a benzamidine moiety using a PEG spacer decreased the activation of coagulation, platelets and the complement system. The decreased protein adsorption, in addition to the specific inhibition of thrombin, effectively enhanced the short-term hemocompatibility characteristics.
authors.affiliation: Institute of Polymer Research Dresden and The Max Bergmann Center of Biomaterials Dresden, Dresden, Germany.
authors.forename: M-F
authors.initials: MF
authors.lastname: Gouzy
authors.forename: C
authors.initials: C
authors.lastname: Sperling
authors.forename: K
authors.initials: K
authors.lastname: Salchert
authors.forename: T
authors.initials: T
authors.lastname: Pompe
authors.forename: U
authors.initials: U
authors.lastname: Streller
authors.forename: P
authors.initials: P
authors.lastname: Uhlmann
authors.forename: C
authors.initials: C
authors.lastname: Rauwolf
authors.forename: F
authors.initials: F
authors.lastname: Simon
authors.forename: F
authors.initials: F
authors.lastname: Böhme
authors.forename: B
authors.initials: B
authors.lastname: Voit
authors.forename: C
authors.initials: C
authors.lastname: Werner
mesh_terms: D000327:Adsorption; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D001550:Benzamidines / Q000737:chemistry* / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D001769:Blood; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D008299:Maleic Anhydrides / Q000737:chemistry*; D008422:Materials Testing; D015539:Platelet Activation / Q000235:genetics / Q000502:physiology*; D011108:Polymers / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013499:Surface Properties; D013917:Thrombin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D001550:Benzamidines; D001672:Biocompatible Materials; D008299:Maleic Anhydrides; D011108:Polymers; D015842:Serine Proteinase Inhibitors; D013917:Thrombin; C032157:benzamidine