Three-Dimensional Respiratory Epithelial Tissue Constructs With Perfusable Microvasculature

The invention provides two vascularized, multi-chip models for the alveoli and the small airway. Both models comprise a perfusable three-dimensional (3D) microvascular network consisting of human primary microvascular endothelial cells, fibroblasts, and pericytes with a differentiated lung epithelial layer exposed at the air-liquid interface (ALI) on top, built on a high-throughput, 64-chip microfluidic plate platform. The platform does not require the support of a permeable membrane and the epithelial cells are directly seeded on the perfused microvascular network. This allows for direct, physical cell-cell interaction and more physiologically-relevant biological phenomena at the epithelium-capillary interface. The invention also provides several methods of making and methods of using the perfused vascularized, ALI exposed lung epithelial, multi-chip models for the study of diseases affecting the alveoli and the small airway, and drug screening (e.g., high-throughput screening).