Biomedical Engineering Reference
In-Depth Information
This further study demonstrated the need for mechanical stresses as well
as low-density scaffolds in rotating bioreactors for bone tissue engineering.
Key studies undertaken in recent years to illustrate progress in this fi eld
are included in Table 5.1.
5.4.5 Cartilage
Topographical differences in the thickness of native cartilage create com-
plexity in the replication of its structure and mechanical properties in con-
structs
in vitro
as well as
in vivo
. Thickness and matrix content of cartilage
joint depends on the amount of load experienced by each layer (Brama
et al.
, 2000; Rogers
et al.
, 2006). This also results in mechanically different
zones classifi ed according to their depth from the articular surface: superfi -
cial, middle and deep (Reinholz
et al.
, 2004). Cartilage constructs grown in
stirred tank reactors demonstrated some potential. In static conditions carti-
lage tissue of less than 0.1mm thick with a rough surface was produced, and
a smooth surface was obtained with thickness ranging from 0.3 to 0.5 mm
(Freed and Vunjak-Novakovic, 1997b). However, due to poor mass transfer
capacity, the system failed to provide clinically-sized implants, which need
to be about 2-5 mm thick (Freed and Vunjak-Novakovic, 1997b). In another
study with a hollow fi ber reactor, cartilage tissue with a thickness of 1 mm
was obtained. However, it has still not reached the thickness required for
viability (Potter
et al.
, 1998).
Experiments performed using bioreactors that use laminar fl ow condi-
tions have shown strong bulk mechanical properties due to high glycos-
aminoglycan (GAG) content (Vunjak-Novakovic
et al.
, 2002). Tissues with
low peripheral GAG content have also been achieved using this system
(Marsano
et al.
, 2006). Increasing hydrostatic pressure has been positively
correlated with increased GAG content in constructs, especially by chondro-
cytes found in the middle of the construct. Chondrocytes, particularly in this
region of scaffolds, have shown increased calcium response and ECM depo-
sition (Mizuno, 2005). Perfusion systems have been used in cartilage tissue
engineering for matrix synthesis of chondrocytes (Strehl
et al.
, 2005; Zhao
and Ma, 2005; Minuth
et al.
, 2004). Gray
et al.
(1988) had demonstrated that
an acidic environment is detrimental to deposition of ECM and subsequent
regeneration of cartilage. Given a decrease in pH due to metabolic activity of
chondrocytes, perfusion fl ow can be seen as a means of cancelling this effect.
Hydrostatic pressure and complex fl uid shear force present in these systems
stimulate greater DNA content as well as GAG and collagen deposition than
in static controls (Dunkelman
et al.
, 1995; Davisson
et al.
, 2002a).
Davisson and colleagues have found that continuous perfusion results
in a signifi cantly higher DNA and sulfatedglycosaminoglycan content than
