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 pO2 (p(ti)O2), 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)O2 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.