Defining a model to predict the distribution of topically applied growth factors and other solutes in excisional full-thickness wounds

Controversy over the efficacy of many topical wound treatments, particularl y growth factors, is common, with many clinical practitioners still confuse d as to the real value of these agents. A serious lack of knowledge appears to exist concerning the diffusion and distribution of topically applied so lutes in wounds. Without this basic understanding there seems little chance of accurately predicting the therapeutic window of drugs targeted at cellu lar activities, such as division and chemotaxis, and processes, such as col lagen lattice deposition and contraction, occurring below the surface of th e granulating layer. This study was designed to determine the absorption an d distribution of a number of radiolabeled solutes (water, sodium chloride, lidocaine) and growth factors (basic fibroblast growth factor, epidermal g rowth factor) applied topically to full-thickness excisional wounds in rats during the early (2 d), mid (7 d), and late (12 d) stages of repair. Resul ts showed that water and sodium penetrated deepest into wound sites and tha t changes in water distribution and retention in the wound paralleled the h ealing process. Multiple stepwise regression showed that molecular weight a nd tissue depth, but not day of healing, were significant factors in predic ting the concentration of each solute in wound and underlying tissue sites. This finding was consistent with a tissue diffusion model developed in thi s study. Basic fibroblast growth factor and epidermal growth factor only pe netrated slightly into the upper granulating layers of the wound site, and calculation of therapeutic doses, based on the percentage of applied solute reaching the deeper granulating layers, is presented.