Molecular tuning of a benzene-1,3,5-tricarboxamide supramolecular fibrous hydrogel enables control over viscoelasticity and creates tunable ECM-mimetic hydrogels and bioinks.

Hydrogels are an important class of materials for applications in cell culture and tissue engineering; however, traditional synthetic covalent hydrogels lack the native tissue dynamics and hierarchical fibrous structure found in the extracellular matrix (ECM). These dynamic and fibrous nanostructures have been shown to be imperative in obtaining the correct cell/material interactions, and thus critical for biomedical applications. Consequently, the challenge to engineer functional dynamics in a fibrous hydrogel and recapitulate native ECM properties remains a bottle-neck to biomimetic hydrogel environments for cell culture. In this study, we report the molecular tuning of a self-assembling, supramolecular benzene-1,3,5-tricarboxamide (BTA) hydrogelator via simple modulation of hydrophobic substitutents. This tuning resulted in fibrous hydrogels with accessible viscoelasticity over 5 orders of magnitude, while maintaining a constant equilibrium storage modulus. Using recently developed synthetic methodology, we created BTA hydrogelators with 12, 16, 18, 20 and 24 external hydrophobic carbon atoms, and observed that the hydrophobics controlled the viscoelasticity and stress relaxation time scales in a logarithmic fashion. The BTA hydrogels with 16, 20, and 24 hydrophobic carbons were shear-thinning, self-healing, extrudable, injectable, and could be 3D printed into multiple layers. These hydrogels showed high cell viability for chondrocytes and hMSCs, 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 could be ported onto other 1D self-assembling structures. The molecular control and design of hydrogel network dynamics can push the field of supramolecular chemistry towards designing new ECM-mimicking hydrogelators for numerous cell culture and tissue engineering applications and give access towards highly biomimetic bioinks for bioprinting. This article is protected by copyright. All rights reserved.