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

Comprehensive Summary 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 Zn 2+ 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 Zn 2+ 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.