Hyaluronic Acid Click Hydrogels Emulate the Extracellular Matrix

Hydrogels are used to create 3D microenvironments with properties that direct cell function. The current study demonstrates the versatility of hyaluronic acid (HA)-based hydrogels with independent control over hydrogel properties such as mechanics, architecture, and the spatial distribution of biological factors. Hydrogels were prepared by reacting furan-modified HA with bis-maleimide-poly(ethylene glycol) in a Diels-Alder click reaction. Biomolecules were photopatterned into the hydrogel by two-photon laser processing, resulting in spatially defined growth factor gradients. The Young's modulus was controlled by either changing the hydrogel concentration or the furan substitution on the HA backbone, thereby decoupling the hydrogel concentration from mechanical properties. Porosity was controlled by cryogelation, and the pore size distribution, by the thaw temperature. The addition of galactose further influenced the porosity, pore size, and Young's modulus of the cryogels. These HA-based hydrogels offer a tunable platform with a diversity of properties for directing cell function, with applications in tissue engineering and regenerative medicine.