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.