Project Grant 2225554

This three-year, $500,000 project grant from the National Science Foundation's Biological Sciences program (CFDA 47.074) supports research at the University of Vermont to define environmental design criteria for directing differentiation of type 1 and type 2 lung alveolar epithelial cells. The University of Colorado-Denver and University of Iowa are sub-awardees on the project. Researchers will utilize novel tissue engineering approaches incorporating hydrogels derived from decellularized human lungs to evaluate the effects of physiologically relevant extracellular matrix composition and stiffness on differentiation. In silico modeling will also be used to direct empirical studies and develop a holistic differentiation control framework. The project aims to determine specific extracellular matrix components and tunable microenvironmental stiffness that regulate stemness and cell differentiation. Findings seek to inform development of new biomaterials to guide lung cell development and further understanding of fundamental lung development and repair mechanisms, with broader applicability to cell-extracellular matrix interactions enabling differentiation in other organ systems.