Establishment of novel method for spinal fusion using bone allograft and collagen-binding basic fibroblast growth factor

• Project/Area Number: 26861210
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kitasato University
• Principal Investigator: Inoue Gen 北里大学, 医学部, 准教授 (80594209)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: コラーゲン / 同種骨 / コラーゲン結合型成長因子 / 成長因子 / 骨癒合 / 多血小板血漿

Outline of Final Research Achievements

In spinal surgery, allogenic bone is often applied to the fusion surgery. However, studies have shown that the use of allograft alone has limited efficacy for achievement of the bone fusion. In the present study, we developed an allogenic bone powder (BP) with basic fibroblast-derived growth factor containing a polycystic kidney disease domain (PKD) and collagen-binding domain (CBD) from Clostridium histolyticum collagenase (ColH) and investigated the stimulatory effects of bFGF-PKD-CBD combined with allogenic bone powder (BP) on bone growth in a rat lumbar posterolateral fusion surgery model. BP mixed with either PBS (PBS/BP) or 0.58 nmoles bFGF-PKD-CBD (bFGF-PKD-CBD /BP) was grafted into intertransverse space of rats lumbar spine.bFGF-PKD-CBD/ BP composite accelerates callus formation compared to PBS/BP in a rat lumbar posterolateral fusion surgery model. Our results suggest that bFGF-PKD-CBD/BP may be useful for promoting spinal bone fusion in the clinical setting.

Research Products

• [Journal Article] Spinal Epidural Hematoma after Thoracolumbar Posterior Fusion Surgery without Decompression for Thoracic Vertebral Fracture. (2016)
  • Author(s): Minato T, Miyagi M, Saito W, Shoji S, Nakazawa T, Inoue G, Imura T, Minehara H, Matsuura T, Kawamura T, Namba T, Takahira N, Takaso M.
  • Journal Title: Case Rep Orthop Volume: - Pages: 6295817-6295817
  • DOI: 10.1155/2016/6295817
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase (2016)
  • Author(s): Sekiguchi H, Uchida K, Inoue G, Matsushita O, Saito W, Aikawa J, Tanaka K, Fujimaki H, Miyagi M, Takaso M.
  • Journal Title: J Biomed Mater Res A Volume: 104 Issue: 6 Pages: 1372-1378
  • DOI: 10.1002/jbm.a.35670
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Common iliac vein injury during L5-S1 posterior lumbar interbody fusion in a patient with systemic lupus erythematosus receiving steroid treatment: A case report. (2016)
  • Author(s): Saito W, Inoue G, Nakazawa T, Imura T, Miyagi M, Uchida K, Namba T, Shirasawa E, Takahira N, Takaso M.
  • Journal Title: J Orthop Sci. Volume: - Issue: 5 Pages: 962-966
  • DOI: 10.1016/j.jos.2015.12.011
  • Peer Reviewed
• [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: 10 Issue: 1 Pages: 59-59
  • DOI: 10.1186/s13018-015-0201-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] 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] Efficacy of anti-nerve growth factor therapy for discogenic neck pain in rats. (2014)
  • Author(s): Sainoh T, Sakuma Y, Miyagi M, Orita S, Yamauchi K, Inoue G, Kamoda H, Ishikawa T, Suzuki M, Kubota G, Oikawa Y, Inage K, Sato J, Nakamura J, Aoki Y, Takaso M, Toyone T, Takahashi K, Ohtori S
  • Journal Title: Spine (Phila Pa 1976). Volume: 39 Issue: 13 Pages: E757-E762
  • DOI: 10.1097/brs.0000000000000340
  • 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: 21 Issue: 3 Pages: 425-431
  • DOI: 10.3171/2014.5.spine13656
  • Peer Reviewed
• [Journal Article] Inhibiting IκB kinase-β downregulates inflammatory cytokines in injured discs and neuropeptides in dorsal root ganglia innervating injured discs in rats. (2014)
  • Author(s): Kobori S, Miyagi M, Orita S, Gemba T, Ishikawa T, Kamoda H, Suzuki M, Hishiya T, Yamada T, Eguchi Y, Arai G, Sakuma Y, Oikawa Y, Aoki Y, Toyone T, Takahashi K, Inoue G, Ohtori S
  • Journal Title: Spine (Phila Pa 1976). Volume: 39 Issue: 15 Pages: 1171-1177
  • DOI: 10.1097/brs.0000000000000374
  • Peer Reviewed
• [Journal Article] Acceleration of bone union after structural bone grafts with a collagen-binding basic fibroblast growth factor anchored-collagen sheet for critical-size bone defects. (2014)
  • Author(s): Ueno M, Uchida K, Saito W, Matsushita O, Yogoro M, Nishi N, Ogura T, Hattori S, Inoue G, Tanaka K, Takahira N, Takaso M.
  • Journal Title: Biomed Mater. Volume: 9 Issue: 3 Pages: 035014-035014
  • DOI: 10.1088/1748-6041/9/3/035014
  • Peer Reviewed / Acknowledgement Compliant
• [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
• [Presentation] 人工コラーゲンゲル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 (2015)
  • Author(s): 関口裕之、内田健太郎、井上 玄、相川 淳、齋藤 亘、宮城正行、藤巻寿子、大貫裕子、高相晶士
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山国際会議場（富山県富山市）
  • Year and Date: 2015-10-22
• [Presentation] The effectiveness of teriparatide for insertional torque of pedicle screws in patients with postmenopausal osteoporosis (2014)
  • Author(s): Inoue G, Ueno M, Nakazawa T, Imura T, Saito W, Uchida K, Takahira N, Takaso M
  • Organizer: The 10th Meeting of the International Research Society of Spinal Deformities
  • Place of Presentation: Sapporo (Japan)
  • Year and Date: 2014-06-29 – 2014-07-02
• [Presentation] Anti-bFGF neutralizing antibody reduces grial cell activation in dorsal horn in rats CFA- induced discitis. (2014)
  • Author(s): Inoue G, Uchida K, Fujimaki H, Sekiguchi H, Ueno M, Saito W, Nakazawa T, Imura T, Takahira N, Takaso M
  • Organizer: The 41th Annual Meeting of the International Society for the Study of the Lumbar Spine
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2014-06-03 – 2014-06-07
• [Presentation] Effect of anti-bFGF neutralizing antibody on neuropathic pain induced by spinal nerve ligation in rats. (2014)
  • Author(s): Fujimaki H, Inoue G, Uchida K, Sekiguchi H, Ueno M, Saito W, Takahira N, Takaso M
  • Organizer: The 41th Annual Meeting of the International Society for the Study of the Lumbar Spine
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2014-06-03 – 2014-06-07