Engineering a bioartificial liver prototype using cell loaded macroporous hydrogel scaffolds

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.

Funding Status:

This studentship is funded by University of Brighton and is worth at least £60,300 over 3 years, subject to satisfactory progress.

UK and EU students -

For UK and EU students this comprises £4620 per year (for 3 years) to cover annual tuition fees and a contribution towards living expenses of £15,480 per year (for 3 years).

International students -

For suitable students from outside of the UK/EU the funding will comprise £14,400 per year (for 3 years) to cover annual international tuition fees and a contribution towards living expenses of £6170 per year (for 3 years).

The value of the studentship will be raised to take into account any rise in annual tuition fees.