Development of Novel Hybrid Bone Substitute with Stem cells and Growth Factors

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 15209050
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: YOSHIKAWA Hideki Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (60191558)
• Co-Investigator(Kenkyū-buntansha): SUGANO Nobuhiko Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70273620) ; MYUOI Akira Osaka University, Hospital, Associate Professor, 医学部附属病院, 助教授 (10263261) ; TSUMAKI Noriyuki Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (50303938)
• Project Period (FY): 2003 – 2006
• Keywords: bone regeneration / bone substitute / mesenchymal stem cell / osteoblast / tissue engineering / hydroxyapatite

Research Abstract

We developed a fully interconnected porous hydroxyapatite (IP-CHA) by adopting the "form-gel" technique. The interconnected porous structure facilitates tissue engineering by allowing the introduction of bone cells, rhBMP-2, or vasculature into the pores. IP-CHA combined with rat marrow mesenchymal cells showed abundant bone formation inside the pore areas. IP-CHA combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) completely repaired the bony defect of rabbit radius. IP-CHA/BMP composite with insertion of epigastric vessels exhibited abundant new bone formation in the pores of the deep portion close to the inserted vessels. The 3-dimensional fully interconnected porous structure of IP-CHA encourages bone ingrowth in the material and eventually leads to good incorporation of the material into host bone. The synthetic scaffold can be prefabricated into specific sizes and shapes to match bone defects, and even into composite with solid form of HA in order to reinforce its initial mechanical strength.

Research Products

• [Journal Article] Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice. (2007)
  • Author(s): Otsuru, S., Tamai, K., Yamazaki, T., Yoshikawa, H., Kaneda, Y.
  • Journal Title: Biochem Biophys Res Commun 354 Pages: 453-458
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 医工連携による次世代人工骨・人工関節の開発 (2007)
  • Author(s): 吉川秀樹
  • Journal Title: 生産と技術 59 Pages: 86-88
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. (2006)
  • Author(s): Hirao, M., Tamai, N., Tsumaki, N., Yoshikawa, H., Myoui, A.
  • Journal Title: Journal of Biological Chemistry 281 Pages: 31079-33192
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dual hydroxyapatite composite with porous and solid parts : Experimental study using canine lumbar interbody fusion model. (2006)
  • Author(s): Kaito, T., Mukai, Y., Nishikawa, M., Ando, W., Yoshikawa, H., Myoui, A.
  • Journal Title: J Biomed Mater Res B Appl Biomater 78 Pages: 378-384
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibitory effect of ribbon-type NFkB decoy olidodeoxynucleatides on osteoclast induction and activity in vitro and in vivo. (2006)
  • Author(s): Kunugiza, Y., Tomita, T., Tomita, N., Morishita, R., Yoshikawa, H.
  • Journal Title: Arthritis Research ＆ Therapy 8 Pages: R103
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Potential roles of bone morphogenetic proteins (BMPs) in skeletal repair and regeneration. (2006)
  • Author(s): Nakase, T., Yoshikawa, H.
  • Journal Title: Journal of Bone and Mineral Metabolism 24 Pages: 425-433
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Multidetector-CT evaluation of bone substitutes remodeling after revision hipsurgery. (2006)
  • Author(s): Nishii, T., Sugano, N., Miki, H., Koyama, T., Yoshikawa, H.
  • Journal Title: Clinical Orthopaedics and Related Research 442 Pages: 158-164
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. (2006)
  • Author(s): Okamoto, M., Murai, J., Yoshikawa, H., Tsumaki, N.
  • Journal Title: Journal of Bone Mineral Research 21 Pages: 1022-1033
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Hydroxyapatite augmentation for bone atrophy in total ankle replacement in rheumatoid arthritis. (2006)
  • Author(s): Shi, K., Hayashida, K, Hashimoto, J., Sugamoto, K., Kawai, H., Yoshikawa, H.
  • Journal Title: Journal of Foot and Ankle Surgery 45 Pages: 316-321
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 遺伝子改変マウスを用いたBMPシグナルによる骨軟骨形成機構の解析 (2006)
  • Author(s): 妻木範行, 吉川秀樹
  • Journal Title: Arthritis 4 Pages: 4-9
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 骨折治癒とBMP (2006)
  • Author(s): 中瀬尚長, 吉川秀樹
  • Journal Title: CLINICAL CALCIUM 16 Pages: 35-45
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 骨格発生におけるBMPと関連分子群の生物活性 (2006)
  • Author(s): 妻木範行, 吉川秀樹
  • Journal Title: CLINICAL CALCIUM 16 Pages: 67-72
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] BMPシグナルと骨形成・骨吸収 (2006)
  • Author(s): 妻木範行, 村井純子, 岩井貴男, 岡本美奈, 吉川秀樹
  • Journal Title: The Bone 20 Pages: 343-348
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 連通気孔構造を有するハイドロキシアパタイト人工骨の臨床応用,物理学的特性・臨床的特徴・問題点 (2006)
  • Author(s): 名井陽, 玉井宣行, 荒木信人, 藤井昌一, 冨田哲也, 古野雅彦, 吉川秀樹
  • Journal Title: 日整会誌 80 Pages: 262-269
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 連通多孔体ハイドロキシアパタイトを用いた腫瘍外科治療 (2006)
  • Author(s): 吉川秀樹
  • Journal Title: 関節外科 25 Pages: 999-1001
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Multidetector-CT evaluation of bone substitutes remodeling after revision hip surgery. (2006)
  • Author(s): Nishii, T., Sugano, N., Miki, H., Koyama, T., Yoshikawa, H.
  • Journal Title: Clinical Orthopaedics and Related Research 442 Pages: 158-164
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite. (2005)
  • Author(s): Kaito, T., Myoui, A., Takaoka, K., Saito, N., Nishikawa, M., Tamai, N., Ohgushi, H., Yoshikawa, H.
  • Journal Title: Biomaterials 26 Pages: 73-79
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification. (2005)
  • Author(s): Kishida, Y., Hirao, M., Tamai, N., Nampei, A., Fujimoto, T., Nakase, T., Shimizu, N., Yoshikawa, H., Myoui, A.
  • Journal Title: Bone 307 Pages: 607-621
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alendronate inhibits bone resorption at the bone-screw interface. (2005)
  • Author(s): Miyaji, T., Nakase, T., Azuma, Y., Shimizu, N., Uchiyama, Y., Yoshikawa, H.
  • Journal Title: Clinical Orthopaedics and Related Research 430 Pages: 195-201
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The effect of simulated microgravity by three-dimensional clinostat on bone tissue engineering. (2005)
  • Author(s): Nishikawa, M., Ohgushi, H., Tamai, N., Osuga, K., Uemura, M., Yoshikawa, H., Myoui, A.
  • Journal Title: Cell Transplantation 14 Pages: 829-835
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. (2005)
  • Author(s): Oshima, K., Nampei, A., Matsuda, M., Iwaki, M., Fukuhara, A., Hashimoto, J., Yoshikawa, H., Shimomura I.
  • Journal Title: Biochem Biophys Res Commun 331 Pages: 520-526
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A new biotechnology for articular cartilage repair : subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2). (2005)
  • Author(s): Tamai, N., Myoui, A., Hirao, M., Kaito, T., Ochi, T., Tanaka, J., Takaoka, K., Yoshikawa, H.
  • Journal Title: Osteoarthritis and Cartilage 13 Pages: 405-417
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The role of bone morphogenetic proteins in endochondral bone formation. (2005)
  • Author(s): Tsumaki, N., Yoshikawa, H.
  • Journal Title: Cytokine Growth Factor Reviews 16 Pages: 279-285
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Bone tissue engineering with porous hydroxyapatite ceramics. (2005)
  • Author(s): Yoshikawa, H., Myoui, A.
  • Journal Title: Journal of Artificial Organs 8 Pages: 131-136
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 膝関節疾患に対する再生医療の現状 (2005)
  • Author(s): 中村憲正, 中田研, 名井陽, 吉川秀樹
  • Journal Title: Orthopaedics 18 Pages: 149-155
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 連通多孔体ハイドロキシアパタイトと骨髄間葉系細胞を用いた骨再生 (2005)
  • Author(s): 西川昌孝, 名井陽, 大串始, 池内正子, 玉井宣行, 吉川秀樹
  • Journal Title: 別冊整形外科 47 Pages: 7-11
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 骨・軟骨の再生医療 (2005)
  • Author(s): 中村憲正, 吉川秀樹
  • Journal Title: 臨床と研究 82 Pages: 983-986
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 骨を生まれ変わらせる-人工骨による骨組織再生 (2005)
  • Author(s): 海渡貴司, 名井陽, 吉川秀樹
  • Journal Title: Biophilia 1 Pages: 28-34
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 運動器の再生医療の現状と展望 (2005)
  • Author(s): 吉川秀樹
  • Journal Title: 理学療法学 32 Pages: 441-444
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Capillary vessel network integration by inserting a vascular pedicle enhances bone formation in tissue-engineered bone using interconnected porous hydroxyapatite ceramics. (2004)
  • Author(s): Akita, S., Tamai, N., Myoui, A., Nishikawa, M., Kaito, T., Takaoka, K., Yoshikawa, H.
  • Journal Title: Tissue Engineering 10 Pages: 789-795
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia. (2004)
  • Author(s): Horiki, M., Imamura, T., Okamoto, M., Hayashi, M., Murai, J., Myoui, A., Ochi, T., Miyazono, K., Yoshikawa, H., Tsumaki, N.
  • Journal Title: Journal of Cell Biology 65 Pages: 433-445
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Calcium hydroxyapatite ceramic implants in bone tumor surgery. A long term follow-up study. (2004)
  • Author(s): Matsumine, A., Myoui, A., Kusuzaki, K., Araki, N., Seto, M., Yoshikawa, H., Uchida, A.
  • Journal Title: Journal of Bone and Joint Surgery 86B Pages: 719-725
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Healing of a chondral fragment of the knee in an adolescent after internal fixation. A case report. (2004)
  • Author(s): Nakamura, N., Horibe, S., Iwahashi, T., Kawano, K., Shino, K., Yoshikawa, H.
  • Journal Title: Journal of Bone and Joint Surgery 86A Pages: 2741-2746
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Matrix extracellular phosphoglycoprotein (MEPE) is highly expressed in osteocytes in human bone. (2004)
  • Author(s): Nampei, A., Hashimoto, J., Hayashida, K., Tsuboi, H., Shi, K., Tsuji, I., Miyashita, H., Yamada, T., Matsukawa, N., Matsumoto, M., Morimoto, S., Ogihara, T., Ochi, T., Yoshikawa, H.
  • Journal Title: Journal of Bone and Mineral Metabolism 22 Pages: 176-184
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Bone tissue engineering using novel interconnected porous hydroxyapatite ceramics combined with marrow mesenchymal cells : Quantitative and tree-dimentional image analysis. (2004)
  • Author(s): Nishikawa, M., Myoui, A., Ohgushi, H., Ikeuchi, M., Tamai, N., Yoshikawa, H.
  • Journal Title: Cell Transplantation 13 Pages: 367-376
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Low-intensity pulsed ultrasound accelerates maturation of callus in patients treated with opening-wedge high tibial osteotomy by hemicallotasis. (2004)
  • Author(s): Tsumaki, N., Kakiuchi, M., Sasaki, J., Ochi, T., Yoshikawa, H.
  • Journal Title: Journal of Bone and Joint Surgery 86A Pages: 2399-2405
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 新規全気孔連通型HA多孔体NEOBONEを用いた骨欠損に対する治療 (2004)
  • Author(s): 玉井宣行, 名井陽, 荒木信人, 秋田鐘弼, 中瀬尚長, 海渡貴司, 村瀬剛, 上田孝文, 越智隆弘, 吉川秀樹
  • Journal Title: 関節外科 23 Pages: 100-107
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 人工骨材料と骨・関節修復、新規全気孔連通型HA多孔体NEOBONEを用いた骨・関節修復 (2004)
  • Author(s): 玉井宣行, 名井陽, 橋本英雄, 西川昌孝, 藤井昌一, 中瀬尚長, 橋本淳, 上田孝文, 越智隆弘, 吉川秀樹
  • Journal Title: 分子リウマチ 1 Pages: 107-112
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 連通多孔体型ハイドロキシアパタイトの開発と再生医療への展開 (2004)
  • Author(s): 名井陽, 吉川秀樹
  • Journal Title: 骨・関節・靭帯 17 Pages: 1205-1215
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Smad6/Smurfl overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia. (2004)
  • Author(s): Horiki, M., Imamura, T., Okamoto, M., Hayashi, M., Murai, J., Myoui, A., Ochi, T., Miyazono, K., Yoshikawa, H., Tsumaki, N.
  • Journal Title: Journal of Cell Biology 65 Pages: 433-445
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Localization of bone morphogenetic protein-2 in human osteoarthritic cartilage and osteophyte. (2003)
  • Author(s): Nakase, T., Miyaji, T., Tomita, T., Kaneko, M., Kuriyama, K., Myoui, A., Sugamoto, K., Ochi, T., Yoshikawa, H.
  • Journal Title: Osteoarthritis Cartilage 11 Pages: 278-284
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. (2003)
  • Author(s): Nishikawa, M., Myoui, A., Tomita, T., Takahi, K., Nampei, A., Yoshikawa, H.
  • Journal Title: Arthritis and Rheumatism 48 Pages: 2670-2681
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 骨移植と人工骨 (2003)
  • Author(s): 吉川秀樹, 名井陽
  • Journal Title: Current Therapy 21 Pages: 48-51
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Possible roles of bone morphogenetic proteins and transforming growth factor-bs in the pathogenesis of OPLL and OLF. p.59-63 (2006)
  • Author(s): Yoshikawa, H.
  • Total Pages: 5
  • Publisher: Springer
  • Description: 「研究成果報告書概要(和文)」より