Jammed Polyelectrolyte Microgels for 3D Cell Culture Applications: Rheological Behavior with Added Salts

The yielding and jamming behaviors of packed granular-scale microgels enable their use as a support medium for 3D printing stable shapes made from liquid phases; under low levels of applied stress, jammed microgel packs behave like elastic solids and provide support to spatially patterned fluid structures. When swollen in cell growth media, these microgels constitute a biomaterial for bioprinting and 3D cell culture applications. However, interactions between polyelectrolytes commonly used in microgels and multivalent ions present in cell growth media may lead to drastic and adverse changes in rheological behavior or cell performance. To elucidate these interactions, we design polyelectrolyte microgels with anionic, cationic, and zwitterionic charged species and investigate their rheological behaviors in CaCl₂ solutions. We find the rheological behavior of anionic and cationic microgels follow polyelectrolyte scaling laws near jamming concentrations; the rheological properties of zwitterionic microgels become independent of CaCl₂ at high concentrations. We explore the potential application of these microgels as biomaterials for 3D cell culture through studies of short-term cell viability, population growth, and metabolic activity. We find that the short-term viability of cells cultured in polyelectrolytes is highly dependent on the chemical composition of the system. In addition, we find that anionic and zwitterionic microgels have minimal effects on the short-term viability and metabolic activity of cells cultured in microgel environments across a wide range of rheological properties.