Shape-Changing Photodegradable Hydrogels for Dynamic\n3D Cell Culture

Abstract

Inspired\nby natural examples of swelling-actuated self-folding, we utilize\nphotodegradable hydrogels as dynamically tunable, shape-changing scaffolds\nfor culturing cells. Poly­(ethylene glycol) diacrylate-based thin films\nincorporating <i>ortho</i>-nitrobenzyl (<i>o</i>-NB) moieties are transformed from flat 2D sheets to folded 3D structures\nby exposure to 365 nm UV light. As the UV light is attenuated through\nthe thickness of the gel, a cross-link density gradient is formed.\nThis gradient gives rise to differential swelling and a bending moment,\nresulting in gel folding. By tuning the UV light dose and the molar\nratio of photodegradable to nondegradable species, both the initial\ndegree of folding and the relaxation of tubular structures can be\naccurately controlled. These self-folding photodegradable gels were\nfurther functionalized with a cell-adhesive RGD peptide for both seeding\nand encapsulation of C2C12 mouse myoblasts. Light-induced folding\nof RGD functionalized hydrogels from flat sheets to tubular structures\nwas demonstrated 1 or 3 days after C2C12 seeding. The C2C12s remained\nadhered on the inner walls of folded tubes for up to 6 days after\nfolding. The minimum measured diameter of a tubular structure containing\nC2C12s was 1 mm, which is similar to the size of muscle fascicles.\nFurthermore, the viability of encapsulated C2C12s was not adversely\naffected by the UV light-induced folding. This is the first account\nof a self-folding material system that allows 2D–3D shape change\nin the presence of both seeded and encapsulated cells at a user-directed\ntime point of choice.