A novel dual-flow bioreactor simulates increased fluorescein permeability in epithelial tissue barriers.

Serena Giusti, Tommaso Sbrana, Margherita La Marca, Valentina Di Patria, Valentina Martinucci, Annalisa Tirella, Claudio Domenici, Arti Ahluwalia

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Permeability studies across epithelial barriers are of primary importance in drug delivery as well as in toxicology. However, traditional in vitro models do not adequately mimic the dynamic environment of physiological barriers. Here, we describe a novel two-chamber modular bioreactor for dynamic in vitro studies of epithelial cells. The fluid dynamic environment of the bioreactor was characterized using computational fluid dynamic models and measurements of pressure gradients for different combinations of flow rates in the apical and basal chambers. Cell culture experiments were then performed with fully differentiated Caco-2 cells as a model of the intestinal epithelium, comparing the effect of media flow applied in the bioreactor with traditional static transwells. The flow increases barrier integrity and tight junction expression of Caco-2 cells with respect to the static controls. Fluorescein permeability increased threefold in the dynamic system, indicating that the stimulus induced by flow increases transport across the barrier, closely mimicking the in vivo situation. The results are of interest for studying the influence of mechanical stimuli on cells, and underline the importance of developing more physiologically relevant in vitro tissue models. The bioreactor can be used to study drug delivery, chemical, or nanomaterial toxicity and to engineer barrier tissues.
    Original languageEnglish
    JournalBiotechnology journal
    Volume9
    Issue number9
    DOIs
    Publication statusPublished - Sept 2014

    Keywords

    • Bioreactors
    • Caco-2 cells
    • Epithelial barriers
    • Fluorescein
    • In vitro model

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