Ausarbeitung und Etablierung von Methoden zur Analyse und Kultivierung von tierischen Zellen

Animal cell cultures play a crucial role in biopharmaceutical research and industry. Their use enables not only the production of life-saving medication but also fundamentally contributes to a better understanding of diseases and physiological processes, facilitating the development of innovative therapies. Analysis of the cultured cells has an essential importance in this context. To meet the increasing demand of biopharmaceuticals, the focus for producing
suspension cells lies in the analysis and optimization of their productivity. In the first part of this work, a method for more time-efficient and potentially cost-effective monitoring of the productivity of antibody-producing CHO cells using flow cytometry was established. Using this method, a high agreement with the traditionally calculated productivity of the cells throughout the cultivation period was shown. When culturing adherent cells, researchers aim to continually improve mimicking the in vivo conditions of the cells. This requires individualized cultivation systems with complex geometries and integrated sensors. For the complex fabrication of these systems, 3D printing offers exciting possibilities. However, before application in cell culture, the biocompatibility of
the 3D-printed materials must be ensured. Simultaneously, for use in cell culture, the sterilizability of the systems is a fundamental prerequisite. Therefore, in the second part of this work, the biocompatibility of a new heat-resistant material was investigated. No negative impact of the steam-sterilized material on the growth of yeast cells and mouse fibroblasts was observed, however a negative effect on suspension cultures of human embryonic kidney cells was noted.
The study thus demonstrates the great potential of the material for rapid prototyping of easily sterilizable cell culture systems while confirming the essentiality to specifically tailor biocompatibility testing to the intended use of the material. In the third part of this work, 3D printing was used to develop a microfluidic perfusion system enabling the integration, cultivation, and analysis of hydrogel-based 3D cell cultures. Using hydrogels, which can mimic the extracellular matrix as close as possible, is an essential step towards in vitro cell culture models closely replicating physiology and pathological processes
in the body. The developed perfusion system enables the easy analysis of cells cultured in the hydrogel in a defined microenvironment.