An Electrospun Poly-Ethylene Oxide/Cerium (III) Nitrate Dressing for Delayed Debridement and Improved Wound Healing of Warfighter Contact Burns

Abstract

Introduction: Thermal burns account for 5-10% of casualties sustained in present-day conflicts and are expected to be one of the most common wounds to occur in future conflicts. Timely debridement of necrotic burn tissue can greatly reduce the chances of mortality and late-stage complications. However, future conflicts are anticipated to occur in austere environments where surgical debridement may not be plausible and casualty evacuations significantly delayed. Without access to prompt surgical interventions and standard treatment, burn wounds can progress (become deeper and more extensive) and become highly susceptible to infection. Several studies have demonstrated that topical applications of Cerium (III) Nitrate (Cen) can be used to delay the need for surgical eschar removal, a delay which may be forced upon injured warfighters in austere environments. The proof-of-concept studies described herein suggest that an electrospun dressing with a Polyethylene Oxide (PEO) shell and CeN core could prolong the time before surgical intervention is required and/or mitigate late-stage burn pathophysiologies in Prolonged Field Care (PFC) scenarios. Materials and Methods: Coaxially electrospun PEO dressings with a CeN payload were synthesized for application in a swine burn model. Dressings were first evaluated ex vivo using a Lactate Dehydrogenase (LDH) assay to confirm that no cytotoxic effects were present. Then, one female Yorkshire pig was anesthetized and received ten 5 cm x 5 cm contact burns with a brass burn device that was heated to 100°C. The deep-partial thickness wounds were randomly assigned to one of five treatment groups: 1) 1-Layer of the PEO/CeN dressing, 2) 4-Layers of the PEO/CeN dressing, 3) 4-layers of a control electrospun PEO dressing, 4) Flammacerium® cream (silver sulfadiazine 1%, cerium nitrate 2.2%), or 5) the PFC standard of care (SOC; gauze). Wounds were observed over an 18-day period, with surgical debridement occurring on Day 4 for all wounds. Transepidermal water loss, depth to debridement, and histologic measurements of necrosis were utilized to assess the burns. Research was conducted in compliance with the Animal Welfare Act, the implementing Animal Welfare regulations, and the principles of the Guide for the Care and Use of Laboratory Animals, National Research Council. The facility’s Institutional Animal Care and Use Committee approved all research conducted in this study. The facility where this research was conducted is fully accredited by AAALAC International. Experimental design and statistical comparisons were approved by an accredited epidemiologist and biostatistician. Results: The PEO/CeN dressings did not elicit a cytotoxic response ex vivo. Compared to the PFC SOC, treatments containing CeN reduced the amount of necrotic tissue produced by second-degree thermal injuries, as evidenced both histologically and in the depth required to reach viable tissue during surgical debridement. Importantly, the dressing did not adversely impact the live tissue surrounding the burn site. Conclusions: There are currently no field dressings that can delay the need for immediate debridement and thereby promote burn wound healing. This proof-of-concept study strongly suggests that the electrospun PEO/CeN dressing could fulfill this unmet medical need and advocates for further evaluation for use in imminent PFC scenarios.