Biomedical Engineering Reference
In-Depth Information
Mixed bioreactors used in this study could only produce tissue layers 50-70 µm
thick (Bursac
et al.
, 1999). This limitation was due to poor mass transport
throughout the scaffolding, both synthetic and natural (Radisic and Vunjak-
Novakovic, 2005; Folkman and Hochberg, 1973). Collagen as well as PGA
scaffolds in a rotating bioreactor showed some improvement in terms of
cell infi ltration and metabolism, yet the tissue size failed to reach clinically
relevant standards (Carrier
et al.
, 1999). The poorly oxygenated tissue was
only 100 to 200 µm thick. Subsequent studies have focused on altering the
bioreactor design and cell seeding methodology (Radisic
et al.
, 2003; Radisic
et al.
, 2004; Bursac
et al.
, 2003). Rotating bioreactors were also shown to
produce in laminar conditions of 0.001Pa shear stress that stimulates myo-
cardium cells to grow and differentiate. Shear stresses on the order of 0.1Pa
have been found to have a debilitating effect on tissue growth (Bilodeau
and Mantovani, 2006). Cultures performed in perfusion bioreactors have
resulted in tissue as thick as 1-2 mm (Carrier
et al.
, 2002). Constructs were
characterized by uniform cell distribution and expression of cardiac cell
markers (Radisic
et al.
, 2005; Vunjak-Novakovic
et al.
, 1996). Recent experi-
ments have been conducted using a triple perfusion bioreactor (Dvir
et al.
,
2006). The bioreactor allowed for a homogenous fl uid fl ow along the bio-
reactor cross-section. Its design maximized the amount of perfusion a cel-
lular construct experienced. The system featured a fl ow-distributing mesh
to create an equal fl uid velocity and shear stress along the cell-construct
cross-section. It also implemented a more than 95% open pore net that
held the construct while subjecting it to medium fl ow. Papadaki
et al.
(2001)
have also studied the electrophysiological function of cardiac muscle using
scaffolds coated with laminin in a rotating bioreactor. The resulting con-
struct conducted electrical impulses at approximately the speed of those in
a native tissue.
5.4.3 Heart valves
An essential part of bioreactor design for tissue engineering of the heart
valves is replicating their behavior
in vivo
(Hoerstrup
et al.
, 2000a; Dumont
et al.
, 2002; Hildebrand
et al.
, 2004). Systolic and diastolic phases of the heart
valve motion are simulated by pulsatile medium fl ow and closing of the
valves respectively. This approach has also been taken in vascular tissue
engineering (Narita
et al.
, 2004; Sodian
et al.
, 2002). Studies using a diastolic
pulse duplicator (DPD) bioreactor simulated only the diastolic phase of the
cardiac cycle due to the amount of dynamic strain experienced during that
period of time. The stented leafl ets experienced continuous circulation of
4ml/min for nutrition delivery and waste removal. Tissues that were being
loaded either continuously or prestrained proved to be mechanically stron-
ger. Also, tissues experiencing continuous dynamic strain showed thicker
