| Project/Area Number |
18K16646
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 56020:Orthopedics-related
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
Saito Ryusuke 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (80815770)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 骨形成 / 骨形成促進 / スカフォールド / 骨再生 |
|---|
| Outline of Final Research Achievements |
Nude mice have been extensively used to investigate the potency of tissue engineering strategies for bone repair. we compared ectopic bone formation in nude vs wild type mice. It was shown that calcium-phosphate scaffolds (CopiOs) loaded with different concentrations of recombinant human BMP6 lack bone forming capacity when implanted ectopically in wild type mice. However, in nude mice 40 ng/mm3 rhBMP6 was sufficient to generate relevant volumes of new bone. Injection of TNF-α blocking antibodies did not restore the bone forming capacity. The abrogation of bone formation was associated with dense cellular infiltration of host cells and in particular with the presence of CD3+ T-lymphocytes. Remarkably, type 1 collagen gels loaded with calcium and coated with rhBMP6 generated new bone in immune competent mice despite the significant presence of CD3+ cells and the prevalence of a pro-inflammatory M1 reaction confirmed by gene expression analysis.
|
| Academic Significance and Societal Importance of the Research Achievements |
バイオマテリアルの骨形成に対し、生体でおきる宿主の炎症反応が強く寄与することが示唆されきていたが、その詳しい機序は不明であった。組換えヒトBMP6を負荷したリン酸カルシウム足場（CopiO）は、ヌードマウスでで骨形成を認めたが、野生型では骨形成能を欠いた。カルシウムとrhBMP6を負荷した1型コラーゲンゲルの検討と合わせ、カルシウム結晶のサイズの違いとCa放出動態の違いにより、足場間に骨形成能の違いが生まれる可能性を示唆した。バイオマテリアルにおよる骨形成における炎症と免疫調節の役割を示し、免疫能力のある微小環境における効率的な骨形成のための新しい足場特性に必要な要件を提供します。
|
