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Development of completely autologous aortic valves by a novel concept of regenerative medicine

Research Project

Project/Area Number 24659641
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

TAKAMIZAWA Keiichi  独立行政法人国立循環器病研究センター, 研究所, 研究員 (10163312)

Co-Investigator(Kenkyū-buntansha) NAKAYAMA Yasuhide  独立行政法人国立循環器病研究センター, 研究所, 室長 (50250262)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心臓弁 / 再生医療 / 組織工学 / 移植 / 大動脈弁 / 自己組織 / 生体内組織工学
Research Abstract

A 3D printer, which can easily reproduce the 3D-shape and size of native heart valves, was used to produce the molds for a tri-leaflet, valved conduit with a sinus of Valsalva. Biovalves were obtained from completely autologous connective tissue, containing collagen and fibroblasts, within 2 months following the subcutaneous embedding of the molds. In vitro evaluation, using a pulsatile circulation circuit, showed excellent valvular function with a durability of at least 10 days. The Biovalves were implanted in goats through an apicoaortic bypass procedure. Smooth movement of the leaflets with minimal regurgitation were observed. After 1 month of implantation, smooth white leaflets were observed with minimal thrombus formation. Functional, autologous, 3D-shaped heart valves with clinical application potential were formed following in-body embedding of specially designed molds.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results) Presentation (17 results) (of which Invited: 5 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] In-body tissue engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding2014

    • Author(s)
      Nakayama Y, Takewa Y, Sumukura H, Yamanami M, Matsui Y, Oie T, Kishimoto Y, Arakawa M, Ohnuma K, Kanda K, Tatsumi E
    • Journal Title

      J Biomed Mater Res B Appl Biomater

      Volume: (in press) Issue: 1 Pages: 1-10

    • DOI

      10.1002/jbm.b.33186

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preparation of an autologous heart valve with a stent (stent-biovalve) using the stent eversion method2014

    • Author(s)
      Mizuno T, Takewa Y, Sumikura H, Ohnuma K, Moriwaki T, Yamanami M, Oie T, Tatsumi E, Uechi M, Nakayama Y
    • Journal Title

      J Biomed Mater Res B Appl Biomater

      Volume: Dec 9 Issue: 5 Pages: 1-10

    • DOI

      10.1002/jbm.b.33086

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acceleration of rubust "biotube" vascular graft fabrication by in-body tissue architecture technology using a novel eosin Y-releasing mold2014

    • Author(s)
      Nakayama Y, Tsujinaka T
    • Journal Title

      J Biomed Mater Res B Appl Biomater

      Volume: 102B Issue: 2 Pages: 231-238

    • DOI

      10.1002/jbm.b.32999

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-Euclidean Stress-Free Configuration of Arteries Accounting for Curl of Axial Strips Sectioned from Vessels.2013

    • Author(s)
      Takamizawa K, Nakayama Y
    • Journal Title

      J Biomechanical Engineering

      Volume: 135 Issue: 11

    • DOI

      10.1115/1.4025328

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stress Distribution in a Bilayer Elastic Model of a Coronary Artery2013

    • Author(s)
      Takamizawa K, Nakayama Y
    • Journal Title

      J Applied Mechanics

      Volume: 16 Issue: 4 Pages: 59-65

    • DOI

      10.1115/1.4007863

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo evaluation of an in-body, tissue-engineered, completely autologous valved conduit (biovalve type VI) as an aortic valve in a goat model2013

    • Author(s)
      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, Nakayama Y
    • Journal Title

      J Artif Organs

      Volume: 25 Issue: 2 Pages: 176-184

    • DOI

      10.1007/s10047-012-0679-8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Implantation study of small-caliber "biotube" vascular grafts in a rat model.2013

    • Author(s)
      Yamanami M
    • Journal Title

      J Artif Organs

      Volume: 99(2) Issue: 1 Pages: 59-65

    • DOI

      10.1007/s10047-012-0676-y

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Observation of local elastic distribution in aortic tissues under static strain condition by use of a scanning haptic microscope2013

    • Author(s)
      Moriwaki T, Oie T, Takamizawa K, Murayama Y, Fukuda T, Omata S, Nakayama Y
    • Journal Title

      J Artif Organs

      Volume: 16 Issue: 1 Pages: 91-97

    • DOI

      10.1007/s10047-012-0674-0

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo evaluation of an in-body, tissue-engineered, completely autologous valved conduit (biovalve type VI) as an aortic valve in a goat model2013

    • Author(s)
      Takewa Y
    • Journal Title

      J Artif Organs

      Volume: 17

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hyperbranched polymeric "star vectors" for effective DNA or siRNA delivery2012

    • Author(s)
      Nakayama Y
    • Journal Title

      Acc Chem Res

      Volume: 45 Issue: 7 Pages: 994-1004

    • DOI

      10.1021/ar200220t

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 3Dプリンターによるバイオバルブ開発の可能性拡大2014

    • Author(s)
      中山泰秀, 武輪能明, 上地正実, 神田計一, 川尻英長, 水野壮司, 船山麻理菜, 森脇健司, 逢坂真吾, 田地川勉, 大家智憲, 田中孝晴, 杉浦寿史, 巽英介
    • Organizer
      第13回日本再生医療学会
    • Place of Presentation
      京都国際会館
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 人工弁の現状と今後の方向性 : 自己組織からなる心臓人工弁Biovalveの開発2013

    • Author(s)
      武輪能明, 中山泰秀, 山南将志, 熱田祐一, 岸本諭, 伊達数馬, 住倉博仁, 大沼健太郎, 水野壮司, 神田圭一, 田地川勉, 田中孝晴, 妙中義之, 巽英介
    • Organizer
      第51回日本人工臓器学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 人工弁の今後の方向性 : 3Dプリンターの医療分野での応用 :バイオバルブ開発の3D的発展2013

    • Author(s)
      中山泰秀, 武輪能明, 上地正実, 神田圭一, 大家智憲, 大野正順
    • Organizer
      第51回日本人工臓器学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Systemic application of a completely autologous aortic valved conduit (BIOVALVE type VII) prepared by in body tissue architecture technology in a goat model2013

    • Author(s)
      Nakayama Y, Takewa Y, Sumikura H, Yamanami M, Ohmuma K, Kanda K, Tatsumi E
    • Organizer
      The Society for Heart Valve Disease, 7 th Bienarial Congress
    • Place of Presentation
      イタリア、ベニス
    • Related Report
      2013 Final Research Report
  • [Presentation] 体内バイオプロセスを用いた移植用自己組織体の自動合成2013

    • Author(s)
      中山泰秀
    • Organizer
      有機合成のニュートレンド2013
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Systemic application of a completely autologous aortic valved conduit (BIOVALVE Type VII) prepared bu in body tissue architecture technology in a goat model2013

    • Author(s)
      Y. Nakayama, Y. Takewa, H. Sumikura, M. Yamanami, K. Ohnuma, K. Kanda, E. Tatsumi
    • Organizer
      The Society for Heart Valve Disease, 7th Biennial Congress
    • Place of Presentation
      イタリア、ベニス
    • Related Report
      2013 Annual Research Report
  • [Presentation] 人工弁の現状と今後の方向性 3Dプリンターの医療分野での活用 バイオバルブ開発の3D的発展2013

    • Author(s)
      中山 泰秀, 武輪 能明, 上地 正実, 神田 圭一, 田地川 勉, 大家 智憲, 大野 正順
    • Organizer
      日本人工臓器学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 人工弁の現状と今後の方向性 自己組織からなる心臓人工弁 Biovalveの開発2013

    • Author(s)
      武輪 能明, 中山 泰秀, 山南 将志, 熱田 祐一, 岸本 諭, 伊達 数馬, 住倉 博仁, 大沼 健太郎, 水野 壮司, 神田 圭一, 田地川 勉, 田中 孝晴, 妙中 義之, 巽 英介
    • Organizer
      日本人工臓器学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 体内バイオプロセスを用いた移植用自己組織体の自動合成2013

    • Author(s)
      中山泰秀
    • Organizer
      有機合成のニュートレンド2013(招待講演)
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] In Vivo-Tissue Engineered Autologous Aortic Valved Conduits (BIOVALVEs type VII) : Preparation and Evaluation2012

    • Author(s)
      Nakayama Y, Takewa Y, Sumikura H, Matsui Y, Yamanami M, Kishimoto Y, Arakawa M, Ohmuma K, Tajikawa T, Kansa K, Taenaka Y, Tatsumi E
    • Organizer
      European Society for Artificial Organs
    • Place of Presentation
      ドイツ、ロストック
    • Related Report
      2013 Final Research Report
  • [Presentation] Completely autologous biotube vascular grafts : eosin Y significantly promoted in vivo formation of functional biotubes in a short term2012

    • Author(s)
      Nakayama Y, Tsujinaka T
    • Organizer
      European Society for Cardiology 2012
    • Place of Presentation
      ドイツ、ミュンヘン
    • Related Report
      2013 Final Research Report
  • [Presentation] 生体内組織形成術 : 自分の移植物を自分の体内で作れる新技術2012

    • Author(s)
      中山泰秀, 神田圭一, 武輪能明, 上地正実, 渡辺太治, 山南将志
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Development of cardiovascular tissues by in body tissue architecture technology2012

    • Author(s)
      Nakayama Y
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Development of Cardiovascular Tissues by In Body Tissue Architecture Technology2012

    • Author(s)
      中山泰秀
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 生体内組織形成術:自分の移植物を自分の体内で作れる新技術2012

    • Author(s)
      中山泰秀
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Completely autologous biotube vascular grafts: eosin Y significantly promoted in vivo formation of functional biotubes in a short term2012

    • Author(s)
      Nakayama Y
    • Organizer
      European Society for Cardiology 2012
    • Place of Presentation
      ドイツ、ミュンヘン
    • Related Report
      2012 Research-status Report
  • [Presentation] In Vivo-Tissue Engineered Autologous Aortic Valved Conduits (BIOVALVEs type VII): Preparation and Evaluation2012

    • Author(s)
      Nakayama Y
    • Organizer
      European Society for Artificial Organs
    • Place of Presentation
      ドイツ、ロストック
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] ステント及びステント付き人工弁2013

    • Inventor(s)
      中山泰秀
    • Industrial Property Rights Holder
      国立循環器病研究センター
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-010954
    • Filing Date
      2013-01-24
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞構造体の製造方法、及び該方法により製造された細胞構造体2012

    • Inventor(s)
      中山泰秀
    • Industrial Property Rights Holder
      国立循環器病研究センター
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-149993
    • Filing Date
      2012-07-03
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 移植用人工組織体製造のための鋳型基材2012

    • Inventor(s)
      中山泰秀
    • Industrial Property Rights Holder
      国立循環器病研究センター
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-116780
    • Filing Date
      2012-05-22
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞構造体の製造方法、及び該方法により製造さ れた細胞構造体2012

    • Inventor(s)
      中山泰秀
    • Industrial Property Rights Holder
      国立循環器病研究センター
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-149993
    • Filing Date
      2012-07-03
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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