Biomedical Engineering Reference
In-Depth Information
In further studies, the authors demonstrated the potential of heterotopic fi brob-
lasts (from dermis, nasal, and oral mucosa) for tracheal epithelial regeneration.
Regeneration of epithelial cells in contact with different heterotopic fi broblasts
showed different characteristics in structure, development of cilia, secretion of
mucins, and expression of ion and water channels, for example, aquaphorines and
Na
+
/K
+
ATPase. In contact with nasal fi broblasts, however, no mature and fully
functional tracheal epithelium was generated
in vitro
. Dermal fi broblasts induced
the generation of an epidermal like epithelium. Especially the cocultivation with
fi broblasts from the oral mucosa induced the regeneration of a morphologically
and functionally regular tracheal epithelium. This was comparable to the regenera-
tion of epithelium
in vitro
after cocultivation with tracheal fi broblasts. Fibroblasts
from the tracheal and the oral mucosa expressed keratinocyte growth factor, epi-
dermal growth factor, and hepatocyte growth factor. Fibroblasts from the oral
mucosa enhanced proliferation and migration of epithelial cells
in vitro
similarly
to the tracheal fi broblasts. Since the explantation of oral mucosa is clearly less
invasive than that of tracheal mucosa, there seems to be a very promising method
available now to develop scaffolds with a functionally adequate epithelium for the
tracheal reconstruction [97].
In 2008, the same group used this technique of cocultivation of epithelial cells
and tracheal fi broblasts to produce a tracheal scaffold seeded with cells
in vitro
and
applied the tissue-engineered scaffold for the tracheal reconstruction in rats [98].
The authors could demonstrate a fully functional epithelium
in vivo
. Besides the
cocultivation of tracheal epithelial cells and fi broblasts, also the cocultivation of
tracheal epithelial cells and mesenchymal stem cells for the “
in vitro
” reconstruc-
tion of a fully functional tracheal epithelium is described in the literature. The
epithelium thus produced showed morphological, histological, and functional
characteristics of the tracheal mucosa. The authors assumed that the cocultivation
with mesenchymal stem cells could play a main role in tissue engineering in
future [99] .
13.2.2.2
Vascular Supply of Tracheal Constructs
A problem not adequately solved so far is the vascular supply of scaffolds and of
tissue constructs developed from these scaffolds
in vivo
. In contrast to other paren-
chymal organs, the trachea is supplied by a network of small blood vessels which
is evidently not easy to generate. Microanastomoses were not successful in animal
models [100, 101] and therefore not further persecuted. It is known from the lit-
erature that after tracheal reconstruction, the capillary network present at the
anastomosis proceeded in the direction of the implant only 2 cm at maximum and
that this process of revascularization took several months [102]. In tracheal
implants, which were longer than 3 cm, there was a lysis of the epithelium with a
consecutive destruction of the basal membrane followed by the development of
granulomatous tissues producing a tracheal stenosis. While bioreactors allow the
growth of autologous cells [103] and functional tissues and are routinely used for
the generation of osteochondral constructs, and tissue-engineered heart valves,
there are very few studies showing the application of bioreactors for the generation
