Since the 1960s, total joint-replacement components made of
ultra-high molecular weight polyethylene (referred to as polyethylene
hereafter in this paper) have been sterilized with 25 to 40 kGy of gamma
radiation1,2.
During the 1990s, many orthopaedic manufacturers in the United States
transitioned from gamma sterilization in air to gamma sterilization in a
low-oxygen atmosphere to reduce oxidation of polyethylene components during
shelf
storage1,3.
Post-irradiation oxidation during shelf storage was recognized to reduce the
mechanical properties of the polyethylene, leading to embrittlement of the
polymer4-10.
Oxidative embrittlement following gamma irradiation in air and subsequent
shelf storage in air for more than five years has been proposed as a factor
contributing to clinical failure of conventional polyethylene components used
for unicondylar11
as well as total knee
replacement7,8,12,13.
The clinical implications of polyethylene degradation in hip replacements
remain controversial. Sutula et
al.6 observed that
retrieved gamma-sterilized liners that showed a subsurface white band after
being cut with a microtome also had evidence of rim cracking and delamination.
However, studies of cemented Charnley components retrieved after long-term
use2,14
demonstrated no association between the polyethylene density (a surrogate
measure of oxidation) and the implantation time or the clinical wear rate. A
limitation shared by previous retrieval studies of hip replacements that had
been gamma-sterilized in air was that the shelf life of the implants was not
determined. In a recent radiographic wear analysis of polyethylene liners that
had been gamma-sterilized in air and for which the shelf life had been
ascertained, Hopper et
al.15 found no
association between shelf life and the in vivo wear rate of a conforming,
second-generation implant design.
Historically, the conventional dose of 25 to 40 kGy of gamma radiation was
intended for sterilization, whereas, today, irradiation is also recognized to
result in beneficial crosslinking of the
polyethylene1.
Consequently, gamma sterilization in a low-oxygen environment with barrier
packaging remains an industry standard and is currently used for conventional
components as well as for certain formulations of highly crosslinked
polyethylene components in hip
replacement1,16,17.
Other formulations of highly crosslinked polyethylene, which are subsequently
remelted, are stored in gas-permeable packaging and sterilized with ethylene
oxide and gas
plasma1,16,17.
Regardless of the packaging environment, gamma sterilization produces free
radicals within polyethylene. These free radicals react with oxygen diffusing
into the amorphous regions of the polymer, or the free radicals may recombine
to form covalent
crosslinks17.
Radiation-induced crosslinking, even when performed in the presence of air,
has immediate benefits with regard to the clinical performance of hip
replacements. Hopper et
al.15 reported that
the clinical wear rate of liners that have been gamma-sterilized in air is 50%
lower than that of gas-sterilized liners. On the other hand, the fate and
long-term importance of residual free radicals produced by gamma sterilization
of polyethylene acetabular liners remain unclear.
In vivo, the articulating surfaces of polyethylene components are exposed
to joint fluid containing filtered plasma augmented by biomolecules, such as
lubricious proteins, that are produced by the synovial
membrane18,19.
In addition to dissolved oxygen and other
gases20, the
synovial fluid of patients with arthritis is also known to contain reactive
oxygen radicals (e.g., superoxide
radicals)21,22.
The oxygen dissolved in synovial fluid is derived from filtered plasma,
whereas oxygen radicals are thought to be produced by poorly regulated
metabolic
pathways23. In the
study by
Lund-Olesen24, an
average partial pressure of oxygen (and standard deviation) of 43 ± 15
mm Hg was measured in patients with osteoarthritis. The oxygen content may be
as low as zero in patients with rheumatoid arthritis, but it has been measured
to be an average of 27 ± 19 mm
Hg18,24.
Published data suggest that, except in certain patients with rheumatoid
arthritis, the biological environment for polyethylene components contains
dissolved molecular
oxygen18,20,24,
albeit at a partial pressure that is lower than the 160 mm Hg found under
standard conditions in air.
Although degradation of gamma-sterilized polyethylene occurs in vivo,
little is known about the magnitude and distribution of such degradation in
modular acetabular liners with a short shelf life. The objective of this study
was to characterize the mechanical properties and oxidation levels in a series
of traceable liners, produced from a single resin, that had been
gamma-irradiated in air but had been implanted after less than a year of shelf
life, prior to the development of any subsurface oxidation or white bands due
to aging in air. We hypothesized that in vivo degradation would vary as a
function of the location on the liner surface.
Traceable acetabular liners were obtained as a result of the
collaboration of two orthopaedic implant retrieval programs located in the
Northeastern and Midwestern regions of the United States. The manufacturer and
serial numbers of the retrieved liners were obtained from the patients'
operative notes or from the inscriptions on the rim of the liners. The serial
numbers permit a manufacturer to trace the production history of a specific
polyethylene component.
The cementless acetabular liners that we evaluated were manufactured by
either Biomet (Warsaw, Indiana) or Zimmer (Warsaw, Indiana), both of whom
agreed to trace the sterilization date, sterilization method, resin, and
conversion method of the polyethylene liners on the basis of the serial
number. The traceable acetabular liners were of the first or second-generation
designs produced by each manufacturer.
We studied the mechanical properties and oxidation profiles of
consecutively traced GUR 415 acetabular liners that had been gamma-sterilized
in air. GUR 415 was chosen because the natural history of this resin following
gamma sterilization in air and shelf-aging in air has been well established in
the
literature9,25.
We included liners that had a shelf life of less than one year prior to
implantation, which is early in the degradation process of polyethylene that
has been gamma-sterilized in air and prior to the evolution of a subsurface
peak in oxidation9.
Fourteen traceable liners met our study inclusion criteria. The liners were of
four designs, with seven Hexloc (Biomet), two Ringloc (Biomet), four
Harris-Galante Porous (HGP; Zimmer), and one Trilogy (Zimmer). Twelve of these
liners were revised because of loosening, wear, and/or osteolysis; one was
revised because of recurrent dislocation; and one was revised because of
disassociation of the liner. All of the liners were expeditiously stored in a
subzero freezer after retrieval, for an average of 0.6 year (range, 0.1 to 0.9
year), to minimize ex vivo changes to the polyethylene prior to
characterization9.
The liners had been in vivo for an average of 10.3 years (range, 5.9 to
13.5 years) and had had an average shelf life of 0.3 year (range, 0.0 to 0.8
year).
Characterization of Mechanical Properties, Oxidation, and Wear
The mechanical behavior of the retrieved liners was characterized by the
small-punch test. Disk-shaped specimens of 0.5 mm in thickness and 6.4 mm in
diameter were used, as detailed
previously26-28.
The specimens were placed in a custom-built apparatus and were deformed
against a hemispherical punch moving at a constant displacement rate of 0.5
mm/min. The specimens were prepared from as many as four cylindrical cores
removed perpendicular to the worn articulating surface of each retrieved
liner, as described
previously29. Two
specimens were obtained from each core: the first specimen was machined
starting within 25 µm of the articulating surface, and the second specimen
was machined between 1.5 and 2 mm in depth from the surface.
The sampling locations were chosen to facilitate comparisons with previous
research on shelf-aged polyethylene that had been gamma-sterilized in air. For
example, previous studies of shelf-aging of polyethylene have demonstrated a
peak in density, attributed to oxidation, at a depth of 1 to 2
mm25. Substantially
reduced mechanical properties following shelf-aging have been measured with
the small-punch test when polyethylene liners were sampled at a depth of 1.5
to 2 mm compared with when the properties were measured near the
surface4. The
sampling locations for the small-punch test were determined with respect to
the actual, as-explanted component geometry.
A total of seventy-seven specimens were tested from the fourteen liners in
this study so that an average of six specimens were evaluated for each
component. Difficulties in machining the miniature specimens, due to the small
size or thickness of the liners, and severe wear sometimes precluded our
obtaining the desired total number of specimens. Thus, the total number of
specimens evaluated for each liner ranged between one and eight. However, the
location of each specimen (worn or unworn, or surface or subsurface) was known
so that it could be accounted for in the statistical analysis.
The small-punch test results in a load-versus-displacement curve from which
the initial peak load, the ultimate load, and the ultimate displacement were
obtained. The work to failure, calculated as the area under the
load-displacement curve, was used as a measure of toughness. Wilcoxon tests
were used to compare the properties at the different locations of the
liners.
A microtome was used to obtain 200-µm sections from spherical bearing
portions of the liners, in both worn (loaded) and unworn (unloaded) regions.
Sections were also obtained from the superior and inferior parts of the rim,
when sufficient material was available. We were able to obtain sections from
the worn bearing regions of all retrieved liners. However, iatrogenic damage
or previous destructive testing prevented sectioning of the unworn bearing of
three liners, the inferior part of the rim of six liners, and the superior
part of the rim of one liner.
The thin sections were soaked for six hours in boiling heptane to extract
adsorbed lipids, which might interfere with the oxidation
analysis30. The
extracted polyethylene sections were then scanned through their thickness in
0.2-mm-deep increments (thirty-two scans per sampled location) with use of
Fourier transform infrared spectroscopy.
The rim sections were scanned normal to the flat, outward face to a maximum
depth of 3 mm. Because the outward face of the rim was sampled in line with
the thickness of the spherical bearing, the concept of rim thickness was not
applicable at this location. We sampled to a depth of 3 mm from the outward
face of the rim for the purposes of comparison with the surface profiles
collected with respect to the bearing surface.
The oxidation index was calculated in accordance with the American Society
for Testing and Materials standard F2102 as the area ratio of the carbonyl
peak (between 1670 and 1850 cm-1) to the 1370 cm-1
reference peak (between 1327 and 1394 cm-1) from the Fourier
transform infrared
spectra3,31,32.
As the standard for the oxidation index of polyethylene includes the area
under both ester carbonyl and ketone carbonyl absorbances (approximately 1740
and 1718 cm-1, respectively), we also inspected the distribution of
carbonyl species for all scanned sections to evaluate the mechanism of
oxidation in the bearing and rim locations.
The oxidation index profiles typically exhibited a maximum near, or
slightly below, the surface (Fig.
1). The magnitude of the oxidation peak as well as the location of
the peak relative to the surface was determined. In both loaded and unloaded
regions of the liners, the oxidation values in the rim, bearing surface, and
backside surface of the liners were compared with one another with use of
paired t tests.
To aid in the interpretation of the mechanical property and oxidation
measurements, we measured the thickness of the liners in the loaded and
unloaded regions with a calibrated digital micrometer. Iatrogenic damage or
previous destructive testing prevented reliable measurement of the thickness
in the worn regions of four liners. The wear of the remaining ten liners was
calculated by subtracting the thickness of the liner in the worn regions from
that in the unworn regions. An average wear rate was calculated by dividing
the measured wear by the time in vivo, as described
previously14. An
insufficient quality and number of radiographs precluded reliable radiographic
measurement of the wear for the majority of these retrieved inserts.
There was regional variation in the mechanical properties of the
liners (Table I). The ultimate
load, for example, was observed to vary by >90% near the surface of the
retrieved liners (Fig. 2). The
degradation of the surface regions of the liners (both worn and unworn) was
greater and more variable than that in the subsurface regions of the liners
(Table I,
Fig. 2). The ultimate load was
lower near the surface in both the worn (p = 0.03) and the unworn (p = 0.02)
regions (Fig. 2).
Regional variation was also observed in the oxidation levels of the liners
(Figs. 3 and
4). On the average, the rim and
the unloaded bearing surface showed evidence of severe oxidation after
long-term in vivo aging, but these trends were not typically observed on the
loaded bearing surface or near the backside of the liners. Oxidation in the
unloaded, inferior part of the rim was greater than that on the unloaded
bearing surface (mean difference in oxidation index, 1.0 unit; p = 0.003);
similar behavior was observed in the loaded region of the liners (mean
difference in oxidation index, 3.2 units; p = 0.0002). Oxidation was also
observed to be greater on the bearing surface than on the backside surface
(mean difference in oxidation index, 1.9 units [p = 0.0008] for the unloaded
region and 0.79 unit [p = 0.02] for the loaded region). We also observed a
difference in the oxidation of the worn and unworn regions of the bearing
surface (mean difference in oxidation index, 1.3 units; p = 0.05).
Maximum oxidation occurred approximately 0.9 mm (range, 0 to 3 mm) from the
bearing surface in both the worn and the unworn locations. At the superior and
inferior parts of the rim, the peak oxidation occurred closer to the surface,
at mean depths of 0.6 and 0.4 mm (range, 0 to 1.2 mm), respectively. The
average 0.5-mm difference in peak location between the rim and the bearing
surface was observed in both the superior worn (p = 0.05) and inferior unworn
(p = 0.04) locations of the liner.
Examination of the Fourier transform infrared spectra in the carbonyl
region revealed that ketones, with a characteristic absorption at 1718
cm-1, were the primary species present at the surface and
subsurface locations of the liners (Figs.
5-A, 5-B, and 5-C) as well as at the rim
(Fig. 5-C). The intensity, but
not the distribution, of carbonyl species was observed to vary in the worn and
unworn locations of the bearing surface. At the locations of maximum carbonyl
concentration near the surface, secondary absorbance peaks (shoulders) in the
spectra were clearly appreciated at 1740 cm-1 and 1698
cm-1 in both the bearing regions of the liners and the rim. The
1740-cm-1 peak is attributed to esters, whereas the
1698-cm-1 peak is attributed to acids or a,
ß-unsaturated ketones and esters in
polyethylene33.
The liners in this series were extensively worn. The average wear depth was
2.6 mm (range, 0.9 to 4.9 mm), and the average wear rate was 0.24 mm/yr
(range, 0.08 to 0.41 mm/yr).
The results of this study provide quantification of the magnitude of
in vivo oxidation of polyethylene liners. We observed that, overall, the rim
was more severely oxidized than the bearing surface, which in turn was more
oxidized than the backside of the liner. The results support the hypothesis
that access to oxygenated body fluids is a key mechanism of in vivo
degradation, at least of GUR 415 liners that were gamma-sterilized in air.
Because of their short shelf life, none of the inserts would have exhibited a
subsurface oxidation peak near the bearing surface, the backside surface, or
the rim when the components were implanted, and therefore the differences in
magnitude and distribution of oxidation observed in our retrieved liners were
the consequence of in vivo aging.
Polyethylene degradation and wear took place, on the average, over a
time-frame spanning a decade. We postulated that, on the bearing surface, in
vivo oxidation occurred slowly over time and concurrently with material
removal due to wear. In about 50% of the liners, the maximum oxidation at the
worn surface was comparable with that on the backside surface
(Fig. 3). We postulated that,
when wear progresses faster than in vivo oxidation, the polyethylene
in contact with the femoral head does not have the opportunity to degrade
substantially prior to removal. In this study, a subsurface peak occurred near
the worn surface of some liners, suggesting that wear may have been
progressing more slowly than the in vivo oxidation process. Finally,
the peak oxidation in the loaded region appeared to be lower than that in the
unloaded region (Figs. 3,
4, and
5); this suggests that contact
with the femoral head may have limited the access of oxygenated body fluids to
the polyethylene surface. The regional variations in polyethylene properties
found in this study reconcile previous contradictory observations of increased
rim damage following gamma
sterilization6
together with a reduced wear rate at the bearing surface following gamma
sterilization15
that decreased with increases in implantation
time2,34.
Additional studies of acetabular liners gamma-sterilized in a gamma-inert
environment, preferably retrieved after long implantation times but with
minimal wear, are needed to confirm our hypothesis that the femoral head
protects the articulating surface from in vivo oxidation.
The distribution of mechanical properties in the retrieved liners was
different from that observed after long-term
shelf-aging4. The
lowest values for the mechanical properties were found near the surface (at a
depth of =0.5 mm) as opposed to the subsurface regions of the liners, which
were sampled at a depth of 1.5 to 2 mm
(Fig. 2); these findings were
consistent with the oxidation profiles. In contrast, in a previous
study4, liners that
had been subjected only to long-term shelf-aging in the presence of air and
had never been implanted exhibited greater degradation of mechanical
properties in subsurface locations when they were evaluated with the same
small-punch-test sampling protocol as we employed. Taken together, these
findings suggest that in vivo exposure alters the distribution of mechanical
properties within the polyethylene compared with the properties following
shelf-aging.
This study was limited to modular GUR 415 acetabular liners that had been
subjected to a 25 to 40-kGy dose of gamma sterilization while in air-permeable
packaging. Because of changes in resin and packaging of polyethylene
components that occurred in the 1990s, we did not have access to, and thus
could not compare our current results with, control GUR 415 liners or those
that had been in vivo for a short period; consequently, we were unable to
quantify the long-term in vivo degradation rates in this study. Furthermore,
the analysis of these liners should not be extrapolated to polyethylene that
was gamma-sterilized in a gamma-inert environment or to formulations of highly
crosslinked polyethylene that were processed with doses of gamma radiation
exceeding 40 kGy. None of the liners in this study were produced from any
formulation of highly crosslinked polyethylene.
The scope of the testing in this study was limited in some cases by the
geometry of the retrieved liners and by severe wear. We addressed this
limitation by segregating our data by sampling location
(Fig. 2) and, when appropriate,
by using paired statistical test methods to evaluate oxidation data collected
at different locations from the same component
(Fig. 3). The difficulties with
sampling and with material availability, inherent in an analysis of retrieved
first-generation components, underscore the importance of continuing this
research with more contemporary implant designs. However, the sampling
difficulties in no way alter our conclusion that severe regional oxidation of
acetabular liners may occur in vivo after gamma sterilization in air.
This retrieval study was designed to elucidate the mechanisms of in vivo
degradation, not to examine relationships between oxidation and clinical wear.
The average wear rate of the liners in this series (0.2 mm/yr) was
approximately two times greater than the generally accepted average clinical
wear rate of conventional polyethylene liners (0.1
mm/yr)35,36.
Although the high wear rates in this series were consistent with the
predominance of clinical failures due to osteolysis and aseptic loosening,
these implants do not necessarily reflect the typical distribution of wear
performance in a patient population. In light of the multiple factors that
influence the clinical wear performance of
polyethylene37, a
much greater number of implants of a single design would be needed to evaluate
relationships between in vivo oxidation and clinical performance.
It is too early to draw conclusions about the effects of in vivo
degradation on contemporary barrier-packaged and gamma-sterilized components.
It remains to be seen whether in vivo degradation influences the mechanisms of
fatigue wear, such as pitting and delamination, which are prevalent in knee
replacement
components11,38.
Additional research also will be needed to determine the effect of in vivo
degradation (if any) on the recently developed highly crosslinked and
thermally treated polyethylene materials that have been developed for hip and
knee replacement1.
?