生体医工学部
研究活動の概要

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。

2013年の主な研究成果
  • 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た。
  • 新たなMRI造影剤システムを開発し、移植幹細胞の生体内遊走に加えて生死割合を低侵襲的に追跡することに成功した。また、類似の造影剤により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。
  • 分子動的界面の構築により幹細胞の拍動心筋分化への誘導効率を飛躍的に向上させた。
  • 病因物質除去機構の新たな治療戦略DNCSをリウマチ疾患に対して応用し、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。
  • 体内組織工学を用いて、TAVI用のステント付完全自己組織大動脈弁を開発し、ヤギ動物実験において検証を行っている。
研究業績
  1. Mahara A, Chen H, Agudelo C, Ishihara K and Yamaoka T. Cell-rolling microchip for the detection of circulating-tumor cells. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 246, ,2013.
  2. Munisso MC, Mahara A, Tachibana Y, Kang J, Obika S, and and Yamaoka T. Hepatocyte-specific gene delivery with galactose-bearing cationic polymers with different molecular structures. Advances in Science and Technology. 86,86-91,2013.
  3. Seo J, Kakinoki S, Yamaoka T, and and Yui N. Movable Polyrotaxane Surfaces for Modulating Cellular Adhesion via Specific RGD-Integrin Binding. Advances in Science and Technology. 86,59-62,2013.
  4. Kang J, Mori T, Kitazaki H, Niidome T, Takayama K, Nakanishi Y and Katayama Y. Kinase activity of protein kinase Cα in serum as a diagnostic biomarker of human lung cancer. Anticancer Research. 33,485-488,2013.
  5. 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. Artif Organs. , ,2013.
  6. Kato N, Kawaguchi AT, Kishida A and Yamaoka T. Static Cardiomyoplasty With Synthetic Elastic Net Suppresses Ventricular Dilatation and Dysfunction After Myocardial Infarction in the Rat: A Chronic Study .ARTIFICIAL ORGANS. 37,593-599,2013.
  7. Iwai R, Haruki R, Nemoto Y and Nakayama Y. Enhanced Transfection Efficiency of Poly(N,N-dimethylaminoethyl methacrylate)-Based Deposition Transfection by Combination with Tris(hydroxymethyl)aminomethane. BIOCONJUGATE CHEMISTRY. 24,159-166,2013.
  8. Endo K, Naito Y, Ji X, Nakanishi M, Noguchi T, Goto Y, Nonogi H, Ma X, Weng HC, Hirokawa G, Asada T, Kakinoki S, Yamaoka T, Fukushima Y and Iwai N. MicroRNA 210 as a Biomarker for Congestive Heart Failure. BIOLOGICAL & PHARMACEUTICAL BULLETIN. 36,48-54,2013.
  9. Iwai R, Nemoto Y and Nakayama Y. The effect of electrically charged polyion complex nanoparticle-coated surfaces on adipose-derived stromal progenitor cell behaviour. BIOMATERIALS. 34,9096-9102,2013.
  10. Seo JH, Kakinoki S, Inoue Y, Nam K, Yamaoka T, Ishihara K, Kishida A and Yui N. The significance of hydrated surface molecular mobility in the control of the morphology of adhering fibroblasts. BIOMATERIALS. 34,3206-3214,2013.
  11. Munisso MC, Mahara A, Tachibana Y, Kang JH, Obika S and Yamaoka T. Hepatocyte-specific gene delivery with galactose-bearing cationic polymers with different molecular structures. BIOMEDICAL APPLICATIONS OF SMART TECHNOLOGIES. 86,86-91,2013.
  12. Agudelo CA and Yamaoka T. Magnetic resonance imaging detection of an uncommon granuloma formation after endothelial progenitor cells transplantation. BIO-MEDICAL MATERIALS AND ENGINEERING. 23,555-566,2013.
  13. Toita R, Nakao K, Mahara A, Yamaoka T and Akashi M. Biodistribution of vaccines comprised of hydrophobically-modified poly(gamma-glutamic acid) nanoparticles and antigen proteins using fluorescence imaging. BIOORGANIC & MEDICINAL CHEMISTRY. 21,6608-6615,2013.
  14. Hun Kang J, Mori T, Kitazaki H, Niidome T, Takayama K, Nakanishi Y and Katayama Y. Serum protein kinase Cα as a diagnostic biomarker of cancers. Cancer Biomarkers. 13,99-103,2013.
  15. Toita R, Murata M, Abe K, Narahara S, Piao JS, Kang JH and Hashizume M. A nanocarrier based on a genetically engineered protein cage to deliver doxorubicin to human hepatocellular carcinoma cells. CHEMICAL COMMUNICATIONS. 49,7442-7444,2013.
  16. Iwai R, Yamanami M, Namoto Y and Nakayama Y. Rapid in vivo maturation of BIOTUBE vascular grafts by giant drops patching of adipose-derived stromal cells (ADSCs). EUROPEAN HEART JOURNAL. 34,808,2013.
  17. Toita R, Murata M, Abe K, Narahara S, Piao JS, Kang JH, Ohuchida K and Hashizume M. Biological evaluation of protein nanocapsules containing doxorubicin. INTERNATIONAL JOURNAL OF NANOMEDICINE. 8,1989-1999,2013.
  18. Nishi S, Nakayama Y, Ishibashi-Ueda H, Yoshida M and Yonetani H. Treatment of rabbit carotid aneurysms by Hybrid stents (microporous thin polyurethane stent grafts);Preservation of side-branches. J Biomaterials Applications. , ,2013.
  19. 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 astent (stent-biovalve) using the stent eversion method. J Biomed Mater Res B ApplBiomater. , ,2013.
  20. Moriwaki T, Oie T, Takamizawa K, Murayama Y, Fukuda T, Omata S and Nakayama Y. Surface density mapping of natural tissue by a scanning haptic microscope (SHM). J Med Eng Technol. 37,96-101,2013.
  21. Tateishi T, Kyomoto M, Kakinoki S, Yamaoka T, and and Ishihara K. Reduced platelets and bacteria adhesion on poly(ether ether ketone) by photoinduced and self-initiated graft polymerization of 2-methacryloyloxyethyl phosphorylcholine. J. Biomedical Materials Research Part A. , ,2013.
  22. Takamizawa K and Nakayama Y. Stress Distribution in a Bilayer Elastic Model of a Coronary Artery. JOURNAL OF APPLIED MECHANICS-TRANSACTIONS OF THE ASME. 80, ,2013.
  23. Moriwaki T, Oie T, Takamizawa K, Murayama Y, Fukuda T, Omata S and Nakayama Y. Observation of local elastic distribution in aortic tissues under static strain condition by use of a scanning haptic microscope. JOURNAL OF ARTIFICIAL ORGANS. 16,91-97,2013.
  24. Sawa Y, Tatsumi E, Tsukiya T, Matsuda K, Fukunaga K, Kishida A, Masuzawa T, Matsumiya G, Myoui A, Nishimura M, Nishimura T, Nishinaka T, Okamoto E, Tokunaga S, Tomo T, Yagi Y and Yamaoka T. Journal of Artificial Organs 2012: the year in review. JOURNAL OF ARTIFICIAL ORGANS. 16,1-8,2013.
  25. Takewa Y, Yamanami M, Kishimoto Y, Arakawa M, Kanda K, Matsui Y, Oie T, Ishibashi-Ueda H, Tajikawa T, Ohba K, Yaku H, Taenaka Y, Tatsumi E and Nakayama Y. In vivo evaluation of an in-body, tissue-engineered, completely autologous valved conduit (biovalve type VI) as an aortic valve in a goat model. JOURNAL OF ARTIFICIAL ORGANS. 16,176-184,2013.
  26. Yamanami M, Ishibashi-Ueda H, Yamamoto A, Iida H, Watanabe T, Kanda K, Yaku H and Nakayama Y. Implantation study of small-caliber biotube vascular grafts in a rat model. JOURNAL OF ARTIFICIAL ORGANS. 16,59-65,2013.
  27. Agudelo CA, Tachibana Y and Yamaoka T. Synthesis, properties, and endothelial progenitor cells labeling stability of dextranes as polymeric magnetic resonance imaging contrast agents. JOURNAL OF BIOMATERIALS APPLICATIONS. 28,473-480,2013.
  28. Kakinoki S, Yui N and Yamaoka T. Platelet responses to dynamic biomaterial surfaces with different poly(ethylene glycol) and polyrotaxane molecular architectures constructed on gold substrates. JOURNAL OF BIOMATERIALS APPLICATIONS. 28,544-551,2013.
  29. Liu Y, Inoue Y, 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. 25,474-486,2013.
  30. Kakinoki S, Seo JH, Inoue Y, Ishihara K, Yui N and Yamaoka T. A large mobility of hydrophilic molecules at the outmost layer controls the protein adsorption and adhering behavior with the actin fiber orientation of human umbilical vein endothelial cells (HUVEC). JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION. 24,1320-1332,2013.
  31. Takamizawa K and Nakayama Y. Non-Euclidean Stress-Free Configuration of Arteries Accounting for Curl of Axial Strips Sectioned From Vessels. JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME. 135, ,2013.
  32. Kim CW, Toita R, Kang JH, Li K, Lee EK, Zhao GX, Funamoto D, Nobori T, Nakamura Y, Mori T, Niidome T and Katayama Y. Stabilization of cancer-specific gene carrier via hydrophobic interaction for a clear-cut response to cancer signaling. JOURNAL OF CONTROLLED RELEASE. 170,469-476,2013.
  33. Seo JH, Kakinoki S, Inoue Y, Yamaoka T, Ishihara K and Yui N. Inducing Rapid Cellular Response on RGD-Binding Threaded Macromolecular Surfaces. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 135,5513-5516,2013.
  34. Hsu YI, Masutani K, Kimura Y and Yamaoka T. A Novel Bioabsorbable Gel Formed from a Mixed Micelle Solution of Poly(oxyethylene)-block-poly(L-lactide) and Poly(oxyethylene)-block-poly(D-lactide) by Concomitant Stereocomplexation and Chain Extension. MACROMOLECULAR CHEMISTRY AND PHYSICS. 214,1559-1568,2013.
  35. Ando H, Oshima M, Nakayama Y and Nakayama A. Polyethylene glycol-solvolyzed poly-(L)-lactic acids and their stereocomplexes with poly-(D)-lactic acid. POLYMER DEGRADATION AND STABILITY. 98,958-962,2013.
  36. Nakayama A, Yamano N, Kawasaki N and Nakayama Y. Synthesis and biodegradation of poly(2-pyrrolidone-co-epsilon-caprolactone)s. POLYMER DEGRADATION AND STABILITY. 98,1882-1888,2013.
  37. Yamaoka T, Njatawidjaja E, Kasai A, Agudelo CA, Ehashi T, Kakinoki S, Kato S and Mahara A. Elastic/adhesive double-layered PLA-PEG multiblock copolymer membranes for postoperative adhesion prevention. POLYMER DEGRADATION AND STABILITY. 98,2168-2176,2013.
  38. Takiyama N, Mizuno T, Iwai R, Uechi M and Nakayama Y. In-body tissue-engineered collagenous connective tissue membranes (BIOSHEETs) for potential corneal stromal substitution. J Tissue Eng Regen Med. , ,2013.
  39. 山岡 哲二. 移植幹細胞の分布と生死をモニターする高分子化MRI造影剤. Drug Delivery System. 28,24-34,2013.
  40. 山岡 哲二. Gd用いた高分子化MRI造影剤により移植幹細胞を定量的に評価. Medical Tribune. 46,7,2013.
  41. 柿木 佐知朗. ペプチド複合型バイオアクティブバイオマテリアル－ポリ乳酸スキャホールドへのペプチド修飾法の開発と末梢神経再生への展開－. PEPTIDE NEWSLETTER JAPAN. 90,16-20,2013.
  42. 柿木 佐知朗, 山岡 哲二. 神経. 再生医療における臨床研究と製品開発. ,35-40,2013.
  43. 中山 泰秀. 生体内組織形成術による弁再生. 再生医療叢書. 3,127-148,2013.
  44. 山岡 哲二. 柿木 佐知朗, 馬原 淳. バイオロジカルスキャホールドと脱細胞組織. 再生医療叢書【2】組織工学. ,91-121,2013.
  45. 山岡 哲二. 人工血管─脱細胞組織をベースにした再生型小口径血管─. 人工臓器. 42,184-187,2013.
  46. 馬原 淳, 山岡 哲二. 内皮細胞接着性ペプチドで修飾した脱細胞化小口径Long bypass graftの開発. 人工臓器. 42,39-40,2013.
  47. 中山 泰秀, 武輪 能明. 安全性の高い人工弁材料の開発. 体内埋め込み医療材料の開発とその理想的な性能・デザインの要件. ,137-140,2013.
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