Biomedical Engineering Reference
In-Depth Information
d
n
3
r
4
n
g
|
1
Figure 1.1 Functionalized drug carriers for active targeting of cancer cell.
20
Immo-
bilization of the RGD sequence allows effective active binding to (target-
ing) cancer cells and then localized delivery of the drug cargo that is
released upon degradation of the polymeric carrier.
which the RGD sequence plays a critical role.
23
RDG is recognized and bind
via integrins (a
5
b
1
, a
V
b
1
, a
V
b
3
, a
V
b
5
, a
V
b
6
, a
V
b
8
and a
IIb
b
3
) cell adhesion
receptors that bind to the extracellular matrix (ECM) proteins.
16,18,23-25
It has been demonstrated that laminins and collagens also contain RGD
sequences but
.
these are inaccessible,
thus are not
typically used for
surface modifications.
Many integrins are expressed in various tissues; however there is some
population which are expressed only in a certain type of cell or tissues. The
integrin receptors, which were found in human osteoblasts and are typically
used to regulate bone cell responses, are the fibronectin receptor
(a
5
b
1
),
16,18,23-27
vitronectin receptor (a
V
b
3
),
28
and the type I collagen receptor
(a
2
b
1
).
16,18,23-27
For this reason modification—functionalization—of implant
surfaces with biomolecules/protein to mediated cell adhesion to substrates
via integrins has recently become one of the most interesting approaches
in the development of new biomaterials including drug carriers that are
capable of targeting specific sides.
15,29-33
It has been already suggested that the RGD peptide, which interacts with
the a
V
b
3
and a
V
b
5
integrin sub-units, commonly associated with vitronectin,
increases biointegration of implants. Matsuura also demonstrated that RGD
contributes to the osteoconductive effect of hydroxyapatite more than tita-
nium.
34
This phenomenon is associated with higher anity and adsorption
capability of protein to hydroxyapatite surface than to titanium surface.
The positive effects of the RGD peptide on regulation of cell adhesion have
been confirmed in many in vitro as well as in vivo studies. Elmengaard
35
has
shown that RGD peptide-coated porous-coated titanium implant signifi-
cantly increased bone formation on and around the implant. In this study a
cyclic RGD (Figure 1.2), which interacts with both a
V
b
3
and a
V
b
5
integrin
sub-units has been immobilized on unloaded press-fit titanium implants.
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