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骨形态发生蛋白 2 基因和血管内皮生长因子蛋白递送增强牙种植体周围骨再生。

Enhanced bone regeneration around dental implant with bone morphogenetic protein 2 gene and vascular endothelial growth factor protein delivery.

机构信息

Ministry Education Key Laboratory for Oral Biomedical Engineering, School of Stomatology, Wuhan University, Wuhan, China.

出版信息

Clin Oral Implants Res. 2012 Apr;23(4):467-73. doi: 10.1111/j.1600-0501.2011.02164.x. Epub 2011 Mar 28.

Abstract

OBJECTIVE

To evaluate the synergistic effect of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) on the repair of bone defects around dental implants.

MATERIAL AND METHODS

Five groups of scaffold were fabricated by a freeze-drying method, including pure chitosan/collagen scaffold; scaffold loaded with adenoviruses expressing BMP-2, adenoviruses expressing VEGF, both adenoviruses expressing BMP-2 and VEGF, VEGF protein and adenovirus expressing BMP-2. In vitro studies examined whether bone marrow stromal cells were responsive to these scaffolds over time. Bone formation capacity, bone-to-implant contact, as well as removal torque values were investigated in vivo. Differences between the various groups were statistically analyzed using the one-way analysis of variance test.

RESULTS

The in vitro study revealed a burst and rapid release of VEGF with a sustained high-level expression of BMP-2 in scaffold combined with VEGF protein and adenoviruses expressing BMP-2. Histomorphometry demonstrated that scaffolds expressing BMP-2 enhanced more bone formation compared with other groups; VEGF alone is insufficient to promote bone formation. New bone formation in the bone defects around dental implants, bone-to-implant contact and mean peak removal torque showed statistically significant difference for the adenoviral vector encoding human bone morphogenetic protein 2 (Ad-BMP-2) and VEGF protein and adenovirus expressing BMP-2 groups. Furthermore, scaffold combined with VEGF protein and Ad-BMP-2 represented the best outcomes in this model.

CONCLUSIONS

A combination of BMP-2 gene and VEGF protein could have a synergistic effect in promoting bone healing.

摘要

目的

评估骨形态发生蛋白 2(BMP-2)和血管内皮生长因子(VEGF)联合对种植体周围骨缺损修复的协同作用。

材料和方法

采用冷冻干燥法制备 5 组支架,包括纯壳聚糖/胶原支架;负载表达 BMP-2 的腺病毒、表达 VEGF 的腺病毒、同时负载表达 BMP-2 和 VEGF 的腺病毒、VEGF 蛋白和表达 BMP-2 的腺病毒的支架。体外研究检测骨髓基质细胞对这些支架随时间的反应。体内研究检测骨形成能力、骨-种植体接触以及去除扭矩值。采用单因素方差分析对各组间的差异进行统计学分析。

结果

体外研究显示,VEGF 呈爆发式快速释放,与 VEGF 蛋白和表达 BMP-2 的腺病毒结合的支架中 BMP-2 呈持续高水平表达。组织形态计量学显示,与其他组相比,表达 BMP-2 的支架促进了更多的骨形成;单独使用 VEGF 不足以促进骨形成。种植体周围骨缺损中,新骨形成、骨-种植体接触和平均峰值去除扭矩在携带人骨形态发生蛋白 2(Ad-BMP-2)的腺病毒载体和 VEGF 蛋白和表达 BMP-2 的组之间存在统计学差异。此外,支架与 VEGF 蛋白和 Ad-BMP-2 联合使用在该模型中效果最佳。

结论

BMP-2 基因和 VEGF 蛋白的联合使用可能具有协同促进骨愈合的作用。

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