Promoting collaboration between biotechnology and engineering sciences is one of the goals of BioRegio STERN Management GmbH. The “Engineering – Life Sciences – Automation cluster initiative” (ELSA) was created to accelerate this process. A particularly successful example of this type of collaboration between the sectors is Reutlingen-based biotechnology company Cellendes GmbH, which was founded in 2009 as a spin-off of the Natural and Medical Sciences Institute (NMI) at the University of Tübingen by biologists Dr. Brigitte Angres and Dr. Helmut Wurst. In conjunction with partners, Cellendes has achieved what many biotechnologists still dream of – the automated production of hydrogels for three-dimensional cell cultivation.

To develop new drugs to treat diseases such as cancer, their effects must be tested beforehand on diseased cell material – i.e. cancerous cells, for example. These types of cells can now be cultivated in an artificial environment. However, to ensure they also react as they do in the human body, the matrix surrounding them needs to be as authentic as possible. With 3-D Life hydrogel, Cellendes GmbH has developed an outstanding artificial environment for cultivating cells. Its three-dimensional nature enables researchers to get closer to a cell’s natural environment – the body – than with previous, 2-D models. As a result, the cells in 3-D Life hydrogel also react more naturally to the drugs to be tested.

To ensure such 3-D cultures are available to the pharmaceutical industry in sufficiently large numbers, fast and automated production using robots is a must. Cellendes GmbH has therefore joined forces with Tecan, one of the largest manufacturers of laboratory technology and a specialist supplier of robot technology in automated processes from Switzerland, and the Zurich University of Applied Sciences (ZHAW). The joint project was created in the Swiss competence centre TEDD, Tissue Engineering for Drug Development and Substance Testing. It was co-financed by Gebert Rüf Stiftung. “We contributed the reagents for the gels, Tecan provided the robot and ZHAW performed the tests under the supervision of Prof. Ursula Graf-Hausner,” says Dr. Brigitte Angres, co-founder and managing director of Cellendes GmbH. The project was successful and proved that fast, automated production of 3-D cultures using this gel is possible. “We’ve taken a giant step forward with the transition from manual production to an automated high-throughput process,” she states with conviction.

Without automation, the hydrogel has to be produced by pipetting and mixing by hand from the individual reagents. The gel consists essentially of two solutions that contain various polymers. They can still be changed biomimetically – in other words, various biologically active substances can be linked to imitate the natural cell environment even more effectively. One of the polymers is modified in such a way that it can be separated from cells, with the result that they can move in the hydrogel much as they do in body tissue. After the desired cells have been added to one of the solutions, the two polymers can be mixed and crosslinked to form a gel through a chemical reaction. “This process is actually performed manually by every researcher at his/her laboratory bench, but automation makes this technology also accessible to a high-throughput industrial environment such as the pharmaceutical industry,” explains Angres. The robot can pipette all reagents directly into 96 well plates in the desired sequence and required volume. The resultant time savings are considerable.

Industry still mainly uses 2-D cell cultures, yet switching to 3-D cultures is on the rise thanks to such impressive test results. “Research in this field is still relatively new,” explains Angres. However, she says production of more complex cultures from various cell types is planned in the future. “For example, we’re working on cultivating tumour cells together with fibroblasts, which play an important role in the continuing growth of many tumours, and with cells from the immune system to cultivate an environment as it occurs in the body.” This makes the artificial environment for the tumour cells even more realistic, thus raising the hope of being able to more reliably identify potential new active substances to treat cancers in the future. Dr. Klaus Eichenberg, Managing Director of BioRegio STERN Management GmbH, is equally convinced: “Cellendes GmbH is an excellent example for the successful integration of biotechnology and automation technology.”

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