CELL - BASED NANOCOMPOSITES AND BIOMOLECULES FOR BONE TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 547

TABLE 16.2. Types of Growth Factors Used in Various Materials for Bone Regeneration

Materials Form Growth factors Animal model References

Refs 31,33

Collagen Sponge BMP - 2 Goat, rat, rabbit

Ref 34 Gelatin Hydrogel BMP - 2 Rabbit

Rat Ref 36

TGF - β 1+IGF - 1

Alginate Hydrogel Mouse Ref 32

TGF - β 3+BMP - 2

PLGA Scaffold VEGF Rat Ref 38

VEGF+BMP - 4 Mouse Ref 30

PLLA Scaffold TGF - β 3 Sheep Ref 37

HA/TCP Porous implant TGF - β 2 Dog Ref 35

tissue-engineered constructs to induce bony formation. Certain secreting pro-
teins such as Wnts are known to be involved in cellular differentiation such as
osteogenesis 40 . Notch signaling has been also said to have a non-promotive role in
osteogenic differentiation of progenitor cells as ALP activity, osteocalcin, type I
collagen and in vitro calcifi cation were suppressive 41 .
Heparan sulfate (HS) was assessed as a potential osteogenic agent in a rat
model 42 . Five g of HS was incorporated in the fi brin glue scaffolds and the release

kinetics were analysed. More than 50% of HS was released with an initial burst
phase in the fi rst four hours, followed by a sustained release over four days during
which 100% of HS was released. The released HS led to improved wound healing
over a three-month period and increased ALP, RUNX-2 and osteopontin gene
expression. In contrast, minimal healing was seen in the absence of HS after one
and three months of implantation 42 . Growth factors such as FGF-2 and BMP-2
are susceptible to proteolytic degradation 43 . As such, HS comes in handy as it
binds to several soluble proteins such as heparin-binding growth factors, provid-
ing a protective shield from extracellular proteases and aiding specifi c binding to
their respective cell surface receptors 44 .
Although researchers have established promising experimental data on dif-
ferent cells derived from various origins on a wide range of materials, much work
is needed to be done in order for full scale production of these tissue-engineered
bone grafts. The physiological mechanical properties and the remodeling of
tissues for the restoration of physiological function are deemed to be one of the
deciding factors for tissue engineering constructs to replace current bone grafts.
Some have suggested that using additional tools such as “smart” scaffolds and
bioreactors can accelerate the development of tissue engineered materials for
various applications 45 . Bioreactors help create a “natural” environment for cell
proliferation, growth and differentiation at optimal conditions such as 37 °C, 5%
CO 2 , and so on. Specialized bioreactors may also include features such as cyclic,
rotational, or static loading to stress the cells to facilitate quicker extracellular
matrix deposition or to increase mechanical strength of the material construct,
and so on.

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