Biomedical Engineering Reference
In-Depth Information
minute amounts, but upon the appearance of favorable conditions it triggers a full response. The
C3 convertase complexes will cleave C3 in C3a and C3b. Especially C3b is an important compo-
nent since it can act as an opsonin, making the surface it sticks to very attractive for the cellular
components of the immune system (lymphocytes and leukocytes). It can also process C5 to C5b
upon which sequential association with C6, C7, C8, and C9 will form the terminal complement
complex (TCC). This complex is also known as the membrane attack complex since it can disturb
membranes of cells and bacteria, resulting in cell lysis. In case of medical implants, the opsoniza-
tion effect of C3b is especially worrying, since this may lead to a severe immune response in the
blood that may result in failure of the device. Also some of the complement proteases have been
implicated in activation of blood coagulation by activating some of the coagulation zymogens.
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17.5.5 L
EUKOCYTES
L eu kocy tes d i rect ly i interact wit h synt het ic su r faces i in t he blood.
2,55
This interaction may be guided
by proteins of the complement system (e.g., C3b). The normal function of leukocytes is to attack
foreign bodies and if possible present (peptide-) parts on their surface (antigen-presenting cells).
These so-called antigen-presenting cells will induce the production of antibodies by the B-cells.
Monocytes will attempt to remove pathogens or foreign bodies from the circulation by simply
ingesting them by phagocytosis. The neutrophiles will attack by producing peroxides and oxygen
radicals, attacking the surface. The interaction of leukocytes with implanted materials will result
in an infl ammatory response.
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This can be dangerous in case of a severe response (high fever,
organ failure, and coma). Most materials however will elicit merely a moderate to mild infl amma-
tory response that is however chronic. In solid tissues the infl ammation results in the encapsulation
of the implant into a fi brous capsule to minimize the interaction of the implant with the body. In
fact the tissue is protected from further interaction by encapsulation. In the blood this response is
of course not possible, but upon interaction of the surface with monocytes, TF will be presented on
the membrane of these cells.
56,57
This TF will give rise to local coagulation and lead to the forma-
tion of a thrombus on the surface. Consequently, the function of the implant will be compromised,
and in the worst case, distant embolization may occur when parts of the surface clot release. This
can seriously compromise the health of the patient. The presence of a clot on the blood-contacting
device almost always results in stenosis of a blood vessel and will therefore often lead to removal
of the device from the patient.
17.6 SURFACES OF BLOOD-CONTACTING DEVICES
There is a large range of devices that are intended for direct contact with blood. In principle almost
all implanted devices will contact blood, except the ones that are implanted into solid tissues, and
the formation of a thrombus on the surface can be advantageous, since coagulation is a part of the
wound healing and tissue regeneration response.
Biomedical devices that function in contact with blood are for instance, arterial stents, synthetic
vessels, heart valves, catheters, guide-wires for percutaneous transluminal coronary angioplasty
(PTCA), blood bags, hemodialysis fi lters, tubes of heart-lung machine, vena cava fi lters, etc. Since
the effects of these implants can be systemic, the most vigorous testing of these devices is required.
Toxic molecules as well as infl ammatory molecules are easily spread throughout the whole body.
Of course the biomedical industry has come up with a variety of strategies to minimize toxicity,
infl ammatory response, and biomaterial-induced coagulation to prevent premature failure of the
device. There are roughly four major strategies that have been pursued over the last decades: (i)
produce the blood-contacting device from inert materials or polymers; (ii) coat the implant with a
polymer that contains favorable blood compatibility characteristics; (iii) generate a single endothe-
lial cell layer on the blood contacting surface of an implant; and (iv) make the implant from living
tissue
in vitro
, so called tissue engineering.
