Advances in microscale
3D cell culture systems have helped to elucidate
cellular physiology, understand mechanisms of stem cell differentiation,
produce pathophysiological models, and reveal important cell–cell
and cell–matrix interactions. An important consideration for
such studies is the choice of material for encapsulating cells and
associated extracellular matrix (ECM). This Review focuses on the
use of alginate hydrogels, which are versatile owing to their simple
gelation process following an ionic cross-linking mechanism in situ,
with no need for procedures that can be potentially toxic to cells,
such as heating, the use of solvents, and UV exposure. This Review
aims to give some perspectives, particularly to researchers who typically
work more with poly(dimethylsiloxane) (PDMS), on the use of alginate
as an alternative material to construct microphysiological cell culture
systems. More specifically, this Review describes how physicochemical
characteristics of alginate hydrogels can be tuned with regards to
their biocompatibility, porosity, mechanical strength, ligand presentation,
and biodegradability. A number of cell culture applications are also
described, and these are subcategorized according to whether the alginate
material is used to homogeneously embed cells, to micropattern multiple
cellular microenvironments, or to provide an outer shell that creates
a space in the core for cells and other ECM components. The Review
ends with perspectives on future challenges and opportunities for
3D cell culture applications.