Fast Self-Healing Hyaluronic Acid Hydrogel with a Double-Dynamic Network for Skin Wound Repair

Developing extracellular matrix-derived hydrogel with a fast self-healing capacity to provide a sustainable moist environment able to accelerate wound healing is highly desired for full-thickness skin wound repair. In this study, a fast self-healing hyaluronic acid hydrogel with a dual dynamic network was constructed through a primary reversible acylhydrazone bond formed between aldehyde-modified hyaluronic acid, 3,3'-dithiobis (propionyl hydrazide) (DTP), and secondary dynamic ionic interactions between κ-carrageenan (KC) and K⁺. Because of the presence of various dynamic covalent bonds such as the acylhydrazone bond, disulfide bond, and noncovalent bonds including hydrogen bonding and ionic interactions, as well as the notable thermoreversible nature of KC, the resultant hydrogel could be self-healed rapidly within 30 min under physiological temperature with a self-healing efficiency of 100%, which was significantly better than other hyaluronic acid hydrogels, as reported previously. Besides, the hydrogel displayed excellent cytocompatibility. According to this study, the hydrogel was administered into the wounds and achieved a superior performance of promoting full-thickness skin wound healing by increasing granulation tissue formation, deposition of collagen as well as the acceleration of re-epithelialization and neovascularization, compared to commercial products, e.g., gauze and 3 M hydrocolloid. We also anticipate that this strategy of double-dynamic network cross-linking can be adopted to fabricate self-healing materials for multiple applications.