Molecular Tuning of a Benzene‐1,3,5‐Tricarboxamide Supramolecular Fibrous Hydrogel Enables Control over Viscoelasticity and Creates Tunable ECM‐Mimetic Hydrogels and Bioinks

Abstract Traditional synthetic covalent hydrogels lack the native tissue dynamics and hierarchical fibrous structure found in the extracellular matrix (ECM). These dynamics and fibrous nanostructures are imperative in obtaining the correct cell/material interactions. Consequently, the challenge to engineer functional dynamics in a fibrous hydrogel and recapitulate native ECM properties remains a bottle‐neck to biomimetic hydrogel environments. Here, the molecular tuning of a supramolecular benzene‐1,3,5‐tricarboxamide (BTA) hydrogelator via simple modulation of hydrophobic substituents is reported. This tuning results in fibrous hydrogels with accessible viscoelasticity over 5 orders of magnitude, while maintaining a constant equilibrium storage modulus. BTA hydrogelators are created with systematic variations in the number of hydrophobic carbon atoms, and this is observed to control the viscoelasticity and stress‐relaxation timescales in a logarithmic fashion. Some of these BTA hydrogels are shear‐thinning, self‐healing, extrudable, and injectable, and can be 3D printed into multiple layers. These hydrogels show high cell viability for chondrocytes and human mesenchymal stem cells, establishing their use in tissue engineering applications. This simple molecular tuning by changing hydrophobicity (with just a few carbon atoms) provides precise control over the viscoelasticity and 3D printability in fibrillar hydrogels and can be ported onto other 1D self‐assembling structures. The molecular control and design of hydrogel network dynamics can push the field of supramolecular chemistry toward the design of new ECM‐mimicking hydrogelators for numerous cell‐culture and tissue‐engineering applications and give access toward highly biomimetic bioinks for bioprinting.