Innovative Platform for the Advanced Online Monitoring of Three-Dimensional Cells and Tissue Cultures
Sebastian Kreß,
Roland Schaller-Ammann,
Jürgen Feiel,
Joachim Wegener,
Joachim Priedl,
Wolf Dietrich,
Cornelia Kasper,
Dominik Egger
Affiliations
Sebastian Kreß
Department of Biotechnology, Institute of Cell and Tissue Culture Technologies, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria
Roland Schaller-Ammann
Health—Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010 Graz, Austria
Jürgen Feiel
Health—Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010 Graz, Austria
Joachim Wegener
Faculty of Chemistry and Pharmacy, Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany
Joachim Priedl
Health—Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstrasse 2, 8010 Graz, Austria
Wolf Dietrich
Department of Gynecology and Obstetrics Tulln, Karl Landsteiner University of Health Sciences, Alter Ziegelweg 10, 3430 Tulln, Austria
Cornelia Kasper
Department of Biotechnology, Institute of Cell and Tissue Culture Technologies, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria
Dominik Egger
Department of Biotechnology, Institute of Cell and Tissue Culture Technologies, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria
The use of 3D cell cultures has gained increasing importance in medical and pharmaceutical research. However, the analysis of the culture medium is hardly representative for the culture conditions within a 3D model which hinders the standardization of 3D cultures and translation of results. Therefore, we developed a modular monitoring platform combining a perfusion bioreactor with an integrated minimally invasive sampling system and implemented sensors that enables the online monitoring of culture parameters and medium compounds within 3D cultures. As a proof-of-concept, primary cells as well as cell lines were cultured on a collagen or gelatin methacryloyl (GelMA) hydrogel matrix, while monitoring relevant culture parameters and analytes. Comparing the interstitial fluid of the 3D models versus the corresponding culture medium, we found considerable differences in the concentrations of several analytes. These results clearly demonstrate that analyses of the culture medium only are not relevant for the development of standardized 3D culture processes. The presented bioreactor with an integrated sampling and sensor platform opens new horizons for the development, optimization, and standardization of 3D cultures. Furthermore, this technology holds the potential to reduce animal studies and improve the transferability of pharmaceutical in vitro studies by gaining more relevant results, bridging the gap towards clinical translation.
