Construction of the strategy on innovative tissue repair and bone regeneration using biological properties of carbon nano-materials

• Project/Area Number: 18K19627
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Hokkaido University
• Principal Investigator: YOKOYAMA ATSURO 北海道大学, 歯学研究院, 教授 (20210627)
• Co-Investigator(Kenkyū-buntansha): 山本 悟 北海道大学, 歯学研究院, 助教 (10344524) ; 平田 恵理 北海道大学, 歯学研究院, 助教 (10722019) ; 高野 勇太 北海道大学, 電子科学研究所, 准教授 (60580115)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: カーボンナノマテリアル / カーボンナノホーン / マクロファージ / チタン / 表面処理 / 骨形成 / カーボンナノ物質 / インプラント / カーボンナノチューブ / GBR膜 / 組織修復 / サイトカイン

Outline of Final Research Achievements

In this study, to establish new strategy on tissue and bone regeneration with the biological characteristics of CNHs, titanium was coated with CNHs with using electrodeposition. CNH/Ti was implanted in rat bone. Inflammatory cytokines and gene expression of macrophages cultured on CNH/Ti and Ti were analyzed and also fluorescent immunostaining was carried out.
CNH/Ti promoted bone formation in early stage.The amounts of TNFα and IL-6 on CNH / Ti were significantly lower than those on Ti, and there was no significant difference in IL-10.Gene Ontology analysis by microarray showed genes related to transcription, repair and replication of macrophage DNA in CNH / Ti were down-regulated compared to Ti. More macrophages with high intensity for CD206 was observed on CNH/T compared with Ti. Therefore, it was suggested that CNHs on the Ti surface regulate transcription, repair and replication of DNA of macrophage, and effect on M2 macrophage polarization.

Academic Significance and Societal Importance of the Research Achievements

インプラント材料として広く臨床応用されているチタン表面を炭素のみから構成される新素材であるカーボンナノホーン（CNHs）でコーティングすることにより初期の骨形成が促進されることが明らかとなり，また，CNHsが組織修復に関与するM2マクロファージの分極に影響している可能性が示された．これらの成果は，インプラントにおける骨再生の新たなストラテジーの構築に大きく寄与するとともに，新素材であるCNHsを用いた新たなインプラント材料の開発に発展するものと考えられ，将来のさらなる展開が期待される．

Research Products

• [Int'l Joint Research] フランス国立科学研究所(CNRS)(フランス)
• [Int'l Joint Research] フランス国立科学研究所(CNRS)(フランス)
• [Int'l Joint Research] フランス国立科学研究所(CNRS)(フランス)
• [Journal Article] Carbon nanohorn coating by electrodeposition accelerate bone formation on titanium implant (2021)
  • Author(s): Takada Sari、Hirata Eri、Sakairi Masatoshi、Miyako Eijiro、Takano Yuta、Ushijima Natsumi、Yudasaka Masako、Iijima Sumio、Yokoyama Atsuro
  • Journal Title: Artificial Cells, Nanomedicine, and Biotechnology Volume: 49 Issue: 1 Pages: 20-29
  • DOI: 10.1080/21691401.2020.1865388
  • Peer Reviewed / Open Access
• [Journal Article] Fate of Carbon Nanotubes Locally Implanted in Mice Evaluated by Near-Infrared Fluorescence Imaging: Implications for Tissue Regeneration (2019)
  • Author(s): Hirata Eri、Yudasaka Masako、Ushijima Natsumi、Sakaguchi Norihito、Maeda Yukari、Tanaka Takeshi、Kataura Hiromichi、Yokoyama Atsuro
  • Journal Title: ACS Applied Nano Materials Volume: 2 Issue: 3 Pages: 1382-1390
  • DOI: 10.1021/acsanm.8b02267
  • Peer Reviewed
• [Presentation] チタン表面に修飾したカーボンナノホーンに誘導されるマクロファージ遺伝子発現解析 (2020)
  • Author(s): 木村貞仁，平田恵理，高田紗理，横山敦郎
  • Organizer: 日本補綴歯科学会第129回学術大会
• [Presentation] カーボンナノホーン修飾チタン上で培養したマクロファージの極性と遺伝子発現の検索 (2020)
  • Author(s): 徐易坤，平田恵理，木村貞仁，横山敦郎
  • Organizer: 第10回ナノカーボンバイオシンポジウム
• [Presentation] Macrophage behavior on the titanium electrodeposited carbon nanohorn . (2019)
  • Author(s): Sadahito Kimura, Eri Hirata, Sari Takada, Masatoshi Sakairi, Masako Yudasaka, Atsuro Yokoyama
  • Organizer: NT19 20th International Conference on the Science and Application of Nanotubes and Low-Dimensional Materials
  • Int'l Joint Research
• [Presentation] カーボンナノホーン修飾チタン上でのマクロファージの挙動 (2019)
  • Author(s): 木村貞仁,平田恵理, 髙田紗理, 坂入正敏,湯田坂雅子,横山敦郎
  • Organizer: 第九回ナノカーボンバイオシンポジウム
• [Presentation] Observation of Carbon Nanotubes Locally Implanted in Mice: Implications for Tissue Regeneration. (2019)
  • Author(s): Eri Hirata, Masako Yudasaka, Yukari Maeda, Takeshi Tanaka, Hiromichi Kataura, Atsuro Yokoyama
  • Organizer: 7th International Conference for young chemists.
  • Int'l Joint Research
• [Presentation] Applications of carbon nanomaterials in bone tissue engineering. (2019)
  • Author(s): Eri Hirata
  • Organizer: CNRS Institut de Biologie Mol?culaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Th?rapeutique IBMC seminaire.
  • Int'l Joint Research / Invited
• [Presentation] Near-infrared photoluminescent imaging of carbon nanotubes locally implanted in mice. (2018)
  • Author(s): Eri Hirata, Masako Yudasaka, Yukari Maeda, Takeshi Tanaka, Hiromichi Kataura, Atsuro Yokoyama
  • Organizer: the 256th American Chemical Society National Meeting
  • Int'l Joint Research
• [Presentation] Macrophage behavior on the carbon nanohorn coated anodized titanium (2018)
  • Author(s): Sadahito Kimura, Eri Hirata, Sari Takada, Masatoshi Sakairi, Masako Yudasaka, Atsuro Yokoyama
  • Organizer: The 11th Congress of Asian Academy of Osseointegration 2018
  • Int'l Joint Research
• [Presentation] Activation of macrophage on the carbon nanohorn functionalized anodized titanium. (2018)
  • Author(s): Sadahito Kimura, Eri Hirata, Sari Takada, Masatoshi Sakairi, Masako Yudasaka, Atsuro Yokoyama
  • Organizer: The 66th Annual meeting of Japanese Association for Dental Research
  • Int'l Joint Research
• [Presentation] In vivo Kinetics of Carbon Nanotubes Locally Implanted in Mice (2018)
  • Author(s): Eri Hirata, Masako Yudasaka, Yukari Maeda, Takeshi Tanaka, Hiromichi Kataura, Atsuro Yokoyama
  • Organizer: The 66th Annual meeting of Japanese Association for Dental Research
  • Int'l Joint Research
• [Presentation] 静菌作用を付与したカーボンナノホーンの開発. (2018)
  • Author(s): 前田由佳利，平田恵理, 髙田紗理, 坂入正敏, 木村貞仁, 横山敦郎.
  • Organizer: 日本バイオマテリアル学会 北海道ブロック第3回研究会
• [Presentation] 骨伝導性向上を目的としたカーボンナノホーンによる陽極酸化チタンの表面修飾. (2018)
  • Author(s): 木村貞仁, 髙田紗理，坂入正敏，湯田坂雅子，平田恵理，横山敦郎.
  • Organizer: 日本バイオマテリアル学会 北海道ブロック第3回研究会
• [Presentation] カーボンナノホーンのミノサイクリン担持による静菌作用の付与. (2018)
  • Author(s): 前田由佳利，平田恵理, 髙田紗理, 坂入正敏, 木村貞仁, 横山敦郎
  • Organizer: 日本補綴学会第127回学術大会
• [Presentation] カーボンナノホーン修飾陽極酸化チタン上でのマクロファージの活性. (2018)
  • Author(s): 木村貞仁,平田恵理, 髙田紗理, 坂入正敏,湯田坂雅子,横山敦郎.
  • Organizer: 第八回ナノカーボンバイオシンポジウム