title: Assessment of skin barrier function and biochemical changes of ex vivo human skin in response to physical and chemical barrier disruption.
abstract: Topical dermatotherapy is intended to be used on diseased skin. Novel drug delivery systems even address differences between intact and diseased skin underlining the need for pre-clinical assessment of different states of barrier disruption. Herein, we studied how short-term incubation in culture media compared to incubation in humidified chambers affects human skin barrier function and viability. On both models we assessed different types and intensities of physical and chemical barrier disruption methods with regard to structural integrity, biophysical parameters and cytokine levels. Tissue degeneration and proliferative activity limited the use of tissue cultures to 48h. Viability is better preserved in cultured tissue. Tape-stripping (50×TS) and 4h sodium lauryl sulfate (SLS) pre-treatment were identified as highly reproducible and effective procedures for barrier disruption. Transepidermal water loss (TEWL) values reproducibly increased with the intensity of disruption while sebum content and skin surface pH were of limited value. Interleukin (IL)-6/8 and various chemokines and proteases were increased in tape-stripped skin which was more pronounced in SLS-treated skin tissue extracts. Thus, albeit limited to 48h, cultured full-thickness skin maintained several barrier characteristics and responded to different intensities of barrier disruption. Potentially, these models can be used to assess pre-clinically the efficacy and penetration of anti-inflammatory compounds.
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany. Electronic address: nadine.doege@charite.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Döge
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: araks_avetisyan@yahoo.de.
authors.forename: Araks
authors.initials: A
authors.lastname: Avetisyan
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: sabrina.hadam@charite.de.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hadam
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: eva.barbosa-pfannes@charite.de.
authors.forename: Eva Katharina Barbosa
authors.initials: EKB
authors.lastname: Pfannes
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: fiorenza.rancan@charite.de.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Rancan
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: ulrike.blume-peytavi@charite.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: annika.vogt@charite.de.
authors.forename: Annika
authors.initials: A
authors.lastname: Vogt
mesh_terms: D018925:Chemokines / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010447:Peptide Hydrolases / Q000378:metabolism; D012629:Sebum / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*; D012967:Sodium Dodecyl Sulfate / Q000378:metabolism; D013501:Surface-Active Agents / Q000378:metabolism; D053832:Surgical Tape; D046509:Tissue Culture Techniques / Q000379:methods; D014870:Water Loss, Insensible / Q000502:physiology
chemical_list: D018925:Chemokines; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D010447:Peptide Hydrolases
keywords: Dermatotherapy; Ex vivo skin culture; Inflammation; Skin barrier function; Skin chemokines; Skin physiological parameters; Skin proteases