Martin, John Thomas
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PublicationNanofibrous Disc-Like Angle Ply Structure for Total Disc Replacement in a Small Animal Model(2015-01-01) Martin, John ThomasLow back pain affects 85% of the population and carries a socioeconomic price tag of $100 billion USD per year. Lumbar intervertebral disc disease is strongly implicated as a causative factor in back pain, as degeneration, which is ubiquitous in the population, leads to loss of normal spine function. For these reasons, our lab has developed disc-like angle ply structures (DAPS) for total disc replacement. These cell-seeded replacements are designed to match the natural hierarchical structure and function of the native disc and correct spinal kinematics after end-stage disc disease. In this dissertation, I describe the development of a rat caudal spine (tail) model of total disc replacement as a platform to evaluate DAPS in vivo; an external fixation system that immobilized caudal vertebrae at the site of implantation was required for DAPS retention and a radiopaque scaffold was developed to confirm intervertebral DAPS positioning. A detailed analysis of the DAPS in vitro growth trajectory was performed to select the optimum pre-culture duration before implantation. Cell-seeded DAPS were subsequently implanted in the rat tail and evaluated by histological, mechanical, and MRI analyses. DAPS successfully restored the mechanical properties of the native motion segment in compression, providing the first evidence of the efficacy of engineered disc replacements. Adaptations of the implant to the in vivo environment were identified; there was a reduction in glycosaminoglycan after implantation, structural modifications to the NP material, and no evidence of vertebral integration. In tackling the first of these issues, a pre-culture strategy that primed DAPS for the in vivo environment was developed; using a rat subcutaneous model, implant phenotype was best conserved post-implantation using a pre-culture strategy with a transient high dose of TGF-b3. Future work will address maintenance of NP structure, vertebral integration and scaling up to human sizes. In my work, the most promising finding was that DAPS replicated compressive motion segment mechanical properties after implantation supporting the idea that engineered biological disc replacement is a possibility for clinical treatment of advanced disc disease.