A novel physiologic skin mode has been developed utilizing human neonatal dermal fibroblasts cultured on a biodegradable, polyglycolic or polyglactic acid, mesh. The proliferating cells stretch across the mesh opening and secrete native growth factors, collagens and other extracellular matrix proteins to produce an in vitro human dermal tissue. Human keratinocytes can also be cultured onto this dermal tissue to form a living cultured skin with both dermal and epidermal components. Preliminary studies in mini-pigs and athymic mice indicate that the cultured dermis can rapidly adhere to full-thickness wounds, vascularize, and support epithelial coverage and wound closure with reduced wound contraction and scarring. Dermal tissue has been widely reported not to be immunologically rejected. The technology described here offers the potential for a universal dermal replacement that could be used under thin autologous epidermal grafts or widely-meshed grafts, or as a base for cultured, autologous keratinocytes to form a composite skin substitute. Support of this gran would allow further in vitro characterization of the cultured skin model and additional pre-clinical studies to optimize its application in therapeutic skin replacement. These studies are expected to lead directly to clinical trials in patients with full-thickness skin wounds.
