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Delivery of Biological Agents for Spinal Fusion
Spinal fusion failure, or pseudoarthrosis, is a significant cause of failed back surgery syndrome (FBSS). FBSS occurs in up to 35% of surgeries and often results in chronic pain and disability, which accounts for the interest in developing pharmacologic strategies to improve fusion rates in initial procedures.
The only therapeutic agent currently approved by the Food and Drug Administration for spinal fusion surgery is recombinant human bone morphogenetic protein-2 (rhBMP-2), a growth factor in the bone morphogenetic protein (BMP) family that has been shown to improve fusion rates in clinical studies. Although generally successful in augmenting fusion, rhBMP-2 treatment has been associated with complications and adverse effects.
The Johns Hopkins Spinal Fusion Laboratory is interested in developing improved therapeutic delivery techniques for spinal fusion procedures, including strategies involving the combined delivery of BMP family proteins and other biological agents.
We are studying the effects of the osteoporosis drug teriparatide (a parathyroid hormone analog) on spinal fusion in an animal model and in combination with BMP-2 delivery. Future work will explore using other bioactive compounds and alternative delivery strategies for better control of delivery kinetics.
Effects of Localized Radiation Therapy on Spinal Structure and Stability
Traditionally, radiation therapy has been used to treat metastatic lesions in the spine. The advent of stereotactic radiosurgery has enabled clinicians to deliver even higher doses of focused radiation, allowing for noninvasive treatment of spinal tumors previously considered “radiation resistant.”
Stereotactic radiosurgery for these lesions is extremely promising, yet recent clinical studies have shown that the procedure can increase the risk of compression fractures of the vertebrae, especially in patients with osteoporosis. This radiation-related deterioration of bone quality is a critical consideration for spinal oncology patients who require fusion procedures.
We are developing an animal model to study the long-term effects of high-dose, focused radiation on spinal structure and biomechanical integrity. Further, we seek to determine whether fractionated radiation delivery, as opposed to single higher radiation doses, can prevent post-radiation spinal compression fractures.
More important, we will also explore the use of various therapies to mitigate post-radiation fracture risk, including teriparatide. These therapies are used to increase bone density in osteoporotic patients.
Tissue Engineering and Stem Cell-based Approaches to Spinal Fusion
In spinal fusion surgery, the current “gold standard” treatment involves autografting bone from the patient’s iliac crest. This technique is limited by bone supply, and is associated with donor site morbidity and a failure rate of 5% to 35%. There is a critical need for bone graft substitutes that can also reduce the rate of pseudoarthrosis.
Tissue engineering is a promising new strategy. By combining osteoconductive carriers, which support bone growth, with growth factors that stimulate bone formation or bone-growing stem cells, tissue engineering approaches aim to replicate — or even surpass — the properties of native bone.
Our laboratory is collaborating with Warren Grayson, Ph.D., in the Department of Biomedical Engineering at The Johns Hopkins University, to develop a bioactive “scaffold” system to enhance rates of solid spinal fusion in an animal model. We are also working with the Laboratory for Craniofacial and Orthopaedic Tissue Engineering to study the use of various stem and progenitor cell types in spinal fusion surgery. By seeding our scaffold system with optimal bone-growing stem cells, we aim to achieve solid spinal fusion rates better than those attained with conventional substitutes or even the patient’s own bone.