Cascade Reaction of Thiol-Disulfide Exchange Potentiates Rapid Fabrication of Polymer Hydrogels.

We report a rapid cross-linking strategy for the fabrication of polymer hydrogels based on a thiol-disulfide cascade reaction. Specifically, thiolated polymers (e.g., poly(ethylene glycol), hyaluronic acid, sodium alginate, poly(acrylic acid), and poly(methylacrylic acid)) can be cross-linked via the trigger of Ellman's reagent, resulting in the rapid formation of hydrogels over 20-fold faster than that via the oxidation in air. The gelation kinetics of hydrogels can be tuned by varying the polymer concentration and the molar ratio of Ellman's reagent and free thiols. The obtained hydrogels can be further functionalized with functional moieties (e.g., targeting ligands) for the selective adhesion of cells. This approach is applicable to various natural and synthetic polymers for the assembly of hydrogels with a minimized gelation time, which is promising for various biological applications.