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 appropriate mechanical cues and geometric guidance to support tissue-specific 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. Here, we report a shear-induced method to fabricate one-dimensional gel noodles with enhanced macroscopic alignment using dipeptide-based gelators. By optimizing the extensional viscosity and shear flow conditions, we produced thin segments of gel noodles with improved internal alignment compared to traditional syringe-pump extrusion. Polarized optical microscopy and small-angle neutron scattering confirmed superior fibrillar orientation in the thin noodles. Mechanical testing revealed that enhanced alignment led to a ~400-fold increase in tensile stress resistance of 2NapFF, with ultimate stress rising from 20-50 kPa in thick noodles to 10-20 MPa in the thin segments. The method was effective across multiple gelators, including LD-2NapFF, 4BPFF, and 1ThNapFF, demonstrating its broad applicability for tuning macroscopic alignment in gel noodles. The biological relevance of thin 4BPFF noodles was demonstrated in C2C12 myoblast cultures, which showed improved cell adhesion, elongation, and myogenic differentiation compared to the thick segment. These findings demonstrate a simple and scalable approach to fabricate aligned supramolecular gels with tunable architecture and biological compatibility, suitable for applications in muscle regeneration and tissue engineering.