Biological tissues are not a random assembly of cells but a hierarchical and tightly controlled three-dimensional (3D) organization of various cell types. Current systems for modeling human biology, however, are predominantly based on the two-dimensional (2D) culture of human cells and animal models of tissue and organ function. As a crucial complement to these systems, 3D cell assemblies are increasingly being used in modeling tissue development and diseases, for in vitro drug screening, and as in vivo replacements for damaged tissues and organs. Yet most 3D cell culture systems start with clusters or a random assembly of cells with the assumption that the originally random cells can appropriately self-organize over time. However, this premise has been recognized to be questionable.

The overarching goal of this research is to engineer functional 3D tissue mimics through programmable cell assembly. Our approach is inspired by Minecraft, a popular video game that uses individual 3D cubes as voxels to create a virtual world. We use cell-encapsulated hydrogel particles as voxels, assemble the voxels to create hierarchical and organized 3D structures, and exploit biophysical and biochemical cues to program the assemblies to functional tissues. The central hypothesis is that such programmable cell assembly allows for precisely delineated cell phenotypes and thus highly functional tissues. The vision of this research integrates three aspects: (i) voxelated bioprinting, (ii) modular biomaterials, and (iii) functional tissue mimics. This research will provide a suite of tools for programmable engineering of 3D tissue mimics for basic and applied biomedicine.

Current research directions include:

• Development of voxel bioprinting platform
• Modular biomaterials with tailored biophysical and biochemical properties to understand and control cell-matrix and cell-cell interactions behavior
• Engineering functional tissue mimics for basic and translational biomedicine