^{A Rodent Excision Model for Ischemia-Impaired Wound Healing}

Abstract

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.

Animal experimental models of ischemic wounds – A review of literature

“…A rat study by Gould et al, 15 Moor et al, 16 Trujillo et al 21 and Hofmann et al 23 brought the possibility of testing various treatment methods in the ischemic and control areas of one animal.…”

“…(A–D) Creation of circular full‐thickness wounds (1.5 cm) on the ischemic and non‐ischemic side. Adapted from Hofmann et al 23 …”

“…This model was also used by Tur et al 25 in order to investigate the effects of hydrogen peroxide cream on ischemic wound healing. The Adapted from Hofmann et al 23 ischemic time was reduced from 24 to 7 h as described by Constantine and Bolton. 24 They compared a group treated with hydrogen peroxide cream to a group treated with a placebo.…”

“…Four surgical approaches carried out on the abdomens of the rats were examined by Hofmann et al 23 in order to find a reliable and reproducible ischemic model of delayed wound healing. A minimally invasive model was created through ligation and dissection of the inferior epigastric bundle in the right inguinal region (Figure 4A).…”

Comparison and Evaluation of Seven Animal Models of Ischemic Skin Wound: A Review Article

“…The most popular is an H-shaped cutaneous flap model developed by Quirinia et al [150]. The technique has been modified numerous times since then and is still commonly used for ischemic wound studies not only in rats but also in other animals [151,152,153]. Several problems have been reported for this model.…”