Establishment Of Of Hypertrophic Scar Model And Dynamical Experimental Study On Its Development

Hypertrophic scar formation remains the major problem for severely burned patients who survive their injuries. This scarring can result in both cosmetic and functional deformities. One of the major problems in dealing with this complication is the lack of an adequate animal model with which to test various possible therapeutic modalities.We had attempted to establish an animal model of hypertrophic scarring by transplanting full-thickness human skin grafts onto the backs of nude mice and then subjecting the grafts to an episode of burn. We found, accidentally, that obvious local hypertrophic scars developed in mice not subjected to burn insults after the epidermis and upper portions of the dermis of the human skin grafts were shed. Based on this finding, we further investigated the feasibility of establishing an animal model of hypertrophic scarring by transplanting human skin grafts onto nude mice without burning. Main results and conclusions are as below:1. After transplantation, the epidermis and upper portions of the dermis of the human skin grafts began to stiffen, change from pink to brownish yellow and then to black with cocked edges, and fall off by degrees. After the epidermis and upper portions of the dermis of the human skin grafts were shed, local scars developed. 54 of 60 nude mice (90.0 percent) developed significant, persistent hypertrophic scars. Scar hypertrophy reached a peak approximately 5 months after transplantation, with an average maximal thickness of 3.20 mm (maximum, 5.10 mm). On average, scar hypertrophy persisted for 135 days. The dermis layer of the scars thickened significantly and the demarcation between the papillary and reticular layers of dermis was obscure; collagen fibers were dense, with derangements in collagen bundles, which were horizontally arranged in the profound dermis and nodular or swirled in the superficial dermis. Cells and microvessels increased within the dermis and karyomitosis was obvious. These scars were extremely similar to human hypertrophyic scar both in gross appearance and histology.2. Tissues from various stages of model sccar were harvested to examine TGF-β1 by immunohistochemical method. Results show that TGF-β1 were highly expressed in the scar tissues 1 and 3 months later after human skin graft transplantation, whereas the expression was obviously declined in the scar tissues 6 months later.3. Fibroblasts cultured from model scar tissue are extremely similar in morphology to those from human hypertrophic scar, and the cellular proliferation (by MTT method) and collagen synthesis ability(by ~3H-proline uptaken) between them are of no significant difference.4. Comprared with collagenase activity in human nommal skin, collagenase activity was significantly reduced in model scar tissue, which showed that the degradation of ollagen was deficient as in human hypertrophic scar.5. Special fragment of human HLA-A gene could be detected by PCR both in model scar tissue and human hypertrophic scar or skin tissue, but the production was lower in model scar tissue. The result shows that there was human resourced DNA in model scar tissue, while human was not the only resource.6. Obvious scar proliferation only developed in group under full-thickness human skin graft transplantation, not in groups under epidermal human skin graft transplantation nor full-thickness rat skin graft transplantation. So it's the human skin itself, not other surroundings such as cytokines, growth factors or wound liquids, determined whether scar proliferation would happen.7. Because nude mice are immunodefective of T cells, the rejection against transplanted human skin graft is weak and incomplete, so the profound dermis of weaker antigenicty can survive the rejection after transplantation and might be the base of later scar proliferation.Considered together, the animal model of hypertrophic scarring can be established by transplanting human skin grafts onto nude mice, and this model can reproduce hypertrophic scars readily. The hypertrophic scars can persist for a long time and possess the genetic and histologic properties of human hypertrophic scars, and they are also controllable and comparable to human hypertrophic scars, thus making possible the observation of the entire process of hypertrophic scar formation. As a result, it will facilitate further research on the pathogenesis of hypertrophic scarring and provide an important tool for clinical and laboratory study of this pathologic condition.