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.
Keywords: alginate; biomaterials; cell culture; microencapsulation; three-dimensional.