Background to research and synopsis
Cardiovascular diseases (CVD) are a huge burden in the UK and a leading cause of death in the country. Myocardial infarction (MI) is one of the most common causes of CVD. Current treatments are able to mitigate the MI symptoms but unable to repair the damaged tissue. Heart transplantation becomes a final treatment option, however, the lack of organ donors and lifelong reliance on immune-suppressants are major hindrances. In this project, we propose the development of a biodegradable tissue-engineering scaffold to create a Bioengineered Heart Tissue (BHT) using a relatively unexplored family of natural, biocompatible and biodegradable polymers called Polyhydroxyalkanoates (PHAs). PHAs are FDA approved polymers produced by bacteria under nutrient limiting conditions. A multifunctional PHA based Tissue Engineering scaffold will be manufactured using 3D printed PHA constructs impregnated with Vascular Endothelial Growth Factor (VEGF) for enhanced vascularization and other active factors. The scaffold will include human iPSC-CMs and endothelial cells
co-printed in the scaffold using suitable hydrogel materials such as alginate/gelatin within the stable structural matrix provided by the PHA scaffold. A functional BHT will be built using a perfusion bioreactor, resulting in a ‘3D’ functional heart tissue.
Recent publications by supervisors that are relevant to the project
Pooja Basnett, Elena Marcello, Barbara Lukasiewicz, Bijal Panchal, Rinat Nigmatullin, Jonathan C. Knowles, Ipsita Roy 2018, Biosynthesis and characterization of a novel, biocompatible medium chain length polyhydroxyalkanoate by Pseudomonas mendocina CH50 using coconut oil as the carbon source. Journal of Materials Science: Materials in Medicine, Nov 30;29(12):179. doi: 10.1007/s10856-018-6183-9.
C. Constantinides, P. Basnett, B. Lukasiewicz, R. Carnicer, E. Swider, Q. A. Majid, M. Srinivas, C. Carr, I. Roy 2018, In Vivo Tracking and 1H/19F MRI of Biodegradable Polyhydroxyalkanoate/Polycaprolactone Blend Scaffolds Seeded with Labeled Cardiac Stem Cells, ACS Applied Materials Interfaces: Aug 1;10(30): 25056-25068.
Barbara Lukasiewicz, Pooja Basnett, Rinat Nigmatullin, Rupy Matharu, Jonathan C. Knowles and Ipsita Roy 2018, Binary Polyhydroxyalkanoate Systems for Soft Tissue Engineering, Acta Biomaterialia 71: 225-234.
Andrea V. Bagdadi, Maryam Safari, Prachi Dubey, Pooja Basnett, Panagiotis Sofokleous, Eleanor Humphrey, Ian Locke, Mohan Edirisinghe, Cesare Terracciano, Aldo R. Boccaccini, Jonathan C. Knowles, Sian E. Harding, Ipsita Roy, 2016 Poly(3-hydroxyoctanoate), a promising new material for cardiac tissue engineering, Journal of Tissue Engineering and Regenerative Medicine, Sep 30. doi: 10.1002/term.2318. [Epub ahead of print]
Ounzain, S., Kobayashi, S., Peterson, R., He, A., Samani, N.J., Menick, D.R., Pu, W.T., Liang, Q. and Chong, Nelson W. 2012. Cardiac expression of STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4. Molecular and Cellular Biology. 32 (10), pp. 1830-1843.
Candidates should normally have a minimum classification of 2.1 in their Bachelor Degree or equivalent and preferably a Masters degree. Applicants whose secondary level education has not been conducted in the medium of English should also demonstrate evidence of appropriate English language proficiency normally defined as IELTS: 6.5 (overall score with not less than 6.0 in any of the individual elements).
Please follow this link to apply for the programme most appropriate to your research, please note that the programme appears as MPhil on UCAS, however there is an option on the form to request PhD via MPhil, which is the standard route:
To make your application for (SLS6):
Interviews will be held in June/July 2019. The Studentship title is SLS6 Fee Waiver School of Life Sciences. Please include this in your application, you must also list the Project Code in order for us to allocate your application correctly.