Bone regeneration and clinical application using the hybrid nanogel scaffolds

• Project/Area Number: 17K11849
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Toshiro Yamamoto 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40347472)
• Co-Investigator(Kenkyū-buntansha): 松田 修 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164) ; 足立 哲也 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10613573) ; PEZZOTTI G. 京都工芸繊維大学, 材料化学系, 教授 (70262962) ; 金村 成智 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70204542)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ナノゲル / 骨再生 / ラマン分光法 / 多孔性ナノゲル架橋ハイブリッドゲル / 間葉系幹細胞 / 配向性 / バイオマテリアル / 足場材料 / エクソソーム / 再生医学 / 細胞・組織 / 歯学

Outline of Final Research Achievements

Because of coming super-ageing-society, for alveolar bone loss due to ageing and periodontal disease, it has been expected to conduct regenerative remedies of periodontal tissue, utilizing scaffold and mesenchymal stem cell（MSC）. So, regeneration of periodontal tissue is very important in improving QOL. In existing treatment for bone loss, the quality of regenerated bone tissue has not been promising. In this study, we developed new scaffold “FD-NanoCliP-gel” that enable us to regulate the orientation of Hydroxy-Apatite（HAp）and the distribution of the Matrix vesicles and analyzed bone quality of regenerated bone tissue, for the purpose of development of core manufacturing technology in newly bone regenerative medicine.

Academic Significance and Societal Importance of the Research Achievements

多孔性ナノゲル架橋ハイブリッドゲル（Nano CliP gel: nanogel-cross linked-porous freeze-dried gel）はその表面の化学的性状により、カルシウムやリンイオンを吸着することで、力学機能を発揮するc軸方向へHAP結晶の成長を促していることが明らかとなった。Nano CliPゲルはアテロコラーゲンと比較して、結晶配向性の高い剛性と弾性を併せ持つ再生骨組織を構築することから、骨質の低下した骨疾患患者や高齢者に対して、良質の骨組織を提供する新たな骨再生医療の基盤技術になり得る。

Research Products

• [Journal Article] Osteogenic response of mesenchymal progenitor cells to natural polysaccharide nanogel and atelocollagen scaffolds: A spectroscopic study (2019)
  • Author(s): Horiguchi Satoshi、Adachi Tetsuya、Rondinella Alfredo、Boschetto Francesco、Marin Elia、Zhu Wenliang、Tahara Yoshiro、Yamamoto Toshiro、Kanamura Narisato、Akiyoshi Kazunari、Pezzotti Giuseppe、Mazda Osam
  • Journal Title: Materials Science and Engineering: C Volume: 99 Pages: 1325-1340
  • DOI: 10.1016/j.msec.2019.02.043
  • Peer Reviewed
• [Journal Article] Transplantation of dental pulp‐derived cell sheets cultured on human amniotic membrane induced to differentiate into bone (2019)
  • Author(s): Takizawa Shigeta、Yamamoto Toshiro、Honjo Ken‐Ichi、Sato Yoshiki、Nakamura Koya、Yamamoto Kenta、Adachi Tetsuya、Uenishi Toshihiro、Oseko Fumishige、Amemiya Takeshi、Yamamoto Yoshiaki、Kumagai Wataru、Kita Masakazu、Kanamura Narisato
  • Journal Title: Oral Diseases Volume: 25 Issue: 5 Pages: 1352-1362
  • DOI: 10.1111/odi.13096
• [Journal Article] In situ molecular vibration insights into the antibacterial behavior of silicon nitride bioceramic versus gram-negative Escherichia coli (2019)
  • Author(s): Boschetto Francesco、Adachi Tetsuya、Horiguchi Satoshi、Marin Elia、Paccotti Niccol?、Asai Tenma、Zhu Wenliang、McEntire Bryan J.、Yamamoto Toshiro、Kanamura Narisato、Mazda Osam、Ohgitani Eriko、Pezzotti Giuseppe
  • Journal Title: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy Volume: 223 Pages: 117299-117299
  • DOI: 10.1016/j.saa.2019.117299
• [Journal Article] Osteogenic Enhancement of Zirconia-Toughened Alumina with Silicon Nitride and Bioglass? (2019)
  • Author(s): Pezzotti、Marin、Zanocco、Boschetto、Zhu、McEntire、Bal、Adachi、Yamamoto、Mazda
  • Journal Title: Ceramics Volume: 2 Issue: 4 Pages: 554-567
  • DOI: 10.3390/ceramics2040043
• [Journal Article] Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration. (2018)
  • Author(s): Sato Y, Yamamoto K, Horiguchi S, Tahara Y, Nakai K, Kotani SI, Oseko F, Pezzotti G, Yamamoto T, Kishida T, Kanamura N, Akiyoshi K, Mazda O.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 15824-15824
  • DOI: 10.1038/s41598-018-33892-z
  • Peer Reviewed / Open Access
• [Journal Article] Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal. (2018)
  • Author(s): Yamamoto K, Kishida T, Nakai K, Sato Y, Kotani SI, Nishizawa , Yamamoto T, Kanamura N, Mazda O.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 8463-8463
  • DOI: 10.1038/s41598-018-26745-2
  • Peer Reviewed / Open Access
• [Journal Article] Vibrational monitor of early demineralization in tooth enamel after in vitro exposure to phosphoridic liquid (2017)
  • Author(s): Pezzotti G, Adachi T, Gasparutti I, Vincini G, Zhu W, Boffelli M, Rondinella A, Marin E, Ichioka H, Yamamoto T, MARUNAKA Y, Kanamura N
  • Journal Title: Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy Volume: 173 Pages: 19-33
  • DOI: 10.1016/j.saa.2016.08.036
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Normal human gingival fibroblasts undergo cytostasis and apoptosis after long-term exposure to butyric acid (2017)
  • Author(s): Shirasugi M, Nishioka K, Yamamoto T, Nakaya T, Kanamura N
  • Journal Title: Biochem Biophys Res Commun Volume: 482 Issue: 4 Pages: 1122-1128
  • DOI: 10.1016/j.bbrc.2016.11.168
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of aprotinin, a protease inhibitor, action on the trafficking of epithelial Na+ channels (ENaC) in renal epithelial cells using a mathematical model. (2017)
  • Author(s): Sasamoto, K., Marunaka, R. #, Niisato, N., Sun, H., Taruno, A., Pezzotti, G., Yamamoto, T., Kanamura, N., Zhu, W., Nishio, K., Inui, T., Eaton, D.C., & Marunaka, Y.
  • Journal Title: Cell Physiol Biochem Volume: 41 Issue: 5 Pages: 1865-1880
  • DOI: 10.1159/000471934
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Actions of quercetin, a polyphenol, on blood pressure. (2017)
  • Author(s): Marunaka, Y., Marunaka, R., Sun, H., Yamamoto, T., Kanamura, N., Inui, T. & Taruno, A.
  • Journal Title: Molecules Volume: 22 Issue: 2 Pages: 209-209
  • DOI: 10.3390/molecules22020209
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 生体アパタイトの配向性を制御する多孔性ナノゲル架橋ハイブリッドゲルを用いた骨再生 (2019)
  • Author(s): 足立哲也, 山本俊郎, 田原義朗, Pezzotti Giuseppe, 松田修, 秋吉一成, 金村成智
  • Organizer: 第41回日本バイオマテリアル学会大会
• [Presentation] 生体アパタイトの配向性を制御するFD-NanoCliP-gelを用いた3次元骨組織の構築と分光学的解析 (2019)
  • Author(s): 堀口智史, 足立哲也, 田原義朗, 山本俊郎, 秋吉一成, Giuseppe Pezzotti, 松田 修, 金村成智
  • Organizer: 第40回日本炎症・再生医学会
• [Presentation] Osteoblast-like cells transplantation treatment of large scale bone defect using direct reprogramming technique and 3D scaffold. (2018)
  • Author(s): Sato Y, Yamamoto K, Nakai K, Oseko F, Hasegawa A, Kishida T, Mazda O, Yamamoto T, Kanamura N.
  • Organizer: 13th Asian Congress of Oral & Maxillofacial Surgery
  • Int'l Joint Research
• [Presentation] Fast and highly spatially resolved detection of early dental caries by spectrally resolved Raman spectroscopy for Special Needs Patients. (2018)
  • Author(s): Yamamoto T, Adachi T, Horiguchi S, Pezzotti G, Kanamura N.
  • Organizer: 24th International Association for Disability and Oral Health Congress, 31 August-2 September 2018
  • Int'l Joint Research
• [Presentation] Development of a SiYAION glaze for improved osteoconductivity of dental implants. (2018)
  • Author(s): Yamamoto T, Adachi T, Horiguchi S, Rondinella A, Boschetto F, Marin E, McEntire BJ, Bock R, Mazda O, Kanamura N, Pezzotti G.
  • Organizer: 96th General Session & Exhibition 2018 of the IADR
  • Int'l Joint Research
• [Presentation] Detection of early dental caries by spectrally resolved Raman spectroscopy. (2018)
  • Author(s): Adachi T, Horiguchi S, Amemiya T, Yamamoto T, Kanamura N, Pezzotti G.
  • Organizer: 96th General Session & Exhibition 2018 of the IADR
  • Int'l Joint Research
• [Presentation] Establishment of bone regeneration therapy by direct conversion using rat fibroblasts. (2018)
  • Author(s): Sato Y, Yamamoto K, Nakai K, Oseko F, Kishida T, Mazda O, Yamamoto T, Kanamura N.
  • Organizer: 40TH Asia Pacific Dental Congress
  • Int'l Joint Research
• [Presentation] ダイレクト・コンバージョン技術を用いた新規骨再生療法の開発. (2018)
  • Author(s): 中井 敬, 佐藤良樹, 山本健太, 足立哲也, 足立圭司, 大迫文重, 雨宮 傑, 山本俊郎, 金村成智.
  • Organizer: 第61回秋季日本歯周病学会学術大会
• [Presentation] Application of Silicon Nitride Ceramics Stimulate Bone Regeneration in Dental Implants. (2017)
  • Author(s): Adachi T, Yamamoto T,Amemiya T, McEntire BJ, Bal BS, Mazda O, Kanamura N, Pezzotti G.
  • Organizer: The 2017 IADR/AADR/CADR General Session & Exhibition.
  • Int'l Joint Research
• [Presentation] Human Periosteal-derived Cell Sheets Cultured on Amniotic Membrane Substrate (2017)
  • Author(s): Amemiya T , Adachi T, Asai T , Adachi K , Oseko F, Yamamoto T, Kanamura N
  • Organizer: The 2017 IADR/AADR/CADR General Session & Exhibition.
  • Int'l Joint Research