Genetically Modified Skin Substitutes: Preparation and Use

Skin loss due to burns or ulcers is a major medical problem and is the motivation for the development of skin substitutes and skin replacement technologies, many of which have had some success in the clinic (1 –4 ). Methods exist for the growth of large numbers of epidermal keratinocytes as well as dermal fibroblasts. These cells have been combined with various analogs of the dermis to fabricate composite skin substitutes. Different types of dermal matrices have been developed including a porous sponge of collagen and glycosaminoglycan (5 ,6 ) and a fibroblast contracted collagen lattice (7 ,8 ). We and others have had success with a dermal analog of acellular human dermis that is deepithelialized and rendered completely acellular (9 –12 ). Acellular dermis is relatively nonimmunogenic and retains many of its structural elements after processing. Skin substitutes using acellular dermis can be formed in vitro and subsequently transplanted to athymic mice, generating a well-differentiated and fully pigmented epidermis with many characteristics of normal skin (11 ,12 ).