Growth factor technology may be beneficial in wound management, but many growth factors have little effect on recruitment or activation of inflammatory cells. Thus, these factors may have minimal efficacy in contaminated wounds. Thrombin is a natural early initiator of cellular responses to injury causing vascular changes and chemotactic and mitogenic effects on inflammatory cells. A single topical application of thrombin or synthetic thrombin receptor-activating peptide (TRAP-508) accelerates healing of surgical incisions by up to 80 percent (1,2), and enhances closure of open wounds 50 - 100 percent relative to controls (3). Histology indicates an early transient accumulation of inflammatory cells in TRAP-508-treated wounds suggesting possible efficacy in reducing wound infection. The potential of TRAP-508 to activate cellular antimicrobial effects will be determined using 1) polyvinyl alcohol(PVA) sponge implants with or without TRAP-508 in rats with controlled infections, 2) assessment of in vitro and in vivo bactericidal activity of cells recruited into sponges, and 3) analysis of TRAP-508 activation of neutrophils to release superoxides and myeloperoxidase into wound fluid. These studies will determine the potential for development of TRAP-508 products to accelerate healing and reduce infection in acute and chronic wounds.
