FIGURE 1.

Schematic representation of the hybrid 3D system, combining a vascularized stromal with a parenchymal epithelial compartment. Alginate porous 3D scaffolds are prepared by freeze-drying and particle leaching. In step 1, outgrowth endothelial cells (OEC) and fibroblasts are co-seeded on the scaffold and tubular-like endothelial structures are formed. In step 2, epithelial cells suspended in alginate gel-precursor solution are added to the pre-vascularized scaffold for in situ hydrogel formation. Epithelial organoids are formed within pores in close contact with tubular-like structures, fibroblasts and their ECM, establishing heterotypic cell-cell and cell-matrix interactions. The 3D system can be imaged by confocal microscopy, processed for histology or easily dissolved for cell recovery and downstream analysis.