Moldable Hyaluronan Hydrogel Enabled by Dynamic Metal–Bisphosphonate Coordination Chemistry for Wound Healing

Abstract

Biomaterial‐based regenerative approaches would allow for cost‐effective off‐the‐shelf solution for the treatment of wounds. Hyaluronan (HA)‐based hydrogel is one attractive biomaterial candidate because it is involved in natural healing processes, including inflammation, granulation, and reepithelialization. Herein, dynamic metal–ligand coordination bonds are used to fabricate moldable supramolecular HA hydrogels with self‐healing properties. To achieve reversible crosslinking of HA chains, the biopolymer is modified with pendant bisphosphonate (BP) ligands using carbodiimide coupling and chemoselective “click” reactions. Hydrogel is formed immediately after simple addition of silver (Ag+) ions to the solution of HA containing BP groups (HA‐BP). Compared with previous HA‐based wound healing hydrogels, the HA‐BP·Ag+ hydrogel is highly suitable for clinical use as it can fill irregularly shaped wound defects without the need for premolding. The HA‐BP·Ag+ hydrogel shows antimicrobial properties to both Gram‐positive and Gram‐negative bacterial strains, enabling prevention of infections in wound care. In vivo evaluation using a rat full‐thickness skin wound model shows significantly lower wound remaining rate and a thicker layer of regenerated epidermis as compared with the group left without treatment. The presented moldable and self‐healing supramolecular HA hydrogel with “ready‐to‐use” properties possesses a great potential for regenerative wound treatment.