Highlights d SCHEEPDOG programs electrical cues to herd cell migration via ''electrotaxis'' d Programmable electrical control allows cellular groups to perform any 2D maneuver d Precise control is possible because cells time-average x-and y-electric fields d Electrotaxis occurs across many cell types and species and can be a powerful tool

Directed cell migration is critical across biological processes spanning healing to cancer invasion, yet no tools allow such migration to be interactively guided. We present a new bioreactor that harnesses electrotaxis-directed cell migration along electric field gradients-by integrating multiple independent electrodes under computer control to dynamically program electric field patterns, and hence steer cell migration. Using this platform, we programmed and characterized multiple precise, two-dimensional collective migration maneuvers in renal epithelia and primary skin keratinocyte ensembles. First, we demonstrated on-demand, 90-degree collective turning. Next, we developed a universal electrical stimulation scheme capable of programming arbitrary 2D migration maneuvers such as precise angular turns and directing cells to migrate in a complete circle. Our stimulation scheme proves that cells effectively timeaverage electric field cues, helping to elucidate the transduction time scales in electrotaxis. Together, this work represents a fundamentally different platform for controlling cell migration with broad utility across fields.

The extracellular matrix is the biophysical environment that scaffolds mammalian cells in the body. The main constituent is collagen. In physiological tissues, collagen network topology is diverse with complex mesoscopic features. While studies have explored the roles of collagen density and stiffness, the impact of complex architectures remains not well‐understood. Developing in vitro systems that recapitulate these diverse collagen architectures is critical for understanding physiologically relevant cell behaviors. Here, methods are developed to induce the formation of heterogeneous mesoscopic architectures, referred to as collagen islands, in collagen hydrogels. These island‐containing gels have highly tunable inclusions and mechanical properties. Although these gels are globally soft, there is regional enrichment in the collagen concentration at the cell‐scale. Collagen‐island architectures are utilized to study mesenchymal stem cell behavior, and it is demonstrated that cell migration and osteogenic differentiation are altered. Finally, induced pluripotent stem cells are cultured in island‐containing gels, and it is shown that the architecture is sufficient to induce mesodermal differentiation. Overall, this work highlights complex mesoscopic tissue architectures as bioactive cues in regulating cell behavior and presents a novel collagen‐based hydrogel that captures these features for tissue engineering applications.