Packed-bed bioreactors for mammalian cell culture: Bioprocess and biomedical applications

Meuwly, F.; Ruffieux, P.-A.; Kadouri, A.; Stockar, Urs von

doi:10.1016/j.biotechadv.2006.08.004

Cited by 91 publications

(56 citation statements)

References 65 publications

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“…Taking advantage of the great progress in the development of new technologies, and of the contribution of computational fluid dynamics, a wide array of dynamic bioreactors have been devised (from the simplest stirred-or suspension-based culture systems, to the more complex membrane-based reactors, and their more sophisticated versions, that include load-, continuously perfused-/pulsed-systems, and multi-compartmentalised bioreactors, able to generate highly controlled microenvironments) (Török et al, 2001, Martin & Vermette, 2005Catapano & Gerlach, 2007;Meuwly et al, 2007, Guzzardi et al 2011. However, despite all of these technological efforts, none of these bioreactors, are, at present, able to provide optimal conditions for the long-term maintenance of large tissue-like masses in culture.…”

Section: Bioreactors and Relative Microgravity Conditionmentioning

confidence: 99%

New Models for the In Vitro Study of Liver Toxicity: 3D Culture Systems and the Role of Bioreactors

Mazzoleni¹,

Steimberg²

2012

The Continuum of Health Risk Assessments

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Section: Bioreactors and Relative Microgravity Conditionmentioning

confidence: 99%

New Models for the In Vitro Study of Liver Toxicity: 3D Culture Systems and the Role of Bioreactors

Mazzoleni¹,

Steimberg²

2012

The Continuum of Health Risk Assessments

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“…From orbitally mixed Petri dishes, to continuous stirredtank reactors, up to the more sophisticated hollow fiber (HF), coaxial HF and multi-coaxial HF, Couette-Taylor or airlift bioreactors, the technological progress allowed to improve further oxygen and nutrients supply to cultured cell/tissue structures; however, even in the case of the recently developed packed-bed bioreactors, these devices still do not allow to generate optimal conditions for the long-term culture of functional tissue-like masses (for detailed reviews on the subject see [55,58]). The current generation of bioreactors has, in fact, been developed to support the rapid growth of cells in solution and not the culturing of tissue engineered constructs [38].…”

Section: Bioreactorsmentioning

confidence: 99%

Modelling tissues in 3D: the next future of pharmaco-toxicology and food research?

2008

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The development and validation of reliable in vitro methods alternative to conventional in vivo studies in experimental animals is a well-recognised priority in the fields of pharmaco-toxicology and food research. Conventional studies based on two-dimensional (2-D) cell monolayers have demonstrated their significant limitations: the chemically and spatially defined three-dimensional (3-D) network of extracellular matrix components, cell-to-cell and cell-to-matrix interactions that governs differentiation, proliferation and function of cells in vivo is, in fact, lost under the simplified 2-D condition. Being able to reproduce specific tissue-like structures and to mimic functions and responses of real tissues in a way that is more physiologically relevant than what can be achieved through traditional 2-D cell monolayers, 3-D cell culture represents a potential bridge to cover the gap between animal models and human studies. This article addresses the significance and the potential of 3-D in vitro systems to improve the predictive value of cell-based assays for safety and risk assessment studies and for new drugs development and testing. The crucial role of tissue engineering and of the new microscale technologies for improving and optimising these models, as well as the necessity of developing new protocols and analytical methods for their full exploitation, will be also discussed.

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“…The latest generation of PBRs can achieve a density of more than 10 8 cells/mL with mammalian cells (Meuwly et al, 2005). With the right choice of carrier and medium, practically any mammalian cell can grow and produce recombinant proteins in a stationary PBR.…”

Section: Introductionmentioning

confidence: 99%

Oxygen supply for CHO cells immobilized on a packed-bed of Fibra-Cel® disks

Meuwly¹,

Loviat

Ruffieux

et al. 2006

Biotechnol. Bioeng.

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Packed-bed bioreactors (PBR) have proven to be efficient systems to culture mammalian cells at very high cell density in perfusion mode, thus leading to very high volumetric productivity. However, the immobilized cells must be continuously supplied with all nutrients in sufficient quantities to remain viable and productive over the full duration of the perfusion culture. Among all nutrients, oxygen is the most critical since it is present at very low concentration due to its low solubility in cell culture medium. This work presents the development of a model for oxygenation in a packed-bed bioreactor system. The experimental system used to develop the model was a packed-bed of Fibra-Cel disk carriers used to cultivate Chinese Hamster Ovary cells at high density ( approximately 6.1 x 10(7) cell/mL) in perfusion mode. With the help of this model, it was possible to identify if a PBR system is operated in optimal or sub-optimal conditions. Using the model, two options were proposed, which could improve the performance of the basal system by about twofold, that is, by increasing the density of immobilized cells per carrier volume from 6.1 x 10(7) to 1.2 x 10(8) cell/mL, or by increasing the packed-bed height from 0.2 to 0.4 m. Both strategies would be rather simple to test and implement in the packed-bed bioreactor system used for this study. As a result, it would be possible to achieve a substantial improvement of about twofold higher productivity as compared with the basal conditions.

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Packed-bed bioreactors for mammalian cell culture: Bioprocess and biomedical applications

Cited by 91 publications

References 65 publications

New Models for the In Vitro Study of Liver Toxicity: 3D Culture Systems and the Role of Bioreactors

New Models for the In Vitro Study of Liver Toxicity: 3D Culture Systems and the Role of Bioreactors

Modelling tissues in 3D: the next future of pharmaco-toxicology and food research?

Oxygen supply for CHO cells immobilized on a packed-bed of Fibra-Cel® disks

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