Resumen de A computational study of intervertebral disc degeneration in relation to changes in regional tissue composition and disc nutrition
Carlos Eduardo Ruiz Wills
Up to 85% of the world population suffers from low back pain, a clinical condition often related to the intervertebral disc (IVD) degeneration (DD). Altered disc cell nutrition affects cell viability and can generate catabolic cascades that degrade the extracellular matrix (ECM). Also, a major degenerative biochemical change in the disc is the proteoglycan (PG) loss, which affects the osmotic pressure and hydration that is critical for cell nutrition. However, the relationship between biochemical degradation and nutrition along degeneration is unclear. The effect of cartilage endplates (CEP) tissue changes through known composition data remains unknown as well. Experiments have limited capacity in the study of multiple IVD interactions, while theoretical models are promising tools to this aim. Thus, this PhD thesis used computer models to study the relationship between disc degeneration and cell nutrition, and focuses on indirect mechanotransduction phenomena that occur in the IVD. Porohyperelastic IVD finite element models, including all tissues, were used. Such models consider the role of solid-fluid interaction within the IVD. In Chapter 3 a convergence study was performed to access the stability of local predictions under fast load rates. In Chapter 4 the models were updated by adding the viscoelastic collagen fibres of the annulus fibrosus (AF) and the osmotic pressure of the nucleus pulposus (NP). They were coupled to a transport-cell viability model, and a design of experiment (DOE) was used to study the effect of disc composition on cell nutrition. In Chapter 5 the transport model was modified to allow PG updates, depending on PG half-life and PG production related to predicted oxygen pressure. In Chapter 6, a composition-dependent permeability formulation was created for the CEP to focus on the impact of CEP degradation. Three days of diurnal load cycle were simulated for all transport-cell viability simulations. Solute concentrations were evaluated along the mid-sagittal plane path. Chapter 3 showed that unrealistic spatial oscillations in the fluid velocity predictions were due to material discontinuities. Previous stabilization strategies did not eliminate the oscillations. However, the creation of a material transition zone combined with local refinement reduced them by 91%. The model obtained warranted the stability of local calculations for long lasting loads. Chapter 4 results revealed that none of DOE combinations affected the cell viability, and that water reductions altered the most disc nutrition. Moreover, NP degeneration might affect the AF nutrition, possibly explaining the tears found in grade III discs. In Chapter 5, IVD nutrition affected the PG content, which seemed to simulate natural ageing. Also, PG loss altered disc mechanical behaviour but neither cell viability nor nutrition. However, the inclusion of NP dehydration reduced solute levels, which might activate catabolic processes. Chapter 6 showed that CEP permeability would increase with DD. Also, CEP degeneration alone produced NP dehydration under compression, which affected disc nutrition. The results suggested that the CEP might play a key role in DD. Interestingly, cell death was predicted when CEP degeneration was combined to AF and NP degeneration, questioning the paradigm that CEP calcification might be responsible for cell death along DD. This PhD thesis identified different paths related to DD. On one hand, NP dehydration and PG loss reduced glucose at the inner AF, weakening the latter due to inflammation and enzyme activation. Meanwhile, nutrition regulated the PG content, which can explain natural ageing but probably not accelerated degeneration processes. However, CEP degeneration caused NP dehydration, and the combined degeneration of all disc tissues activated the cell death. All these simulated events are important to understand DD and might promote the development of new experimental explorations and treatment strategies
