Acceleration of full-thickness wound healing in normal rats by the synthetic thrombin peptide, TP508

Thrombin is an essential factor in hemostasis, inflammation, and tissue rep air. The synthetic thrombin peptide, TP508, binds to high-affinity thrombin receptors and mimics cellular effects of thrombin at sites of tissue injur y. Treatment of full-thickness excisional wounds in normal rats with a sing le topical application of 0.1 mu g TP508 (14 pmol/cm(2)) reproducibly accel erates wound closure, yielding wounds that on average close 39% more than c ontrols by day 7 (p < 0.001). Wounds treated with 1.0 mu g TP508 are 35% an d 43% (p < 0.001) smaller than controls on day 7 and 10, respectively. The early rate of closure is similar to 40% greater in TP508-treated than vehic le-treated wounds (20 versus 14 mm(2)/day) and remains higher through day 7 . Breaking strength after closure is slightly greater (15-23%) in wounds tr eated with TP508 than with saline alone. Histologic comparisons show that T P508 enhances recruitment of inflammatory cells to the wound site within 24 hours post-injury. TP508 treatment also augments revascularization of inju red tissue, as evidenced at day 7 by the larger size of functional vessels in the granulation tissue and by the directed development of blood vessels to wounds. These studies raise the possibility that TP508 may be clinically useful in management of open wounds.