Mesh Size Regulates Diffusion in Calcium Alginate Hydrogels: a Spatiotemporal Approach Combining Experiments and COMSOL-Based Modeling

This study systematically investigates the relationship between mesh size and solute diffusivity in calcium-alginate hydrogels using tetramethyl-rhodamine isothiocyanate dextran as a model solute. Hydrogels were prepared at different alginate concentrations and characterized for storage modulus, swelling ratio, and mesh size. Local and effective diffusion coefficients were determined by fitting spatiotemporal fluorescence profiles with a COMSOL diffusion model, revealing a clear decrease in diffusivity with increasing hydrogel concentration and decreasing mesh size. Our analysis demonstrated high reproducibility for most formulations. Experimental data were compared to predictions of a multiscale diffusion model integrating free volume and obstruction theory, with further refinement using empirical corrections for dextran shape and flexibility. While theoretical models slightly underestimated measured diffusion coefficients most probably due to gel microheterogeneity, incorporation of molecular corrections improved predictive accuracy albeit that a systemic difference remains. The findings confirm that solute mobility in alginate hydrogels is governed by the mesh size of the network, thus supporting rational hydrogel design for controlled release applications. • Mesh size critically controls TRITC-dextran 40 diffusion in alginate hydrogels. • Solute diffusivity in hydrogel can be estimated with COMSOL Multiphysics. • Local differences in solute diffusivity in the hydrogels were observed. • Solute molecular feature correction improves agreement of theory with experiments.