Examination of hybrid bone grafts using nano DDS and artificial bones

• Project/Area Number: 23390459
• 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: MORI Yoshiyuki 東京大学, 医学部附属病院, 准教授 (70251296)
• Co-Investigator(Kenkyū-buntansha): SAIJO Hideto 東京大学, 医学部附属病院, 講師 (80372390) ; TEI Yuichi 東京大学, 工学系研究科, 教授 (30345053) ; YANO Fumiko 東京大学, 医学系研究科, 特任助教 (80529040)
• Co-Investigator(Renkei-kenkyūsha): KATAOKA Kazunori 東京大学, 工学系研究科, 教授 (00130245) ; OGASAWARA Toru 東京大学, 医学部附属病院, 講師 (20359623)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2011: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 骨再生用移植片 / 骨再生 / 生理活性物質 / 骨移植片 / ナノDDS

Research Abstract

By further integrating research that we had performed, this study was aimed to develop hybrid-type bone grafts for bone regeneration that were efficiently replaced into bone tissues. We identified osteogenic genes and bioactive factors with the bio-sensor and developed the osteogenic differentiation protocol using the nano drug delivery of the genes and factors. Focusing on iPS cells as a cell source for bone regeneration, we attempted to establish an in vitro differentiation protocol from the cells. Finally, we generated hybrid-type bone grafts that consisted of artificial bones and osteoblastic cells generated from stem cells, and examined their bone healing ability in animal experiments.

Research Products

• [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 I, Yamamoto K, Honnami M, Sakai T, Ohba S, Echigo R, Suzuki S, Chung UI, Sasaki N, Mochizuki M
  • Journal Title: J Vet Med Sci Volume: 76(2) Pages: 229-235
• [Journal Article] Generation of Col2a1-EGFP-iPS cells for monitoring chondrogenic differentiation. (2014)
  • Author(s): Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H.
  • Journal Title: PLoS ONE Volume: 8
  • DOI: 10.1371/journal.pone.0074137
  • Peer Reviewed
• [Journal Article] Clinicalresentation of epignathus teratoma with cleft palate; and duplication of cranial base, tongue, mandible, and pituitary gland (2014)
  • Author(s): K. Hoshi et al
  • Journal Title: J Craniofac Surg. Volume: 25(5) Pages: 1486-1491
  • DOI: 10.1097/scs.0b013e3182953b1f
  • Peer Reviewed / Open Access
• [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(36) Pages: 9056-9062
• [Journal Article] Generation of Col2a1-EGFP iPS cells for monitoring chondrogenic differentiation (2013)
  • Author(s): Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
  • Journal Title: PLoS ONE Volume: 8(9)
• [Journal Article] Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein (BMP) signaling (2013)
  • Author(s): Ogasawara T, Ohba S, Yano F, Kawaguchi H, Chung UI, Saito T, Yonehara Y, Nakatsuka T, Mori Y, Takato T, Hoshi K
  • Journal Title: J Cell Physiol Volume: 228(1) Pages: 163-171
• [Journal Article] Submucous cleft palate : variations in bony defects of the hard palate (2013)
  • Author(s): Mori Y, Hoshi K, Takato T, Takahashi M, Hirano Y, Kanno Y, Ohkubo K, Saijo H
  • Journal Title: Br J Oral Maxillofac Surg Volume: 51
• [Journal Article] Usefulness of agarose mold as a storage container for three-dimensional tissue-engineered cartilage (2013)
  • Author(s): Mori Y, Kanazawa S, Watanabe M, Suenaga H, Nagata S, Fujihara Y, Takato T, Hoshi K
  • Journal Title: Mater Sci Appl Volume: 4(8) Pages: 73-73
• [Journal Article] Hollow fiber module applied for effective proliferation and harvest of cultured chondrocytes (2013)
  • Author(s): Mori Y, Watanabe M, Nakagawa S, Asawa Y, Nishizawa S, Saijo H, Nagata S, Fujihara Y, Takato T, Hoshi K
  • Journal Title: Mater Sci Appl Volume: 4(8) Pages: 62-7
• [Journal Article] Clinical presentation of epignathus teratoma with cleft palate ; and duplication of cranial base, tongue, mandible, and pituitary gland (2013)
  • Author(s): Maeda Y, Suenaga H, Sugiyama M, Saijo H, Hoshi K, Mori Y, Takato T
  • Journal Title: J Craniofac Surg Volume: 24(4) Pages: 1486-91
• [Journal Article] Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein(BMP) signaling. (2013)
  • Author(s): Ogasawara T, Ohba S, Yano F, KawaguchiH, Chung UI, Saito T, Yonehara Y, NakatsukaT, Mori Y, Takato T, Hoshi K.
  • Journal Title: J Cell Physiol Volume: 228(1) Pages: 163-171
  • DOI: 10.1002/jcp.24116
  • Peer Reviewed
• [Journal Article] Hollow Fiber Module Applied for Effective Proliferation and Harvest of Cultured Chondrocytes (2013)
  • Author(s): Mori Y, Watanabe M, Nakagawa S, Asawa Y, Nishizawa S, Saijo H, Nagata S, Fujihara Y, Takato T, Hoshi K
  • Journal Title: Materials Sciences and Applications Volume: 4 Pages: 62-67
  • DOI: 10.4236/msa.2013.48a008
  • Peer Reviewed
• [Journal Article] Submucous cleft palate : variations in bony defects of the hard palate (2013)
  • Author(s): Mori Y, Hoshi K, Takato T, Takahashi M, Hirano Y, Kanno Y, Ohkubo K, Saijo H
  • Journal Title: British Journal of Oral and Maxillofacial Surgery Volume: 51 Pages: 220-223
  • DOI: 10.1016/j.bjoms.2013.01.015
  • Peer Reviewed
• [Journal Article] Bone healing by sterilizable calcium phosphate tetrapods eluting osteogenic molecules (2013)
  • Author(s): Maeda Y, Hojo H, et al.
  • Journal Title: Biomaterials Volume: 34 Pages: 5530-5537
  • DOI: 10.1016/j.biomaterials.2013.03.089
  • Peer Reviewed
• [Journal Article] Development and evaluation of tetrapod-shaped granular artificial bones (2012)
  • Author(s): Choi S, Liu IL, Yamamoto K, Igawa K, Mochizuki M, Sakai T, Echigo R, Honnami M, Suzuki S, Chung UI, Sasaki N
  • Journal Title: Acta Biomater Volume: 8(6) Pages: 2340-7
• [Journal Article] Mandibular body ostectomy for correction of mandibular prognathism - a technical note (2012)
  • Author(s): Mori Y, Susami T, Saijo H, Okubo K, Uchino N, Hoshi K, Takato T
  • Journal Title: Oral Sci Int Volume: 9(1) Pages: 21-25
• [Journal Article] The efficacy of dental therapy for an adult case of Henoch-Schönlein Purpura (2012)
  • Author(s): Abe M, Mori Y, Saijo H, Hoshi K, Ohkubo K, Ono T, Takato T
  • Journal Title: Oral Sci Int Volume: 9(2) Pages: 59-62
• [Journal Article] Facial morphology and occlusion of a patient with fibrodysplasia ossificans progressiva (FOP): a case report. (2012)
  • Author(s): Takahumi Susami
  • Journal Title: Special Care in Dentistry Volume: 32 Pages: 165-170
  • DOI: 10.1111/j.1754-4505.2012.00260.x
  • 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) Pages: 2340-2347
  • DOI: 10.1016/j.actbio.2012.02.019
  • Peer Reviewed
• [Journal Article] et al The development of a serum-free medium utilizing the interaction between growth factors and biomaterials. (2012)
  • Author(s): Kumiko Iwata
  • Journal Title: Biomaterials Volume: 33(2) Pages: 444-454
  • DOI: 10.1016/j.biomaterials.2011.09.056
  • Peer Reviewed
• [Journal Article] Extraction of 6 molars under general anesthesia in patient with fibrodysplasia ossificans progressiva (2011)
  • Author(s): Mori Y, Susami T, Haga N, Tamura K, Kanno Y, Saijo H, Takato T
  • Journal Title: J Oral Maxillofac Surg Volume: 69(7) Pages: 1905-10
• [Journal Article] Extraction of 6 molars under general anesthesia in patient with fibrodysplasia ossificans progressiva (2011)
  • Author(s): Yoshiyuki Mori
  • Journal Title: Journal of Oral and Maxillofacial Surgery Volume: 69(7) Pages: 1905-1910
  • DOI: 10.1016/j.joms.2010.12.011
  • Peer Reviewed
• [Journal Article] Bone regeneration by the combined use of tetrapod-shaped calcium phosphate granules with basic fibroblast growth factor-binding ion complex gel in canine segmental radial defects
  • Author(s): Honnami M, Choi S, Liu IL, Kamimura W, Taguchi T, Hojo H, Shimohata N, Ohba S, Koyama H, Nishimura R, Chung UI, Sasaki N, Mochizuki M
  • Journal Title: J Vet Med Sci Volume: (in press)
• [Presentation] Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions (2013)
  • Author(s): Kanke K, Saito S, Hojo H, Lichtler AC, Chung UI, Ohba S
  • Organizer: Cell symposia 2013- Stem cells to model and treat human disease
  • Place of Presentation: Los Angeles, CA, USA
• [Presentation] Stepwise differentiation of pluripotent stem cells into osteoblasts with four small molecules under a serum-free condition (2013)
  • Author(s): Kanke K, Saito T, Hojo H, Lichtler AC, Chung UI, Ohba S
  • Organizer: 35th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Baltimore, MD, USA
• [Presentation] Novel approach for the differentiation of embryonic stem cells into osteoblasts under a chemically-defined condition (2013)
  • Author(s): Kanke K, Hojo H, Lichtler AC, Chung UI, Ohba S
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: Kobe, Japan
• [Presentation] Outcome of the surgical-orthodontic treatment in patients with clefts using the two-stage surgery combining maxillary distraction with mandibular setback osteotomies (2013)
  • Author(s): Mori Y, Susami T, Saijo H, Uchino N, Ohkubo K, Inokuchi T, Okayasu M, Uwatoko K, Hoshi K, Takato T
  • Organizer: 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies
  • Place of Presentation: Florida USA , Hilton Orlando Lake Buena Vista
• [Presentation] in situ Tissue Engineering 型カスタムメイド人工骨の骨癒合状態のCT による評価 (2013)
  • Author(s): 菅野勇樹, 西條英人 , 鄭雄一, 森良之, 高戸毅
  • Organizer: 第58回日本口腔外科学会総会・学術大会
  • Place of Presentation: 福岡
• [Presentation] Outcome of the surgical-orthodontic treatment in patients with clefts using the two-stage surgery combining maxillary distraction with mandibular setback osteotomies (2013)
  • Author(s): Mori Y, Susami T, Saijo H , Uchino N, Ohkubo K, Inokuchi T, Okayasu M, Uwatoko K, Hoshi K, Takato T
  • Organizer: 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies
  • Place of Presentation: Florida, USA
• [Presentation] Postoperative evaluation of custom-made artificial bones fabricated by inkjet printers using computed tomography (2013)
  • Author(s): Kanno Y, Saijo H, Mori Y, Chung UI, Takato T
  • Organizer: Frontiers 2013 EPFL Symposium
  • Place of Presentation: Lausanne, Switzerland
• [Presentation] Need for orthognathic sugery and its prediction in early mixed dentition in patients with bilateral cleft lip and palate. (2013)
  • Author(s): Okayasu M , Susami T , Inocuchi T , Ohkubo K , Uchino N , Uwatoko K , Ogasawara T , Ssaijo H , Mori Y , Takato T
  • Organizer: 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies
  • Place of Presentation: Florida, USA
• [Presentation] Palatal index for evaluation of the palatal morphology in patients with uniateral cleft lip and palate (2013)
  • Author(s): Inokuchi T, Susami T, Okayasu M, Uchino N, Uwatoko K, Ohkubo K, Ogasawara T, Saijo H, Mori Y, Takato T
  • Organizer: 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies
  • Place of Presentation: Florida, USA
• [Presentation] 口腔扁平上皮癌の発生過程においてサイレンシングされる遺伝子のゲノム網羅的探索 (2013)
  • Author(s): 阿部雅修, 森良之, 安部貴大, 末永英之, 古賀陽子, 瀬戸一郎, 西條英人, 星和人, 髙戸毅
  • Organizer: 第67回日本口腔科学会総会
  • Place of Presentation: 栃木（栃木県総合文化センター ）
• [Presentation] in situ Tissue Engineering型カスタムメイド人工骨の骨癒合状態のCTによる評価 (2013)
  • Author(s): 菅野勇樹，西條英人 ，鄭雄一， 森良之 ，高戸毅
  • Organizer: 第58回日本口腔外科学会総会・学術大会
  • Place of Presentation: 福岡（福岡国際会議場）
• [Presentation] Gli1 Participates in the Indian Hedgehog-mediated Osteogenesis during Endochondral Ossification (2012)
  • Author(s): Hojo H, Ohba S, Yano F, Saito T, Ikeda T, Nakajima K, Komiyama Y, Nakagata H, Suzuki K, Takato T, Kawaguchi H, Chung UI
  • Organizer: 34th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Minneapolis, MN, USA
• [Presentation] Osteo-chondrogenic Function of BMP is Directed Toward Osteogenesis by Hh-Gli1 in the Perichondrium (2012)
  • Author(s): Hojo H, Ohba S, Taniguchi K, Shirai M, Yano F, Saito T, Ikeda T, Nakajima K, Komiyama Y, Nakagata N, Suzuki K, Mishina Y, Yamada M, Konno T, Takato T, Kawaguchi H, Kambara H, Chung UI
  • Organizer: 34th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Minneapolis, MN, USA
• [Presentation] Prevention and Repair of Cartilage Degeneration by a Novel Small Thienoindazole-derivative Compound (2012)
  • Author(s): Yano F, Hosaka Y, Fukai A, Saito T, Hojo H, Ohba S, Kawaguchi H, Chung UI
  • Organizer: 2012 World Congress on Osteoarthritis
  • Place of Presentation: Barcelona, Spain
• [Presentation] 下顎枝矢状分割術における超音波骨切削器(ピエゾサージェリーシステム[〇!R])を用いたShort lingual osteotomy (SLO) (2012)
  • Author(s): 森良之, 末永英之, 古賀陽子, 菅野勇樹, 杉山円, 瀬戸一郎, 西條英人, 星和人, 高戸毅
  • Organizer: 第57回(公社)日本口腔外科学会総会・学術集会
  • Place of Presentation: パシフィコ横浜会議センター, 神奈川県横浜市
• [Presentation] 下顎枝矢状分割術における超音波骨切削器（ピエゾサージェリーシステム®）を用いたShort lingual osteotomy (SLO). (2012)
  • Author(s): 森良之
  • Organizer: 第57回日本口腔外科学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] 上下顎手術における骨延長術の役割. (2012)
  • Author(s): 森良之
  • Organizer: 第38回日本口腔外科学会教育研修会 口腔四学会合同研修会
  • Place of Presentation: 京都
• [Presentation] Nanogの間葉系細胞骨分化能促進効果はBMPシグナルとの相互作用とNFATc1の誘導を介する. (2012)
  • Author(s): 小笠原徹
  • Organizer: 第57回日本口腔外科学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] チタンメッシュトレーを用いた海綿骨細片(PCBM)による二次的下顎顎骨再建後にインプラントを用いて咬合回復を行なった1例 (2012)
  • Author(s): 杉山円
  • Organizer: 第67回日本口腔科学会学術集会
  • Place of Presentation: 広島
• [Presentation] 当科における生体内吸収性PLLA/HA骨接合プレート（Super Fixsorb MX） 治療成績とその合併症. (2012)
  • Author(s): 瀬戸一郎
  • Organizer: 第57回日本口腔外科学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] 口腔前癌病変悪性化におけるエピジェネティクスを指標としたリスクマーカーのゲノム網羅的探索 (2011)
  • Author(s): 阿部雅修, 森良之, 西條英人, 安部貴大, 杉山円, 古賀陽子, 高戸毅
  • Organizer: 第35回日本頭頸部癌学会
  • Place of Presentation: ウィンクあいち, 名古屋
• [Presentation] A 2-stage surgery combining mandibular distraction with a Le Fort I maxillary osteotomy in a patient with hemifacial microsomia (2011)
  • Author(s): Mori Y, Susami T, Saijo H, Ohkubo K, Kanno Y, Suenaga H, Seto I, Hoshi K, Takato T
  • Organizer: 9th European Craniofacial Congress
  • Place of Presentation: Salzburg, Austria, Salzburg Congress
• [Presentation] A 2-stage surgery combining mandibular distraction with a Le Fort I maxillary osteotomy in a patient with hemifacial microsomia (2011)
  • Author(s): Yoshiyuki Mori
  • Organizer: 9th European Craniofacial Congress
  • Place of Presentation: Salzburg, Austria
• [Book] 「15章消化器疾患 5口腔疾患」内科学, 門脇孝・永井良三総編集 (2012)
  • Author(s): 森良之・高戸毅
  • Publisher: 西村書店(東京)
• [Book] 「１５章消化器疾患 ５口腔疾患」内科学（門脇孝･永井良三編） (2012)
  • Author(s): 森良之
  • Total Pages: 1929
  • Publisher: 西村書店
• [Remarks] 東京大学医学部附属病院顎口腔外科・歯科矯正歯科ホームページ
  • URL: http://plaza.umin.ac.jp/~oralsurg/
• [Remarks] 東京大学医学部附属病院 顎口腔外科・歯科矯正歯科
  • URL: http://plaza.umin.ac.jp/~oralsurg/
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~oralsurg/