Deferoxamine Preconditioning of Irradiated Tissue Increases Fat Graft Volume Retention
John Flacco, BS, Dre Irizarry, MD, Charles Blackshear, MD, Geoffrey Gurtner, MD, Michael Longaker, MD, PhD, Derrick Wan, MD.
Stanford University, Stanford, CA, USA.
Purpose.Hypovascularity due to irradiation therapy causes the skin to become fibrotic and causes soft tissue to atrophy. Fat grafting has been shown to improve the quality of irradiated skin, but volume retention of the graft is significantly decreased. Deferoxamine is an FDA-approved iron-chelating medication, that has been shown to increase angiogenesis. Preconditioning of irradiated sites with this compound may reduce radiation induced ischemia and enhance fat graft survival. Methods.Immunocompromised nude-mice underwent external beam irradiation of the scalp. Five weeks later, mice either received seven deferoxamine treatments (1mg in 100ul) or saline subcutaneously to the irradiated area every other day. Laser Doppler analysis (LDA) was recorded prior to irradiation, following irradiation, and 24 hours following each treatment. Human fat grafts were then injected in the subcutaneous plane of the scalp and volume retention measured by CT scan over 8 weeks. Finally, skin and fat samples were evaluated histologically for vasculature, dermal thickness, and fat graft quality.Results.After 4 treatments with deferoxamine, a significant increase in microvasculature was observed using LDA.There was also significance with the development of microvasculature in the fat graft with LDA. Using microCT, we observed a significant increase in fat graft volume retention with the deferoxamine treated group compared to the saline treated group, and this was paralleled by improved histologic staining of skin and fat grafts. Conclusion.Our results show increased microvasculature and increased fat graft volume retention with deferoxamine treatment. Deferoxamine treatment may also promote beneficial effects in dermal thickness and in quality scoring of the fat grafts, thus leading to a potential clinical application in radiation damaged soft tissue.
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