Tissue Engineering · 2007 · 12 citations · 22 references
EngineeringBioengineeringBiomedical EngineeringBiomaterialsBioreactor DesignTissue EngineeringBioreactor OperationCell CultureCell Culture BioreactorsCell Culture TechnologyContinuous Bioreactor OperationMammalian Cell CultureBioreactor Culture SystemsBioreactor-based Cell ExpansionCell Culture ConditionsCell Phenotype CharacterizationHollow Fiber BioreactorsPrimary Cell CulturePrimary CellsWaste Product Removal
Primary human cells require a well‑defined culture environment with continuous nutrient and oxygen supply and waste removal, yet existing hollow‑fiber bioreactors only permit post‑culture characterization, making it difficult to assess medium additives or culture conditions on viability, expansion, and differentiation. The study developed the SlideReactor, a miniaturized hollow‑fiber bioreactor, to enable continuous microscopic observation of cells during culture. The SlideReactor implements a predefined operational concept for diverse cell types and was tested by culturing primary human hepatocytes, fibroblasts, keratinocytes, and several cell lines while continuously observing them. In 40 experiments, the SlideReactor proved feasible, allowing determination of process parameters and continuous observation, and it offers a simple, cost‑efficient tool for cell characterization and optimization of culture conditions.
Certain cell types, especially primary human cells, favor a well-defined culture environment offering continuous supply of nutrients and oxygen and waste product removal. Several bioreactors based on special matrices or hollow fibers have been developed that provide such conditions. However, characterization of matrix re-organization or growth of tissue within these systems is possible only after culture termination. Evaluation of the influence of certain medium additives or culture conditions (e.g., temperature, oxygenation) on cell viability, expansion, and differentiation within these systems remains a challenging task. The SlideReactor, a miniaturized hollow fiber–based bioreactor, was developed to enable the observation of cells during culture. An operation concept offering predefined conditions for various cell types has been designed. For proof of concept, primary human cells (hepatocytes, fibroblasts, keratinocytes) and cell lines (HepG2, HuH7, C3A, WiDr, SkHep1) were cultured and observed. A series of experiments (n = 40) showed the feasibility of the set-up; determination of process parameters and continuous observation is possible. The SlideReactor may serve as a simple and cost-efficient tool for cell characterization and optimization of cell-culture conditions.
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Leonard M. Flendrig, J.W. La Soe, George G.A. Jörning et al. · Journal of Hepatology · 1997 · 250 citations · Full text