自己組織化ナノパターン構造薄膜による3次元配列制御された生体組織形成

• Project/Area Number: 17680035
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Tohoku University (2007); Hokkaido University (2005-2006)
• Principal Investigator: 田中 賢 Tohoku University, 多元物質科学研究所, 准教授 (00322850)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥28,860,000 (Direct Cost: ¥22,200,000、Indirect Cost: ¥6,660,000); Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2006: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2005: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 自己組織化 / ナノ材料 / 移植・再生医療 / 医療・福祉 / 細胞・組織 / 多孔質膜 / 血管内皮細胞 / 細胞接着 / 再生医療 / 足場 / 多孔質 / 増殖 / 分化 / 幹細胞 / ハニカム

Research Abstract

血管内皮細胞、平滑筋細胞などを材質、孔径、孔形状(配向性)、膜厚の異なる孔貫通型および非貫通型多孔質薄膜(ハニカムフィルム)の片面で培養することで、細胞の接着率、接着形態、増殖性、細胞外マトリックス産生、機能を調べた。例えば、血管内皮細胞の増殖性は、孔径5μmで最大となった。ハニカムフィルム上の細胞の接着点(焦点接着タンパク質のビンキュリン)を調べたところ、孔径5μmのハニカムフィルム上でビンキュリンの発現量が増大することを見出した。孔径5μmのハニカムフィルム上では、細胞増殖率やIV型コラーゲン、ラミニン、フィブロネクチン、エラスチンなどの細胞外マトリックスの産生能が高いことから、代表的な細胞接着性のタンパク質であるフィブロネクチン(Fn)の吸着構造がハニカムフィルムの構造によって決定され、それが細胞の増殖あるいは機能に影響を及ぼしていることが示唆された。チロシン(Tyrosin397)がリン酸化されたFAK(pY397FAK)は、平膜上に比べハニカムフィルム上では約3倍FAKが活性化されていることがわかった。ビンキュリンがRGD部位を認識してFnと結合し、形成される接着点でFAKの活性化が起こる。ハニカムフィルム上のFnの吸着構造が接着点の増加をもたらし平膜上に比べハニカムフィルム上のpY397FAK発現量が観測されたと考えられる。ハニカムフィルム(孔径5μm)上のFAKの活性化が、FAK活性化に続く増殖や機能発現に関係する下流のシグナル伝達系に関係し、最終的に細胞の増殖や機能が高まっていることが示唆された。一方、孔貫通型のハニカムフィルムの両面で血管内皮細胞と平滑筋細胞細胞を効率よく共培養できることから、血管組織再生用の足場として有効であることがわかった。

Research Products

• [Journal Article] Formation of hydroxyapatite on self-organized honeycomb-patterned polymer film (2008)
  • Author(s): M. Tanaka
  • Journal Title: Colloids and Surfaces A: Physicochemical and Engineering Aspects 313-314 Pages: 515-518
  • Peer Reviewed
• [Journal Article] Effect of pore size of honeycomb films on the morphology, adhesion and cytoskeletal organization of cardiac myocytes (2008)
  • Author(s): K. Arai
  • Journal Title: Colloids and Surfaces A: Physicochemical and Engineering Aspects 313-314 Pages: 530-535
  • Peer Reviewed
• [Journal Article] Effect of honeycomb-patterned structure on chondrocyte behavior in vitro (2008)
  • Author(s): Y. Fukuhira
  • Journal Title: Colloids and Surfaces A: Physicochemical and Engineering Aspects 313-314 Pages: 520-525
  • Peer Reviewed
• [Journal Article] Control of neural stem cell differentiation on honeycomb films (2008)
  • Author(s): A. Tsuruma
  • Journal Title: Colloids and Surfaces A: Physicochemical and Engineering Aspects 313-314 Pages: 536-540
  • Peer Reviewed
• [Journal Article] Enhanced cell survival and yield of rat small hepatocytes by honeycomb-patterned films (2008)
  • Author(s): S. Tsukiyama
  • Journal Title: Jp. J. Appl. Phys. 47 Pages: 1429-1434
  • Peer Reviewed
• [Journal Article] 神経細胞:バイオマテリアルによる神経幹/前駆細胞の増殖・分化制御 (2008)
  • Author(s): 田中 賢
  • Journal Title: バイオマテリアル-生体材料- 26 Pages: 23-32
  • NAID: 10021140400
• [Journal Article] ハニカムフィルムによる細胞機能の制御 (2008)
  • Author(s): 田中 賢
  • Journal Title: Bioindustry 26 Pages: 26-33
• [Journal Article] Effect of pore size of self-organized honeycomb-patterned polymer films on spreading, focal adhesion, proliferation, and function of endothelial cells (2007)
  • Author(s): M. Tanaka
  • Journal Title: J. Nanosci. Nanotech 7 Pages: 763-772
  • Peer Reviewed
• [Journal Article] Effects of honeycomb-patterned surface topography on the adhesion and signal transduction of porcine aortic endothelial cells (2007)
  • Author(s): S. Yamamoto
  • Journal Title: Langmuir 23 Pages: 8114-8120
  • Peer Reviewed
• [Journal Article] Stress Relaxation and Fluctuation of Living Cells Measured by Atomic Force Microscopy (2007)
  • Author(s): T. Okajima
  • Journal Title: Jp. J. Appl. Phys. 46 Pages: 5552-5555
  • Peer Reviewed
• [Journal Article] Small diameter porous biodegradable membranes enhance adhesion and growth of human cultured epidermal keratinocyte and dermal fibroblast cells (2007)
  • Author(s): J.R. McMillan
  • Journal Title: Tissue Engineering 13 Pages: 789-798
  • Peer Reviewed
• [Journal Article] Platelet adhesion to endothelial cells cultured on various hydrogel scaffolds (2007)
  • Author(s): Y.M. Chen
  • Journal Title: Biomaterials 28 Pages: 1752-1760
  • Peer Reviewed
• [Journal Article] Stress relaxation of HepG2 cells measured by atmic force microscopy (2007)
  • Author(s): T. Okajima
  • Journal Title: Nanotechnology 18 Pages: 84010-84014
  • Peer Reviewed
• [Journal Article] Time-Resolved In-Situ ATR-IR Observations of Water Sorption Process into a Poly (2-methoxyethyl acrylate) (PMEA) Film (2007)
  • Author(s): S. Morita
  • Journal Title: Langmuir 23 Pages: 3750-3761
  • Peer Reviewed
• [Journal Article] Direct observation of biocompatibility of PMEA (poly(2-methoxyethyl acrylate)) using Atomic Force Microscopy (2007)
  • Author(s): T. Hayashi
  • Journal Title: Biointerphase 2 Pages: 119-125
  • Peer Reviewed
• [Journal Article] Phase Angle Description of Perturbation Correlation Analysis and Its Application to Time-Resolved IR Spectra (2007)
  • Author(s): S. Morita
  • Journal Title: Appl. Spec 61 Pages: 867-872
  • Peer Reviewed
• [Journal Article] Blood Compatibility and Water Structure-Comparative Study between 2-Methoxyet hylacrylate-and 2-Methoxyethylmethacrylate-based random copolymers (2007)
  • Author(s): E. Hirota
  • Journal Title: J. Biomed. Mater. Res 81A Pages: 710-719
  • Peer Reviewed
• [Journal Article] Honeycomb-Like Architecture Produced by Living Bacteria, Gluconacetobacter xylinus (2007)
  • Author(s): Y. Uraki
  • Journal Title: Carbohydrate Polymers 69 Pages: 1-6
  • Peer Reviewed
• [Journal Article] 細胞機能制御を目指した自己組織化材料の設計 (2007)
  • Author(s): 田中 賢
  • Journal Title: ケミカルエンジニアリング 52 Pages: 27-34
• [Journal Article] ライフサイエンスにおける自己組織化技術:自己組織化パターン表面と細胞との相互作用 (2007)
  • Author(s): 山本貞明
  • Journal Title: Materials Integration 20 Pages: 67-77
• [Journal Article] Platelet adhesion to endothelial cells cultured on varioushydrogel scaffolds (2007)
  • Author(s): Yong Mei Chen
  • Journal Title: Biomaterials 28(10) Pages: 1752-1760
• [Journal Article] Stress relaxation of HepG2 cells measured by atmic force microscopy (2007)
  • Author(s): Takaharu Okajima
  • Journal Title: Nanotechnology 18
• [Journal Article] Time-Resolved In-Situ ATR-IR Observations of Water Sorption Process into a Poly(2-methoxyethyl acrylate) (PMEA) Film (2007)
  • Author(s): Shigeaki Morita
  • Journal Title: Langmuir 23(7) Pages: 3750-3761
• [Journal Article] Honeycomb-Like Architecture Produced by Living Bacteria, Gluconacetobacter xylinus (2007)
  • Author(s): Yasumitsu Uraki
  • Journal Title: Carbohydrate Polymers 69(1) Pages: 1-6
• [Journal Article] Effect of pore size of self-organized honeycomb-patterned polymer films on spreading, focal adhesion, proliferation, and function of endothelial cells (2007)
  • Author(s): Masaru Tanaka
  • Journal Title: Journal of Nanoscience and Nanotechnology 7(3) Pages: 763-772
• [Journal Article] Small-Diameter Porous Poly (^ε-Caprolactone) Films Enhance Adhesion and Growth of Human Cultured Epidermal Keratinocyte and Dermal Fibroblast Cells (2007)
  • Author(s): James R.McMillan
  • Journal Title: Tissue Engineering 13(4) Pages: 789-798
• [Journal Article] Relationship between adsorbed fibronectin and cell adhesion on a honeycomb-patterned film (2006)
  • Author(s): Sadaaki Yamamoto
  • Journal Title: Surface Science 600(18) Pages: 3785-3791
• [Journal Article] Control of hepatocyte adhesion and function on self-organized honeycomb-patterned polymer film (2006)
  • Author(s): Masaru Tanaka
  • Journal Title: Colloids and Surfaces A : Physicochemical and Engineering Aspects 284-285 Pages: 464-469
• [Journal Article] Topographical control of neurites extension on stripe-patterned polymer films (2006)
  • Author(s): Akinori Tsuruma
  • Journal Title: Colloids and Surfaces A : Physicochemical and Engineering Aspects 284-285 Pages: 470-474
• [Journal Article] Relationship between adsorbed fibronectin and FAK activation on a honeycomb-patterned film (2006)
  • Author(s): Sadaaki Yamamoto
  • Journal Title: Journal of Surface Science Society of Japan 27(10)
• [Journal Article] Fabrication of ECM Adsorbed Honeycomb Films which can Control the Cell Adhesion. (2006)
  • Author(s): Hiroshi Sunami
  • Journal Title: Colloids and Surfaces A : Physicochemical and Engineering Aspects 284-285 Pages: 548-551
• [Journal Article] Biodegradable honeycomb-patterned film composed of poly(lactic acid) and dioleoylphosphatidylethanolamine (2006)
  • Author(s): Yukako Fukuhira
  • Journal Title: Biomaterials 27 Pages: 1797-1802
• [Journal Article] Biomedical application of patternd polymer films prepared by self-organization (2006)
  • Author(s): Masatsugu Shimomura
  • Journal Title: Journal of Surface Science Society of Japan 27 Pages: 170-175
• [Journal Article] 最近の進歩,ナノテクノロジー -ボトムアップ型ナノテクノロジー- (2006)
  • Author(s): 田中 賢
  • Journal Title: 人工臓器 35(3) Pages: 151-154
• [Journal Article] Suppression of Neural Stem Cell Differentiation by Honeycomb-Patterned Films (2006)
  • Author(s): Akinori Tsuruma
  • Journal Title: IFMBE Proceedings 14 Pages: 3425-3428
• [Journal Article] ハニカム構造を有するポリマーフィルムでの神経幹細胞の分化と増殖制御 (2006)
  • Author(s): 鶴間章典
  • Journal Title: 再生医療 5(3) Pages: 61-67
• [Journal Article] ハニカムフィルムを用いた組織再生 (2006)
  • Author(s): 田中 賢
  • Journal Title: バイオマテリアル-生体材料- 24(3) Pages: 152-161
• [Journal Article] 水分子の自己組織化 (2006)
  • Author(s): 田中 賢
  • Journal Title: NITTO DENKO/日経サイエンス 72
• [Journal Article] Design and preparation of nano-biointerfaces by self-organization (2006)
  • Author(s): Masaru Tanaka
  • Journal Title: JAPAN NANONET BULLETIN 7
• [Journal Article] ナノインプリントによるナノピラー細胞培養シート (2006)
  • Author(s): 森脇雅也
  • Journal Title: BIO INDUSTRY 23(2) Pages: 5-8
• [Journal Article] 自己組織化マイクロパターン高分子薄膜の開発と高度再生治療への応用 (2006)
  • Author(s): 山本貞明
  • Journal Title: 化学工業 57(1) Pages: 27-35
• [Journal Article] Correlation between the Structure of Water in the Vicinity of Carboxybetaine Polymers and Their Blood-Compatibility (2006)
  • Author(s): H.Kitano
  • Journal Title: Langmuir 15(4) Pages: 11932-11940
• [Journal Article] ハニカムフィルムを用いた蛋白質吸着および細胞接着の制御 (2006)
  • Author(s): 角南寛
  • Journal Title: 再生医療 5(1) Pages: 96-101
• [Journal Article] -Study of Blood Compatibility with Poly(2-Methoxyethylacrylate)-Relationship between Surface Structure, Water Structure and Platelet Compatibility in 2-Methoxyethylacrylate/2-Hydroxyethylmethacrylate Diblock Copolymer (2006)
  • Author(s): E.Hirota
  • Journal Title: J.Biomed. Mater. Res. 76A Pages: 540-550
• [Journal Article] 新規高分子多孔質薄膜を用いた消化器系細胞の機能制御 (2005)
  • Author(s): 田中 賢
  • Journal Title: Journal of Gastrointestinal Researh (G.I. Research) 8月号 Vol.13 NO.4
• [Journal Article] Superhydrophobic and Lipophobic Properties of Self-Organized Honeycomb and Pincushion Structures (2005)
  • Author(s): H.Yabu
  • Journal Title: Langmuir 21(8) Pages: 3235-3237
• [Journal Article] Structure of Water Incorporated in Sulfobetaine Polymer Films as Studied by ATR-FTIR (2005)
  • Author(s): H.Kitano
  • Journal Title: Macromolecular Bioscience 5(4) Pages: 314-321
• [Journal Article] Morphological changes in neurons by self-organized pattemed films (2005)
  • Author(s): A.Tsuruma
  • Journal Title: e-Journal of Surface Science and Nanotechnology 3 Pages: 82-85
• [Journal Article] 細胞培養基材:パターン化高分子フィルム (2005)
  • Author(s): 下村政嗣
  • Journal Title: ソフトナノテクノロジー-バイオマテリアル革命- 第3編 第3章 Pages: 165-174
• [Journal Article] Production of mesoscopically patterned cellulose film (2005)
  • Author(s): Junji Nemoto
  • Journal Title: Bioresource Technology 96(17) Pages: 1995-1958
• [Journal Article] 自己組織化マイクロパターン高分子膜の開発と高度再生医療への応用 (2005)
  • Author(s): 山本貞明
  • Journal Title: 化学工業 57 Pages: 27-35
• [Journal Article] Morphological changes in neurons by self-organized patterned films (2005)
  • Author(s): A.Tsuruma
  • Journal Title: e-J.Surf.Sci.Nanotech 3 Pages: 159-164
• [Journal Article] 自己組織化によるナノバイオインターフェイスの設計と創製 (2005)
  • Author(s): 田中 賢
  • Journal Title: Japan Nanonet Bulletin(メールマガシン) 92
• [Journal Article] 自己組織化によるポリマー微細加工とナノバイオインターフェース (2005)
  • Author(s): 山本貞明
  • Journal Title: M&BE Vol.2 Pages: 69-76
• [Presentation] 原子間顕微鏡によるハニカム構造フィルム上での血管内費細胞の初期接着形態観察 (2007)
  • Author(s): 山本貞明
  • Organizer: 第27回表面科学講演大会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-02
• [Presentation] ハニカムパターン化フィルムによる膵島細胞接着形態制御 (2007)
  • Author(s): 築山周作
  • Organizer: 第56回高分子討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-09-20
• [Presentation] 細胞サイズ以下の多孔構造が細胞骨格構造へ及ぼす影響 (2007)
  • Author(s): 角南寛
  • Organizer: 第56回高分子討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-09-20
• [Presentation] Early celllar response to micro-patterned surfaces in the absence of adfesion proteins (2007)
  • Author(s): S. Yamamoto
  • Organizer: EBS2007
  • Place of Presentation: Brighton, UK
  • Year and Date: 2007-09-13
• [Presentation] Porous film grafts allow support, transfer and delivery of live human cells to wounded model mice (2007)
  • Author(s): J. R McMillan
  • Organizer: TERMIS EU meeting
  • Place of Presentation: London, UK
  • Year and Date: 2007-09-04
• [Presentation] 自己組織化ソフトマテリアルによる細胞機能制御 (2007)
  • Author(s): 田中 賢
  • Organizer: ソフトインターフェース研究会
  • Place of Presentation: 福岡
  • Year and Date: 2007-09-04
• [Presentation] Effect of pore size and 3D structure of honeycomb-patterned polymer films on the initial spreading process of endothelial cells (2007)
  • Author(s): S. Yamamoto
  • Organizer: IVC-17/ICSS-13 and ICN+T
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2007-07-05
• [Presentation] 内皮細胞の表面糖衣の摩擦低減効果 (2007)
  • Author(s): 陳咏梅
  • Organizer: 第56回高分子学会年次大会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-31
• [Presentation] 貫通型ハニカムフィルムを用いた両面培養技術の開発 (2007)
  • Author(s): 角南寛
  • Organizer: 第56回高分子学会年次大会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-30
• [Presentation] 膵島細胞の培養基材としてのハニカムパターン化フィルムによる接着形態制御 (2007)
  • Author(s): 築山周作
  • Organizer: 第56回高分子学会年次大会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-30
• [Presentation] 自己組織化ハニカムフィルムの孔径変化による神経幹・前駆細胞の分化・増殖制御機構 (2007)
  • Author(s): 鶴間章典
  • Organizer: 第56回高分子学会年次大会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-30
• [Presentation] 血管内皮細胞の初期伸展に及ぼすハニカムフィルム細孔径の影響 (2007)
  • Author(s): 山本貞明
  • Organizer: 第56回高分子学会年次大会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-29
• [Presentation] 自己組織化による細胞機能制御材料の創製 (2007)
  • Author(s): 田中 賢
  • Organizer: 東北大学多元研講演会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-15
• [Presentation] Effect of pore size and 3D structure of honeycomb-patterned polymer films on the initial spreading process of endothelial cells (2007)
  • Author(s): S. Yamamoto
  • Organizer: AFM BioMed Conference
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2007-04-21
• [Presentation] Honeycomb-patterned Film Providing a Long-term Hepatocyte Survival and Preservation of Hepatospecific Functions (2007)
  • Author(s): S. Tsukiyama
  • Organizer: 2007 Annual Meeting of Biomaterials
  • Place of Presentation: Chicago, USA
  • Year and Date: 2007-04-20
• [Book] 多孔体の精密構造と機能・物性評価, 21.多孔質高分子薄膜 (2008)
  • Author(s): 田中 賢
  • Publisher: サイエンス&テクノロジー
• [Book] 「ハニカム構造高分子膜自己組織化ナノマテリアル」、フロンティアテクノシリーズNo.9-フロントランナー85人が語るナノテクノロジーの新潮流-、第4章 10節 (2007)
  • Author(s): 田中 賢
  • Publisher: フロンティア出版
• [Book] 「自己組織化多孔質薄膜による細胞の増殖・分化・機能制御」、バイオとナノの融合II-新生命科学の応用-、第IV部第14章 (2007)
  • Author(s): 田中 賢
  • Publisher: 北海道大学出版
• [Book] 自己組織化ナノマテリアルー-フロントランナー85人が語るナノテクノロジーの新潮流- (2007)
  • Author(s): 田中 賢
  • Total Pages: 392
  • Publisher: フロンティア出版
• [Book] 機能物質の集積膜と応用展開 (2006)
  • Author(s): 藪 浩
  • Total Pages: 305
  • Publisher: シーエムシー出版
• [Book] ナノマイクロテクノロジー,先端医療シリーズ37,人工臓器・再生医療の最先端 (2005)
  • Author(s): 田中 賢
  • Publisher: 先端技術研究所