It has been increasingly realized that the conventional planar cell cultures do not necessarily reproduce human physiology in vitro due to their limited ability to reproduce the structural and functional complexity of the in vivo counterparts, often resulting in biased outcomes of biological and pharmacological interrogations. On the other hand, the animal models, while competent in reproducing the complex physiology, their discrepancy in anatomy and the genetics against the humans inevitably lead to the mismatch in response towards drugs, chemicals, and toxins, thus resulting in inaccurate predictions. These facts apply to essentially every scenario that we can imagine, ranging from basic science discoveries in cell biology where studies are performed on single-cell levels all the way to systems biology where investigations at the tissue/organ levels are conducted—simply because that the three-dimensional, hierarchical microenvironment intertwined with multi-component biochemical and biophysical cues are so important that they significantly affect every level of biological function—from individual cells to tissue building units and to organs.