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Open Access 01-12-2022 | Ionizing Radiation | Research

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin

Authors: Hendrik Lintel, Darren B. Abbas, Christopher V. Lavin, Michelle Griffin, Jason L. Guo, Nicholas Guardino, Andrew Churukian, Geoffrey C. Gurtner, Arash Momeni, Michael T. Longaker, Derrick C. Wan

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

Background

Radiation-induced skin injury is a well-known risk factor for impaired wound healing. Over time, the deleterious effects of radiation on skin produce a fibrotic, hypovascular dermis poorly suited to wound healing. Despite increasing understanding of the underlying pathophysiology, therapeutic options remain elusive. Deferoxamine (DFO), an iron-chelating drug, has been shown in prior murine studies to ameliorate radiation-induced skin injury as well as improve wound healing outcomes in various pathologic conditions when administered transdermally. In this preclinical study, we evaluated the effects of deferoxamine on wound healing outcomes in chronically irradiated murine skin.

Methods

Wild-type mice received 30 Gy of irradiation to their dorsal skin and were left to develop chronic fibrosis. Stented excisional wounds were created on their dorsal skin. Wound healing outcomes were compared across 4 experimental conditions: DFO patch treatment, vehicle-only patch treatment, untreated irradiated wound, and untreated nonirradiated wounds. Gross closure rate, wound perfusion, scar elasticity, histology, and nitric oxide assays were compared across the conditions.

Results

Relative to vehicle and untreated irradiated wounds, DFO accelerated wound closure and reduced the frequency of healing failure in irradiated wounds. DFO augmented wound perfusion throughout healing and upregulated angiogenesis to levels observed in nonirradiated wounds. Histology revealed DFO increased wound thickness, collagen density, and improved collagen fiber organization to more closely resemble nonirradiated wounds, likely contributing to the observed improved scar elasticity. Lastly, DFO upregulated inducible nitric oxide synthase and increased nitric oxide production in early healing wounds.

Conclusion

Deferoxamine treatment presents a potential therapeutic avenue through which to target impaired wound healing in patients following radiotherapy.

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Title: Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin
Authors: Hendrik Lintel
Darren B. Abbas
Christopher V. Lavin
Michelle Griffin
Jason L. Guo
Nicholas Guardino
Andrew Churukian
Geoffrey C. Gurtner
Arash Momeni
Michael T. Longaker
Derrick C. Wan
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Ionizing Radiation
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-022-03479-4

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Abstract

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