Chapter 13: Engineered 3D Matrices with Spatiotemporally Tunable Properties

Many landmark mechanobiological discoveries have stemmed from two-dimensional (2D) cell culture experimentation – so-called flat biology. Despite these important results, with significant evidence that cells cultured in three-dimensional (3D) materials often exhibit behaviors more akin to those in vivo when compared against conventional 2D platforms (e.g. Petri dishes, multiwell plates), exciting opportunities exist toward engineering customizable 3D biomaterials to study and direct complex cell fates in vitro. In this chapter, we outline the effects of culture dimensionality on cell mechanobiology and discuss material design principles for culturing cells within more physiologically relevant contexts. In addition, we highlight strategies for four-dimensional (4D) mechanobiology studies in which cell-laden synthetic matrices can be modified in 3D space on demand over time to recapitulate evolving heterogeneity within complex tissue and organs.