Internally-driven cell-sheet shape transformations via oriented forces in collagen matrices

Morphogenesis, the biological process that leads to differentiated and complex shapes of tissues and organisms, is driven partly by directional cell forces. A potential platform to replicate this process is by using anisotropic hydrogels, which are hydrophilic and biocompatible, as tissue scaffolds. In this study, we demonstrate programmable shape transformation of cell-laden collagen matrices by leveraging orientational order to control collective cell forces. We fabricate polyethylene glycol (PEG)-based hydrogels, with fibrin-like morphologies, templated by a lyotropic chromonic liquid crystal. First, we characterize the anisotropic hydrogel microstructures by scattering and microscopy. Thereafter, we embed human dermal fibroblasts in collagen and grow them on PEG hydrogels. Cells align following the anisotropic cues and remodel the collagen accordingly. For uniformly oriented hydrogels, we quantify the relationship between cell orientation, elastic moduli, and macroscopic contraction of the matrices. Using a photopatterning setup, we impose spatially heterogeneous to guide the cells, and induce shape changes of the cell-laden collagen. This approach offers a new platform for studying morphogenesis and advancing bio-fabrication and tissue engineering.