CELL - BASED NANOCOMPOSITES AND BIOMOLECULES FOR BONE TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 546

TABLE 16.1. Continued

Cells Function References

5. The expression of Cbfa - 1 was not signifi cant in
samples treated with 1

, 25 - dihydroxyvitamin D3 and
dexamethasone at 3, 10 and 20 days as compared to
the controls. No expression of type II or III Cbfa-1 was
seen regardless of time point or treatment.

α

Ref 23 Adipose -

derived
stem cells

1. Vitamin D3, -glycerophosphate and ascorbic acid were

required for mineralization.
2. Type I collagen secretion was upregulated by ascorbic
acid and

β

- glycerophosphate.
3. Vitamin D3 induced osteonectin, osteopontin and
osteocalcin expression.
4. Vitamin D3,

β

- glycerophosphate and ascorbic acid
had a synergistic effect on sustained osteoblastic
transcriptional gene expression such as runt- related
transcription factor - 2 (RUNX - 2) and TAZ.

β

CTGF during the early stages of osteogenic differentiation 24 . Specifi cally, BMP - 2
and BMP-7 are some of the predominant BMPs used and are able to induce
osteogenic differentiation and bone healing. In a study involving 450 patients
with acute, diaphyseal, open tibial fractures, the risk of secondary intervention
was greatly decreased in the rhBMP-2 group as compared to the control group
(standard of care for long bone repair) 25 ; rhBMP-2 seeded on resorbable collagen
sponge can be used in spinal fusion and open fractures in patients as it is FDA-
approved, while rhBMP-7 and bovine collagen or OP-1 is also FDA-approved
and can be utilized as an alternative option to autografts in long bone non-unions
and lumbar spinal fusion.
Despite the use of BMPs being potent inductors of osteogenic differentia-
tion, the amounts of BMPs needed vary in humans and in animal studies. In
humans, greater levels of BMPs are required for osteogenesis than in animals. It
is evident that BMPs elicit a favorable response when added in culture medium
or in material substrates. Yet there is a variability in terms of patient response to
BMP treatment and minute amounts of BMPs in the nanogram range are suffi -
cient to trigger bone formation in vivo 26 - 28 . On the other hand, at least a magni-
tude of six orders was reported to result in osteogenesis in human with a matrix
substrate 29 . A controlled-delivery system of biomolecules or therapeutic agents
can be achieved using tissue-engineered biomaterials.
Besides BMPs, other growth factors which are important for bone formation
include insulin-like growth factor 1 (IGF-1), fi broblast growth factor (FGF-2) and
vascular endothelial growth factor (VEGF). Table 16.2 shows the types of growth
factors used in polymeric substrates for bone repair 30 - 38 .
Smad, Smurf and Tob proteins are also part of the intricate network of the
osteogenic pathway 39 . The administration of such growth factors can be utilized in