Described herein is a three-dimensional cell culture scaffold composition comprising an absorbent rigid (AR) component, and in some embodiments, further comprises a gel component. The absorbent rigid component preferably comprises a glass fiber material. It is a surprising finding of the present invention that an AR component having a void volume of between approximately 70% and 95% results in a three-dimensional cell culture composition that allows for robust, high-throughput screening and high-content screening accessible tissue models with preserved cell morphology, heterogeneity of cell types and cell populations, extracellular matrix constituents, functional cell-cell and cell-extracellular matrix interactions and signaling with sufficient specificities to tissue physiology and pathology.