To investigate the antibacterial effect of augmenting a biological dressing with polymer films containing silver nanoparticles. Biological dressings, such as Biobrane, are commonly used for treating partial-thickness wounds and burn injuries. Biological dressings have several advantages over traditional wound dressings. However, as many as 19% of wounds treated with Biobrane become infected, and, once infected, the Biobrane must be removed and a traditional dressing approach should be employed. Silver is a commonly used antimicrobial in wound care products, but current technology uses cytotoxic concentrations of silver in these dressings. We have developed a novel and facile technology that allows immobilization of bioactive molecules on the surfaces of soft materials, demonstrated here by augmentation of Biobrane with nanoparticulate silver. Surfaces modified with nanometer-thick polyelectrolyte multilayers (PEMs) impregnated with silver nanoparticles have been shown previously to result in in vitro antibacterial activity against Staphylococcus epidermidis at loadings of silver that are noncytotoxic. We demonstrated that silver-impregnated PEMs can be nondestructively immobilized onto the surface of Biobrane (Biobrane-Ag) and determined the in vitro antibacterial activity of Biobrane-Ag with Staphylococcus aureus. In this study, we used an in vivo wound infection model in mice induced by topical inoculation of S aureus onto full-thickness 6-mm diameter wounds. After 72 hours, bacterial quantification was performed. Wounds treated with Biobrane-Ag had significantly (P < 0.001) fewer colony-forming units than wounds treated with unmodified Biobrane (more than 4 log10 difference). The results of our study indicate that immobilizing silver-impregnated PEMs on the wound-contact surface of Biobrane significantly reduces bacterial bioburden in full-thickness murine skin wounds. Further research will investigate whether this construct can be considered for human use.