Shear-Induced Anisotropic Supramolecular Gel Noodles for Improved Cell Guidance in Polarized Tissue Engineering.

Tissue engineering and regenerative medicine applications require the integration of multifunctional materials, offering tissue-specific mechanical cues and geometric guidance to support cell differentiation. In this context, supramolecular gel noodles formed by ionic cross-linking of pre-assembled micellar networks offer unique opportunities for creating anisotropic soft materials. However, controlling fibrillar alignment over extended lengths remains a challenge. Herein, a shear-induced method to fabricate 1D gel noodles with enhanced macroscopic alignment using dipeptide-based gelators is reported. By implementing a two-stage extrusion protocol, we generate a thin tail segment with a distinct flow history that exhibits higher retained alignment than the pump-driven segment. Polarized optical microscopy and small-angle neutron scattering confirm superior fibrillar orientation in the thin segment, and mechanical testing reveals up to ∼400-fold increase in nominal stress at failure. The method is effective across multiple gelators, demonstrating its broad applicability for tuning macroscopic alignment in gel noodles. Preliminary C2C12 culture on the thin segment demonstrates improved cell adhesion, elongation, and increased MyoD expression compared to the thick segment. These findings provide a scalable route to introduce anisotropy in supramolecular gel noodles through processing history, and we present cell culture data as proof of compatibility and contact guidance relevant to aligned tissue-mimetic scaffolds.