Skin and Vascular Grafts

Skin is a highly proliferative and regenerative tissue. It consists of two main layers: the dermis, whose main cellular components are stromal cells or fibroblasts, and the epidermis, whose main cellular components are epidermal cells at various stages of differentiation into keratinocytes (Figure 6.4). Both cell types grow well in culture, and ex vivo cultivation is not the limiting factor with this tissue. Interestingly, transplanted dermal fibroblasts have proven to be surprisingly nonimmunogenic.

Skin transplants and engineered skin technologies have been applied to victims of burns and patients with diabetic ulcers who have severe problems with skin healing. To treat these problems, skin may be cultured ex vivo and applied to the affected areas. Technologically this cell therapy is relatively well developed, and currently there are several “engineered skin” products available, including ApligrafW (Organogenesis Inc.) and DermagraftW (Advanced Bio Healing Inc.). Figure 6.5 shows an expansion bioreactor for creating skin grafts from human foreskins developed by Advanced Tissue Sciences Inc., the now defunct company that originally developed DermagraftW. The bioreactor is constructed with one mechanical hinge and two ports for constant “bleed-feed” flow (left panel). The graft products—which are similar to autologous skin grafts without hair follicles—are easily removed from the bioreactor, as shown in the right panel. In spite of these successes, important challenges remain in bringing such products to wide clinical use. The relatively high cost of the

FIGURE 6.4 The cellular arrangement and differentiation in skin. The cross section of skin and the cellular arrangement in the epidermis and the differentiation stages that the cells undergo.

FIGURE 6.5 Advanced Tissue Sciences bioreactor for culture of their skin product, Trachyte, derived from human foreskins

extensive testing, processing, and quality control that is required for such allogeneic products are a significant barrier to adoption for procedures for which effective therapies already exist. However, these products have introduced tissue engineering technologies to the clinic and have paved the way for future products.