(LR-051) Pre-clinical In vitro, Ex vivo and In vivo Evaluation of a Copper-based Antimicrobial Wound Dressing for Burns

Tricia Conti, MS – iFyber, LLC; Mehmet Ozturk, PhD – iFyber, LLC; Fahimeh Tabatabai, PhD – iFyber, LLC; Michael Solis, BS – University of Miami; Joel Gil, MS – University of Miami; Alexander Higa, BS – University of Miami; Stephen Davis, BS – University of Miami

Introduction: The use of copper as an antimicrobial dates back to ca. 2600-2200 BC in ancient writings involving the use of copper in wounds and to sanitize drinking water. Despite this longstanding knowledge of the interaction of copper-containing materials and the microbial world, few products have emerged to combat wound infections. Currently, there are only two 510(k) cleared copper-based wound care dressings by the FDA. Reported here is a detailed pre-clinical study of a new copper-based antimicrobial hydrogel wound dressing intended for the treatment of burn wounds.

Methods: A copper-based antimicrobial wound dressing technology for burns is presented. In vitro and in vivo pre-clinical models were used to assess both the antimicrobial properties of the dressing as well as its cytotoxicity potential and wound healing capabilities. Antimicrobial assays were conducted against 3 Gram positive and 3 Gram negative bacteria, yeast, and mold, in vitro, as well as a viable human ex vivo skin model of acute wounds . Finally, a three-degree burn model in pigs was used to study wound healing and clearing of a Methicillin-resistant Staphylococcus aureus (MRSA) infection.

Results: Prototype copper-based burn dressings exhibited >4-log reduction for microbes studied, in vitro, and showed significantly (p≤0.05) greater efficacy relative to two commercial wound dressings. Results from 3D human dermal tissue explant testing indicate that the copper dressings exhibit a 6 log reduction in biofilm formation and support reformation of an epithelium. Copper also appears to upregulate the expression of important human cytokines such as MIP-1a/MIP-1b and TIM-3, VCAM-1, and ENA-78. Finally, results from a 10-animal wound study (infected and non-infected) show significant (p≤0.05) reduction in MRSA by the copper dressings relative to controls. Both infected and non-infected wounds treated with the copper exhibited an enhanced rate of healing compared to controls as evidenced by the increase in percent epithelialization and granulation tissue formation at day 6, 10 and 14.

Discussion: The copper coated fibers within the dressings provided high antimicrobial activity in vitro, ex vivo, and in vivo, with the added benefit of upregulating pro-wound healing markers in an ex vivo viable human tissue assay. The dressings also exhibited important anti-biofilm properties, in vivo, and enhanced rate of wound healing relative to controls. Collectively, these results highlight copper – one of 25 elements essential to life – as an alternative to the current standards of care in antimicrobial wound care.