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

Abstract

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) via 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. In vitro assays demonstrate that the GA–Zn–Rh hydrogels exhibit potent antibacterial activity against Staphylococcus aureus and Escherichia coli, 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.