Biomedical Engineering Reference
In-Depth Information
observed physiologically in development and wound healing. It is recognized that basic fibroblast
growth factor (bFGF) function to promote such angiogenesis. The growth factors stimulate the appro-
priate cells (e.g., endothelial cells), already present in the body, to migrate from the surrounding tis-
sue, proliferate, and finally differentiate into blood vessels
[9]
. However, it is not always expected
that the angiogenesis activity will be sustained when these proteins are injected in the solution form,
probably because of their diffusional excretion from the injected site is rapid. One possible way for
enhancing the
in-vivo
efficacy is to achieve its controlled release over an extended time period by
incorporating the growth factor in a polymeric carrier. If this carrier is biodegradable and harmonized
with tissue growth, it will work as a scaffold for tissue regeneration in addition to its function as a
matrix for the growth factor release. The use of angiogenic factors is a popular approach to induce
neovascularization. Among them, bFGF plays a multifunctional role in stimulation of cell growth and
tissue repair. However, bFGF has a very short half-life when injected and is unstable in solution. To
overcome these problems, bFGF was encapsulated within alginate, gelatin, agarose/heparin, collagen,
or poly(ethylene-
co
-vinyl acetate) carriers
[10-12]
. According to the results of these studies, it is con-
ceivable to incorporate the angiogenic factor in a sustained releasing system and use it prior to the
implantation. Some studies have demonstrated that bFGF achieved promoted angiogenesis when used
in combination with delivery matrices and scaffolds
[13]
.
There are other growth factors currently used in tissue regeneration. Hepatocyte growth factor
(HGF) is originally discovered as a protein factor to accelerate hepatocyte proliferation. Previous
studies have demonstrated that HGF has great potentials for proliferation, differentiation, mitogen-
esis, and morphogenesis of various cells
[14]
. Therefore, HGF can be used for various tissue engi-
neering applications where angiogenesis is needed. However, since growth factors such as HGF have
very short half-life, when they are injected into the body they lose their biological activities rapidly.
Sustained release technologies have been employed for different drugs and proteins to overcome this
problem.
Osteoinductive properties of bone morphogenetic protein (BMP) family have attracted much
attention in terms of bone regeneration because BMP has high potentials to promote the differen-
tiation of stem cells into ostogenic linage. BMPs belong to the transforming growth factor-β (TGF-
β) superfamily and play an important role in osteogenesis and bone metabolism. It is strong enough
to induce bone formation even at ectopic sites, such as subcutis and muscles. There are at least 15
types of BMP currently reported, and some recombinant human BMPs (rhBMP) are available at large
amounts by the recombinant DNA technology. Among them, rhBMP-2 and rhBMP-7 (OP-1) have
already been clinically applied to repair the critical-sized bone defect and accelerate healing
[15]
.
Osteogenic growth factors such as TGF-β, BMPs, and bFGF can induce bone formation in both ecto-
pic and orthotopic sites
in vivo
.
Table 14.1
summarizes the characteristics of growth factors used in
tissue engineering.
Since rhBMP-2 has become available, many animal studies on the induction of bone formation
by implantation of rhBMP-2 using various carriers have been performed
[16]
. However, the use of
BMP alone requires large amounts of protein because of its short half-life. Furthermore, the response
to BMPs varies between animal species. Moreover, primates need larger amounts of BMP (up to mil-
ligrams) compared to rodents. Aging has also been reported to lead to a reduction in response. To
overcome these problems and reduce the amounts of BMP required, developments in new types of
scaffold and combined treatments with other reagents which can enhance bone regeneration are under
investigation.
