Fully-funded PhD Studentship: Engineering a bioartificial liver prototype using cell loaded macroporous hydrogel scaffolds

University of Brighton Doctoral College

University of Brighton

Themes: biomedical engineering, cell biology, materials science, fluid dynamics
 
Location: Moulsecoomb, Brighton
College: College of Life, Health and Physical Sciences
Research group: Biomaterials Research Group
Deadline: Wednesday 9 March, 23:59.
Project in brief
The aim of the project is to address unmet clinical need in the development of clinically effective bioartificial liver device. The project will test the hypothesis that a cell loaded cryogel scaffold, with appropriate blood flow dynamics and ability to support a metabolising cell load, may be used to design a prototype bioreactor. The PhD student will ideally have a bioengineering background and work within a Biomaterials and Engineering research team to develop a novel approach to the design and testing of a prototype device. Such systems could be applied more broadly to other artificial organ applications but in this application would have the potential to act as a bridge to liver transplant or regeneration following acute liver decompensation.
Project supervisors
Lead: Dr Susan Sandeman
Second: Dr Irina Savina
Third: Dr Cyril Crua
Other collaborators
•Dr Nathan Davies, Institute for Liver and Digestive Health, UCL
•Prof Jan Stange, Albutec Gmbh, Germany
Project in detail
The World Health Organisation estimates that over 650 million people suffer from liver disease globally and more than 170,000 European deaths occur from cirrhosis alone each year. Liver disease remains the 5th most common cause of death across Europe and costs more than €15.8bn per annum in total health costs and financial loss through reduced economic productivity. With the alarming increase in obesity coupled with an ageing population the impact of liver disease is set to become an even greater health concern for the European community over the next decade.
Acute and acute on chronic liver failure carry high mortality rates and disease management remains a major challenge. Liver transplant is currently the only effective treatment option for patient with acute liver decompensation. However, the severe shortage of donor organs means that one in seven patients die before a donor organ can be found. Bioartificial liver (BAL) systems offer replacement of liver function using a tissue engineering approach. However, key problems with current experimental BAL systems exist in design efficacy, in low oxygenation levels for bioreactor hepatocytes, the absence of cell-cell signalling for normal hepatocyte function, poor scaffold selection for simulation of the in vivo hepatocyte microenvironment and insufficient blood contact for cells to function at an appropriate level for clinical impact. There remains no BAL design with proven clinical efficacy.
Cryogelation technology offers a progressive approach to BAL design as a bioscaffold which maintains a perfused, highly oxygenated microenvironment for three dimensional attachment and growth of hepatocyte cultures over time. Cryogels are ideal biocompatible, polymeric matrices for the cultivation of mammalian cells in the design of bioreactor systems. They are produced by freezing an aqueous solution of monomers or polymers and gelation occurs in the frozen state. The ice crystals act as a porogen leaving a highly interconnected porous structure on defrost without the need for additional washing for the removal of pore template. Cryogels have mechanically strong pore walls and possess shape memory so that they can be hydrated or dehydrated without collapsing their structure. They have an interconnected pore system with a pore size range allowing free passage of micro- and macroparticles within a cell suspension, plasma or blood. Work by the group suggests that cryogel constructs offer a suitable environment for long-term incubation of functional hepatocytes in a BAL model. However, the most appropriate porous scaffold formulation, cell loading capacity and fluid dynamic profile remain unknown. The aim of the project is thus to test the hypothesis that a cell loaded cryogel scaffold, with appropriate blood flow dynamics and ability to support a metabolising cell load, may be used to design a prototype bioreactor. The PhD student will ideally have a bioengineering background and work within a Biomaterials and Engineering research team to develop a novel approach to the design and testing of a prototype device. Such systems could be applied more broadly to other artificial organ applications but in this application would have the potential to act as a bridge to liver transplant or regeneration following acute liver decompensation.
The student will work within an interdisciplinary team of engineers and biomedical materials scientists with links to an international network of academic, clinical and industrial researchers interested in novel biomaterials approaches to tissue replacement.
Entry requirements
Academic entry requirements
Applicants should have a minimum of a 2:1 undergraduate degree and desirably hold or expect to achieve excellent grades in a masters degree, in a relevant subject from a UK university or comparable qualifications from another recognised university.
Applicants are also required to submit a 1,000 word research proposal.
English language entry requirements
Applicants whose first language is not English, must have successfully completed a Secure English language Test (SELT) in the last two years. Applicants who have obtained or are studying for a UK degree may apply without a SELT. However, the university may request a SELT is taken as part of any award made.
English language IELTS requirements are 6.5 overall and minimum 6.0 for writing.
If you have an English language qualification other than IELTS, please contact us to see if you are eligible to apply for a studentship. The UK Home Office will not accept TOEFL tests as proof of meeting the English language requirements.
Eligibility
Current doctoral students and those already in possession of a doctorate are not eligible to apply.
Funding
This studentship is worth at least £60,300 over three years, subject to satisfactory progress.
UK and EU students
For UK and EU students this comprises £4,620 per year (for three years) to cover annual tuition fees and a contribution towards living expenses of £15,480 per year (for three years).
International students
For suitable students from outside of the UK/EU the funding will comprise £14,400 per year (for three years) to cover annual international tuition fees and a contribution towards living expenses of £6,170 per year (for three years).
The value of the studentship will be raised to take into account any rise in annual tuition fees.
For more details please see here

Funding information

Funding applies to:

Open to applicants from a range of countries

Contacts and how to apply

Administrative contact and how to apply:

If you have questions about making an application, funding or entry requirements for this project, get in touch with Lynne at the Doctoral College.
01273 644763
l.mcchesney2@brighton.ac.uk

Application deadline:

9 March 2016