Bioinspired Coordination for Fabricating Self-healing and Injectable Hydrogels with Antibacterial and Immunoregulatory Activities†

Abstract

Inspired by the molecular mechanism of mussel adhesion, here, we developed a class of injectable and self-healing hydrogels based on natural polysaccharide hyaluronic acid (HA). The dynamic property of hydrogels is derived from histidine-metal coordination, which widely exists in the mussel adhesive plaque. To mimic components of mussel byssal threads, we first grafted histidine-containing peptides onto the HA chains. Followed by the addition of Zn²⁺ ions, the modified HA could then transform into a pH-sensitive hydrogel network (HA-His-Zn) with tunable sol-gel transitions. The dynamic metal-ligand coordination could significantly enhance the mechanical properties of HA hydrogels and also endow them with self-healing and injectable abilities. In addition, the HA-His-Zn hydrogels could also exhibit antibacterial and immunoregulatory activities due to the bioactive Zn²⁺ ions. These results, together with the dynamic properties and good biocompatibility, indicated that the HA-His-Zn hydrogels could be applied as a class of easy-to-handle scaffold materials for regeneration medicine, particularly for tissue traumas with chronic inflammations and infections.