title: Human barrier models for the in vitro assessment of drug delivery.
abstract: In vitro test systems gain increasing importance in preclinical studies to increase the predictivity and reduce animal testing. Of special interest herein are barrier tissues that guard into the human body. These barriers are formed by highly specialized tissues such as the skin, the airways, and the intestine. However, to recapitulate these tissues, researchers are currently restricted by a lack of suitable supporting scaffolds. In this study, we present biological scaffolds based on decellularized porcine gut segments that offer a natural environment for cell growth and differentiation. Employing these scaffolds, human barrier models of the skin, the airways, and the intestine that mimic the natural histological architecture of the respective tissue are generated. These models show tissue specific barrier properties, such as the stratification of the skin, the mucociliary phenotype of the airways, and polarization of the intestinal epithelium. To investigate the transport characteristics of the intestinal test system, we incubated the tissue models with fluorescein (Papp<1 × 106cm/s), propranolol (Papp>7 × 106cm/s), and rhodamin123 (ratio 2.45). The here presented biological scaffolds facilitate the in vitro generation of human barrier models that might represent useful tools for drug delivery studies.
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schweinlin
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany.|Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Wuerzburg, Josef-Schneider-Straße 11, 97080, Wuerzburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Lodes
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lotz
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Wuerzburg, Josef-Schneider-Straße 11, 97080, Wuerzburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hackenberg
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany.|Translational Center Wuerzburg "Regenerative Therapies for Oncology and Musculoskeletal Diseases", Würzburg branch of the Fraunhofer IGB, Roentgenring 11, 97070, Wuerzburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Steinke
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Roentgenring 11, 97070, Wuerzburg, Germany. Heike.Walles@uni-wuerzburg.de.|Translational Center Wuerzburg "Regenerative Therapies for Oncology and Musculoskeletal Diseases", Würzburg branch of the Fraunhofer IGB, Roentgenring 11, 97070, Wuerzburg, Germany. Heike.Walles@uni-wuerzburg.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: Translational Center Wuerzburg "Regenerative Therapies for Oncology and Musculoskeletal Diseases", Würzburg branch of the Fraunhofer IGB, Roentgenring 11, 97070, Wuerzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Groeber
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004847:Epithelial Cells; D005347:Fibroblasts; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000648:ultrastructure; D015603:Keratinocytes; D008855:Microscopy, Electron, Scanning; D009297:Nasal Mucosa / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013552:Swine; D054457:Tissue Scaffolds
chemical_list: D004364:Pharmaceutical Preparations
keywords: Alternative to animal testing; Drug delivery; Human barrier tissue; In vitro model; Tissue engineering