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The use of biopolymers in the development of an "artificial liver" for utilization in cases of liver failure.

The aim is to place healthy hepatic cells into biodegradable
biopolymers (such as poly-lactide-co-glycolide), implant
them into laboratory animals and demonstrate that the cells
survive and function in these animals.

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 is found. 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 formation. 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 proliferation. 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 microscope. 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.
Acronym: 
BIOPOLYMER
Project ID: 
2 202
Start date: 
01-11-1999
Project Duration: 
88months
Project costs: 
950 000.00€
Technological Area: 
Medical devices technology (instrumentation, medical imaging, radiology)
Market Area: 

Raising the productivity and competitiveness of European businesses through technology. Boosting national economies on the international market, and strengthening the basis for sustainable prosperity and employment.