Biomedical Engineering Reference
In-Depth Information
(see Figure 5). To investigate the effect of VEGF-B, Silvestre et al. implanted
collagen matrices into live rats and injected the growth factor into some of the
matrices (71). The injections promoted the formation of new blood vessels,
known as angiogenesis, in the matrices.
One of the molecular interactions that is most important to implants is the
immune response (see also this volume, Part III, section 4). The immune re-
sponse is what rejects foreign transplants into the body, and the trigger for this
response is a set of cell-surface molecules that the body recognizes as being for-
eign. While in theory engineered tissues should have the native set of surface
molecules and not be subject to an immune response, experiments have shown
that even autograft tissues can produce unexpected immune reactions (28).
Another large class of molecules is cell adhesion molecules (CAMs). These
are responsible for cells binding to each other, to extracellular matrix, and to any
other surface. There has been a large amount of research into CAMs, so that we
now know which CAMs are present on the surface of each cell and what ex-
tracellular components each CAM binds (62), information vital to producing
tissues that are strongly bound together.
Many other families of molecules involved in cell signaling are known to
exist, and there are likely signaling molecules that have not yet been discovered.
Recent research shows that cell signaling acts in cascades, where signals intro-
duced at different times and in different combinations have widely varying ef-
fects on a cell's development. While our understanding of cell signaling is
rapidly improving, it will be many years before all cell signaling pathways are
known.
2.1.2. Submicron Solid Mechanics
A theoretical model for the solid deformation of a biological tissue is based
on the microstructure of that tissue. Until recently, researchers could only exam-
ine the bulk behavior of tissues. In the past decade such methods as optical
tweezers and scanning-force microscopy have been developed that allow inves-
tigation of tissue behavior at the molecular level (12). New understanding of
molecular behavior allows for improved models of bulk behavior.
Investigations of molecular behavior are now common. Evans and Ritchie
used atomic force microscopy (AFM) to investigate the strength of molecular
adhesion bonds (Figure 6), and also developed computational models to predict
this behavior (18) (Figure 7).
Molecular experiments are useful in increasing our understanding of mo-
lecular interactions, but perhaps more important, molecular models can now be
scaled up to predict bulk mechanical behavior of tissues. Kwan and Woo created
a constitutive model for aligned collagenous tissue by taking a simple stress-
strain model for a single collagen fiber and calculating the effect of many of
