ABSTRACT
During high-throughput drug screening, in vitro models are fabricated and the effects of therapeutics on the models evaluated in high throughput—for example, with automated liquid handling systems and microplate reader-based high-throughput screening (HTS) assays. The most frequently-used model systems for HTS, 2D models, do not adequately model the in vivo 3D microenvironment—an important aspect of which is the extracellular matrix—and therefore, 2D models may not be appropriate for drug screening. Instead, tissue-engineered 3D models with extracellular matrixmimicking components are destined to become the preferred in vitro systems for HTS. However, for 3D models, such as 3D cell-laden hydrogels and scaffolds, cell sheets, and spheroids as well as 3D microfluidic and organ-on-a-chip systems, to replace 2D models in HTS, they must be compatible with high-throughput fabrication schemes and evaluation methods. In this review, we summarize HTS in 2D models and discuss recent studies that have successfully demonstrated HTScompatible 3D models of high-impact diseases, such as cancers or cardiovascular diseases.