Development of a Radiotherapy-Induced Wound Model in Wistar Rats: Simulating Post-Radiation Skin and Soft Tissue Complications for Therapeutic Evaluation

<b>Background/Objectives</b>: Radiotherapy can severely impair skin and soft tissue healing, particularly when high doses or subsequent surgical interventions are involved. Robust experimental platforms that replicate clinically relevant radiation-impaired wound healing remain limited. This study aims to establish a reproducible experimental model for radiation-induced cutaneous injury using contemporary clinical radiotherapy techniques. <b>Methods</b>: A Wistar rat model was developed using single-dose external beam irradiation delivered by clinical-grade volumetric modulated arc therapy (VMAT; 6 MV FFF), at doses of 20 Gy or 30 Gy. Animals were distributed in five distinct groups: G1-control, G2-20 Gy irradiation only, G3-20 Gy irradiation followed by excision, G4-excision only, G5-30 Gy irradiation only. Standardized full-thickness skin excision (1.5 × 1.5 cm) was performed one-week post-irradiation to simulate surgical intervention in pre-irradiated tissue. Animals were monitored for up to 42 days, through skin damage macroscopic scoring, body weight, hematological and biochemical parameters, and a qualitative histological exam. <b>Results</b>: Single-dose irradiation with 20 Gy induced moderate, self-limiting radiation dermatitis with complete healing. When combined with delayed excision, 20 Gy irradiation resulted in more severe and prolonged wound healing impairment, and transient systemic alterations. Excision alone produced controlled wounds with predictable healing. Exploratory observations following 30 Gy irradiation revealed severe cutaneous injury and marked systemic involvement, with a high mortality rate. <b>Conclusions</b>: This study establishes a foundational model for radiation-impaired wound healing using clinical-grade VMAT delivery and standardized delayed excision. The 20 Gy-based protocols provide an ethically sustainable and experimentally tractable platform for future mechanistic and therapeutic studies.