title: The use of skin models in drug development.
abstract: Three dimensional (3D) tissue models of the human skin are probably the most developed and understood in vitro engineered constructs. The motivation to accomplish organotypic structures was driven by the clinics to enable transplantation of in vitro grown tissue substitutes and by the cosmetics industry as alternative test substrates in order to replace animal models. Today a huge variety of 3D human skin models exist, covering a multitude of scientific and/or technical demands. This review summarizes and discusses different approaches of skin model development and sets them into the context of drug development. Although human skin models have become indispensable for the cosmetics industry, they have not yet started their triumphal procession in pharmaceutical research and development. For drug development these tissue models may be of particular interest for a) systemically acting drugs applied on the skin, and b) drugs acting at the site of application in the case of skin diseases or disorders. Although quite a broad spectrum of models covering different aspects of the skin as a biologically acting surface exists, these are most often single stand-alone approaches. In order to enable the comprehensive application into drug development processes, the approaches have to be synchronized to allow a cross-over comparison. Besides the development of biological relevant models, other issues are not less important in the context of drug development: standardized production procedures, process automation, establishment of significant analytical methods, and data correlation. For the successful routine use of engineered human skin models in drug development, major requirements were defined. If these requirements can be accomplished in the next few years, human organotypic skin models will become indispensable for drug development, too.
authors.affiliation: Institute of Chemistry and Biological Chemistry, Zurich University of Applied Sciences (ZHAW), Einsiedlerstrasse 31, 8820 Waedenswil, Switzerland.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Mathes
authors.affiliation: Developmental and Molecular Pathways (DMP), Novartis Institutes for BioMedical Research (NIBR), Fabrikstrasse 22, 4056 Basel, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Ruffner
authors.affiliation: Institute of Chemistry and Biological Chemistry, Zurich University of Applied Sciences (ZHAW), Einsiedlerstrasse 31, 8820 Waedenswil, Switzerland. Electronic address: ursula.graf@zhaw.ch.
authors.forename: Ursula
authors.initials: U
authors.lastname: Graf-Hausner
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods / Q000639:trends; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006801:Humans; D008954:Models, Biological; D009924:Organ Culture Techniques / Q000379:methods / Q000639:trends; D012871:Skin Diseases / Q000188:drug therapy* / Q000473:pathology; D012879:Skin Physiological Phenomena / Q000187:drug effects*
chemical_list: D003879:Dermatologic Agents
keywords: Disease; Drugs; Equivalents; Skin