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在小型猪中使用大肠杆菌衍生的重组人骨形态发生蛋白-2/羟基磷灰石进行腰椎后外侧融合术。

Posterolateral lumbar fusion using Escherichia coli-derived rhBMP-2/hydroxyapatite in the mini pig.

作者信息

Kong Chang-Bae, Lee Jae Hyup, Baek Hae-Ri, Lee Choon-Ki, Chang Bong-Soon

机构信息

Department of Orthopedic Surgery, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul 139-706, Korea.

Department of Orthopedic Surgery, College of Medicine, Seoul National University, Seoul Metropolitan Goverment Seoul National University Boramae Medical Center, 41 Boramae-Gil, Seoul 156-707, Korea.

出版信息

Spine J. 2014 Dec 1;14(12):2959-67. doi: 10.1016/j.spinee.2014.06.007. Epub 2014 Jun 14.

DOI:10.1016/j.spinee.2014.06.007
PMID:24937799
Abstract

BACKGROUND CONTEXT

Hydroxyapatite (HA) is used as a bone graft extender for posterolateral spinal fusion in human. It is also useful as a recombinant human bone morphogenetic protein (rhBMP)-2 carrier because of its high affinity for rhBMP-2.

PURPOSE

To assess the osteoinductivity of Escherichia coli-derived rhBMP-2 (E-BMP-2) using HA granules as a carrier and to evaluate the bone-forming ability depending on the different dosages of E-BMP-2.

STUDY DESIGN

A mini-pig lumbar posterolateral fusion model using microcomputed tomography (μCT) scanning.

PATIENT SAMPLE

Thirty-one adult male mini pigs were randomized into a single control group (n=8) without E-BMP-2 and two experimental groups with two different doses of E-BMP-2 (1 mg per side, n=8 and 3 mg per side, n=15).

OUTCOME MEASURES

Outcome was measured by plain radiography, manual palpation, CT, three-dimensional μCT, and histologic examinations.

METHODS

Bilateral intertransverse process arthrodesis was performed, and E-BMP-2 (0, 1.0, 3.0 mg per side) was implanted into the intertransverse space using HA granules as a carrier.

RESULTS

Three mini pigs were removed because of death. Among 28 experimental subjects, 19 animals achieved solid bony union. The fusion rates were 37.5% for control group, 71.4% for 1 mg group, and 84.6% for 3 mg group. Fusion rates were significantly different among groups (p=.031). However, there was no statistically significant difference in fusion rates between 1 and 3 mg groups (p=.587). Thirty-eight intertransverse fusion masses of 19 subjects underwent μCT scanning. The bone volumes determined by μCT were 12,603±3,240 mm(3) for control group, 18,718±3,000 mm(3) for 1 mg group, and 26,768±7,256 mm(3) for 3 mg group, and the difference between groups was statistically significant (p<.001).

CONCLUSIONS

This study shows that E-BMP-2 has osteoinductive activity in dose-dependent fashion, and porous HA granule is suitable for E-BMP-2 carrier in a porcine posterolateral fusion model. These preliminary findings suggest that E-BMP-2-adsorbed porous HA granules could be a novel effective bone graft substitute.

摘要

背景

羟基磷灰石(HA)在人类后外侧脊柱融合术中用作骨移植增强剂。由于其对重组人骨形态发生蛋白(rhBMP)-2具有高亲和力,它也可用作rhBMP-2载体。

目的

评估以HA颗粒为载体的大肠杆菌衍生的rhBMP-2(E-BMP-2)的骨诱导活性,并根据E-BMP-2的不同剂量评估其成骨能力。

研究设计

使用微型计算机断层扫描(μCT)扫描的小型猪腰椎后外侧融合模型。

患者样本

31只成年雄性小型猪被随机分为一个无E-BMP-2的单一对照组(n = 8)和两个使用两种不同剂量E-BMP-2的实验组(每侧1 mg,n = 8;每侧3 mg,n = 15)。

观察指标

通过X线平片、手法触诊、CT、三维μCT和组织学检查来测量结果。

方法

进行双侧横突间关节融合术,并使用HA颗粒作为载体将E-BMP-2(每侧0、1.0、3.0 mg)植入横突间间隙。

结果

3只小型猪因死亡被剔除。在28只实验对象中,19只动物实现了牢固的骨融合。对照组的融合率为37.5%,1 mg组为71.4%,3 mg组为84.6%。各组间融合率差异有统计学意义(p = 0.031)。然而,1 mg组和3 mg组之间的融合率无统计学显著差异(p = 0.587)。对19只实验对象的38个横突间融合块进行了μCT扫描。μCT测定的骨体积,对照组为12,603±3,240 mm³,1 mg组为18,718±3,000 mm³,3 mg组为26,768±7,256 mm³,组间差异有统计学意义(p < 0.001)。

结论

本研究表明E-BMP-2具有剂量依赖性的骨诱导活性,多孔HA颗粒在猪后外侧融合模型中适合作为E-BMP-2载体。这些初步研究结果表明,吸附E-BMP-2的多孔HA颗粒可能是一种新型有效的骨移植替代物。

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