^* A Rodent Excision Model for Ischemia-Impaired Wound Healing

Delayed wound healing and the potentially resulting chronic wounds are a challenging clinical problem. Available therapeutic strategies are limited in both number and efficacy. For developing and establishing novel treatment approaches appropriate clinically relevant animal models are essential. The aim of the study was to establish a reliable and reproducible delayed wound healing model, which simulates the clinical scenario of compromised vascular tissue perfusion (hypoxia/ischemia). Therefore a standard rodent ischemic flap model was modified by challenging the tissue with ascending degrees of ischemia using different surgical approaches (minimal, mild, moderate, and severe ischemic invasive approach). Then a full-thickness circular wound was excised in both the non-/hypoperfused flap area and in the normally perfused contralateral region serving as an internal control. Wound healing progress was compared. Superficial tissue perfusion was measured by Laser Doppler imaging technique, which showed persistent ischemia in the moderate and severe invasive surgical approaches 7 days after wounding. Wound closure assessed by planimetric analysis occurred significantly slower in the ischemic wounds compared to the contralateral nonischemic wounds in the moderate invasive approach. Histologic evaluations in this approach showed signs of tissue necrosis and impaired angiogenesis in the ischemic wounds. Therefore, it can be concluded that this clinically relevant animal model is suitable to study mechanism in ischemia-impaired wound healing. Furthermore, it allows evaluating the efficacy of therapeutic strategies for impaired wound healing and comparing the results with an internal control wound.