Diels-Alder Click-Based Hydrogels for Direct Spatiotemporal Postpatterning via Photoclick Chemistry.

Click chemistry not only has been applied to the design of hydrogel scaffolds for 3D cell culture, but also is an efficient way for hydrogel postfunctionalization and spatiotemporal patterning. To the best of our knowledge, only azide-alkyne cycloaddition (SPAAC) has been exploited by combining photoinitiated thiol-ene click reaction to realize the 3D patterning of hydrogels. In this work, the cyclohexene derivative, which "clicked" by functional groups between furyl and maleimide, were successfully functionalized by thiol-modified molecules or peptides through thiol-ene click reaction. It illustrates a hydrogel that formed via Diels-Alder (DA) click chemistry between furyl-modified hyaluronic acid and bimaleimide functional PEG molecule can be allowed for the directly photoactivated thiol-ene chemistry for hydrogel spatiotemporal patterning. Since the cyclohexene derivatives produced by DA reaction can be employed in all subsequent 3D network patterning by using photoclick reactions, it suggests a new way to design and postfunctionalize all of the DA click-based hydrogels with specific regional bioactive cues.