Structural integration of skin equivalents grafted to Lewis and Sprague-Dawley rats.

Bilayered skin equivalents, composed of a sheet of epidermal cells overlying a collagen lattice populated with fibroblasts, quickly become structurally integrated with the surrounding host skin after grafting to Lewis rats. Three days after transplantation, the skin equivalent lies on a bed of host granulation tissue and is loosely attached to the adjoining host dermis. Blood vessels begin to invade the collagen lattice by 5 days after grafting. By the 7th day a fully keratinized, hypertrophic epidermis covers the surface of the graft and blood vessels penetrate the lattice to the base of the epidermis. Vascularization of the graft is accompanied by activation and proliferation of the fibroblasts and by a condensation of the collagen matrix. During the 2nd week after grafting, the collagen fibrils become organized into thin fibers that show a basketweave pattern of birefringence when examined using polarized light. By 1 month the structure of the skin equivalent has become stabilized. The fibroblasts now resemble the quiescent fibrocytes of normal, resting dermis and the epidermis remains moderately hypertrophic. One to two years after grafting to Sprague-Dawley rats, the skin equivalents do not appear hypertrophic. The graft lacks secondary derivatives such as hair follicles and sweat glands, presumably because the stem cells are lost during the isolation of the epidermal cells. Grafts that are prepared using epidermal cells overlying a collagen gel without fibroblasts give rise to raised, linear scars within 2 weeks.