Patterning hydrogels in three dimensions towards controlling cellular interactions

The 3-dimensional (3D) interaction between cells and extracellular matrix (ECM) constitutes a dynamic regulatory system for directing tissue formation and homeostasis, as well as regeneration in response to injury. As such, significant progress has been made in the field of tissue engineering to develop 3D hydrogels capable of promoting cell viability and many of these important ECM interactions. However, the spatial patterning of hydrogels in 3D, motivated by the microscale heterogeneity of native tissue architectures, has only recently been a focus. Here, we review efforts to date to engineer structurally and/or biochemically patterned 3D hydrogels to control cellular behavior for regenerative medicine applications. Such techniques can be separated into two categories: stereolithographic “bottom-up” methods that pattern structures during layer-by-layer fabrication and post-gelation techniques involving modification of a uniform, pre-formed hydrogel. Many techniques in each group are further compatible with cell encapsulation, providing a valuable set of models for studying cell-cell signaling or for the engineering of new tissues.