Development of prevention and treatment methods for dental caries in elderly based on bio-mineralization mechanisms

• Project/Area Number: 17H04382
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Conservative dentistry
• Research Institution: Osaka University
• Principal Investigator: Hayashi Mikako 大阪大学, 歯学研究科, 教授 (40271027)
• Co-Investigator(Kenkyū-buntansha): 奥山 克史 朝日大学, 歯学部, 准教授 (00322818) ; 松田 康裕 北海道医療大学, 歯学部, 講師 (50431317) ; 山本 洋子 大阪大学, 歯学研究科, 招へい教員 (60448107)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 歯学 / 象牙質 / 耐酸性 / 再石灰化 / コラーゲン / バイオミネラリゼーション / 歯質 / 根面う蝕 / 亜鉛 / エックス線光電子分光法 / 架橋

Outline of Final Research Achievements

In this study, anti-carious effects by ions such as Ca and F taken in dentin were investigated using novel particle and X-ray beam technologies with an aim of changing dental clinical practice from the conventional "drill and fill" to biological treatments based on bio-mineralization. The results of PIXE/PEGE and XRD analyses demonstrated that Zn incorporated into superficial dentin improved the anti-carious effect of dentin due to limit the deterioration of dentin collagen.

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、高齢者の問題である根面う蝕を予防し、効果的に治療するために、歯質に含まれるフッ素イオンに加えて、亜鉛イオンが有効であることを示した。とりわけ、先端的な量子・X線ビーム技術を用いて、歯質内の元素の濃度分布や化学結合状態をイメージングすることで、う蝕予防および進行抑制のメカニズムについて元素レベルでの深い理解を構築できたことは学術的意義が高い。さらに、この結果を用いて、効果的な 「削らない」う蝕予防・治療技術および材料開発につなげることが期待され、社会的な貢献に繋がる研究成果である。

Research Products

• [Journal Article] Comprehensive micro-mechanical characterization of experimental direct core build-up resin composites with different amounts of filler contents (2019)
  • Author(s): Koytchev E, Yamaguchi S, Shin-No Y, Suzaki N, Okamoto M, Imazato S, Datcheva, Hayashi M
  • Journal Title: Dental Materials Journal Volume: 38 Issue: 5 Pages: 743-749
  • DOI: 10.4012/dmj.2018-190
  • NAID: 130007723251
  • ISSN: 0287-4547, 1881-1361
  • Year and Date: 2019-09-27
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo. (2019)
  • Author(s): Okamoto Motoki、Takahashi Yusuke、Komichi Shungo、Ali Manahill、Watanabe Masakatsu、Hayashi Mikako
  • Journal Title: International Endodontic Journal Volume: ー Issue: 7 Pages: 1051-1062
  • DOI: 10.1111/iej.13099
  • Peer Reviewed
• [Journal Article] Lithium-containing surface pre-reacted glass fillers enhance hDPSC functions and induce reparative dentin formation in a rat pulp capping model through activation of Wnt/β-catenin signaling (2019)
  • Author(s): Ali Manahil、Okamoto Motoki、Komichi Shungo、Watanabe Masakatsu、Huang Hailing、Takahashi Yusuke、Hayashi Mikako
  • Journal Title: Acta Biomaterialia Volume: 96 Pages: 594-604
  • DOI: 10.1016/j.actbio.2019.06.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protein S100-A7 Derived from Digested Dentin Is a Critical Molecule for Dentin Pulp Regeneration (2019)
  • Author(s): Komichi Shungo、Takahashi Yusuke、Okamoto Motoki、Ali Manahil、Watanabe Masakatsu、Huang Hailing、Nakai Takeo、Cooper Paul、Hayashi Mikako
  • Journal Title: Cells Volume: 8 Issue: 9 Pages: 1002-1002
  • DOI: 10.3390/cells8091002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fluorine distribution from fluoride-releasing luting materials into human dentin (2019)
  • Author(s): Okuyama K, Matsuda Y, Yamamoto H, Tamaki Y, Saito T, Hayashi M, Yoshida Y, Sano H, Sato T, Koka M
  • Journal Title: Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms Volume: 456 Pages: 16-20
  • DOI: 10.1016/j.nimb.2019.06.047
  • Peer Reviewed / Open Access
• [Journal Article] Antibacterial effect of a fluoride-containing ZnO/CuO nanocomposite (2019)
  • Author(s): Matsuda Y, Okuyama K, Yamamoto H, Fujita M, Abe S, Sato T, Yamada N, Koka M, Sano H, Hayashi M, Sidhu SK, Saito T
  • Journal Title: Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms Volume: 458 Pages: 184-188
  • DOI: 10.1016/j.nimb.2019.06.039
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Application of a direct pulp capping cement containing S-PRG filler (2018)
  • Author(s): Takahashi Yusuke、Okamoto Motoki、Komichi Shungo、Imazato Satoshi、Nakatsuka Toshiyuki、Sakamoto Shuji、Kimoto Katsuya、Hayashi Mikako
  • Journal Title: Clinical Oral Investigations Volume: 23 Issue: 4 Pages: 1723-1731
  • DOI: 10.1007/s00784-018-2596-6
  • Peer Reviewed
• [Journal Article] Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases (2018)
  • Author(s): Okamoto Motoki、Takahashi Yusuke、Komichi Shungo、Cooper Paul R.、Hayashi Mikako
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 10690-10690
  • DOI: 10.1038/s41598-018-29112-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel evaluation method of dentin repair by direct pulp capping using high-resolution micro-computed tomography (2018)
  • Author(s): Okamoto Motoki、Takahashi Yusuke、Komichi Shungo、Ali Manahil、Yoneda Naomichi、Ishimoto Takuya、Nakano Takayoshi、Hayashi Mikako
  • Journal Title: Clinical Oral Investigations Volume: - Issue: 8 Pages: 1-9
  • DOI: 10.1007/s00784-018-2374-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pulp regeneration by 3-dimensional dental pulp stem cell constructs. (2018)
  • Author(s): Itoh Y, Sasaki JI, Hashimoto M, Katata C, Hayashi M, ;Imazato S.
  • Journal Title: Journal of Dental Research Volume: 97 Issue: 10 Pages: 1137-1143
  • DOI: 10.1177/0022034518772260
  • Peer Reviewed
• [Journal Article] Teaching of posterior composites in dental schools in Japan: 30 years and beyond. (2018)
  • Author(s): Hayashi M, Yamada T, Lynch C, Wilson NHF
  • Journal Title: Journal of Dentistry Volume: 76 Pages: 19-23
  • DOI: 10.1016/j.jdent.2018.02.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] HipOP mesenchymal population has high potential for repairing injured peripheral nerves (2018)
  • Author(s): Yamauchi et al.
  • Journal Title: J. Cellular Biochem. Volume: 印刷中 Issue: 6 Pages: 4836-4844
  • DOI: 10.1002/jcb.26684
  • Peer Reviewed
• [Journal Article] Use of PIXE/PIGE for sequential Ca and F measurements in root carious model (2017)
  • Author(s): Yagi K.、Yamamoto H.、Uemura R.、Matsuda Y.、Okuyama K.、Ishimoto T.、Nakano T.、Hayashi M.
  • Journal Title: Scientific reports Volume: 7 Issue: 1 Pages: 13450-13450
  • DOI: 10.1038/s41598-017-14041-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of a root canal treatment model in the rat (2017)
  • Author(s): Yoneda Naomichi、Noiri Yuichiro、Matsui Saori、Kuremoto Katsutaka、Maezono Hazuki、Ishimoto Takuya、Nakano Takayoshi、Ebisu Shigeyuki、Hayashi Mikako
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 3315-3315
  • DOI: 10.1038/s41598-017-03628-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Influence of polymerization properties of 4-META/MMA-based resin on the activity of fibroblast growth factor-2 (2017)
  • Author(s): Kitagawa H, Takeda K, Tsuboi R, Hayashi M, Sasaki JI, Imazato S.
  • Journal Title: Dental Materials Journal Volume: 36 Issue: 6 Pages: 724-730
  • DOI: 10.4012/dmj.2016-372
  • NAID: 130006224946
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Japan pioneering the caries treatemnts based on MI policy (2019)
  • Author(s): Hayashi, M
  • Organizer: China and Japan Friendship Hospital 35th anniversary
  • Int'l Joint Research / Invited
• [Presentation] Japan pioneering the guideline of treating caries based on MI policy (2019)
  • Author(s): Hayashi, M
  • Organizer: 1st Cons Asia Meeting
  • Int'l Joint Research / Invited
• [Presentation] How recent research advances to combat root caries (2019)
  • Author(s): Hayashi, M
  • Organizer: 97th IADR General Session - Geriatric Dentistry Group Symposium
  • Int'l Joint Research / Invited
• [Presentation] How Japan to achieve cavity-free future though all generations (2019)
  • Author(s): Hayashi, M
  • Organizer: ACFF Global Expert Panel Meeting 2019
  • Int'l Joint Research / Invited
• [Presentation] う蝕撲滅をどのように実現するか：臨床現場での取り組み (2019)
  • Author(s): 林 美加子
  • Organizer: 口腔衛生学会2019年学術大会
  • Invited
• [Presentation] ACFFの概念「2026年以降に生まれる子供はう窩を形成しない」を実現するために (2019)
  • Author(s): 林 美加子
  • Organizer: 口腔衛生学会2019年学術大会
  • Invited
• [Presentation] Evaluation of fluoride uptake into dentin over long-term using micro-PIXE/PIGE. (2019)
  • Author(s): Uemura R, Yamamoto H, Yagi K, Naito K, Amo M, Suzuki N, Hayashi N
  • Organizer: 97th International Association for Dental Research General Session
  • Int'l Joint Research
• [Presentation] Carious preventive effect of zinc ions penetrated into dentin (2019)
  • Author(s): Naito K, Uemura R, Yamamoto H, Iwami Y, Matsuda Y, Okuyama K, Hayashi M
  • Organizer: 97th International Association for Dental Research General Session
  • Int'l Joint Research
• [Presentation] Bioactivity and Biocompatibility of Lithium Contained Surface Pre-Reacted Glass Fillers (2019)
  • Author(s): Ali MS, Okamoto M, Komichi S, Watanabe M, Huang H, Takahashi Y, Hayashi M
  • Organizer: 97th International Association for Dental Research General Session
  • Int'l Joint Research
• [Presentation] The role of mTOR signal on reactionary and reparative dentin formation in vivo. (2019)
  • Author(s): Okamoto M, Takahashi Y, Komichi S, Ali MS, Watanabe M, Huang H, Cooper P, Hayashi M
  • Organizer: Pulp Biology and Regeneration Group Satellite Meeting
  • Int'l Joint Research
• [Presentation] Mechanical properties of fiber-reinforced CAD/CAM resin composite (2019)
  • Author(s): Suzaki N,Yamaguchi S, Hirose N, Imazato S, Hayashi M
  • Organizer: 4th meeting of the IADR APR 201
  • Int'l Joint Research
• [Presentation] Measurement of various ions in human teeth using in-air micro beam PIXE/PIGE (2018)
  • Author(s): Naito K, Yagi K, Yamamoto H, Iwami Y, Matsuda Y, Okuyama K, Yamada N, Koka M, Sato T, Hayashi M
  • Organizer: 16th International Conference On Nuclear Microprobe technology and Applications
  • Int'l Joint Research
• [Presentation] Lithium Ions Contained S-PRG Fillers Facilitated hDPSCs Migration and Functional Vascularity. (2018)
  • Author(s): Ali MS, Okamoto M, Komichi S, Watanabe M, Takahashi Y, Hayashi M.
  • Organizer: 96th International Association for Dental Research General Session
  • Int'l Joint Research
• [Presentation] Biocompatibility of S-PRG filler cements in rat subcutaneous implantation model. (2018)
  • Author(s): Okamoto M, Ali MS, Komichi S, Watanabe M, Naruse H, Itoh Y, Takahashi Y, Hayashi M
  • Organizer: 96th International Association for Dental Research General Session
  • Int'l Joint Research
• [Presentation] High-frequency waves promote periapical healing by inducing cell growth factors. (2018)
  • Author(s): Matsui S, Maezono H, Kuremoto K, Yoneda N, Ebisu S, Yumoto H, Ishimoto T, Nakano T, Noiri Y, Hayashi M
  • Organizer: 96th International Association for Dental Research General Session
  • Int'l Joint Research
• [Presentation] Assessment of novel ex vivo biofilm models using oral sample (2018)
  • Author(s): Klanliang K, Maezono H, Yamaguchi M, Sotozono M, Matsui S, Yoneda N, Noiri Y, Hayashi M
  • Organizer: The IFEA 11th World Endodontic Congress
  • Int'l Joint Research
• [Presentation] Dentin permeability and bactericidal effects of MDPB-containing cavity disinfectant (2018)
  • Author(s): Hirose N, Kitagawa H, Maezono H, Hayashi M, M Haapasalo, Imazato S
  • Organizer: 96th International Association for Dental Research General Session
  • Int'l Joint Research
• [Presentation] 多種イオンによる根面象牙質のう蝕抑制の検討 (2018)
  • Author(s): 内藤克昭、八木香子、山本洋子、岩見行晃、松田康裕、奥山克史、石本卓也、中野貴由、林 美加子
  • Organizer: 第149回日本歯科保存学会秋季学術大会
• [Presentation] UVA活性リボフラビン処理による根面う蝕予防効果の検討 (2018)
  • Author(s): 上村怜央、三浦治郎、八木香子、松田康裕、林美加子
  • Organizer: 大阪大学歯学会第64回総会
• [Presentation] 口腔サンプルを用いた新規ex vivoバイオフィルムモデルの開発 (2018)
  • Author(s): 前薗葉月、クランリアン キッティピット、外園真規、松井沙織、米田直道、野杁由一郎、林 美加子
  • Organizer: 第39回日本歯内療法学会学術大会
• [Presentation] Measurement of various ions in human teeth using in-air micro beam PIXE/PIGE (2018)
  • Author(s): 内藤克昭、八木香子、山本洋子、岩見行晃、松田康裕、奥山克史、山田尚人、江夏昌志、佐藤隆博、林 美加子
  • Organizer: 第13;回先進原子力科学技術に関する連携重点研究討論会
• [Presentation] 歯髄創傷治癒過程におけるProtein S100-A7の局在解析 (2018)
  • Author(s): 小道俊吾、高橋雄介、岡本基岐、Manahil. S. Ali、渡邉昌克、林 美加子
  • Organizer: 第148回日本歯科保存学会春季学術大会
• [Presentation] Riboflavin-UVA treatment prevents root fracture and caries by promoting collagen crosslinking. (2017)
  • Author(s): Hayashi M
  • Organizer: The University of Hong and Osaka University Joint Scientific Symposium- Current and Future Challenges in Dentistry
  • Int'l Joint Research / Invited
• [Presentation] Japan’s pioneering Guideline for treating caries. (2017)
  • Author(s): Hayashi M
  • Organizer: MI World Symposium in Tokyo
  • Int'l Joint Research / Invited
• [Presentation] How best to shift from invasive treatment to preventive care. (2017)
  • Author(s): Hayashi M
  • Organizer: 10th VIDEC
  • Int'l Joint Research / Invited
• [Presentation] Early diagnosis and bonded restorations are the keys to rescue endodontically treated teeth with vertical root fracture. (2017)
  • Author(s): 林 美加子
  • Organizer: 第38回日本歯内療法学会
  • Int'l Joint Research / Invited
• [Presentation] インプラント治療における抜歯基準の再考 － 救済すべき、あるいは救済できる垂直性歯根破折歯の要件は何か. (2017)
  • Author(s): 林 美加子
  • Organizer: 第47回日本口腔インプラント学会
  • Invited
• [Presentation] In-air micro-beam PIXE/PIGEによるCaを含有したグラスアイオノマーセメントを塗布した根面象牙質の耐酸性評価 (2017)
  • Author(s): 八木香子、山本洋子、上村怜央、奥山克史、松田康裕、鈴木耕拓、林 美加子
  • Organizer: 第146回日本歯科保存学会春季学術大会
• [Presentation] UVA活性リボフラビン処理による象牙質う蝕予防・進行抑制効果の検討 (2017)
  • Author(s): 上村怜央、三浦治郎、八木香子、松田康裕、林 美加子
  • Organizer: 第147回日本歯科保存学会秋季学術大会
• [Presentation] In-air micro-beam PIXE/PIGEを用いた各種イオンの歯質内分布 (2017)
  • Author(s): 内藤克昭、八木香子、山本洋子、松田康裕、奥山克史、林 美加子
  • Organizer: 第147回日本歯科保存学会秋季学術大会
• [Presentation] グラスファイバー配合強化型レジンを用いた間接法レジン支台築造の開発 (2017)
  • Author(s): 須崎尚子、新野侑子、廣瀬奈々子、山口 哲、今里 聡、林 美加子
  • Organizer: 第147回日本歯科保存学会秋季学術大会