Biomedical Engineering Reference
In-Depth Information
6.4.3 Time Scales of Mass Transfer
The importance of mass transfer in tissue and cellular function is often overlooked. The
limitations imposed by molecular diffusion become clear if the average displacement
distance with time is plotted for diffusion coefficients that are typical for biological
entities of interest in tissue function (Figure 6.29). The diffusional penetration lengths over
physiological time scales are surprisingly short and constrain the in vivo design and
architecture of organs. The same constraints are faced in the construction of an ex vivo
device, and high mass transfer rates into cell beds at physiological cell densities may be
difficult to achieve.
The biochemical characteristics of the microenvironment are critical to obtaining proper
tissue function. Much information exists about the biochemical requirements for the growth
of continuous cell lines. For continuous cell lines, these issues revolve around the provision
of nutrients and the removal of waste products. In cultures of primary cells, the nutrients
may have other roles and directly influence the physiological performance of the culture.
For instance, recently it has been shown that proline and oxygen levels play an important
role in hepatocyte cultures.
In most cases, oxygen delivery is likely to be an important consideration. Too much oxy-
gen will be inhibitory or toxic, while too little may alter metabolism. Some tissues, like the
liver, kidney, and brain, have high oxygen requirements, while others require less.
Controlling oxygen at the desired concentration levels, at the desired uniformity, and at
the fluxes needed at high cell densities is likely to prove to be a challenge. Further, the oxy-
gen and nutritional requirements may vary among cell types in a reconstituted tissue that is
comprised of multiple cell types. These requirements further complicate nutrient delivery.
Thus, defining, designing, and controlling the biochemical characteristics of the microenvi-
ronment may prove difficult, especially given the constraints imposed by diffusion and any
requirements for a particular microgeometry.
EXAMPLE PROBLEM 6.7
How are specific oxygen uptake rates measured?
Solution
Most data on specific oxygen uptake rates are obtained with cells in suspension using standard
respirometers. However, to obtain accurate and representative data for primary cells, they need to
be adherent. This challenge has led to the design of a novel in situ respirometer, shown in
Figure 6.30. This respirometer has been used to measure the oxygen uptake rates of hepatocytes
in culture (OUR of 1.0
moles/million cells/hr). A similar device has been used to measure the
OUR in bone marrow cultures, giving results of 0.03 to 0.04
m
m
moles/million cells/hr which are
similar to the in vivo uptake rates.
