Effects of insulin-like growth factor-I and insulin-like growth factor binding protein-1 on wound healing in a dermal ulcer model.

The effects on wound healing of insulin-like growth factor-I with and without insulin-like growth factor binding protein-1 were studied in a rabbit ear dermal ulcer model under both nonischemic and ischemic conditions. Wounds 6 mm in diameter were made on the ventral surface of rabbit ears for a total of 272 wounds in the nonischemic group and 77 wounds in the ischemic group. Insulin-like growth factor-I in varying doses (1 to 43 microg) and in combination with varying molar ratios of the binding protein were added at time of wounding to each wound. Wounds were analyzed histomorphometrically on day 7 after wounding. We found that insulin-like growth factor-I or binding protein alone at varying doses did not have any effects on wound healing parameters. Low to moderate doses (1 microg and 4 microg, respectively) of the combination of insulin-like growth factor-I with the binding protein in a molar ratio of 5:1 or 11:1 showed a 52% increase (p < 0.05) in new granulation tissue in the nonischemic model compared with controls but did not significantly augment new granulation tissue formation in the ischemic wound model. A high dose (43 microg) at a 10:1 molar ratio of growth factor to binding protein was required to elicit significantly enhanced wound healing in ischemic wounds. These results indicate that insulin-like growth factor binding protein-1 modulates the effects of insulin-like growth factor-I in promoting wound healing in vivo and that the combination is a highly effective vulnerary compound with effects comparable in magnitude with other growth factors previously tested in this model.