Abstract
Multicellular cancer spheroids (MCSs) have emerged as a promising in vitro model that replicates many features of solid tumors in vivo. Biomimetic hydrogel scaffolds for MCS growth offer a broad spectrum of biophysical and biochemical cues that help to recapitulate the behavior of natural extracellular matrix, essential for regulating cancer cell behavior. This perspective highlights recent advances in the development of hydrogel environments for MCS growth, release, and drug screening. We review the use of different types of hydrogels for MCS growth, the effect of biophysical and biochemical cues on MCS fate, the isolation of MCSs from hydrogel scaffolds, the utilization of microtechnologies, and the applications of MCSs grown in hydrogels. We conclude with the discussion of new research directions in the development of hydrogels for MCS growth.