Biomedical Engineering Reference
In-Depth Information
diameter or hollow fi bers. A radial fl ow of media was applied from an outer
compartment with an outer diameter of 7.92 mm through a tissue compart-
ment with a volume of 0.33 mL to an inner compartment. Despite improved
mass transfer in these reactors, they yield tissues that are also fi ber-like in
geometry and are of limited use in Large mass culture (Wolfe
et al.
, 2002).
The convective transport through hepatocyte clusters in a hollow fi ber
bioreactor has been noted to be caused by Starling fl ows (Demetriou
et al.
,
1986) or pressure gradient (Kim
et al.
, 2000). Oxygen and nutrient delivery
in these systems promotes viability and functionality of porcine and human
primary cultures. Nonetheless, new liver tissue formation also depends on
the deposition of extracellular matrix (ECM) that helps to maintain tissue
morphology yet at the same time increases resistance to fl ow within the new
tissue (Todd
et al.
, 1993). Among the disadvantages posed by the use of these
systems are cell sedimentation, cell viability and induction of liver-specifi c
metabolic processes.
The continuous rotation of the medium inside the rotating wall vessel
(RWV) bioreactor was shown to cause uniform cell distribution throughout
the scaffold, the development of tight junctions and enzyme secreting ducts
(Duke
et al.
, 1993; Smith
et al.
, 1996). The laminar fl ow conditions minimize
the resistance within the construct and the shear stress to which it is sub-
jected. One limitation of the RWV bioreactor is that it is unable to produce
a clinically relevant tissue size. Some recent studies in the engineering of
liver tissue in bioreactors are listed in Table 5.1.
5.4.2 Myocardium
The bioreactors used for myocardial tissue engineering aim to grow the
constructs that restore functionality of the damaged tissue through appro-
priate mechanical and physiological stimuli. Oxygen and glucose are the
principal necessities for maintaining the continuous rhythmic cardiac cycle
(Zimmermann
et al.
, 2000). An appropriate cell source is necessary for myo-
cardial regeneration. After numerous studies with fetal cardiomyocytes,
skeletal myoblasts, bone marrow stem cells, adipose stem cells, endothelial
progenitors, native cardiac progenitor cells and embryonic stem cells, the
latter have been deemed the most appropriate based on their pluripotency
(Leor
et al.
, 2005; Vunjak-Novakovic
et al.
, 2006). Although numerous stud-
ies have been conducted with this tissue, a greater understanding of the
effects of parameters applied in bioreactors on myocardial development is
needed, and the use of bioreactors helps in this area (Vunjak-Novakovic
et al.
, 2006; Chen
et al.
, 2008). Bioreactors used in myocardium tissue regen-
eration need to reproduce contractile and electrical stimuli found
in vivo
.
Three-dimensional cardiac muscle constructs have been produced using
rotating and perfusion reactors (Freed and Vunjak-Novakovic, 1997a).
