Reversible Control of Network Properties in Azobenzene-Containing Hyaluronic Acid-Based Hydrogels

Biomimetic hydrogels fabricated from biologically derived polymers, such as hyaluronic acid (HA), are useful for numerous biomedical applications. Due to the dynamic nature of biological processes, it is of great interest to synthesize hydrogels with dynamically tunable network properties where various functions (e.g., cargo delivery, mechanical signaling) can be changed over time. Among the various stimuli developed to control hydrogel properties, light stands out for its exquisite spatiotemporal control; however, most light-based chemistries are unidirectional in their ability to manipulate network changes. Here, we report a strategy to reversibly modulate HA hydrogel properties with light, using supramolecular cross-links formed via azobenzene bound to β-cyclodextrin. Upon isomerization with 365 nm or 400-500 nm light, the binding affinity between azobenzene and β-cyclodextrin changed and altered the network connectivity. The hydrogel mechanical properties depended on both the azobenzene modification and isomeric state (lower for cis state), with up to a 60% change in storage modulus with light exposure. Furthermore, the release of a fluorescently labeled protein was accelerated with light exposure under conditions that were cytocompatible to encapsulated cells. These results indicate that the developed hydrogels may be suitable for applications in which temporal regulation of material properties is important, such as drug delivery or mechanobiology studies.