title: Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.
abstract: Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI) and Department of Pharmacy, Saarland University, Saarbrücken, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Mardas
authors.initials: M
authors.lastname: Daneshian
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Bouwstra
authors.affiliation: Università degli Studi di Milano, Department of Health, Animal Science and Food Safety (VESPA), Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caloni
authors.affiliation: Epithelix Sàrl, Geneva, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Constant
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK.
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
authors.affiliation: Translational Center Regenerative Therapies for Oncology and Musculoskeletal Diseases, Würzburg Branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB) and Department of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Dandekar
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Center for Infection Research (HZI), Braunschweig, Germany.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Fabian
authors.affiliation: Across Barriers GmbH, Saarbrücken, Germany.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Haltner
authors.affiliation: Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.|Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.affiliation: Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Hasiwa
authors.affiliation: MatTek Corporation, Ashland, MA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hayden
authors.affiliation: MatTek In Vitro Life Science Laboratories, Bratislava, Slovak Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Kandarova
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Khare
authors.affiliation: Empa - Swiss Federal Institute for Materials Science & Technology, St. Gallen, Switzerland.
authors.forename: Harald F
authors.initials: HF
authors.lastname: Krug
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Pesticide Safety, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kneuer
authors.affiliation: Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.affiliation: Unilever Research Colworth, Sharnbrook, UK.|Department of Chemical and Process Engineering, University of Surrey, Guildford, UK.
authors.forename: Guoping
authors.initials: G
authors.lastname: Lian
authors.affiliation: Technical University Berlin, Germany;|TissUse Incorporated, Spreenhagen, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Marx
authors.affiliation: Translational Center Regenerative Therapies for Oncology and Musculoskeletal Diseases, Würzburg Branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB) and Department of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Metzger
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ott
authors.affiliation: EURL ECVAM, Systems Toxicology Unit, Institute for Health and Consumer Protection, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Pilar
authors.initials: P
authors.lastname: Prieto
authors.affiliation: Therapeutics Research Centre, School of Medicine, University of Queensland, Translational Research Institute, Brisbane, Queensland; University of South Australia, Adelaide, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: 3Rs Management and Consulting ApS, Lyngby, Denmark.
authors.forename: Erwin L
authors.initials: EL
authors.lastname: Roggen
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety, Berlin, Germany.
authors.forename: Tewes
authors.initials: T
authors.lastname: Tralau
authors.affiliation: Danone corporation, Nutricia Research, Utrecht, The Netherlands.
authors.forename: Claudia
authors.initials: C
authors.lastname: van den Braak
authors.affiliation: Translational Center Regenerative Therapies for Oncology and Musculoskeletal Diseases, Würzburg Branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB) and Department of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI) and Department of Pharmacy, Saarland University, Saarbrücken, Germany.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D035843:Biomedical Research; D018929:Cell Culture Techniques; D004847:Epithelial Cells; D006801:Humans; D007422:Intestines; D008168:Lung; D023421:Models, Animal; D010539:Permeability; D012867:Skin; D018675:Toxicity Tests
keywords: cytotoxicity; epithelial cell culture; in vitro models; permeability; transport studies