Photoinduced Dithiolane Crosslinking, Exchange, and Depolymerization for Dynamic Hydrogels

Synthetic hydrogel chemistries have commonly been used in tissue culture scaffolds because of their tunable mechanical properties and ability to incorporate key biochemical elements of the cellular microenvironment. Dynamic hydrogels are increasingly being utilized to more faithfully recapitulate the time and position dependent processes found in the native cellular niche. However, to recreate multiple dynamic processes, orthogonal chemistries are often required, necessitating complex syntheses and limiting widespread adoption of these approaches. In this work, 1,2-dithiolanes, a five membered heterocycle containing an intrinsically reactive disulfide bond, are used as dynamic hydrogel crosslinkers, resulting in dynamic disulfide bonds capable of responding to multiple stimuli. Because of the ring strain of these molecules, 1,2-dithiolanes absorb light in the UV range and are capable of an initiator free photopolymerization. Using lipoic acid as a model dithiolane, disulfide crosslinks are formed in physiological conditions, enabling cellular encapsulation through initiator free dithiolane ring opening polymerization. These hydrogels incorporate multiple dynamic responses into a single chemistry, including stress relaxation, stiffening, viscoelasticity, and photopatterning. These unique material capabilities are demonstrated in dynamic 2D and 3D cell culture applications, showcasing a generalizable strategy for designing materials with multiple dynamic outputs that can be controlled spatiotemporally, all enabled by a single chemistry.