Scarless wound repair: a human fetal skin model

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Abstract
Animal studies demonstrate that the fetus heals cutaneous wounds by reformation of normal tissue architecture without scar formation. We have developed a new model to study human fetal skin wound healing. Grafts of human fetal skin placed onto athymie mice retain the morphologic features of normal development, although they differentiate at an accelerated rate when placed cutaneously compared to subcutaneously. Fullthickness skin grafts from human fetuses at 15 (n=12), 17 (n=ll), 18 (n=25), 19 (n=20) and 22 (n=13) weeks gestational age were placed onto athymie (nu/nu) mice in 2 locations: (1) cutaneously onto a fascial bed and thereby exposed to air or (2) subcutaneously in a pocket under the murine panniculus carnosus. Linear incisions were made in each graft 7 days after transplantation. Grafts were harvested at 7, 14 and 21 days postwounding and analyzed histologically for scar formation. By hematoxylin & eosin and Mallory’s trichrome stains, complete epidermal and dermal graft wound healing without scar formation was demonstrated in the subcutaneous grafts at each gestational age studied. In contrast, scar was seen at all time points in the cutaneous grafts in both the incisional wound and at the interface of the fetal human skin graft and adult mouse skin, regardless of fetal skin gestational age. Our results demonstrate that: (1) human fetal skin can heal without a scar in a subcutaneous adult environment; (2) scarless repair does not depend upon either perfusion by fetal serum or the unique amniotic fluid intrauterine environment; (3) in contrast to subcutaneous grafts, cutaneous grafts of 15, 17, 18, 19 and 22 week gestation fetal skin heal with scar.