Bioactive herbal supramolecular hydrogels with a hierarchical nanofibrillar structure <i>via</i> metal ion mediated co-assembly

Supramolecular hydrogels assembled from natural herbal small molecules represent a promising platform for the development of biocompatible and multifunctional soft biomaterials. In this study, we report a novel multicomponent supramolecular hydrogel system constructed from the co-assembly of glycyrrhizic acid (GA) and rhein (Rh) <i>via</i> Zn²⁺ modulation. The introduction of Zn²⁺ not only reinforces the mechanical stiffness and toughness of the GA-Rh hydrogel network through complexation but also improves its antibacterial efficacy and anti-inflammatory capacity. Notably, a hierarchical nanofibrillar gel network with an internal multiscale structure is formed, in which a micron-scale pore network formed by the GA nanofibrils and a submicron-scale pore network formed by the GA-Rh co-assembled nanofibrils synergistically contributed to the overall structural integrity and biological performance. <i>In vitro</i> assays demonstrate that the GA-Zn-Rh hydrogels exhibit potent antibacterial activity against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, excellent biocompatibility, and pronounced anti-inflammatory effects. This work provides valuable insights into the relationships between nanostructure and functionality in multicomponent bioactive herbal hydrogels, offering a supramolecular strategy to mimic the synergistic therapeutic principles of traditional Chinese medicine. These findings pave the way for the development of nature-inspired bioactive hydrogels for wound healing and broader biomedical applications.