This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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