Background: Radiation therapy is a mainstay in the treatment of many malignancies, but collateral damage to surrounding tissue, with resultant hypovascularity, fibrosis, and atrophy, can be difficult to reconstruct. Fat grafting has been shown to improve the quality of irradiated skin, but volume retention of the graft is significantly decreased. Deferoxamine (DFO) is an FDA-approved iron-chelating medication for acute iron intoxication and chronic iron overload that has also been shown to increase angiogenesis. Our study evaluated the effects of DFO treatment on irradiated skin and subsequent fat graft volume retention.
Methods: Mice underwent irradiation to the scalp followed by treatment with deferoxamine or saline injections and perfusion was analyzed using laser Doppler analysis (LDA). Similarly, a transdermal deferoxamine patch was developed to deliver DFO and perfusion studies were subsequently performed. Human fat grafts were then placed beneath the scalp and retention was also followed up to eight weeks radiographically. Finally, histologic evaluation and biomechanical testing of overlying skin was performed to evaluate effects of deferoxamine preconditioning.
Results: Treatment with DFO resulted in significantly increased perfusion, as demonstrated by LDA and CD31 immunofluorescent staining (*p < 0.05). This was observed with both DFO injection as well as transdermal DFO delivery. Importantly, fat graft volume retention was significantly increased when the irradiated recipient site was preconditioned with DFO (*p < 0.05). Finally, improved skin biomechanics with reduced stiffness was noted following DFO treatment.
Conclusions: Our results demonstrated increased perfusion with DFO treatment, which was also associated with improved fat graft volume retention. Preconditioning with DFO may thus enhance fat graft outcomes for soft tissue reconstruction following radiation therapy.

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