Oxygen Transport in Bioreactors for Engineered Vascular Tissues - Computational Modeling in Tissue Engineering - page 292

result, as would be expected since transmural flow is driven by pressure. When
peak pressures of 25 mmHg or greater were implemented, corresponding
to h Pe r,O2 i of 4.7 and higher, the DO profile shifted in the direction of transmural
flow as shown in Fig. 10 a.
The 1D COMSOL model was extended to glucose to by altering the Michaelis-
Menten constants, glucose diffusivity in tissue, and C 0 as listed in Table 1 . The
glucose consumption rate and K m for glucose in dermal fibroblasts were reported
to be 9.25 fmol/min/cell and 1.5 mM, respectively [ 30 , 31 ]. The boundary values
for glucose, C 0 , were again assumed to be the same because of a high recirculating
flow rate, but now computed from a macroscopic mass balance on glucose within
the bioreactor in between culture medium changes. The glucose concentration
profiles within the tissue are shown in Fig. 10 b for C 0 = 25 mM (the standard
glucose concentration for DMEM used in experiments). Similar to the DO profile,
increasing P peak yields greater uniformity in the concentration profile for glucose;
however, lower pressures yield larger effects when L p = 10 -6 cm/s/Pa. For
pressures as low as 5 mmHg, a greater shift in the glucose concentration profile
occurs compared to a similar pressure for DO. This difference can be attributed
largely to the diffusivity of glucose being two orders of magnitude less than
oxygen, as shown in Table 1 , which increases the impact of transmural flow on its
transport relative to oxygen.
5 Discussion
The computations and measurements presented here provide insight on DO pro-
files in tubular tissue constructs during operation of several bioreactor configu-
rations, highlighting the improvement in DO uniformity over static culture. The
DO transport models under steady-flow demonstrate improved uniformity when
controlled transmural flow was combined with axial flow. The DO concentration
profile in the tissue is greater and more uniform when transmural flow is incor-
porated versus a more simplistic bioreactor using only axial flow through the
lumen. Model results of outlet DO values agreed with measurements collected
during culture of fibrin-based tubular tissue constructs in the bioreactor system.
Implementation of transmural flow must also take into consideration the lumenal
pressure and interstitial shear stress, which the models predict can lead to tissue
failure (bursting) and cell damage or death, respectively, at higher transmural flow
rates. For these reasons, the combination of transmural and axial flow is superior to
transmural flow only.
The models were further extended to assess the potential benefits of cyclic
perfusion for DO delivery beyond the benefits of mechanical stimulation to the
tissue. In analyzing a pulsed stretch-flow bioreactor, a symmetric 3D model
revealed the extensive level of fluid mixing between the lower manifold and
bottom of the chamber. Mixing helps to provide uniform nutrient delivery as
the fluid flows up around the lower manifold and then around the constructs.