MECHANICAL AND BIOCHEMICAL EFFECTS OF IL-1B AND DYNAMIC LOADING ON INTERVERTEBRAL DISCS

Intervertebral disc (IVD) degeneration is a cell-mediated multifactorial process influenced by mechanical and biochemical factors. IL-1β, a proinflammatory cytokine, has been widely implicated in the promotion and amplification of degenerative pathways, yet its relationship with mechanical loading remained poorly defined. This dissertation aimed to investigate the combined effects of IL-1β stimulation and dynamic loading on the biochemical and mechanical properties of intervertebral discs utilizing a series of in vitro tissue culture studies. The main findings of this dissertation were: (1) IL-1β increased IL-6 production in rat caudal IVD tissues, with injection-based delivery evoking the greatest inflammatory response, suggesting a more localized and potent inflammatory effect, even compared to sham injections (Study 1); (2) dynamic compressive loading led to increased joint laxity in rat caudal functional spinal units, as measured by an increased neutral zone length and decreased tensile stiffness, with no significant effects of IL-1β at the whole functional spinal unit level, indicating that IL-1β may not substantially alter functional spinal unit mechanics in isolation (Study 2); (3) at the annulus fibrosus level, IL-1β increased peel stiffness, supporting the hypothesis that inflammation alone could alter interlamellar adhesion, while a combination of IL-1β and cyclic tensile strain (CTS) significantly reduced adhesion strength, demonstrating a synergistic effect of inflammatory and mechanical stimuli (Study 3). These results suggest that IL-1β exerts measurable effects on the interlamellar matrix that lies between adjacent layers of the annulus fibrosus, but its impact on the intralamellar matrix and whole functional spinal unit mechanics remains unclear and may be confounded by variability in the data. Supplementary analyses addressed unresolved questions from the main studies, showing that compressive loading may have reduced IL-6 production, perhaps through enhanced cytokine clearance or limitations of the culturing device, and that needle puncture injuries had a measurable increase in joint laxity, particularly in loaded functional spinal units. The culmination of this dissertation is a greater understanding of the inflammatory response as stimulated during tissue culturing and a comprehensive characterization of the mechanical effects of IL-1β and dynamic loading at the levels of the annulus fibrosus and the whole functional spinal unit.