526 Non-Cytotoxic Ultrathin Antimicrobial Hydrogel Dressings Containing Ionic and Metallic Silver

Abstract

Preventing wound infections is a major unresolved healthcare challenge. More than 2.1 million U.S. patients seek treatment for burns annually. These wounds, when infected, do not progress through the normal healing process. To address this problem, we have developed an ultrathin microfilm dressing that delivers a non-cytotoxic, yet effective dose of antimicrobial silver ions to the wound bed. Microfilms were fabricated as polyvinyl alcohol hydrogel sheets coated with a polymeric nanofilm containing 0.1 mg/in2 of ionic and metallic silver. In contrast, commercial antimicrobial dressings Aquacel® Ag, Acticoat® and Silverlon® contain 1.2, 16.1 and 54.6 mg/in2 of silver, respectively. Cytotoxicity of microfilms was compared to that of Aquacel Ag and Silverlon using MTT cytotoxicity assay. Release of silver from these dressings over 3 days in a simulated wound fluid was also characterized. An ISO 22196-compliant study was used to measure in-vitro antimicrobial activity. A porcine wound healing study evaluated local tissue response and wound healing characteristics following repeated application of microfilm to partial-thickness wounds over 14 days. Furthermore, porcine wound colonization studies were conducted to evaluate antimicrobial activity of microfilm in wounds contaminated with 103 CFU P. aeruginosa over 5 days post-surgery. Microfilms were non-cytotoxic whereas Aquacel Ag and Silverlon were cytotoxic. This was consistent with up to 10x lower release of silver ions from microfilms. In vitro, microfilms reduced 5 Log10 units of bacterial loads, including MRSA and VRE, on their surface for >3 days. The porcine wound healing study concluded that materials of microfilms had no significant effect on epithelial growth, granulation tissue formation, critical cellular responses, or acute inflammation following multiple applications until complete wound closure. Contaminated porcine wounds treated with Telfa pads (control) had robust P. aeruginosa colonization of >105 CFU/wound, while those treated with microfilm or Acticoat had significantly less (>2 Log10 lower) bacterial burden. The difference between the CFU in microfilm and Acticoat groups was insignificant. Our antimicrobial microfilm dressing is a pioneering advance because it is effective in clearing microbial burden in wounds without causing cytotoxicity, which is in stark contrast to conventional antimicrobial dressings. Microfilms are applied to wound with each bandage change followed by longer intervals as the wounds heal. Microfilm conform intimately to the wound bed where it reduces bacterial load thus allowing normal wound healing. Microfilms slough off as wounds heal or rinsed off with saline at bandage changes.