THE MECHANISM OF EXCISIONAL FETAL WOUND REPAIR IN-VITRO IS RESPONSIVETO GROWTH-FACTORS

We have investigated the ability of fetal rat skin to heal an excision al wound in, vitro. Skin from the backs of E17-E19 rats was wounded us ing a 1-mm diameter cutting needle and suspended in culture on a 6-pin cradle for 72 h. Neither contraction nor epithelial closure was obser ved within wounds created in skin from E19 embryos. In contrast, wound s in E17 skin contracted to 35-50% of their original area over 72 h, a lthough, in the absence of serum, complete wound closure was not obser ved. Addition of FBS at the time of culture resulted in the movement o f the epithelium over the dermal margins of the wound to effect comple te closure. Histological sections through these healed wounds revealed an epithelial bridge spanning the dermal margins of the wound. A simi lar mechanism of repair was observed in the presence of day 14 adult w ound fluid. The response of wounds in E17 skin to a range of growth fa ctors was then assessed in an attempt to reproduce the serum response under defined conditions. Insulin-like growth factor I or epidermal gr owth factor did not significantly affect wound closure. Basic fibrobla st growth factor, transforming growth factor-beta, or platelet-derived growth factor did promote wound closure although, in contrast to the serum-induced response, wound histology revealed repair had been achie ved by dermal fibroblasts that occupied the space between the epitheli al margins of the healed wound. We have therefore shown that the epith elial component of fetal wound repair proceeds in organ-cultured fetal skin in the absence of an adhesive substrate over which to migrate an d is dependent on the source of trophic factors. The inability of skin taken from the E19 embryo to heal in vitro suggests a developmental s witch in the mechanism of wound epithelialization.