Dynamic Shape-changing Hydrogels for Tissue Engineering
In embryogenesis and morphogenesis, cell clusters or sheets organize into units of increasing complexity from multi-cell layers, to tissues, organs and eventually whole organisms. Dynamic changes in shape are an essential part of morphogenesis and even the most complex biological structures are formed from fairly simple units through numerous shape transformation steps. Although nature has found ways to elegantly exploit shape transformation in plants and animals, the field is much newer to polymer scientists and engineers. Furthermore, tissue engineers are only starting to explore shape transformation for cell and tissue culture. Current shape changing scaffolds are not permissive of self-folding actuation at arbitrary time points nor are they permissive of step-wise folding, similar to what is observed during morphogenesis and development. The subject of this manuscript is on shape-changing photodegradable hydrogels for cell and tissue culture. We first discuss the physical basis for how light is used to pattern differences in swelling throughout a hydrogel film. The differences in swelling are balanced by the hydrogel’s network elasticity, resulting in folding of free-floating hydrogels. Beyond demonstrating shape-change as a proof of concept, we systematically review the effect of material, chemical, and physical parameters on curvature. Next, we discuss the use of planar sheet geometries and spatiotemporal light patterning to actuate hydrogel folding with different mean and Gaussian curvatures that are relevant for human biology. Finally, we demonstrate that the hydrogels are capable of supporting 2D seeded cell culture and 3D encapsulation. Mammalian cells on the hydrogel scaffolds are shape changed at arbitrary time points and remain viable. We thus demonstrate photodegradable hydrogel shape change as a viable concept for dynamic, 4D cell culture.