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The development of supramolecular polyrotaxane-based architectures enhancing growth factor activity for bone regeneration.

Research Project

Project/Area Number 17K11901
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YAMAGUCHI Satoshi  東京医科歯科大学, 生体材料工学研究所, 非常勤講師 (00280628)

Co-Investigator(Kenkyū-buntansha) 由井 伸彦  東京医科歯科大学, 生体材料工学研究所, 教授 (70182665)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords骨再生 / ポリロタキサン / BMP / Noggin / siRNA / VEGF / メラトニン / カルボン酸 / ポリカルボン酸 / ポリグルタミン酸 / βーシクロデキストリン / BMP2 / 骨再生医療
Outline of Final Research Achievements

The aim of this study is to develop supramolecular polyrotaxane(PRX)-based architectures enhancing growth factor activity for bone regeneration. We’ve achieved the following results during the 3 year research period. 1) The gene silencing of noggin by GALA/ DMAE-SS-PRX/siRNA ternary polyplexes enhanced osteogenic differentiation efficiency of BMP2 through the suppression noggin expression.2)The inclusion complex of melatonin(MLT) with 2-hydroxypropyl β-cyclodextrin (HP-β-CD) was prepared to improve the water solubility. Its complex promoted osteogenic differentiation in MC3T3-E1 cells. 3) Polycarboxylates, especially poly(glutamic acid), showed their capability to intensify the osteoinductivity of BNP2. 4) The VEGF- immobilized supramolecular PRX surfaces with low mobility stimulated network formation in vascular endothelial cells.

Academic Significance and Societal Importance of the Research Achievements

歯牙欠損、疾患(腫瘍、嚢胞など)に対する手術、歯周病などにより生じた顎骨骨量減少は自然回復が見込めない。そのため機能回復、審美性回復のために自家骨移植が行われているのが現状である。手術侵襲を伴う骨移植に代わる骨再生医療開発の意義は大きく、盛んに研究が行われており実用化に近づいている。超分子ポリロタキサンを応用した骨再生医療はこれまでに無い新しい方法であり、骨再生を促す成長因子の効率、効果を上昇させ得ることが本研究により実証された。ポリロタキサン使用により成長因子使用量減少が期待でき、新しい治療法の安全性向上、対価減少に繋がる。3年間の本研究により臨床応用の可能性が具体化したと考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 4 results) Remarks (2 results)

  • [Journal Article] 硫酸化ポリロタキサンによるBMP2活性亢進と骨再生への試み2020

    • Author(s)
      寺内正彦, 田村篤志, 山口 聰, 依田哲也, 由井伸彦
    • Journal Title

      バイオマテリアル ー生体材料ー

      Volume: 38 Pages: 24-25

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polyelectrolyte Complexes between Polycarboxylates and BMP-2 for Enhancing Osteogenic Differentiation: Effect of Chemical Structure of Polycarboxylates2019

    • Author(s)
      Terauchi Masahiko、Tamura Atsushi、Tonegawa Asato、Yamaguchi Satoshi、Yoda Tetsuya、Yui Nobuhiko
    • Journal Title

      Polymers

      Volume: 11 Issue: 8 Pages: 1327-1327

    • DOI

      10.3390/polym11081327

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stimulation of Microvascular Networks on Sulfonated Polyrotaxane Surfaces with Immobilized Vascular Endothelial Growth Factor2019

    • Author(s)
      Hyodo Katsuya、Arisaka Yoshinori、Yamaguchi Satoshi、Yoda Tetsuya、Yui Nobuhiko
    • Journal Title

      Macromolecular Bioscience

      Volume: 19 Issue: 4 Pages: 1800346-1800346

    • DOI

      10.1002/mabi.201800346

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced cellular uptake and osteogenic differentiation efficiency of melatonin by inclusion complexation with 2-hydroxypropyl β-cyclodextrin2018

    • Author(s)
      Terauchi Masahiko、Tamura Atsushi、Yamaguchi Satoshi、Yui Nobuhiko
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 547 Issue: 1-2 Pages: 53-60

    • DOI

      10.1016/j.ijpharm.2018.05.063

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A silencing-mediated enhancement of osteogenic differentiation by supramolecular ternary siRNA polyplexes comprising biocleavable cationic polyrotaxanes and anionic fusogenic peptides2018

    • Author(s)
      Inada Takasuke、Tamura Atsushi、Terauchi Masahiko、Yamaguchi Satoshi、Yui Nobuhiko
    • Journal Title

      Biomaterials Science

      Volume: 6 Issue: 2 Pages: 440-450

    • DOI

      10.1039/c7bm01100h

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potentiating bioactivity of BMP-2 by polyelectrolyte complexation with sulfonated polyrotaxanes to induce rapid bone regeneration in a mouse calvarial defect2017

    • Author(s)
      Terauchi Masahiko、Inada Takasuke、Kanemaru Tomoki、Ikeda Go、Tonegawa Asato、Nishida Kei、Arisaka Yoshinori、Tamura Atsushi、Yamaguchi Satoshi、Yui Nobuhiko
    • Journal Title

      Journal of Biomedical Materials Research Part A

      Volume: 105 Issue: 5 Pages: 1355-1363

    • DOI

      10.1002/jbm.a.36016

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] メラトニン包接化合物による細胞内取込機能と骨分化誘導能評価2019

    • Author(s)
      寺内正彦, 田村篤志, 山口聰, 依田哲也, 由井伸彦
    • Organizer
      第36回シクロデキストリンシンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分解性ポリロタキサン/siRNA複合体の遺伝子サイレンシングを介した骨形成促進2019

    • Author(s)
      稲田大佳輔,寺内正彦,山口聰,依田哲也
    • Organizer
      第64回日本口腔外科学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Bone regeneration with bone morphogenetic protein-2 amplified by supramolecular sulfonated polyrotaxane2019

    • Author(s)
      Masahiko Terauchi, Atsushi Tamura, Satoshi Yamaguchi, Tetsuya Yoda, Nobuhiko Yui.
    • Organizer
      第41回日本バイオマテリアル学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分子可動性ポリロタキサン表面への血管内皮細胞成長因子の固定化が血管ネットワーク形成に及ぼす影響2019

    • Author(s)
      兵頭克弥, 山口聰, 依田哲也
    • Organizer
      第73回日本口腔科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Design of sulfonated polyrotaxane surfaces to activate vascular endothelial cells.2018

    • Author(s)
      Katsuya Hyodo,Yoshinori Arisaka,Satoshi Yamaguchi,Nobuhiko Yui.
    • Organizer
      5th TERMIS World Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Induction of vascular network in vitro on polyrotaxane surfaces with vascular endothelial growth factors.2018

    • Author(s)
      Katsuya Hyodo,Yoshinori Arisaka,Satoshi Yamaguchi,Tetsuya Yoda,Nobuhiko Yui.
    • Organizer
      13th Asian Congress on Oral and Maxillofacial Surgery
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inclusion complexation of melatonin with 2-hydroxypropyl β-cyclodextrin for enhancing osteogenic differentiation.2018

    • Author(s)
      Masahiko Terauchi, Atsushi Tamura, Nobuhiko Yui, Satoshi Yamaguchi
    • Organizer
      13th Asian Congress on Oral & Maxillofacial Surgery
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 硫酸化ポリロタキサン基材を用いた血管内皮細胞増殖因子の表面導入.2018

    • Author(s)
      有坂慶紀, 兵頭克弥, 山口 聰, 由井伸彦.
    • Organizer
      第67回高分子学会年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 血管内皮細胞のネットワーク化を亢進するポリロタキサン表面の構築.2018

    • Author(s)
      兵頭克弥,有坂慶紀,山口 聰,由井伸彦.
    • Organizer
      第47回医用高分子シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] ポリロタキサンの分子可動性調節と成長因子導入による血管ネットワーク形成の促進.2018

    • Author(s)
      兵頭克弥,有坂慶紀,山口 聰,依田哲也,由井伸彦.
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] β-シクロデキストリン誘導体を用いたmelatoninとの包接錯体形成による細胞内取り込み量と骨分化誘導能の評価2018

    • Author(s)
      寺内正彦, 山口聰
    • Organizer
      第72回NPO法人日本口腔科学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 骨形成を促進する硫酸化ポリロタキサン/BMP-2複合体による頭蓋骨欠損モデルの再生2018

    • Author(s)
      寺内正彦, 田村篤志, 山口聰, 由井伸彦
    • Organizer
      第47回医用高分子シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 歯槽骨再生を目指した硫酸化ポリロタキサン/骨形成因子複合体の骨誘導能評価2018

    • Author(s)
      寺内正彦, 田村篤志, 山口聰, 由井伸彦
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 硫酸化ポリロタキサン/骨形成因子複合体によるマウス頭蓋骨欠損モデル骨形成促進効果2017

    • Author(s)
      寺内正彦, 稲田大佳輔, 田村篤志, 山口聰, 由井伸彦
    • Organizer
      第39回日本バイオマテリアル学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 血管内皮細胞を活性化するための硫酸化ポリロタキサン表面の設計2017

    • Author(s)
      兵頭克弥、有坂慶紀、山口聰、由井伸彦
    • Organizer
      第39回日本バイオマテリアル学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Bone regeneration using bone morphogenetic protein-2 with supramolecular sulfonated polyrotaxane in mouse calvarial defect model.2017

    • Author(s)
      Terauchi M, Inada T, Tamura A, Yamaguchi S, Yui N
    • Organizer
      7th International Conference on Mechanics of Biomaterials and Tissues.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enhanced bone regeneration of bone morphogenetic protein-2 by the complexation with sulfonated polyrotaxane.2017

    • Author(s)
      Terauchi M, Inada T, Tamura A, Yui N, Yamaguchi S.
    • Organizer
      30th annual congress of Taiwanese Association of Oral and Maxillofacial Surgeons.
    • Related Report
      2017 Research-status Report
  • [Remarks] 東京医科歯科大学 生体材料工学研究所 有機生体材料学分野

    • Related Report
      2018 Research-status Report
  • [Remarks] 東京医科歯科大学 生体材料工学研究所 有機生体材料学分野

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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