Protein-based Biointerfaces to Control Stem Cell Differentiation - Biointerfaces: Where Material Meets Biology - page 7

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Figure 1.2 Mechanism of protein immobilization on the surface via three different
mechanisms: chemical linking, 36 physiosorption and the linker-free (via
active radicals) approach. 13,37,38

Not only was the increase in bone formation observed, but also a significant
reduction in presence of fibrous tissue around the implant was evidenced. 35
Because the RGD coating can be relatively easily applied to the surface it
offers a cost-effective way to enhance the early osseo-integration of press-
fitted clinical implants.
One of the interesting features of this approach was the use of cyclic
peptide. Cells typically show higher integrin binding a nity to the cyclic
RGD sequence and previous studies have shown that cyclic peptides are
more stable when immobilized to complex and three-dimensional sub-
strates. 39,40 Another important feature of cyclic RGD peptides is their high
selectiveness toward the a V integrin, which regulates activation of the
osteoblast-specific transcription factor (core binding factor alpha-1/runt
related transcription factor 2 during osteogenesis). 41 These peptides show
also more resistance to enzymatic cleavage, 42 and may also promote a more
stable cell-ligand bond. The integrin anity and specificity to the RGD
peptide is affected by both steric conformation and the amino-acid se-
quences flanking the RGD peptide. 43,44 Mooney 40 has also demonstrated
that a linear RGD peptide promoted osteogenic differentiation of pre-
osteoblasts (MC3T3-E1) but did not induce differentiation of hBMSCs or D1
stem cells. At the same time matrices that presented the higher-anity cyclic
form of this adhesion ligand enhanced osteoprogenitor differentiation in
three dimensions.
In vivo studies by Elmengaard 35 on press-fit titanium alloy implants coated
with cyclic RGD and its effect on bone ongrowth showed that after 4 weeks,
cyclic RGD coating significantly stimulated bone formation directly at the
interface. A two-fold increase in bone growth was found for RGD-coated

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