Development of high performance artificial bone

2011 Fiscal Year Final Research Report

• Project/Area Number: 20240043
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: The University of Tokyo
• Principal Investigator: TEI Yuichi 東京大学, 大学院・工学系研究科, 教授 (30345053)
• Co-Investigator(Kenkyū-buntansha): SAKAI Takamasa 東京大学, 大学院・工学系研究科, 教授 (70456151)
• Project Period (FY): 2008 – 2011
• Keywords: 人工臓器学 / 再生医工学

Research Abstract

Artificial bones are inferior to autograft and allograft bone in performance, leaving clinicians dissatisfied. We integrated the method to control 3D shape of artificial bones made of calcium phosphate powder materials, which have high biocompatibility, biosafety and biodegradability, and the method to endow biomaterials with bioactivity, which controls the function of surrounding cells, and created two types of novel artificial bones : custom-made artificial bone and tetrapod-shaped artificial bones.

Research Products

• [Journal Article] Effect of trehalose coating on basic fibroblast growth factor release from tailor-made artificial bone implant (2011)
  • Author(s): Choi S, Lee J, Igawa K, Suzuki S, Mochizuki M, Nishimura R, Chung U, Sasaki N.
  • Journal Title: J Vet Med Sci Volume: 73 Pages: 1547-1552
  • Peer Reviewed
• [Journal Article] Examination of the theories of rubber elasticity using an ideal polymer network (2011)
  • Author(s): Akagi Y, Katashima T, Katsumoto Y, Fujii K, Matsunaga T, Chung U, Shibayama M, Sakai T.
  • Journal Title: Macromolecules Volume: 44 Pages: 5817-5821
  • Peer Reviewed
• [Journal Article] Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling (2011)
  • Author(s): Yonezawa T, Lee J, Hibino A, Asai M, Hojo H, Ha B, Teruya T, Nagai K, ChungU, Yagasaki K, Woo J.
  • Journal Title: Biochem Biophys Res Commun Volume: 409 Pages: 260-265
  • Peer Reviewed
• [Journal Article] Precise control and prediction of hydrogel degradation behavior (2011)
  • Author(s): Li X, Tsutsui Y, Matsunaga T, Shibayama M, Chung U, Sakai T.
  • Journal Title: Macromolecules Volume: 44 Pages: 3567-3571
  • Peer Reviewed
• [Journal Article] SANS Studies on Tetra-PEG Gel under Uniaxial Deformation (2011)
  • Author(s): Matsunaga T, Asai H, Akagi Y, Sakai T, Chung U, Shibayama M.
  • Journal Title: Macromolecules Volume: 44 Pages: 1203-1210
  • Peer Reviewed
• [Journal Article] A novel method for designing and fabricating custom-made artificial bones (2011)
  • Author(s): Saijo H, Kanno Y, Mori Y, Suzuki S, Ohkubo K, Chikazu D, Yonehara Y, ChungU, Takato T.
  • Journal Title: Int J OralMaxillofac Surg Volume: 40 Pages: 955-960
  • Peer Reviewed
• [Journal Article] Structure and dymanics of tetra-PEG gel by Brownian dynamics (2010)
  • Author(s): Hashimoto Y, Takasu M, Kawamoto S, Oda T, Nagao H, Sakai T, Chung U.
  • Journal Title: Trans Mater Res Soc Japan Volume: 35 Pages: 547-553
  • Peer Reviewed
• [Journal Article] Highly elastic and deformable hydrogel formed from tetra-arm polymers (2010)
  • Author(s): Sakai T, Matsunaga T, Akagi Y, Kurakazu M, Chung U, Shibayama M.
  • Journal Title: Macromolecular Rapid Commun Volume: 31 Pages: 1954-1959
  • Peer Reviewed
• [Journal Article] Coordination of chondrogenesis and osteogenesis by hypertrophic chondrocytes in endochondral bone development (2010)
  • Author(s): Hojo H, Ohba S, Yano F, Chung U.
  • Journal Title: J Bone Miner Metab Volume: 28 Pages: 489-502
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of endochondral ossification by HIF2A during skeletal growth and osteoarthritis development (2010)
  • Author(s): Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, and Kawaguchi H.
  • Journal Title: Nature Med Volume: 16 Pages: 678-683
  • Peer Reviewed
• [Journal Article] Synthesis and mechanical properties of a nanocomposite gel consisting of a tetra-PEG/clay network (2010)
  • Author(s): Fukasawa M, Sakai T, Chung U, Haraguchi K.
  • Journal Title: Macromolecules Volume: 43 Pages: 4370-4378
  • Peer Reviewed
• [Journal Article] Trehalose inhibits oral xerosis by protecting cell membrane (2010)
  • Author(s): Mori Y, Yano F, Shimohata S, Suzuki S, Chung U, Takato T.
  • Journal Title: Int J Oral Maxillofac Surg Volume: 36 Pages: 916-921
  • Peer Reviewed
• [Journal Article] Enhancement of bone formation ex vivo and in vivo by a helioxanthin-derivative (2010)
  • Author(s): Nakajima K, Komiyama Y, Hojo H, Ohba S, Yano F, Nishikawa N, Aburatani H, Takato T, Chung U.
  • Journal Title: Biochem Biophys Res Commun Volume: 395 Pages: 502-508
  • Peer Reviewed
• [Journal Article] Targeted deletion of the Nesp55 DMR provides evidence for another principal imprinting control region within Gnas and a mouse model of autosomal dominant pseudohypoparathyroidism type Ib (2010)
  • Author(s): Frohlich LF, Mrakovcic M, Steinborn S, Chung U, Bastepe M, Juppner H.
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 9275-9280
  • Peer Reviewed
• [Journal Article] Oxytetracycline induces chondrogenic differentiation without promoting terminal differentiation (2010)
  • Author(s): Hojo H, Yano F, Ohba S, Igawa K, Nakajima K, Komiyama Y, Ikeda T, Yonezawa T, Woo J, TakatoT, Nakamura K, Kawaguchi H, Chung U.
  • Journal Title: J Bone Miner Metab Volume: 28 Pages: 489-502
  • Peer Reviewed
• [Journal Article] Evaluation of gelation kinetics of Tetra-PEG gel (2010)
  • Author(s): Kurakazu M, Katashima T, Chijiishi M, Nishi K, Akagi Y, Matsunaga T, Shibayama M, Chung U, Sakai T.
  • Journal Title: Macromolecules Volume: 43 Pages: 3935-3940
  • Peer Reviewed
• [Journal Article] Runx1 and Runx2 cooperate during sternum morphogenesis (2010)
  • Author(s): Kimura A, Inose H, Yano F, Fujita F, Ikeda T, Sato S, Iwasaki M, Jinno T, Ae K, Fukumoto S, Takeuchi Y, Itoh H, Imamura T, Kawaguchi H, Chung U, Martin JF, Iseki S, Shinomiya K, Takeda S.
  • Journal Title: Development Volume: 137 Pages: 1159-1167
  • Peer Reviewed
• [Journal Article] Evaluation of topological defects in Tetra-PEG gels (2010)
  • Author(s): Akagi Y, Matsunaga T, Shibayama M, Chung U, Sakai T.
  • Journal Title: Macromolecules Volume: 43 Pages: 488-493
  • Peer Reviewed
• [Journal Article] Akt1 in chondrocytes controls cartilage calcification during endochondral ossification under physiological and pathological conditions (2010)
  • Author(s): Fukai A, Kawamura N, Saito T, Oshima Y, Ikeda T, Kugimiya F, Higashikawa H, Yano F, Ogata N, Nakamura K, Chung U, Kawaguchi H.
  • Journal Title: Arthritis Rheum Volume: 62 Pages: 826-836
  • Peer Reviewed
• [Journal Article] Mechanisms underlying catabolic and anabolic functions of parathyroid hormone on bone by combination of culture systems of mouse cells (2010)
  • Author(s): Shinoda Y, Kawaguchi H, Higashikawa A, Nakamura K, Chung U, and Ogata N.
  • Journal Title: J Cell Biochem Volume: 109 Pages: 755-763
  • Peer Reviewed
• [Journal Article] Icariin : A potential osteoconductive compound for bone tissue engineering (2010)
  • Author(s): Zhao J, Ohba S, Komiyama Y, Shinkai M, Chung U, Nagamune T.
  • Journal Title: Tissue Eng Part A Volume: 16 Pages: 233-243
  • Peer Reviewed
• [Journal Article] Effects of trehalose and sodium carboxymethyl cellulose on prevention of organ adhesion after laparotomy : apreclinical study (2009)
  • Author(s): Lee S, Miwa Y, Nishimura R, Chung U, Suzuki S, Sasaki N.
  • Journal Title: Jpn J Vet Aneth Surg Volume: 40 Pages: 19-26
  • 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 Volume: 12 Pages: 274-7
  • Peer Reviewed
• [Journal Article] SANS and SLS Studies on Tetra-Arm PEG Gels in As-prepared and Swollen States (2009)
  • Author(s): Matsunaga T, Sakai T, Akagi Y, Chung U, Shibayama M.
  • Journal Title: Macromolecules Volume: 42 Pages: 6245-6252
  • Peer Reviewed
• [Journal Article] Maxillofacial reconstruction using custom-made artificial bones fabricated by inkjet printing technology (2009)
  • Author(s): Saijo H, Kanno Y, Igawa K, Mori Y, Kondo K, Shimizu K, Suzuki S, Chikazu D, Iino M, Sasaki N, Anzai M, Chung U, Takato T.
  • Journal Title: J Artif Organs Volume: 12 Pages: 200-205
  • Peer Reviewed
• [Journal Article] Structure characterization of Tetra-PEG Gel by Small-angle Neutron Scattering (2009)
  • Author(s): Matsunaga T, Sakai T, Akagi Y, Chung U, Shibayama M.
  • Journal Title: Macromolecules Volume: 42 Pages: 1344-51
  • Peer Reviewed
• [Journal Article] Haematopoietic stem cells depend on Gαs-mediated signalling to engraft bone marrow (2009)
  • Author(s): Adams GB, Alley IR, Chung U, Chabner KT, Marsters ES, Chen M, Weinstein LS, Kronenberg HM, Scadden DT.
  • Journal Title: Nature Volume: 459 Pages: 103-7
  • Peer Reviewed
• [Journal Article] Screening of Chondrogenic Factors by a Real-Time Fluorescence Monitoring Cell Line ATDC5-C2ER : Identification of Sorting Nexin 19 as a Novel Factor (2009)
  • Author(s): Kan A, Ikeda T, Saito T, Yano F, Ogata N, Nakamura K, Chung U, Kawaguchi H.
  • Journal Title: Arthritis Rheum Volume: 60 Pages: 3314-3323
  • Peer Reviewed
• [Journal Article] Transcriptional induction of SOX9 by NF-κB family member RelA in chondrogenic cells (2009)
  • Author(s): Ushita M, Saito T, Ikeda T, Yano F, Higashikawa A, Ogata N, Chung UI, Nakamura K, Kawaguchi H.
  • Journal Title: Osteoarthritis Cartilage Volume: 17 Pages: 1065-1075
  • Peer Reviewed
• [Journal Article] 3D spheroid culture system on micropatterned substrates for improved differentiation efficiency of multipotent mesenchymal stem cells (2009)
  • Author(s): Wang W, Itaka K, Ohba S, Nishiyama N, Chung U, Yamasaki Y, Kataoka K.
  • Journal Title: Biomaterials Volume: 30 Pages: 2705-15
  • Peer Reviewed
• [Journal Article] Temporal and spatial changes in element distribution in bone and cartilage (2009)
  • Author(s): Yamamoto K, Igawa K, Ueno H, Yano F, Chung U, Koshima I.
  • Journal Title: J Orthop Sci Volume: 14 Pages: 190-203
  • Peer Reviewed
• [Journal Article] Bone Regeneration Using Collagen Type I Vitrigel with Bone Morphogenetic Protein-2 (2009)
  • Author(s): Zhao J, Shinkai M, Takezawa T, Ohba S, Chung U, Nagamune T. Zhao J, Shinkai M, Takezawa T, Ohba S, Chung U, Nagamune T.
  • Journal Title: J Biosci Bioeng Volume: 107 Pages: 318-323
  • Peer Reviewed
• [Journal Article] Identification of the core element responsive to Runx2 in the promoter of human type X collagengene (2009)
  • Author(s): Higashikawa A, Saito T, Ikeda T, Kamekura S, Kawamura N, Kan A, Oshima Y, Ohba S, Ogata N, Nakamura K, ChungU, Kawag uchi H.
  • Journal Title: Arthritis Rheum Volume: 60 Pages: 166-178
  • Peer Reviewed
• [Journal Article] C/EBPβpromotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57Kip2 (2009)
  • Author(s): Hirata M, Kugimiya F, Ohba S, Kawamura N, Ogasawara T, Kawasaki Y, Fukai A, Ikeda T, Nakamura K, Chung UI, Kawaguchi H.
  • Journal Title: PLoS ONE Volume: 4 Pages: 4543
  • Peer Reviewed
• [Journal Article] Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers (2008)
  • Author(s): Sakai T, Matsunaga T, Yamamoto Y, Ito C, Yoshida R, Sasaki N, Suzuki S, Shibayama M, Chung U.
  • Journal Title: Macromolecules Volume: 41 Pages: 5379-84
  • 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 J-T, Yonezawa T, Takato T, Chung U.
  • Journal Title: Biochem Biophys Res Commun Volume: 376 Pages: 375-379
  • Peer Reviewed
• [Journal Article] Pivotal role of Bcl-2 family proteins in the regulation of chondrocyte apoptosis (2008)
  • Author(s): Oshima Y, Akiyama T, Hikita A, Iwasawa M, Nagase Y, Nakamura M, Wakeyama H, Kawamura N, Ikeda T, Chung U, Hennighausen L, Kawaguchi H, Nakamura K, Tanaka S.
  • Journal Title: J Biol Chem Volume: 283 Pages: 26499-508
  • Peer Reviewed
• [Journal Article] Kruppel-like factor 5 causes cartilage degradation through transactivation of matrix metalloproteinase 9 (2008)
  • Author(s): Shinoda Y, Ogata N, Higashikawa A, Manabe I, Shindo T, Yamada T, Kugimiya F, Ikeda T, Kawamura N, Kawasaki Y, Tsushima K, Takeda N, Nagai R, Hoshi K, Nakamura K, Chung UI, and Kawaguchi H
  • Journal Title: J Biol Chem Volume: 283 Pages: 24682-9
  • Peer Reviewed
• [Journal Article] Phosphorylation of GSK-3βby cyclic GMP-dependent protein kinase II promotes chondrocyte hypertrophy and skeletalgrowth (2008)
  • Author(s): Kawasaki Y, Kugimiya F, Chikuda H, Kamekura S, Ikeda T, Kawamura N, Saito T, Shinoda Y, Higashikawa A, Yano F, Ogasawara T, Ogata N, Hoshi K, Hofmann F, Woodgett JR, Nakamura K, Chung U, Kawaguchi H.
  • Journal Title: J Clin Invest Volume: 118 Pages: 2506-2515
  • Peer Reviewed
• [Journal Article] Enhancement of Angiogenesis Through Stabilization of Hypoxia-inducible Factor-1 by Silencing Prolyl Hydroxylase Domain-2 Gene (2008)
  • Author(s): Wu S, Nishiyama N, Kano MR, Morishita Y, Miyazono K, Itaka K, Chung UI, Kataoka K.
  • Journal Title: Mol Ther Volume: 16 Pages: 1227-34
  • Peer Reviewed
• [Journal Article] Patched1 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.
  • Journal Title: Dev Cell Volume: 14 Pages: 689-699
  • Peer Reviewed
• [Journal Article] Association of microsomal prostaglandin E synthase 1 deficiency with impaired fracture healing, but not with bone loss or osteoarthritis, in mouse models of skeletal disorders (2008)
  • Author(s): Yamakawa K, Kamekura S, Kawamura N, Saegusa M, Kamei D, Murakami M, Kudo I, Uematsu S, Akira S, Chung U, Nakamura K, Kawaguchi H.
  • Journal Title: Arthritis Rheum Volume: 58 Pages: 172-183
  • Peer Reviewed
• [Journal Article] Icariin induce osteoblastic differentiation in vitro by a BMP and runx2 pathway (2008)
  • Author(s): Zhao J, Shinkai M, Ohba S, Chung U, Nagamune T.
  • Journal Title: Biochem Biophys Res Commun Volume: 369 Pages: 444-448
  • Peer Reviewed
• [Journal Article] Development of an osteoblast cell-based 3D continuous perfusion microfluidic system for drug screening (2008)
  • Author(s): Jang K, Sato K, Igawa K, Chung U, Kitamori T.
  • Journal Title: Analytical Bioanalytical Chemistry Volume: 390 Pages: 825-832
  • Peer Reviewed
• [Presentation] Notch/Rbpj/Hes1 signal in chondrocytes modulates terminal stage of endochondral ossification during skeletal growth and osteoarthritis development (2011)
  • Author(s): Hosaka Y, Saito T, Sugita S, Fukai A, Hikata T, Akiyama H, Nakamura T, NakamuraK, Chung UI, Kawaguchi H.
  • Organizer: 33th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: San diego, America
  • Year and Date: 20110916-20
• [Presentation] GSK-3・and GSK-3・modulate early stages of chondrocytes differentiation through phosphorylation of RelA/NF-κB p65 (2011)
  • Author(s): Ito S, Saito T, Hirata M, Ushita m, IkedaT, Nakamura K, Chung UI, Kawaguchi H.
  • Organizer: 2011 World Cogress on Osteoarthritis(OARSI)
  • Place of Presentation: San diego, America
  • Year and Date: 20110915-18
• [Presentation] Molecular network on the C/EBP-bete axis including Runx2, MMP13, and HIF2A controls osteoarthritis development (2010)
  • Author(s): Hirata M, Kugimiya F, Fukai A, Saito T, Yano F, Ikeda T, Nakamura K, Chung UI, Kawaguchi H.
  • Organizer: 2010 World Cogress on Osteoarthritis(OARSI)
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 20100923-26
• [Presentation] Akt in chondrocytes controls cartilage calcification during skeletal growth and asteophyte formation in osteoarthritis (2010)
  • Author(s): Fukai A, Kawamura N, Saito T, Oshima Y, Ikeda T, Yano F, Ogata N, Nakamura K, ChungUI, Kawaguchi H
  • Organizer: 56 th Annual Meeting of the Orthopaedic Research Society(ORS)
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 20100306-09
• [Presentation] Signaling factors coordinating chondrogenesis and osteogenesis in endochondral bone development (2009)
  • Author(s): Chung U.
  • Organizer: The 26th Naito Conferenceon Osteobiology
  • Place of Presentation: Hyogo
  • Year and Date: 20091104-07
• [Presentation] 均一構造を有するtetra-PEGゲルの構造解析 (2009)
  • Author(s): 酒井崇匡、松永拓郎、柴山充弘、鄭雄一
  • Organizer: 第20回高分子ゲル研究討論会
  • Place of Presentation: 東京
  • Year and Date: 2009-01-15
• [Presentation] 新規低分子化合物チエノインダゾール誘導体はRunx1とSox trioを介して永久軟骨再生を誘導する (2008)
  • Author(s): 矢野文子、池田敏之、斎藤琢、緒方直史、木村文子、竹田秀、中村耕三、高戸毅、川口浩、鄭雄一
  • Organizer: 第26回日本骨代謝学会
  • Place of Presentation: 大阪国際会議場、大阪
  • Year and Date: 20081029-31
• [Presentation] A novel small thienoindazole-derivative compound promotes chondrogenic differentiation without inducing hypertrophy through production of Runx1 (2008)
  • Author(s): F. Yano, T. Ikeda, T. Saito, N. Ogata, K. Nakamura, T. Takato, H. Kawaguchi, U. Chung.
  • Organizer: A novel small thienoindazole-derivative compound promotes chondrogenic differentiation without inducing hypertrophy through production of Runx1
  • Place of Presentation: Roma, Italy
  • Year and Date: 20080918-21
• [Book] 図解骨博士が教える「老いない体」のつくり方実践編 (2011)
  • Author(s): 鄭雄一
  • Total Pages: 111
  • Publisher: ワック株式会社
• [Book] 骨博士が教える「老いない体」のつくり方 (2010)
  • Author(s): 鄭雄一
  • Total Pages: 180
  • Publisher: ワック株式会社
• [Remarks]
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp
• [Patent(Industrial Property Rights)] 人工骨構成ユニット及び人工骨構成システム (2010)
  • Inventor(s): 鄭雄一, 他
  • Industrial Property Rights Holder: 東京大学, 他
  • Industrial Property Number: 特許、PCT/JP2010/004690
  • Filing Date: 2010-07-22
  • Overseas
• [Patent(Industrial Property Rights)] 組織癒着防止液及び組織癒着防止方法 (2010)
  • Inventor(s): 鄭雄一, 他
  • Industrial Property Rights Holder: 東京大学, 他
  • Industrial Property Number: 特許、4447640
  • Filing Date: 2010-07-27