Reprint of “Multiphase mixing characteristics in a microcarrier-based stirred tank bioreactor suitable for human mesenchymal stem cell expansion” |
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| Institution: | 1. University of Applied Sciences Mittelhessen, Institute of Bioprocess Engineering and Pharmaceutical Technology, Giessen, Germany;2. Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project group Bioresources, Giessen, Germany;3. Justus Liebig University, Faculty of Biology and Chemistry, Giessen, Germany;4. Kansas State University, Department of Chemical Engineering, Manhattan, KS, USA;1. Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Belgium;2. M3-BIORES, KU Leuven, Kasteelpark Arenberg 30, 3001 Heverlee, Belgium;3. Skeletal Biology and Engineering Research Center, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;4. Pall Life Sciences, Rue de Ransbeek 310, 1120 Brussels, Belgium;5. Department of Materials Engineering, KU Leuven, Kasteelpark Arenberg 44 PB2450, 3001 Heverlee, Belgium;1. The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 214122 Wuxi, China;2. Department of Food Processing Technology, Harare Institute of Technology, Harare, Zimbabwe;1. Dipartimento di Ingegneria Civile, Chimica, Ambientale e dei Materiali, Universitá di Bologna, Via Terracini 28, 40131 Bologna, Italy;2. University College London, Department of Biochemical Engineering, WC1E 7JE, UK;3. University College London, Department of Mechanical Engineering, WC1E 7JE, UK;1. Department of Biomedical Materials Science, School of Dentistry, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS, United States;2. Matrix Biology Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA, United States |
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| Abstract: | Large-scale human mesenchymal stem cell expansion calls for a bioreaction system, that provides a sufficient growth surface. An alternative to static cultivations systems like cell factories are disposable stirred tank reactors. Here, microcarriers provide the required growth surface, but these make it difficult to achieve a complete homogenization in the bioreactor, while avoiding shear stress. To gain insight into this process, we investigated the impact of different power inputs (0.02–2.6 W m?3) on the mixing time (tm). Whereas tm was inversely proportional to agitation in a one-phase-system, aeration resulted in a constant mixing time at 30–70 rpm. A high microcarrier concentration (30 g L?1) and low stirrer speed (30 rpm) in the liquid-solid system caused a 50-fold increase in tm and the formation of a discrete non-mixed upper zone. The effect of the microcarrier concentration on tm became negligible at higher stirrer speeds. In the three-phase system, microcarrier settling was prevented by aeration and a minimal specific power input of 0.6 W m?3 was sufficient for complete homogenization. We confirmed that a low power input during stem cell expansion leads to inhomogeneity, which has not been investigated in the three-phase system up to date. |
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| Keywords: | Mesenchymal stem cell Mixing time Transition flow regime Disposable bioreactor Microcarriers Power input Particle suspension |
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