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。世界初の内径2mm長さ30cmという小口径人工血管の大動物実験開存に成功し、現在臨床化に向けて最終の長期成績の評価を進めている。

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。

2015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、半年の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。
  • 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。
  • 脳動脈瘤塞栓治療用カバードステントの開発を成功させた。医師主導治験に向けた準備を着実に整えている。
  • 生体内組織形成術を利用した自己組織体（バイオチューブ、バイオシート）のFirst-in-Human臨床試験を小児循環器外科と透析外科の２件を実現した。
研究業績
  1. Funayama M, Furukoshi M, Moriwaki T, Nakayama Y. Development of an in vivo tissue-engineered valved conduit (type S biovalve) using a slitted mold. Journal of Artificial Organs. 18, 382-386, 2015.
  2. Funayama M, Matsui Y, Tajikawa T, Sasagawa T, Saito Y, Sagishima S, Mizuno T, Mizuno M, Harada K, Uchida S, Shinoda A, Iwai R, Nakayama Y, Uechi M. Successful implantation of autologous valved conduits with self-expanding stent (stent-biovalve) within the pulmonary artery in beagle dogs. Journal of Veterinary Cardiology. 17, 54-61, 2015.
  3. Funayama M, Sumikura H, Takewa Y, Tatsumi E, Nakayama Y. Development of self-expanding valved stents with autologous tubular leaflet tissues for transcatheter valve implantation. Journal of Artificial Organs. 18, 228-235, 2015.
  4. Funayama M, Takewa Y, Oie T, Matsui Y, Tatsumi E, Nakayama Y. In situ observation and enhancement of leaflet tissue formation in bioprosthetic "biovalve". Journal of Artificial Organs. 18, 40-47, 2015.
  5. Hsu YI, Masutani K, Yamaoka T, Kimura Y. Tuning of Sol-Gel Transition in the Mixed Polymer Micelle Solutions of Copolymer Mixtures Consisting of Enantiomeric Diblock and Triblock Copolymers of Polylactide and Poly(ethylene glycol). Macromolecular Chemistry and Physics. 216, 837-846, 2015.
  6. Hsu YI, Masutani K, Yamaoka T, Kimura Y. Strengthening of hydrogels made from enantiomeric block copolymers of polylactide (PLA) and poly(ethylene glycol) (PEG) by the chain extending Diels-Alder reaction at the hydrophilic PEG terminals. POLYMER. 67, 157-166, 2015.
  7. Iwai R, Tsujinaka T, Nakayama Y. Preparation of Biotubes with vascular cells component by in vivo incubation using adipose-derived stromal cell-exuding multi-microporous molds. Journal of Artificial Organs. 18, 322-329, 2015.
  8. Jinno C, Morimoto N, Mahara A, Liem PH, Sakamoto M, Ogino S, Kakudo N, Inoie M, Fujisato T, Kusumoto K, Suzuki S, Yamaoka T. Inactivation of Human Nevus Tissue Using High Hydrostatic Pressure for Autologous Skin Reconstruction: A Novel Treatment for Giant Congenital Melanocytic Nevi. Tissue Engineering Part C: Methods. 21, 1178-1187, 2015.
  9. Kakinoki S, Sakai Y, Fujisato T, Yamaoka T. Accelerated tissue integration into porous materials by immobilizing basic fibroblast growth factor using a biologically safe three-step reaction. Journal of Biomedical Materials Research Part A. 103, 3790-3797, 2015.
  10. Kakinoki S, Seo JH, Inoue Y, Ishihara K, Yui N, 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. 13, 42-51, 2015.
  11. Kakinoki S, Yamaoka T. Single-Step Immobilization of Cell Adhesive Peptides on a Variety of Biomaterial Substrates via Tyrosine Oxidation with Copper Catalyst and Hydrogen Peroxide. Bioconjugate Chemistry. 26, 639-644, 2015.
  12. Kang JH, Asai D, Toita R, Kawano T, Murata M. Monitoring of phosphorylated peptides by radioactive assay and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Amino Acids. 47, 2377-2383, 2015.
  13. Kawajiri H, Mizuno T, Moriwaki T, Ishibashi-Ueda H, Yamanami M, Kanda K, Yaku H, Nakayama Y. Development of tissue-engineered self-expandable aortic stent grafts (Bio stent grafts) using in-body tissue architecture technology in beagles. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 103, 381-386, 2015.
  14. Kawajiri H, Mizuno T, Moriwaki T, Iwai R, Ishibashi-Ueda H, Yamanami M, Kanda K, Yaku H, Nakayama Y. Implantation study of a tissue-engineered self-expanding aortic stent graft (bio stent graft) in a beagle model. Journal of Artificial Organs. 18, 48-54, 2015.
  15. Kawano T, Murata M, Piao JS, Narahara S, Hamano N, Kang JH, Hashizume M. Systemic Delivery of Protein Nanocages Bearing CTT Peptides for Enhanced Imaging of MMP-2 Expression in Metastatic Tumor Models. International Journal of Medical Sciences. 16, 148-158, 2015.
  16. Kishimoto S, Takewa Y, Nakayama Y, Date K, Sumikura H, Moriwaki T, Nishimura M, Tatsumi E. Sutureless aortic valve replacement using a novel autologous tissue heart valve with stent (stent biovalve): proof of concept. Journal of Artificial Organs. 18, 185-190, 2015.
  17. Kumar P, Hosain MZ, Kang JH, Takeo M, Kishimura A, Mori T, Katayama Y. Suppression of atopic dermatitis in mice model by reducing inflammation utilizing phosphatidylserine-coated biodegradable microparticles. Journal of Biomaterials Science, Polymer Edition. 26, 1465-1474, 2015.
  18. Liem PH, Morimoto N, Mahara A, Jinno C, Shima K, Ogino S, Sakamoto M, Kakudo N, Inoie M, Kusumoto K, Fujisato T, Suzuki S, Yamaoka T. Preparation of Inactivated Human Skin Using High Hydrostatic Pressurization for Full-Thickness Skin Reconstruction. PLOS ONE. 10, , 2015.
  19. Mahara A, Sago M, Yamaguchi H, Ehashi T, Minatoya K, Tanaka H, Nakatani T, Moritan T, Fujisato T, Yamaoka T. Micro-CT evaluation of high pressure-decellularized cardiovascular tissues transplanted in rat subcutaneous accelerated-calcification model. Journal of Artificial Organs. 18, 143-150, 2015.
  20. Mahara A, Somekawa S, Kobayashi N, Hirano Y, Kimura Y, Fujisato T, Yamaoka T. Tissue-engineered acellular small diameter long-bypass grafts with neointima-inducing activity. Biomaterials. 58, 54-62, 2015.
  21. Morimoto N, Mahara A, Shima K, Ogawa M, Jinno C, Kakudo N, Kusumoto K, Fujisato T, Suzuki S, Yamaoka T. The Rapid Inactivation of Porcine Skin by Applying High Hydrostatic Pressure without Damaging the Extracellular Matrix. BioMed Research International. , , 2015.
  22. Morimoto Naoki, Jinno Chizuru, Mahara Atsushi, Kakudo Natsuko, Fujisato Toshia, Kusumoto Kenji, Suzuki Shigehiko, Yamaoka Tetsuji. Verification of the Inactivation of Melanocytic Nevus in vitro Using a Newly Developed Portable High Hydrostatic Pressure Device. Cells Tissues Organs. 201, 170-179, 2015.
  23. Murata M, Narahara S, Kawano T, Hamano N, Piao JS, Kang JH, Ohuchida K, Murakami T, Hashizume M. Design and Function of Engineered Protein Nanocages as a Drug Delivery System for Targeting Pancreatic Cancer Cells via Neuropilin-1. Molecular Pharmaceutics. 12, 1422-1430, 2015.
  24. Murata M, Piao JS, Narahara S, Kawano T, Haman N, Kang JH, Asai D, Ugawa R, Hashizume M. Expression and characterization of myristoylated preS1-conjugated nanocages for targeted cell delivery. Protein Expression and Purification. 110, 52-56, 2015.
  25. Nakayama Y, Takewa Y, Sumikura H, Yamanami M, Matsui Y, Oie T, Kishimoto Y, Arakawa M, Ohmuma K, Tajikawa T, Kanda K, Tatsumi E. In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 103, 1-11, 2015.
  26. Seo JH, Kakinoki S, Yamaoka T, Yui N. Directing Stem Cell Differentiation by Changing the Molecular Mobility of Supramolecular Surfaces. Advanced Healthcare Materials. 4, 215-222, 2015.
  27. Sumikura H, Nakayama Y, Ohnuma, Kishimoto, Takewa Y, Tatsumi E,. In vitro hydrodynamic evaluation of a biovalve with stent (tubular leaflet type) for transcatheter pulmonary valve implantation. Journal of Artificial Organs. 18, 307-314, 2015.
  28. Toita R, Kawano T, Kang JH, Murata M. Applications of human hepatitis B virus preS domain in bio- and nanotechnology. World Journal of Gastroenterology. 21, 7400-7411, 2015.
  29. Yazawa M, Mori T, Nakayama Y, Kishi K. Basic study of soft tissue augmentation by adipose-inductive biomaterial. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 103, 92-96, 2015.
  30. S Somekawa, K Masutani, Yu-I Hsu, A Mahara, Y Kimura , *T Yamaoka. Size-controlled nanomicelles of poly(lactic acid)-poly(ethylene 7 glycol) copolymers with a multiblock configuration. Polymers. 7, 1177-1191, 2015.
  31. Liu Y, Inoue Y, Sakata S, Mahara A, Kakinoki S, Yamaoka T, *Ishihara K. Well-structured Graft-type Phospholipid Polymer for Modified Polyurethane Vascular Prosthesis. Transactions of the Materials Research Society of Japan. 40, 137-140, 2015.
  32. 山岡 哲二. 細胞接着現象を利用したバイオマテリアル. 日本接着学会誌. 51, 151-156, 2015.
  33. 中山 泰秀. 生体内をバイオリアクターとする組織構築. 三次元ティッシュエンジニアリング. , 337-346, 2015.