HUMAN WOUND FLUID FROM ACUTE WOUNDS STIMULATES FIBROBLAST AND ENDOTHELIAL-CELL GROWTH

One proposed mechanism for the beneficial effect of occlusive dressings on healing is the maintenance of contact between the wound bed and accumulated wound fluid, which is thought to contain growth stimulatory substances. We have examined the effect of human wound fluid on the in vitro growth of human dermal fibroblasts and umbilical vein endothelial cells. Acute wound fluid was collected from six patients undergoing split-thickness skin grafting. The acute wound fluid was sterilely collected daily from underneath a vapor-permeable membrane applied to the donor site and changed every 24 hours for 3 days postoperatively. After seeding in optimal growth media (control) on day 0, cultures of human dermal fibroblasts and umbilical vein endothelial cells were supplemented with or without acute wound fluid on the next day (day 1) and on day 3. As determined by cell counts, 2% acute wound fluid stimulated the growth of human dermal fibroblasts (p < 0.05) and umbilical vein endothelial cells (p < 0.01 ) when these cells were cultured in 2% fetal bovine serum and endothelial growth medium, respectively. Wound fluid from postoperative days 1 or 3 caused the same level of stimulation. The addition of an anti-platelet-derived growth factor antibody to wound fluid resulted in a 45% mean reduction in its stimulatory effect on fibroblast growth (p < 0.02), suggesting that platelet-derived growth factor contributes to the observed effect. Acute wound fluid enriched for factors with molecular weights greater than 25 kd caused 30% less growth stimulation than the undialyzed fraction, suggesting that stimulatory factors other than platelet-derived growth factor heterodimers or homodimers (28 to 35 kd) are also involved. We conclude that acute wound fluid stimulates cell growth. The beneficial effect of occlusive dressings may be due in part to the maintenance of contact between the wound and various mitogenic factors, including platelet-derived growth factor or platelet-derived growth factor-like peptides, contained in the wound fluid.