A multifunctional hydrogel dressing loaded with antibiotics for healing of infected wound

Abstract

Wound bacterial infections can significantly delay the healing process and even lead to fetal sepsis. There is a need for multifunctional dressings that possess antibacterial property, tissue adhesive property, self-healing capability, and biocompatibility to effectively treat bacteria-infected wound. In this study, we report a dual dynamically crosslinked hydrogel, OHA-PBA/PVA/Gen, which incorporates the antibiotic gentamicin (Gen) as a dynamic crosslinker. The hydrogel is formed through the formation of Schiff base bonds between phenylboronic acid-grafted oxidized hyaluronic acid (OHA-PBA) and Gen, as well as boronic acid ester bonds between OHA-PBA and polyvinyl alcohol (PVA). This unique composition imparts tissue adhesiveness, injectability and self-healing property to the hydrogel. The hydrogel also exhibits pH-responsive antibiotic release behavior due to the acid-responsive dissociation of Schiff base bonds. As a result, it demonstrates strong antibacterial activity against both Gram-positive bacteria S. aureus and Gram-negative bacteria E. coli through contact killing and diffusion killing mechanisms. Importantly, the OHA-PBA/PVA/Gen hydrogel avoids incorporation of toxic small molecular crosslinking agents, and all the components of the hydrogel are biocompatible, ensuring its biosafety. In a S. aureus-infected wound mouse model, this hydrogel effectively eradicated bacteria and promoted angiogenesis, leading to significantly accelerated wound healing. These results highlight the potential of the dual dynamically crosslinking hydrogel OHA-PBA/PVA/Gen as a multifunctional wound dressing for the treatment of bacteria-infected wound.