CELL - BASED NANOCOMPOSITES AND BIOMOLECULES FOR BONE TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 544

Cell

Growth factors

Material

Figure 16.1. A typical tissue-engineered material construct, with the addition of cells and
growth factors.

facilitate osteogenic differentiation of cells. For instance, dexamethasone stimu-
lates proliferation and aids in the osteogenic lineage differentiation, ascorbic acid
and 1,25-Dihydroxyvitamin D3 can be used for osteogenic induction, promotion
of the deposition of matrix, increasing alkaline phosphatase (ALP) activity and
osteocalcin production 12 . Ascorbic acid plays a role in the conversion of proline
residues in collagen to hydroxyproline. -glycerophosphate acts as a form of

phosphate supply and plays a role in mineralization and osteoblastic processes.
Free phosphates can induce the expression of osteoblastic markers such as osteo-
pontin 13 . Other functions of phosphates include the production and nuclear
export of an important osteogenic regulatory gene called core-binding factor

β

- 1
(cbfa - 1) 14 . Osteogenic supplements such as dexamethasone are often added in
culture medium to direct osteogenic differentiation of either mesenchymal stem
cells (MSCs), progenitor cells, or osteoblasts. Dexamethasone are bound to
regulatory proteins and modulating the transcription of osteogenic genes 15 - 19 .
Encapsulated human mesenchymal stem cells (hMSCs) exhibited an osteogenic
effect when dexamethasone was released in a sustained manner over a month in
a poly(ethylene glycol) (PEG) hydrogel due to the hydrolysis of the lactide ester
bonds, where ALP and cbfa-1 were enhanced 16 . Table 16.1 shows an overview of
the effects of various culture media supplements for osteogenesis in vitro 20 - 23 .
Some of the benefi ts of using differentiation medium are expansion of cell number
and cellular maturity, yet there may be an increased risk of cell contamination
during culture, cell aging, time loss in terms of direct application of cells into
patient, and so on.
BMPs are members of the transforming growth factor-

α

) family
that are potent stimulators of bone regeneration. For instance, BMP-2, BMP-7,
and so on, have been evaluated and shown that they have the capability to
heal bone defects in vitro and in vivo . One particular study demonstrated that
by using recombinant adenoviruses expressing BMPs, BMP-6 and BMP-9,
in addition to BMP-2 showed the highest osteogenic activity (and to a lesser
degree, BMP - 4 and BMP - 7) in both in vitro and in vivo settings. The osteogenic
BMPs regulate a set of downstream target genes such as Ids, Dlx, and

β (TGF - β