A porcine collagen-derived matrix as a carrier for recombinant human bone morphogenetic protein-2 enhances spinal fusion in rats
A porcine collagen-derived matrix as a carrier for recombinant human bone morphogenetic protein-2 enhances spinal fusion in rats
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DOI：
10.1016/j.spinee.2008.08.009
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发表时间：
2009-01-01
期刊：
影响因子：
4.5
通讯作者：
Wang, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Miyazaki, Masashi;Morishita, Yuichiro;Wang, Jeffrey C.
背景：重组骨形态发生蛋白（rhBMP）已成功用于临床试验。然而，需要大剂量的 rhBMP 才能诱导足够的骨修复。胶原海绵 (CS) 未能更持续地释放 rhBMP。正在进行的研究旨在设计能够更加受控和持续释放蛋白质的载体。 E-Matrix 是一种可注射的支架基质，可增强 rhBMP 活性并刺激骨再生。 目的：本研究的目的是测试 E-Matrix 作为 CS 中 rhBMP 的载体，并通过使用大鼠脊柱融合模型检验其在临床应用中的可行性。 患者样本：总共 80 只 8-16 周龄的 Lewis 大鼠分为 9 组。 研究设计/设置：大鼠脊柱融合模型。 结果指标：在第 4、6 和 8 周时拍摄射线照片。处死大鼠，取出脊柱并通过手动触诊、高分辨率微型计算机断层扫描（micro-CT）和组织学分析进行评估。 方法：I组动物仅植入CS（阴性对照）；II组动物植入含有10μg rhBMP-2的CS（阳性对照）；III组动物植入含有3μg rhBMP-2的CS； IV组动物，具有含有3μg rhBMP-2和E-Matrix的CS；具有含有1μg rhBMP-2的CS的V组动物； VI组动物，具有含有1μg rhBMP-2和E-Matrix的CS；具有含有0.5μg rhBMP-2的CS的VII组动物；具有含有0.5μg rhBMP-2和E-Matrix的CS的VIII组动物；结果：射线照相评估、显微 CT 和手动触诊显示 BMP-2 和 E-Matrix 组（IV、VI 和 VIII）以及高剂量 BMP-2 组（II 和 III）的所有大鼠均出现脊柱融合。 3μg rhBMP-2组(V)中的4个棘融合，0.5μg rhBMP-2组(VII)中的1个棘融合。第 I 组（单独的 CS）和 IX 组（单独的 E-Matrix）中没有刺融合。第 IV 组中 L4 横突顶端和 L5 横突基部之间区域的新骨体积与第 II 组中观察到的体积相当。 结论：在大鼠脊柱融合模型中，E-基质作为 rhBMP-2 的载体增强了脊柱融合。本研究结果表明，E-Matrix作为生长因子载体可能适用于脊柱融合，并可能提高融合部位rhBMP-2的活性。 (C) 2009 Elsevier Inc. 保留所有权利。
BACKGROUND CONTEXT: Recombinant bone morphogenetic proteins (rhBMPs) have been used successfully in clinical trials. However, large doses of rhBMPs were required to induce adequate bone repair. Collagen sponges (CSs) have failed to allow a more sustained release of rhBMPs. Ongoing research aims to design carriers that allow a more controlled and sustained release of the protein. E-Matrix is a injectable scaffold matrix that may enhance rhBMP activity and stimulate bone regeneration.PURPOSE: The purpose of this study was to test E-Matrix as a carrier for rhBMPs in a CS and examine its feasibility in clinical applications by using a rat spinal fusion model.PATIENT SAMPLE: A total of 80 Lewis rats aged 8-16 weeks were divided into nine groups.STUDY DESIGN/SETTING: Rat spinal fusion model.OUTCOME MEASURES: Radiographs were obtained at 4 6, and 8 weeks. The rats were sacrificed and their spines were explanted and assessed by manual palpation, high-resolution micro-computed tomography (micro-CT), and histologic analysis.METHODS: Group I animals were implanted with CS alone (negative control) Group II animals with CS containing 10 mu g rhBMP-2 (positive control): Group III animals with CS containing 3 mu g rhBMP-2; Group IV animals with CS containing 3 mu g rhBMP-2 and E-Matrix; Group V animals with CS containing 1 mu g rhBMP-2; Group VI animals with CS containing 1 mu g rhBMP-2 and E-Matrix; Group VII animals with CS containing 0.5 mu g rhBMP-2; Group VIII animals with CS containing 0.5 mu g rhBMP-2 and E-Matrix; and Group IX animals with CS and E-Matrix without rhBMP-2.RESULTS: Radiographic evaluation, micro-CT, and manual palpation revealed spinal fusion in all rats in the BMP-2 and E-Matrix groups (IV, VI, and VIII) and high-dose BMP-2 groups (II and III). Four spines in the 3 mu g rhBMP-2 group (V) fused, and one spine in the 0.5 mu g rhBMP-2 group (VII) exhibited fusion. No spines were fused in Groups I (CS alone) and IX (E-Matrix alone). The volume of new bone in the area between the tip of the L4 transverse process and the base of the L5 transverse process in Group IV was equivalent to the volumes observed in Group II.CONCLUSION: E-matrix enhances spinal fusion as a carrier for rhBMP-2 in a rat spinal fusion model. The results of this study suggest that E-Matrix as a growth factor carrier may be applicable to spinal fusion and may improve rhBMP-2's activity at the fusion site. (C) 2009 Elsevier Inc. All rights reserved.