Application of artificial periosteum containing BMP-2 to the treatment of refractory bone disease and bone nonunion.

• Project/Area Number: 17K11750
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Okayama University
• Principal Investigator: Kimura-Ono Aya 岡山大学, 大学病院, 助教 (20584626)
• Co-Investigator(Kenkyū-buntansha): 大野 充昭 岡山大学, 医歯薬学総合研究科, 准教授 (60613156) ; 窪木 拓男 岡山大学, 医歯薬学総合研究科, 教授 (00225195) ; 三野 卓哉 岡山大学, 医歯薬学総合研究科, 助教 (10625718) ; 宝田 剛志 岡山大学, 医歯薬学総合研究科, 研究教授 (30377428) ; 笈田 育尚 岡山大学, 医歯薬学総合研究科, 助教 (50625720)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: BMP-2 / 骨再生 / 難治性疾患 / 難治性骨欠損 / 人工骨膜 / 骨膜 / 感染

Outline of Final Research Achievements

Recently, we successfully regenerated the cortical bone-like bone, which is important to maintain the long-term stability of regenerated bone, using Escherichia coli-derived rhBMP-2 (E-rhBMP-2) adsorbed in PLGA membrane in rat model. The purpose of this study was to evaluate the E-rhBMP-2/PLGA membrane using peri-implantitis canine model. First, we generated the peri-implantitis model using beagle dogs and transplanted the autogenous bone to evaluate this animal model. Interestingly, autogenous bone graft could not recover the bone defect caused by peri-implantitis. Next, we transplanted the β-TCP containing E-rhBMP-2 in bone defects and covered with PLGA membrane containing E-rhBMP-2. Only β-TCP containing E-rhBMP-2 was transplanted as control group. As a result, PLGA membrane containing E-rhBMP-2 induced bone formation compared with control group. In conclusion, the PLGA membrane containing E-rhBMP-2 was efficient in bone formation in a peri-implantitis model in beagle dogs.

Academic Significance and Societal Importance of the Research Achievements

本申請研究において，未だ治療に苦慮しているインプラント周囲炎に対して，BMP-2含有PLGAメンブレン (BMP-2含有人工骨膜)を応用した新規治療法を提案することが可能な大変有意義な結果が得られた．また超高齢社会に伴い，骨折による高齢者の機能低下や死亡が問題となっている．例えば，代表的な寝たきり原因である大腿骨頸部骨折の25～40％に発生する難治性骨折・骨癒合不全は，長期に渡って患者を苦痛と機能障害で苦しめるのみならず，医療・介護費の増大につながるため，予後改善が臨床的・医療経済学的に喫緊の課題とされており，本研究の発展が患者のみならず，医療経済学的にも大変有意義な成果に繋がると考える．

Research Products

• [Journal Article] Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment (2018)
  • Author(s): Nguyen Ha Thi、Ono Mitsuaki、Oida Yasutaka、Hara Emilio Satoshi、Komori Taishi、Akiyama Kentaro、Nguyen Ha Thi Thu、Aung Kyaw Thu、Pham Hai Thanh、Tosa Ikue、Takarada Takeshi、Matsuo Koichi、Mizoguchi Toshihide、Oohashi Toshitaka、Kuboki Takuo
  • Journal Title: Journal of Bone and Mineral Research Volume: 34 Issue: 2 Pages: 327-332
  • DOI: 10.1002/jbmr.3598
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] マウス薬剤関連性顎骨壊死モデルにおける BMP-2の骨形成能の検討 (2020)
  • Author(s): 三海晃弘, 大野充昭, 納所秋二, 土佐郁恵, 縄稚久美子, 大野 彩, 窪木拓男, 大橋俊孝
  • Organizer: 岡山大学次世代研究拠点シンポジウム 2020
• [Presentation] 大型動物歯槽骨欠損モデルを用いた大腸菌由来rhBMP-2の骨再生能の検討 (2020)
  • Author(s): 田仲由希恵 ，大野充昭，納所秋二 ，石橋 啓，三海晃弘，土佐郁恵， 笈田育尚 ，大野 彩 ，秋山謙太郎 ，大橋俊孝，入江洋之，窪木 拓男
  • Organizer: 岡山大学次世代研究拠点シンポジウム 2020
• [Presentation] Bone-inducing effects of rhBMP-2 and rhFGF-2 in bone marrow microenvironment (2020)
  • Author(s): Shuji Nosho, Mitsuaki Ono, Akihiro Mikai, Kumiko Nawachi, Aya Kimura-Ono, Emilio S Hara, Takuo Kuboki, Toshitaka Oohashi
  • Organizer: International Association for Dental Research (IADR) 98th General Session and Exhibition and 49th Annual Meeting of the American Association for Dental Research (AADR)
  • Int'l Joint Research
• [Presentation] BMP-2 local administration for MRONJ-mice induced partial bone regeneration (2020)
  • Author(s): Akihiro Mikai, Mitsuaki Ono, Shuji Nosho, Ikue Tosa, Emilio S Hara, Aya Kimura-Ono, Kumiko Nawachi, Takuo Kuboki, Toshitaka Oohashi
  • Organizer: International Association for Dental Research (IADR) 98th General Session and Exhibition and 49th Annual Meeting of the American Association for Dental Research (AADR)
  • Int'l Joint Research
• [Presentation] A new function of Type XVIII collagen in Basement Membrane of Oral Mucosa: a regulator of Keratinization (2019)
  • Author(s): Ha Thi Thu Nguyen, Mitsuaki Ono, Emilio Satoshi Hara, Taishi Komori, Midori Edamatsu, Tomoko Yonezawa, Aya Kimura-Ono, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi
  • Organizer: 11th international conference on proteoglycans in Kanazawa
  • Int'l Joint Research
• [Presentation] Evaluating minimally important differences in OHRQOL appraisal after prosthodontic rehabilitation. (2018)
  • Author(s): Nakagawa S, Kimura-Ono A, Kurosaki Y, Koyama E, Numoto K, Tokumoto K, Mino T, Hara ES, Maekawa K, Kuboki T
  • Organizer: The 96th General Session & Exhibition of the IADR.
  • Int'l Joint Research
• [Presentation] Novel function of BMP-2 to prohibit bone formation in marrow environment. (2018)
  • Author(s): Nguyen HT, Ono M, Oida Y, Hara ES, Komori T, Akiyama K, Nguyen HTT, Aung KT, Pham HT, Oohashi T, Kuboki T
  • Organizer: The American Society of Bone and Mineral Research.
  • Int'l Joint Research
• [Presentation] Analysis bacterial flora of infected shunt in dialysis patients and its relation to oral flora. (2018)
  • Author(s): Nguyen HTT, Ono M, Kimura-Ono A, Komori T, Koyama E, Oohashi T, Kuboki T
  • Organizer: The 66th Annual Meeting of Japanese Association for Dental Research.
• [Presentation] 臨床応用に向けたイヌソケットプリザベーションモデルの構築ならびに大腸菌由来BMP2/βTCP複合体の有効性の検討 (2017)
  • Author(s): 納所秋二，大野充昭，三海晃弘，笈田育尚，小盛大志，土佐郁恵，大野 彩，窪木拓男．
  • Organizer: 第48回 日本口腔インプラント学会学術大会