Biomedical Engineering Reference
In-Depth Information
fabricating 3D tissues. Many researchers have tried to incorporate
growth factors within polymer scaffolds because they can be simply
mixed within both hard porous materials and soft matrix gels, and
then biodegradation of the scaffold leads to the slow release of the
growth factors (Fig. 6c.2). Heparin, which moors several growth
factors to an extracellular matrix (ECM), is often loaded into the
scaffolds to control their release. Recently, covalent immobilization
of growth factors to scaffold materials has been investigated, and it
has been successful in localized and sustained growth factor delivery.
As described previously, different growth factors contribute
to vascular structure formation at different phases. Therefore,
the delivery of a single growth factor seems to be insufficient for
vascularization in regenerating tissues, and the controlled release of
multiple growth factors is now the challenge. The controlled release
of two growth factors with a dual-factor release system has been
reported [14-16]. The system has two different releasing speeds,
VEGF held by the scaffold and PDGF-BB held by the poly(lactide-
glycolid) (PLG) microsphere in the scaffold, where VEGF is released
faster than PDGF.
Instead of protein delivery, complementary deoxyribonucleic
acid (cDNA) for growth factor- or gene-modified cells has also been
applied to neovascularization of engineered tissues. Furthermore
several research studies have demonstrated the positive effects of
in vitro preconditioning under a hypoxic state [17]. Vascular growth
factors induced by ischemic signals in vitro seem to accelerate
primary blood vessel formation when the constructs are implanted
in vivo.
Proper control of multiple growth factors using a combination
of various techniques may improve vascularization in bioengineered
tissues.
6c.5
Coculture System Using Blood Vessel-
Composing Cells
A recent promising approach for neovascularization is to coculture
the cells that make up blood vessels with the target cells (Fig. 6c.3).
Many studies have demonstrated that cocultured endothelial cells
spontaneously form vascular-like networks in engineered tissues
in vitro and that the endothelial cells connect to host blood vessels
