Skin substitutes for wound healing and development of animal alternative assays

In this review we describe a number of skin substitutes which are under development for advanced wound healing therapies and for use as animal alternative (in vitro assays). Skin tissue engineering is a multi-disciplinary subject which requires each construct to be specifically designed for its particular future application. We describe our choices made with regards to cell types, dermal matrix, the logistics of production and transport as well as the development of "patient and clinician friendly" protocols for application of novel wound healing therapies. Two skin substitutes have been developed for clinical applications: i) healing of therapy-resisistant chronic wounds and ii) improved scar formation in deep 3^rd degree burns. We also describe a number of skin substitutes being developed in compliance with the 3Rs (reduction, refinement and replacement of test animals). One assay is aimed at wide spread implementation as a complete animal replacement and is an assay which may determine the potency of a sensitizing substance. Three other assays are specialized assays aimed at reduction and refinement of the use of test animals. These three assays represent human physiologically relevant wound healing and adverse scar models (hypertrophic and keloid scar). Such assays are aimed at testing novel therapeutics in the future and are considered to be far superior to current animal models since animals do not form adverse scars which are comparable to humans.