Biomedical Engineering Reference
In-Depth Information
spinner fl ask bioreactor, demonstrating the need for shear stress stimulation
of osteoblasts for growth factor pathway activation and stress fi ber forma-
tion (Sikavitsas
et al.
, 2002).
Capillary distance is also critical for proliferation of osteoblasts. Perfusion
fl ow reactors have produced constructs with higher phenotypic activity of
osteoblasts while increasing extracellular matrix production and mineraliza-
tion (Altman
et al.
, 2002). Optimal fl ow rate of 0.1 mL/min for 80% porous
scaffolding seeded with 2 × 10
6
osteoblasts has been reported to produce
maximal proliferation in a perfusion bioreactor (Porter
et al.
, 2001). The
same group has also reported that 2 mL/min fl ow rate caused upregulation
of osteopontin and osteonectin while signifi cantly reducing proliferation.
The effect of convection on rat stromal cells has shown that convection does
positively infl uence uniform distribution of cells without altering prolifera-
tion rates. Flow and spinner systems have induced higher alkaline phospha-
tase production after seven days. Osteocalcin was unaffected by changing
bioreactor conditions. A micro-carrier matrix system studied by Botchwey
and colleagues has also induced increased alkaline phosophatase produc-
tion in rotating bioreactor versus static conditions. Simulations and particle
analysis have calculated an almost circulatory trajectory with velocity of 98
mm/s and shear stress 3.9 dynes/cm
2
.
It is also important for a successful bioreactor to implement mechanical
conditioning for the tissue. The stretchable membrane substrate mecha-
nism has been widely studied as a way of introducing tensile and compres-
sive forces in a monolayer culture. Uniaxial stretching has been suggested
to closely model the
in vivo
conditions. Osteoponin has been stimulated
with uniaxial as well as biaxial strains (Owan
et al.
, 1997; Walker
et al.
,
2000). However, these technologies need to be successfully translated into
a 3D model. A piston model that compresses a perfused construct has been
used for cartilage and vascular systems (Ochoa and Vicanti, 2002; Pei
et al.
,
2002). Different motors can be utilized to simulate desired frequency and
strain rate. Another system that resulted in increased RNA synthesis used
microporous gelatin beads and osteoblasts subjected to cyclical compres-
sion in columns (Shelton and El Haj, 1992). Magnetic particles have also
been used to stimulate mechanically osteoblast cultures inside the per-
fusion bioreactor (Dobson
et al.
, 2002). The particles varied in size and
were coated with protein in order to attach and stimulate calcium channel
receptors. The translational and rotational movement experienced by the
cell-particle system resulted in torsional and translational forces applied
to the cellular membrane of cells. These forces have been documented to
stimulate actin fi lament stiffening, upregulation of osteoponin and greater
secretion of ECM proteins (Cartmell
et al.
, 2002). The study conducted by
Yu
et al.
(2004) on PLAGA scaffolds had shown that rotating wall bioreac-
tors can encourage cellular proliferation and uniform distribution of cells.
