Again, figure 1 depicts the production of Apligraf. Dermal fibroblast cells are poured over a collagen matrix that already resides in the nutrient media. At day 6, after the dermal fibroblasts have had time to develop and remodel the collagen matrix, the upper layer epidermal keratinocyte cells are spread on top. In the final step, at at day 20 the upper layer of the epidermis is exposed to air in order to develop the tough outer stratum corneum. This process takes about 10 days.

Histologically, figure 2 on the right shows that Apligraf and natural human skin are essentially the same structurally, although the engineered skin does lack sweat glands and hair follicles.