The assembly of cells into tissue arises from a tight coordination of multivariate signals, where dynamic materials properties and cellular activities converge to define form and function. Over the past decade, biofabrication techniques have enabled simple means to precisely define soft and hard materials in 3D constructs often in the presence of living cells. However, there is often a disconnect between the complex structures we fabricate and the ways that cells interpret their surrounding environment. Here I will present our work using designer cell culture materials to understand and control cell decision making, and how we can leverage this information to 3D biofabrication. First, I will show how simple hydrogel culture materials can help normalize a stem cell population towards a useful therapeutic state. Next, I will present our unique twist on printing in granular matrices, using a jammed suspension of cells and microgels, where cell activity is dictated by the biophysical and biochemical properties of the microenvironment. Finally, I will demonstrate how these jammed yield-stress matrices can accommodate more than soft materials, with an example of printing complex bioceramic architectures. These and other composite hydrogel-based model systems are changing the way in which fundamental biological questions can be probed, which will aid our understanding of biological processes while revealing new design parameters for regenerative biomaterials and biofabrication approaches.
