The recalcitrance of bacterial biofilms to current antimicrobials has presented a major cause of clinical recurrence of wound infections. These biofilm-associated infections are often present in polymicrobial nature associated with the presence of Pseudomonas aeruginosa and Staphylococcus aureus creating a large heterogeneity that shares a common resistance to current antimicrobials making pathogen eradication extremely challenging. In this study, we overcome the intrinsic biofilm barriers by delivering ultrasmall-sized silver nanoparticles (AgNP) using a smart hydrogel system that allows slow and sustained release of silver ions mediating successful accumulation and penetration of bacterial biofilms. The antibiofilm efficacy of the AgNP hydrogel was assessed using ex vivo porcine wound polymicrobial biofilms. Treatment with AgNP hydrogel resulted in significant dispersion of early to mature biofilms, 2–5-log reduction of bacteria compared to untreated controls. This approach overcomes the enhanced tolerance and resistance of polymicrobial biofilms by using the combined benefits of smart delivery system and the antibiofilm properties of ultrasmall AgNPs to ensure biofilm complete destruction and elimination.

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