Cells in microgels: 3D printed microtissues and three-dimensional cell migration

In most natural settings, cells thrive in 3D complex environments. The demand of studying cells in 3D has led to the development of many 3D growth media and various bio-printing techniques. Most 3D growth media use bio-degradable polymer networks; during 3D bio-printing cell-loaded polymeric filaments are spatially arranged that solidify during the printing process to preserve the shape. However, the spatial variation in network structure and the transience of degradable gels make quantitative cell behavior studies in these materials extremely challenging. Moreover, the general approaches of 3D bio-printing rely on intimate interactions between cells and specialized materials. Instead, we have developed a 3D growth medium from the jammed system of granular polyelectrolyte microgels that allows for 3D culture of cells. We find that single cell motility can be altered by varying inter-microgel pore spacing in 3D growth media. The self-healing nature of this growth media allows creation of highly precise tissue like structures by direct injection of cells inside the sacrificial 3D media. Finally, we have characterized the macroscopic rheological behaviors of this 3D medium and related them to the classic polyelectrolyte physics scaling laws that control single-microgel elasticity This work provides a revised approach of 3D cell culture and bio-printing and yields principles for predicting cellular migration and creating complex structures of cells with direct implications for tissue-engineering.