Guiding Cell Network Assembly using Shape‐Morphing Hydrogels

Abstract

Forces and relative movement between cells and extracellular matrix (ECM) are crucial to the self‐organization of tissues during development. However, the spatial range over which these dynamics can be controlled in engineering approaches is limited, impeding progress toward the construction of large, structurally mature tissues. Herein, shape‐morphing materials called “kinomorphs” that rationally control the shape and size of multicellular networks are described. Kinomorphs are sheets of ECM that change their shape, size, and density depending on patterns of cell contractility within them. It is shown that these changes can manipulate structure‐forming behaviors of epithelial cells in many spatial locations at once. Kinomorphs are built using a new photolithographic technology to pattern single cells into ECM sheets that are >10× larger than previously described. These patterns are designed to partially mimic the branch geometry of the embryonic kidney epithelial network. Origami‐inspired simulations are then used to predict changes in kinomorph shapes. Last, kinomorph dynamics are shown to provide a centimeter‐scale program that sets specific spatial locations in which ≈50 µm‐diameter epithelial tubules form by cell coalescence and structural maturation. The kinomorphs may significantly advance organ‐scale tissue construction by extending the spatial range of cell self‐organization in emerging model systems such as organoids.

4D biofabrication via instantly generated graded hydrogel scaffolds

“…Compared with 3D scaffolds, 4D scaffolds with the ability to reconfigure their shapes during culture show huge potential for morphodynamic tissue engineering. Hydrogels that harness non-uniform swelling [ 43 , 54 , [56] , [57] , [58] ], post-programmed anisotropic internal strains [ 59 , 60 ], or cell contractile forces [ [61] , [62] , [63] ] can accomplish this task. However, in addition to the stringent requirements regarding material cytocompatibility, the fabrication process, and imposed stimulation, complexity in fabrication and lack of controllability present a significant impedance to 4D tissue engineering.…”

Synthetic living machines: A new window on life

“…Microfluidic approaches as well as engineered matrices offer a cell-extrinsic based control for signaling cues ( Brassard and Lutolf, 2019 ). For instance, shape-morphing materials dubbed kinomorphs can rationally control the shape and size of multicellular networks ( Viola et al., 2020 ). Additionally, self-organization of intestinal organoids-on-a-chip using scaffold was shown to enable regulation of morphological specifications.…”

User-defined, temporal presentation of bioactive molecules on hydrogel substrates using supramolecular coiled coil complexes

“…62,63 These traction forces are ubiquitous and implicated in dynamic tissue processes (e.g. contraction), [62][63][64] and they may induce remodeling of the supramolecular coiled coil system. Since the conjugated T-peptide provides open and dynamic sites for coiled coil complexes to form, we postulate that cells may be able to reorganize the physical locations of the A-peptide motifs on the NorHA hydrogel surface through traction forcesthus providing a dynamic surface that leads to increased cell area.…”