251replacement therapies for respiratory diseases. Emerging research areas that are
likely to contribute toward this goal are summarized below.
13.10 Decellularized Scaffold Characterization
and Repopulation
Decellularized lung scaffold will be most probably the platform of choice for whole
lung organ engineering in the near future. A variety of techniques for measurement
of micro and macromechanical properties of tissues are available (Suki 2014 ) and if
employed regularly will help to determine whether the mechanical properties of
fully recellularized lungs correspond to the ones of the native organ. Standardization
of decellularization protocols and proteomic analysis will also be essential for
ensuring experimental reproducibility between different lung tissue engineering
labs.
The choice of cell types to be used for recellularization of lung scaffolds will be
equally important. Regarding the epithelial compartment, PSC-derived multipotent
proximal, such as basal cells, and distal, such as type II AEC or LNEPs, stem/pro-
genitor cells will, most probably, be the best options. In this case, novel protocols
for targeted delivery of these cells to the corresponding areas of the decell con-
structs will be needed.
Restoration of endothelial barrier function will be indispensable for lung scaf-
fold functionality, and recent reports of efficient re-endothelialization of decell
human and murine lungs (Ren et al. 2015 ; Stabler et al. 2016 ) (about 75% in the
case of human lungs) indicate that this problem may be solved soon. Additional cell
lineages with specific functions, such as lung fibroblasts and pleural cells, will also
need to be derived from PSCs and incorporated to the recellularized scaffolds.
13.11 3D Bioprinting
The decell-recell model for bioartificial lung generation, while promising, presents
certain limitations including availability of and access to native scaffolds, inefficient
and uncontrolled engraftment of epithelial cells, and loss of ECM proteins during
decellularization. An alternative approach that may overcome these limitations is
3D bioprinting for “de novo” generation of functional tissue units. Although the size
of 3D bioprinted constructs had been a major limitation in the past, a recent publica-
tion (Kang et al. 2016 ) suggests that 3D bioprinting of human-scale, structurally
stable constructs may be within reach.
Despite its complex cellular composition, the respiratory system is characterized
by two main functional compartments, namely, the trachea/airways whose main
role is to conduct air and the alveolar space where gas exchange takes place. The
13 Development and Bioengineering of Lung Regeneration