| Project/Area Number |
16300156
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Osaka University |
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Principal Investigator |
AKASHI Mitsuru Osaka University, Graduate School of Engineering, Professor, 大学院工学研究科, 教授 (20145460)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Ikuro Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院医歯学総合研究科, 教授 (20082282)
KIDA Toshiyuki Osaka University, Graduate School of Engineering, Associate Professor, 大学院工学研究科, 助教授 (20234297)
MATSUSAKI Michiya Osaka University, Graduate School of Engineering, Assistant Professor, 大学院工学研究科, 助手 (00419467)
WATANABE Junji Osaka University, Graduate School of Engineering, Associate Professor, 大学院工学研究科, 特任助教授 (60323531)
AJIRO Hiroharu Osaka University, The Center for Advanced Medical Engineering and Informatics, Lecturer, 特任講師 (50437331)
金子 達雄 大阪大学, 大学院工学研究科, 助手 (20292047)
菅谷 博之 東レ(株), 機能材料研究所・医療システム研究室, 主任研究員
舩木 隆文 (株)BMTハイブリッド, 研究員
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2005: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | Thrombomodulin / Anticoagulant Activity / Biomedical Material / Polymeric thinfilm / Physical Adsorption / Polysulfone / Surface / Industry-University Alignment / プロテインC活性 |
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| Research Abstract |
Human thrombomodulin (hTM) is an endothelial cell-associated protein with potent natural anticoagulant activity by converting thrombin from a procoagulant protease to an anticoagulant. We previously reported the immobilization of hTM onto polymeric film surface by covalent bond formation with the surface of the substrates. We discovered that hTM-immobilized materials had excellent properties for inhibiting both the coagulation and platelet aggregation of human blood. However, the activity of bioactive proteins is decreased through the covalent immobilization process, and chemical immobilization also has the risk of leaving remnant chemical contaminants such as condensation reagents and chemical linkers. In this study, we focused on the physical adsorption of hTM onto a polymeric biomaterial surface because physical adsorption can prevent denaturation and leave no remnant chemical reagents.
The adsorption of hTM onto polysulfone (PSF) films was analyzed quantitatively by quartz crystal microbalance (QCM) analysis. The adsorption constant and the maximum adsorption amount, calculated by the assumption of a Langmuir-type adsorption, showed that hTM adsorbed with a relatively weak interaction onto the PSF film. The physically adsorbed hTM showed high co-enzymatic activity for the activation of protein C, as well as anticoagulant activity. Furthermore, the surface wettability of the PSF film was easily controllable by the physical adsorption of hydrophobic and hydrophilic bioactive proteins. The anticoagulant activity of hTM adsorbed on the surface of dialyzer was also confirmed by ex vivo animal studies. The various biocompatible nanofilms were fabricated by layer-by-layer assembly, which can be applied for hTM adsorption.
We have successfully developed the blood-compatible biomedical materials by physical adsorption of hTM onto polymeric thinfilms, clarified the adsorption mechanism of hTM, and obtained significant knowledge about blood-compatible biomedical materials.
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