An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy

Purpose: To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury.Methods: A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software.Results: No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.Conclusions: We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.