Oral Implantology and Regenerative Dental Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan.
J Biomed Mater Res A. 2011 Sep 15;98(4):488-98. doi: 10.1002/jbm.a.33117. Epub 2011 Jun 16.
The purpose of this study is to evaluate the osteoconductivity of three different bone substitute materials: α-tricalcium phosphate (α-TCP), (β-TCP), and hydroxyapatite (HA), combined with or without simvastatin, which is a cholesterol synthesis inhibitor stimulating BMP-2 expression in osteoblasts. We used 72 Wistar rats and prepared two calvarial bone defects of 5 mm diameter in each rat. Defects were filled with the particles of 500-750 μm diameter combined with or without simvastatin at 0.1 mg dose for each defect. In the control group, defects were left empty. Animals were divided into seven groups: α-TCP, β-TCP, HA, α-TCP with simvastatin, β-TCP with simvastatin, HA with simvastatin, and control. The animals were sacrificed at 6 and 8 weeks. The calvariae were dissected out and analyzed with micro CT. The specimens were evaluated histologically and histomorphometrically. In α-TCP group, the amount of newly formed bone was significantly more than both HA and control groups but not significantly yet more than β-TCP group. Degradation of α-TCP was prominent and β-TCP showed slower rate while HA showed the least degradation. Combining the materials with Simvastatin led to increasing in the amount of newly formed bone. These results confirmed that α-TCP, β-TCP, and HA are osteoconductive materials acting as space maintainer for bone formation and that combining these materials with simvastatin stimulates bone regeneration and it also affects degradability of α-TCP and β-TCP. Conclusively, α-TCP has the advantage of higher rate of degradation allowing the more bone formation and combining α-TCP with simvastatin enhances this property.
α-磷酸三钙(α-TCP)、β-磷酸三钙(β-TCP)和羟基磷灰石(HA),以及它们与辛伐他汀(一种刺激成骨细胞中 BMP-2 表达的胆固醇合成抑制剂)联合使用的效果。我们使用 72 只 Wistar 大鼠,在每只大鼠的颅骨上制备两个直径为 5 毫米的骨缺损。将 500-750μm 粒径的颗粒填入这些缺陷中,每个缺陷中填入的颗粒与或不与 0.1mg 剂量的辛伐他汀结合。在对照组中,缺陷处不填充任何物质。动物被分为七组:α-TCP 组、β-TCP 组、HA 组、α-TCP 联合辛伐他汀组、β-TCP 联合辛伐他汀组、HA 联合辛伐他汀组和对照组。在 6 周和 8 周时,处死动物。取出颅骨并使用微 CT 进行分析。对标本进行组织学和组织形态计量学评估。在α-TCP 组中,新形成的骨量明显多于 HA 组和对照组,但尚未显著多于β-TCP 组。α-TCP 降解明显,β-TCP 降解速度较慢,HA 降解最少。将材料与辛伐他汀联合使用会增加新形成的骨量。这些结果证实,α-TCP、β-TCP 和 HA 是具有成骨能力的材料,可作为骨形成的空间维持物,将这些材料与辛伐他汀联合使用可刺激骨再生,并影响α-TCP 和β-TCP 的降解性。总之,α-TCP 具有较高的降解率,可促进更多的骨形成,并且将α-TCP 与辛伐他汀联合使用可增强这种特性。