Regulation of spheroid formation and function by microenvironmental geometric configuration

The effects of microenvironmental geometric configurations on hepatocyte self-assembly were investigated for the first time. Primary hepatocytes were cultured on a flat surface and in differently shaped hollow lumens of two gel types: a native hydrogel (alginate) and a synthetic hydrogel (polyethylene glycol, PEG). The lumens were in the shapes of a cylinder, triangular prism and square column. The results of cell morphology and functionality revealed that a better culture environment for rapid spheroid formation was achieved in the hollow lumens of alginate gel than on the flat surface. Among the lumen configurations, the cylindrical one was the best. Additionally, differences between cell behaviors on a flat surface and in a hollow cylinder lumen were more evident in the PEG hydrogel. Hence, a microenvironment with the proper geometric morphology can benefit the aggregation of hepatocytes and facilitate spheroid formation.