In vitro cell-culture techniques attempt to recreate biological architectures in order to test drugs, study cellular mechanisms, or reconstitute functional tissues. Several challenges associated with recapitulating the physical and chemical cues that tissues experience in vivo still need to be resolved. To overcome the limitations of current methods used to pattern spatially and geometrically resolved multicellular three-dimensional (3D) tissues in very soft biomimetic hydrogels, we use sacrificial scaffolds to temporarily accommodate cell-aggregates in 3D before transferring them to a reconstituted extracellular matrix (ECM). We have already shown that (1) this sacrificial micromolding approach promotes cyst-formation and proper polarization of established epithelial cell lines, (2) our methods allow us to quantify the localization of cytoskeletal filaments within a reconstituted tissue as a function of time, and (3) we can control the lumenization of epithelial cells as a function of tissue size. Herein, we present the potential of this technique for studying the interactions of 3D tissues with foreign objects like drugs or drug-carriers in a physiologically relevant microenvironment. To the best of our knowledge, this is the first work that describes the non-intrusive localization of microcarriers within the lumen of an intestinal cyst in vitro (Figure 1). We use this method to investigate the effect of different micro- and nano-topographies on drug-delivery across epithelial barriers in 3D.

Materials and methods for studying the drug-delivery of microcarriers across the apical barrier of reconstituted 3D epithelial tissues

248th National Meeting (2014)

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