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Effects of External Volume Expansion in Irradiated Skin
Jorge Lujan-Hernandez, M.D., Michael S. Chin, M.D., Oksana O. Babchenko, Elizabeth Bannon, M.S., Heather Strom, M.A., Ronald Ignotz, Ph.D., Yuan-Chyuan Lo, Ph.D., Thomas J. Fitzgerald, M.D., Janice F. Lalikos, M.D..
University of Massachusetts, Worcester, MA, USA.

Introduction:
External Volume Expansion (EVE) treatment prepares breast reconstruction recipient sites for fat grafting. It has gained clinical popularity, but for patients receiving radiotherapy (XRT), results with EVE treatment vary. The reasons for sub-optimal effects of EVE on irradiated tissue have not been fully understood. Based on our previous work with both EVE and XRT, we developed a new translational model in the mouse to investigate the effects of EVE in chronic skin fibrosis after radiation exposure.
Methods:
Twenty-Eight SKH1-E mice received 50Gy of beta-radiation to each flank. Animals were monitored until chronic radiation fibrosis developed (8 weeks). EVE was then applied to one side for 6hrs on 5 consecutive days. The opposite side served as control. Hyperspectral Imaging (HSI) was used to assess perfusion changes before and after EVE. Mice were sacrificed at 5 days (n=14) and 15 days (n=14) after last EVE application for histological analysis. Tissue samples were stained for vascularity with IHC (CD31) and collagen composition was analyzed by scar index (Picro-Sirius red).
Results:
All animals developed skin fibrosis 8 weeks post-radiation, and changes in perfusion confirmed skin damage. EVE application induced edema on treated sides. Five days post-application, HSI showed both were hypo-perfused at comparison with pre-irradiation levels; with the EVE side 13% more ischemic than the untreated (p<0.001). Perfusion returned to control side levels by day 15. Collagen composition showed no difference in scar index analysis. Blood vessel density increased 21% by day 5 in EVE versus control.
Conclusion:
EVE temporarily augments radiation-induced hypo-perfusion, likely due to transient edema. Fibrosis remained unchanged after EVE, which did not affect collagen composition, possibly accounting for the limited expansion seen clinically in patients. However, pro-angiogenic EVE effects were maintained in irradiated tissues. This suggests that EVE still could positively influence the success of fat grafting in irradiated tissues.
Changes in skin perfusion per Hyper-Spectral Imaging


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