Experimental ischemic wounds: Correlation of cell proliferation and insulin‐like growth factor I expression and its modification by different local IGF‐I release systems

We investigated cell proliferation and local insulin‐like growth factor‐I (IGF‐I) expression in ischemic wounds after topical application of IGF‐I through different delivery systems. IGF‐I dressings were fabricated from an IGF‐I containing polyvinyl alcohol film placed on a standard hydrogel dressing. In vitro, the release of IGF‐I from this dressing was assessed by enzyme‐linked immunosorbent assay. For animal experiments, a standardized ischemic skin flap containing a full‐thickness wound was created on the back of male Sprague‐Dawley rats. An identical wound outside the flap served as control. We initially investigated intracutaneous pO 2 (p ti O 2 ), cell proliferation, and local IGF‐I expression. In a second setting, wounds were treated either with IGF‐I dissolved in methylcellulose gel or with an IGF‐I dressing, and ulcer size and cell proliferation were assessed. In vitro, approximately 60% of IGF‐I was released from the IGF‐I dressing, compared to a 97% release from methylcellulose gel. In vivo, ischemic wounds showed less cell proliferation and decreased IGF‐I expression than nonischemic wounds. A lower local p ti O 2 correlated with larger wound size, less cell proliferation, and decreased IGF‐I expression. Ulcer size was reduced after treatment with either IGF‐I dressing or methylcellulose gel. However, cell proliferation only increased after treatment with IGF‐I dressing, but not after methylcellulose gel treatment. We conclude that IGF‐I expression is decreased in ischemic wounds and correlates with low cell proliferation. This can be reversed by local IGF‐I application, but the efficacy of treatment depends on the delivery system.