Analyses on physical and biological factors regulating spontaneous articular cartilage regeneration induced by DN gel

• Project/Area Number: 24300169
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Hokkaido University
• Principal Investigator: KITAMURA NOBUTO 北海道大学, 医学(系)研究科(研究院), 准教授 (80447044)
• Co-Investigator(Kenkyū-buntansha): YASUDA Kazunori 北海道大学, 大学院医学研究科, 特任教授 (20166507) ; GONG Jian Ping 北海道大学, 大学院先端生命科学研究院, 教授 (20250417) ; KUROKAWA Takayuki 北海道大学, 大学院先端生命科学研究院, 准教授 (40451439) ; KONDO Eiji 北海道大学, 大学院医学研究科, 特任教授 (60374724)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 生体機能材料 / 再生医学 / 骨・軟骨代謝学 / 軟骨再生

Outline of Final Research Achievements

This study investigated to develop a clinical applicable DN gel implant and elucidated physical and biological factors regulating the DN gel-induced cartilage regeneration. (1) We developed a 0.5-mm thick gel implant. (2) We found that a 1.0-mm DN gel implant induced in vivo cartilage regeneration in a rabbit model. (3) We observed that DN gel induced in vivo cartilage regeneration regardless of location in which the DN gel was implanted in the joint. (4) We observed that DN gel induced in vivo cartilage regeneration regardless of the size of osteochondral defect. (5) We found that DN gel induced in vivo cartilage regeneration in a sheep model. (6) We found that the hyaluronic acid was a useful molecule to promote cartilage regeneration induced by DN gel.

Research Products

• [Journal Article] Proteoglycans and glycosaminoglycans improve toughness of biocompatible double network hydrogels (2014)
  • Author(s): Zhao Y, Nakajima T, Yang JJ, Kurokawa T, Liu J, Lu J, Mizumoto S, Sugahara K, Kitamura N, Yasuda K, Daniels AU, Gong JP
  • Journal Title: Advanced Materials Volume: 22 Issue: 3 Pages: 436-42
  • DOI: 10.1002/adma.201303387
  • Peer Reviewed
• [Journal Article] Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel (2014)
  • Author(s): Fukui T, Kitamura N, Kurokawa T, Yokota M, Kondo E, Gong JP, Yasuda K
  • Journal Title: Journal of Materials Science-Materials in Medicine Volume: 25 Issue: 4 Pages: 1173-82
  • DOI: 10.1007/s10856-013-5139-3
  • Peer Reviewed
• [Journal Article] Hyaluronic acid enhances the effect of the PAMPS/PDMAAm double-network hydrogel on chondrogenic differentiation of ATDC5 cells (2014)
  • Author(s): Nobuto Kitamura, Takayuki Kurokawa, Takaaki Fukui, Jian Ping Gong, Kazunori Yasuda
  • Journal Title: BMC Musculoskeletal Disorders Volume: 15 Issue: 1 Pages: 222-222
  • DOI: 10.1186/1471-2474-15-222
  • NAID: 120005468150
  • Peer Reviewed / Open Access
• [Journal Article] Significant Increase in the Young's Modulus of ATDC5 Cells during Chondrogenic Differentiation Induced by PAMPS/PDMAAm Double-Network Gel: Comparison with Induction by Insulin (2014)
  • Author(s): Eijiro Maeda, Takehiro Tsutsumi, Nobuto Kitamura, Takayuki Kurokawa, Jian Ping Gong, Kazunori Yasuda, Toshiro Ohashi
  • Journal Title: Journal of Biomechanics Volume: 47 Issue: 13 Pages: 3408-3414
  • DOI: 10.1016/j.jbiomech.2014.07.021
  • Peer Reviewed
• [Journal Article] Biomechanical comparisons of the adhesion strength of polymethylmethacrylate cement to the zirconia ceramic componentand the cobalt-chromium alloy component in total knee arthroplasty (2014)
  • Author(s): Kumahashi N, Uchio Y, Kitamura N, Satake S, Iwamoto Y, Yasuda K.
  • Journal Title: J Orthop Sci Volume: 19 Issue: 6 Pages: 940-947
  • DOI: 10.1007/s00776-014-0639-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of Culture on the PAMPS/PDMAAm Double–Network Gel on Chondrogenic Differentiation of Mouse C3H10T1/2 Cells: In Vitro Experimental Study (2014)
  • Author(s): Yusuke Inagaki, Nobuto Kitamura, Takayuki Kurokawa, Yasuhito Tanaka, Jian Ping Gong, Kazunori Yasuda, Harukazu Tohyama
  • Journal Title: BMC Musculoskeletal Disorders Volume: 15 Issue: 1 Pages: 320-320
  • DOI: 10.1186/1471-2474-15-320
  • Peer Reviewed / Open Access
• [Journal Article] A quantitative technique to create a femoral tunnel at the averaged center of the anteromedial bundle attachment in anatomic double-bundle anterior cruciate ligament reconstruction (2013)
  • Author(s): Kai S, Kondo E, Kitamura N, Kawaguchi Y, Inoue M, Amis AA, Yasuda K
  • Journal Title: BMC Musculoskelet Disord Volume: 14 Issue: 1 Pages: 189-189
  • DOI: 10.1186/1471-2474-14-189
  • Peer Reviewed
• [Journal Article] Development of a salmon-derived crosslinked atelocollagen sponge disc containing osteogenic protein-1 for articular cartilage regeneration: in vivo evaluations with rabbits. (2013)
  • Author(s): Mori H, Kondo E, Kawaguchi Y, Kitamura N, Nagai N, Iida H, Yasuda K
  • Journal Title: BMC Musculoskeletal Disorders Volume: 14 Issue: 1 Pages: 174-174
  • DOI: 10.1186/1471-2474-14-174
  • Peer Reviewed
• [Journal Article] ヒアルロン酸合成ハイドロゲルがATDC5細胞に対して有する軟骨分化誘導効果をin vitroで促進する (2013)
  • Author(s): 吉川勝久、北村信人、安田和則、黒川孝之、グン剣萍、野原裕
  • Journal Title: 日本関節病学会誌 Volume: 32 Pages: 9-15
  • Peer Reviewed
• [Journal Article] Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect : Short-term results (2013)
  • Author(s): Matsuda H, Kitamura N (2 番), Yasuda K (最後), 他 4 名
  • Journal Title: BMC Musculoskelet Disord Volume: 14 Issue: 1 Pages: 50-59
  • DOI: 10.1186/1471-2474-14-50
  • NAID: 120005228371
  • Peer Reviewed
• [Journal Article] Hyaluronic acid affects the in vitro induction effects of synthetic PAMPS and PDMAAm hydrogels on chondrogenic differentiation of ATDC5 cells, depending on the level of con- centration (2013)
  • Author(s): Yoshikawa K, Kitamura N (2 番), Yasuda K (最後), 他 6 名
  • Journal Title: BMC Musculoskelet Disord Volume: 14 Issue: 1 Pages: 56-63
  • DOI: 10.1186/1471-2474-14-56
  • Peer Reviewed
• [Journal Article] Poly (2-acrylamido-2-methylpropanesulfonic acid) gel induces articular cartilage regeneration in vivo: Comparisons of the induction ability between single- and double-network gels. (2012)
  • Author(s): Ogawa M
  • Journal Title: J Biomed Mater Res A Volume: Sep 100 (9) Issue: 9 Pages: 2244-2251
  • DOI: 10.1002/jbm.a.34165
  • Peer Reviewed
• [Presentation] Biomechanical Evaluations Of A Novel Hydroxyapatite-coated PAMPS/PDMAAm Double-network Hydrogel As A Potential Artificial Cartilage Having Adhesive Ability To The Bone (2015)
  • Author(s): Wada S, Kitamura N, Nonoyama T, Semba S, Onodera J, Kawaguchi Y, Yokota M, Higa K, Kiyama R, Kurokawa T, Gong JP, Yasuda K
  • Organizer: The 61st Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: MGM Grand, Las Vegas, USA
  • Year and Date: 2015-03-28 – 2015-03-31
• [Presentation] Synthetic PAMPS gel activates TGF-beta/BMP signaling pathway during the chondrogenic differentiation of ATDC5 cells (2015)
  • Author(s): Goto K, Kitamura N, Kimura T, Semba S, Kurokawa T, Gong JP, Tanaka S, Yasuda K
  • Organizer: The 61st Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: MGM Grand, Las Vegas, USA
  • Year and Date: 2015-03-28 – 2015-03-31
• [Presentation] PAMSゲルによるATDC５細胞のインスリン非依存性軟骨分化誘導シグナルの解明 (2015)
  • Author(s): 後藤佳子、北村信人、和田進、安田和則、木村太一、津田真寿美、田中伸哉、仙葉慎吾、黒川孝幸、グンチェンピン
  • Organizer: 第128回北海道整形災害外科学会
  • Place of Presentation: 札幌医科大学臨床教育研究棟（北海道・札幌市）
  • Year and Date: 2015-01-31 – 2015-02-01
• [Presentation] ATDC５細胞におけるPAMSゲル誘導軟骨分化特異的シグナル伝達経路の解明 (2014)
  • Author(s): 後藤佳子、北村信人、木村太一、仙波慎吾、黒川孝幸、Ping Gong、田中伸哉、安田和則
  • Organizer: 第29回日本整形外科学基礎学術集会
  • Place of Presentation: 城山観光ホテル（鹿児島県・鹿児島市）
  • Year and Date: 2014-10-09 – 2014-10-10
• [Presentation] Deficiency of Macrophage Migration Inhibitory Factor Gene Delays Bone Tendon Healing: A Biomechanical and Biological Study (2014)
  • Author(s): Onodera J, Kondo E, Kawaguchi Y, Kitamura N, Yasuda K
  • Organizer: The 60th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: Hyatt Regency New Orleans, New Orleans, Louisiana
• [Presentation] Biomechanical Characterization of Rapid Chondrogenic Differentiation of ATDC5 Cells Cultured on PAMPS/PDMAAm Double-Network Gel (2014)
  • Author(s): Maeda E, Tsutsumi T, Kurokawa T, Kitamura N, Gong JP, Yasuda K, Ohashi T
  • Organizer: The 60th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: Hyatt Regency New Orleans, New Orleans, Louisiana
• [Presentation] Hyaluronic Acid Enhances In Vitro Induction Effects of Synthetic PAMPS And PDMA Am Hydrogels on Chondrogenic Differentiation of ATDC5 Cells (2013)
  • Author(s): Yoshikawa K, Kitamura N, Kurokawa T, Nohara Y, Gong JP, Yasuda K
  • Organizer: The 9th Biennial International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine
  • Place of Presentation: Metro Toronto Convention Centre, Toronto, Canada
• [Presentation] PAMPS/PDMAAmダブルネットワークゲルが誘導する関節軟骨自然再生に対してヒアルロン酸ナトリウムの関節内投与が与える効果 (2013)
  • Author(s): 福井孝明、北村信人、黒川孝幸、横田正司、ぐん剣萍、安田和則
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張メッセ国際会議場、幕張
• [Presentation] DNゲルによるATDC5細胞の軟骨分化誘導に関する力学的機序の解明－1細胞の力学的特性の変化とアクチン修飾タンパク質発現との関連－ (2013)
  • Author(s): 前田英次郎、提健博、黒川孝幸、北村信人、Jian Ping Gong、安田和則、大橋俊朗
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張メッセ国際会議場、幕張
• [Presentation] PAMPS/PDMAAmダブルネットワークゲルが誘導するATDC5細胞の軟骨分化過程における細胞力学特性解析 (2013)
  • Author(s): 前田英次郎、堤健博、黒川孝幸、北村信人、グン剣萍、安田和則、大橋俊朗
  • Organizer: 第42回日本臨床バイオメカニクス学会
  • Place of Presentation: 神戸国際会議場、神戸
• [Presentation] Hyaluronic Acid Enhances In Vitro Induction Effects of Synthetic PAMPS and PDMAAm Hydrogels on Chondrogenic Differentiation of ATDC5 Cells (2013)
  • Author(s): Yoshikawa K, Kitamura N, Kurokawa T, Nohara Y, Gone TP,
  • Organizer: The 59th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: Henry B. Gonzalez Convention Center (USA)
• [Presentation] In Vivo Effects of Intra-Articular Hyaluronic Acid Administration on Hyaline Cartilage Regeneration Induced by PAMPS-PDMAAm Double-Network Hydrogel. (2013)
  • Author(s): Fukui T, Kitamura N, Kurokawa T, Kondo E, Yokota M, Gong TP.
  • Organizer: The 59th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: Henry B. Gonzalez Convention Center (USA)
• [Presentation] Implantation of a thin double-network gel sheet can induce spontaneous articular cartilage regeneration in vivo in a large osteochondral defect. (2012)
  • Author(s): Kitamura N, Matsuda H, Kurokawa T, Arakaki K, Gong
  • Organizer: The 10th World Congress of the International Cartilage Repair Society
  • Place of Presentation: Fairmont - The Queen Elizabeth Hotel (Canada)
• [Presentation] Gene expression profiles of the regenerated cartilage tissue induced by implantation of a novel double-network hydrogel : comparisons with the immature articular (2012)
  • Author(s): Imabuchi R, Ohmiya Y, Kwon HJ, Onodera S, Kitamura N,
  • Organizer: The 10th World Congress of the International Cartilage Repair Society
  • Place of Presentation: Fairmont - The Queen Elizabeth Hotel (Canada)