Cell-sheet shape transformation by internally-driven, oriented forces

During morphogenesis, cells collectively execute directional forces that
drive the programmed folding and growth of the layers, forming tissues and
organs. The ability to recapitulate aspects of these processes in vitro
will constitute a significant leap forward in the field of tissue
engineering. Free-standing, self-organizing, cell-laden matrices are
fabricated using a sequential deposition approach that uses liquid
crystal-templated hydrogel fibers to direct cell arrangements. The
orientation of hydrogel fibers is controlled using flow or boundary cues,
while their microstructures are controlled by depletion interaction and
probed by scattering and microscopy. These fibers effectively direct cells
embedded in a collagen matrix, creating multilayer structures through
contact guidance and by leveraging steric interactions amongst the cells.
In uniformly aligned cell matrices, oriented cells exert traction forces
that can induce preferential contraction of the matrix. Simultaneously,
the matrix densifies and develops anisotropy through cell remodeling. Such
an approach can be extended to create cell arrangements with arbitrary
in-plane patterns, allowing for coordinated cell forces and
pre-programmed, macroscopic shape changes. This work reveals a
fundamentally new path for controlled force generation, emphasizing the
role of a carefully designed initial orientational field for manipulating
shape transformations of reconstituted matrices.