Biomedical Engineering Reference
In-Depth Information
2.3. Millimeter-Centimeter Scale
A living tissue is subject to continual stresses applied by the tissues around
it and the fluids flowing throughout. These stresses have profound effects on the
cells in the tissue. To control the behavior of these cells, a tissue engineer must
often apply these forces in the lab, which requires both a knowledge of what
stresses and strains a cell will respond to and how to apply them.
2.3.1. Effects of Solid Deformation on Cells
Cells living on an extracellular matrix are stressed and strained as the ma-
trix is deformed. Often these deformations influence the behavior of the cell that
a tissue engineer is trying to control, a process known as mechanotransduction.
This is most evident in the fabrication of structural tissues such as cartilage,
heart valves, and blood vessels.
Structural tissues are composed almost entirely of extracellular matrix com-
ponents: heart valves and blood vessels are usually over 80% type I collagen in
combination with a few other ECM components and a small percentage of cells.
The cells, smooth muscle cells and fibroblasts, produce the ECM. For a tissue to
have the correct mechanical properties, the ECM must be produced in adequate
quantities and aligned in a certain direction. It is the forces applied by the ECM
on the cells that control the cellular production of ECM.
Applying deformation to tissues and observing the results can elucidate the
mechanotransduction process. McKnight and Frangos grew human vascular
smooth muscle cells on a collagen matrix and applied cyclic uniaxial stretch at
various strain rates (57). The smooth muscle cells produce aligned collagen only
when subjected to strains and strain rates similar to those they would be sub-
jected to physiologically. Chapman et al. performed similar work and found that
physiological cyclic stretching inhibits cell growth (13). These works together
suggest that applying physiologically appropriate stretching to a smooth muscle
cell will keep the cell in a steady state where it can be used to produce ECM
without the cell proliferating.
Articular cartilage, which bears the loads in all synovial joints, is also pro-
duced by cells, in this case chondrocytes. Physiologically, cartilage is rarely
subjected to tension but is often compressed. Efforts in tissue engineering of
cartilage have focused logically on the response of chondrocytes to compres-
sion. Sah et al. have shown that, while static compression inhibits protein pro-
duction of chondrocytes in an explanted cartilage sample, dynamic compression
promotes production of proteins in general and dynamic compression at various
rates promotes production of specific proteins (68).
2.3.2. Modeling of Solid Deformation
Understanding the deformation of tissues requires constitutive models to
describe the tissue's solid mechanics. Continuum models may be derived from a