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肝素结合纤维蛋白与骨形态发生蛋白-2用于兔模型脊柱融合的最佳条件。

Optimal condition of heparin-conjugated fibrin with bone morphogenetic protein-2 for spinal fusion in a rabbit model.

作者信息

Hong Jae-Young, Kang Sun-Woong, Kim Jung-Wook, Suh Seung-Woo, Ko You-Jin, Park Jung-Ho

机构信息

Department of Orthopedics, Korea University Ansan Hospital, Ansan, South Korea.

Next-Generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon, Republic of Korea.

出版信息

Cytotherapy. 2014 Oct;16(10):1441-8. doi: 10.1016/j.jcyt.2014.04.005. Epub 2014 Jun 13.

Abstract

BACKGROUND AIMS

Heparin-conjugated fibrin (HCF) is a carrier for long-term release of bone morphogenetic protein-2 (BMP-2) and has been shown to promote bone formation in animal models. We performed an experimental study to determine the optimal dose of BMP-2 with an HCF carrier that promotes bone formation comparable to that of autograft while minimizing complications in spinal fusion.

METHODS

Twenty-four rabbits underwent posterolateral fusion of the L5-6 spinal segments. Different concentrations of HCF BMP-2 (1/10, 1/20, 1/30 or 1/40) were implanted in the spines of experimental rabbits, and autograft or INFUSE was implanted in the spines of control animals. Eight weeks after treatment, spinal fusion efficacy was evaluated by plain radiography, micro-computed tomography (micro-CT), mechanical testing and histomorphometry.

RESULTS

Similar to autograft, the 1/40 HCF BMP-2 showed significant bone formation on micro-CT and histomorphometry with mechanical stability. However, the other HCF BMP-2 concentrations did not show significant bone formation compared with autograft. Although conventional BMP-2 (INFUSE) led to higher bone formation and stability, it also led to excessive ectopic bone and fibrous tissue formation.

CONCLUSIONS

This study suggests the optimal concentration of BMP-2 using HCF for spinal fusion, which may decrease the complications of high-dose conventional BMP-2.

摘要

背景目的

肝素结合纤维蛋白(HCF)是骨形态发生蛋白-2(BMP-2)长期释放的载体,已证实在动物模型中可促进骨形成。我们进行了一项实验研究,以确定与自体骨移植促进骨形成效果相当且能将脊柱融合并发症降至最低的HCF载体BMP-2的最佳剂量。

方法

24只兔子接受L5-6节段的后外侧融合术。将不同浓度的HCF BMP-2(1/10、1/20、1/30或1/40)植入实验兔的脊柱,将自体骨移植或INFUSE植入对照动物的脊柱。治疗8周后,通过X线平片、显微计算机断层扫描(micro-CT)、力学测试和组织形态计量学评估脊柱融合效果。

结果

与自体骨移植相似,1/40 HCF BMP-2在micro-CT和组织形态计量学上显示出显著的骨形成且具有力学稳定性。然而,与自体骨移植相比,其他HCF BMP-2浓度未显示出显著的骨形成。虽然传统的BMP-2(INFUSE)导致更高的骨形成和稳定性,但也导致了过多的异位骨和纤维组织形成。

结论

本研究提示了用于脊柱融合的HCF BMP-2的最佳浓度,这可能会减少高剂量传统BMP-2的并发症。

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