Biomedical Engineering Reference
In-Depth Information
factors(FGFs)andvascularendothelialgrowthfactors(VEGFs)stim-
ulate blood vessel differentiation (angiogenesis). The hepatocyte
growth factor (HGF) also has angiogenic activity. In the field of tis-
sue engineering, growth factors are now recognized as a fundamen-
tal requirement, in addition to cells and materials (either synthetic
substrates or naturally occurring matrices).
The prolonged retention and activity of growth factors on cells
or surrounding environment (i.e., the extracellular matrix [ECM]
or artificial implant scaffold) is considered to be advantageous in
regenerative medicine applications, until the repair process is ini-
tiated or even completed. However, most growth factors act in a dif-
fusible manner and are generally unstable in a tissue environment,
whenexogenouslyapplied;forexample,thehalf-lifeofintravenously
administered bFGF is very short (1-2 min).
2
Thus, many attempts
have been made to improve the performance of growth factors (i.e.,
their active period and stability). One approach is the controlled
releaseofgrowthfactorsviathedevelopmentormodificationofthe
carriermaterialsthatareusedforthedeliveryofthesemolecules.
3
,
4
The other approach is the modification of growth factors for immo-
bilization on, or for high-a
nity binding to, cells or scaffold bioma-
terials.Thischapterfocusesonthelatterapproach,especiallyonthe
engineering of growth factors using recombinant means to confer
bindinga
nity.
17.2 Diffusible and Nondiffusible Actions of
Growth Factors
Figure 17.1 summarizes the modes of action of growth factors in
cells. Diffusible interactions (e.g., endocrine, paracrine, autocrine,
and intracrine) and nondiffusible interactions (e.g., juxtacrine and
matricrine) are known to occur. It is also known that each growth
factor does not necessarily have a single mechanism of action at the
cellular level.
Most growth factors act in a diffusible manner, interact with the
cognate receptor on the cell membrane, and form a complex. This
interactioninducesthephosphorylationofthereceptorandtriggers
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