D. B. Abbas1, M. B. Griffin2, C. V. Lavin2, N. J. Guardino2, E. J. Fahy2, C. E. Berry2, H. Lintel2, J. L. Guo2, L. Kameni2, G. C. Gurtner3, M. T. Longaker2, D. C. Wan2 1Mayo Clinic, Department Of Surgery, Rochester, MN, USA 2Stanford University, Division Of Plastic And Reconstructive Surgery, Palo Alto, CA, USA 3University Of Arizona, Department Of Surgery, Tucson, AZ, USA
Introduction: Deferoxamine treatment has been shown to be a safe and effective therapy to mitigate radiation fibrosis in both small and large animal studies. Therapeutic dosages have not been well-established with deferoxamine yet. With this study, we aim to determine if these effects are dose dependent.
Methods: Six red Duroc pigs (three months old) were irradiated with a single fraction of 30 Gy bilaterally. The pigs were allowed to recover for 12 weeks to allow chronic fibrosis to develop. The pigs were divided into 5 different treatment conditions: normal skin, irradiated skin with no patch (IR control), 0.5mg patch, and 1.0mg patch, and 2.0mg patch(A). The pigs were treated with daily patch changes for 4 weeks following recovery. Biopsies were obtained following 4 weeks of treatment. The pigs were then harvested after 8 total weeks of treatment. Throughout the treatment period, in vivo skin elasticity measuremetns were performed weekly with a suction cutometer device until the pigs were harvested.
Results: Dermal thickness was noted to be significantly lower in the 1 and 2mg cohort than the IR control or 0.5mg cohort at both 16- and 20-weeks post-wounding (B). Collagen ultrastructure displayed that 1 and 2mg DFO treatment groups more closely resembled normal skin groups compared to the control or 0.5mg patch groups. (C). Collagen density was also significantly lower in the 1 and 2 mg DFO cohort compared to 0.5mg or IR control groups (D). CD31+ expression was significantly higher in the 1 and 2mg DFO group compared to all other conditions except the normal skin (E). At 16 weeks post-radiation, the 1mg patch condition was significantly more elastic than the 0.5 and 2mg patch conditions. However, by 20 weeks post-radiation, the elasticity of the 1 and 2mg patch conditions equalized, while maintaining significantly improved elasticity than the 0.5mg patch (F).
Conclusion: 1 and 2 mg DFO patches significantly improve radiation fibrosis compared to the 0.5mg patch.
