Achieving 3-D Structural Uniformity in Cellulose Gel Beads via Salt Screening

Cellulose microgel beads fabricated using the dropping technique suffer from structural irregularity and mechanical variability. This limits their translation to biomedical applications that are sensitive to variations in material properties. Ionic salts are often uncontrolled by-products of this technique, despite the known effects of ionic salts on cellulose assembly. In this study, the coagulation behavior of cellulose/salt solutions was explored as a way to combat these challenges. An ionic salt (NaCl) was added to a cellulose solution (cellulose/NaOH/urea) prior to coagulation in a hydrochloric acid bath. Quantification of the bead geometry and characterization of the pore architecture revealed that balancing the introduction of salt with the resultant solution viscosity is more effective at reducing structural variability and diffusion limitations than other pre-gelling techniques like thermal gelation. Three-dimensional visualization of the internal pore structure of neat cellulose, thermo-gel, and salt-gel beads revealed that adding salt to the solution is the most effective way to achieve 3-D structural uniformity throughout the bead. Coupled with nanoindentation, we confirmed that the salt produced during coagulation plays a critical role in mechanical variability, and that adding salt to the solution before dropping into the coagulation bath completely screens this effect, producing uniform microgel beads with reproducible mechanical properties.