Anisotropic liquid crystalline hydrogels direct 2D and 3D myoblast alignment

Tissue development and regeneration are governed by processes that span subcellular signaling, cell-cell interactions, and the integrated mechanical properties of cellular collectives with their extracellular matrix. Synthetic biomaterials that can emulate the hierarchical structure and supracellular mechanics of living systems are paramount to the realization of regenerative medicine. Recent reports detail directed cell alignment on mechanically anisotropic but stiff liquid crystalline polymer networks (LCNs). While compelling, the potential implementation of these materials as tissue engineering scaffolds may be hindered by the orders of magnitude larger stiffness than most soft tissue. Accordingly, this report prepares liquid crystalline hydrogels (LCHs) that synergize the anisotropic mechanical properties intrinsic to LCNs with the cytocompatibility and soft mechanics of PEG hydrogels. LCH are prepared via sequential oligomerization and photopolymerization reactions between liquid crystalline (LC) monomers and poly(ethylene glycol) (PEG)-dithiol. Despite their low liquid crystalline content, swollen LCH oligomers are amenable to rheological alignment via direct ink write 3D printing. Mechanically anisotropic LCHs support C2C12 myoblast culture on their surface and direct their alignment in the stiffest direction. Further, C2C12s can be encapsulated within LCH oligomers and 3D-printed, whereby mechanical anisotropy of the LCH directs myoblast polarization in 3D.