IGF-I and TGF-β1 application by a poly-(D,L-lactide)-coated cage promotes intervertebral bone matrix formation in the sheep cervical spine
IGF-I and TGF-β1 application by a poly-(D,L-lactide)-coated cage promotes intervertebral bone matrix formation in the sheep cervical spine
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DOI：
10.1097/00007632-200208150-00006
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发表时间：
2002-08-15
期刊：
影响因子：
3
通讯作者：
Haas, NP
中科院分区：
文献类型：
--
作者：
Kandziora, F;Schmidmaier, G;Haas, NP
研究设计.采用绵羊颈椎椎体间融合模型，通过聚-（D，L-丙交酯）（PDLLA）涂层椎间融合器联合应用胰岛素样生长因子-I（IGF-I）和转化生长因子-β-1（TGF-β 1），确定其效果。本研究的目的是确定一种新的PDLLA载体系统的有效性，并评估在羊颈椎模型中组合应用IGF-I和TGF-β 1的效果。生长因子如骨形态发生蛋白-2已被证明可以促进脊柱融合，并克服自体骨移植物的缺点。促进脊柱融合的最佳生长因子和递送这种生长因子的最佳方法仍然是一个讨论的问题。在这项研究中，32只绵羊接受了C3-C4椎间盘切除和融合术：（自体三皮质髂嵴骨移植物; n = 8）、第2组（钛融合器; n = 8）、第3组（涂有PDLLA载体的钛融合器; n = 8）和第4组（涂有PDLLA载体的钛融合器，包括IGF-I [5% w/w]和TGF-β 1 [1% w/w; n = 8）。分析血样、体重和体温。分别于术前、术后1、2、4、8、12周行X线片检查。在同一时间点，测量椎间隙高度、椎间角和脊柱前凸角。12周后，处死动物，并使用动物在松弛和伸展时的功能性X线照片评价融合部位。进行定量计算机断层扫描以评估骨矿物质密度、骨矿物质含量和骨痂体积。在屈曲、伸展、轴向旋转和侧弯时对运动节段C3-C4进行生物力学测试。确定刚度、活动范围、中性区和弹性区。采用组织形态学和组织形态计量学分析，并采用多色序列标记法确定新骨形成的时间范围。在血细胞计数、体重和体温方面，组间无差异。在12周内，第2 - 4组椎间融合器的椎间角值显著高于植骨。功能影像学评估显示，第4组的残余屈伸运动显著低于其他组。含IGF-I和TGF-β 1的PDLLA涂层融合器显示骨密度、骨矿物质含量和骨痂体积值显著较高。与其他组相比，第4组的旋转和弯曲平均刚度显著较高，旋转活动度、中性区和弹性区显著较低。尽管第4组中只有一只动物在12周后表现出牢固的骨融合，但骨密度测量评价显示，与其他组相比，使用含IGF-I和TGF-β 1的PDLLA涂层融合器的组中骨基质形成进展更快。多色连续标记显示第4组椎间骨基质形成加速。结果表明，颈椎椎间融合器的PDLLA涂层作为生长因子的输送系统是有效的。尽管在12周随访期间，通过PDLLA涂层椎间融合器应用IGF-I和TGF-β 1不能实现牢固的骨融合，但这些生长因子显著增加了椎间骨基质形成的结果。需要进行额外的长期研究来确定联合应用IGF-I和TGF-β 1是否能够成功实现脊柱融合。
Study Design. A sheep cervical spine interbody fusion model was used to determine the effect of combined insulin-like growth factor-I (IGF-I) and transforming growth factor-beta-1 (TGF-beta1) applied by a poly-(D,L-lactide) (PDLLA) coated cage.Objectives. The purpose of this study was to determine the effective of a new PDLLA carrier system, and to evaluate the effect of combined IGF-I and TGF-beta1 application in a sheep cervical in a sheep cervical spine model.Summary and Background Data. Growth factors such as bone morphogenic protein-2 have been shown to promote spine fusin and to overcome the disadvantages of an autologous bone graft. The optimum growth factor for promoting spinal fusion and the optimum method for delivering such growth factors are still a matter of discussion.Method. In this study, 32 sheep ungerwent C3-C4 discectomy and fusion: Group 1 (autologous tricortical iliac-crest bone graft; n = 8), Group 2 (titanium cage; n = 8), Group 3 (titanium cage coated with a PDLLA carrier; n = 8), and Group 4 (titanium cage coated with a PDLLA carrier including IGF-I [5% w/w] and TGF-beta1 [1% w/w; n = 8). Blood samples, body weight, and body temperature were analyzed. Radiographic scans were performed before and after surgery, then at 1, 2, 4, 8, and 12 week, respectively. At the same time points, the disc space height, intervertebral angle, and lordosis angle were measured. After 12 weeks, the animals were killed, and fusion sites were evaluated using functional radiographic views of the animals in flaxion and extension. Quantitative computed tomographic scans were performed to assess bone mineral density, bone mineral content, and bony callus volume. Biomechanical testing of the motion segment C3-C4 was performed in flexion, extension, axial rotation, and lateral bending. The stiffness, range of motion, neutral zone, and elastic zone were determined. Histomorphologic and histomorphometric analysis was performed, and polychrome swquential labeling was used to determine the time frame of new bone formation.Results. There were no differences between the groups in terms of blood counts, body weitht, and temperature. Over a 12-week period, cage Groups 2 to 4 showed significantly higher values for the intervertebral angle than for the bone graft. Functional radiographic assessment showed significantly lower residual flexion-extension movement in Group 4 than in any other group. The PDLLA-coated cages with IGF-I and TGF-beta1 showed significantly higher values for bone mineral density, bone mineral content, and bony callus volume. The average stiffness in rotation and bending was significantly higher, and the range of motion, neutral zone, and elastic zone in rotation were significantly lower in Group 4 than in any other group. Although only one animal in Group 4 demonstrated solid bony fusion agter 12 weeks, dhitomorthometric evaluation showed a more progressed bone matrix formation in the group that had PDLLA-coated cages with IGF-I and TGF-beta1 than in any oter group. Polychrome sequential labeling showed accelerated intervertebral bone matrix frmation in Group 4.Conclusions. The findings showed that PDLLA coating of cervical spine interbody fudion cages as a delivery system for growth factors was effective. Although IGF-I and TGF-beta1 application by a PDLLA-coated interbody cage was not able to avhieve a solid bony fusion during the 12-week follow-up period, these growth factors significantly increased the results of interbody bone matrix formation Additional longer-term studies are required to determine whether combined IGF-I and TGF-beta1 application leads to a successful spinal fusion.