Biomedical Engineering Reference
In-Depth Information
This observation leads to the conclusion that tissue function is a property of cell-cell
interactions. The size of the functional subunits is on the order of 100
m
m, whereas the size
scale of a cell is 10
m. Each organ is then comprised of tens to hundreds of millions of
functional subunits. The sizing of organs represents an evolutionary challenge that is also
faced by tissue engineering in scaling up the function of reconstituted tissues ex vivo.
The tissue and organ microenvironment is thus very complex. To achieve proper recon-
stitution of organ function, these dynamic, chemical, and geometric variables must be accu-
rately replicated. This is a challenging task, and the following sections are largely devoted to
developing quantitative methods to describe the microenvironment. These methods can then
be used to develop an understanding of key problems, formulation of solution strategy, and
analysis for its experimental implementation.
The microcirculation connects all the microenvironments in every tissue to the larger
“whole body” environment. With few exceptions, essentially all metabolically active cells
in the body are located within a few hundred
m
m from a capillary. The capillaries provide
a perfusion environment that connects every cell (the cell at the center of Figure 6.22)toa
source of oxygen and sink for carbon dioxide (the lungs), a source of nutrients (the small
intestine), the clearance of waste products (the kidney), and so forth. The engineering of these
functions ex vivo is a main focus of bioreactor design. Such culture devices have to appropri-
ately simulate or substitute for respiratory, gastrointestinal, and renal functions. Further,
these cell culture devices have to allow for the formation of microenvironments and thus
must have perfusion characteristics that allow for uniformity down to the 100-micron-length
scale. These are stringent design requirements.
m
6.3.2 Estimating Tissue Function from “Spec Sheets”
Most analysis in tissue engineering is performed with approximate calculations and
estimations based on physiological and cell biological data—a tissue spec sheet, so to speak
(see Table 6.8). These calculations are useful to interpret organ physiology, and they provide
a starting point for an experimental program. Some examples follow.
The respiratory functions of blood:
Remarkably insightful calculations leading to interpreta-
tion of the physiological respiratory function of blood have been carried out. The basic func-
tionalities and biological design challenges can be directly derived from tissue spec sheets.
Blood needs to deliver about 10 mM of O
2
per minute to the body. The gross circulation rate
is about 5 liters per minute. Therefore, blood has to deliver to tissues about 2 mM oxygen per
liter during each pass through the circulation. The pO
2
of blood leaving the lungs is about
90 to 100 mmHg, while pO
2
in venous blood at rest is about 35 to 40 mmHg. During strenu-
ous exercise, the venous pO
2
drops to about 27 mmHg. These facts state the basic require-
ments that circulating blood must meet to deliver adequate oxygen to tissues.
The solubility of oxygen in aqueous media is low and can be represented by
½
O
¼
a
O
2
pO
ð
6
:
17
Þ
2
2
where the Henry's law coefficient is about 0.0013 mM per mmHg. The oxygen that can be
delivered with a partial pressure change of 95 - 40
55 mmHg is thus about 0.07 mM,
far below the required 2 mM (by a factor of about 30-fold). Therefore, the solubility or
oxygen content of blood must be substantially increased, and the concentration dependency
¼
