This study presents a standardized and fast procedure for preparation of small skin grafts. The grafts, when laid onto an acute wound and a chronic wound, were associated with complete healing of the wounds. Similar and identical grafts have, in animal studies, been shown to reepithelialize full-thickness skin wounds. There are several mechanisms by which transplantation of small skin fragments might exert a positive effect on wound healing. First, graft take by incorporation and revascularization of the transplanted tissues may occur. This is very likely to have happened in our study, based upon the observations of isolated epithelial islands in the grafted wounds. Second, the supply of new cells, such as keratinocytes and fibroblasts, to the wound may, together with the proliferative stimulus of the wound environment, lead to proliferation, differentiation, and migration of the grafted skin. This mechanism is supported by the observation of epithelial islands in the grafted wounds that expanded and coalesced during the healing process in this study. It is also supported by reports that have shown accelerated healing in wounds transplanted with autologous cultured fibroblasts and keratinocytes[18–20] as verified by sequential histologies and identification of the transplanted cells by gene marking. Such studies have concluded that the cells survive and incorporate into the tissues of the healing wound. Third, it is plausible that the grafted skin secrete one or several growth factors into the wound milieu, which are capable of augmenting the healing process. This presumes that the growth factors work in an autocrine and/or paracrine fashion and require that the cells of the transplanted tissues, or native cells in the wound environment, are capable of responding to growth factors or other cytokines released by the skin grafts. Our study could not determine whether such a mechanism was of any significance for the observed healing response, but this view is supported by other studies that have demonstrated accelerated healing of human leg ulcers transplanted with allogenic keratinocytes and fibroblasts.[21,22] Such allogeneic cells are unable to survive in the long term due to incompatibility with the host, although it was initially reported otherwise.
The minced skin technique used in this study is likely to be faster than the commonly used pinch grafting procedure. A direct comparison was however not performed. The STSG harvested in this study is also thinner than a typical pinch graft that often contains a significant portion of dermis. In our experience, a thin STSG donor site heals with minimal cosmetic impairment when evaluated one half to a year postoperatively. Pinch graft donor sites at a similar time point are, on the contrary, often highly visible as depigmented spotty areas exhibiting typical scar tissue.
In comparison with cultured autologous keratinocytes, we see several advantages with the procedure studied herein. First, the tissue is available immediately whereas keratinocytes need typically 3 to 4 weeks of culture to obtain a sufficient amount of cells.[23,24] Second, keratinocyte culturing is very labor-intensive and relies on specialized laboratory equipment and facilities and therefore it is profanely expensive. Finally, keratinocyte grafting is a 2-stage procedure involving harvest of the donor skin necessitating a small surgical procedure and, at a later stage, when the cultures are ready, a transplant procedure must be performed. The advantage with cultured keratinocytes is, however, the virtually unlimited amounts of cells that may be obtained by serial propagation and subculture of the keratinocytes in vitro. For the relatively small wound, this is probably not necessary and it is quite possible that donor site size may be kept low by spreading the minced skin grafts extensively, thereby obtaining a high expansion factor. This remains to be studied in detail.
Another possible advantage of minced skin grafts is that they also contain a dermal support. The importance of a dermal tissues for the enhancement of transplantation of cultured keratinocytes has previously been stressed,[17,24,26,27] and, if absent, the take rate of keratinocytes is often poor.
In relation to traditional split-thickness skin grafting and meshing, the minced skin technique offers the possibility of greater expansion. Greater expansion will, however, also lead to longer healing times and lower efficiency. We therefore do not believe that the minced skin procedure presented here would exclude traditional grafting, but we may consider it as a first line of treatment in the outpatient clinic as it offers a standardized and easily available treatment option for therapy-resistant skin ulcers.
Xpansion was supplied by Applied Tissue Technologies, Newton, Mass.
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