Biomedical Engineering Reference
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subcutaneously in rats. The results of this study demonstrated ectopic bone formation and sustained
osteogenic activity. Recent in-vivo study with a similar setup of calcium phosphate-BMP-2 coating
and titanium implants with BMP-2 passively deposited showed increased volume of bone deposition
[52] . Bone interface coverage was highest for coated implants bearing no BMP-2, followed by coated
implants bearing either incorporated only, or incorporated and adsorbed BMP-2; it was however lowest
for uncoated implants bearing adsorbed BMP-2. This study showed the importance of using calcium
phosphate coating to deliver BMP-2 at the bone-implant interface. A recent study in-vivo has shown
that BMP-2 adsorbed biomimetic calcium phosphate coating was osteoinductive, but not highly effica-
cious [71] . The use of such biomimetic coating has been reviewed in the literature for their applications
in clinical orthopedics and dentistry [72] . Such attempts have shown that titanium surface can be modi-
fied at the micro- and nanometer scales with HA/calcium phosphate coating which can deliver osteoin-
ductive factors and effectively induce osseointegration at the bone-implant interface.
6.2.3.3 Organic Nanoscale SAMs
Another way of biochemical modification of titanium surface is through SAMs. This technique
involves adsorption and self-assembly of single layers of molecules on a substrate. Molecular self-
assembly of alkane phosphate SAMs on metal oxides like TiO 2 and Al 2 O 3 have been reported [73,74] .
The hydrophilicity of these alkane phosphate SAMs can be modified with a hydroxy-terminated end
group. When smooth and rough titanium surfaces coated with hydroxy-terminated (hydrophilic) and
methyl-terminated (hydrophobic) alkane phosphate SAMs were exposed to human fibroblasts, more
fibroblasts were found on smooth surface. The researchers concluded that surface wettability was
much less important than surface roughness [75] . But recent studies have concentrated on the role
of SAMs in the formation of HA on titanium substrate. Titanium wafers with carboxyl ( COOH),
hydroxyl ( OH), phosphate ( PO 4 H 2 ), and sulfonic acid ( SO 3 H) end group SAMs were placed
in SBF. The sulfonic acid ( SO 3 H) and carboxyl ( COOH) end groups produced a predominantly
crystalline HA. Furthermore, the carboxyl ( COOH) end group yielded the thickest layer which pos-
sessed crystalline characteristics very similar to that of the human bone [76] . A similar in-vitro study
on titanium coated with amine ( NH 2 ), thiol ( SH), and sulfonic acid ( SO 3 H) end group SAMs
showed that thiol ( SH) end group favored the formation of HA ( Figure 6.5 ), resulting in a layer
with a thickness of about 10 μm [77] . In-vivo study was performed with titanium surface with three
coatings: self-assembled monolayer of phosphonate molecules (SAMP), SAMP RGD peptide,
or HA. Histological analysis showed abundant new bone formation around all of the three groups,
though higher enhanced formation was apparent in the two SAMP groups [78] . Self-assembled RGD
peptide-modified surfaces have also been highlighted as one of the most promising and novel meth-
ods to enhance osteoblast function. In-vitro study using rat calvarial osteoblasts on gold-coated tita-
nium surfaces with self-assembled RGDC monolayer showed enhanced cell attachment, increased cell
spreading, and significantly greater cell proliferation on the RGDC-coated surfaces [79] . Such studies
showed that SAMs could be used to control the physicochemical properties (e.g., wettability) and bio-
chemical composition of titanium surface to influence the response of host tissue.
6.2.3.4 Hydrogels on Titanium Surface
Hydrogel is a network of polymer chains that swell in aqueous solution. Hydrogel is composed of long
polymer chains connected by cross-links. The cross-links may be biodegradable or nonbiodegrada-
ble and are ionic interactions between polyelectrolyte chains. Cross-linking of polymer molecules
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