Development of bone-inducing artificial bone

• Project/Area Number: 24240069
• 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: Chung Ung-il 東京大学, 工学(系)研究科(研究院), 教授 (30345053)
• Co-Investigator(Kenkyū-buntansha): OHBA Shinsuke 東京大学, 大学院工学系研究科, 准教授 (20466733) ; SAKAI Takamasa 東京大学, 大学院工学系研究科, 准教授 (70456151)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥46,280,000 (Direct Cost: ¥35,600,000、Indirect Cost: ¥10,680,000); Fiscal Year 2015: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000); Fiscal Year 2014: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000); Fiscal Year 2013: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2012: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: 生体材料 / トランスレーショナルリサーチ / 人工骨 / 再生 / 骨 / バイオマテリアル / シグナル分子 / 低分子化合物

Outline of Final Research Achievements

In order to treat bone defect and deformity, we need to use artificial bone. We attempted to enhance its performance by clarifying signaling network for bone formation and integrating it with artificial bone. As a result, we succeeded in differentiating pluripotent stem cell into osteoblastic cells in vitro using 4 small-molecule compounds without using serum, protein or gene. By loading these compounds onto artificial bone and controlling their release, we also succeeded in treating bone defect model in animals within a short period.

Research Products

• [Int'l Joint Research] 南カリフォルニア大学(米国)
• [Journal Article] Reliable hydrogel with mechanical ‘fuse link’ in an aqueous environment (2015)
  • Author(s): Kondo S, Hiroi T, Han Y, Kim M, Shibayama M, Chung U, Sakai T
  • Journal Title: Adv Mater Volume: 27 Issue: 45 Pages: 7407-7411
  • DOI: 10.1002/adma.201503130
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Design of Hydrogels for Biomedical Applications (2015)
  • Author(s): Kamata H, Li X, Chung U, Sakai T
  • Journal Title: Adv Healthcare Mater Volume: 4 Issue: 16 Pages: 2360-2374
  • DOI: 10.1002/adhm.201500076
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Signaling pathways regulating the specification and differentiation of the osteoblast lineage (2015)
  • Author(s): Hojo H, Ohba S, Chung U
  • Journal Title: Regenerative Therapy Volume: 1 Pages: 57-62
  • DOI: 10.1016/j.reth.2014.10.002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histochemical and Radiological Study of Bone Regeneration by the Combinatorial Use of Tetrapod-Shaped Artificial Bone and Collagen (2015)
  • Author(s): Uryu T, Matsumoto N, Namaki S, Mashimo T, Tamagawa T, Yasumitsu T, Okudera M, Komiyama K, Chung U, Honda K, Arai Y, Yonehara Y
  • Journal Title: Journal of Hard Tissue Biology Volume: 24 Issue: 2 Pages: 199-210
  • DOI: 10.2485/jhtb.24.199
  • NAID: 130005065059
  • ISSN: 1341-7649, 1880-828X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Augmentation of Flat Bone Area Using Tetrapod-Shaped Artificial Bone in Rats (2015)
  • Author(s): Iwata J, Namaki S, Mashimo T, Honda K, Chung U, Yonehara Y
  • Journal Title: Journal of Hard Tissue Biology Volume: 24 Issue: 1 Pages: 69-76
  • DOI: 10.2485/jhtb.24.69
  • NAID: 130004848445
  • ISSN: 1341-7649, 1880-828X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gli1 haploinsufficiency leads to decreased bone mass with an uncoupling of bone metabolism in adult mice. (2014)
  • Author(s): Kitaura Y, Hojo H, Komiyama Y, Takato T, Chung UI, Ohba S
  • Journal Title: PLoS ONE Volume: 9(10) Issue: 10 Pages: e109597-e109597
  • DOI: 10.1371/journal.pone.0109597
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Molecular and structural patterns of bone regeneration in surgically created defects containing bone substitutes. (2014)
  • Author(s): Elgali I, Igawa K, Palmquist A, Lennerås M, Xia W, Choi S, Chung U, Omar O, Thomsen P
  • Journal Title: Biomaterials Volume: 35 Issue: 10 Pages: 3229-3242
  • DOI: 10.1016/j.biomaterials.2013.12.084
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions. (2014)
  • Author(s): Kanke K, Masaki H, Saito T, Komiyama Y, Hojo H, Nakauchi H, Lichtler AC, Takato T, Chung UI, Ohba S
  • Journal Title: Stem Cell Reports. Volume: 6 Issue: 6 Pages: 751-760
  • DOI: 10.1016/j.stemcr.2014.04.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of the long-term effects on rabbit bone defects between Tetrabone and β-tricalcium phosphate granules implantation. (2014)
  • Author(s): Choi S, Liu IL, Yamamoto K, Honnami M, Ohba S, Echigo R, Sakai T, Igawa K, Suzuki S, Nishimura R, Chung UI, Sasaki N, Mochizuki M
  • Journal Title: J Artif Organs Volume: 14 Issue: 4 Pages: 344-351
  • DOI: 10.1007/s10047-014-0778-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Implantation of tetrapod-shaped granular artificial bones or β-tricalcium phosphate granules in a canine large bone-defect model. (2014)
  • Author(s): Choi S, Liu IL, Yamamoto K, Honnami M, Sakai T, Ohba S, Echigo R, Suzuki S, Nishimura R, Chung UI, Sasaki N, Mochizuki M.
  • Journal Title: J Vet Med Sci Volume: 76 Pages: 229-235
  • NAID: 130003382365
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hedgehog-Gli activators direct osteo-chondrogenic function of bone morp hogenetic protein toward osteogenesis in the perichondrium. (2013)
  • Author(s): Hojo H, et al.
  • Journal Title: J Biol Chem Volume: 288 Issue: 14 Pages: 9924-9932
  • DOI: 10.1074/jbc.m112.409342
  • Peer Reviewed
• [Journal Article] Bone healing by sterilizable calcium phosphate tetrapods eluting osteoge nic molecules. (2013)
  • Author(s): Maeda Y, Hojo H, et al.
  • Journal Title: Biomaterials Volume: 34 Issue: 22 Pages: 5530-5537
  • DOI: 10.1016/j.biomaterials.2013.03.089
  • Peer Reviewed
• [Journal Article] Cell-sheet technology combined with a thienoindazole derivative small comnound TD-198946 for cartilage regeneration (2013)
  • Author(s): Yano F, Hojo H, et al.
  • Journal Title: Biomaterials Volume: 34 Issue: 22 Pages: 5581-5587
  • DOI: 10.1016/j.biomaterials.2013.04.008
  • Peer Reviewed
• [Journal Article] Repair of rabbit segmental femoral defects by using a combination of tetrapod-shaped granular artificial bones and basic fibroblast growth factor-binding ion complex gel. (2013)
  • Author(s): Honnami M, Choi S, Liu I, Kamimura W, Taguchi T, Hojo H, Shimohata N, Ohba S, Koyama H, Nishimura R, Chung UI, Sasaki N, Mochizuki M
  • Journal Title: Biomaterials Volume: 34 Issue: 36 Pages: 9056-9062
  • DOI: 10.1016/j.biomaterials.2013.08.014
  • Peer Reviewed
• [Journal Article] Changes in Bone Regeneration by Trehalose Coating and Basic Fibroblast Growth Factor after Implantation of Tailor-Made Bone Implants in Dogs (2013)
  • Author(s): Choi S et al.
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 6 Pages: 721-726
  • DOI: 10.1292/jvms.12-0244
  • NAID: 130003362113
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Development and evaluation of tetrapod-shaped granular artificial bones (2012)
  • Author(s): Sungjin Choi
  • Journal Title: Acta Biomaterialia Volume: (掲載確定済) Issue: 6 Pages: 2340-2347
  • DOI: 10.1016/j.actbio.2012.02.019
  • Peer Reviewed
• [Journal Article] C/EBPβand RUNX2 cooperate to degrade cartilage with MMP13 as the target and HIF-2αas theinducer in chondrocytes (2012)
  • Author(s): Hirata M、Kugimiya F、Fukai A、Saito T、Yano F、Ikeda T、Mabuchi A、Sapkota BR、Akune T、Nishida N、Yoshimura N、NakagawaT、Tokunaga K、Nakamura K、Chung UI、Kawaguchi H
  • Journal Title: Human Molecular Genetics Volume: Vol.21 Issue: 5 Pages: 1111-1123
  • DOI: 10.1093/hmg/ddr540
  • Peer Reviewed
• [Journal Article] Famotidine suppresses osteogenic differentiation of tendon cells in vitro and pathological calcification of tendon in vivo (2012)
  • Author(s): Yamamoto K, Hojo H, 他
  • Journal Title: J Orthop Res Volume: 30 Issue: 12 Pages: 1958-1962
  • DOI: 10.1002/jor.22146
  • Peer Reviewed
• [Presentation] Introduction of messenger RNA into knee articular cartilages using polyplex nanomicelle (2015)
  • Author(s): Aini H, Itaka K, Chung U, Ohba S
  • Organizer: 2015 World Congress on Osteoarthritis
  • Place of Presentation: Seattle, USA
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] Gremlin1 induced by excessive mechanical stress loading enhances cartilage degradation (2015)
  • Author(s): Chang S, Kobayashi H, Okada K, Okuma T, Mori Y, Kawata M, Yano F, Kawaguchi H, Chung U, Tanaka S, Saito T
  • Organizer: 2015 World Congress on Osteoarthritis
  • Place of Presentation: Seattle, USA
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] Development of high-performance structural biomaterials through controlling 3D shape (2014)
  • Author(s): 鄭 雄一（Chung, Ung-il）
  • Organizer: 日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-07-24 – 2014-07-26
  • Invited
• [Presentation] 1. Development of implant devices for skeletal reconstruction by precise control of 3D shape (2013)
  • Author(s): Chung U (鄭 雄一)
  • Organizer: The 4th Asian Biomaterials Congress
  • Place of Presentation: 香港科学技術大学・中国
  • Invited
• [Presentation] PREVENTION AND REPAIR OF CARTILAGE DEGENERATION BY A NOVEL SMALL THIENOINDAZOLE-DERIVATIVE COMPOUND (2012)
  • Author(s): Fumiko Yano
  • Organizer: 2012 World Congress on Osteoarthritis
  • Place of Presentation: バルセロナ、スペイン
• [Remarks] 鄭 研究室
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/
• [Remarks] 鄭雄一研究室
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/
• [Remarks] 鄭 雄一 研究室
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/
• [Remarks] 鄭 雄一 研究室
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/
• [Patent(Industrial Property Rights)] 眼科治療用ゲル材料 (2016)
  • Inventor(s): 鄭 雄一 他
  • Industrial Property Rights Holder: 鄭 雄一 他
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-000913
  • Filing Date: 2016-01-06