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Title: Extended duration simulation and testing of cellular and decellularised heart valve roots
Author: Desai, Amisha
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2019
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Heart valve disease can affect people of all ages, and can be treated by either valve repair or valve replacement surgery. Currently available replacement heart valves, including mechanical prostheses, bioprostheses, autografts and allografts improve patient survival and quality of life, but have limitations. Key limitations include the risk of immunological reaction and the lack of growth potential and regeneration, which is of particular importance in young patients. To address these limitations, low concentration sodium dodecyl sulphate (SDS) decellularised human aortic, human pulmonary, porcine aortic and porcine pulmonary heart valve roots have been developed. Decellularisation of allografts would potentially reduce the risk of immunological reaction, and the development of a decellularised porcine pulmonary heart valve root would potentially provide an option for right ventricular outflow reconstruction in younger patients who have undergone the Ross Procedure. Before moving to clinical trials, the functional performance of decellularised heart valve roots needs to be pre-clinically assessed appropriately to determine mechanical safety. Whilst there are recommended test methods in place for the in vitro functional performance assessment of newly manufactured and modified surgical replacement heart valves, they need to be optimised or replaced with novel methods suitable for decellularised heart valve roots, due to their time dependent viscoelastic properties. The main aim of this research was to optimise in vitro hydrodynamic and biomechanical performance test methods and develop a novel real time fatigue test method for biological heart valve roots. The secondary aim was to apply the developed in vitro test methods to cellular and decellularised (human and porcine) heart valve roots to evaluate the effect of decellularisation, prior to the decellularised heart valve roots being implanted in patients for clinical trials. In collaboration with NHS Blood and Transplant, Tissue and Eye Services, in vitro biomechanical and hydrodynamic performance of decellularised human aortic and pulmonary heart valve roots was evaluated for the first time in this research. This research determined that the hydrodynamic and functional biomechanical performance of human aortic and pulmonary heart valve roots was not affected by decellularisation treatment. Decellularisation, however, significantly altered some of the directional material properties of pulmonary and aortic heart valve root leaflets. To support clinical translation of decellularised porcine pulmonary heart valve roots, material properties of pulmonary heart valve roots was evaluated following 12 months implantation in sheep. In addition, the effect of the processing steps of cryopreservation and decellularisation on the material properties of porcine pulmonary heart valve roots was investigated. Cryopreservation was shown not to alter the material properties of cellular porcine pulmonary heart valve roots, however, decellularisation did have an effect on the material properties of the porcine pulmonary heart valve root wall. Following 12 months implantation in sheep, the decellularised porcine pulmonary heart valve root wall and leaflets showed a trend for decreasing stiffness and strength; becoming more like the cellular ovine, potentially indicating constructive remodelling. A novel method was developed to investigate the real time fatigue of biological heart valve roots, which was then applied to porcine cellular aortic heart valve roots and porcine decellularised aortic heart valve roots at 120 bpm under physiological cyclic pressures for a maximum of 1.2 million cycles. The results showed no fatigue difference between the cellular and decellularised heart valve roots. Overall, a portfolio of in vitro pre-clinical test methods were developed, optimised and applied to assess the hydrodynamic, biomechanical and fatigue performance of biological heart valve roots including decellularised human and porcine heart valve roots. The in vitro pre-clinical test methods developed in this study will lead to the refinement of in vivo large animal studies and revision of international standards; and the data will help in the development of the next generation of replacement biological heart valve roots, such as decellularised heart valve roots.
Supervisor: Jennings, Louise Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available