title: Immobilization of human thrombomodulin onto poly(ether urethane urea) for developing antithrombogenic blood-contacting materials.
abstract: Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. In this study, focussing on the application of TM for biomedical materials, recombinant human TM (hTM) was immobilized onto the polymers for medical use, and the evaluation of their antithrombogenicity and the interaction with platelets were investigated. As the base polymer for immobilization reaction, poly(ether urethane urea) (PEUU), which was reported to have good blood compatibility, was used. hTM-immobilized PEUU showed superior antithrombogenic activity, such as the prolongation of plasma recalcification time and the inhibition of thrombin-induced platelet aggregation, though the amount of immobilized hTM was very small (i.e. less than 1 microgram/cm2). Platelet adhesions onto hTM-immobilized PEUU were not observed. These results show that the immobilization of hTM does not change the native good blood compatibility of PEUU, but provides excellent anticoagulant activity.
authors.affiliation: Department of Applied Chemistry and Chemical Engineering, Faculty of Engineering, Kagoshima University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kishida
authors.forename: Y
authors.initials: Y
authors.lastname: Ueno
authors.forename: N
authors.initials: N
authors.lastname: Fukudome
authors.forename: E
authors.initials: E
authors.lastname: Yashima
authors.forename: I
authors.initials: I
authors.lastname: Maruyama
authors.forename: M
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000991:Antithrombins / Q000138:chemical synthesis / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D008855:Microscopy, Electron, Scanning; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011140:Polyurethanes / Q000138:chemical synthesis / Q000494:pharmacology*; D018180:Thrombomodulin / Q000502:physiology*
chemical_list: D000991:Antithrombins; D001672:Biocompatible Materials; D010975:Platelet Aggregation Inhibitors; D011140:Polyurethanes; D018180:Thrombomodulin; C044690:polyetherurethane urea