Biomedical Engineering Reference
In-Depth Information
fibrin-collagen gel) in dorsal full-thickness excisional wounds in mice. They demonstrated that these
cells considerably stimulate the regeneration of the skin by the mouse organism. Wound closure and
re-epithelialization were significantly greater than those in wounds treated by fibrin-collagen gel only.
Higher microvessel density, bigger capillary diameters, and thicker epithelial tissue were observed by
applying these stem cells. However, the stem cells did not integrate into the skin tissue, but promoted
the skin tissue regeneration by secreted trophic factors.
The use of stem cells might be dangerous, though, since stem cells might differentiate into harm-
ful cells or may secrete factors that enhance formation and growth of cancer cells. In this context, the
interaction between the tumor cells and their microenvironment is crucial for tumor development, and
stem cells may have a large influence on it. On the other hand, mesenchymal stem cells are recruited to
and accumulate in tumors. There, they contribute to the angiogenesis of the tumors and suppress anti-
tumor immune responses (
Cuiffo and Karnoub, 2012
). Furthermore, it could be shown that cancer cells
are able to induce malignant transformation of MSCs
in vitro
via paracrine effects (
Liu et al., 2012
).
Generally, the risk of tumor formation depends on the origin of the stem cells, the extent of their
ex
vivo
expansion, the induced differentiation, and the site/route of administration. Differences can also be
found between embryonic stem cells, which are pluripotent, and adult stem cells, which are multipotent.
Therefore, utmost care has to be exercised concerning the choice of the used cells in tissue engineering.
Even if stem cells were safe enough to use, the question remains whether or not the cells should
be used in their stem cell phenotype—as a 'growth factor factory'—or whether or not they should be
differentiated to skin cells before implantation. And when keratinocytes are used, can they be used
in their undifferentiated form, or do they need to be differentiated
in vitro
to form an epithelium be-
fore implantation? Thus far, this cannot be answered completely. Often undifferentiated stem cells
are employed to utilize their regenerative potential; but these might be involved in tumor formation,
as described earlier. Concerning the keratinocytes,
Koch et al. (2012)
and
Michael et al. (2013b)
used
nondifferentiated cells for bioprinting and implanted them also in a nondifferentiated state. In the ani-
mals, they could detect a beginning differentiation. This means that the body with its growth factors
could be enough to provide a suitable environment for the differentiation of the cells and the formation
of a stable epithelium.
13.4
CONCLUSION
Bioprinting bears the promise of “building” skin in its full complexity, despite the fact that printed skin
tissue is far from its natural archetype and lacks most of its functions. The possibility of transferring
biomaterial, including cells, macromolecules, and growth factors, to exactly the desired 3D position in
a (skin) tissue is the unique feature and major strength of bioprinting. The different printing technolo-
gies might meet the requirements for clinical or commercial applications (e.g. high throughput, high
resolution, epithelium-like high cell density, and a mechanically stable ECM) to a different degree.
However, all of these techniques have further potential for improvement. Skin is particularly suitable for
improving bioprinting technologies. Starting with just the two major cell types in skin—fibroblasts and
keratinocytes—tissue was already printed. The complexity can be increased gradually by integrating
further cell types. Thus, the missing functions may be added bit by bit.
The functional and aesthetical enhancement of printed tissue should be the focus of future research
since the printed skin equivalents are still inchoate. The integration of a vascular network is one of the
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