Transdermal Deferoxamine Enhances Wound Healing Of Frostbite Injury In A Mouse Model
Hendrik Lintel, BS, Darren B. Abbas, MD, Michelle Griffin, MBChB, PhD, Nick Guardino, BS, Amanda Spielman, BS, Jason L. Guo, PhD, Christopher V. Lavin, MS, Geoffrey C. Gurtner, MD, Michael T. Longaker, MD, MBA, Derrick C. Wan, MD.
Stanford University, Stanford, CA, USA.
PURPOSE: Frostbite injury occurs upon exposure of skin to extreme cold temperature. The resulting vasoconstriction and thrombosis leads to local tissue ischemia with intracellular ice crystal formation further contributing to cellular damage. Rewarming can lead to reperfusion injury via reactive oxygen species formation, further worsening the inflammatory cascade. Deferoxamine (DFO), an iron chelator, has been shown previously to improve vasculogenesis and reduce reactive oxygen species production when applied transcutaneously. In this study, we evaluated the effect of transdermal DFO on the healing of frostbite injury in mice. METHODS: Fifteen C57BL/6 mice were wounded on their dorsal skin through the ‘continuous freeze’ method of a previously described murine frostbite injury model (A). The mice were divided equally into three treatment groups: an untreated control, a vehicle-only patch, and a 1 mg/cm2 DFO-loaded patch with patches changed every two days after wounding. Following wounding, gross wound appearance was photographed and wound perfusion and skin elasticity were assessed via laser Doppler and Cutometer, respectively. Data analysis was done via one-way ANOVA to compare means between the treatment groups with statistical significance determined at p<0.05.
RESULTS: Frostbite wounds treated with DFO appeared to have a grossly improved wound healing rate with minimal eschar formation compared to controls (B). Laser doppler analysis demonstrated an increased perfusion index in DFO-treated wounds relative to the untreated and vehicle-only wounds throughout the healing process (C). Skin elasticity analysis revealed wounds treated with DFO also had a statistically significant improvement in skin elasticity from a comparable baseline compared to vehicle-only treated wounds throughout healing up to post-operative day 14 (POD14) (D).
CONCLUSION: Transdermal deferoxamine appears to improve wound healing in a murine model of frostbite demonstrated by accelerated healing rate and improved wound perfusion and thus presents an interesting potential therapeutic avenue for frostbite injury management.
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