Biomedical Engineering Reference
In-Depth Information
the printing needs to be safe, rapid, and cost-effective. Thus, several adaptations are needed on the way
from bench to bedside and different challenges need to be met.
13.3.6
TECHNICAL AND BIOMEDICAL CHALLENGES
A scale-up of the printed skin substitutes is necessary, especially with regard to large burn injuries. This
is partly a technical challenge. The printing area of most printers is too small and the printing velocity
of several printers is too low, since often, these printers are not yet throughput-optimized. While scal-
ing up the printing area is just an engineering task, there will be fundamental limits for the printing
velocity. Parallel printing with multiple print heads may increase the printing velocity further on toward
a high-throughput system. However, a scale-up is also a biological challenge, since a great many of
skin cells are needed for large burn wounds. Thus, appropriate cell sources and culture conditions are
necessary.
For the production, storage, and delivery of the printed skin substitutes, high standards of quality and
safety need to be applied, usually good manufacturing practice (GMP) conditions and the like. The appro-
priate guidelines include adequate quality management and quality control (including self-inspection),
appropriately trained personnel, suitable premises and equipment, and an extensive documentation of all
steps of the manufacture, storage, and distribution of products (ISPE, 2014). In terms of printing setups,
numerous technical adaptations must therefore be implemented to meet GMP standards. These include
the encapsulation of the printing area into a laminar flow hood to ensure sterility as well as the use of
disposable printing process and cell culture components to minimize contamination (
Chang et al., 2011
).
To avoid infection of the cells and the skin tissues, an integration of the different process steps (e.g.
isolation of cells from a biopsy, if required; cell culture; bioprinting; and the tissue culture) in one ster-
ile environment would be advantageous.
Walles et al. (2014)
established an integrated system without
a bioprinting system. This “tissue factory” is capable of producing up to 5000 tissue pieces per month
fully automated.
13.3.7
STEM CELLS AS POSSIBLE CELL SOURCES FOR BIOPRINTING OF SKIN
On top of the technical challenges, the question on the source of printed cells remains. Ideally, autolo-
gous cells should be used to avoid rejection and transmission of (viral) diseases. Although it is quite
feasible to propagate enough cells from a skin biopsy prior to a planned surgical intervention of, for
example, a small chronic wound, in the case of extensive burn injuries, donor skin for biopsies to gain
autologous cells is scarce. Therefore, other cell sources are needed. In this context, the use of stem cells
has been proposed. They are abundantly present in the different organs, since most tissue is capable
of self-renewal (
Metcalfe and Ferguson, 2008
). The use of adult stem cells is not restricted by ethical
considerations, and adult stem cells can be found in bone marrow, adipose tissue, blood, and skin. In
particular, stem cells derived from adipose tissue (ASCs) are very advantageous as they are easy to
isolate and propagate, and are abundant in humans (
Zuk et al., 2001
; Kuhbier et al., 2010). Apart from
their differentiation to bone, cartilage, and fat, they can also be differentiated to endothelial cells to
promote quick vascularization of skin substitutes (
Auxenfans et al., 2011
). Moreover, stem cells from
sweat glands are easy to gain and propagate; they also enhance vascularization (
Danner et al., 2012
).
As an alternative to print skin tissue,
Skardal et al. (2012)
printed stem cells (amniotic fluid-derived
stem cells or AFS, and bone marrow-derived mesenchymal stem cells or MSCs embedded in
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