Molecularly Engineered Supramolecular Thermoresponsive Hydrogels with Tunable Mechanical and Dynamic Properties

Synthetic supramolecular polymers and hydrogels in water are emerging as promising biomaterials due to their modularity and intrinsic dynamics. Here, we introduce temperature sensitivity into the nonfunctionalized benzene-1,3,5-tricarboxamide (BTA-EG₄) supramolecular system by incorporating a poly(N-isopropylacrylamide)-functionalized (BTA-PNIPAM) moiety, enabling 3D cell encapsulation applications. The viscous and structural properties in the solution state as well as the mechanical and dynamic features in the gel state of BTA-PNIPAM/BTA-EG₄ mixtures were investigated and modulated. In the dilute state (c ∼μM), BTA-PNIPAM acted as a chain capper below the cloud point temperature (T_cp = 24 °C) but served as a cross-linker above T_cp. At higher concentrations (c ∼mM), weak or stiff hydrogels were obtained, depending on the BTA-PNIPAM/BTA-EG₄ ratio. The mixture with the highest BTA-PNIPAM ratio was ∼100 times stiffer and ∼10 times less dynamic than BTA-EG₄ hydrogel. Facile cell encapsulation in 3D was realized by leveraging the temperature-sensitive sol-gel transition, opening opportunities for utilizing this hydrogel as an extracellular matrix mimic.