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Embryotoxicity of titanium alloy implant composition metal by mouse ES / iPS cells

Research Project

Project/Area Number 16K11668
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dental engineering/Regenerative dentistry
Research InstitutionOsaka Dental University

Principal Investigator

IMAI Koichi  大阪歯科大学, 歯学部, 教授 (90103100)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsチタン合金 / Ti-6Al-4V / 発生毒性 / in vitro / EST法 / インプラント / 表面処理 / フッ化水素酸 / チタン / フッ酸 / 口腔インプラント / 純チタン / EST
Outline of Final Research Achievements

The in vitro embryotoxicities of metals (Ti, V, Al, Nb, Ta, and Zr) used in a commercially available implant made of titanium alloy were examined by the EST protocol, demonstrating no embryotoxicity for any metal, except vanadium. The survival rates of mouse 3T3, ES-D3, and iPS cells based on the MTT method were lower in the fluoride-treated group than in the negative controls (i.e., untreated ground powder and plate made of titanium alloy).
In addition, the test solution, prepared by immersing corroded, ground powder (hydrofluoric acid-treated ground powder of Ti-6Al-4V plate (ASTM F136)) into a cell culture medium, reduced the rates of contraction in teratomas, due to differentiation, in both ES-D3 and iPS cells, as compared with untreated titanium alloy. However, the ALP activities showed no significant difference. No embryotoxicity was demonstrated, even though the experimental conditions were more severe than the conditions on actual use.

Academic Significance and Societal Importance of the Research Achievements

チタン合金インプラントのヒトの正常な新生児誕生に関係する生殖・発生毒性リスクについては未知である.フッ化物が含まれた歯磨や洗口剤の使用についてのチタン合金製インプラント腐食物についての発生毒性リスクの情報は存在しない.今回,EST法でバナジウム含有合金に発生毒性リスクの可能性が判明し,医療用Ti-6Al-4V合金研削粉がES-D3細胞とマウス由来iPS細胞の正常な分化に影響することが判明したことは学術的にも影響は大きいと考えられる.今回のin vitro実験のみではヒトの発生毒性リスクが存在する可能性は難しいが,さらに社会的にも多方面から発生毒性研究の継続を期待するものである.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Study of Differentiation Level by Three-dimensional Culture of Mouse ES Cells on Titanium Alloy Powder2018

    • Author(s)
      Imai K, Shirai T, Akiyama M, Zenyu M, Yoshida T, Okamura T, Shida M, Shimizu H, Morita S, Tominaga K, Masuno K, Matsumoto H, Nishikawa T.
    • Journal Title

      Journal of Oral Tissue Engineering

      Volume: 15 Issue: 3 Pages: 159-164

    • DOI

      10.11223/jarde.15.159

    • NAID

      130006730877

    • ISSN
      1348-9623, 1880-0823
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of Fluoride Contamination on Titanium Surface on Cell Viability and Cell Differentiation of ES-D3 Cells2017

    • Author(s)
      Imai K, Zennyu K, Yoshida T, Ono Y, Kumabe S, Nishikawa T.
    • Journal Title

      Journal of Oral Tissue Engineering

      Volume: 15 Issue: 1 Pages: 35-40

    • DOI

      10.11223/jarde.15.35

    • NAID

      130006394587

    • ISSN
      1348-9623, 1880-0823
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of Embryotoxicity by Four Kinds of Fluorine Compounds Based on Embryonic Stem Cell Test (EST) Protocol2016

    • Author(s)
      Imai K, Oshima H, Hashimoto Y, Akiyama M, Zennyu M, Yoshida T, Nishikawa T. Masuno K, Matsumoto H.
    • Journal Title

      Journal of Oral Tissue Engineering

      Volume: 14 Issue: 2 Pages: 91-97

    • DOI

      10.11223/jarde.14.91

    • NAID

      130005243472

    • ISSN
      1348-9623, 1880-0823
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 純チタン腐食物の変異原性について -フッ化水素酸処理の影響-2018

    • Author(s)
      今井 弘一, 橋本 典也, 秋山 真理, 白井 翼, 吉田 貴光
    • Organizer
      第8回臨床ゲノム医療学会"大阪学術大会"
    • Related Report
      2018 Annual Research Report
  • [Presentation] インプラントで用いられるチタン腐食物の変異原性2018

    • Author(s)
      今井 弘一, 橋本 典也, 秋山 真理, 白井 翼, 善入 雅之, 西川 哲成
    • Organizer
      第16回日本再生歯科医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Ti-6Al-4V合金のフッ化水素酸溶液による腐食生成物の発生毒性2018

    • Author(s)
      今井 弘一, 橋本 典也, 秋山 真理, 白井 翼, 中井 真理子, 横山 直史
    • Organizer
      第13回ナノ・バイオメディカル学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] チタン表面のフッ化水素酸処理における発生毒性への影響2018

    • Author(s)
      今井 弘一, 橋本 典也, 秋山 真理, 白井 翼, 西川 哲成, 本田 義知
    • Organizer
      第48回日本口腔インプラント学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] フッ化水素酸処理のTi-6Al-4V合金がES細胞の細胞増殖と細胞分化に与える影響2018

    • Author(s)
      今井 弘一, 橋本 典也, 秋山 真理, 白井 翼
    • Organizer
      バイオインテグレーション学会第8回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] チタン合金インプラント組成金属イオンのin vitro発生毒性について2017

    • Author(s)
      今井 弘一, 橋本 典也,西川 哲成
    • Organizer
      第47回日本口腔インプラント学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 近未来の再生医療と生物学的安全性試験への胚性幹細胞の応用2016

    • Author(s)
      今井 弘一
    • Organizer
      日本再生歯科医学会第8回シンポジウム
    • Place of Presentation
      鹿児島大学桜ヶ丘キャンパス(鹿児島県・鹿児島市)
    • Year and Date
      2016-07-18
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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