COVID-19: 3D Bioprinted Tissue Models for Respiratory Viruses

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

We have established protocols for culturing primary human small airway epithelial cells and alveolar cells in a transwell air-liquid-interface (ALI) model. Tissue biofabrication has been optimized in a 96-well plate format, including the formation of a microvessel network. We are positioning these lung tissue models platforms for testing infectivity of viral variants and anti-viral therapeutics for programs at NCATS, NIH and the broader research and drug development community. We have also developed a vascularized perfused lung epithelial tissue model in a high throughput microfluidics platform to assess of viral infection vasculature leakiness and permeability and thrombotic events seen in COVID-19 patients. We have characterized extensively the infectivity of the MatTek's tracheobronchial and alveolar cultures with SARS-CoV2 and IAV. We have also assessed the anti-viral effects of a focused number of compounds identified from HTS. In collaboration with Sara Cherry at the University of Pennsylvania, we have identified that Pharmacological activation of STING blocks SARS-CoV-2 infection. We continue to explore additional relevant therapeutic opportunities from drug screens at UPenn. We have worked with NICHD Sequencing Core lab and scientists at the Texas Biomedical Research Institute to implement scRNAseq studies on tracheobronchial and alveolar lung tissue models infected with IAV and SARS-CoV2. Some of the results have been published and some data analysis is currently on-going. We have assessed infectivity of intestine tissues (Mattek) and neural spheroids models with SARS-CoV2