Formation of Cell Aggregates Using Microfabricated Hydrogel Chambers for Assembly into Larger Tissues

Abstract

This paper presents a fabrication process for cell aggregates with controlled shapes that can be used as building units for constructing relatively large tissue models. Microfabricated hydrogel-based chambers with non-adhesive surface characteristics were prepared via a micromolding process. Alginate was used as the hydrogel matrix, which facilitated the efficient formation of aggregates from cells retained inside the microchamber. We employed several types of toroidal and lattice-shaped hydrogel microchambers with different geometries. We examined the effect of cell type on the aggregate formation process using NIH-3T3, C2C12, and HepG2 cells and clearly observed that aggregation behavior is highly dependent on cell type. In addition, we tried to construct 2-layered capillarylike tissues by stacking heterotypic toroidal cell aggregates, which mimic blood vessels. The presented cell aggregate-based tissue fabrication process could become a versatile approach for preparing complex and scaffold-free 3D tissue models.