Biomedical Engineering Reference
In-Depth Information
PERFUSION
The circulatory system provides blood flow to organs that is then distributed into the
microenvironments. Overall, the perfusion rates in a human are about 5 liters/min/70 Kg,
or about 0.07 ml/cc/min. With 500 million cells per cc, this is equivalent to 0.14
l/million
cells/min. These numbers represent a whole body average. There are differences in the
perfusion rates of different organs that typically correlate with their metabolic activity.
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CELL MOTION
As described earlier, cells are motile and move at different rates. Neutrophils can move
several cell diameters in a minute, while adherent cell types, such as keratinocytes, fibro-
blasts, and endothelial cells, move on the order of a cell diameter per hour. These motilities
represent rapid processes compared to cell replication and differentiation. Neutrophils have
to be able to respond rapidly to invading microorganisms, while the adherent cell types
mentioned move in response to dynamic tissue needs.
Size and Geometry
GEOMETRY
The geometric shapes of microenvironments vary (see Figure 6.25), and so do their
dimensionalities. Many microenvironments are effectively curved 2-D surfaces. The cellular
arrangement in bone marrow has been shown to have a fractal geometry with effective
dimensionality of 2.7, while the brain is a 3-D structure.
WHAT DETERMINES THE SIZE OF THE MICROENVIRONMENT?
The answer to this question is not clear. At the lower limit is the size of a single cell,
about 10
m. A cell aggregate must be some multiple of this distance. The factors determin-
ing the upper limit are not clear. However, estimates of effective growth factor signal prop-
agation distances and experimental evidence of oxygen penetration distances suggest that
the dynamics of cell communication and cell metabolic rates are important in determining
the size scale of the microenvironment. These distances are determined by the process of
diffusion. In both cases, the estimated length scale is about 100 to 200
m
m. The stability
issues associated with coordinating cellular functions grow with an increased number of
cells and may represent a limitation in practice.
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6.3.5 Biomaterials
Biomaterials for tissue engineering present several challenges. There are basically three
length scales of interest. The shortest is at the biochemical level, where concerns include
the specific chemical features of the ECM and interactions with cellular receptors. Intact
ECM components can be used to coat support material to ensure appropriate interactions
among the cells and their immediate environment. More sophisticated treatments involve
the synthesis of specific binding sequences from ECM protein and presenting them in various
ways to the cells. Particular cellular arrangements can be obtained by micropatterning such
materials. A combination of material manufacturing, biochemistry, and genetics is required
to address these issues.
