循環器疾患の撲滅を目指し、医工学的・再生医学的手法を駆使した新たな先進的医工学領域の提言と、治療法・医療デバイスの開拓を進めている。人工血管・人工弁等の従来型外科的デバイスに、自己組織化、あるいは、自己組織誘導型機能を搭載することで、再生型かつ生涯型の新たなバイオマテリアルを開発する。本年度、内径2mm長さ30cmという世界に類を見ない臨床応用可能なサイズの異種脱細胞人工血管を開存させることに成功した。

工学系研究者を中心に構成されている部でありながら、センター内外の臨床医・基礎医・獣医・生化学系研究者の参画を得て、機能性材料化学と細胞・組織制御技術との融合に基づいて、循環器系疾患に対する新たな戦略開発に焦点をあて、新たな治療システムの創出をとおして若手研究者の育成にも注力する。本年度の主な具体的内容を以下に示す。

• 内皮誘導型内腔を有する脱細胞小口径血管により2mm30cmという世界に類を見ないロングバイパスに成功し、中期開存性も確認された。
• 新たなMRI造影剤システムを開発し、これまで撮像が困難であった脳毛細血管の詳細撮像に成功した。
• 病因物質除去機構の新たな治療戦略DNCSを透析アミロイドーシス治療用に設計し、病因物質を肝臓に集積し排除することに成功した。
• 生分解性ハイドロゲルを心筋梗塞部位にインジェクトする心筋梗塞後の左心室リモデリング治療法の確立と有効性を明らかとした。
• 早期・探索的臨床試験拠点整備事業の研究成果であるカバードステントのデバイス仕様の確定を行い、医師主導治験に向けた準備を着実に整えている。

1. Asai D, Toita R, Murata M, Katayama Y, Nakashima H and Kang JH. Peptide substrates for G protein-coupled receptor kinase 2. FEBS Letters. 588, 2129-2132, 2014.
2. Ehashi T, Kakinoki S and Yamaoka T. Water absorbing and quick degradable PLLA/PEG multiblock copolymers reduce the encapsulation and inflammatory cytokine production. Journal of Artificial Organs. 17, 321-328, 2014.
3. Ehashi T, Takemura T, Hanagata N, Minowa T, Kobayashi H, Ishihara K and Yamaoka T. Comprehensive Genetic Analysis of Early Host Body Reactions to the Bioactive and Bio-Inert Porous Scaffolds. PLOS ONE. 9, , 2014.
4. Ishida Y, Sakakibara S, Terashi H, Hashikawa K and Yamaoka T. Development of a novel method for decellularizing a nerve graft using a hypertonic sodium chloride solution. The International journal of Artificial Organs. , , 2014.
5. Kakinoki S and Yamaoka T. Thermoresponsive elastin/laminin mimicking artificial protein for modifying PLLA scaffolds in nerve regeneration. Journal of Materials Chemistry B. 2, 5061-5067, 2014.
6. Kakinoki S, Mahara A and Yamaoka T. Endothelial cell adhesion on ePTFE substrate immobilized with REDV peptide via tyrosine residue. Peptide Science. , , 2014.
7. Kakinoki S, Nakayama M, Moritani T and Yamaoka T. Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid). Frontiers in Chemistry. 18, 38-45, 2014.
8. Kakinoki S, Sakai Y, Takemura T, Hanagata N, Fujisato T, Ishihara K and Yamaoka T. Gene chip/PCR-array analysis of tissue response to 2-methacryloyloxyethyl phosphorylcoline (MPC) polymer surfaces in a mouse subcutaneous transplantation system. Journal of Biomaterials Science, Polymer Edition. , , 2014.
9. Kakinoki S, Seo J-H , Inoue Y, Ishihara K, Yui N and Yamaoka T. Mobility of the Arg-Gly-Asp ligand on the outermost surface of biomaterials suppresses integrin-mediated mechanotransduction and subsequent cell functions. Acta Biomaterialia. e-pub, , 2014.
10. Liu Y, Inoue S, Sakata S, Kakinoki s, Yamaoka T and Ishihara K. Effects of molecular architecture of phospholipid polymers on surface modification of segmented polyurethanes. Journal of Biomaterials Science, Polymer Edition. 25, 474-486, 2014.
11. Liu Y, Inoue Y , Mahara A, Kakinoki S, Yamaoka T and Ishihara K. Durable Modification of Segmented Polyurethane for Elastic Blood-Contacting Devices by Graft-type 2-Methacryloyloxyethyl Phosphorylcholine Copolymer. Journal of Biomaterials Science, Polymer Edition. , , 2014.
12. Mahara A, Chen H, Ishihara K and Yamaoka T. Phospholipid polymer–based antibody immobilization for cell-rolling surfaces in stem cell purification system. Journal of Biomaterials Science, Polymer Edition. , , 2014.
13. Mahara A, Morimoto N, Sakuma T, Fujisato T and Yamaoka T. Complete Cell Killing by Applying High Hydrostatic Pressure for Acellular Vascular Graft Preparation. Biomed Research International. , , 2014.
14. Mahara A, Sago M, Yamaguchi H, Ehashi T, Minatoya K, Tanaka H, Nakatani T, Moritani T, Fujisato T and Yamaoka T. Micro-CT evaluation of high pressure-decellularized cardiovascular tissues transplanted in rat subcutaneous accelerated-calcification model. Journal of Artificial Organs. , , 2014.
15. Mizuno T, Takewa Y, Sumikura H, Ohnuma K, Moriwaki T, Yamanami M, Oie T, Tatsumi E, Uechi M and Nakayama Y. Preparation of an autologous heart valve with a stent (stent-biovalve) using the stent eversion method. Journal of Biomedical Materials Research Part B-Applied Biomaterials. 102, 1038-1045, 2014.
16. Munisso M. C and Yamaoka T. Reliable assessment and quantification of the fluorescence-labeled antisense oligonucleotides in vivo. BioMed Research International . , , 2014.
17. Munisso MC, Obika S and Yamaoka T. Nucleic acid delivery systems based on poly(galactosyl ureaethyl methacrylate-b-dimethylamino ethyl methacrylate) diblock copolymers. Carbohydrate Polymers. 114, 288-296, 2014.
18. Nakayama Y and Tsujinaka T. Acceleration of robust "biotube" vascular graft fabrication by in-body tissue architecture technology using a novel eosin Y-releasing mold. Journal of Biomedical Materials Research Part B-Applied Biomaterials. 102, 231-238, 2014.
19. Nishi S, Nakayama Y, Ishibashi-Ueda H and Masato Y. Occlusion of canine aneurysms using microporous self-expanding stent grafts: Long-term follow-up. Clinical Neurology and Neurosurgery. 122, 34-41, 2014.
20. Nishi S, Nakayama Y, Ishibashi-Ueda H, Yoshida M and Yonetani H. Treatment of rabbit carotid aneurysms by hybrid stents (microporous thin polyurethane-covered stents): Preservation of side-branches. Journal of Biomaterials Applications. 28, 1097-1104, 2014.
21. Sakakibara S, Ishida Y, Hashikawa K, Yamaoka T and Terashi H. Intima/medulla reconstruction and vascular contraction-relaxation recovery for acellular small diameter vessels prepared by hyperosmotic electrolyte solution treatment. Journal of Artificial Organs. 17, 169-177, 2014.
22. Seo J-H, Kakinoki S, Yamaoka T and Yui N. Directing stem cell differentiation by changing the molecular mobility of supramolecular surfaces. Advanced Healthcare Materials . e-pub, , 2014.
23. Sumikura H, Nakayama Y, Ohnuma K, Takewa Y and Tatsumi E. In Vitro Evaluation of a Novel Autologous Aortic Valve (Biovalve) With a Pulsatile Circulation Circuit. Artificial Organs. 38, 282-289, 2014.
24. Tachibana Y, Enmi J, Agudelo CA, Iida H and Yamaoka T. Long-term/bioinert labeling of rat mesenchymal stem cells with PVA-Gd conjugates and MRI monitoring of the labeled cell survival after intramuscular transplantation. Bioconjugate Chemistry. 25, 1243-1251, 2014.
25. Tachibana Y, Munisso MC, Kamata W, Kitagawa M, Harada-Shiba M and Yamaoka T. Quick nuclear transportation of siRNA and in vivo hepatic ApoB gene silencing with galactose-bearing polymeric carrier. Journal of Biotechnology. 175, 15-21, 2014.
26. Tateishi T, Kyomoto M, Kakinoki S, Yamaoka T and Ishihara K. Reduced platelets and bacteria adhesion on poly(ether ether ketone) by photoinduced and self-initiated graft polymerization of 2-methacryloyloxyethyl phosphorylcholine. Journal of Biomedical Materials Research Part A. 102, 1342-1349, 2014.
27. Toita R, Kang JH, Kim CW, Shiosaki S, Mori T, Niidome T and Katayama Y. Effect of peptide content on the regulation of transgene expression by protein kinase C alpha-responsive linear polyethylenimine-peptide conjugates. Colloids and Surfaces B:Biointerfaces. 123, 123-129, 2014.