Biomedical Engineering Reference
In-Depth Information
3 Oxygen
The main mechanism by which cells acquire their energy is through oxidative
phosphorylation [
2
]. In this process oxygen serves as an oxidizing agent that
facilitates the flux of electrons through progressively lower energy states, which
allows for a large extraction of free energy used to synthesize adenosine tri-
phosphate (ATP) molecules. Apart from energy production, oxygen has proven to
be a potent modulator of cell behavior that can change cellular phenotype [
56
],
stimulate matrix production by the cells [
94
] or induce angiogenesis by the release
of angiogenic factors [
26
]. Molecular oxygen however has a low solubility in
culture medium and is rapidly consumed by the cells in order to meet their con-
tinuous energy demands. These factors make soluble oxygen very prone to become
depleted during culture [
42
].
To what extent in time and space oxygen might become depleted within a
carrier is not only regulated by the intrinsic mass transport properties of the carrier
alone. A major influence comes from the cells themselves. This includes the
cellular demand for dissolved oxygen, expressed by the cellular oxygen uptake
rate (OUR), which is known to be controlled by many factors.
Firstly, cells harvested from distinct tissue types in the body can have signifi-
cant differences in OUR [
109
]. Secondly, the availability of oxygen to the cells is a
strong determinant of mitochondrial respiration. When cells are exposed to oxygen
tensions below a critical value, the redox state of cytochrome oxidase or the
respiration rate itself is partially limited [
12
]. This effect can be captured by a
Michaelis-Menten kinetic [
34
],
c
O
2
x
;
y
;
z
; ð Þ
K
q
þ
c
O
2
x
;
y
;
z
;
t
Qx
;
y
;
z
;
t
ð
Þ
Q
max
ð
Þ
where Q is the oxygen uptake rate (mol cell
-1
h
-1
); Q
max
is the maximal OUR
(mol cell
-1
h
-1
); and K
q
the oxygen tension at half of the maximal consumption
rate (mol m
-3
). Both kinetic parameters were furthermore shown to be dependent
upon specific cell-material interactions [
45
,
80
]. This relation could have important
consequences related to biomaterial choice and cell remodeling behavior.
Underlying the total drop in oxygen tension inside the carrier is the effective
number of metabolically active cells. Cell growth inside a biomaterial carrier can
be modeled in many ways. This ranges from simple linear or piece-wise linear
relationships with available nutrient concentrations [
84
] to more detailed models
such as the modified Contois equation,
"
#
A
cell
c
O
2
ð
x
;
y
;
z
;
t
Þ
P
C
x
;
y
;
z
;
t
ð
Þ
c
cell
Þ
dx
;
y
;
z
;
t
ð
Þ
K
C
c
cell
ke
cell
þ
c
O
2
ð
x
;
y
;
z
;
t
where P
i
denotes the cell growth kinetic function (cell m
-3
day
-1
); c
cell
is the cell
density (cell m
-3
); A
cell
is the homogeneous growth rate (day
-1
); K
C
is the
modified Contois saturation constant; e
cell
is the cell volume fraction (V
cell
/V); V
cell
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