Biomedical Engineering Reference
In-Depth Information
O
C
O
Phosphatidylcholine
O
CH
2
C
O
CH
3
O
C
H
N
+
H
2
C
O
P
OCH
2
CH
2
CH
3
O
−
CH
3
2-methacryloyloxyethyl phosphorylcholine
O
CH
3
O
N
+
P
O
CH
3
C
O
CH
2
CH
2
O
CH
2
CH
2
H
2
C
C
O
−
CH
3
CH
3
FIGURE 17.12
Structure of di-palmitoyl phosphatidylcholine (PC) and 2-methacryloyloxyethyl phos-
phorylcholine (MPC).
means that there remains a risk of infection. Finally, these coatings are sensitive to storage condi-
tions, which make them not very practical or economical.
17.6.3 L
IVING
C
ELL
L
AYER
AS
B
OUNDARY
L
AYER
The most optimal contact layer for a blood-contacting device would be a functional layer of endothe-
lial cells.
85
The endothelium is the inner layer of the blood vessels (Figure 17.3). The technique from
which scientists attempt to produce a fully biological device or tissue is called tissue engineering and
will be discussed later (Section 17.6.4). The control of hemostasis is one of the important functions
of the endothelium. The endothelium secretes a number of molecules that play important roles in the
regulation of coagulation, fi brinolysis, and infl ammation. Heparan sulfate is exposed on the surface
of endothelial cells and can catalyze the inhibition of thrombin and FXa by AT, a function that is
mimicked by the anticoagulant drug heparin (Figure 17.5). Also activators of plasmin are secreted
and these result in the degradation of formed thrombi. Formation of IL-10 and NO can reduce the
infl ammatory response and counteract the function of proinfl ammatory cytokines. As a result, the
formation of an endothelial cell layer on blood-contacting devices has been a favorite subject of many
biomedical engineers. Formation of an active and self-regenerating endothelial layer has been used to
improve the performance of especially synthetic blood vessels.
92
One strategy attempts to make the
endothelial cell layer form spontaneously after implantation of the device. The surface of the device
is modifi ed in such a way that it is an attractive substrate for endothelial cells.
28,93
Often extracellular
matrix proteins like collagens, elastins, and fi bronectin are used. Unfortunately, the proteins are not
exclusively favorable for endothelial cells, but also accommodate other cell types like leukocytes and
platelets, resulting in coagulation on such surfaces. In animal models, ingrowth of endothelial cells
from the original vessel walls has been demonstrated to occur under optimal conditions. In human
patients, however, the endothelial cells of the vessel walls demonstrate poor proliferation, indicating
that no endothelialization occurs from the existing vessel walls.
94
-
97
Endothelial progenitor cells (EPC) are not fully differentiated cells that are predestined to form
endothelial cells. These cells are generated in the bone marrow and released in the circulation and
