Antimicrobial hydrogel foam dressing with controlled release of gallium maltolate for infection control in chronic wounds

Effective treatment of infection in chronic wounds is critical to improve patient outcomes and prevent severe complications, including systemic infections, increased morbidity, and amputations. Current treatments, including antibiotic administration and antimicrobial dressings, are challenged by the increasing prevalence of antibiotic resistance and patients' sensitivity to the delivered agents. Previous studies have demonstrated the potential of a new antimicrobial agent, Gallium maltolate (GaM); however, the high burst release from the GaM-loaded hydrogel gauze required frequent dressing changes. To address this need, we developed a hydrogel foam-based wound dressing with GaM-loaded microspheres for sustained infection control. First, the minimal inhibitory and bactericidal concentrations (MIC and MBC) of GaM against two <i>Staphylococcus aureus</i> strains isolated from chronic wounds were identified. No significant adverse effects of GaM on dermal fibroblasts were shown at the MIC, indicating an acceptable selectivity index. For the sustained release of GaM, electrospraying was employed to fabricate microspheres with different release kinetics. Systematic investigation of loading and microsphere size on release kinetics indicated that the larger microsphere size and lower GaM loading resulted in a sustained GaM release profile over the target 5 days. Evaluation of the GaM-loaded hydrogel dressing demonstrated cytocompatibility and antibacterial activities with a zone of inhibition test. An equine distal limb wound model was developed and utilized to demonstrate the efficacy of GaM-loaded hydrogel foam <i>in vivo</i>. This antimicrobial hydrogel foam dressing displayed the potential to combat methicillin-resistant <i>S. aureus</i> (MRSA) infection with controlled GaM release to improve chronic wound healing.