Gold-Coated NIR Stents in Porcine Coronary Arteries
Elazer R. Edelman, MD, PhD; Philip Seifert, MS; Adam Groothuis, MS; Alisa Morss, MS;
Danielle Bornstein, BS; Campbell Rogers, MD
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Background—As endovascular stents are altered to add functionality, eg, by adding radiopaque coatings, biocompatibility
may suffer.
Methods and Results—We examined the vascular response in porcine coronary arteries to stainless steel gold-coated NIR
stents (7-cell, Medinol, Inc). Stents, 9 and 16 mm in length, were left bare or coated with a 7-␮m layer of gold. Physical
and material effects were examined in four different gold-coated stent types, two at each length that either had the
coating applied to the standard strut, ie, gold coated thicker than controls, or had the coating applied to thinned struts,
ie, gold coated of the same thickness as control struts. Simple gold coating exacerbated intimal hyperplastic and
inflammatory reactions over 28 days, but postplating thermal processing smoothed the coating surface and negated the
adverse tissue response to gold. The relative amounts of base steel and gold coating and their resistances to expansion
and collapse determined the extent of stent recoil.
Conclusions—Gold coatings enhance the radiopacity of steel stents, but not without effects on vascular repair. Material
effects predominate and can be abrogated by heating coated stents to alter surface finish and material purity. Clinical
results may suffer unless consideration is given to material and physical effects of gold. (Circulation. 2001;103:429434.)
Key Words: restenosis 䡲 stents 䡲 thermal processing 䡲 vasculature 䡲 vascular repair
A
s novel designs and surface preparations have produced
endovascular stents with dramatically reduced thrombosis and restenosis, the focus now is on increasing ease of use.
Radiopacity in particular is poor with stainless steel and
worse when struts are made thinner or spaced farther apart.
Changes in design, material, or surface coatings that increase
opacity cannot reduce overall functionality and biocompatibility. Stainless steel enables stents to be expanded within
tortuous and eccentric lesions. Other metals and materials
may not have dynamics that are as favorable. Similarly, as the
biological sequelae of implantation are increasingly well
defined, it becomes clear that stainless steel is relatively inert
within the vasculature. Metal coatings may alter every phase
of the response to vascular implantation, including thrombosis, inflammation, and proliferation.
Gold in particular has been touted as a potential coating for
stents. Of all the radiopaque metals, gold is the easiest to
work with by virtue of its low melting point and high
malleability. On the other hand, there are disturbing reports
that gold-coated stents incite an exaggerated vascular response.1 We sought to define the biological reaction to
gold-coated stents implantation and to determine whether the
response stemmed from a fundamental limitation of the
physical and material effects of gold or the processes by
which the metal was applied.
Methods
Stents
Seven-cell stainless steel NIR stents (Medinol, Inc), 9 and 16 mm in
length, were left intact or coated with a 7⫾2.5-␮m gold layer. The
2-step plating process included generation of a “seed layer” to
optimize adherence before plating. Because gold plating increased
strut thickness by twice the coating depth, stents were electropolished to remove an equivalent 7 ␮m of steel from all sides of the
struts before plating to maintain constant strut dimensions. In all, 5
different gold-plated stents were examined, and each coated stent
was compared with uncoated devices subjected to identical processing except for gold plating. The performance of each set of
gold-coated stents was compared with that of matched stainless steel
controls taken from the same lot of material. Four sets of studies
were performed. In the first two, 16-mm stents were used; in the
latter two, 9-mm stents were used. In studies 1 and 4 (Table), when
the coating was applied, the strut thickness was increased by the
twice the thickness of the gold coating. In studies 2 and 3, stent struts
were electropolished before coating so that the thickness after gold
coating was identical to that of the standard stainless steel stents (the
Table). As a frame of reference using a known standard, in concert
with study 2, three animals received a single stainless steel PalmazSchatz stent (Cordis/Johnson and Johnson) in two coronary arteries.
In a final set of experiments, the standard gold coating was compared
with gold coating subjected to a thermal processing step intended to
smooth the gold surface and potentially remove embedded
impurities.
Received July 14, 2000; revision received August 30, 2000; accepted September 1, 2000.
From the Harvard-MIT Division of Health Sciences and Technology (E.R.E., P.S., A.G., D.B., C.R.) and the Department of Mechanical Engineering
(A.M.), Massachusetts Institute of Technology, Cambridge, Mass, and the Department of Medicine, Cardiovascular Division, Brigham and Women’s
Hospital and Harvard Medical School (E.R.E., C.R.), Boston, Mass.
Correspondence to Dr Elazer R. Edelman, Massachusetts Institute of Technology, Division of Health Sciences and Technology, 77 Massachusetts Ave,
Room 16-343, Cambridge, MA 02139. E-mail [email protected]
© 2001 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
429
430
Circulation
January 23, 2001
Stainless Steel and Gold-Coated Coronary Arterial Stent Implant Studies
n
Coating
Balloon:Artery
Intimal Thickness, mm
Injury Score
Recoil, %
Lumen, mm2
9
None
1.08⫾0.03
0.19⫾0.03
0.05⫾0.02
22⫾5
3.29⫾0.38
9
Gold
1.08⫾0.02
0.24⫾0.04
0.05⫾0.02
11⫾5*
4.19⫾0.50
6
None
1.15⫾0.03
0.21⫾0.03
0.02⫾0.18
13⫾1
4.52⫾0.59
6
Gold
1.13⫾0.01
0.26⫾0.05
0.06⫾0.08
17⫾1*
4.01⫾0.72
6
Palmaz-Schatz
1.24⫹0.03
0.34⫹0.04*
0.62 ⫹0.27
20 ⫹1
2.21⫹0.39*
6
None
1.09⫾0.04
0.28⫾0.03
0.08⫾0.03
10⫾3
5.10⫾0.54
6
Gold
1.08⫾0.06
0.37⫾0.04
0.19⫾0.11
18⫾3*
3.07⫾0.45*
8
None
1.13⫾0.06
0.14⫾0.02
0.02⫾0.01
15⫾1
4.59⫾0.70
7
Gold
1.03⫾0.03
0.21⫾0.05*
0.16⫾0.01*
18⫾2
4.04⫾0.53
7
Baked
1.12⫾0.02
0.15⫾0.02
0.01⫾0.01
17⫾2
4.61⫾0.42
Study 1, 16-mm
standard strut
Study 2, 16-mm
polished strut
Study 3, 9-mm
polished strut
Study 4, 9-mm
standard strut
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*Statistically different (P⬍0.05) from controls.
Topographical and Elemental Analyses
The surface of the gold-coated stents was evaluated before and after heat
treatment. Surface morphology was determined via an SEM (Leo
438VP) with a backscatter detector (Leo 400 Centaurus BSD). Elemental analysis was performed with energy dispersive x-ray spectroscopy
(IXRF Analyzer, model 500). Auger electron spectroscopy (PHI 660)
examined the outer stent surface. Surface topography was defined with
atomic force microscopic analysis (Topometrix Explorer) of 10⫻10-␮m
areas and on two linear scans across the face.
Surgical Procedure
Seventy-eight stents were implanted2 in 40 domestic swine (weight, 30
to 40 kg). Thirty-five animals survived perioperatively; those that died
were excluded from further analysis. Animals were fed standard chow
and water, and aspirin (325 mg, Sigma Chemical Co) was administered
once daily throughout the postoperative period from the day before
surgery. After anesthesia induction, animals received nifedipine 10 mg
SL, bretylium 5 mg/kg IV, and cefazolin 500 mg IV. A 7F coronary
guiding catheter (AR1 or Hockey Stick, Scimed Life Systems) was
advanced to the coronary ostia via the right femoral artery. After
administration of heparin (200 U/kg IV) and nitroglycerin (100 ␮g IC),
angiography of the left and right coronary arteries was performed in
orthogonal planes. Sections of each coronary artery judged to be 2.5 to
3.5 mm in diameter were chosen for stent deployment. A single standard
stainless steel or gold-coated stent was placed in two of the three
arteries.2 All stents were mounted on 3.0- to 4.0-mm angioplasty
balloons (20 mm, SCIMED Ranger) to provide ratios of balloon/stent to
artery of ⬇1.1:1. Stents were advanced over an angioplasty guidewire
(High Torque Floppy, Guidant, Inc) to suitable segments of the coronary
artery and inflated at 8-atm pressure for 30 seconds. Nitroglycerine 100
␮g IC was again administered, and angiography was repeated in
orthogonal views. On completion of the procedure, the femoral artery
was ligated, and cefazolin 500 mg IV was administered. The ratios of
balloon/stent to artery were calculated angiographically from balloon
and preplacement lumen diameters measured with digital calipers
offline on cine film.
Twenty-eight days after implantation, animals were anesthetized and
euthanized with KCl 40 mEq IV. The hearts were removed, and the
coronary arteries were perfused with Ringer’s lactate solution infused
into the aortic root at 100 mm Hg, followed by 4% paraformaldehyde in
0.1 mol/L sodium phosphate buffer fixative. The coronaries were
dissected, and stented sections were isolated and immersion fixed in 4%
paraformaldehyde fixative. Stented arterial segments were oriented
longitudinally and embedded with a methacrylate formulation.3 Multiple sections 5 ␮m thick were cut with a tungsten carbide knife
(Delaware Diamond Knives) on an automated microtome (Leica, Inc)
from the proximal and distal ends and the midpoint of each stented
segment. Sections were stained with hematoxylin and eosin and with ver
Hoeff’s elastin stain. Computer-assisted digital planimetry measured
lumen, neointimal, and medial cross-sectional areas. Luminal diameter
was calculated from luminal area, and stent diameter was calculated
from the area bounded by the internal elastic lamina. Histological late
loss of luminal diameter was calculated as the difference between stent
and luminal diameters. Recoil was calculated as the difference between
balloon size at implantation and histologically determined stent diameter. Inflammation was determined by quantitative determination of the
number of multinucleated giant cells and by immunostaining for porcine
CD45 (allotypic variant, Serotec Ltd) with a low-temperature antigen
retrieval and a tyramide signal amplification system kit (Dako, Inc). The
percent of immunopositive CD45 cells was semiquantitatively measured in the neointima in 5 fields.4 Injury scores were determined as
described.5
Statistical Analysis
For each stented segment, results from each end and the middle were
averaged to minimize sampling error. Data are presented as
mean⫾SE. For each of the four studies, coated and uncoated groups
were compared with the use of unpaired Student’s t test, with
P⬍0.05 considered significant. ANOVA was used for comparisons
of the three groups in the fourth study.
Results
Topographic and Elemental Analysis
The surface of the gold-plated stents is evident in the
microscopic images (Figure 1). The roughness of the standard
gold plating was equivalent to that of standard stainless steel,
and heat treatment smoothed the surface of the gold plating
without erosion. Heated gold layers were smooth but thin
enough to reveal the underlying granular interface of the
stainless steel (Figure 1c and 1d). The differences between
Edelman et al
Gold-Coated Stents
431
Figure 1. SEMs of gold-plated NIR stent
surfaces (a, b) and after heat treatment (c,
d) at ⫻350 (a, c) and ⫻1500 (b, d).
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the surfaces were confirmed by atomic force microscopy. The
average roughness of the unheated gold-coated stents was
more than twice the value for heated stents, with a
3.3-fold– greater mean peak-to-valley height in profile
(Figure 2). Although surface roughness was reduced with
heating, there was no discernible difference in surface
elemental density by energy dispersive x-ray spectroscopy
or Auger analysis between the nonheated and heated
surfaces. More iron was detected to have diffused into the
gold coating of the heated stent, but in none of the stents
did iron reach the stent surface. Initial Auger surveys of
the gold-coated and heated gold-coated stents showed only
oxygen and carbon at the outermost surface. After several
cycles of sputtering, the carbon layer was greatly reduced,
and only gold was detected. No trace contaminants were
detected on the surface of the stents.
Biological Response
The biological responses to stainless steel and gold-coated stents
28 days after implantation were compared. Ratios of balloon to
artery for all devices ranged from 1.03 to 1.2 (the Table) and did
not correlate with ultimate neointimal size. Two different stent
lengths (9 and 16 mm) were examined, and the coating either
was applied to struts whose thickness was equivalent to that of
the control stents or reduced by twice the thickness coating
depth. No stents were thrombosed at harvest. Differences were
observed in the reaction of stainless steel stents of different
dimensions (Table); comparisons were made only within specific experiments, not across experiments.
In every experiment, gold-coated stents produced a greater
neointima than their stainless steel counterparts, the difference being more profound with shorter stents. Neointimal
thickness was increased by 24% and 26% in the long stents
and by 33% and 57% in the short stents of standard and
thinned strut thicknesses, respectively (the Table and Figure
3). In marked contrast, heat processing rendered the responses to gold-coated stents indistinguishable from uncoated
stainless steel stents (Figure 3). Although the injury scores in
all sections were low (⬍0.2), in all but study 1, they were
higher in the gold-coated stents. Because the ratios of balloon
to artery were similar between stent types, the observed
differences in injury score likely reflect late effects rather
than acute implantation-related injury alone. Palmaz-Schatz
stents provoked greater intimal thickness (0.34⫾0.04 mm) at
Figure 2. Three-dimensional atomic
force micrographs demonstrated surface
topography of gold-coated NIR stents
before (a) and after (b) heat treatment.
Average roughness of heat-treated
stents was less than half of nonheated
gold stents (59.9⫾22.4 vs 154.6⫾5.4),
and mean maximum peak-to-valley
excursion was ⬎3-fold lower (86.4⫾7.7
vs 284.4⫾3.9).
432
Circulation
January 23, 2001
a higher injury score (0.6⫾0.3) with lower lumen areas
(2.21⫾0.4 mm2) than any of the gold-coated devices.
The reduction in neointima with thermal processing of
gold-coated stents correlated with a reduction in inflammation to levels equivalent to uncoated stents. The number of
porcine CD45-positive cells per five high-power neointimal
fields in nonheated gold-coated stents (134.0⫾18.5) was
2.6-fold greater than the reaction in uncoated stainless steel
stents (45.6⫾9.1) or heated gold devices (41.3⫾7.6,
P⬍0.0001; Figure 3). Similarly, CD45-positive cells in the
neointima represented 14.8⫾0.4%, 5.6⫾0.8%, and
5.7⫾1.5% of the total cells for steel, gold-coated, and heated
gold stents, respectively, and the number of multinucleated
giant cells increased in gold-plated but not heated gold-coated
stents: 8.4⫾0.6, 13.2⫾2.2 (P⬍0.02), and 8.6⫾0.9 giant cells
per section for steel, gold-coated, and heated, gold-coated
stents, respectively.
Strut Thickness
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The application of a coating by necessity changes the thickness of
the stent strut. We examined struts of two thicknesses, one that
increased the strut thickness by virtue of the gold coating and one
with the same strut thickness achieved by electropolishing of the
steel stent before coating. When the coated stent struts were
polished to equalize coated and uncoated stent thickness, there was
less stainless steel and more soft gold in coated struts, and these
stents exhibited a greater propensity for recoil (Table). Correspondingly, when the amount of steel was kept constant and the goldcoated struts were therefore thicker, recoil dropped. The impact of
recoil on luminal diameter is synergistic with intimal hyperplasia.
For example, recoil was so much less in the coated 16-mm stents
when the 7-␮m coating was added to a standard thickness strut that
the ultimate lumen size was greater for the gold-coated stents
despite greater tissue growth.
Discussion
As endovascular stents are altered to add functionality,
biocompatibility may suffer. Indeed, gold coatings of a stent
type other than that used here elicited greater restenosis than
similar uncoated stainless steel devices.1 We now report that
although gold coating of stainless steel improves radiopacity,
the mode of coating processing determines the hyperplastic
and inflammatory reactions. The reduced compatibility of
gold-coated stents was completely negated by postplating
heating. Moreover, the relative amounts of base and coating
metals, and their respective resistances to expansion and
collapse, determine stent recoil.
Biomedical Applications of Gold
Because of its malleability and relatively low melting point,
gold is one of the easiest metals to manipulate, and for ⬎5000
years, gold has adorned jewelry, weapons, goblets and
silverware, homes, and statuary.6 Gold dental fillings and
prostheses were used ⬎3000 years ago.7–9 Early rehabilitation in facial nerve paralysis involved placement of gold
weights or springs in the lower eyelid,10 and gold materials
were a major part of cranioplasty.11 Gold has been used in
electromechanical devices by virtue of high electrical conductivity and corrosion resistance and in a broad spectrum of
applications in biology, pharmacology, and medicine. The
Figure 3. Photomicrographs (a; ⫻200), extent of neointimal
thickness (b; mm), and degree of inflammation (c; % porcine
CD45-positive cells in neointima) 28 days after implantation of
9-mm stainless steel stents left intact (Bare; open bars), goldcoated NIR stents (Royal; solid bars), and flash-heated postplated NIR stents (Baked; gray bars). Arrow indicates internal
elastic lamina; *, sites of stent struts.
Edelman et al
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cellular compatibility of this material is high, as evidenced by
its use as a tracer compound following cell motility and
defining cell structure with electron microscopy. Ease of use,
coupled with atomic weight and density, might make gold a
natural material for enhancing endovascular implant radiovisibility. Gold is, however, subject to corrosion in chlorinerich environments and is perhaps 100 times less resistant than
316L stainless steel.12 Thus, a central question is whether
stents with surface gold would elicit untoward tissue responses and, if so, whether such a response was an obligate
material reaction or controllable through manipulation of
metal or surface properties.
Our knowledge of gold biocompatibility stems in part from
studies of the effects of dental prostheses and other goldplated implants. The most biocompatible of six single-phase
dental metal alloys was the one with the greatest gold
content.13 Gold has been used to mark catheters, the ends of
balloons, portions of guidewires, and stents. Gold markings
have extended from isolated dots to coatings over terminal
rings or the entire stent surface. The juxtaposition of two
dissimilar materials and differences in surface and mechanical properties can generate profound effects. Surface applications that remove the oxide layer that covers stainless steel
may make this inert material less compatible. Surface modifications can create substrate-film mismatches, film defects,
volume changes, alterations in film microstructure, impurities, anisotropic growth, or electrostatic effects. Thus, the
possibility of surface breaks and cracks from tensile stress or
of buckling or curling with compression arises. Metallic
coating alterations in charge, hydrophobicity, and texture, as
well as surface composition, can influence thrombogenic
potential, endothelial regeneration, and intimal hyperplasia.
Rougher surfaces increase thrombosis, mural injury, intimal
hyperplasia,14 and altered endothelial cell migration,15 and
platelets adhere with greater affinity to materials with high
surface potential materials and hydrophobicity.16
The earliest clinical use of gold-plated stents was in the
genitourinary tract.17,18 Gold-plated stainless-steel prostatic
stents produced fewer acute irritative symptoms, no greater
infections, and minimally greater encrustations than nitinol
stents.17 Gold-coated endovascular stents have also fared
well, especially compared with other metals such as copper.
Copper, but not gold,19 increased the thrombogenic potential
of stents, and gold-plated stents produced fewer macroscopic
and histopathologic changes in dog aortae than silver- or
copper-plated or Teflon- or silicone-coated devices. Copperplated stents in particular eroded the vessel wall, with marked
thrombus formation and aortic rupture.20 Hehrlein et al14
coated the surface of stainless steel Palmaz-Schatz stents with
platinum, gold, or copper by electrochemical deposition or
argon ion bombardment. Four weeks after implantation, 6 of
14 galvanized stents, but none of the uncoated or ionbombarded stents, were occluded by a thrombus. Similarly,
neointimal hyperplasia was increased in galvanized coated
stents compared with stents coated by ion implantation. In
both study groups, the most electropositive coating (platinum
or gold) induced markedly less neointimal formation than the
least electropositive (copper). Thrombogenic properties of
bare and gold-coated stents in flow loops did not differ.21
Gold-Coated Stents
433
Nonetheless, recent articles1 have indicated that gold coatings on stents may not be as compatible as their stainless steel
counterparts. Seven hundred thirty patients at a single center
were randomized to receive a standard stainless steel or 5-␮m
gold-coated slotted tube stents. Stent occlusion at 30 days was
4-fold higher and the probability of death, myocardial infarction or target lesion revascularization after 1 year was almost
twice as great in the gold-plated group. The stents used in that
study (InFlow Gold) were different in design and material
than those we examined, and the reaction to the gold coating
reported in that study1 was far greater than anything we
observed. Gold-coated stents in our study failed to elicit a
reaction greater than that observed in clinically used devices;
the neointima formed in all of the gold-coated stents was less
than that observed with Palmaz-Schatz stents placed in
identical animals under similar conditions. Thus, it is increasingly clear that even subtle changes in the processing of metal
plating can have profound effects on the biocompatibility of
a coated device. Some gold-plating techniques clearly endow
stents with an excessive inflammatory or proliferative reaction. However, others may not, and those that do can be made
more compatible with additional processing.
Benefits of Postplating Processing
A number of possible interrelated effects might explain why
heating gold-coated stents removed adverse material-tissue interactions, including smoothing of the stent surface, removal of
impurities, and strengthening of the gold stent interface. The
relative bioinertness of stainless steel arises primarily from the
overlying oxide layer. Application of a metal coat requires
removal of this layer. The intergranular spaces of the stainless
steel must then be covered by the coating or establish nidi for
corrosion and potential reservoirs for contaminants. Coatings
that are incomplete, are highly porous, flake with wear, or crack
with stent expansion expose the underlying metal. Organic
contaminants, such as long-chain acids used as surfactants or
cyanate salts used in plating process, can become trapped in
these intergranular spaces. Heating can disintegrate these contaminants and smooth the surface of the gold coating. Average
roughness values for the heated stents were half of the nonheated
and comparable to plain stainless steel devices. Intergranular
spaces or pores in a porous material within the coating might be
sealed or covered over.
Noble metals are minimally chemically reactive, and within
the transition elements, gold is the noblest. Mineral gold is not a
pure metal but rather an alloy. Harvested ores may contain more
silver than gold. Even gold processed to 99.99% purity retains
100 ppm silver, 20 ppm copper, and 30 ppm other base metals.22
Although it is not clear whether these levels of impurities can
alter tissue responses, minor amounts of nickel, molybdenum,
and chromium eluted from metal stents can increase thrombogenicity and leukocyte activation in bench-top assays.23 The
diffusivity of a compound is temperature dependent, and at some
temperatures, the diffusivity is so low that no movement can be
detected. The distance one metal will traverse into another
during heating is the square root of the product of the diffusivity
of the one metal into the other at the specific heating temperature
and the time that the material is exposed to that temperature. The
diffusivity of gold into stainless steel is so low that it will not
434
Circulation
January 23, 2001
move substantially from the coating even at elevated temperatures. Iron, in contrast, which is 74% of 316L stainless steel, will
not flow through gold at room temperature but can diffuse
completely through a 7-␮m gold layer with 100-second exposure to a temperature that will raise its diffusivity to 10⫺8 cm2/s.
We did observe enhanced iron diffusion into the heated gold
coating (although it was not sufficient to reach the surface),
virtually no impurities in the coating, and no difference in the
surface gold elemental content of baked and unheated goldplated stents.
Nonetheless, even limited metal diffusion can have significant
mechanical advantages. Elemental diffusion creates a tighter
bond between the gold coat and underlying stainless steel that
minimizes the mechanical trauma from buckling or cracking
with differential expansion. These theoretical effects, coupled
with our data, suggest that if gold coatings are to be applied to
stents, they should undergo some type of thermal processing.
Recoil, Intimal Hyperplasia, and Luminal Stenosis
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Coatings by necessity changes strut thickness and expansion
dynamics. The latter may become especially problematic when
stent and coating metals are of different material strengths.
Standard coating techniques increase strut thicknesses by twice
the coating depth and strengthen devices against expansion and
recoil. If the thickness is kept constant but some of the original
metal is replaced with a softer substitute, there will be less
resistance to expansion and recoil. When the thrombotic, inflammatory, and proliferative responses to the metal coating combine
with recoil, there is a complementary effect on luminal integrity.
A metal that elicits a greater vascular response but resists recoil
to a greater extent than control stents may in fact produce a
greater luminal diameter. This was the case for the 16-mm stents
used in the second set of studies whose coating was laid down on
unmodified struts. In contrast, when there is enhanced recoil and
a significant vascular response, luminal diameter may be decreased even more than anticipated. That we did not observe the
expected lower recoil of gold-coated stents in study 4 likely
reflects the difficulty in making these measurements in an
animal model system at the terminus of the experiments. Further
work in metallurgy and material science will enable independent
optimization of stent coatings and strength.
Conclusions
Coated, plated, and surface-modified stents are the devices of
the future. Analysis of their reactivity is complex and multifactorial, including interdependence of surface and bulk
properties of the materials and composite devices. There is a
tradeoff between radiopacity and the dynamics of stent
expansion, recoil, and intimal hyperplasia. In a 21st century
version of the alchemist’s dream, postplating processing can
turn “plain gold” into “better gold,” reducing inflammatory
and intimal hyperplastic reactions.
Quo ferrea primum desinet ac toto surget gens aurea
mundo [The age of iron comes to an end. In every
region of the world the golden race appears anew.]
P. Vergili Maronis. Ecloga Quarta, 8 –10.
Acknowledgments
We acknowledge grant support from the National Institutes of
Health (GM/HL-49039, HL-60407 to Dr Edelman; HL-03104 to Dr
Rogers) and a gift from Medinol, Ltd. Dr Edelman is an Established
Investigator of the American Heart Association. We are further
grateful for intellectual input from Dr Jacob Richter and Professors
Larry Kaufman and Robert Rose and for the expert technical
assistance of Stefan Hesselberg. Surface analysis made use of
MRSEC Shared Facilities supported by the National Science Foundation (DMR-9400334).
References
1. Kastrati A, Schomig A, Dirschinger J, et al. Increased risk of restenosis
after placement of gold-coated stents: results of a randomized trial comparing gold-coated with uncoated steel stents in patients with coronary
artery disease. Circulation. 2000;101:2478 –2483.
2. Kjelsberg MA, Seifert P, Edelman ER, et al. Design dependent variations
in coronary stent stenosis are measured as precisely by angiography as by
histology. Journal of Invasive Cardiology. 1998;10:142–150.
3. Rogers C, Welt FG, Karnovsky MJ, et al. Monocyte adhesion and neointimal hyperplasia in rabbits: coupled inhibitory effects of heparin.
Arterioscler Thromb Vasc Biol. 1996;16:1312–1318.
4. Garasic J, Edelman ER, Squire JC, et al. Stent and artery geometry
determine intimal thickening independent of deep arterial injury. Circulation. 2000;101:812-818.
5. Schwartz RS, Huber KC, Murphy JG, et al. Restenosis and proportional
neointimal response to coronary artery injury: results in a porcine model.
J Am Coll Cardiol. 1992;19:267–274.
6. Niemi L. Structure, corrosion and biocompatibility of dental Ag-Pd-Cu(Au)-(Zn) alloys. Proc Finn Dent Soc. 1986;82(suppl 1-2):1–30.
7. Hagman HC. 3,000 years of dental gold. Dent Lab Rev. 1979;54:28 –30.
8. Harris JE, Iskander Z, Farid S. Restorative dentistry in ancient Egypt: an
archaeologic fact! J Mich Dent Assoc. 1975;57:401– 404.
9. Loevy HT, Kowitz AA. The dawn of dentistry: dentistry among the
Etruscans. Int Dent J. 1997;47:279 –284.
10. Linder TE, Pike VE, Linstrom CJ. Early eyelid rehabilitation in facial
nerve paralysis. Laryngoscope. 1996;106:1115–1118.
11. Sanan A, Haines SJ. Repairing holes in the head: a history of cranioplasty
[see comments]. Neurosurgery. 1997;40:588 – 603.
12. Steinemann SG. Metal implants and surface reactions. Injury. 1996;
27(suppl 3):SC16 –SC22.
13. Grill V, Sandrucci MA, Basa M, et al. The influence of dental metal
alloys on cell proliferation and fibronectin arrangement in human
fibroblast cultures. Arch Oral Biol. 1997;42:641– 647.
14. Hehrlein C, Zimmermann M, Metz J, et al. Influence of surface texture
and charge on the biocompatibility of endovascular stents. Coron Artery
Dis. 1995;6:581–586.
15. Palmaz J, Benson A, Sprague E. Influence of surface topography on endothelialization of intravascular metallic material. JVIR. 1999;10:439–444.
16. Seeger J, Ingegno MP, Bigatan E, et al. Hydrophilic surface modification
of metallic endoluminal stents. J Vasc Surg. 1995;22:327–336.
17. Yachia D, Aridogan IA. Comparison between first-generation (fixedcaliber), and second- generation (self-expanding, large caliber) temporary
prostatic stents. Urol Int. 1996;57:165–169.
18. Holmes SA, Miller PD, Crocker PR, et al. Encrustation of intraprostatic
stents: a comparative study. Br J Urol. 1992;69:383–387.
19. Nikolaychik V, Sahota H, Keelan MH Jr, et al. Influence of different stent
materials on endothelialization in vitro. J Invasive Cardiol. 1999;11:410–415.
20. Tanigawa N, Sawada S, Kobayashi M. Reaction of the aortic wall to six
metallic stent materials. Acad Radiol. 1995;2:379 –384.
21. Herrmann R, Schmidmaier G, Markl B, et al. Antithrombogenic coating
of stents using a biodegradable drug delivery technology. Thromb
Haemost. 1999;82:51–57.
22. Dähne W. Gold refining and gold recycling. In: Schmidbaur H, ed. Gold:
Progress in Chemistry, Biochemistry, and Technology. New York, NY:
John Wiley & Sons Inc; 1999:119 –142.
23. Tarnok A, Mahnke A, Muller M, et al. Rapid in vitro biocompatibility
assay of endovascular stents by flow cytometry using platelet activation
and platelet-leukocyte aggregation. Cytometry. 1999;38:30 –39.
Gold-Coated NIR Stents in Porcine Coronary Arteries
Elazer R. Edelman, Philip Seifert, Adam Groothuis, Alisa Morss, Danielle Bornstein and
Campbell Rogers
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Circulation. 2001;103:429-434
doi: 10.1161/01.CIR.103.3.429
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