Guided Functional Re-engineering of the Mitral Valve
Lead Research Organisation:
University of Leeds
Department Name: Mechanical Engineering
Abstract
The aim of this Fellowship is to research and develop tissue-engineered chordae tendineae and leaflets for mitral valve reconstruction in the heart. Mitral valve stenosis and mitral valve regurgitation are the most significant and frequent causes of valve dysfunction in the mitral position in the heart. Regardless of the nature (acquired or congenital) and underlying cause of mitral valve dysfunction, a number of common changes occur in the valve components. These include deformation, tethering, tissue thickening and/or calcification, fusion, retraction, stretching, dilatation, or rupture. Conventional therapies for mitral valve dysfunction most frequently focus on the repair or replacement of the valve. Mitral valve repair is the gold standard for mitral valve dysfunction and usually employs synthetic biomaterials or chemically treated tissue, such as pericardium, taken from donors. Both approaches only deliver inert or biocompatible material solutions that cannot regenerate or grow with the patient, and may, subsequently calcify, become rigid and eventually degenerate. Ideally, surgeons would prefer tissue taken from the patient (autologous), since it will retain viability and regenerate. In most cases, however, autologous tissue is not available, and even if it is available, this is not an ideal solution. Functional tissue engineering (FTE) is an attractive alternative, which employs scaffolds repopulated with appropriate cells taken from the indented patient, and physically conditioned in the laboratory with a view to producing viable replacement tissues with appropriate functionality prior to implantation, which will have the potential to regenerate in the patient. The intention of this multidisciplinary project is to develop and evaluate FTE simulation systems that will deliver dynamic cell culture conditions to appropriate natural tissue matrices repopulated with cells, to investigate how the biomechanical and biochemical environment can direct the development of mitral tissue-equivalents in the laboratory. The approach of this Fellowship to tissue engineering of the mitral valve involves the use of tissue matrices of both human and porcine origin that have been treated to remove the immunogenic cells, reseeded with the patient's own cells and physically conditioned in the laboratory, in order to produce biological and biomechanical functionality of the graft prior to implantation. This will create an immediate regeneration potential in response to the cyclic loading in the body. The use of decellularised-only matrices in reconstructive surgery does offer an alternative approach and will be investigated. The proposed research postulates that simulation of the type of mechanical strain that mitral tissue encounters in the body will stimulate the cells to produce tissues with similar properties in the laboratory. In particular it is hypothesised that cyclic uniaxial tensile strain will produce mitral valve chordae-equivalent tissue while biaxial cyclic strain will generate mitral valve leaflet-equivalent tissue.
People |
ORCID iD |
Sotirios Korossis (Principal Investigator) |
Publications
Fidalgo C
(2018)
A sterilization method for decellularized xenogeneic cardiovascular scaffolds.
in Acta biomaterialia
Theodoridis K
(2016)
Effects of combined cryopreservation and decellularization on the biomechanical, structural and biochemical properties of porcine pulmonary heart valves.
in Acta biomaterialia
Bolland F
(2007)
Development and characterisation of a full-thickness acellular porcine bladder matrix for tissue engineering.
in Biomaterials
Repanas A
(2015)
Coaxial Electrospinning as a Process to Engineer Biodegradable Polymeric Scaffolds as Drug Delivery Systems for Anti-Inflammatory and Anti- Thrombotic Pharmaceutical Agents
in Clinical & Experimental Pharmacology
Zia S
(2023)
Development of a dual-component infection-resistant arterial replacement for small-caliber reconstructions: A proof-of-concept study.
in Frontiers in bioengineering and biotechnology
Iablonskii P
(2015)
Tissue-engineered mitral valve: morphology and biomechanics †.
in Interactive cardiovascular and thoracic surgery
Joda A
(2016)
Multiphysics simulation of the effect of leaflet thickness inhomogeneity and material anisotropy on the stress-strain distribution on the aortic valve.
in Journal of biomechanics
Roberts N
(2016)
Regional biomechanical and histological characterization of the mitral valve apparatus: Implications for mitral repair strategies.
in Journal of biomechanics
Marino M
(2016)
Cardiovascular biomechanics in health and disease.
in Journal of biomechanics
Description | Discipline Hopping |
Amount | £103,628 (GBP) |
Funding ID | G0601737 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2007 |
End | 03/2008 |
Description | European Commission (EC) |
Amount | € 3,340,211 (EUR) |
Funding ID | 317512 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 01/2013 |
End | 12/2016 |
Description | Innovation and Knowledge Centre |
Amount | £4,893,965 (GBP) |
Funding ID | EP/G032483/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2009 |
End | 10/2014 |
Description | Platform Grant |
Amount | £869,162 (GBP) |
Funding ID | EP/F043872/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2008 |
End | 06/2013 |
Description | Programme Grant |
Amount | £4,536,887 (GBP) |
Funding ID | EP/G012172/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2009 |
End | 06/2015 |
Description | Research Equipment Initiative |
Amount | £232,183 (GBP) |
Funding ID | BB/F011105/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2008 |
End | 07/2019 |
Description | Corlife oHG |
Organisation | Corlife OHG |
Country | Germany |
Sector | Private |
PI Contribution | Coordinator of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Collaborator Contribution | Partner of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Impact | Joint supervision of 1 multidisciplinary PhD project. Disciplines involved: biology, engineering, physics, chemistry, computational modelling |
Start Year | 2011 |
Description | Eindhoven University of Technology |
Organisation | Eindhoven University of Technology |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Coordinator of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Collaborator Contribution | Partner of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Impact | Joint supervision of 1 multidisciplinary PhD project. Disciplines involved: biology, engineering, physics, chemistry. |
Start Year | 2011 |
Description | RWTH Aachen University |
Organisation | RWTH Aachen University |
Department | Helmholtz Institute for Biomedical Engineering |
Country | Germany |
Sector | Academic/University |
PI Contribution | Coordinator of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Collaborator Contribution | Partner of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Impact | Joint supervision of 1 multidisciplinary PhD project. Disciplines involved: biology, engineering, physics, chemistry, surgery |
Start Year | 2011 |
Description | University of Padua |
Organisation | University of Padova |
Country | Italy |
Sector | Academic/University |
PI Contribution | Coordinator of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Collaborator Contribution | Partner of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Impact | Joint supervision of 3 multidisciplinary PhD project. Disciplines involved: biology, engineering, physics, chemistry, medicine, surgery |
Start Year | 2011 |
Description | University of Patras |
Organisation | University of Patras |
Country | Greece |
Sector | Academic/University |
PI Contribution | Coordinator of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Collaborator Contribution | Partner of Marie Curie Initial Training Network TECAS (Tissue Engineering Solution for Cardiovascular Surgery) |
Impact | Joint supervision of 3 multidisciplinary PhD project. Disciplines involved: biology, engineering, physics, chemistry |
Start Year | 2011 |
Company Name | Tissue Regenix Group PLC |
Description | |
Year Established | 2006 |
Impact | The dCELL® process involves the creation of biological scaffolds which are essentially inert. By removing DNA and cellular material from biological tissues, the patient's cells can repopulate and colonize creating new, like for like tissue, which is recognized and accepted by the body, significantly reducing the risk of rejection, and stimulating a natural healing process. |
Website | http://www.tissueregenix.com |
Description | Industrial Stakeholder Meetings |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | The events were focused on directly disseminating the research results to the industrial and clinical communities, which a view to the clinical translation and commercial exploitation of the research findings. Three collaborations were established as a result of these events with private companies, including Corlife oHG, LLS ROWIAK GmbH and Collplant Holdings Ltd. |
Year(s) Of Engagement Activity | 2013,2014,2015 |
Description | Patient Focus Seminar |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Patient focus seminars, delivered by academics and clinicians to selected patient groups, addressing patient priorities and concerns, and promoting TE valve therapies, interventions and technologies. |
Year(s) Of Engagement Activity | 2011,2013,2014,2015,2016 |
Description | Primary School Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Primary School Workshops, conducted on the basis of visits to local schools. The workshops involved research-related exhibits, activities and seminars, tailored for the pupil audience. |
Year(s) Of Engagement Activity | 2010,2011,2013,2014 |
Description | Summer School Weeks for Secondary Education Students |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Summer School Weeks were organised for secondary educations students and teachers, who spent a week receiving first-hand experience from scientists, engineers and clinicians, in the form of lectures, practicals and scientific exhibits. The events also provided teachers with research-oriented ideas, resources and practices for enhancing their teaching practice. |
Year(s) Of Engagement Activity | 2013,2014,2015 |