This is a revised application to examine the efficacy of sequential application of two cytokines GM-CSF and bFGF on healing of chronic wounds in humans, compared to placebo or to each cytokine alone. The major hypothesis is that since GM-CSF and bFGF have each been shown to accelerate healing in animal models of impaired healing and appear to work during different phases of the healing process, sequential application will have an additive or synergistic effect to speed wound closure.
The first aim will test that hypothesis via a prospective, randomized, double blinded and placebo-controlled trial involving 80 patients with chronic pressure ulcers.
Aim 2 will be to determine endogenous wound levels of numerous cytokines and their receptors using RT/PCR and ELISA techniques at timepoints before, during and after completion of topical wound therapy, testing the secondary hypothesis that greater responses to sequential therapy will occur in wounds that are initially low in endogenous levels of GM-CSF and/or bFGF. An additional aim will examine the function of wound fibroblasts in contracting fibroblast-populated collagen lattices before any treatment, after the GM-CSF phase, and after completion of sequential therapy. Identical time points will be studied on wounds that receive a single cytokine. This last aim tests the hypothesis that 1) treatment with GM-CSF will increase the activity of wound fibroblasts and 2) this increased activity will be reflected in the ability of cultured fibroblasts to contract collagen lattices in vitro.
