Local effect of simvastatin combined with different osteoconductive biomaterials and collagen sponge on new bone formation in critical defects in rat calvaria

Abstract Purpose To evaluate the local effect of simvastatin (SVT) combined with deproteinized bovine bone (DBB) with hydroxyapatite/β-tricalcium phosphate biphasic ceramics (HA/TCP) and with collagen sponge (CS) on bone repair in critical size defects (CSDs) in rat calvaria. Methods Forty-two 5-mm diameter CSDs were made bilaterally in the calvaria of 18 rats. The animals were allocated according to the type of biomaterial and associations used to fill the CSD. After 8 weeks, the animals were euthanized, and their calvaria were evaluated for repaired tissue composition using histologic and histometric analyses. Results In the histometric analysis, the use of SVT showed to increase bone formation in the CSDs when combined with all the bone substitutes tested in this study (p<0.05). Greater bone formation was observed in the groups with SVT compared to the groups without SVT. Conclusions The use of SVT without the need for a vehicle and combined with a commercially available biomaterial may be a cheaper way to potentiate the formation of bone tissue without the need to produce new biomaterials. Therefore, SVT combined with DBB induced significantly greater new bone formation than did the other treatments.

摘要 研究目的：评估辛伐他汀（simvastatin, SVT）联合脱蛋白牛骨（deproteinized bovine bone, DBB）、羟基磷灰石/β-磷酸三钙双相陶瓷（hydroxyapatite/β-tricalcium phosphate biphasic ceramics, HA/TCP）以及胶原海绵（collagen sponge, CS）对大鼠颅骨临界尺寸骨缺损（critical size defects, CSDs）骨修复的局部作用。
研究方法：对18只大鼠的颅骨双侧制备42个直径5mm的临界尺寸骨缺损。根据用于填充骨缺损的生物材料类型及联合方案对动物进行分组。术后8周安乐处死动物，采用组织学与组织计量学分析方法评估其颅骨修复组织的组成。
研究结果：组织计量学分析显示，在本研究测试的所有骨替代材料中，联合辛伐他汀使用均可显著提升临界尺寸骨缺损内的骨形成量（p<0.05）；与未联合辛伐他汀的组别相比，联合辛伐他汀的各组骨形成量更高。
研究结论：无需使用递送载体、联合市售生物材料使用辛伐他汀，或许可成为一种更为经济的骨组织形成增强方案，无需开发新型生物材料。其中，辛伐他汀联合脱蛋白牛骨组的新骨形成量显著优于其他所有治疗组。