Development of the injectable biomaterials for vertebral fracture healing

• Project/Area Number: 17K16701
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kitasato University
• Principal Investigator: Saito Wataru 北里大学, 医学部, 講師 (60439099)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 人工コラーゲン / コラーゲン結合型成長因子 / 椎体骨折 / 椎体圧迫骨折 / 骨癒合 / 局所投与 / 骨形成タンパク / 再生医学 / 生理活性 / 細菌

Outline of Final Research Achievements

The prevalence of patients with vertebral fracture continues to increase in aging societies, including Japan. Here, we developed an artificial collagen-based bone formation system consisting of poly(Pro-Hyp-Gly)n, which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to collagen-binding domain (CBD) of Clostridium histolyticum collagenase. We examined the formation abilitiy of four collagen-binding bFGF consisting consisting of bFGF-s3, bFGF-s2b-s3, bFGF-s3b, and bFGF-s3a-s3b in a mice femoral fracture model. As bFGF-s3a-s3b showed the highest capacity to induce callus formation in the mice fracture model, bFGF-s3a-s3b-loaded artificial collagen gel (ACG) applied the in rat vertebral fracture model and induced bone formation. In addition, combination of bFGF-s3a-s3b and BMP2 promote bone formation. The poly(Pro-Hyp-Gly)n/bFGF-s3a-s3b/BMP-2 construct may therefore have the potential to promote bone formation in clinical settings.

Academic Significance and Societal Importance of the Research Achievements

我が国においても高齢者における骨折は脳血管疾患、高齢による衰弱に次ぐ寝たきり原因の3位であり、椎体骨折後の死亡率は骨折を有しない場合の約4倍の死亡率になるとの報告もある。高齢化の進む我が国の65 歳以上における骨折治療に要する年間医療費の総額は約6000 億円と推測されており、この額は65 歳以上の年間医療費の約4%を占めている。従って高齢者の骨折治癒法の確立は医学的、医療経済的、社会的に重要な意味を持つ。本シーズは、椎体骨折に伴う患者、家族の身体的・精神的苦痛の軽減に加え、経済的な負担軽減、そして医療費の軽減に重要な意義を持つ。

Research Products

• [Journal Article] Risk factors associated with prolonged intensive care unit stay after posterior spinal fusion for Duchenne muscular dystrophy. (2020)
  • Author(s): Saito W, Inoue G, Shirasawa E, Imura T, Nakazawa T, Miyagi M, Uchida K, Matsuda H, Akazawa T, Takaso M.
  • Journal Title: J Orthop Sci Volume: - Issue: 3 Pages: 332-336
  • DOI: 10.1016/j.jos.2020.03.014
  • Peer Reviewed
• [Journal Article] Prediction tool for high risk of surgical site infection in spinal surgery. (2020)
  • Author(s): Namba T, Ueno M, Inoue G, Imura T, Saito W, Nakazawa T, Miyagi M, Shirasawa E, Takahashi O, Takaso M
  • Journal Title: Infect Control Hosp Epidemiol Volume: 24 Issue: 7 Pages: 1-6
  • DOI: 10.1017/ice.2020.107
  • Peer Reviewed
• [Journal Article] Occupational Characteristics of Low Back Pain Among Standing Workers in a Japanese Manufacturing Company (2020)
  • Author(s): Inoue G, Uchida K, Miyagi M, Saito W, Nakazawa T, Imura T, Shirasawa E, Akazawa T, Orita S, Inage K, Takaso M, Ohtori S
  • Journal Title: Workplace Health Saf Volume: 68 Issue: 1 Pages: 13-23
  • DOI: 10.1177/2165079919853839
  • Peer Reviewed / Open Access
• [Journal Article] Effect of single injection of recombinant human bone morphogenetic protein-2-loaded artificial collagen-like peptide in a mouse segmental bone transport model (2019)
  • Author(s): Tazawa R, Minehara H, Matsuura T, Kawamura T, Uchida K, Saito W, Inoue G, Takaso M.
  • Journal Title: Biomed Res Int Volume: - Pages: 1014594-1014594
  • DOI: 10.1155/2019/1014594
  • Peer Reviewed / Open Access
• [Journal Article] Regression of Retro-odontoid Pseudotumor Using External Orthosis without Atlantoaxial Fusion (2019)
  • Author(s): Nakazawa T, Inoue G, Imura T, Miyagi M, Saito W, Shirasawa E, Kawakubo A, Takaso M
  • Journal Title: JBJS Case Connect Volume: 9 Issue: 3 Pages: e0329-e0329
  • DOI: 10.2106/jbjs.cc.18.00329
  • Peer Reviewed / Open Access
• [Journal Article] The impact of switching once-weekly teriparatide to denosumab in osteoporosis patients (2019)
  • Author(s): Miyagi M, Fujimaki H, Naruse K, Suto K, Inoue G, Nakazawa T, Imura T, Saito W, Uchida K, Shirasawa E, Takahira N, Takaso M
  • Journal Title: J Orthop Sci Volume: 24 Issue: 1 Pages: 153-158
  • DOI: 10.1016/j.jos.2018.08.001
  • Peer Reviewed / Open Access
• [Journal Article] Safety and Efficacy of Treatment for Scolios Is Secondary to Spinal Muscular Atrophy Fused to Lumbar 5 Level (2018)
  • Author(s): Takei S, Miyagi M, Saito W, Imura T, Inoue G, Nakazawa T, Shirasawa E, Uchida K, Akazawa T, Takahira N, Takaso M
  • Journal Title: Spine Surgery and Related Research Volume: 2 Issue: 4 Pages: 294-298
  • DOI: 10.22603/ssrr.2017-0093
  • NAID: 130007500798
  • ISSN: 2432-261X
  • Year and Date: 2018-10-26
  • Peer Reviewed / Open Access
• [Journal Article] adiographic and Clinical Outcomes From the Use of S2 Alar Screws in Surgery for Adult Spinal Deformity (2018)
  • Author(s): Nakazawa T, Inoue G, Imura T, Miyagi M, Saito W, Shirasawa E, Uchida K, Takahira N, Takaso M
  • Journal Title: Global Spine J Volume: 8 Issue: 7 Pages: 668-675
  • DOI: 10.1177/2192568218762378
  • Peer Reviewed / Open Access
• [Journal Article] The Relationship between Preoperative Echocardiographic Evaluation and Spinal Deformity in Patients with Neuromuscular Scoliosis (2018)
  • Author(s): Saito W, Inoue G, Imura T, Nakazawa T, Miyagi M, Shirasawa E, Uchida K, TakasoM
  • Journal Title: Spine Surgery and Related Research Volume: 2 Issue: 1 Pages: 48-52
  • DOI: 10.22603/ssrr.2017-0018
  • NAID: 130006321439
  • ISSN: 2432-261X
  • Peer Reviewed / Open Access
• [Journal Article] Perioperative Evaluation of Respiratory Muscle Strength after Scoliosis Correction in Patients with Duchenne Muscular Dystrophy (2017)
  • Author(s): Saito Wataru、Mizuno Kosuke、Inoue Gen、Imura Takayuki、Nakazawa Toshiyuki、Miyagi Masayuki、Shirasawa Eiki、Uchida Kentaro、Takaso Masashi
  • Journal Title: Asian Spine Volume: 11 Issue: 5 Pages: 787-787
  • DOI: 10.4184/asj.2017.11.5.787
  • Peer Reviewed / Open Access
• [Journal Article] Basic Fibroblast Growth Factor-Anchored Multilayered Mesenchymal Cell Sheets Accelerate Periosteal Bone Formation (2017)
  • Author(s): Uchida K, Inoue G, Matsushita O, Horikawa K, Sekiguchi H, Saito W, Takano S, Fujimaki H, Miyagi M, Takaso M.
  • Journal Title: Biomed Res Int Volume: 4371460 Pages: 1-8
  • DOI: 10.1155/2017/4371460
  • Peer Reviewed / Open Access
• [Journal Article] Spinal correction in patients with Fukuyama congenital muscular dystrophy (2017)
  • Author(s): Saito Wataru、Namba Takanori、Inoue Gen、Imura Takayuki、Miyagi Masayuki、Nakazawa Toshiyuki、Shirasawa Eiki、Uchida Kentaro、Takaso Masashi
  • Journal Title: J Orthop Sci Volume: 22 Issue: 4 Pages: 658-664
  • DOI: 10.1016/j.jos.2017.02.005
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Freeze-Dried Allograft Bone with Human Basic Fibroblast Growth Factor Containing a Collagen-Binding Domain From Clostridium Histolyticum Collagenase on Bone Formation After Lumbar Posterolateral Fusion Surgery in Rats (2017)
  • Author(s): Inoue G, Uchida K, Matsushita O, Fujimaki H, Saito W, Miyagi M, Sekiguchi H, Nishi N, Ohtori S, Yogoro M, Takaso M.
  • Journal Title: Spine Volume: 印刷中 Issue: 17 Pages: 995-1001
  • DOI: 10.1097/brs.0000000000002074
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 塩基性線維芽細胞増殖因子と局所硬化デキストランゲルを用いた新規骨形成促進法の有用性 (2018)
  • Author(s): 庄司真太郎、内田健太郎、関口裕之、井上 玄、齋藤 亘、宮城正行、村田幸佑、川久保 歩、高相晶士
  • Organizer: 第33回日本整形外科学会基礎学術集会
• [Presentation] 小児期側彎症手術における各手術手技段階での血液損失の検討 術中出血低減の試み (2017)
  • Author(s): 白澤栄樹、齋藤 亘、宮城正行、井上 玄、井村貴之、中澤俊之、高相晶士
  • Organizer: 第66回日本整形災害外科学会
• [Presentation] 胸椎に直接浸潤した非小細胞肺癌に対し部分椎体切除を併用し腫瘍を一塊に摘出しえた1例 (2017)
  • Author(s): 米田昌広、白澤栄樹、井上 玄、齋藤 亘、中澤俊之、井村貴之、宮城正行、高相晶士
  • Organizer: 第66回日本整形災害外科学会
• [Patent(Industrial Property Rights)] 骨再生用組成物、骨再生用組成物キット、骨再生用部材および骨再生方法 (2018)
  • Inventor(s): 内田健太郎、齋藤 亘、庄司真太郎、高相晶士 等
  • Industrial Property Rights Holder: 内田健太郎、齋藤 亘、庄司真太郎、高相晶士 等
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018