AUGMENTATION OF LUMBAR INTERBODY FUSION USING LOCALIZED GENE THERAPY

Participants: D. Scott, E.P. Frankenburg, K.A. Sweet, B. Nolan, R. Taylor, D.C. Kayner, M.W. Stock, J. Wong, S.A. Goldstein

Keywords: localized gene therapy, tissue engineering, spine fusion.

Introduction

Lumbar interbody fusion have been promoted to treat a variety of conditions including disc disruptions, translational instability, infection, tumors, iatrogenic instability and failure of posterolateral fusion. Clinical experience has demonstrated the need and benefit of bone graft augmentation to promote fusion, but the morbidity associated with autograft harvest and concerns about the use of allografts has led to continued efforts to develop effective graft substitutes. This study is designed to investigate the use of localized gene therapy in combination with interbody fusion devices to promote fusion.

Methods

Five groups of sheep underwent two-level lateral spine fusion with the use of titanium interbody cages provided by Spinal Concepts, Inc. The cages, which were placed across L3-L4 and L5-L6, were filled with a variety of gene-activated matrices or a control. Controls in this study were autograft, harvested from lateral processes that were resected between L3 and L6. A collagen type I sponge was used as the delivery matrix in all experimental groups and included a variety gene or gene combinations, including PTH as well as angiogenic factors. A total of 27 sheep have been entered into the study. After several days of post surgical recuperation, all animals were transported to a farm environment to encourage normal levels of activity. All animals will be sacrificed at 12 weeks post surgery and evaluated for biomechanical stability and then histologic evidence of fusion and bony filling of the cages.

Progress

All surgeries have been completed and 26 of the sheep have already been euthanized and biomechanically tested. The cage/vertebral body constructs for these animals are currently being processed to produce histologic sections for light microscopic and scanning electron microscopic evaluation. It is expected that data will be available for review and statistical analysis within two months.