Chapter 6 - High-throughput three-dimensional cellular platforms for screening biophysical microenvironmental signals

Abstract

Cells in vivo are subjected continuously to multiple biochemical and biophysical stimuli from their microenvironment that regulate cell fate and function. Although two-dimensional (2D) platforms to check cell responses to various microenvironmental factors have been established, these methods lack physiological relevance. Macroscale three-dimensional (3D) cell culture platforms were developed to provide physiologically relevant environments. However, most of these systems failed to analyze the effects of biophysical stimuli on high throughput. Screening microenvironmental factors is essential to mimic an in vitro model of physiological conditions. Multiple trial-and-error methods with a number of experimental conditions are required to analyze the appropriate microenvironmental factors, making the screening process complex, laborious, and expensive. High-throughput (HT) microscale cell culture platforms offer a cost-effective alternative to macroscale 3D cell cultures and allow efficient microenvironmental screening. This chapter introduces a variety of techniques to build microscale 3D cell culture platforms. The different HT and combinatorial platforms investigating the effects of various biophysical cues on cells are discussed in detail. Creating microscale tissue arrays on an HT platform is extremely useful for drug screening when recreating normal or diseased state tissues. These systems could also be extrapolated to incorporate combinations of multiple microenvironmental factors to analyze their synergistic effects on cell behaviors.