Dynamic covalent constructed self-healing hydrogel for sequential delivery of antibacterial agent and growth factor in wound healing

Abstract

The conventional injectable hydrogels as wound dressing materials frequently encounter bacterial infection and lack self-healing ability. Besides, the hydrogels injected into the irregular wound sites are easily damaged by external forces, which further hinder wound healing. To make up for these deficiencies, we developed a novel hydrogel with the unique properties including dynamic covalent based self-healing, antibacterial and sequential drug release. This injectable and self-healing hydrogel was constructed via the dynamic reaction of aminated gelatin (NGel), adipic acid dihydrazide (ADH) and oxidized dextran (ODex). After injection or damage, the broken hydrogel pieces performed excellent self-healing capability to generate an integral hydrogel owing to dynamic imine and acylhydrazone bonds. Meanwhile, bFGF@PLGA microspheres and chlorhexidine acetate (CHA) were embedded into the hydrogels. This bFGF@PLGA/CHA/hydrogel presented a good biodegradability, and it could retain the morphological stability after swelling. Moreover, bFGF@PLGA/CHA/hydrogels achieved the sequential release of CHA and bFGF during the drug release assay. When topically applied onto the wound skin of rats, the hydrogels can effectively prevent infection at the early stages due to the rapid release of CHA, then further accelerate cell proliferation and wound healing through the sustained release of bFGF. These results indicate that the proposed self-healing hydrogel with sequential release properties is a highly promising dressing material for wound healing.