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Biomaterials combined with Engineered Growth Factors with collagen binding affinity for tissue regeneration.

Research Project

Project/Area Number 18500371
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionThe Institute of Physical and Chemical Research (2007)
Kanagawa Academy of Science and Technology (2006)

Principal Investigator

KITAJIMA Takashi  The Institute of Physical and Chemical Research, Nano Medical Engineering Laboratory, Contract Researcher (40399556)

Co-Investigator(Kenkyū-buntansha) ITO Yoshihiro  RIKEN, Nano Medical Engineering Laboratory, Chief Scientist (40192497)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,070,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsRegenerative Medicine / Tissue Engineering / Growth Factors / Blood Vessels
Research Abstract

We engineered growth factors (EGF, HGF, VEGF etc) to confer collagen binding activity by fusion of fibronectin collagen-binding domain (CBD). Resulting engineered growth factors showed stable binding activity. Cell growth promotion activity was also improved when they were combined with collagen. One of such fusion protein (CBD-HGF) immobilized to the culture vessels continued to stimulate growth of endothelial cells without medium change. That is, additional factor was unnecessary during prolonged culture. This will be suitable for developing culture system (or bioreactor) of growing large number of cells for cell-implantation therapy.
We further examined CBD-HGF on the applicability to regenerative medicine by combining with tissue engineering materials as follows.
1) Small caliber artificial blood vessels (3mm in diameter, ePTFE) were combined with CBD-HGF and implanted into dog femoral artery. The implanted vessels showed earlier endothelialization (4weeks) as compared to control vessels and native HGF treated vessels. The fusion HGF may be used to develop implantable vessels with long patency for bypass graft of coronary artery.
2) Collagen sponges combined with CBD-HGF induced extensive angiogenesis by 2 weeks after implantation into rat subcutaneous tissue, while control and HGF-treated sponge showed minimal angiogenesis. The sponge may be useful to repair ischemic cardiac tissues, leg ulcer etc.
3) CBD-HGF infused to balloon-injured carotid artery of rats promoted endothelialization of denuded areas. It may be used to prevent restenosis after angioplasty using balloon catheter.
The results of the present study indicated the applicability of collagen-binding growth factor (s) in the following ways;
1) Culture system for cell therapy, 2) biomaterial combined with growth factor activity to induce tissue repair and 3) medicine to induce tissue repair.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2008 2007 2006

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (12 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Covalently immobilized biosignal molecule materials for tissue engineering2008

    • Author(s)
      Ito, Y.
    • Journal Title

      Soft Matter 4

      Pages: 46-56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor fusion protein having collagen-binding activity(CBD-HGF)accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.2008

    • Author(s)
      Ohkawara N, Ueda H, Shinozaki S, Kitajima T, Ito Y, Asaoka H, Kawakami A, Kaneko E, Shimokado K.
    • Journal Title

      J Atheroscle Thromb. 14(4)

      Pages: 185-91

    • NAID

      10022606861

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor fusion protein having collagen-binding activity (CBD-HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.2007

    • Author(s)
      Ohkawara N, et. al.
    • Journal Title

      J Atheroscler Thromb. 14

      Pages: 185-191

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A fusion protein of hepatocyte growth factor for immobilization to collagen.2007

    • Author(s)
      Kitajima, T., et. al.
    • Journal Title

      Biomaterials 28

      Pages: 1989-1997

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor fusion protein having collagen-binding activity(CBD-HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.2007

    • Author(s)
      Ohkawara N, et. al.
    • Journal Title

      J Atheroscler Thromb. 14

      Pages: 185-191

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A fusion protein of hepatocyte growth factor for Immobilization to collagen.2007

    • Author(s)
      Kitajima, T., et. al.
    • Journal Title

      Biomaterials 28

      Pages: 1989-1997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A fusion protein of hepatocyte growth factor for immobilization to collagen.2007

    • Author(s)
      Kitajima, T., Terai, H., Ito, Y.
    • Journal Title

      Biomaterials 28

      Pages: 1989-97

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ex vivo Expansion of Human cord Blood Hematopoietic progenitor cellsusing Glutaraldehyde-fixed Human Bone Marrow Stromal Cells.2006

    • Author(s)
      Ito, Y., et. al.
    • Journal Title

      J. Biosci. Bioeng. 102

      Pages: 467-469

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ex vivo Expansion of Human Cord Blood Hematopoietic progenitor cells using Glutaraldehyde-fixed Human Bone Marrow Stromal Cells.2006

    • Author(s)
      Ito, Y., et. al.
    • Journal Title

      J. Biosci. Bioeng. 102

      Pages: 467-469

    • NAID

      110006148700

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ex vivo expansion of human cord blood hematopoietic progenitor cells using glutaraldehyde-fixed human bone marrow stromal cells.2006

    • Author(s)
      Ito, Y., Hasuda, H., Kitajima, T., Kiyono, T.
    • Journal Title

      J.Biosci.Bioeng. 102

      Pages: 467-9

    • NAID

      110006148700

    • Related Report
      2006 Annual Research Report
  • [Presentation] フィブリン結合性EGF融合蛋白質2008

    • Author(s)
      北嶋 隆、櫻木 誠、伊藤嘉浩
    • Organizer
      日本再生医療学会(第7回)
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-03-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Fibrin-binding fusion protein of EGF2008

    • Author(s)
      Kitajima, T., Sakuragi, M., Ito, Y.
    • Organizer
      Japanese Society for Regenerative Medicine.
    • Place of Presentation
      Nagoya Congress Center
    • Year and Date
      2008-03-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] フィブリン結合性EGF融合蛋白質2008

    • Author(s)
      北嶋 隆、櫻木 誠、伊藤 嘉浩
    • Organizer
      第7回再生医療学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-03-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] マトリックス結合性増殖因子の設計と組織再生への応用2007

    • Author(s)
      北嶋 隆、伊藤嘉浩
    • Organizer
      高分子討論会(第56回)
    • Place of Presentation
      名古屋工業大学
    • Year and Date
      2007-09-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Production of Matrix binding growth factors and its application for tissue Regeneration.2007

    • Author(s)
      Kitajima, T., Ito, Y.
    • Organizer
      The Society of Polymer Science Symposium
    • Place of Presentation
      Nagoya Institute of Technology
    • Year and Date
      2007-09-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] マトリックス結合性増殖因子の設計と応用2007

    • Author(s)
      北嶋 隆、伊藤 嘉浩
    • Organizer
      第55回高分子討論会
    • Place of Presentation
      名古屋工業大学
    • Year and Date
      2007-08-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] A Fusion Protein for Immobilization of Hepatocyte Growth Factor to Collagen.2006

    • Author(s)
      Kitajima, T. and Ito, Y
    • Organizer
      NANO-BIO TOKYO 2006
    • Place of Presentation
      東京大学
    • Year and Date
      2006-12-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A Fusion Protein for Immobilization of Hepatocyte Growth Factor to Collagen.2006

    • Author(s)
      Kitajima, T, Ito, Y
    • Organizer
      NANO-BIO TOKYO 2006
    • Place of Presentation
      University of Tokyo
    • Year and Date
      2006-12-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 組織工学材料への増殖因子固定化2006

    • Author(s)
      北嶋 隆、伊藤 嘉浩
    • Organizer
      日本バイオマテリアル学会大会(第8回)
    • Place of Presentation
      東京(アルカディア市ケ谷)
    • Year and Date
      2006-11-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Immobilization of growth factors to tissue-engineering materials.2006

    • Author(s)
      Kitajima, T., Ito, Y
    • Organizer
      Japanese Society for Biomaterials.
    • Place of Presentation
      Arcadia Ichigaya(Tokyo)
    • Year and Date
      2006-11-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FNCBD-HGFによるラット傷害頚動脈再内皮化促進作用2006

    • Author(s)
      上田浩樹、羽鳥薫、篠崎昇平、大河原奈々、渡辺喬士、今井豊、金子英司、北嶋隆、伊藤嘉浩、下門顕太郎
    • Organizer
      日本動脈硬化学会(第38回)
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2006-07-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Promotion of re-endothelialization of rat injured carotid artery by FNCBD-HGF2006

    • Author(s)
      Ueda, et. al.
    • Organizer
      Japanese Society for Atherosclerosis.
    • Place of Presentation
      Tokyo International Forum
    • Year and Date
      2006-07-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] フィブリン結合性成長因子2006

    • Inventor(s)
      伊藤嘉浩・北嶋隆
    • Industrial Property Rights Holder
      理化学研究所
    • Filing Date
      2006-11-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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