Advances in bioactive hydrogels to probe and direct cell fate

Advanced cell culture techniques are increasingly needed to better understand basic cell physiology, predict in vivo response, and engineer de novo functional tissue substitutes. Toward this concept, hydrogels have emerged as biomimetic in vitro culture systems that allow cells to be grown in or on user-defined microenvironments that recapitulate many critical aspects of native tissue. Hydrogel biofunctionality can be engineered predictably and precisely via the tailorability of the hydrogel's chemical and mechanical properties, each of which directly influences cell fate. In this review, we highlight state-of-the-art hydrogel platforms that have been used to assay and define cell behavior, placing an emphasis on recent directions in systems that offer dynamic control of material properties in time and space. We review current understanding of cell-material interactions in 2D and discuss recent and future efforts, as well as challenges, in extending this work to 3D. Ultimately, advances in hydrogel culture systems, synthetic approaches, and biological assays that can be performed in 3D are providing new opportunities to recapitulate fully the native cell niche.