Introducing Hyaluronic Acid into Supramolecular Polymers and Hydrogels

[Image: see text] The use of supramolecular polymers to construct functional biomaterials is gaining more attention due to the tunable dynamic behavior and fibrous structures of supramolecular polymers, which resemble those found in natural systems, such as the extracellular matrix. Nevertheless, to obtain a biomaterial capable of mimicking native systems, complex biomolecules should be incorporated, as they allow one to achieve essential biological processes. In this study, supramolecular polymers based on water-soluble benzene-1,3,5-tricarboxamides (BTAs) were assembled in the presence of hyaluronic acid (HA) both in solution and hydrogel states. The coassembly of BTAs bearing tetra(ethylene glycol) at the periphery (BTA-OEG(4)) and HA at different ratios showed strong interactions between the two components that led to the formation of short fibers and heterogeneous hydrogels. BTAs were further covalently linked to HA (HA-BTA), resulting in a polymer that was unable to assemble into fibers or form hydrogels due to the high hydrophilicity of HA. However, coassembly of HA-BTA with BTA-OEG(4) resulted in the formation of long fibers, similar to those formed by BTA-OEG(4) alone, and hydrogels were produced with tunable stiffness ranging from 250 to 700 Pa, which is 10-fold higher than that of hydrogels assembled with only BTA-OEG(4). Further coassembly of BTA-OEG(4) fibers with other polysaccharides showed that except for dextran, all polysaccharides studied interacted with BTA-OEG(4) fibers. The possibility of incorporating polysaccharides into BTA-based materials paves the way for the creation of dynamic complex biomaterials.