Strategic development of a novel implant system to achieve bone regeneration without cell transplantation

• Project/Area Number: 19390509
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: TAKATO Tsuyoshi The University of Tokyo, 医学部附属病院, 教授 (90171454)
• Co-Investigator(Kenkyū-buntansha): CHIKADU Daichi 東京大学, 医学部附属病院, 講師 (30343122) ; OGASAWARA Toru 東京大学, 医学部附属病院, 講師 (20359623) ; NISHIYAMA Nobuhiro 東京大学, 大学院・医学系研究科, 准教授 (10372385) ; TEI Yuichi 東京大学, 大学院・医学系研究科, 教授 (30345053)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2009: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: 再生医療 / 骨再生 / 人工骨 / 移植・再生医療 / 再生医学 / シグナル伝達 / トランスレーショナルリサーチ / 骨再生療法 / 化合物スクリーニング / 化合物デリバリーシステム / インクジェットプリンター / Colla1GFP / 骨再生インプラント / 三次元造形法 / 骨分化シグナル / siRNA / ナノ送達システム

Research Abstract

This study aims to develop a novel bone regeneration system which helps or substitutes for cell transplantation. Among three pillars for regenerative medicine, we tried to improve two factors : "signal" and "scaffold". The combined use of nano-carriers and biomaterials induced the activation of osteogenic signal in cells around bone defect sites, which enabled bone regeneration without cell transplantation. In addition, we developed a technique for three-dimensional imaging followed by rapid prototyping to generate tailor-made artificial bone that fitted into defect sites.

Research Products

• [Journal Article] Immunological response to tissue-engineered cartilage derived from auricular chondrocytes and a PLLA scaffold in transgenic mice (2010)
  • Author(s): Fujihara Y, et al.
  • Journal Title: Biomaterials 31 Pages: 1227-1234
  • Peer Reviewed
• [Journal Article] Bone regeneration within a tailor-made tricalcium phosphate bone implant with both horizontal and vertical cylindrical holes transplanted into the skull of dogs (2009)
  • Author(s): Choi SJ, Lee JI, Igawa K, Sugimori O, Suzuki S, Mochizuki M, Nishimura R, Chung UI, Sasaki N.
  • Journal Title: J Artif Organs 12(4) Pages: 274-74
  • Peer Reviewed
• [Journal Article] Maxillofacial reconstruction using custom-made artificial bones fabricated by inkjet printing technology (2009)
  • Author(s): Saijo H, Igawa K, Kanno Y, Mori Y, Kondo K, Shimizu K, Suzuki S, Chikazu D, Iino M, Anzai M, Sasaki N, Chung UI, Takato T.
  • Journal Title: J Artif Organs 12(3) Pages: 200-5
  • NAID: 10025351463
  • Peer Reviewed
• [Journal Article] Unilateral expansion of a narrow mandibular dental arch combined with bimaxillary osteotomies in a patient with hypoglossia (2009)
  • Author(s): Mori Y, Susami T, Chikazu D, Saijo H, Sakiyama M, Matsuzaki M, Abe M, Wada M, Iino M, Takato T.
  • Journal Title: Int J Oral Maxillofac Surg. Jun ; 38(6) Pages: 689-93
  • Peer Reviewed
• [Journal Article] A distinctive role of the leukotriene B4 receptor BLT1 in osteoclastic activity during bone loss (2009)
  • Author(s): Hikiii H, et al.,
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 21294-21299
  • Peer Reviewed
• [Journal Article] Evaluation of 15 mandibular reconstructions with Dumbach Tit an Mesh-System and particulate cancellous bone and marrow harvested from bilateral posterior ilia (2009)
  • Author(s): Iino M, et al.
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107
  • Peer Reviewed
• [Journal Article] Identification of genes targeted by CpG island methylator phenotype in neuroblastomas, and their possible integrative involvement in poor prognosis (2008)
  • Author(s): Abe M., Watanabe N., McDonell N., Takato T., Ohira M., Nakagawara A., Toshikazu Ushijima
  • Journal Title: Oncology
  • Peer Reviewed
• [Journal Article] A case of tumoural calcinosis in the temporomandibular joint associated with systemic sclerosis (2008)
  • Author(s): Chikazu D., Mori Y., Saijo H., Fujihara H., Ko E. C., Hikiji H., Yonehara Y., Takato T.
  • Journal Title: Int J Oral Maxillofac Surg 37(2) Pages: 190-193
  • Peer Reviewed
• [Journal Article] Intraoral reconstruction of the soft palate following tumor resection using a mucoperiosteal flap supplied by the greater palatine vessels (2008)
  • Author(s): Chikazu D., Mori Y., Saijo H., Hasegawa Y., Fujihara H., Suenaga H., Ko EC., Yonehara Y., Takato T.
  • Journal Title: Asian J Oral Maxillofac Surg 19 Pages: 203-206
  • Peer Reviewed
• [Journal Article] Development of high-throughput screening system for osteogenic drugs using a cell-based sensor (2008)
  • Author(s): Hojo H., Igawa K., Ohba S., Yano F., Nakajima K., Komiyama Y., Ikeda T., Lichtler AC., Woo JT., Yonezawa T., Takato T., Chung UI.
  • Journal Title: Biochem Biophys Res Commun 14 ; 376 (2) Pages: 375-9
  • Peer Reviewed
• [Journal Article] Patchedl haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity (2008)
  • Author(s): Ohba, S., Kawaguchi, H., Kugimiya, F., Ogasawara, T., Kawamura, N., Saito, T., Ikeda, T., Fujii, K., Miyajima, T., Kuramochi, A., Miyashita, T., Oda, H., Nakamura, K., Takato, T., Chung, U.I.
  • Journal Title: Dev Cell 14 Pages: 689-69
  • Peer Reviewed
• [Journal Article] Metastasis of prostate cancer to the mandibular condyle (2008)
  • Author(s): Saijo H., Chikazu D., Mori Y., Hikiji H., Yonehara Y., Takato T.
  • Journal Title: Asian J Oral Maxillofac Surg 20 Pages: 86-88
  • Peer Reviewed
• [Journal Article] Clinical application of artificial bone in the maxillofacial region (2008)
  • Author(s): Saijo H., Chung UI., Igawa K., Mori Y., Chikazu D., IinoM., Takato T.
  • Journal Title: J Artif Organs 11 Pages: 171-176
  • NAID: 10025350281
  • Peer Reviewed
• [Journal Article] A case of tumoural calcinosis in the temporomandibular joint associated with systemic sclerosis. (2008)
  • Author(s): Chikazu D et al.,
  • Journal Title: Int J Oral Maxillofac Surg 37 Pages: 190-193
  • Peer Reviewed
• [Journal Article] Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondroytes (2008)
  • Author(s): Kawasaki-Y et al.,
  • Journal Title: J Clin Invest 118 Pages: 2506-2515
  • Peer Reviewed
• [Journal Article] Patchedl haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity. (2008)
  • Author(s): Ohba S et al.,
  • Journal Title: Dev Cell 14 Pages: 669-689
  • Peer Reviewed
• [Journal Article] Secondary correction of bilateral cleft lip and nasal defbrmity by simultaneous placement of an Abbe flap, septal cartilage graft, and cantilevered ihac bone graft (2008)
  • Author(s): Yoshiyuki Yonehara
  • Journal Title: Joumal of Oral and Maxillofacial Surgely 66 Pages: 581-588
  • Peer Reviewed
• [Journal Article] Controlled delivery of bFGF to recipient bed enhances the vascularization and viability of an ischemic skin flap (2008)
  • Author(s): Yuko Fujihara
  • Journal Title: Wound Repair and Regeneration 16 Pages: 125-131
  • Peer Reviewed
• [Journal Article] Marked and Independent Prognostic Significance of The CpG Island Methylator Phenotype in Neuroblastomas (2007)
  • Author(s): Abe M., Westermann F., Nakagawara A., Takato T., Schwab M., Ushijima T.
  • Journal Title: Cancer Lett 247(2) Pages: 253-258
  • Peer Reviewed
• [Journal Article] Intraoral Reconstruction of soft palate with the greater palatine vessels-supplying mucoperiosteal flap following the resection of the tumor (2007)
  • Author(s): Chikazu D., Mori Y., Saijo H., Hasegawa Y., Fujihara H., Suenaga H., Ko E. C, Yonehara Y., Takato T.
  • Journal Title: Asian J. Oral Maxillofac. Surg. 19 (4) Pages: 203-206
  • Peer Reviewed
• [Journal Article] Yonehara Cyclooxygenase-2 activity is essential for the osseointegration of dental implants (2007)
  • Author(s): Chikazu D., Tomizuka K., Ogasawara T., Saijo H., Koizumi T., Mori Y.
  • Journal Title: Int.J.Oral.Maxillofac.Surg. 36 Pages: 441-446
  • Peer Reviewed
• [Journal Article] Bone regeneration by regulated in vivo gene transfer using biocompatible polyplex nanomicelles (2007)
  • Author(s): Itaka K., Ohba S. (co-first), Miyata K., Kawaguchi H., Nakamura K., Takato T., Chung U.I., Kataoka K.
  • Journal Title: Mol Ther 15(9) Pages: 1655-1662
  • Peer Reviewed
• [Journal Article] Identification of a potent combination of osteogenic genes for bone regeneration using embryonic stem (ES) cell-based sensor (2007)
  • Author(s): Ohba S., Ikeda T., Kugimiya F., Yano F., Lichtler A. C., Nakamura K., Takato T., Kawaguchi H., Chung U. I.
  • Journal Title: FASEB J 21(8) Pages: 1777-1787
  • Peer Reviewed
• [Journal Article] A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner (2007)
  • Author(s): Ohba S., Nakajima K., Komiyama Y., Kugimiya F., Igawa K., Itaka K., Moro T., Nakamura K., Kawaguchi H., Takato T., Chung U. I.
  • Journal Title: Biochem Biophys Res Commun 357(4) Pages: 854-860
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 activity is essential for the osseointegration of dental implants (2007)
  • Author(s): Daichi Chikazu
  • Journal Title: International journal of Oral and Maxillofacial Surgery 36 Pages: 441-446
  • Peer Reviewed
• [Presentation] A novel thienoindazole-derivative small compound induces chondrogen ic differentiation without promoting hypertrophy through Runxl (2009)
  • Author(s): Yano F, et al.
  • Organizer: 31th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2009-09-11
• [Presentation] 3次元有限要素解析によるインクジェットプリンタを用いた人工骨の構造最適化 (2009)
  • Author(s): 井川和代, 西條英人, 菅野勇樹, 近津大地, 飯野光喜, 森良之鄭雄一, 高戸毅, 何建梅
  • Organizer: 第54回日本口腔外科学会総会
  • Place of Presentation: 札幌コンベンションセンター, 北海道
• [Presentation] カスタムメイド人工骨移植後の移植位置評価 (2009)
  • Author(s): 菅野勇樹, 西條英人, 井川和代, 大久保和美, 近津大地, 森良之, 飯野光喜, 鄭雄一, 高戸毅
  • Organizer: 第54回日本口腔外科学会総会
  • Place of Presentation: 札幌コンベンションセンター, 北海道
• [Presentation] Cyclooxygenase-2は膜性骨の骨折治癒における key factor である (2009)
  • Author(s): 近津大地, 藤川由美子, 末永英之, 杉山円, 古賀陽子, 阿部雅修, 西條英人, 森良之, 飯野光喜, 高戸毅
  • Organizer: 第54回日本口腔外科学会総会
  • Place of Presentation: 札幌コンベンションセンター, 北海道
• [Presentation] Finite Element Analysis of The Chin Augmentation Using Custom-Made Tricalcium Phosphate Implant (2009)
  • Author(s): Igawa K, Takato T, Yamamoto K, Suzuki S, Chung UI, He J.
  • Organizer: 11th ESPRAS Congress
  • Place of Presentation: Rhodes, Greece
• [Presentation] 下顎骨半側切除後のプレート再建に三次元立体モデルによりシミュレーションを施行した1例 (2008)
  • Author(s): 菅野勇樹, 西條英人, 森良之, 末永英之, 山田陽子, 前田祐二郎, 近津大地, 飯野光喜, 高戸毅
  • Organizer: 第62回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 福岡
• [Presentation] Development of Mini-Tetrapod Bone Fillers (2008)
  • Author(s): Igawa K., Tomizuka K., Choi S., Yamamoto K., Takato T., Sasaki N., Chung U.I.
  • Organizer: 86th General Session & Exhibition of the IADR
  • Place of Presentation: Toronto, Canada
• [Presentation] Development of high-throughput screening system for osteogenic drugs using cell-based sensor (2008)
  • Author(s): Hojo H., Igawa K., Ohba S., Yano F., Nakajima N., Komiyama K., Ikeda T., Lichtler AC., Woo JT., Yonezawa Y, Takato T., Chung UI.
  • Organizer: 30th annual meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Quebec, Canada
• [Presentation] Improvement in Wound Healing by a Novel Synthetic Collagen-gel Dressing in Diabetic Mice (2008)
  • Author(s): Chikazu D., Taguchi T., Koyama H., Hikiji H.., Fujihara H., Suenaga H., Saijo H., Mori Y., Iino M., Takato T.
  • Organizer: 8th Asian Congress on Oral and Maxillofacial Surgery
  • Place of Presentation: Bangkok, Thailand
• [Presentation] A novel small thienoindazole-derivative compound promotes chondroge nic difterentiaiion without inducing hypertrophy ilireugh pioduction of Runx1. (2008)
  • Author(s): Yano F et al.,
  • Organizer: 2008 OARSI (The Osteoarthritis Research Society International)
  • Place of Presentation: Roma, Italy
• [Presentation] 三次元積層造形法によるカスタムメイド人工骨の作成法 (2007)
  • Author(s): 菅野勇樹, 西條英人, 末永英之, 近津大地, 森良之, 米原啓之, 高戸毅
  • Organizer: 第52回日本口腔外科学会総会
  • Place of Presentation: 名古屋
• [Presentation] Patched1機能不全による Hedgehog シグナルの活性化は, Runx2のDNA結合・転写活性を競合阻害している抑制型Gli3産生を低下させることによって骨量を増加させる (2007)
  • Author(s): 大庭伸介, 藤井克則, 宮島剛, 倉持朗, 宮下俊之, 織田弘美, 中村耕三, 高戸毅, 川口浩, 鄭雄一
  • Organizer: 第25回日本骨代謝学会
  • Place of Presentation: 大阪
• [Presentation] 顎顔面領域におけるカスタムメイド人工骨の応用 (2007)
  • Author(s): 西條英人, 鄭雄一, 森良之, 末永英之, 菅野勇樹, 近津大地, 米原啓之, 高戸毅
  • Organizer: 第52回日本口腔外科学会総会
  • Place of Presentation: 名古屋
• [Presentation] Application of Custom-made Artificial Bones in the Maxillofacial Region (2007)
  • Author(s): Saijo H., Tei Y., Mori Y., Suenaga H., Chikazu D., Yonehara Y., Takato T.
  • Organizer: AAOMS 89th Annual Meeting, Scientific Sessions & Exhibition In conjunction with the JSOMS and KAOMS
• [Presentation] Tailor-made tricalcium phosphate bone implant directly fabricated by a three-dimensional ink-jet printer (2007)
  • Author(s): Igawa K., Mochizuki M., Sugimori O., Shimizu K., Yamazawa K., Kawaguchi H., Nakamura K., Takato T., Nishimura R., Suzuki S., Anzai M., Chung U.I., Sasaki N.
  • Organizer: The 45th Annual Meeting of the Japanese Society for Artificial Organs and the 2nd Meeting of the International Federation for Artificial Organs
  • Place of Presentation: Osaka
• [Presentation] A Novel Method for Designing Custom-made Artificial Bones (2007)
  • Author(s): Kanno Y., Saijo H., Kondo K., Mori Y., Chikazu D., Yonehara Y., Chun U.I., Takato T.
  • Organizer: TERMIS-AP
  • Place of Presentation: Tokyo
• [Book] Tissueengineering of bone and cartilage(IBMS Bone Key) (2009)
  • Author(s): Ohba S, Yano F, Chung U.
• [Book] 日本口腔外科学会雑誌(各社のインプラントとその特徴) (2009)
  • Author(s): 西條英人
• [Book] 日本口腔外科学会雑誌(再建下顎におけるインプラント治療) (2009)
  • Author(s): 高戸毅, 西條英人
• [Book] 再生医療の現状-医工連携の立場から-(日本学術会議、学術の動向) (2009)
  • Author(s): 高戸毅
• [Book] 頭蓋顔面の骨延長・私の工夫 (2009)
  • Author(s): 高戸毅, ら
  • Total Pages: 6
  • Publisher: 全日本病院出版会
• [Book] 「頭蓋顎顔面外科最近の進歩」第2版9-(2)成長発育がら見た治療法あ選択. (2008)
  • Author(s): 高戸毅, 森良之
  • Publisher: 克誠堂出版
• [Book] 口と歯の事典 (2008)
  • Author(s): 高戸 毅
  • Total Pages: 436
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~oralsurg/
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~oralsurg/archive.html
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~oralsurg/archive.html#original