252
simplest functional units that can model the respective in vivo compartments are a
single trachea or airway, a tube-like structure lined by a pseudostratified epithelium
and a single alveolar sac, a grape-like structure composed of clusters of alveoli, and
hollow cavity-like structures lined by type I and II AECs. In both cases, 3D bioprint-
ing can be used to initially reconstruct these units in laboratory scale by determining
the optimal starting ECM composition, elastic modulus, and growth factor environ-
ment of the bioprinted construct (Fig. 13.3c). As with decell scaffolds, multipotent
proximal or distal progenitors can be used for seeding of the epithelial surface, and
additional cell types such as PSC-derived fibroblasts or chondrocytes can be incor-
porated at defined positions to provide structural stability.
Eventually, 3D bioprinting of a human-scale, bioartificial lung may become pos-
sible by scaling up and assembling of functional proximal and distal lung units with
optimal biomechanical and cellular properties.
In summary, advances in our ability to model lung development in vitro with
human PSCs combined with emerging bioengineering techniques are rapidly trans-
forming the field and are likely both to further our understanding of normal develop-
ment and to facilitate therapeutic applications of these in the years to come.
Acknowledgments Andrew A. Wilson is supported by R01DK101501 and Laertis Ikonomou by
grants R01 HL111574 and R01 HL124280.
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