FIGURE 4. Examples of laboratory uses of tissue-engineered skin.

Reconstructed human skin based on de-epidermized acellular dermis has various uses — examples include the study of skin pigmentation, melanoma invasion and skin graft contraction. a, For skin pigmentation studies, melanocytes were added to reconstructed skin containing keratinocytes and fibroblasts, cultured for 10 days and then sectioned and stained with eosin and haematoxylin to show their general morphology. Melanocytes are identified by immunostaining for S100, and are distributed in the basal keratinocyte layer. In this study, keratinocytes have formed a well-attached epithelium with finger-like projections into the dermis that are known as rete ridges. b, Investigation of the contribution of fibroblasts to skin pigmentation. The melanocytes used were obtained from a pale-skinned donor and combined in a 5/95 melanocyte/keratinocyte ratio. Fibroblasts were included in the left-hand model and omitted from the right-hand model. The reconstructed skin models were cultured for 10 days, with two discs 8 mm in diameter removed after 5 days and replaced with material lacking any additional melanocytes for comparison. As can be seen, the omission of fibroblasts led to spontaneous pigmentation in this reconstructed skin model⁶³. c, To study melanoma invasion, the human melanoma cell line (HBL) was added to reconstructed human skin containing keratinocytes and fibroblasts, and a section through this reconstructed skin was stained with eosin and haematoxylin for general morphology. Melanoma cells were specifically identified by staining with the HMB45 antibody using a red endpoint (arrows). Penetration of melanoma cells through the epidermis into the dermis can be seen clearly⁶⁶. d, Demonstration of the use of this model to study skin graft contraction. De-epidermized acellular human dermis, to which only keratinocytes had been added, were cultured in an air–liquid interface for 10 days. The ability of keratinocytes to gather in the underlying dermis is evident^{69, 70, 71}.