Controlled remodeling of hydrogel networks and subsequent crosslinking: A strategy for preparation of alginate hydrogels with ultrahigh density and enhanced mechanical properties

Spherical alginate hydrogels - microbeads - are usually prepared via ionic crosslinking by dripping the alginate solution into a solution of divalent cations. However, the applicable concentration of alginate solution in current fabrication methods is limited to a maximum of 2-2.5 wt% due to the high viscosity of alginate in an aqueous solution. In this work, we propose a simple strategy, a remodeling of polymer networks and subsequent crosslinking process (RsC process), to prepare uniform alginate microbeads with ultrahigh alginate density, up to ≈38 wt%, via size reduction to 34% of the initial size. The uniform, ionically crosslinked alginate microbeads are shrunk via solvent exchange using an organic solvent while maintaining the spherical morphology. The shrunken state of alginate microbeads is fixed via secondary crosslinking of the alginate. Alginate hydrogels prepared via the RsC process show enhanced, controllable mechanical properties. This simple approach may be applied to any type of alginate-based hydrogel of various size, shape, and structure to prepare hydrogels with high alginate density with tailored mechanical properties.