Given the complexity of lung formation and physiology, there is a fundamental interest in developing an in vitro model of the lung to investigate lung morphogenesis, homeostasis of epithelial cell populations, and pathophysiology in highly controlled constructs. Culturing primary alveolar cells inherently requires a 3D environment to recreate cystic structures that are physiologically relevant. However, alveolus-like structure formation has only been observed in naturally derived networks that present cells with a myriad of uncontrollable cues and are unable to be patterned after cell encapsulation. Our lab uses poly(ethylene glycol) (PEG)-based thiol-ene gel systems that allow for controlled incorporation of pendant bio-functional peptides and cleavable crosslinks, which creates a well-defined and highly tunable cytocompatible scaffold.
Within the roughly spherical alveoli, epithelial cells reside in a polar environment, lying at the interface of the basement membrane and the air space. To create a more biologically appropriate model with which to study alveolar development and repair processes, we have developed a method for recreating the cyst-like structure of the alveolus using PEG-based photodegradable microparticles as a template to guide hollow cyst formation. With this model, we aim to study fundamental lung development processes as well as investigate disease pathways, such as pulmonary fibrosis.