Collaborative Research: ENG-BIOTECH: Engineering Biomedical Systems to Investigate Extracellular Matrix Regulation of Airway Basal Cell Stemness and Differentiation

About This Grant

The human respiratory system relies on airway basal cells (BCs), a type of stem cell, to keep lungs healthy. These cells replace damaged cells and help remove debris and pathogens through a process called mucociliary clearance. The extracellular matrix (ECM), a network of proteins that provides structural support for these cells, significantly influences the ability of BCs to replicate and transform into different types of airway cells. Unfortunately, existing laboratory models do not fully mimic lung ECM, particularly factors like composition and stiffness, making it difficult to study how these environmental conditions influence BC behavior. This project aims to create a new material that simulates the composition and stiffness of lung tissue, which will allow researchers to control precisely the environment around BCs so they can explore how these factors affect how the cells grow, replicate, and differentiate into cells necessary for proper lung function. Results from this research may lead to new treatments for lung diseases, especially conditions that damage the airways. Beyond advancing lung disease research, this project will promote interest in science, technology, engineering, and mathematics (STEM) careers among middle school students, particularly in underserved rural communities. Through a partnership with the educational app Couragion, the research findings will be transformed into interactive content, offering students a fun and engaging way to explore scientific careers. This research aims to engineer a biomaterial platform to investigate how the extracellular matrix (ECM) influences airway basal stem cell (BC) self-renewal and differentiation. Current models such as air-liquid interface cultures and 3D organoids do not fully replicate the dynamic mechanical and biochemical environment of the lung ECM. To address these limitations, poly(ethylene glycol)-based hydrogels that can dynamically stiffen to precisely control ECM composition and stiffness will be used. This interdisciplinary approach combines expertise in materials science, stem cell biology, and regenerative medicine to develop an advanced platform for studying cell-matrix interactions. The study will examine how variations in ECM stiffness and protein composition affect BC renewal and differentiation, and harness these environmental cues to reproducibly control cellular function. BC responses to tunable biomaterials will be assessed, focusing on outcomes such as cell proliferation, differentiation capacity, and gene expression. This project addresses significant gaps in understanding how the mechanical and biochemical ECM properties regulate BC function, with wide-reaching implications for tissue regeneration and disease modeling. The ability to separately control ECM stiffness and composition will offer new insights into how lung development and repair are managed at the cellular level. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.