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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11668
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Osaka 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
• 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

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.

Free Research Field

歯科理工学

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．