Biomedical Engineering Reference
In-Depth Information
example, osteochondral region or ACL-bone interface. Some reviews and
studies not covered in this chapter are listed in Table 5.1.
5.4.1 Liver
The success of bioreactors for engineering liver tissue is based upon optimal
oxygen delivery, nutrient transport and waste removal in a heavily popu-
lated construct. The cultures need to perform detoxifi cation and regulation
functions in order to heal parenchyma or at least slow down damage caused
by liver failure. In order to meet clinical needs, bioreactors for liver tis-
sue engineering must be able to perform the functions of one-third of the
liver for up to several weeks (Catapano and Gerlach, 2007). High density
within the construct is crucial for supporting proper cell-to-cell signaling.
Neo-sinusoids also depend on proper spatial distribution of cells, prevent
necrosis in the deeper parts of the scaffold, and ensure uniform enzyme
expression, depending on the zone of the liver construct. There are no stan-
dardized requirements for liver tissue engineering bioreactors; therefore,
bioreactor designs and parameters vary greatly (Catapano, 1996; Allen and
Bathia, 2002). An ideal bioreactor for this type of tissue needs to estimate
and control concentrations of different metabolites within the construct and
at the cell surface. The metabolite concentrations should resemble those
measured
in vivo
. Resistance to internal transport should be minimized, and
the bioreactor should allow for tissue reconstruction to mimic the structure
of native tissue and permit similar enzymatic activity.
Studies using 3D scaffolds have used oxygen microcarriers to enhance
oxygen delivery throughout the construct (Gerlach
et al.
, 1994; Flendrig
et al.
, 1997). The recycle mode in perfusion reactors maximizes cellular
activity while keeping transport resistance low. Continuous-fl ow bioreac-
tors have shown some success in
in vitro
and large animal studies as well as
clinical trials.
Hepatocytes cultured outside the hollow fi ber bioreactors, in so called
shell-and-tube confi guration, were bound to microcarriers or formed
clumps that did not require vascular networks and were not limited by the
size of the fi bers. However, in combination with hemodialysis or low-fl ux
hemo-fi ltration membranes, these experiments yielded poor mass transport
(Watanabe
et al.
, 1997).
Hepatocyte culture performed in the coaxial hollow fi ber reactors indi-
cated a need for radial convection if the distance between the coaxial fi ber
walls is greater than 250 µm; otherwise the tissue begins to lose its viabil-
ity (Macdonald
et al.
, 1998). Another study aimed at reproducing the liv-
er's acinar structure and physiology using four coaxial fi bers. The cells were
located between either two inner semi-permeable tubes of 3 and 1.2 mm in
