Development of a chronic skin defect model and a study of cytokine secretion using the model

In this study, we established a delayed healing chronic type wound model in order to investigate the etiology of chronic wound healing, including wound contraction. Establishment of the model was important for clarification of the mechanism(s) of chronic wound healing and wound contraction and for use in evaluating therapeutic efficacy. A pedicled skin flap was raised beneath the panniculus carnosus membrane on the backs of mice, and after the loose connective tissue at the base of the flap was completely removed surgically, the flap was replaced and sutured. Seven days after surgery, a full-thickness defect measuring 1.5 x 1.5 cm was made in the center of the skin flap. At that time, a defect of the same size, including the panniculus carnosus membrane, was made in another group of mice as controls, and changes with time in wound area were compared between the two groups. The exudate retained on the wound surface was collected, and various cytokines contained in the exudate were measured. In the control group, the wound rapidly contracted and almost completely epithelialized and closed 21 days after surgery. On the other hand, the wound area was significantly larger in the delayed model than in the control animals during the observation period, revealing a delay in wound contraction. Transforming growth factor-beta, interleukin-1beta, and tumor necrosis factor-alpha in the exudates from the wound of the model were significantly higher than in those of the control group, whereas interleukin-6 was low in the model. From these results, it was concluded that this model could be a useful experimental system for studies on wound contraction as well as clarifying the mechanism of so called chronic type wounds.