Establishment of a Hypertrophic Scar Model by Transplanting Full-Thickness Human Skin Grafts onto the Backs of Nude Mice

Background: Hypertrophic scarring is a pathologic hallmark of a previous dermal injury in humans, but many aspects related to its biology and therapy remain unclear, at least in part because of the lack of an ideal animal model. This study was designed to investigate whether hypertrophic scars could be reproduced by transplanting full-thickness human skin grafts onto the backs of nude mice. Methods: There were a total of five animal groups, with 15 nude mice each in groups 1 through 4 and five nude mice in the control group. The mice in groups 1 through 4 underwent transplantation of full-thickness human skin grafts onto their backs, and the status of local scar development was observed after the epidermis and upper portions of the dermis were shed. Histologic examination of the scar tissues was performed 1, 3, and 6 months after transplantation for groups 1, 2, and 3, respectively. Histologic examinations were not performed for group 4, but the duration of scar hypertrophy was assessed. Mice in the control group underwent transplantation of full-thickness rat skin grafts onto their backs, and the status of local scar development was observed after the epidermis and upper portions of the dermis were shed. Results: Fifty-four of 60 nude mice (90.0 percent) undergoing transplantation of full-thickness human skin grafts developed obvious and persistent hypertrophic scars, which were red, hard, and elevated out of the surrounding skin even 6 months after transplantation. Histologic examinations revealed abundant collagen deposition and inflammatory infiltration in these scars. Nevertheless, no hypertrophic scars were observed in mice transplanted with full-thickness rat skin grafts. Conclusions: The intrinsic properties of human skin are the determinant of hypertrophic scar formation. The hypertrophic scar model can be established by transplanting human skin grafts onto nude mice, resulting in obvious, persistent hypertrophic scars that have both macroscopic and histologic properties similar to human hypertrophic scars. This model makes possible the observation of the entire process of hypertrophic scar formation. Thus it is an ideal tool for studying hypertrophic scar.