Establishment of an Uncomplicated Radiation-delayed Wound Healing Model Using Irradiation in Pigs

Radiation-delayed wounds require diverse therapeutic strategies to achieve effective healing. However, the development of novel therapies with a radiation-delayed wound healing model is hindered by the lack of standardized animal models. In this study, the authors propose and verify a procedure to establish a radiation-delayed wound healing model in pigs. Two female pigs received a single 18-Gy dose of a 6-MeV electron beam per 18 cm x 8 cm area. Three areas were treated on the paraspinal dorsal skin surface of each pig, with 2 on the left side of the spine and 1 on the right. Wounds were periodically created on the 2 pigs at 1 of the following time points: (1) 2 weeks post radiation (PR2 group; n = 4), (2) 4 weeks post radiation (PR4 group; n = 4), and (3) 6 weeks post radiation (PR6 group; n = 4). A partial-thickness wound was created by excising the skin, superficial fat layer, and superficial fascia while preserving the deep fat and deep fascia. Wound contraction was evaluated, and histological analysis was performed at 2 and 4 weeks after wounding. The control wounds displayed complete reepithelialization at week 4. However, the PR6 group showed delayed wound healing for the entire experimental period. Furthermore, compared with the control group, the PR6 group demonstrated excessive acute and chronic inflammation and exhibited incomplete reepithelialization at week 4. These findings suggest skin wounding 6 weeks after irradiation is most suitable for the induction of a delayed wound healing model. Using this protocol, the authors safely generated a delayed wound healing model without acute complications from irradiation.