Evaluation of the osteoconductivity of α-tricalcium phosphate, β-tricalcium phosphate, and hydroxyapatite combined with or without simvastatin in rat calvarial defect

Abstract

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.