Merk Sharp and Dohme LLC 1 article published in JoVE Bioengineering Reconstituting Cytoarchitecture and Function of Human Epithelial Tissues on an Open-Top Organ-Chip Varone Antonio1, Adya Panchal2, Magdalena Kasendra3, Barrile Riccardo2,3 1Merk Sharp & Dohme LLC, 2Department of Biomedical Engineering, University of Cincinnati, 3 The present protocol describes the capabilities and the essential culture modalities of the Open-Top Organ-Chip for the successful establishment and maturation of full-thickness organ-on-chip cultures of primary tissues (skin, alveolus, airway, and intestine), providing the opportunity to investigate different functional aspects of the human epithelial/mesenchymal and vascular niche interface in vitro.