The role of ecm composition in bioengineered lung barrier formation

The lung is susceptible to many incurable diseases that eventually require a lung transplant. With a shortage of donor lungs for these patients, a promising alternative is recellularization of decellularized lungs, that offers the native complex architecture with minimal immune response. Improvements in decellularization technique and seeding strategies have resulted increasing quality of recellularized organ scaffolds, however these engineered tissues are limited. A major hurdle is the formation and maturation of functional gas exchange barriers, resulting in sever edema post-transplantation in animal models. A better understanding of how the decellularized extracellular matrix (dECM) interacts with the alveolar epithelium to modulate barriers, specifically tight junctions (TJ) and adherens junctions (AJ), is integral to producing a functional whole lung replacement. The majority of matrix proteins are preserved within dECM scaffolds, such as, collagens, elastin, laminin, fibronectin, and GAGs, but there are reports of up to a 50% loss of some of these components compared to native ECM. We hypothesize that the ECM composition is essential for cell colonization and mature barrier formation in dECM scaffolds. This research aims to replenish the depleted dECM lung scaffold using a novel, lung-specific, solubilized matrix surface treatment. With this approach we can investigate specific ECM components, and identify those integral to the formation of mature the gas exchange barriers.