Biomedical Engineering Reference
In-Depth Information
17.5
INTERACTION OF BLOOD WITH SYNTHETIC SURFACES
17.5.1 P
ROTEIN
A
DSORPTION
Upon fi rst contact of blood with a synthetic surface, a rapid adsorption of plasma proteins will occur.
This protein adsorption is not static and over time the composition of the adsorbed protein layer will
change. This effect is called the Vroman effect, after Leo Vroman who fi rst described this phenom-
enon in the late 1960s.
19
-
21
According to Vroman and coworkers, fi rst the most abundant, and often
small, proteins will adsorb, however with low affi nity. These proteins will be replaced by, often
larger, proteins with higher affi nity for the surface, which are in general less prevalent in the blood.
The mechanism of protein adsorption on synthetic surfaces still a much debated phenomenon. Pro-
tein adsorption is dependent on the physicochemical characteristics of the surface.
21
-
25
Some of these
characteristics can be controlled during the synthesis of the surface, namely chemical composition,
surface charge and hydrophilicity, surface topography, etc. In many cases adsorbed proteins will
partly or completely denature, changing their structure and consequently their function.
21,25
Conse-
quently, the nature of the surface can be radically changed by protein adsorption, like surface charge,
and synthetic surface modifi cations that can become covered by adsorbed proteins. One can state that
the surface of an implant rarely contacts cells and tissues. In fact it is the layer of adsorbed proteins
that determines the behavior of cells and tissues in contact with synthetic surfaces.
26
-
28
Given that the response of blood (coagulation, infl ammation, complement activation) toward
synthetic surfaces is governed by the nature of the adsorbed protein, directing protein adsorption
is considered a valuable tool to control blood compatibility of surfaces. Many attempts have been
made to either produce a completely protein-repellent surface or to manipulate protein adsorption in
such a fashion that the desired cell-surface interaction is obtained. However of the protein-guiding
surfaces none has been proven reliable and successful when in contact with fl owing blood
in vivo
.
Several blood compatibility strategies will be discussed in a later section (Section 17.6).
17.5.2 C
OAGULATION
Blood coagulation is an essential part of the repair mechanism of the vascular system. The integrity
of blood vessels has to be maintained, and therefore a complex mechanism of vessel repair has
evolved.
1,29,30
Upon injury of a blood vessel, a primary plug is generated consisting mainly of plate-
lets. This platelet plug primarily avoids further blood loss from the circulation.
31
This plug further
activates a complex system of proteins, the coagulation system. Activation of coagulation leads to a
stable blood clot, which avoids bleeding from the injury site.
5,17
In a second phase the damaged cell
layers are repaired and the blood clot is removed in a process called fi brinolysis.
31,32
The control of coagulation is of vital importance. The balance between coagulation and antico-
agulation, called hemostasis, has to be controlled tightly. When the balance changes toward coagu-
lation, thrombosis, and stroke or myocardial infarction may follow. In case of the balance shifting
toward anticoagulation, excessive bleeding and hemorrhage, for example, in the joints or in the
brain may follow. It is clear that the delicate balance of the coagulation system should not be dis-
turbed by blood-contacting devices. Unfortunately, contact of synthetic surfaces with blood usually
disturbs the balance and very often induces coagulation and consequently thrombus formation.
17
Thrombus formation is triggered by two different pathways, the intrinsic and the extrinsic.
Both pathways lead to the activation of the common pathway in which the central enzyme thrombin
catalyzes the formation of fi brin from the plasma protein fi brinogen, resulting in a stable blood clot.
All these systems will be discussed to generate a further understanding of the problems faced by
biomedical engineers in trying to design blood-compatible surfaces.
17.5.2.1 Common Pathway
The central enzyme in blood coagulation is thrombin. This enzyme digests fi brinogen and thereby
induces the formation of fi brin fi bers and a fi brin network, stabilizing the thrombus or clot. The
