Interpenetrating Polymer Network Hydrogels Formed Using Antibiotics as a Dynamic Crosslinker for Treatment of Infected Wounds

Abstract Antibacterial hydrogels, particularly antibiotic‐loaded hydrogels, are promising wound dressing materials for treatment of bacteria‐infected wound. However, it is challenging to achieve sustained release of antibiotics from hydrogels through physical encapsulation of the antibiotics. Herein, an interpenetrating polymer network P(AA‐co‐HEMA)_Gen hydrogel is reported with double crosslinking formed by free radical polymerization of 2‐hydroxyethyl methacrylate (HEMA) and acrylic acid (AA), while using the antibiotic gentamicin (Gen) as the dynamic physical crosslinker. Gentamicin is incorporated into the hydrogel networks via electrostatic interaction between the carboxyl groups of poly(acrylic acid) and the amino groups of gentamicin, which leads to pH‐responsive drug release and a significant increase in mechanical strength (i.e., elastic modulus, viscous modulus, and compressive modulus). More importantly, the hydrogels with optimal compositions demonstrate long‐lasting antibacterial activity against both Gram‐positive bacteria (Staphylococcus aureus) and Gram‐negative bacteria (Escherichia coli) over 28 d. The in vivo studies that are conducted in an S. aureus‐infected full‐thickness skin wound model demonstrate that the double crosslinking hydrogels loaded with gentamicin eliminate bacteria in the wounds more effectively and significantly accelerate wound healing as compared to 3M dressing and the control without any treatment. Taken together, this antibiotic‐loaded interpenetrating polymer network hydrogel is potentially a promising wound dressing material for the treatment of bacteria‐infected wound.