| dc.description.abstract | The degeneration of the intervertebral disc (IVD) is a multi-factorial process which entails changes in the tissue biomechanics, physical attributes, cellularity and biochemical composition, which reduces the capacity of the IVD to transmit load and provide flexibility and also reduces its shock absorbing capacity. Initiation and progression of IVD degeneration are often asymptomatic, and degeneration is commonly only perceived in cases when severe pain appears. Severe IVD degeneration is associated with low back pain (LBP), and in many cases, this condition leads to living with a disability. Although LBP has a high prevalence in society, there is no cost-effective treatment or therapy to cure or alleviate a painful IVD. Moreover, there are limited pre-clinical testing methods to evaluate the performance of emerging treatments and therapies that focus on repairing, replacing or regenerating a degenerated IVD. The aim of this thesis was to design in vitro models that replicate the physiological feature of human intervertebral disc degeneration. Considering this, two experimental approaches, which used as degenerative initiators either overloading or the integration of overloading with enzyme digestion by trypsin, were used in this study. The methods included loading/recovery periods that simulate the diurnal loading characteristics of the spine in a reduced time frame. Independent of the mechanism of degeneration, all the methods designed in this project included an equilibrium stage, which included static loading or a combination of static and two loading/recovery periods to stabilise the disc response to loading. The application of hyperphysiological loading (2.6+-1 MPa) led to a reduction of the disc height, no significant increase of the stiffness, and significant damage in the annulus fibrosus (AF), which may correspond to cases of moderate disc degeneration (Grade III). Similarly, using multiple degenerative initiators, i.e. combination of overloading and enzymatic digestion of the extracellular matrix by trypsin, in a hybrid model of degeneration, also resulted in a reduction of the disc height, slight increase of stiffness and microstructural damage at the AF. Therefore, the degeneration achieved in the hybrid model may also be classified as moderate disc degeneration (Grade III). In this project, it was not possible to replicate cases of severe and very severe degeneration, but the overall testing protocol developed as part of this research provides a valuable platform for further research to investigation parameters such as increasing the exposure time of the IVD to the digestive enzyme, or increasing overloading magnitude and number of cycles, which may be advantageous to induce characteristics representative of more severe degeneration. | en_GB |
