Mixed‐Solvent‐Induced Phase Separation Enables Anisotropy and Strengthening of Hydrogels Composed of Flexible Network Chains

Abstract Achieving anisotropy in hydrogels is key to replicating the structural and mechanical properties of biological tissues. However, inducing anisotropy in hydrogel systems composed solely of flexible amorphous polymers is challenging, as these polymers typically exhibit thermally unstable anisotropic states, i.e., they are easy to disorient. In this study, a mixed‐solvent‐induced phase‐separation approach to stabilize the orientation of such hydrogel networks after pre‐stretching is introduced. Using polyacrylamide, a flexible polymer with a persistence length on the order of 10 −1 nm, as a model system, it is demonstrated that phase separation in a mixed solvent leads to the formation of dense and dilute polymer phases, with the dense phase effectively locking the anisotropy through robust inter‐ and intra‐polymer interactions. A series of characterizations confirm that partial orientation can be preserved in the prestretched, phase‐separated gel upon relaxation, resulting in significant mechanical enhancement along the orientation direction, including improvements in fracture stress, Young's modulus, and fracture toughness. The generality of this method, showing its effectiveness in other hydrogel systems and its adaptability to different solvent combinations is also validated. This work presents an unconventional strategy for preparing anisotropic hydrogels that typically struggle to maintain structural integrity.