ENHANCEMENT OF LUMBAR FUSION W/ RHBMP 2/ COLLAGEN OR LMP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 腰椎融合术在人类中很常见，但骨愈合失败是一种常见的并发症。通过重组DNA技术合成的骨诱导生长因子已被证明在异位部位诱导骨形成。重组人骨形态发生蛋白-2(rhBMP-2)在兔模型脊柱融合中是有效的。为了确定生长因子在人类中的剂量和愈合速度，使用了非人类灵长类动物模型。在灵长类动物体内制造骨骼所需的剂量比预期的要高。生长因子通过微创方法在中空的钛螺纹融合器内输送。这项工作导致了一项人类试点临床试验的启动，并在一年的随访中获得了出色的结果。研究的重点是微调剂量和研究替代载体材料，包括用于后外侧脊柱的不同陶瓷材料组合。我们研究了BMP-2的新载体，并继续研究LMP-1，我们发现抗压缩的胶原基质是一种有效的载体，这将进入人体试验。将重组人骨形态发生蛋白-2植入猴子体内，并使用缓释载体(膏体形式)，这些结果表明该糊剂不如以前的载体有效。2006年，我们测试了一种拟议的重组人骨形态发生蛋白-2的临床配方，并将其与一项成功的临床试验中使用的早期配方进行了比较。这项测试表明，建议的配方不像原始配方那样有效，并导致修订了寻求FDA批准的战略。第二项研究将直接比较重组人骨形态发生蛋白-2和类似的骨形态发生蛋白-7产品的疗效。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lumbar spinal fusion is commonly performed in humans but the failure of bone union is a frequent complication. Osteoinductive growth factors synthesized by recombinant DNA technology have been shown to induce bone formation in heterotopic sites. Recombinant human BMP-2 (rhBMP-2) has been effective in generating spine fusions in a rabbit model. To determine the dose of the growth factor in humans and to determine the speed of healing, a non-human primate model is used. Higher doses than expected were required to make bone in the primate. The growth factor was delivered inside a hollow titanium threaded fusion cage through a minimally invasive approach. This work resulted in the initiation of a human pilot clinical trial with excellent results at one year follow up. Studies have focused on fine tuning the dose and studying alternative carrier materials including different combinations of ceramic materials for use in the posterolateral spine. We investigated new carriers for BMP-2 and continued studies with LMP-1 and we found that a compression resistant collagen matrix was an effective carrier and this will move on to human trials. Monkeys implanted with rhBMP-2 with a slower release carrier (paste form) and these results demonstrated that the paste was not as effective as previous carriers. In 2006 we tested a proposed clinical formulation of rhBMP-2 and compared it to an earlier formulation that was used in a successful clinical trial. This test demonstrated that the proposed formulation was not as active as the original formulation and resulted in a revised strategy for seeking FDA approval. A second study will directly compare the efficacy of rhBMP-2 to a similar BMP-7 product.