Cell and Growth factor deliverly using in situ formed hydrogel for treatment of bone defect

• Project/Area Number: 19K18546
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: 湘南医療大学
• Principal Investigator: Sekiguchi Hiroyuki 湘南医療大学, 臨床医学研究所, 研究員 (90547233)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 骨形成蛋白 / 徐放 / ゲル剤 / 局所硬化ゲル / 骨欠損治療 / 間葉系幹細胞送達 / ヒアルロン酸 / デキストラン / 硬化ゲル / 成長因子 / 幹細胞

Outline of Research at the Start

マウスMSC、CB-GF搭載注入型局所硬化ゲルの有用性をマウス広範囲骨欠損モデルを用いて評価する。また、MHCハプロタイプの異なるマウスを用いて広範囲骨欠損モデルを作成し、同種MSC搭載注入型局所硬化ゲルによる治療の可能性を検討する実用化に向けてヒトMSCを用いた効果検証を免疫不全マウス広範囲骨欠損モデルにより検討する。

Outline of Final Research Achievements

We examined the effectiveness of an in situ-formed hydrogels (IFHGs) made of hyaluronan (IFHG-HA) containing BMP2 for promoting bone formation in a mouse critical size bone defect model. C57/BL6J mice received a 2-mm femoral critical-sized bone defect before being randomly assigned to one of the following treatment groups (n=6): control (no treatment), IFHG-HA only, PBS with BMP2, and IFHG-HA with BMP2. X-ray radiographs were utilized to track new bone formation, and micro-computed tomography and histological examination were performed on new bone formed at the bone defect site two weeks after surgery. Mice treated with PBS with BMP2 and IFHG-HA with BMP2 had greater bone volume (BV) and bone mineral content (BMC) than those receiving control, and successfully achieved consolidation. Mice treated with IFHG-HA with BMP2 had significantly higher BV and BMC than those treated with PBS with BMP2. IFHG-HA may be an effective carrier for BMP2 to enable delivery for bone defect repair.

Academic Significance and Societal Importance of the Research Achievements

外傷や腫瘍掻爬後の広範囲骨欠損は治療に難渋する。治療の長期化に伴う患者の社会復帰の遅延は、患者に肉体的・精神的苦痛を与えるとともに医療費の増加と社会経済的損失に直結する。本研究で開発したゲル剤は広範囲骨欠損治療に重要であると考えられる。

Research Products

• [Journal Article] Expression of nerve growth factor in the callus during fracture healing in a fracture model in aged mice (2022)
  • Author(s): Sekiguchi H, Inoue G, Shoji S, Tazawa R, Kuroda A, Miyagi M, Takaso M, Uchida K
  • Journal Title: Biomed Mater Eng Volume: 33 Issue: 2 Pages: 131-137
  • DOI: 10.3233/bme-211284
  • Peer Reviewed
• [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: - Pages: 207-215
  • DOI: 10.3233/bme-201172
  • Peer Reviewed
• [Journal Article] Wrapping with Basic Fibroblast Growth Factor-Impregnated Collagen Sheet Reduces Rat Sciatic Nerve Allodynia (2019)
  • Author(s): Mukai M, Uchida K, Hirosawa N, Murakami K, Kuniyoshi K, Inoue G, Miyagi M, Sekiguchi H, Shiga Y, Inage K, Orita S, Suzuki T, Matsuura Y, Takaso M, Ohtori S
  • Journal Title: J Orthop Res Volume: 37 Issue: 10 Pages: 2258-2263
  • DOI: 10.1002/jor.24349
  • 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
• [Presentation] BMP-2含有局所硬化ヒアルロン酸ゲルを用いた難治性骨折治療法の有用性 (2020)
  • 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35回日本整形外科学会基礎学術集会