Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 697

fibulin-5 in order to improve their adhesion on matrix and avoid flow-induced
detachment [ 1439 , 1440 ]. Because of their decayed capacity of proliferation, these
modified endothelial cells are also genetically altered to overexpress vascular
endothelial growth factor. A coating of adhesion matrix on the tube exterior
surface allows seeding of smooth myocytes, which are also genetically altered to
overexpress adhesion factors and growth factors.
Mesenchymal stem cells can also be used for the construction of vascular
grafts. Strain influences the differentiation (particularly into smooth myocytes) and
proliferation of mesenchymal stem cells, mechanotransduction depending on the
orientation of cells with respect to the strain axis [ 1441 ]. 25 The implicated signaling
pathway can be affected by the activity of the cytoskeleton and focal adhesions, both
subjected to applied loading.
A better understanding of mechanotransduction processes can improve the tissue
engineering setup. Numerical simulations, once validated, are important because
they: (1) provide the fields of imposed stresses and (2) can optimize the bioreactor
design.

11.4.3.3 Lung Tissue Engineering

Lung design is characterized by an efficient structure-function relationship. The pul-
monary architecture enables ventilation, perfusion, matching of these 2 functions,
and gas exchange across an optimal gas transfer surface area. The anticoagulant
and -immunogenic air-blood interface is immersed in a deformable pump. Because
lung tissue has a limited regeneration capacity in vivo, lung transplantation is used
in some circumstances, but is limited by a shortage of donor organs. In the case of
bone marrow, successful transplantation relies on tissue devitalization followed by
reintroduction of a regenerating cell population. After complete decellularization
of isolated adult rat lungs, the acellular extracellular matrix that preserves the
hierarchical branching structure of its vasculature and airways, i.e., that keeps
scaffolds of vasculature, airways, and alveoli, is reseeded with lung epithelial
and endothelial cells of neonatal lungs and cultured in a bioreactor that retains
the developmental environment of fetal lung [ 1442 , 1443 ]. The resulting tissue
contains alveoli, microvessels, and small airways with the appropriate cell types and
rheology. After sevarl days, the construct can be perfused with blood and ventilated
with physiological pressures.

25 Cyclic uniaxial strain on elastomeric membranes coated by mesenchymal stem cells upregulates
smooth myocyte markers, such as α -actin, caldesmon, calponin, and myosin, until the cells align
perpendicularly to the strain axis. Microgrooves created in the elastomeric cell culture membrane in
the loading direction keep mesenchymal stem cells aligned parallel to the strain axis and change the
cell behavior, with a production increase in calponin-1 and decrease in cartilage matrix markers.
Microgrooves normal to the loading direction lead to attenuation in matrix remodeling and cell
signaling.