Oxygen Transport in Bioreactors for Engineered Vascular Tissues - Computational Modeling in Tissue Engineering - page 287

In practice, the length and thickness of tubular tissue constructs are variable.
Residence time (tissue thickness divided by the average transmural flow velocity)
was therefore used as the independent variable. Figure 5 shows the comparison of
model results (lines) to measured DO concentrations. As shown in the figure, the
average DO concentration decreases linearly with residence time until the
consumption kinetics change (from zeroth to first order) due to low DO concen-
tration, with the transition occurring sooner with increasing cell density. Moreover,
increasing cell density has a large impact on the total DO consumed by the cells
within the tissue, which is also effectively captured by the model.
4 Pulsed Stretch-Flow Bioreactor
As highlighted in the previous section, bioreactor culture incorporating controlled
transmural flow can improve DO uniformity along the axial length of the cultured
tubular constructs. This work was conducted in an effort to evaluate improved
mass transport; however, it is known in the literature that mechanical stimulation
can increase collagen deposition and thus the mechanical properties of engineered
tissues so that they more closely mimic native tissue. Cyclic distension has been
shown to improve these properties of fibrin-based engineered grafts seeded with
nhDFs [ 14 ]. Along with high collagen content, the organization of the cell-
produced collagen fibers is also of critical importance. It should recapitulate the
predominant circumferential alignment of native arteries to provide burst strength
and confer the natural anisotropic mechanical behavior [ 24 ].
A bioreactor system was designed to allow for culture of multiple grafts such
that cyclic distention and cyclic transmural flow could be applied for stimulating
tissue growth. This bioreactor system has the unique advantage of applying all four
parameters that have previously been found to be beneficial for development of
mechanically robust engineered tissues: cyclic stretching [ 9 , 14 , 24 ], transmural
flow [ 22 , 23 ], lumenal flow [ 27 , 29 ], and ablumenal flow [ 15 , 30 ]. This bioreactor
system was shown to produce constructs having burst strengths with the highest
values reported for engineered grafts made from biopolymer scaffolds and would
be sufficient for implantation [ 24 ].
Reported here is an analysis of oxygen transport using this bioreactor system.
The analysis incorporated pulsatile flow through the lumen of fibrin-based tubular
tissue constructs using a combined experimental and computational approach. The
aim of this study was to investigate DO in the tissue, flow profiles in the system,
and to evaluate the theoretical effect of the frequency and volume of pulsatile flow
on the DO concentration profiles within the tissue. Direct measurements of
pressure and DO concentration both for the inlet flow and within the bioreactor
were used to help guide computational analysis.
A schematic of the bioreactor is provided in Fig. 6 . Tubular constructs
were mounted on a custom manifold, which was placed inside a jar of cell
culture medium during operation. A reciprocating syringe pump was connected to