Biomedical Engineering Reference
In-Depth Information
successful history interfacing with blood in mechanical
heart valves attests to its suitability for this application.
A note of caution, however, is in order. Until about
a decade ago, the pyrolytic carbon used so successfully in
mechanical heart valves was produced by a single man-
ufacturer. The material, its many applications in the bi-
ological environment, and the processes for producing
the material were all patented. Since the expiration of
the last of these patents in 1989, other sources for py-
rolytic carbon have appeared that are copies of the
original General Atomic material. When considering al-
ternative carbon materials, it is important to recognize
that the proper combination of physical, mechanical, and
blood-compatible properties is required for the success
of the implant application. Furthermore, because there
are a number of different possible pyrolysis processes, it
should be recognized that each can result in different
microstructures with different properties. Just because
a material is carbon, a turbostratic carbon, or a pyrolytic
carbon does not qualify its use in a long-term human
implant (Haubold and Ely, 1995). For example, pyrolytic
carbons prepared by chemical vapor deposition pro-
cesses, other than the fluidized-bed process, are known
to exhibit anisotropy, nonhomogeneity, and considerable
variability in mechanical properties (Agafonov
et al.
,
1999). Although these materials may exhibit bio-
compatibility, the potential for variability in structural
stability and durability may lead to valve dysfunction.
The original General Atomic-type fluidized-bed pyro-
lytic carbons all demonstrate negligible reactions in the
standard Tripartite and ISO 10993-1 type biocompatibility
tests. Results from such tests are given in
Table 3.2.11-3
(Ely
et al.
, 1998). Pure pyrolytic carbon is so non-reactive
that it can serve as a negative control for these tests.
It is believed that pyrolytic carbon owes its demon-
strated blood compatibility to its inertness and to its
ability to quickly absorb proteins from blood without
triggering a protein denaturing reaction. Ultimately, the
blood compatibility is thought to be a result of the pro-
tein layer formed upon the carbon surface. Baier ob-
served that pyrolytic carbon surfaces have a relatively
high critical surface tension of 50 dyn/cm, which im-
mediately drops to 28-30 dyn/cm following exposure
to blood (Baier
et al.
, 1970). The quantity of sorbed
protein was thought to be an important factor for blood
compatibility. Lee and Kim (1974) quantified the
amount of radiolabeled proteins sorbed from solutions
of mixture proteins (albumin, fibrinogen, and gamma-
globulin). While pyrolytic carbon does absorb albumin, it
also absorbs considerable quantity of fibrinogen as shown
in
Fig. 3.2.11-11
. As can be seen in
Fig. 3.2.11-11
, the
amount of fibrinogen absorbed on pyrolytic carbon sur-
faces is far greater than the amount of albumin on these
surfaces and is comparable to the amount of fibrinogen
that sorbed on SR. The mode of albumin absorption,
Table 3.2.11-3 Biological testing of pure PyC
Test
description
Protocol
Results
Klingman
maximization
ISO/CD 10993-10
Grade 1;
not significant
Rabbit pyrogen
ISO/DIS 10993-11
Nonpyrogenic
Intracutaneous
injection
ISO 10993-10
Negligible irritant
Systemic
injection
ANSI/AAMI/ISO
10993-11
Negative
d
same
as controls
Salmonella
typhimurium
reverse mutation
assay
ISO 10993-3
Nonmutagenic
Physicochemical
USP XXIII, 1995
Exceeds standards
Hemolysis
d
rabbit blood
ISO 10993-4/NIH
77-1294
Nonhemolytic
Elution test
(L929
mammalian
cell culture)
ISO 10993-5,
USP XXIII, 1995
Noncytotoxic
however, appears to be drastically different for these
two materials. Albumin sorbs immediately on the pyro-
lytic carbon surfaces, whereas the buildup of fibrinogen
is much slower. In the case of SR, both proteins sorb
at a much slower rate. It appears that the mode of pro-
tein absorption is important and not the total amount
sorbed.
Nyilas and Chiu (1978) studied the interaction of
plasma proteins with foreign surfaces by measuring di-
rectly the heats of absorption of selected proteins onto
such surfaces using microcalorimetric techniques. They
found that the heats of absorption of fibrinogen, up to
the completion of first monolayer coverage, are a factor
of 8 smaller on pyrolytic carbon surfaces than on the
known thrombogenic control (glass) surface as shown
in
Fig. 3.2.11-12
. Furthermore, the measured net
heats of absorption of gamma globulin on pyrolytic
carbon were about 15 times smaller than those on glass.
They concluded that low heats of absorption onto a for-
eign surface imply small interaction forces with no con-
formational changes of the proteins that might trigger the
clotting cascade. It appears that a layer of continuously
exchanging blood proteins in their unaltered state ''masks''
the pyrolytic carbon surfaces from appearing as a foreign
body.
There is further evidence that the minimally altered
sorbed protein layers on pyrolytic carbon condition blood
compatibility.
Salzman
et al.
(1977),
for
example,
