A study on human thrombomodulin-immobilized antithrombogenic biomaterials

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Thrombomodulin (TM) is a newly described endothelial cell associated protein that functions as a potentnatural anticoagulant by converting thrombin from a protease to an anticoagulant. Recently, the preparation of reconbinant human thrombomodulin (hTM) was achieved by using gene technology, and since then biomaterials containing hTM have been of interest. In this project, we have done the hTM-immobilization onto various polymer surfaces such as poly (acrylic acid) or poly (vinylamine) grafted poly (ether urethane urea) or poly (ethylene) film using water soluble carbodiimide. As the results, it was apparent that hTM activity was retained enough to show its antithrombogenicity. And then hTM was immobilized onto small dialyzer consisting of cellulose film to carry out blood flow test. Moreover, hTM fragment (E456) was immobilized onto poly (ethylene) film and compared its amount of immobilized, activity and antithrombogenicity with native hTM.With regard to the amount of immobilized, it was apparent that the amount of immobilized of hTM fragment is higher than that of native hTM.Finally, as to compare the activity of native hTM and its fragment, the dissociation constants of f-hTM and thrombin by affinity interaction was evaluated using a surface plasmon resonance.