Extensive efforts have been made to understand the effects of extracellular microenvironments on phenotypic activities for a wide array of stem, progenitor, and precursor cells. Hydrogels have emerged as invaluable platforms for examining the effects of extracellular matrix (ECM) properties on cell activities because of their several advantageous features. Specifically, hydrogels are unique materials that enable cell studies in three-dimensional (3D) environments, similar to in vivo environments. Recently, there have been increasing efforts to assemble cell-encapsulating hydrogels; however, hydrogel design strategies for 3D cell cultures have not been systematically discussed to date. Therefore, this review article summarizes current hydrogel designs for 3D cell culture studies and further discusses current challenges and potential resolutions for enhancing the controllability of hydrogel properties and microstructures. The hydrogels discussed herein include those of natural polymers (e.g., collagen, fibrinogen, alginate, and hyaluronic acids), synthetic polymers [e.g., poly(ethylene glycol) (PEG) and its derivatives], and mixtures of natural and synthetic polymers. We envision that hydrogels that enable 3D studies will greatly assist in the understanding of emergent cell behaviors, and ultimately become important biomedical tools for enhancing the quality of in vitro drug screening and clinical treatments. WIREs Syst Biol Med 2012 doi: 10.1002/wsbm.1174
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