title: The mechanism of excisional fetal wound repair in vitro is responsive to growth factors.
abstract: We have investigated the ability of fetal rat skin to heal an excisional wound in vitro. Skin from the backs of E17-E19 rats was wounded using a 1-mm diameter cutting needle and suspended in culture on a 6-pin cradle for 72 h. Neither contraction nor epithelial closure was observed within wounds created in skin from E19 embryos. In contrast, wounds in E17 skin contracted to 35-50% of their original area over 72 h, although, in the absence of serum, complete wound closure was not observed. Addition of FBS at the time of culture resulted in the movement of the epithelium over the dermal margins of the wound to effect complete closure. Histological sections through these healed wounds revealed an epithelial bridge spanning the dermal margins of the wound. A similar mechanism of repair was observed in the presence of day 14 adult wound fluid. The response of wounds in E17 skin to a range of growth factors was then assessed in an attempt to reproduce the serum response under defined conditions. Insulin-like growth factor I or epidermal growth factor did not significantly affect wound closure. Basic fibroblast 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 achieved by dermal fibroblasts that occupied the space between the epithelial margins of the healed wound. We have therefore shown that the epithelial component of fetal wound repair proceeds in organ-cultured fetal skin in the absence of an adhesive substrate over which to migrate and is dependent on the source of trophic factors. The inability of skin taken from the E19 embryo to heal in vitro suggests a developmental switch in the mechanism of wound epithelialization.
authors.affiliation: Cooperative Research Centre for Tissue Growth and Repair, Child Health Research Institute, Woman's and Children's Hospital, North Adelaide, Australia. david.belford@dhn.csiro.au
authors.forename: D A
authors.initials: DA
authors.lastname: Belford
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001769:Blood; D003470:Culture Media; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005865:Gestational Age; D006133:Growth Substances / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009924:Organ Culture Techniques; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011247:Pregnancy; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000196:embryology* / Q000293:injuries*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing
chemical_list: D003470:Culture Media; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I