High-throughput screening techniques

Abstract

The use of laboratory animals has been the ‘standard’ procedure for the dermal safety and efficacy evaluation of consumer, chemical and/or pharmaceutical products for many decades. However, both scientific and ethical considerations have driven the development of alternative methods aiming to reduce, replace and refine animal experimentation (Russell WMS, Burch RL, Hume CW. The principles of humane experimental technique. 1959). Especially, human tissue-engineered skin models demonstrate to be very valuable alternatives for dermal toxicity and efficacy testing. Since human skin models are available in quality ensured commercial companies, they are routinely used by industry for in-house screening and more recently also for regulatory toxicity testing applications. Whereas today only skin corrosion and skin irritation test methods are listed in regulatory guidelines, many new non-animal tissue-based dermal toxicity testing applications are currently in development and validation, including skin sensitization, genotoxicity and phototoxicity. In addition, the adoption of skin model-based tests in regulatory guidelines has stimulated regulatory bodies in other parts of the world such as Brazil, China, India and South Korea to harmonize with the global trend to accept validated alternative methods, indicating that the demand for skin models in the future will be largely increased. To ensure the availability of high-quality skin models in very large quantities, automated production is the ultimate solution. Although the field of high-throughput testing has expanded massively over the last years in pharmacological research, it is rarely used in the assessment of adverse health effects. The reason for that might be the higher complexity of three-dimensional (3D) reconstructed tissues employed in toxicology compared to two-dimensional (2D) systems routinely used for drug discovery applications. Furthermore, there is a lack for standardized test methods that can be implemented in a high-throughput approach. This chapter will focus on new production technologies to generate skin models in sufficient numbers and emerging nondestructive methods to assess tissues.