A Novel Model for Cutaneous Wound Healing and Scarring in the Rat

Background: Current rodent models of wound healing and scarring are flawed because of rapid wound contraction and inconspicuous scarring after healing, which is not closely parallel to the physiologic process in humans. This study aimed to establish a novel model of wound healing and scarring in rats. Methods: Excisional wounds were generated in rat tail or dorsal skin and histologic changes and wound contraction were assessed 2, 10, and 16 days after injury. After healing, rat tail scar was investigated for 24 consecutive weeks by histologic and immunohistochemical staining. Finally, a stretched scar model was generated in rat tail with high or low strain after reepithelialization to mimic human hypertrophic scars. The tail hypertrophic scars were analyzed by histology, immunohistochemical staining, and mRNA quantification 0, 2, 6, 12, and 24 weeks after stretching. Results: Compared with the dorsal wounds, a larger dermal gap percentage (p < 0.05) and more pronounced granulation were found in rat tail wounds. Tail scars remained conspicuous and underwent maturation over 24 weeks after wound healing. In addition, high mechanical strain induced significantly increased scar area (p < 0.01), scar height (p < 0.05), vessel density (p < 0.01) and hypertrophic scar-related molecule expression, and distorted collagen arrangement in rat tail scars. Conclusions: The rat tail model exhibits minor wound contraction and biological features analogous to both normotrophic and hypertrophic scar in humans when generated with or without stretching, respectively. It is a promising new model for studies of both cutaneous wound healing and scarring.