Cell-embedded microgels as emerging miniature 3D tissue-mimics toward biochip-based toxicity screening

Recent developments in synthetic three-dimensional (3D) gel microenvironments for cell culture have enabled the advancement of bioengineered organ-specific cell niches that resemble the native 3D tissue architecture and mechanics. In particular, the application of 3D cell cultures based on miniaturized hydrogel scaffolds for toxicological analyses is attracting increasing interest because of their facile adaptability to on-chip systems and potential as novel in vitro screening tools. We summarize the current progress in microgel-based 3D cells integrated into biochip platforms and their utilization for the in vitro toxicity evaluation of chemicals and drug candidates. We emphasize the development of tissue-mimicking microgel systems combined with automated gel microarray chips and organ-on-a-chip devices. This review begins with the microscale hydrogel scaffolds that encapsulate mammalian cells and are used for in vitro tissue mimicry purposes. Furthermore, an overview of microgel-based tissue modeling approaches to toxicity testing and screening is provided, along with their technical advantages in drug discovery and alternatives to animal testing.