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PhD Scholarship - Design, optimisation, and fabrication of patient-specific multi-phasic total disc replacements to address age-related degenerative disc disease (UQ/Exeter Joint PhD)

Project Description

Spinal problems affect over 80% of the population, the majority of which are aged, representing a major and growing social and an economic burden on health services world-wide, currently costing more than 200 billion USD a year. These problems are frequently associated with the degeneration of the intervertebral disc (IVD), a condition that is highly penetrant within our ageing population and severely limits their ability to participate and contribute to society. Unfortunately, treatments have limited success. Spinal fusion is the sixth most common operating procedure in the US (488,000 per year), but the most costly (total $12.8 billion per year). This procedure can provide pain relief, but can cause increased stress on adjacent tissues, leading to a degenerative cascade. Total disc replacement (TDR) provides an alternative, but current devices show little to no improvement in clinical outcomes over the fusion procedures they are designed to supersede. We believe this situation arises because no current TDRs replicate the unique biophysical (mechanical) properties of the IVD. We propose in this PhD project to develop a ‘design, optimisation, and fabrication’ pipeline for patient-specific multi-phasic TDRs that can be tailored to the mechanical environment of a particular patient’s spine, and through this mechanical-matching, support the generation of new tissue from a patient’s own stem cells. Our collaboration provides the broad range of expertise to achieve this urgently required outcome.

This project will build on previous work performed at the University of Queensland on the construction of regenerative multi-component, multi-phasic scaffolds using a novel additive biofabrication methodology, and differentiation of human tissue-derived stem cells into IVD cells, with added expertise at the University of Exeter in multi-axis spinal loading, and biomechanical optimisation techniques using finite element modelling. Supported by these previous achievements and expertise, this project will focus on the development of a “design, fabricate, optimise (DFO)” total disc replacement (TDR) pipeline.

The successful applicant will investigate the design and fabrication of a multi-scale total disc replacement, develop a finite element model, complete topological optimisation of the TDR design using level-set or gradient-based methods, and validate optimisation algorithms and outputs against in-vitro test data. The optimised disc design produced from this project will form the basis of a patient-specific, regenerative total disc replacement, which will be assessed in vitro for its ability to support the differentiation of human mesenchymal stems into the appropriate cellular phenotypes present in the IVD under loads mimicking those experienced by the IVD in humans.

Funding Notes

This scholarship includes a living stipend of AUD $27,596 (2019) tax free, indexed annually, tuition fees and Overseas Student Health Cover (where applicable). A travel grant of AUD $8,500 per annum, and a training grant of AUD $3,000 are also available over the program.

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