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Standardised Reconstructed Skin Models in Toxicology and Pharmacology: State of the Art and Future Development

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Organotypic Models in Drug Development

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 265))

Abstract

Three-dimensional (3D) reconstructed human skin (RhS) models featuring fully-differentiated characteristics of in vivo human epidermis have been known for almost 40 years. In this chapter, the topic of commercial in vitro tissue models is described, taking RhS models as an example. The need for highly standardised models is evident for regulatory testing purposes, e.g. the classification and labelling of chemicals and formulations, as well as for pharmacology-oriented research and drug development. Following the standardisation of RhS model production by commercial developers, international validation studies and regulatory acceptance, 3D RhS models are now used globally in both industrial and academic research laboratories. Industrial production of standardised 3D RhS models involves GMP-compliant processes together with ISO 9001 documentation in order to control and ensure reproducibility and quality. Key biological, functional, and performance features that are addressed in industrial production include barrier properties, histological and immunohistochemical characterisation, lipid profile characterisation, and tissue viability before and after transport. An up-to-date survey of commercial RhS tissue producers and the regulatory acceptance status of major safety, hazard, and efficacy assays currently available to chemical and pharmaceutical industries is presented in this chapter. Safety and ethical concerns related to the use of human tissue in the industrial production of RhS models are discussed. Finally, innovative approaches to the production of standardised 3D RhS models including automated production, development of more representative 3D RhS models using advanced additive manufacturing tools, microfluidics technologies, and bioprinting are presented. The future outlook for 3D RhS models includes a prevalence of high-quality models which will be fabricated by end-users rather than commercial producers. These will overcome problems with shipments and customs clearance that many users still face when buying RhS from overseas commercial suppliers. Open-source technologies and commercial components for “do-it-yourself” RhS will significantly change the skin model market as well as regulatory acceptance of open-source models during the next decade. All of these developments and improvements will together allow more widespread use of in vitro RhS models for broader application as animal replacements in areas ranging from industrial and regulatory toxicology and pharmacology, to drug development and personalised medicine.

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Authors and Affiliations

  1. Department of Tissue Cultures and Biochemical Engineering, Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, Slovak Academy of Sciences, Bratislava, Slovakia

    Helena Kandarova

  2. Faculty of Chemical and Food Technology, Institute of Biochemistry and Microbiology, Slovak University of Technology in Bratislava, Bratislava, Slovakia

    Helena Kandarova

  3. BioSurfaces, Inc., Ashland, MA, USA

    Patrick J. Hayden

Authors
  1. Helena Kandarova
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  2. Patrick J. Hayden
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Correspondence to Helena Kandarova .

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Editors and Affiliations

  1. Institut für Pharmazie, FU Berlin, Berlin, Germany

    Monika Schäfer-Korting

  2. School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

    Silvya Stuchi Maria-Engler

  3. BASF SE, Experimental Toxicology und Ecology, Ludwigshafen am Rhein, Rheinland-Pfalz, Germany

    Robert Landsiedel

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Kandarova, H., Hayden, P.J. (2020). Standardised Reconstructed Skin Models in Toxicology and Pharmacology: State of the Art and Future Development. In: Schäfer-Korting, M., Stuchi Maria-Engler, S., Landsiedel, R. (eds) Organotypic Models in Drug Development. Handbook of Experimental Pharmacology, vol 265. Springer, Cham. https://doi.org/10.1007/164_2020_417

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