Date of Award
Doctor of Philosophy (PhD)
Dr. Jeremy Mercuri
Dr. Ken Webb
Dr. Melinda Harman
Dr. Sanjitpal Gill
The intervertebral disc (IVD) is a fibrocartilaginous tissue connecting adjacent vertebrae in the spinal column. It comprises three distinct tissues: a gelatinous core known as the nucleus pulposus (NP), concentric fibrous rings encircling the NP known as the annulus fibrosus (AF), and the superior/inferior cartilaginous endplates (CEPs). The complex mechanical interplay of these tissues allows the IVD to withstand complex loading in the spine while maintaining trunk stability and flexibility. IVD pathologies, such as IVD degeneration (IDD) and herniation, are associated with cell-mediated inflammation in vivo. This inflammation creates a catabolic environment which degrades the extracellular matrix (ECM) of the IVD. Since ECM composition influences the mechanical properties of the tissue, this degradation compromises spine biomechanics, which may lead to low back pain, radiculopathy, and disability.
Current treatment strategies for IVD pathologies are either palliative or are aggressive and only partly redress spine biomechanics. Furthermore, current interventions are not regenerative and may induce collateral pathologies in adjacent IVDs due to abnormal biomechanics post-repair. Mechanically robust scaffolds derived from decellularized tissues have the potential to re-establish spine biomechanics, alleviate the underlying pathology, and regenerate the native tissue. We have previously demonstrated the ability to decellularize bovine NP to form acellular bovine NP (ABNP), which exhibited a biomimetic ECM composition, supported cell seeding, and partially restored spine kinematics in an ex vivo model of IVD injury. Despite this, further refinement was necessary to improve its mechanical properties and characterize its regenerative potential. Furthermore, prior to translation, the ABNP must be evaluated using a well-characterized animal model that reproduces clinically relevant aspects of IDD. The goals of this research were to: i) fortify the mechanical properties of the ABNP, ii) determine the in vitro cytocompatibility and regenerative capacity of the ABNP, and iii) characterize a novel animal model of IVD degeneration for future in vivo testing of the implant.