Biomedical Engineering Reference
In-Depth Information
diffusion to the wall of the vessels occurs, resulting in a low concentration of the drug close to the
surface of the device. A well-known example of a coating that contains drugs is found on drug-elut-
ing stents.
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The bare metal is coated with a polymer from which paclitaxel or rapamycin are slowly
released, inhibiting cell growth between the struts of the stent. In this way restenosis, or the reduction
of the vessel lumen is avoided. Therefore the metal contributes to the mechanical properties of the
device (expandibility and strength) while the coating infl uences the biological environment in such
a way that restenosis is greatly reduced. The only downside of these drug-eluting stents is that they
are more expensive, and are consequently often only used in more complicated situations. Therefore,
some long-term clinical studies sometimes showed disappointing results.
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But in straightforward
stent placements, these drug-eluting stents could reduce restenosis from 15% to 20% to less than 2%.
Also several coatings with heparin have been tested and are employed. This sulfated polysaccharide
mimics heparan sulfate that normally appears on the endothelial surface.
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Heparin can cata-
lytically inhibit both factor X and thrombin (Figure 17.5), thus reducing the thrombin generation
and thrombus formation near the coating surface. Because the heparin functions as a catalyst, it
remains active for an extended period. This drug is also robust and can survive common sterilization
protocols, like ethylene oxide gas, UV illumination, or gamma irradiation. There have been several
additional attempts to cover the surface of blood-contacting devices with other drugs that infl uence
coagulation of platelet adhesion and activation. Most of these coatings do show a signifi cant effect
on coagulation, but they are sensitive and will not be stable under sterilization conditions. Also the
economics of some of these coatings is unfavorable, thus too expensive to use routinely.
iii. Biomimetic and bioactive coatings are coatings that try to mimic the chemistry and
topography of the endothelial layer that lines the vessels. In healthy individuals the endo-
thelial cells that line the blood vessels, retain blood hemostasis.
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This means that these
cells counteract disturbances in the balance between coagulation and anticoagulation. To
mimic this endothelial layer one can attempt to obtain a function endothelial cell layer on
the implants. This will be discussed in the next session. Also attempts have been made
to chemically synthesize a biomimetic coating, a coating that resembles the outside of
endothelial cells. One example is the attachment of PLs to surfaces. This will result in a
mono- or bilayer of PLs mimicking the cellular membrane. Also polymers containing the
monomer 2-methacryloyloxyethyl phosphorylcholine (MPC), shown in Figure 17.12, are
examples of biomimetic surfaces.
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MPC contains a side group that is identical to the head group of one of the major PLs of the cell
membrane, phosphatidyl choline (PC). At present stents coated with polymers containing MPC are
available.
In vitro
experiments showed reduced protein adsorption and platelet adhesion, resulting in
improved blood compatibility.
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These fi ndings were confi rmed in animal experiments, but long-
term studies of the performance of MPC coatings in humans are not available at present. In this case
the attempt is to mimic the cellular membrane, but the membranes that contact the circulating blood
in humans have a much more complex structure containing many active proteins. Several attempts
have been made to include some of these proteins in or couple these on polymeric coatings of blood-
contacting devices. For instance, thrombomodulin, which plays an important role in thrombin inac-
tivation, has been coupled with surfaces.
In vitro
experiments demonstrate decreased thrombus
formation on such surfaces.
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Attachment of tissue factor pathway inhibitor (TFPI) onto Dacron
vascular grafts could counteract the excessive growth of cells, often the cause of stenosis of the
graft.
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Also urokinase, a stimulator of the fi brinolysis, the degradation of clots, was coupled with
membranes, but only some
in vitro
experiments were performed, without much success.
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Of course
also other active components can be attached to surfaces, but there are certain major problems with
these bioactive coatings. Firstly, they are laborious and expensive to produce, especially in large
quantities, and the reproducibility is diffi cult to achieve. Secondly, the sterilization of such coatings
is virtually impossible. Therefore the active component has to be included after sterilization, which
