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Investigation of poloxamer cell protective ability via shear sensitive aggregates in stirred aerated bioreactor

Year: 2022

Journal: Biochem. Eng. J., Volume 186, AUG

Authors: Srom, Ondrej; Travnikova, Veronika; Blaha, Lukas; Ciofalo, Manfredi; Soos, Miroslav

Organizations: [A1_FCHI_2022_006]; [A2_FCHI_2021_051]

Keywords: Shear stress; Poloxamer; Stirred aerated vessel; Shear sensitive aggregates; Mass transfer coefficient; Cell culture

Mammalian cell cultivation in bioreactors is widely practiced in the pharmaceutical industry for production of monoclonal antibodies, vaccines and other therapeutic products. During cell culture, ensuring homogeneity and oxygen transport to the cultivation broth is essential for survival and proper cell growth. Due to the lack of a cell wall, mammalian cells are prone to damage by the gas aeration. Common practice how to protect mammalian cells against hydrodynamic forces is usage of poloxamers - synthetic, water-soluble nonionic copolymers. However, poloxamers are never pure compounds and the distribution of molecular weight strongly depends on the production process. This may lead to the final product containing impurities, which may have a negative impact on the protectivity of cells. Therefore, it is of high importance to know whether a particular poloxamer can be used as a cell protective agent. In this paper, we extend the usability of our method based on shear sensitive poly(methyl methacrylate) (PMMA) aggregate probes to investigate the protective capability of poloxamers. Comparative study of three different poloxamers and their impact on maximum effective hydrodynamic stress (tmax) and mass transfer coefficient (kLa) is conducted in the bench-scale 3.5 L Minifors bioreactor.