In Vivo and Ex Vivo Evaluation of the Antithrombogenicity of Human Thrombomodulin Immobilized Biomaterials

Human thrombomodulin (hTM) 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. Focusing on the establishment of the practical evaluation of hTM immobilized materials, the activity of immobilized hTM was evaluated by in vivo and ex vivo blood contacting tests. As the basis for immobilization, regenerated cellulose films and hollow fibers were used. For the in vivo test, hTM immobilized cellular hollow fibers were implanted into dog blood vessels. Using hTM immobilized cellulose hollow fibers, a small scale dialyzer was assembled and its antithrombogenic activity was studied using human blood. As a result, it was revealed that the immobilized hTM still has co-enzymatic activity for activation of Protein C and anticoagulant activity. The coagulation time of the human blood passed through the hTM immobilized small dialyzer was effectively prolonged. It is expected that hTM immobilized cellulose should be a useful antithrombogenic biomaterial.