Biomedical Engineering Reference
In-Depth Information
and homogenous architecture. The non-linear behavior of the dynami-
cally strained tissues suggested increase in collagen as well as cell content.
Continuous medium circulation was hypothesized as the main contributor
to improved tissue formation (Mol
et al.
, 2005). Nonetheless, these engi-
neered leafl ets proved about 10 times weaker than native tissue (Stradins
et al.
, 2004). The advantages noted from the use of DPD bioreactors have
been their ease of use, small size and the maintenance of sterility. Studies
using cyclic fl exures on polymeric scaffolds demonstrated the importance of
controlling the degradation rate of the construct under dynamic conditions
(Engelmayr
et al.
, 2003). Further study can lead to better understanding of
the effects of fl exure on heart valve development.
Pulsatile fl ow conditioning strengthens heart valves mechanically, while
constructs resemble native tissue structurally (Schenke-Layland
et al.
, 2003;
Hoerstrup
et al.
, 2000b). These studies illustrated that, without mechanical
conditioning, constructs lose their structural integrity and strength. Cells, on
the other hand, do not proliferate at an optimal rate. The potential pitfall
in heart valve bioreactor study is failure to replicate intra-corporeal condi-
tions experienced by the heart valves. The aim in this area of research is to
generate heart valves that are able to withstand high physiological stresses
while being implanted
in vivo
. Recent studies and signifi cant fi ndings in bio-
reactor-based tissue engineering of heart valves are listed in Table 5.1.
5.4.4 Bone
There is a long list of factors to consider in bone tissue engineering such as
waste removal and nutrient delivery, mechanical and hydrodynamic forces
must also be taken into account and pressure variations have to be kept
within a certain range. It has been determined
in vitro
that interstitial fl uid
provides the most relevant shear force in terms of stimulating osteoblasts
metabolism (Basso and Heersche, 2002). The major challenge in culturing
clinically relevant bone tissue is limited nutrient diffusion caused by lack of
extensive vasculature development. Cells that proliferate around pores in
the scaffold limit transport throughout the construct (Yang
et al.
, 2001). This
often leads to acceptable growth on the surfaces and limited growth on the
inside of the scaffold (Granet
et al.
, 1998). Fluid fl ow in 3D settings has been
studied extensively (Shelton and El Haj, 1992; Goldstein
et al.
, 2001; Gooch
et al.
, 2001; Sikavitsas
et al.
, 2002; Van Den Colder
et al.
, 2003).
A study by Sikavitsas and colleagues compared cultures in rotating wall
vessel reactors and spinner fl ask reactors. The results had shown that differ-
entiation and mineralization was limited by lack of mechanical stimuli and
lack of fl ow contributed to insuffi ciency of nutrients in rotating-vessel reac-
tors (Sikavitsas
et al.
, 2002). All of these categories were improved inside the
