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Overview of human three-dimensional (3D) skin models used for dermal toxicity assessment – Part 1

corresponding

BART DE WEVER*, DIRK PETERSOHN, KARSTEN R. MEWES
*Corresponding author
Henkel Beauty Care, Henkel AG & Co. KGaA, Henkelstraße 67, 40589 Düsseldorf, Germany

Abstract

Human three-dimensional skin models have become an indispensable tool in current industrial and regulatory toxicity testing activities. Since the early 90’s, several models of the skin have been developed, characterized, validated and accepted as valid replacement method for animal experimentation. In addition current legislative dossiers such as REACH (Registration, Evaluation, Authorization and Restriction of Chemicals), the Cosmetics Directive and the CLP (Classification, Labeling and Packaging) directive continue to stimulate the implementation of skin models in general. Part 1 of this publication will provide an update of the different commercially available skin models in terms of their basic characteristics and testing applications. Part 2, to be published later, will focus in detail on their use for dermal toxicity testing applications including corrosion, skin irritation, phototoxicity, dermal absorption, skin sensitization and genotoxicity testing.


INTRODUCTION

Skin model development in vitro goes back at least 30 years. One of the most important technological breakthroughs was probably the method developed by Pruniéras where human keratinocytes cultivated on a de-epidermised dermis were exposed to the air-liquid interface, which resulted in a fully-differentiated epidermis featuring characteristics of human epidermis in vivo (1, 2). Several other academic laboratories have reported successful reconstruction of epidermis using similar techniques (3, 4, 5, 6). Initially, in vitro epidermal reconstruction models were used purely for basic research interests aimed at obtaining a better overall understanding of skin physiology. Over time it became clear that chemicals could be tested for both efficacy and toxicity and replace current animal test methods.
Because of the attractive market opportunity based on the assumption that in vitro skin models would provide the ultimate research tool for industry to assess cutaneous toxicity and pharmacology of chemical substances, several commercial tissue engineering initiatives, focused on “mass producing” 3D in vitro reconstructed human skin model ...




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