Physicians have long been calling for an inherent antimicrobial wound dressing, which will be a great progress for treating complicated infections. Here, we report a novel bioadhesive hydrogel with inherent antibacterial properties prepared by mixing modified hyaluronic acid (HA) and ε-polylysine (EPL). This hydrogel can effectively kill Gram (+) and (−) bacteria for its high positive charge density on the surface. The sol−gel transition occurs within seconds via horseradish peroxidase enzymatic crosslinking and Schiff base reaction, which also allows the hydrogel to recover completely from destruction quickly within 5 min. In an infected rat wound model, histological studies indicated that the hydrogels effectively killed bacteria on the surface of wounds and accelerated wound healing. Histological analysis indicated that the thickness of the newborn skin, the density of the newborn microvascular, granulation tissue, and the collagen of rats treated with hydrogel dressings were twice as high as those treated by commercial fibrin glue. These results indicate that the HA/EPL hydrogel has great potential as an antibacterial wound dressing for future clinical applications.

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