Natural environment for artificial tissue

During the research for his degree thesis at the Fraunhofer Institute of Interfacial Engineering and Biotechnology, Jan Hansmann developed a reactor enabling the optimal cultivation of in-vitro tissue containing natural blood vessels. The computer-assisted cell culture container simulates the body’s natural environment, from arterial pressure to temperature. At the Annual Meeting of the Fraunhofer Institutes on 18th October 2006 in Bremen, Hansmann was awarded the 1st Hugo Geiger Prize for the Life Sciences.

Damaged tissue or diseased organs can often only be cured by transplantation. However, many more transplant organs are required than are currently available. Patients often have to wait a long time before they can have a transplant. In addition, the body generally does not easily accept foreign tissue. Transplant patients need to take drugs for the rest of their life in order to prevent the rejection of the transplanted tissue.

Prof. Hans-Jörg Bullinger, President of the Fraunhofer Society, presenting Jan Hansmann from the Fraunhofer IGB the 1st Hugo Geiger Prize. (Photo: Fraunhofer IGB)

Autologous transplants might present a potential solution. These transplants are produced from the patient’s own cells and cultivated in the laboratory (in vitro). In recent years, tissue engineering has achieved great success in the field of regenerative medicine. Autologous skin and cartilage transplants are available for transplantation and heart valves are currently being investigated in clinical trials. The engineer (technical cybernetics) Jan Hansmann from the Cell Systems research group at the Fraunhofer Institute of Interfacial Engineering and Biotechnology IGB in Stuttgart has taken a considerable step towards cultivating more complex artificial tissue. For his thesis entitled “Development of a bioreactor for use in vascularised tissue engineering”, Hansmann was awarded the 1st Prize of the Hugo Geiger Prize for the Life Sciences given by the Bavarian government to the Fraunhofer Society.

The bioreactor supplies the matrix

With the new computer-assisted bioreactor it is possible to supply the artery of the vascularised biomatrix in the same way as the beating heart (pulsatile) does. (Photo: Fraunhofer IGB)

The computer-assisted bioreactor is a culture container that Hansmann developed specifically for a vascularised (including natural blood vessels) biomatrix available at the Fraunhofer IGB. The generation of a three-dimensional, organ-like tissue requires not only vital and proliferative cells but also a carrier structure (matrix) on which the cells can grow and form tissue-typical features. “The vascularised biomatrix is a piece of a pig’s small intestine that has had all animal cells removed. The biomatrix possesses an artery for the supply of nutrients and a vein for the removal of metabolic products,” explained Professor Heike Mertsching, head of the Department of Cell Systems at the Fraunhofer IGB. When the remaining blood vessels and capillaries are coated with the patient’s own endothelial cells, it is possible to cultivate organ-specific cells on the carrier structure, grow in co-culture with the endothelial cells and take over tissue-specific functions.
Similar to nature, the piece of tissue contained in the bioreactor is attached to a simulated “blood circulation”. Fresh nutrient solution is added to the culture by way of a tube (artery). A second tube enables the removal of metabolic products (vein). A computer that is connected to the bioreactor regulates the arterial supply of nutrients by way of parameters such as arterial pressure, temperature and flow velocity. “This creates physiological conditions such as can be found in the natural environment in the body,” said Hansmann. The bioreactor pumps the nutrients in the same way as the heart pumps (in fits and starts) the blood through the vessels. “This is of particular advantage because that is the only way to keep the endothelial cells vital so that they do not lose their typical characteristics. Also it can be seen how, and how much, pulse frequency, blood pressure amplitudes or average blood pressure values affect the tissue cells,” emphasised Hansmann.

Trough the construction of this bioreactor, the scientists of the Fraunhofer IGB succeeded in producing an artificial liver tissue from liver and endothelial cells that has a tissue-specific morphology and a function that enables the testing of drugs for toxicity and side effects of metabolic products. Even if the liver is one of the organs with the highest regenerative potential it has been difficult to maintain the vitality and functionality of liver cells under long-term culture conditions in vitro. Endothelial cells in the liver play an important role as filtration barrier and are involved in the molecular regulation of important metabolic processes. “The co-culture with endothelial cells is therefore essential for the generation of artificial liver tissue,” explained Mertsching.

The 3rd Hugo Geiger Prize also went to the Fraunhofer IGB

Apart from Jan Hansmann, Elena Lindemann from the Department of Molecular Biotechnology at the Fraunhofer IGB (supervisor: Dr. Steffen Rupp) was awarded the 3rd Hugo Geiger Prize for her degree thesis entitled “Development of alternative methods for gene expression analysis”. The core of the sensitive method is a high-resolution, two-dimensional DNA gel electrophoresis. The method has been submitted as patent and works without the knowledge of corresponding genome sequences. It can be universally applied with any eukaryotic organism. Gene expression analyses provide information about which genes are active in a cell and translate into proteins.

Source: Fraunhofer IGB -