Development of rapidly constructible bone regeneration materials to treat large bone defect

• Project/Area Number: 21K20978
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kitasato University
• Principal Investigator: Shoji Shintaro 北里大学, 医学部, 助教 (60728202)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 局所硬化ゲル / 多孔質材料 / 骨欠損治療 / 塩基性線維芽細胞増殖因子 / 骨形成促進 / BMP-2 / 成長因子導入 / 細胞導入 / 硬化ゲル

Outline of Research at the Start

広範囲骨欠損は治療に難渋する。本研究ではゲル剤の特性を利用した多孔質材料への迅速な細胞、成長因子導入法の確立と新規材料を用いた骨欠損治療法の開発を目指す。多孔質人工骨への迅速な細胞、成長因子導入法による難治性骨折治療法の確立を目指し、1. 多孔質材料への細胞、成長因子導入に適した硬化ゲルの開発、2. マウス、ラット骨欠損モデルを用いたシーズの有用性の検討、3. 実用化に向けたヒト細胞を用いた検証を行う。

Outline of Final Research Achievements

We examined the effectiveness of in situ-formed gels (IFGs) consisting of hyaluronan (HyA)-tyramine (TA), horseradish peroxidase and hydrogen peroxide enhance the bone formation ability of hydroxyapatite (Hap)/BMP-2 composites for facilitating osteogenesis in refractory fracture model mice. After establishing the refractory fracture model, animals were either treated at the site of fracture with　IFGs-HyA with Hap harboring BMP-2 (IFGs-HyA/Hap/BMP-2). We determined the extent of bone formation at the fracture site according to findings on micro-computed tomography and histological experiments.　Animals treated with IFGs-HyA/Hap/BMP-2 demonstrated significantly greater bone volume, bone mineral content and bone union than those treated with vehicle or IFG-HyA/Hap alone.　IFGs-HyA/Hap/BMP-2 could be an effective treatment option for refractory fractures.

Academic Significance and Societal Importance of the Research Achievements

局所硬化ゲルの多孔質材料への成長因子導入法を確立し、その有用性を示した。本方法は骨欠損治療のみならず、再生医療全般に応用できるものと考えられる。

Research Products

• [Journal Article] Acceleration of bone formation using in situ-formed hyaluronan-hydrogel containing bone morphogenetic protein-2 in a mouse critical size bone defect model (2021)
  • Author(s): Shoji S, Uchida K, Tazawa R, Saito W, Kuroda A, Sekiguchi H, Ishii D, Inoue S, Inoue G, Takaso M
  • Journal Title: Bio-Medical Materials and Engineering Volume: - Issue: 4 Pages: 207-215
  • DOI: 10.3233/bme-201172
  • Peer Reviewed
• [Presentation] BMP-2含有局所硬化ヒアルロン酸ゲルを用いた広範囲骨欠損修復法の有用性 (2021)
  • Author(s): 庄司真太郎、内田健太郎、田澤諒、関口裕之、井上 玄、齋藤亘、宮城正行、黒田晃義、高相晶士.
  • Organizer: 第36回日本整形外科学会基礎学術集会