AUGMENTATION OF INTERBODY LUMBAR FUSIONS

Participants: P.V. Patil, J. Bonadio, R.T. Taylor, K.A. Sweet, B. Nolan, S.A. Goldstein

Keywords: gene therapy, spine, animal model

Introduction

Lumbar interbody fusions have been promoted to treat a variety of conditions including internal disc disruption, translational instability, infection, tumors, iatrogenic instability, and failure of posterolateral fusions. While the benefit of bone graft augmentation has been clearly documented, the morbidity associated with autograft harvest and concerns about the use of allograft support continued efforts to develop suitable substitutes. In this project, we investigate the application of novel local gene-mediated delivery of PTH_1-34 to promote fusion.

Materials and Methods

The experimental procedure performed in this study was a three level interbody fusion of the sheep lumbar spine. The surgical procedure follows directly from currently performed standard procedures in human patients using intervertebral body fusion cages except they were placed from a lateral exposure. The design of the fusion cages are based on FDA approved devices for human use as well as the surgical approach and instrumentation utilized during the surgical procedures.

Four adult female sheep were used in this study. The surgical procedure involved exposure of disc spaces at L3-L4, L4-L5, and L5-L6 through a lateral approach. Once the end plates and discs were carefully exposed and visualized, preparation and final placement of the interbody fusion cages was aided through the use of custom instrumentation. Prior to implantation, a collagen sponge with no incorporated DNA (control), incorporating a fragment of parathyroid hormone (PTH 1-34) and one that included a combination of PTH 1-34 and FGF2 were physically placed within the cage in a manner similar to what is performed when using autograft bone. After implantation of all three cages, the wound was closed in layers and the animals were returned to their cages. At approximately two weeks the animals were then moved to a farm where they remained until sacrifice. Flourochrome labeling was administered at 3, 6, and 9 weeks post-operatively. All animals were sacrificed 12 weeks after placement of the interbody fusion cages.

Results

The data from this preliminary study shows that there is a statistically significant difference between the control cages and the cages that had the GAM (gene activated matrix) with PTH1-34 or PTH/FGF. Sample microradiographs are shown here to demonstrate the differing response. It is also clear that the use of the gene for PTH1-34 can stimulate new bone formation to insure continuity of bone architecture that leads to complete spinal arthrodesis in sheep.