This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Lumbar spinal fusion is commonly performed on 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 nonhuman primate model is used. In 2010, we did surgery on 4 rhesus monkeys to investigate a new ceramic bone graft substitute. Higher doses than expected were required to make bone in the primate. The growth factor was delivered inside a hollow titanium treated fusion cage through a minimally invasive approach. 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. During the reporting period, we tested wrapping the existing BMP-w preparation around a ceramic granule matrix as a bulking agent. This was successful in 2/3s animals to achieve spine fusion. This will move on to human trials.
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