Real-time imaging for innovative design of bone substitute materials.

• Project/Area Number: 15K01278
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NAGAI Akiko 東京医科歯科大学, 生体材料工学研究所, 准教授 (40360599)
• Co-Investigator(Kenkyū-buntansha): 野崎 浩佑 東京医科歯科大学, 生体材料工学研究所, 助教 (00507767) ; 堀内 尚紘 東京医科歯科大学, 生体材料工学研究所, 助教 (90598195)
• Research Collaborator: MASUDA Hiroshi 久留米大学, 医学部, 准教授 (10321861)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 機能性骨補填材 / アパタイトナノ薄膜 / リアルタイムイメージング / 機能性骨補填剤 / 材料表面設計 / リアルタイム評価 / 経時的イメージング / アパタイト / 薄膜 / ライブイメージング / 骨芽細胞 / 骨組織

Outline of Final Research Achievements

In this study, we aimed to evaluate interactions between the living body and implant materials by real-time imaging to develop functional bone substitutes.
Hydroxyapatite nanoparticles were prepared using self-organization of organic molecule. Nano-thin film was formed on glass, and stem cells or osteoblasts were cultured on it. Cell behaviors such as cell attachments or endocytosis could observed in real-time.
Real-time imaging for interactions between bone tissues and implants (hydroxyapatite porous bodies) were observed using the cranial window method. Bone formation started around the damaged bone with lacking in material-side by confocal microscopy observations. The result linked the difference between a bone prosthetic material and an autologous bone in the repair of bone and suggested the idea of development for innovative materials.

Research Products

• [Journal Article] Effects of controlled micro-/nanosurfaces on osteoblast proliferation (2017)
  • Author(s): Iwata Natsuko、Nozaki Kosuke、Horiuchi Naohiro、Yamashita Kimihiro、Tsutsumi Yusuke、Miura Hiroyuki、Nagai Akiko
  • Journal Title: Journal of Biomedical Materials Research Part A Volume: 105 Issue: 9 Pages: 2589-2596
  • DOI: 10.1002/jbm.a.36118
  • Peer Reviewed
• [Journal Article] Regulation of periodontal ligament-derived cells by type III collagen-coated hydroxyapatite (2017)
  • Author(s): Fujita Kazuhisa、Nozaki Kosuke、Horiuchi Naohiro、Yamashita Kimihiro、Miura Hiroyuki、Nagai Akiko
  • Journal Title: Bio-Medical Materials and Engineering Volume: 29 Issue: 1 Pages: 15-27
  • DOI: 10.3233/bme-171709
  • Peer Reviewed
• [Journal Article] Ag nanoparticle?coated zirconia for antibacterial prosthesis (2017)
  • Author(s): Yamada Risa、Nozaki Kosuke、Horiuchi Naohiro、Yamashita Kimihiro、Nemoto Reina、Miura Hiroyuki、Nagai Akiko
  • Journal Title: Materials Science and Engineering: C Volume: 78 Pages: 1054-1060
  • DOI: 10.1016/j.msec.2017.04.149
  • Peer Reviewed
• [Journal Article] Morphological and functional changes in RAW264 macrophage-like cells in response to a hydrated layer of carbonate-substituted hydroxyapatite (2017)
  • Author(s): Igeta K, Kuwamura Y, Horiuchi N, Nozaki K, Shiraishi D, Aizawa M, Hashimoto K, Yamashita K, Nagai A
  • Journal Title: J. Biomed. Mater. Res. A Volume: 105 Issue: 4 Pages: 1063-1070
  • DOI: 10.1002/jbm.a.35997
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Concentration-dependent effects of fibronectin adsorbed on hydroxyapatite surfaces on osteoblast adhesion (2015)
  • Author(s): Matsui N, Nozaki K, Ishihara K, Yamashita K, Nagai A
  • Journal Title: Mater. Sci. Eng. C Volume: 48 Pages: 378-383
  • DOI: 10.1016/j.msec.2014.12.042
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] No Dynamic Changes in Blood-brain Barrier Permeability in Developing Rats Occur during Local Cortex Exposure to Microwaves (2015)
  • Author(s): Masuda H, Hirota S, Ushiyama A, Hirata A, Arima T, Kawai H, Wake K, Watanabe S, Taki M, Nagai A, Ohkubo C
  • Journal Title: In Vivo Volume: 29 Pages: 351-357
  • Peer Reviewed
• [Presentation] 内皮細胞におけるグルコース修飾ハイドロキシアパタイトナノ粒子の細胞内取り込みの探索 (2018)
  • Author(s): 小室博明, 笹野哲郎, 山下仁大, 永井亜希子
  • Organizer: 日本セラミックス協会 2018年年会
• [Presentation] 炭酸置換型アパタイト上におけるRAW264細胞分化 (2017)
  • Author(s): 桑村雄太，堀内尚紘，野崎浩佑，橋本和明，山下仁大，永井亜希子
  • Organizer: 日本セラミックス協会 2017年年会
  • Place of Presentation: 日本大学（東京都千代田区）
  • Year and Date: 2017-03-17
• [Presentation] Electrical and structural evaluation of sodium ion doped beta-tricalcium phosphate (2017)
  • Author(s): Nozaki K, Endo T, Horiuchi N, Yamashita K, Hashimoto K, Itaka K, Nagai A.
  • Organizer: The Tenth International Conference on the Science and Technology for Advanced Ceramics (STAC-10)
  • Int'l Joint Research
• [Presentation] 二価のカルボン酸を用いた板状水酸アパタイトの水熱合成 (2017)
  • Author(s): 堀内 尚紘, 野崎 浩佑, 中村 美穂, 永井 亜希子, 山下 仁大.
  • Organizer: 日本セラミックス協会 第 30 回秋季シンポジウム
• [Presentation] ハイドロキシアパタイトナノ粒子の表面修飾によるトランスフェクション効率の向上 (2017)
  • Author(s): 小室博明, 笹野哲郎, 山下仁大, 永井亜希子
  • Organizer: 日本セラミックス協会 第 30 回秋季シンポジウム
• [Presentation] ナノアパタイトの表面修飾におけるトランスフェクション向上に及ぼす細胞吸収効果. (2017)
  • Author(s): 小室博明, 笹野哲郎, 山下仁大, 永井亜希子
  • Organizer: 第39回日本バイオマテリアル学会大会
• [Presentation] Influence of surface modification for hydroxyapatite nanoparticles by biomolecules on transfection efficiency. (2017)
  • Author(s): Hiroaki Komuro, Tetsuo Sasano, Kimihiro Yamashita, Akiko Nagai.
  • Organizer: International Symposium on Integrated Functionalities (ISIF)
  • Int'l Joint Research
• [Presentation] Carbonate Substitution in Hydroxyapatite Influences on Macrophage Differentiation. (2016)
  • Author(s): Nagai A
  • Organizer: K-J Ceramics 33
  • Place of Presentation: Daejeon, Korea
  • Year and Date: 2016-11-17
  • Int'l Joint Research / Invited
• [Presentation] 細胞足場材料のためのハイドロキシアパタイト薄膜作成 (2016)
  • Author(s): 野副菜摘，堀内尚紘，野崎浩佑，橋本和明，山下仁大，永井亜希子
  • Organizer: 第20回生体関連セラミックス討論会
  • Place of Presentation: 大阪大学（大阪府 吹田）
• [Presentation] Comparison of cytokines secretions from macrophage cultured on hydroxyapatite and carbonated apatite dense ceramics (2015)
  • Author(s): K. Igeta, K. Nozaki, M. Aizawa, K. Yamashita, A. Nagai.
  • Organizer: The International Chemical Congress of Pacific Basin Societies 2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] 炭酸置換アパタイトの作製および炭酸イオンが破骨細胞分化に与える影響 (2015)
  • Author(s): 桑村雄太，堀内尚紘，橋本和明，山下仁大，永井亜希子
  • Organizer: 第25回無機リン化学討論会
  • Place of Presentation: 山形大学（山形県米沢市）
  • Year and Date: 2015-09-28
• [Presentation] ドデカン二酸を用いたハイドロキシアパタイトの水熱合成. (2015)
  • Author(s): 柴田航太郎，堀内尚紘，野崎浩佑，中村美穂，永井亜希子，山下仁大
  • Organizer: 日本セラミックス協会 第28回秋季シンポジウム
  • Place of Presentation: 富山大学（富山県富山市）
  • Year and Date: 2015-09-17
• [Presentation] Hydrothermal synthesis of fibrous hydroxyapatite. (2015)
  • Author(s): K. Shibata, N. Horiuchi, K. Nozaki, M. Nakamura, A. Nagai, K. Yamashita.
  • Organizer: The 5th International Symposium on Advanced Materials Development and Integration of Novel Structured Metallic and Inorganic Materials
  • Place of Presentation: Waseda University (Tokyo, Japan))
  • Year and Date: 2015-06-09
  • Int'l Joint Research