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Gene activated-matrix comprised of self-assemble and multi-functional nano-devise facilitates the bone engineering

Research Project

Project/Area Number 17H01604
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionNagasaki University

Principal Investigator

Asahina Izumi  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30221039)

Co-Investigator(Kenkyū-buntansha) 小守 壽文  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (00252677)
兒玉 幸修  長崎大学, 病院(医学系), 准教授 (50448510)
住田 吉慶  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (50456654)
佐々木 均  長崎大学, 病院(医学系), 教授 (00170689)
鎌倉 慎治  東北大学, 医工学研究科, 教授 (80224640)
三浦 桂一郎  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10634446)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2021: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2020: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2019: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2017: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords骨再生 / 遺伝子 / ベクター / 人工骨基質 / 遺伝子治療 / 遺伝子活性化基質 / 遺伝子導入担体 / 遺伝子送達デバイス / 基質 / 自己組織化デバイス
Outline of Final Research Achievements

This study investigated whether a gene-activated matrix (GAM) composed of nanoballs containing pDNAs encoding BMP4 (pBMP4) could promote bone augmentation. We prepared nanoballs (BMP4-nanoballs) constructed with pBMP4 and dendrigraft poly-L-lysine (a cationic polymer) coated by γ-polyglutamic acid (an anionic polymer) and determined their biological functions in vitro and in vivo. Next, GAMs were manufactured by mixing nanoballs with 2% atelocollagen and β-TCP granules and lyophilizing for bone augmentation. GAMs were then transplanted to rat cranial bone surfaces under periosteum. As results, bone augmentation was clearly recognized for up to 8 weeks in transplanted GAMs containing BMP4-nanoballs. Notably, only 0.001mg of BMP4-nanoballs induced a sufficient volume of new bone, while 1mg of naked pDNAs were required to induce the same level of bone augmentation. These data suggest that applying this anionic vector to appropriate matrices can facilitate GAM-based bone engineering.

Academic Significance and Societal Importance of the Research Achievements

新規遺伝子送達体としてのNanoballを遺伝子活性化基質(gene-activated matrix;GAM)に応用する取り組みは、本研究チーム独自の技術を発展させた従来にない独創的・集約的な研究である。Nanoballは、生体内で早期に分解されることなく、凍結保存により長期保存も可能である。そのため、骨再生局所でその機能を効果的に発揮させる技術を開発できれば、従来の人工骨や成長因子などを応用した代替治療製品にない、廉価で安定供給が見込める汎用性の高い骨再生医療製品を創出できる。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (8 results)

All 2022 2021 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation2021

    • Author(s)
      Masahito Hara,Yoshinori Sumita,Yukinobu Kodama,Mayumi Iwatake, Hideyuki Yamamoto,Rena Shido,Shun Narahara,Takunori Ogaeri,Hitoshi Sasaki and Izumi Asahina
    • Journal Title

      Materials

      Volume: 14 Issue: 22 Pages: 22-22

    • DOI

      10.3390/ma14227097

    • NAID

      120007186847

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene-activated matrix harboring a miR20a-expressing plasmid promotes rat cranial bone augmentation2021

    • Author(s)
      Shido Rena、Sumita Yoshinori、Hara Masahito、Iwatake Mayumi、Narahara Shun、Umebayashi Mayumi、Miura Kei-ichiro、Kodama Yukinobu、Asahina Izumi
    • Journal Title

      Regenerative Biomaterials

      Volume: 8 Issue: 2 Pages: 1-9

    • DOI

      10.1093/rb/rbaa060

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 歯槽骨再生治療を対象とした骨誘導性遺伝子活性化基質の開発研究2022

    • Author(s)
      住田吉慶
    • Organizer
      第21回再生医療学会 シンポジウム13 新しく開発された骨再生研究の最前線
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Effective gene-activated matrix with self-assembly nano-devices for bone engineering.2019

    • Author(s)
      Hara M, Sumita Y, Shido R, Kodama Y, Asahina I
    • Organizer
      International Association for Dental Research (IADR) 97th General Session & Exhibition
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規自己組織化ナノデバイス (Nanoball) を応用した骨誘導性遺伝子活性化基質(GAM)の開発2019

    • Author(s)
      原昌士, 住田吉慶, 四道玲奈, 楢原峻, 朝比奈泉
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] micro RNAを応用した遺伝子活性化基質(GAM)による新規人工骨基質の開発2018

    • Author(s)
      四道玲奈, 住田吉慶, 原昌士, 楢原峻, 朝比奈泉
    • Organizer
      第63回日本口腔外科学会総会・学術大会,
    • Related Report
      2018 Annual Research Report
  • [Presentation] Gene Activated-matrix (GAM) comprised of atelocollagen and plasmid DNA encoding microRNA promotes rat cranial bine augmentation2018

    • Author(s)
      Shido R, Sumita Y, Hara M, Narahara S, Asahina I
    • Organizer
      The American Society for Bone and Mineral Research Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 機能性microRNAを搭載した遺伝子活性化基質(GAM)による骨再生の試み2018

    • Author(s)
      4.四道玲奈, 住田吉慶, 岩竹真弓, 楢原峻, 原昌士, 坂下直美, 朝比奈泉
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2023-01-30  

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