The liver is the organ in which major synthetic and
metabolic pathways preside, therefore liver failure is
incompatible with life. The key functions of the organ are
performed by hepatocytes which make up 80% of its mass.
The implantation of healthy hepatocytes have been proposed
to keep liver failure patients alive until a suitable donor
In this project, the healthy hepatocytes will be implanted
into biodegradable biopolymers which will aid in sustaining
the cells until they form their own extracellular matrix.
Poly-lactic-glycolic acid (PLGA) co-polymers will be further
modified to increase the specificity of the interaction
between the hepatocyte and the biopolymer.
In order to aid in the survival of seeded cells,
biopolymers will be pre-implanted with microspheres
containing angiogenic factors to stimulate vascular tissue
Experimental steps of the project:
1. Isolation of hepatocytes: hepatocytes will be isolated
from the livers of Wistar Albino rats using a
collagenase perfusion technique.
2. Synthesis and characterization of biopolymers and
angiofactor containing microspheres: PLGA and PLAL-ASP
co-polymers will be synthesized and will be further
characterized by gel permeation chromatography, scanning
electron microscopy and mercury porosimetry.
Microspheres will be formed by the inclusion of an
angiogenic factor; vascular endothelial growth factor
VEGF) in the interior. The amount of VEGF entrapped
will be quantified using 125I-VEGF and its functionality
determined by its effects on endothelial cell
3. Implantation and observation of biopolymers in healthy
animals: the biopolymers will be placed in the mesentery
and in vivo fibrovascular tissue ingrowth will be
quantified utilizing an imaging system coupled to a
4. Placement of hepatocytes into the biopolymer and
quantification of their function: following the
optimization of fibrovascular tissue ingrowth,
hepatocytes will be placed in the biopolymer followed by
implantation into healthy animals and their viability
and functionality with respect to time will be measured.
5. Dependent on the success of step 4, this step will be
repeated in animals with hepatic failure.
Keywords: bioengineering, artificial organ, biopolymers.