Transdermal Deferoxamine Improves Excisional Wound Healing In Chronically Irradiated Murine Skin
Hendrik Lintel, BS, Darren B. Abbas, MD, Nick Guardino, BS, Amanda Spielman, BS, Michelle Griffin, MBChB, PhD, 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: Radiation-induced fibrosis is a common chronic sequelae of radiation therapy. Chronic radiation dermatitis is characterized by a hypovascular dermis and a fibrotic state which presents many clinical challenges to healthcare providers, including impaired wound healing. Transdermal deferoxamine (DFO), an iron chelator, has been shown to mitigate radiation-induced skin fibrosis in mice through improved angiogenesis and a reduction in reactive oxygen species production. In this study, we aim to investigate the effects of DFO on excisional wound healing in chronically irradiated skin in a mouse model.
METHODS: Thirty C57BL/6 mice had their dorsal skin irradiated with 30 Gy fractionated over 6 doses of 5 Gy every other day. After waiting 4 weeks post-radiation to allow for the development of chronic fibrosis, two 5mm excisional wounds were created and stented open on the irradiated dorsum of each mouse. The mice were equally divided into 3 groups: an irradiated (IR) control, a vehicle-only patch, and a 1 mg/cm2 DFO-loaded patch. Every two days, patches and dressings were changed, wounds were photographed, and wound perfusion was assessed via laser Doppler until wound closure. Data analysis was done via one-way ANOVA to compare means between the treatment groups with statistical significance determined at p<0.05.
RESULTS: DFO-treated mice grossly demonstrated faster wound closure rates than the vehicle and IR control groups (A). Laser Doppler analysis also revealed increased perfusion in the DFO-treated wounds throughout the wound healing process (B-C). In particular, DFO-treated wounds were found to reach a statistically significant higher perfusion index than vehicle-only patch and IR control wounds at post-operative day 14 (POD14) (D).
CONCLUSION: Transdermal DFO demonstrates potential as a treatment modality to improve wound healing outcomes in chronically irradiated skin due to the advanced wound closure rate and elevated perfusion index noted in this study.
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