Novel scale-up strategy based on three-dimensional shear space for animal cell culture

Li, Chao; Teng, X. N.; Peng, Huadong; Yi, Xiaoping; Zhang, Siliang; Xia, Jian

doi:10.1016/j.ces.2019.115329

Cited by 17 publications

(29 citation statements)

References 43 publications

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“…At the completion of the simulations, postprocessing was performed to determine the volume-averaged SSR and the suspension performance of microcarriers within the spinner flask and BioStar 1.5c. It was shown that the averaged SSR has a linear correlation with agitation speed ( Figure 3 C), which is consistent with the previous study [ 39 ]. As the agitation rate increased, there was also an increase in the SSR in the bioreactor, and the correlation coefficient exceeded 0.99.…”

Section: Resultssupporting

confidence: 92%

Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling

et al. 2022

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Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) hold great potential to generate novel and curative cell therapy products. However, the current large-scale cultivation of hUCMSCs is based on empirical geometry-dependent methods, limiting the generation of high-quantity and high-quality hUCMSCs for clinical therapy. Herein, we develop a novel scale-up strategy based on computational fluid dynamics (CFD) to effectively expand the hUCMSCs in a 3D tank bioreactor. Using a standardized hUCMSCs line on microcarriers, we successfully translated and expanded the hUCMSCs from a 200 mL spinner flask to a 1.5 L computer-controlled bioreactor by matching the shear environment and suspending the microcarrier. Experimental results revealed that the batch-cultured hUCMSCs in bioreactors with an agitation speed of 40 rpm shared a more favorable growth and physiological state, similar to that run at 45 rpm in a 200 mL spinner flask, showing comparability in both culture systems. Notably, the maximum cell density reached up to 27.3 × 105 cells/mL in fed-batch culture, 2.9 folds of that of batch culture and 20.2 times of seeding cells. As such, efficient process optimization and scale-up expansion of hUCMSCs were achieved in the microcarrier-based bioreactor system by the developed CFD simulation strategy, which provided an alternative toolbox to generate massive and standardized curative cell therapy products.

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Section: Resultssupporting

confidence: 92%

Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling

et al. 2022

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“…This relationship between shear rate and agitation speed has been reported in other studies (Borys et al 2018;Campesi et al 2009;Li et al 2020). EDCF is also considered to be closely related to the shear environment and has been used as a scale-up criterion (Hardy et al 2017;Li et al 2020). EDCF in the bioreactor increased non-linearly with the increase of the agitation speed (Fig.…”

Section: Modeling and Analysis Of Hydrodynamic Characteristics Of The Bioreactorssupporting

confidence: 81%

“…The required computational time for each simulation was 40-70 h depending on grid numbers. The CFD model has been validated via comparison of the simulated velocities with the results obtained by the particle image velocimetry (PIV) experiment in our previous work (Li et al 2020), ensuring the simulation result with a high accuracy.…”

Section: Cfd Simulation Setupmentioning

confidence: 99%

A novel scale-up strategy for cultivation of BHK-21 cells based on similar hydrodynamic environments in the bioreactors

Teng

2021

Bioresour. Bioprocess.

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The scale-up of animal cell cultivation is important but remains complex and challenging. In the present study, we propose a novel scale-up strategy for baby hamster Syrian kidney-21 (BHK-21) cell cultivation based on similar hydrodynamic environments. The hydrodynamic characteristics of the different scale bioreactors were determined by computational fluid dynamics (CFD) and further correlated with the agitation speed. The optimal hydrodynamic environment for cell cultivation and vaccine production was determined from the cultivation experiments of BHK-21 cells in 5-L laboratory-scale bioreactors equipped with different impellers at various agitation speeds. BHK-21 cell cultivation was scaled up from 5-L to 42-, 350-, and 1000-L bioreactors by adjusting the agitation speed to make the hydrodynamic features similar to those in the 5-L bioreactor, especially for the shear rate in the impeller zone (γimp) and energy dissipation rate in the tank bulk zone (εtan). The maximum cell density and cell aggregation rate in these scaled-up bioreactors were in the range of 4.6 × 106 ~ 4.8 × 106 cells/mL and 16 ~ 20%, which are comparable to or even better than those observed in the 5-L bioreactor (maximum cell density 4.8 × 106 cells/mL, cell aggregation rate 21%). The maximum virus titer of 108.0 LD50/mL achieved in the 1000-L bioreactor was close to 108.3 LD50/mL that obtained in the 5-L bioreactor. Hence, the scale-up strategy proposed in this study is feasible and can efficiently facilitate the scale-up processes of animal cell cultivation.

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“…Common parameters are related to hydrodynamics like mixing time, stirrer speed, and oxygen mass transfer coefficient [150,151]. However, several authors have demonstrated heterogeneous hydrodynamic fields in mechanically stirred tank reactors (STRs): high shear stresses near to the impeller blade and low ones in the bulk fluid [141,152]. Miniaturized bioreactors have been designed to improve the scale-up with hydrodynamic conditions closer to the conventional STR [153,154].…”

Section: Stirred Tanksmentioning

confidence: 99%

Overview on the hydrodynamic conditions found in industrial systems and its impact in (bio)fouling formation

Fernandes

Gomes

Simões

et al. 2021

Chemical Engineering Journal

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Biofouling is the unwanted accumulation of deposits on surfaces, composed by organic and inorganic particles and (micro)organisms. Its occurrence in industrial equipment is responsible for several drawbacks related to operation and maintenance costs, reduction of process safety and product quality, and putative outbreaks of pathogens. The understanding on the role of operating conditions in biofouling development highlights the hydrodynamic conditions as key parameter. In general, (bio)fouling occurs in a higher extension when laminar flow conditions are used. However, the characteristics and resilience of biofouling are highly dependent on the hydrodynamic conditions under which it is developed, with turbulent conditions being associated to recalcitrant biodeposits. In industrial settings like heat exchangers, fluid distribution networks and stirred tanks, hydrodynamics plays a dual function, affecting the process effectiveness while favouring biofouling formation. This review summarizes the hydrodynamics played in conventional industrial settings and provides an overview on the relevance of hydrodynamic conditions in biofouling development as well as in the effectiveness of industrial processes.

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Novel scale-up strategy based on three-dimensional shear space for animal cell culture

Cited by 17 publications

References 43 publications

Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling

Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling

A novel scale-up strategy for cultivation of BHK-21 cells based on similar hydrodynamic environments in the bioreactors

Overview on the hydrodynamic conditions found in industrial systems and its impact in (bio)fouling formation

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