Shape-Changing Photodegradable Hydrogels for Dynamic 3D Cell Culture

Inspired by natural examples of swelling-actuated self-folding, we utilize photodegradable hydrogels as dynamically tunable, shape-changing scaffolds for culturing cells. Poly­(ethylene glycol) diacrylate-based thin films incorporating ortho-nitrobenzyl (o-NB) moieties are transformed from flat 2D sheets to folded 3D structures by exposure to 365 nm UV light. As the UV light is attenuated through the thickness of the gel, a cross-link density gradient is formed. This gradient gives rise to differential swelling and a bending moment, resulting in gel folding. By tuning the UV light dose and the molar ratio of photodegradable to nondegradable species, both the initial degree of folding and the relaxation of tubular structures can be accurately controlled. These self-folding photodegradable gels were further functionalized with a cell-adhesive RGD peptide for both seeding and encapsulation of C2C12 mouse myoblasts. Light-induced folding of RGD functionalized hydrogels from flat sheets to tubular structures was demonstrated 1 or 3 days after C2C12 seeding. The C2C12s remained adhered on the inner walls of folded tubes for up to 6 days after folding. The minimum measured diameter of a tubular structure containing C2C12s was 1 mm, which is similar to the size of muscle fascicles. Furthermore, the viability of encapsulated C2C12s was not adversely affected by the UV light-induced folding. This is the first account of a self-folding material system that allows 2D–3D shape change in the presence of both seeded and encapsulated cells at a user-directed time point of choice.