Development of novel fracture healing methods using artificical perioteum and collagen-binding growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase

• Project/Area Number: 25670659
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kitasato University
• Principal Investigator: TAKASO Masashi 北里大学, 医学部, 教授 (90439117)
• Co-Investigator(Kenkyū-buntansha): UCHIDA Kentaro 北里大学, 医学部, 助教 (50547578) ; MATSUSHITA Osamu 岡山大学, 医歯(薬)学総合研究科, 教授 (00209537) ; MABUCHI Yo 東京医科歯科大学, その他の研究科, 助教 (50424172) ; INOUE Gen 北里大学, 医学部, 准教授 (80594209)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 人工骨膜 / コラーゲン結合型成長因子 / 間葉系幹細胞 / 細胞積層技術 / 人工骨膜組織 / 機能性人工骨膜

Outline of Final Research Achievements

We attempted to develop a functional artificial periosteum using mesenchymal stem cells (MSCs) and a fusion protein (collagen binding-bFGF, CB-bFGF) consisting of bFGF and the collagen-binding domain (CBD) of Clostridium histolyticum collagenase for bone repair. Artificial periosteum had higher expression of trophic factots than monolayer cultured MSCs. Moreover, the combination of the collage CB-bFGF with artificial periosteum induced bone formation compared to artificial periosteum alone in rat models. Taken together, these properties suggest that the CB-bFGF/artificial periosteum composite is a promising material for bone repair in the clinical setting.

Research Products

• [Journal Article] Acceleration of callus formation during fracture healing using basic fibroblast growth factor-kidney disease domain-collagen binding domain fusion protein combined with allogenic demineralized bone powder. (2015)
  • Author(s): Saito W, Uchida K, Matsushita O, Inoue G, Sekiguchi H, Aikawa J, Fujimaki H, Takaso M.
  • Journal Title: J Orthop Surg Res Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CD11c+ macrophages and levels of TNF-α and MMP-3 are increased in synovial and adipose tissues of osteoarthritic mice with hyperlipidemia. (2015)
  • Author(s): Uchida K, Satoh M, Inoue G, Onuma K, Miyagi M, Iwabuchi K, Takaso M.
  • Journal Title: Exp Clin Immunol Volume: in press Issue: 3 Pages: 551-559
  • DOI: 10.1111/cei.12607
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enhancement of periosteal bone formation by basic fibroblast-derived growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase． (2015)
  • Author(s): Uchida K, Matsushita O, Nishi N, Inoue G, Horikawa K, Takaso M. ．
  • Journal Title: J Tissue Eng Regen Med Volume: in press Issue: 4 Pages: 1165-1172
  • DOI: 10.1002/term.2019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Risk factors for L5-S1 disk height reduction after lumbar posterolateral floating fusion surgery. (2014)
  • Author(s): Inoue G, Takaso M, Miyagi M, Kamoda H, Ishikawa T, Nakazawa T, Imura T, Ueno M, Saito W, Uchida K, Toyone T, Takahashi K, Ohtori S.
  • Journal Title: J Spinal Disord Tech Volume: in press Issue: 5 Pages: E187-E192
  • DOI: 10.1097/bsd.0000000000000088
  • Peer Reviewed
• [Journal Article] Teriparatide increases the insertional torque of pedicle screws during fusion surgery in patients with postmenopausal osteoporosis. (2014)
  • Author(s): Inoue G, Ueno M, Nakazawa T, Imura T, Saito W, Uchida K, Ohtori S, Toyone T, Takahira N, Takaso M.
  • Journal Title: J Neurosurg Spine Volume: in press
  • Peer Reviewed
• [Journal Article] Acceleration of periosteal bone formation by human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase. (2014)
  • Author(s): Uchida K, Matsushita O, Naruse K, Mima T, Nishi N, Hattori S, Ogura T, Inoue G, Tanaka K, Takaso M.
  • Journal Title: J Biomed Mater Res A. Volume: 102 Issue: 6 Pages: 1737-1743
  • DOI: 10.1002/jbm.a.34841
  • Peer Reviewed
• [Journal Article] Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase (2013)
  • Author(s): Saito W, Uchida K, Ueno M, MatsushitaO, Inoue G, Nishi N, Ogura T, Hattori S, Fujimaki H, Tanaka K, Takaso M
  • Journal Title: J Biomed Mater Res A Volume: in press Issue: 9 Pages: 3049-3055
  • DOI: 10.1002/jbm.a.34974
  • Peer Reviewed
• [Journal Article] Triclosan-coated sutures reduce wound infections after spinal surgery: a retrospective, non-randomized, clinical study (2013)
  • Author(s): Ueno M, Saito W, Yamagata M, Imura T, Inoue G, Nakazawa T, Takahira N, Uchida K, Fukahori N, Smimomura K, Takaso M.
  • Journal Title: Spine J Volume: - Issue: 5 Pages: 933-938
  • DOI: 10.1016/j.spinee.2013.06.046
  • Peer Reviewed
• [Presentation] 線維芽細胞増殖因子アンカーリング間葉系細胞積層シートの骨形成能の検討 (2014)
  • Author(s): 内田健太郎、堀川恭佑、井上玄、松下 治、斎藤亘、成瀬康治、藤巻寿子、占部憲、高相晶士.
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • 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] Acceleration of periosteal bone formation by human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase
  • Author(s): Uchida K, Matsushita O, Naruse K, Inoue G, Takaso M.
  • Organizer: World Congress on Controversies, Debates & Consensus in Bone, Muscle & Joint Diseases
  • Place of Presentation: Brussels
• [Presentation] Injectable コラーゲンパウダーとコラーゲン結合型線維芽細胞増殖因子による骨折後の骨形成促進効果の検討
  • Author(s): 斉藤 亘、内田健太郎、上野正喜、井上 玄、大貫裕子、松下治、高相晶士.
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張
• [Presentation] コラーゲン結合性線維芽細胞増殖因子（bFGF-CBD）とコラーゲンシートの併用による同種骨移植後の骨癒合促進
  • Author(s): 上野正喜、内田健太郎、斉藤 亘、余頃瑞希、井上玄、松下治、高平尚伸、高相晶士.
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張
• [Presentation] 脊椎手術におけるコラーゲン結合ドメインを融合した塩基性線維芽細胞増殖因子の骨形成に与える影響
  • Author(s): 井上玄、内田健太郎、上野正喜、斉藤亘、中澤俊之、井村貴之、松下治、高平尚伸、高相晶士.
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張