| EPSRC Reference: |
EP/V029371/1 |
| Title: |
Towards Innovation of Stented Pericardial Aortic Valves for Transcatheter Implantation |
| Principal Investigator: |
Berry, Dr HE |
| Other Investigators: |
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| Project Partners: |
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| Department: |
Sch of Biomedical Sciences |
| Organisation: |
University of Leeds |
| Scheme: |
Standard Research |
| Starts: |
01 October 2021 |
Ends: |
30 September 2024 |
Value (£): |
852,859
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| EPSRC Research Topic Classifications: |
| Biomaterials |
Med.Instrument.Device& Equip. |
| Tissue Engineering |
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Summary on Grant Application Form |
Every day our hearts beat around 100,000 times, pumping blood continuously around our bodies through our circulatory system, with four valves making sure the blood flows in only one direction. As we age, one of those valves, the aortic valve, can narrow, and this leads to progressive dysfunction. This is known as calcific aortic stenosis, and is the most common valvular heart disease in adults, affecting 2-3% of the population by 75 years of age. Aortic stenosis causes a progressive reduction in valve orifice size and severely restricts the normal flow of blood, leading to the onset of angina symptoms, heart failure, and increased mortality rates. Patients only have an average survival duration of 2-4 years if left untreated. Transcatheter aortic valve replacement is the latest revolutionary advance in treating high-risk and very elderly patients who are not eligible for conventional (open-chest) surgical aortic valve replacement. Transcatheter aortic valve replacement is a minimally invasive technique in which a bioprosthetic valve (composed of three tissue leaflets) sits in a (metal alloy) stent and is delivered into the heart via a catheter.
Since the introduction of transcatheter aortic valve implantation (TAVI), studies have seen improvements in outcomes, however important issues remain; these include significant leaks around the device (paravalvular) , disturbance of atrioventricular conduction (heart block necessitating a permanent pacemaker), distortion of the valve stent by calcium deposits (leading to undesirable stress on the valve leaflets), indeterminate long-term durability, and the same risk of calcification induced structural valve degeneration and early failure as conventional surgical bioprosthetic valves due to chemical cross-linking (required to prevent rejection of the valve).
A potential way to reduce the induction of both calcium deposition and adverse immune response in tissue valves, is to combine decellularisation with strategies such as novel cross-linking techniques. Decellularisation removes the cells and cellular debris leaving a protein based scaffold and cross-linking stabilises this scaffold. Sterilisation of the valve also requires investigation, in order to produce a truly off the shelf device.
This multidisciplinary research programme brings together researchers from three institutions with complementary expertise and track record within this field (University of Leeds, Loughborough University, and the Bristol Heart Institute) to investigate techniques for generating a bioprosthetic heart valve that will overcome the disadvantages of current devices. Innovative combinations of decellularisation, cross-linking and sterilisation techniques will be used to engineer a biomaterial for use as replacement valve leaflets. A novel, advanced computational modelling approach to design will be undertaken, guided by clinical imaging, that will optimise stent sizing and implanted shape. Additive manufacturing (3D-printing) methods will be investigated for production of the valve stents. State of the art in vitro physiological simulation systems will also be developed, to assess the functional performance of these innovative bioprosthetic transcatheter aortic valves.
The knowledge gained from this research programme will provide enhanced understanding of the influence of novel bioprocessing techniques on xenogeneic materials, techniques required for optimal stent preparation, and underpin the development of an innovative bioprosthetic transcatheter aortic valve required to greatly improve patient outcomes.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.leeds.ac.uk |