Note: Descriptions are shown in the official language in which they were submitted.
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SELF-SUPPORTING LAMINATED FILMS, STRUCTURAL MATERIALS AND
MEDICAL DEVICES MANUFACTURED THEREFROM AND METHODS OF
MAKING SAME
Cross-Reference to Related Applications
This application claims priority froze U.S. Provisional Patent Application
Serial No.
60/203,835, filed May 12, 2000 which is a continuation-in-part of co-pending
U.S. Patent
Application Serial No. 09/443,929, filed November 19, 1999, from which
priority is claimed.
Background of the Invention
The present invention pertains generally to implantable medical devices and,
more
particularly, to implantable medical devices fabricated of self supporting
laminated films
fashioned into geometric configurations adapted to specific medical uses. More
particularly,
the present invention relates to metal films, foils, wires and seamless tubes,
with increased
mechanical properties, which are suitable for use in fabricating implantable
endoluminal
grafts, stmt-grafts and stmt-graft-type devices. More specifically, the
present invention
comprises endoluminal grafts, stmt-grafts and stmt-graft-type devices that are
fabricated
entirely of self supporting laminated films, foils, wires or seamless tubes
made of
biocompatible metals or of biocompatible materials which exhibit biological
response and
material characteristics substantially the same as biocompatible metals, such
as for example
composite materials.
As opposed to wrought materials that are made of a single metal or alloy,
these
inventive materials are made of at least two layers formed upon one another
into a self
supporting laminate structure. Laminate structures are generally known to
increase the
mechanical strength of sheet materials, such as wood or paper products.
Laminates are used
in the field of thin film fabrication also to increase the mechanical
properties of the thin film,
specifically hardness and toughness. Laminate metal foils have not been used
or developed
because the standard metal forming technologies, such as rolling and
extrusion, for example,
do not readily lend themselves to producing laminate structures. Vacuum
deposition
technologies can be developed to yield laminate metal structures with improved
mechanical
properties. In addition, laminate structures can be designed to provide
special qualities by
including layers that have special properties such as superelasticity, shape
memory, radio-
opacity, corrosion resistance etc.
Metal foils, wires and thin-walled seamless tubes are typically produced from
ingots
in a series of hot or cold forming steps that include some combination of
rolling, pulling,
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extrusion and other similar processes. Each of these processing steps is
accompanied by
auxiliary steps that include cleaning the surfaces of the material of foreign
material residues
deposited nn the material by the tooling and lubricants used in the metal
forming processes.
Additionally, chemical interaction with tooling and lubricant materials and
ambient gases
also introduces contaminants. Some residue will still usually remain on the
surface of the
formed material, and there is a high probability that these contaminating
residues become
incorporated during subsequent processing steps into the bulk of the wrought
metal product.
With decreasing material product size, the significance of such contaminating
impurities
increases. Specifically, a greater number of process steps, and, therefore, a
greater
probability for introducing contaminants, are required to produce smaller
product sizes.
Moreover, with decreasing product size, the relative size of non-metal or
other foreign
inclusions becomes larger. This effect is particularly important for material
thicknesses that
are comparable to the grain or inclusion size. For example, austenitic
stainless steels have
typical grain sizes on the order of magnitude of 10-100 micrometer. When a
wire or foil with
a thickness in this range is produced, there is significant probability that
some grain
boundaries or defects will extend across a large portion or even across the
total thickness of
the product. Such products will have locally diminished mechanical and
carrosion resistance
properties. While corrosion resistance is remedied by surface treatments such
as
electropolishing, the mechanical properties are more difficult to control.
The mechanical properties of metals depend significantly on their
microstructure.
The forming and shaping processes used to fabricate metal foils, wires and
thin-walled
seamless tubes involves heavy deformation of a bulls material, which results
in a heavily
strained and deformed grain structure. Even though annealing treatments may
partially
alleviate the grain deformation, it is typically impossible to revert to well-
rounded grain
structure and a large range of grain sizes is a common result. The end result
of conventional
forming and shaping processes, coupled with annealing, typically results in
non-uniform
grain structure and less favorable mechanical properties in smaller sized
wrought metal
products. It is possible, therefore, to produce high quality homogeneous
materials for special
purposes, such as micromechanical devices and medical devices, using vacuum
deposition
technologies.
In vacuum deposition technologies, materials are formed directly in the
desired
geometry, e.g., planar, tubular, etc. The common principle of the vacuum
deposition
processes is to take a material in a minimally processed form, such as pellets
or thick foils
(the source material) and atomize them. Atomization may be carried out using
heat, as is the
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case in physical vapor deposition, or using the effect of collisional
processes, as in the case of
sputter deposition, for example. In some forms of deposition, a process, such
as laser
ablation, which creates microparticles that typically consist of one or more
atoms, may
replace atomization; the number of atoms per particle may be in the thousands
or more. The
S atoms or particles of the source material are then deposited on a substrate
or mandrel to
directly form the desired object. In other deposition methodologies, chemical
reactions
between ambient gas introduced into the vacuum chamber, i.e., the gas source,
and the
deposited atoms andlor particles are part of the deposition process. The
deposited material
includes compound species that are formed due to the reaction of the solid
source and the gas
source, such as in the case of chemical vapor deposition. In most cases, the
deposited
material is then either partially or completely removed from the substrate, to
form the desired
product.
The rate of film growth is a significant parameter of vacuum deposition
processes. In
order to deposit materials that can be compared in functionality with wrought
metal products,
deposition rates in excess of 1 micrometerslhour are a must and indeed rates
as high as 100
micrometers per hour are desirable. These are high deposition rates and it is
known that at
such rates the deposits always have a columnar structure. Depending on other
deposition
parameters, and most importantly on the substrate temperature, the columns may
be
amorphous or crystalline but at such high deposition rates microcrystalline
structure
development can be expected at best. The difficulty is that the columns
provide a
mechanically weak structure in which crack propagation can occur uninhibited
across the
whole thickness of the deposit.
A special advantage of vacuum deposition technologies is that it is possible
to deposit
layexed materials and thus films possessing exceptional qualities may be
produced (c.~, H.
Holleclc, V. Schier: "Multilayer PVD coatings for wear protection", Surface
ahd Coati~rgs
Teclahology, Vol. 76-77 (1995) pp. 32~-336). Layered materials, such as
superstructures or
multilayers, are commonly deposited to take advantage of some chemical,
electronic, or
optical property of the material as a coating; a common example is an
antireflective coating
on an optical lens.
It has not been recognized until relatively recently that multilayer coatings
may have
improved mechanical properties compared with similar coatings made of a single
layer. The
improved mechanical properties may be due to the ability of the interface
between the layers
to relieve stress. This stress relief occurs if the interface provides a slide
plane, is plastic, or
may delaminate locally. This property of multilayer films has been recognized
in regard with
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their hardness but this recognition has not been translated to other
mechanical properties that
are significant for metal products that may be used in application where they
replace wrought
metal parts.
A technological step that interrupts the film growth results in discontinuous
columns
and prevents crack propagation across the entire film thickness. In this
sense, it is not
necessary that the structure consist of a multiplicity of chemically distinct
layers, as it is
common in the case of thin film technology where multilayers are used. Such
chemical
differences may be useful and may contribute to improved properties of the
materials.
In its simplest form, the inventive process consists of the steps of providing
a
substrate, depositing a first layer of material on the substrate, depositing a
second layer of
material on the first layer of material acid optionally removing the layered
material from the
substrate. The last step is necessary in the case of making foils and seamless
tubes but would
be omitted in the case of malting wires. In this latter case, the substrate
itself is a thin wire
that becomes part of the final product. In more complex cases, the number of
layers is more
than two. There is no limitation regarding the number of layers and regarding
the thickness
of each layer.
As used in this application a "layer" is intended to mean a substantially
uniform
material limited by interfaces between it and adjacent other substantially
homogeneous
layers, substrate, or environment. The interface region between adjacent
layers is an
inhomogeneous region in which extensive thermodynamic parameters may change.
Different
layers are not necessarily characterized by different values of the extensive
thermodynamic
parameters but at the interface, there is a local change at least in some
parameters. For
example, the interface between two steel layers that are identical in
composition and
microstructure may be characterized by a high local concentration of grain
boundaries due to
an interruption of the film growth process. Thus, the interface between layers
is not
necessarily different in chemical composition if it is different in structure.
It is necessary to provide for good adhesion between the layers and this is
usually
achieved by providing for a relatively broad interface region rather than for
an abrupt
interface. The width of the interface region may be defined as the range
within which
extensive thermodynamic parameters change. This range can depend on the
interface area
considered and it may mean the extent of interface microroughness. In other
words, adhesion
may be promoted by increased interface microroughness between adjacent layers.
By providing for a layered structure, the inventive materials consist of a
controlled
maximum size of grains and columns as extended defects in the direction of the
film growth
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(perpendicular to the layers). This limit of the grain or defect size results
in materials that
have increased mechanical strength and particularly increased toughness
compared to their
non-laminated counterparts, both deposited and wrought materials., In
addition, limiting the
extent to which defects and grain boundaries reach across the laminate,
corrosion resistance is
also improved.
Laminated materials will have additional advantages when chemical compositions
of
the layers are chosen to achieve special properties. For example, a radiopaque
material such
as Ta may form one layer of a structure while other layers are chosen to
provide the material
with necessary mechanical and other properties.
Without limiting the scope of application ofthe present invention, the
following are
specific examples of products or devices which may be fabricated using the
laminated film
and process of the present invention: 1) an implantable graft fabricated of
laminated films of
biocompatible metals or biocompatible materials which exhibit ih vivo
biological and
mechanical responses substantially the same as biocompatible metals
(hereinafter referred to
as "metal-like materials"); 2) an implantable stmt-graft device in which a
structural
component, or stmt, and a graft component are each fabricated of laminated
films of metal or
metal-like materials; 3) an implantable stmt-graft-type device in which a
structural support,
such as a stmt, defines openings which are subtended by a web, with both the
stmt and the
web being formed as a single, integral, laminated film or tubular structure
and fabricated of
metals or of metal-like materials, this particular embodiment is hereinafter
referred to as a
"web-stmt;" and 4) planar films, sheets or foils made of laminated
biocompatible metals or
biocompatible materials, suitable for use as medical tissue patches, aerospace
surfaces, such
as leading edges of aircraft wings or helicopter rotors, or as active surfaces
on tail rudders or
wing flaps of aircraft.
Graft E~nbodi~sient
As used herein the term "Graft" is intended to indicate any type of tubular
member
which exhibits integral columnar and circumferential strength and which has
openings which
pass through the thiclaless of the tubular member.
In accordance with a preferred embodiment of the invention, a graft member is
formed as a discrete thin sheet or tube of biocompatible metals or metal-like
material. A
plurality of openings is provided which pass transversely through the graft
member. The
plurality of openings may be random or may be patterned. It is preferable that
the size of
each of the plurality of openings be such as to permit cellular migration
through each
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opening, without permitting fluid flow there through. In this manner, blood
cannot flow
through the plurality of openings, but various cells or proteins may freely
pass through the
plurality of openings to promote graft healing if? vivo. In accordance with
another aspect of
the inventive graft embodiment, it is contemplated that two graft members are
employed,
with an outer diameter of a first graft member being smaller than the inner
diameter of a
second graft member, such that the first graft member is concentrically
engageable within a
lumen of the second graft member. Both the first and second graft members have
a pattern of
a plurality of openings passing there through. The first and second graft
members are
positioned concentrically with respect to one another, with the plurality of
patterned openings
being positioned out of phase relative to one another such as to create a
tortuous cellular
migration pathway through the wall of the concentrically engaged first and
second graft
members. In order to facilitate cellular migration through and healing of the
first and second
graft members irz vivo, it is preferable to provide additional cellular
migration pathways that
communicate between the plurality of openings in the first and second graft
members. These
additional cellular migration pathways may be imparted as 1) a plurality of
projections
formed on either the luminal surface of the second graft or the abluminal
surface of the first
graft, or both, which serve as spacers and act to maintain an annular opening
between the first
and second graft members that permits cellular migration and cellular
communication
between the plurality of openings in the first and second graft members, or 2)
a plurality of
microgrooves, which may be random, radial, helical, or longitudinal relative
to the
longitudinal axis of the first and second graft members, the plurality of
microgrooves being
of a sufficient size to permit cellular migration and propagation along the
groove without
permitting fluid flow there through, the microgrooves serve as cellular
migration conduits
between the plurality of openings in the first and second graft members.
Stet Graft Ernbodirnent
In accordance with another preferred embodiment of the present invention, a
graft
member may be formed as either a thin sheet of material or as a tubular
member, and
mechanically joined to cover a plurality of structural support members. The
graft member
may be used to cover either a luminal or abluminal surface, or both, of an
endoluminal
device. °
A stmt-graft in accordance with the present invention may be formed by
conjoining a
discrete graft member with a plurality of structural support members, such as
a stmt, by
mechanically joining the graft member to regions of the plurality of
structural support
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members. Alternatively, a stmt-graft may be formed by first forming, such as
by vacuum
deposition methods or by etching a pre-existing material blank, a graft member
as a
contiguous thin sheet ~or tube which projects outwardly from at least one
aspect of the
plurality of structural members. The thin sheet is then evened over the
structural members
and brought into a position adjacent a terminal portion of the plurality of
structural members
such that it covers one or both of the putative luminal or abluminal surfaces
of the plurality of
structural members. The graft member is then mechanically joined at an
opposing end, i.e.,
the putative proximal or the putative distal end of the plurality of
structural members.
The stmt-graft is formed entirely of a metal or metal-like material, which, as
opposed
to using conventional synthetic polymeric graft materials, the inventive graft
material exhibits
improved healing response.
Web-Stent Embodi'nent
In accordance with one of the embodiments of the present invention, there is
provided
a stmt-graft-type device, termed a "web-stmt" in which there is at least one
of a plurality of
structural members that provide a primary means of structural support for the
webbed-stmt
device. The plurality of structural members may be arranged in any manner as
is known in
the an of stmt fabrication, e.g., single element forming a circle or ellipse,
a single or plural
elements which form a tubular diamond-like or undulating pattern, in which
adjacent
structural members are spaced apart forming open regions or interstices
between adjacent
structural members. In the present invention, the interstices or open regions
between adjacent
structural members are subtended by a web of material that is the same
material or a material
exhibiting similar biological and mechanical response as the material that
forms the plurality
of structural members. The web may be formed within all or a portion of the
interstitial area
or open regions between the plurality of structural support members.
Method ofMaking Graft, Stent-Graft and Web-Stent
Finally, the present invention provides a method of fabricating the graft,
stmt-graft
and web-stmt devices of the present invention. The inventive method consists
of forming the
device by vacuum deposition of a film, either as a planar sheet or as a tube,
of a
biocompatible material, such as nickel-titanium alloys. The thickness of the
deposited
material is determined by the particular embodiment being fabricated. After
the deposited
film is created, either additive or subtractive methodologies are employed to
define: the
structural members, the interstitial web regions, the graft regions and/or a
plurality of
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openings through the deposited film. Alternatively, a pre-fabricated starting
film of a
biocompatible material, such as Nitinol, may be employed, and the stmt-pattern
formed by
vacuum deposition methods or by conventional metal forming techniques, or by
removing
regions of the pre-fabricated film to form the interstitial regions of the web-
stmt device.
, Where a graft member is being fabricated, the thickness of the deposited or
pre-
fabricated starting film may be less than that where a web-stmt is being
formed, due to the
absence of structural members in the graft member. However, where a stmt-graft
or a web-
stent is being fabricated, structural members may be formed by alternative
methods. The
structural members may be formed by additive techniques by applying a pattern
of structural
members onto a film, such as by vacuum deposition techniques or conventional
metal
forming techniques, such as laminating or casting. Second, subtractive or
selective removal
techniques may be employed to remove material from patterned regions on a
film, such as by
etching a pattern of interstitial regions between adjacent structural members
until a thinner
film is created which forms the web subtending the plurality of structural
members. Where a
pre-existing stmt is employed as the structural members, obviously, the
structural members
do not need to be fabricated or formed.
In accordance with the best mode contemplated for the present invention, the
graft,
the plurality of structural members and the web are fabricated of the same or
similar metals or
metal-like materials. In order to improve healing response, it is preferable
that the materials
employed have substantially homogenous surface profiles at the blood or tissue
contact
surfaces thereof. A substantially homogeneous surface profile is achieved by
controlling
heterogeneities along the blood or tissue-contacting surface of the material.
The
heterogeneities that are controlled in accordance with an embodiment of the
present invention
include: grain size, grain phase, grain material composition, stmt-material
composition, and
surface topography at the blood flow surface of the stmt. Additionally, the
present invention
provides methods of making endoluminal devices having controlled
heterogeneities in the
device material along the blood flow or tissue-contacting surface of the
device. Material
heterogeneities are preferably controlled by using conventional methods of
vacuum
deposition of materials onto a substrate.
The surface of a solid, homogeneous material can be conceptualized as having
unsaturated inter-atomic and intermolecular bonds forming a reactive plane
ready to interact
with the environment. In practice, a perfectly clean surface is unattainable
because of
immediate adsorption of airborne species, upon exposure to ambient air, of O,
OZ, COZ, SO~,
NO, hydrocarbons and other more complex reactive molecules. Reaction with
oxygen
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implies the formation of oxides on a metal surface, a self limiting process,
known as
passivation. An oxidized surface is also reactive with air, by adsorbing
simple, organic
airborne compounds. Assuming the existence of bulk material of homogeneous
subsurface
and surface composition, oxygen and hydrocarbons may adsorb homogeneously.
Therefore,
fuuher exposure to another environment, such as the vascular compartment, may
be followed
by a uniform biological response.
Current metallic vascular devices, such as stems, are made from bulk metals
made by
conventional methods which employ many steps that introduce processing aides
to the metals
make stmt precursors, such as hypotubes. For example, olefins trapped by cold
drawing and
transformed into carbides or elemental carbon deposit by heat treatment,
typically yield large
carbon rich areas in 316L stainless steel tubing manufactured by cold drawing
process. The
conventional stems have marked surface and subsurface heterogeneity resulting
fi~om
manufacturing processes (friction material transfer from tooling, inclusion of
lubricants,
chemical segregation from heat treatments). This results in formation of
surface and
subsurface inclusions with chemical composition and, therefore, reactivity
different from the
bulk material. Oxidation, organic contamination, water and electrolytic
interaction, protein
adsorption and cellular interaction may, therefore, be altered on the surface
of such inclusion
spots. Unpredictable distributions of inclusions such as those mentioned above
provide
unpredictable and uncontrolled heterogeneous surface available for interaction
with plasma
proteins and cells. Specifically, these inclusions interrupt the regular
distribution pattern of
surface free energy and electrostatic charges on the metal surface that
determine the nature
and extent of plasma protein interaction. Plasma proteins deposit
nonspecifically on surfaces
according to their relative affinity for polar or non-polar areas and their
concentration in
blood. A replacement process known as the Vroman effect, Vroman L., The
importance of
surfaces in contact phase reactions, SeT~rinars of Th~onzbosis acrd
Heyyaostasis 1987; 13(1): 79-
85, determines a time-dependent sequential replacement of predominant proteins
at an
artificial surface, starting with albumin, following with IgG, fibrinogen and
ending with high
molecular weight kininogen. Despite this variability in surface adsorption
specificity, some
of the adsorbed proteins have receptors available for cell attachment and
therefore constitute
adhesive sites. Examples are: fibrinogen glycoprotein receptor IIbIIIa for
platelets and
fibronectin RGD sequence for many blood activated cells. Since the coverage of
an artificial
surface with endothelial cells is a favorable end-point in the healing
process, favoring
endothelialization in device design is desirable in implantable vascular
device manufacturing.
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Normally, endothelial cells (EC) migrate and proliferate to cover denuded
areas until
confluence is achieved. Migration, quantitatively more important than
proliferation, proceeds
under normal blood flow roughly at a rate of 25 ~,m/hr or 2.5 times the
diameter of an EC,
which is nominally 10~,m. EC migrate by a rolling motion of the cell membrane,
coordinated
by a complex system of intracellular filaments attached to clusters of cell
membrane integrin
receptors, specifically focal contact points. The integrins within the focal
contact sites are
expressed according to complex signaling mechanisms and eventually couple to
specific
amino acid sequences in substrate adhesion molecules (such as RGD, mentioned
above). An
EC has roughly 16-22% of its cell surface represented by integrin clusters.
Davies, P.F.,
Robotewskyi A., Griem M.L. Endothelial cell adhesion in real time. J. Clip.
hrvest. 1993;
91:2640-2652, Davies, P.F., Robotewslci, A., Griem, M.L., Qualitiative studies
of endothelial
cell adhesion, J.Clir~.lnvest.1994; 93:2031-2038. This is a dynamic process,
which implies
more than 50% remodeling in 30 minutes. The focal adhesion contacts vary in
size and
distribution, but 80% of them measure less than 6 pm', with the majority of
them being about
1 pmt, and tend to elongate in the direction of flow and concentrate at
leading edges of the
cell. Although the process of recognition and signaling to determine specific
attachment
receptor response to attachment sites is incompletely understood, regular
availability of
attachment sites, more likely than not, would favorably influence attachment
and migration.
Irregular or unpredictable distribution of attachment sites, that might occur
as a result of
various inclusions, with spacing equal or smaller to one whole cell length, is
likely to
determine alternating hostile and favorable attachment conditions along the
path of a
migrating cell. These conditions may vary from optimal attachment force and
migration
speed to insufficient holding strength to sustain attachment, resulting in
cell Slough under
arterial flow conditions. Due to present manufacturing processes, current
implantable
vascular devices exhibit such variability in surface composition as determined
by surface
sensitive techniques such as atomic force microscopy, X-ray photoelectron
spectroscopy and
time-of flight secondary ion mass spectroscopy.
There have been numerous attempts to increase endothelialization of implanted
stems,
including covering the scent with a polymeric material (U.S. Patent No.
5,897,911), imparting
a diamond-like carbon coating onto the stmt (U.S. Patent No. 5,725,573),
covalently binding
hydrophobic moieties to a heparin molecule (U.S. Patent No. 5,955,588),
coating a stmt with
a layer of blue to black zirconium oxide or zirconium nitride (U.S. Patent No.
5,649,951),
coating a stmt with a layer of turbostratic carbon (U.S. Patent No.
5,387,247), coating the
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tissue-contacting surface of a stmt with a thin layer of a Group VB metal
(U.S. Patent No.
5,607,463), imparting a porous coating of titanium or of a titanium alloy,
such as Ti-Nb-Zr
alloy, onto the surface of a scent (U.S. Patent No. 5,690,670), coating the
stmt, under
ultrasonic conditions, with a synthetic or biological, active or inactive
agent, such as heparin,
endothelium derived growth factor, vascular growth factors, silicone,
polyurethane, or
polytetrafluoroethylene, U.S. Patent No. 5,891,507), coating a scent with a
silane compound
with vinyl functionality, then forming a graft polymer by polymerization with
the vinyl
groups of the silane compound (U.S. Patent No. 5,782,908), grafting monomers,
oligomers or
polymers onto the surface of a stmt using infrared radiation, microwave
radiation or high
voltage polymerization to impart the property of the monomer, oligomer or
polymer to the
stmt (U.S. Patent No. 5,932,299).
Thus, the problems of thrombogenicity and re-endothelialization associated
with
stems have been addressed by the art in various manners which cover the stmt
with either a
biologically active or an inactive covering which is less thrombogenic than
the stmt material
and/or which has an increased capacity for promoting re-endothelialization of
the stmt situs.
These solutions, however, all require the use of existing stems as substrates
for surface
derivatization or modification, and each ofthe solutions result in a biased or
laminate
structure built upon the stmt substrate. These prior art coated stents are
susceptible to
delaminating and/or cracking of the coating when mechanical stresses of
transluminal
catheter delivery and/or radial expansion izz vivo. Moreover, because these
prior art stems
employ coatings applied to stems fabricated in accordance with conventional
stmt formation
techniques, e.g., cold-forming metals, the underlying stmt substrate is
characterized by
uncontrolled heterogeneities on the surface thereof Thus, coatings merely are
laid upon the
heterogeneous stmt surface, and inherently conform to the topographical
heterogeneities in
the stmt surface and mirror these heterogeneities at the blood contact surface
of the resulting
coating. This is conceptually similar to adding a coat of fresh paint over an
old coating of
blistered paint; the fresh coating will conform to the blistering and
eventually, blister and
delaminate from the underlying substrate. Thus, topographical heterogeneities
are typically
telegraphed through a surface coating. Chemical heterogeneities, on the other
hand, may not
be telegraphed through a surface coating but may be exposed due to cracking or
peeling of
the adherent layer, depending upon the particular chemical heterogeneity.
The current invention entails creating materials specifically designed for
manufacture
of grafts, stents, stmt-grafts and other endoluminal devices. According to a
preferred
embodiment of the invention, the manufacture of grafts, stems, stmt-grafts and
other
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endoluminal devices is controlled to attain a regular, homogeneous atomic and
molecular
pattern of distribution along their surface. This avoids the marked variations
in surface
composition, creating predictable oxidation and organic adsorption patterns
and has
predictable interactions with water, electrolytes, proteins and cells.
Particularly, EC
migration is supported by a homogeneous distribution of binding domains that
serve as
natural or implanted cell attachment sites, in order to promote unimpeded
migration and
attachment. Based on observed EC attachment mechanisms such binding domains
should
have a repeating pattern along the blood contact surface of no less than 1 p.m
radius and 2 pm
border-to-border spacing between binding domains. Ideally, the inter-binding
domain spacing
is less than the nominal diameter of an endothelial cell in order to ensure
that at any given
time, a portion of an endothelial cell is in proximity to a binding domain.
Summary of the Invention
In accordance with the present invention, there is provided a laminated film
structure
and a method of making laminated film structures comprised of at least two of
a plurality of
plied layers of biocompatible metals or biocompatible materials which exhibits
mechanical
properties superior to those of a monolithic film structure of substantially
equal thickness as
the laminated film structure.
In accordance with the present invention, there is provided a web-stmt device,
fabricated of a laminated film, in which there is at least one of a plurality
of structural
members that provides a primary means of structural support for the web-stmt
device. The
plurality of structural members is spaced apart to form open regions or
interstices between
adjacent structural members. In the present invention, a web of material, that
is the same or
similar to the material which forms the plurality of structural members,
subtends the
interstices or open regions between adjacent structural members. The web may
be formed
within all or a portion of the interstitial area or open regions between the
plurality of
structural support members. Both the plurality of interconnected structural
members and the
web may be formed of initially substantially planar materials or of initially
substantially
cylindrical materials.
In accordance with another preferred embodiment of the present invention,
there is
provided a stmt-graft device in which a graft member is formed as a laminated
film of
material and mechanically joined to one or both. of the proximal and distal
ends of the
plurality of structural support members, and covers that surface of the
plurality of structural
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support members which is to form either the luminal or abluminal surface of
the stmt-graft
device. The graft member may be formed either separately or as a contiguous
thin-film
projecting from the plurality of structural members. Where the graft member is
formed as a
contiguous thin-film projecting from the plurality of structural members, the
thin film is
either abluminally everted or luminally inverted and brought into a position
adjacent to the
plurality of structural members such that it covers either, or both, the
luminal or abluminal
surfaces or the plurality of structural members, then is attached at an
opposing end, i. e., the
putative proximal or the putative distal end of the plurality of structural
members.
In accordance with another embodiment of the invention, there is provided a
graft
' 10 formed as a discrete laminated thin sheet or tube of biocompatible metal
or metal-like
materials. A plurality of openings is provided which pass transversely through
the graft
member. The plurality of openings may be random or may be patterned. It is
preferable that
the size of each of the plurality of openings be such as to permit cellular
migration through
each opening, without permitting fluid flow there through. In this manner,
blood cannot flow
through the plurality of openings, but various cells or proteins may freely
pass through the
plurality of openings to promote graft healing a~~ vivo.
In accordance with another aspect of the inventive graft embodiment, it is
contemplated that two graft members are employed, one or both of the graft
members being
formed of laminated films. An outer diameter of a first graft member is
dimensioned smaller
than the an inner diameter of a second graft member, such that the first graft
member is
concentrically engageable within a lumen of the second graft member. Both the
first and
second graft members have a plurality of patterned openings passing there
through. The first
and second graft members axe positioned concentrically with respect to one
another, with the
plurality of patterned openings being positioned out of phase relative to one
another such as
to create a tortuous cellular migration pathway through the wall of the
concentrically engaged
first and second graft members. In order to facilitate cellular migration and
healing of the
first and second graft members, it is preferable to provide additional
cellular migration
pathways that communicate 'between the plurality of openings in the first and
second graft
members. These additional cellular migration pathways may be imparted as 1) a
plurality of
projections formed on either the luminal surface of the second graft or the
abluminal surface
of the first graft, or both, which serve as spacers and act to maintain an
annular opening
between the first and second graft members and permit cellular migration in
order to
communicate between the plurality of openings in the first and second graft
members, or 2) a
plurality of microgrooves, which may be random, radial, helical, or
longitudinal relative to
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the longitudinal axis of the first and second graft members, the plurality of
microgrooves
being of a sufficient size to permit cellular migration. and propagation along
the groove
without permitting fluid flow there through, the microgrooves serve as
cellular migration
conduits between the plurality of openings in the first and second graft
members.
The present invention also provides a method of fabricating the web-stmt
device
which entails providing a planar or tubular laminated film of a biocompatible
material, such
as forming the film by vacuum deposition, then removing interstitial regions
until a thinner
film region is created which forms a web subtending a plurality of structural
members.
Alternatively, a pre-existing conventionally produced sheet or tube of a
biocompatible
material, such as Nitinol, may be etched until a thinner film is created in
the etched regions,
thereby forming the interstitial web areas of the web-stmt device.
Finally, in accordance with the present invention, there is provided an
implantable
endoluminal device that is fabricated from laminated film materials that
present a blood or
tissue contact surface that is substantially homogeneous in material
constitution. More
particularly, the present invention provides an endoluminal graft, stmt, stmt-
graft and web-
stent that is made of a material having controlled heterogeneities along the
blood flow or
tissue-contacting surface of the stmt.
Brief Description of the Figures
Figure 1A is a perspective, partial cross-sectional view of a laminated film
sheet
structure in accordance with the present invention.
Figure 1B is a perspective, partial cross-sectional view of a laminated film
tubular
structure in accordance with the present invention.
Figure 2 is a perspective view of a preferred embodiment of the web-stmt of
the
present invention.
Figure 3 is a perspective view of a stmt-graft in accordance with the present
invention.
Figure 4 is a perspective view of an alternative embodiment of the inventive
stent-
graft.
Figure 5 is a cross-sectional view taken along line 5-5 of Figure 4.
Figure 6 is a cross-sectional view illustrating a pair of support members and
a section
of interstitial web between adjacent supporting members.
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Figure 7 is a cross-sectional view illustrating a pair of support members and
a section
of interstitial web between adjacent supporting members in accordance with an
alternative
embodiment of the present invention.
Figure 8A is a top plan view of a graft or web region with a plurality of
openings
passing there through.
Figure 8B is a top plan view of an alternative embodiment of a graft or web
region of
the present invention with a plurality of openings passing there through.
Figure 8C is a top plan view of a third embodiment of a graft or web region of
the
present invention with a plurality of openings passing there through.
Figure 9A is a transverse cross-sectional view of a first embodiment of a
graft
member in accordance with the present invention.
Figure 9B is a transverse cross-sectional view of a second embodiment of a
graft
member in accordance with the present invention.
Figure 10 is a flow chart diagrammatically illustrating the method of
fabricating the
laminated film graft, stmt-graft and/or web-stmt of the present invention.
Detailed Description of the Preferred Embodiments
According to the present invention, stmt, web-stmt and stmt-graft devices are
provided which preferably exhibit substantially homogenous surface properties.
The
inventive graft, stmt, stent-graft and web-stmt devices may be depositing at
least two layers
of a biocompatible material to form a plied film, either in a planar or
cylindrical
conformation, then either adding a pattern of support members to the film or
removing at
least some regions of the plied film to create thinner regions in the starting
film and defining
relatively thinner and thicker film regions, such as thinner web regions
between adjacent
structural members formed by thicker film regions and/or relatively thinner
graft regions. An
additive methodology may include vacuum deposition or lamination of a pattern
of support
members upon the planar or cylindrical film. A subtractive methodology
includes etching
unwanted regions of material by masking regions to form the structural members
and expose
unmasked regions to the etchant. Additionally, in order to improve ifZ vivo
healing, it is
advantageous to impart openings passing through the web or the graft. The
openings are
preferably produced during the process of forming the web or the graft. The
openings in the
web or the graft may be formed by conventional methods such as
photolithographic
processes, by masking and etching techniques, by mechanical means, such as
laser ablation,
EDM, or micromachining, etc. Suitable deposition methodologies, as are known
in the
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microelectronic and vacuum coating fabrication arts and incorporated herein by
reference; are
plasma deposition and physical vapor deposition which are utilized to impart a
metal layer
onto the stmt pattern.
In accordance with an aspect of the present invention there is provided a
vacuum
deposited device that is fabricated of a material having substantially
homogeneous surface
propeuies across the blood contact surface of the device. Current
manufacturing methods for
fabricating endoluminal stems fail to achieve the desired material properties
of the present
invention. As discussed above, stems are fabricated from bulk metals that are
processed in a
manner that incorporates processing aides to the base metal. Presently, stems
are made from
hypotubes formed from bulk metals, by machining a series of slots or patterns
into the
hyptotube to accommodate radial expansion, or by weaving wires into a mesh
pattern.
The present invention consists of a stmt made of a bulls material having
controlled
heterogeneities on the luminal surface thereof. Heterogeneities are controlled
by fabricating
the bulk material of the stmt to have defined grain sizes that yield areas or
sites along the
surface of the stmt having optimal protein binding capability. The
characteristically
desirable properties of the inventive stmt are: (a) optimum mechanical
properties consistent
with or exceeding regulatory approval criteria, (b) controlling
discontinuities, such as
cracking or pinholes, (c) a fatigue life of 400 MM cycles as measured by
simulated
accelerated testing, (d) corrosion resistance, (e) biocompatibility without
having biologically
significant impurities in the material, (f) a substantially non-frictional
abluminal surface to
facilitate atraumatic vascular crossing and tracking and compatible with
trarlscatheter
techniques for stmt introduction, (g) radiopaque at selected sites and MRI
compatible, (h)
have a luminal surface which is optimized for surface energy and
microtopography, (i)
minimal manufacturing and material cost consistent with achieving the desired
material
properties, and (j) high process yields.
Controlling the surface profile of an endoluminal device is significant
because blood
protein interactions with surfaces of endoluminal devices appear to be the
initial step in a
chain of events leading to tissue incorporation of the endovascular device.
The present
invention is based, in part, upon the relationship between surface energy of
the material used
to make the endoluminal device and protein adsorption at the surface of the
endoluminal
device. The present inventors have found that a relationship exists between
surface free
energy and protein adsorption on metals commonly used in fabrication of
endoluminal
devices. In addition, specific~electrostatic forces resident on the surface of
metal endoluminal
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stents have been found to influence blood interactions with the stmt surface
and the vascular
wall.
In accordance with a preferred embodiment the present invention, the inventive
grafts,
stmt-grafts and web-stems have surface profiles which are achieved by
fabricating the graft,
stmt-graft and web-stmt by the same metal deposition methodologies as are used
and
standard in the microelectronic and nano-fabrication vacuum coating arts, and
which are
hereby incorporated by reference. In accordance with a preferred embodiment
the present
invention, the preferred deposition methodologies include ion-beam assisted
evaporative
deposition and sputtering techniques. In ion beam-assisted evaporative
deposition it is
preferable to employ dual and simultaneous thermal electron beam evaporation
with
simultaneous ion bombardment of the material being deposited using an inert
gas, such as
argon, xenon, nitrogen or neon. Bombardment with inert gas ions during
deposition serves to
reduce void content by increasing the atomic packing density in the deposited
material. The
reduced void content in the deposited material allows the mechanical
properties of that
deposited material to be similar to the bulk material properties. Deposition
rates up to 20
nm/sec are achievable using ion beam-assisted evaporative deposition
techniques.
When sputtering techniques are employed, a 200-micron thick stainless steel
film may
be deposited within about four hours of deposition time. With the sputtering
technique, it is
preferable to employ a cylindrical sputtering target, a single circumferential
source that
concentrically surrounds the substrate that is held in a coaxial position
within the source.
Alternate deposition processes which may be employed to form the stmt in
accordance with the present invention are cathodic arc, laser ablation, and
direct ion beam
deposition. As known in the metal fabrication arts, the crystalline structure
of the deposited
film affects the mechanical properties of the deposited film. These mechanical
properties of
the deposited film may be modified by post-process treatment, such as by, for
example,
annealing.
Materials to make the inventive graft, stmt-graft and web-stmt are chosen for
their
biocompatibility, mechanical properties, i.e., tensile strength, yield
strength, and their ease of
deposition include, without limitation, the following: elemental titanium,
vanadium,
aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon,
magnesium, niobium,
scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys
thereof, such as
zirconium-titanium-tantalum alloys, nitinol, and stainless steel.
During deposition, the chamber pressure, the deposition pressure and the
partial
pressure of the process gases are controlled to optimize deposition of the
desired species onto
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the substrate. As is known in the microelectronic fabrication, nano-
fabrication and vacuum
coating arts, both, the reactive and non-reactive gases are controlled and the
inert or non-
reactive gaseous species introduced into the .deposition chamber are typically
argon and
nitrogen. The substrate may be either stationary or moveable; either rotated
about its
longitudinal axis, moved in an X-Y plane, planatarily or rotationally moved
within the
deposition chamber to facilitate deposition or patterning of the deposited
material onto the
substrate. The deposited material maybe deposited either as a uniform solid
film onto the
substrate, or patterned by (a) imparting either a positive or negative pattern
onto the substrate,
such as by etching or photolithography techniques applied to the substrate
surface to create a
positive or negative image of the desired pattern or (b) using a mask or set
of masks which
are either stationary or moveable relative to the substrate to define the
pattern applied to the
substrate. Patterning may be employed to achieve complex finished geometries
of the
resultant structural supports, web-regions or graft, both in the context of
spatial orientation of
patterns of regions of relative thickness and thinness, such as by varying the
thickness of the
film over its length to impart different mechanical characteristics under
different delivery,
deployment or i~ vivo environmental conditions.
The device may be removed from the substrate after device formation by any of
a
variety of methods. For example, the substrate may be removed by chemical
means, such as
etching or dissolution, by ablation, by machining or by ultrasonic energy.
Alternatively, a
sacrificial layer of a material, such as carbon, aluminum or organic based
materials, such as
photoresists, may be deposited intermediate the substrate and the stmt and the
sacrificial
layer removed by melting, chemical means, ablation, machining or other
suitable means to
free the stmt from the substrate.
The resulting device may then be subjected to post-deposition processing to
modify
the crystalline structure, such as by annealing, or to modify the surface
topography, such as
by etching to expose a heterogeneous surface of the device.
The present invention, therefore, consists of both a material and a process of
making
the inventive material. The inventive material is one for which mechanical
strength and
toughness is important, among other characteristics. In accordance with the
best mode
presently contemplated for the invention, the inventive material consists of
several layers of
316L stainless steel, each of about 10 micrometers thick with no chemical
differences
between them. The layers are defined by interfaces between them that have an
interface
microroughness in excess of 2 nm rms. The cumulative thickness of the
stainless steel film
formed from this material is about 100 micrometers.
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The inventive material is preferably made by positioning a cylindrical copper
mandrel
along the axis of a cylindrical DC magnetron sputtering device. After the
routine preparatory
steps of obtaining a vacuum, admitting Argon sputtering gas, and cleaning the
surface of the
316L stainless steel target, ftlm deposition is carried out at a rate of 50
micrometers per hour
for 12 minutes to obtain the first 10 micrometer thick layer. During the
deposition, a negative
bias voltage of 120 V is applied to the mandrel. The film grows and has a
columnar structure
in which columns reach though the whole thickness. After the first layer is
deposited, the
deposition process is interrupted for a brief period of time (~1 min). This
time is sufficient
for the formation of an adsorptive layer on the freshly deposited film. When
the deposition is
resumed, this adsorptive layer gives rise to columnar growth that that is
different from the
columnar growth of the previous layer only in that the columns are not
continuous. The
deposition process steps are then repeated until the desired cumulative
material thickness is
attained. At that point, the material, still on the mandrel, is removed from
the vacuum
deposition chamber and the copper mandrel is chemically removed. Additional
post-
IS deposition steps of surface finishing, cutting, etc. may be employed.
Turning now to the Figures, there is illustrated alternative preferred
embodiments of
the present invention. In Figures 1A and 1B there is illustrated a multi-
layered plied film in
accordance with the present invention. The inventive film 10 consists of a
plurality of
individual layers 11 laminated upon one another to form the film 10. The
individual layers
may be made of the same biocompatible material, such as a biocompatible metal,
or may be
made of discrete biocompatible materials.
With reference to Figure 2, there is illustrated a web-stmt 20 in accordance
with the
present invention. The web-stmt 20 is formed of a vacuum deposited laminated
planar or
cylindrical film 10. The web-stmt 20 is formed by masking regions of the
material blank
which are to form a plurality of structural members 22, and then etching the
unmasked
regions which then form interstitial webs 24 which subtend interstitial
regions between
adjacent structural members 22. The interstitial webs 24 are etched to a
material thickness
that is less than the thickness of the plurality of structural members 22. It
is preferable to
impart a plurality of openings in the interstitial webs 24 in order to permit
endothelialization
of the luminal surface 26 ofthe interstitial webs 24. The openings may be
imparted as a
random pattern or as a regular pattern in the interstitial web 24, as will be
discussed
hereinafter.
With reference to Figure 3 there is depicted a stmt-graft 30 in accordance
with the
present invention. Stent-graft 30 is formed either from a tubular or planar
laminated film 10,
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which is etched to form the plurality of structural members 32 and
interstitial regions 34
between the structural members 32. In addition, either or both a proximal 36
or a distal 38
graft region of the stmt are provided and project outwardly from terminal
structural members
32. The proximal graft region 36 and the distal graft region 38 are preferably
etched to a
reduced thickness of less than the thickness of the structural members, and
are made with
openings passing there through which promote cellular migration, as will be
discussed
hereinafter.
Under certain applications it may be useful to employ the stmt-graft 30 with
either or
both of the proximal 36 or distal 38 graft regions projecting outwardly from
the structural
supports 32. Additionally, one or more of the plied individual layers 11 that
comprise the
laminate film 10 may project outwardly from the structural supports 32. An
alternative
embodiment of the invention is illustrated in Figures 4 and 5. The alternative
embodiment of
the stmt-graft 30 involves covering the luminal and abluminal surfaces of a
plurality of
structural supports 32 with a luminal graft 36 and an abluminal graft 38. The
luminal graft 36
may initially be formed as the proximal graft region 36 in Figure 3 and be
luminally inverted
39 and passed into the lumen defined by the structural members 32. The
abluminal graft 38
may initially be formed as the distal graft region 38 in Figure 3 and be
abluminally averted 37
over the structural members 32. Alternatively, the luminal graft 36 and the
abluminal graft
38 may be formed as either pre-fabricated discrete graft members made of
biocompatible
metal or metal-like materials that are either tubular or planar then formed
into a tube and
concentrically engaged about the plurality of structural members 32. Portions
of each of the
abluminal graft 38 and the luminal graft 36 are mechanically joined to the
plurality of
structural members 32 or to one and other, thereby effectively encapsulating
the plurality of
structural members 32 between the luminal graft 36 and the abluminal graft 38.
It is
preferable that opposing free ends of each of the abluminal graft 38 and
luminal graft 36 are
mechanically joined to and co-terminus with a terminal portion of the
plurality of structural
members 32. Mechanical joining may be accomplished by methods such as welding,
suturing, adhesive bonding, soldering, thermobonding, riveting, crimping, or
dovetailing. In
accordance with an alternate embodiment of the invention, the interstitial
regions 34 may be
subtended by a web 34, as discussed hereinabove, with reference to Figures 1
and 2.
Those of ordinary skill in the art, will understand and appreciate that
alternative
methods of removing material from areas that form relatively thinner regions
of the stmt,
web-stmt or stmt-graft may be employed. For example, in addition to chemical
etching,
relatively thinner regions may be formed by removing bulk material by ion
milling, laser
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ablation, EDM, laser machine, electron beam lithography, reactive ion etching,
sputtering or
equivalent methods which are capable of reducing the thickness of the material
in either the
graft region or the interstitial web region between the structural members.
Alternatively, the
structural members may be added to the defined interstitial web or graft
regions to form the
device, or the interstitial web or graft regions may be added to pre-existing
structural
members. Additive methods that may be employed include conventional metal
forming
techniques, including laminating, plating, or casting.
Similarly, a wide variety of initial.bulk material configurations may be
employed,
including a substantially planar sheet substrate, an arcuate substrate or a
tubular substrate,
which is then processed by either subtractive or additive techniques discussed
above.
By forming the structural members, the interstitial web and/or the graft of an
integral,
monolithic material, both the circumferential or hoop strength of the
resultant device, as well
as the longitudinal or columnar strength of the device are enhanced over
conventional stent-
graft devices. Additional advantages of the present invention, depending upon
fabrication
methods, may include: controlled homogeneity and/or heterogeneity of the
material used to
form the device by deposition methodologies, enhanced ability to control
dimensional and
mechanical characteristics of the device, the ability to fabricate complex
device
conformations, ability to pattern and control the porosity of the web and/or
graft regions, and
a monolithic one-piece construction of a device which yields a minimized
device profile and
cross-sectional area. The devices of the present invention have relatively
thicker and thinner
regions, in which the thinner regions permit radial collapse of the device for
endoluminal
delivery. The inventive device exhibits superior column strength that permits
smaller
introducer size and more readily facilitates deployment of the device.
As illustrated in Figures 6 and 7, the web and/or graft regions, 44, 54
between
adjacent structural members 42, 52 may be co-planar with either the luminal or
abluminal
surface of the structural members 42, or may be positioned intermediate the
luminal 51 and
abluminal 56 surfaces of the structural members 52.
In accordance with a preferred embodiment of the present invention, the web
regions
of the inventive web-stmt, the graft regions of the inventive stmt-graft and
the inventive
graft have a plurality of openings which pass through the thiclness of the
material used to
fabricated the inventive devices. Each of the plurality of openings is
dimensioned to permit
cellular migration through the opening without permitting blood leakage or
seepage through
the plurality of openings. The plurality of openings may be random or may be
patterned.
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However, in order to control the effective porosity of the device, it is
desirable to impart a
pattern of openings in the material used to fabricate the inventive device.
Figures 8A-8C depict several examples of patterned openings in a section of
material
used to make the inventive web-stmt, graft regions of the stmt-graft, and the
inventive graft.
Figure 8A depicts a material 60 with a plurality of circular openings 64
passing through the
material substrate 62. The plurality of circular openings is patterned in a
regular array of
rows and columns with regular inter-opening spacing 65 between adjacent
openings. In the
particular embodiment illustrated the diameter of each of the plurality of
openings is about 19
pm, with an inter-opening spacing in each row and column of about 34 p.m on
center. The
thickness of the material 62 is approximately 10 Vim. Figure 8B illustrates
another example
of a pattern of a plurality of openings useful in the present invention. The
material 62, which
again is approximately 10 p,m in thickness, has a plurality of openings 66 and
67 passing
there through. The pattern of the plurality of openings 66 and 67 is an
alternating slot pattern
in which the plurality of openings 66 are arrayed adjacent one and other
forming a y-axis
oriented array 68 relative to the material 62, while a plurality of openings
67 are arrayed
adjacent one and other forming an x-axis oriented array 69' relative to the
material 62. The y-
axis-oriented array 68 and the x-axis-oriented array 69 are then positioned
adjacent one and
other in the material 62. In this particular example, the inter-array spacing
between the y-
axis-oriented array 68 and the x-axis-oriented array 69 is about 17 wm, while
each of the
plurality of openings has a length of about 153 pm and a width of about l7p.m.
Finally,
Figure 8C illustrates a material 60 in which the material substrate 62 has a
regular array of a
plurality of diamond-shaped openings 63 passing through the material substrate
62. As with
the alternative embodiments exemplified in Figures 8A and 8B, the dimension of
the plurality
of diamond-shaped openings 63 is of sufficient size to permit cellular
migration through the
openings 63, while preventing blood flow or seepage through the plurality of
openings 63.
Figures 9A and 9B illustrate alternate preferred embodiments of the graft 70
and graft
80 in accordance with the present invention. Graft 70 consists generally of
concentrically
positioned luminal graft member 74 and abluminal graft member 72 and an
interfacial region
74 where the luminal surface of the abluminal graft member 72 and the
abluminal surface of
the luminal graft member 74 are in immediate juxtaposition with one and other.
Both the
luminal 74 and the abluminal 72 graft members are fabricated in accordance
with the
methodologies described above, and are provided with a plurality of patterned
openings 73 in
the abluminal graft member 72 and a plurality of patterned openings 75 in the
luminal graft
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member 74. The plurality of patterned openings 74 and 75 are positioned out of
phase
relative to one another. By positioning the plurality of patterned openings 74
and 75 in an
out-of phase relationship, there is no continuous opening that passes through
the interfacial .
region 76 which would permit blood flow or seepage from the lumen of the
graft. However,
in order to permit cellular migration from the abluminal surface of the graft
to the lumen of
the graft, the interfacial region 76 should have microroughness [not shown]
which is oriented
either randomly or selectively, such as helically or circumferential, about
the interfacial
region 76. The microroughness preferably has a peak-to-valley depth of between
about 5p to
about 65p, most preferably between about l Op to 15~, may be either on the
luminal surface
of the abluminal graft 72 or on the abluminal surface of the luminal graft 74,
or both. The
microroughness spans the surface area region between adjacent pairs of
openings 74, 75, and
the microroughness depth permits cellular migration across the surfaces
between adjacent
openings 74 and 75. The microroughness is not large enough to permit fluid
passage through
the inter-opening regions at the interface between the luminal graft 74 and
the abluminal graft
72. This property of permitting cellular growth is similar to the difference
between the
porosity of expanded polytetrafluoroethylene grafts which do not require pre-
clotting, and the
much larger porosity of polyester or DACRON grafts which require pre-clotting
to prevent
fluid seepage there from.
Figure 9B illustrates an alternative embodiment of the inventive graft 80 in
which an
abluminal graft member 82 is concentrically positioned about a luminal graft
member 84.
Each of the abluminal graft member 82 and the luminal graft member 84 having a
plurality of
patterned openings 83, 85, respectively, passing there through. As with the
embodiment
depicted in Figure 9A, the plurality of patterned openings 83 and 85 are
positioned in an out-
of phase relationship to one and other in order to prevent forming a
continuous opening
between the luminal and abluminal surfaces of the graft 80. However, unlike
the
embodiment in Figure 9A, there is no corresponding interfacial region 74.
Rather, an annular
open region 87 is positioned intermediate the luminal graft member 84 and the
abluminal
graft member 82. The annular open region 87 is created by providing a
plurality of
microprojections 86 that project either radially inward from the luminal
surface of the
abluminal graft member 82 or radially outward from the abluminal surface of
the luminal
graft member 84. The plurality of microprojections 86 act as spacers which
abut the
opposing surface of either the luminal graft member 84 or the abluminal graft
member 82
which bound the annular open region 87. The height of the microprojections 86
and,
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therefore, the size of the annular open region 87, are dimensioned such that
cells may migrate
through the annular open region 87, while blood flow or seepage will not occur
between the
lumen and the abluminal surface of the graft 80.
According to a specific aspect of the graft embodiment of the present
invention, the
size of the plurality of openings in the luminal graft member 74, 84 may be
different than the
size of the plurality of openings in the abluminal graft member 72, 82. For
example, the
plurality of openings in the abluminal graft member 74, 84 preferably have a
larger size than
the plurality of openings in the luminal graft member 72, 84, while still
retaining the out-of
phase relationship between the plurality of openings in the luminal 72, 82 and
the abluminal
74, 84 graft members. Where circular openings are provided, it is preferable
that the luminal
72, 82 and the abluminal 74, 84 graft members have openings having diameters
of between
about 5 p,m and 100 pm.
Additionally, a third member may be interposed between the luminal 72, 82 and
the
abluminal 82, 84 graft members. The third member will preferably have a very
fine plurality
of openings, such as on the order of between 2-10 p, and permits use of a
higher porosity in
the luminal and abluminal grafts, without the need to maintain an out-of phase
relationship
between the openings in the ~luminal 72, 82 and the abluminal 74, 84 graft
members.
Finally, the method 90 for fabricating the inventive grafts, stmt-grafts and
web-stems
of the invention is illustrated in the process flow diagram in Figure 10. As
previously
discussed above, a starting blank of material by vacuum depositing a starting
blank of a
biocompatible metal or metal-like laminated film 94. Then a determination is
made whether
to employ an additive or a subtractive method 96 for forming the graft, stmt-
graft or web-
stent. If an additive method is selected 97, the structural supports are built
upon the starting
blank 100, either by vacuum deposition techniques or by conventional metal
forming
techniques. If a subtractive method is selected 95, the regions to remain are
masked 98, then
the unmasked regions are removed, such as by chemical etching or sputtering,
to form the
interstitial web regions, graft regions and/or openings in either the
interstitial web regions
and/or graft regions 99.
The following examples are provided in order to illustrate the alternative
embodiments of the invention, and are not intended to limit the scope of the
invention.
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Example 1: Stent Formation By Sputtering
A ceramic cylindrical substrate is introduced into a deposition chamber with
capabilities of glow discharge substrate cleaning and sputter deposition of
carbon and
stainless steel. The deposition chamber is evacuated to a pressure less than
or equal to 2 x 10-
Torr. Pre-cleaning of the substrate is conducted under vacuum by glow
discharge. The
substrate temperature is controlled to achieve a temperature between about 300
and 1100
degrees Centigrade. A bias voltage between -1000 and +1000 volts is applied to
the substrate
sufficient to cause energetic species arriving at the surface of the substrate
to have
hyperthermal energy between 0.1 eV and about 700 eV, preferably between 5-50
eV. The.
deposition sources are circumferential and are oriented to deposit from the
target
circumferentially about the substrate.
During deposition, the deposition pressure is maintained between 0.1 and 10
mTorr.
A sacrificial carbon layer of substantially uniform thickness (~5%) between 10
and 500
Angstroms is deposited circumferentially on the substrate. After depositing
the carbon layer,
a cylindrical film of stainless steel is deposited onto the sacrificial carbon
layer on the
cylindrical substrate at a deposition rate between about 10 to 100
microns/hour. After
formation of the stainless steel film, the substrate is removed from the
deposition chamber
and heated to volatilize the intermediate sacrificial carbon layer between the
substrate and the
film. After removing the carbon intermediate layer, the stainless steel film
is removed from
the substrate and exhibits material properties similar to the bulls stainless
steel target and
surface properties characterized by controlled heterogeneities in grain size,
material
composition and surface topography. A series of patterns are then machined
into the resultant
stainless steel film to form a stmt by electrical discharge machining (EDM) or
laser cutting
the film.
Example 2: Stent Formation by Sputtering
The same operating conditions are followed as in Example l, except that the
substrate
is tubular and selected to have a coefficient of thermal expansion different
than that of the
resultant stmt. No intermediate layer of sacrificial carbon is deposited onto
the substrate,
and the outer surface of the substrate is etched with a pattern of recesses
defining a desired
stmt pattern. The substrate is mounted onto a rotational jig within the
deposition chamber
and rotated at a uniform rate during deposition. Tantalum is used as the
target material and
deposited into the recesses of the substrate from a single stationary source.
After deposition,
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the temperature of the substrate and the deposited stmt are controlled to
impart diametric
differential in the substrate and stmt and permit removal of the stmt from the
substrate.
Example 3: Stent Formation by Ion Beam-assisted Evaporative Deposition
A cylindrical substrate is introduced into a deposition chamber that has
capabilities of
substrate rotation and precise positioning, glow discharge substrate cleaning,
ion beam-
assisted evaporative deposition, and cylindrical magnetron sputtering. The
deposition
sources are (a) dual electron beam evaporative sources placed adjacent to one
another at the
base of the. deposition chamber at a fixed distance from the substrate, these
are used with
simultaneous argon ion impingement onto the substrate from a controlled ion
beam source,
and (b) a cylindrical magnetron sputtering source with a carbon target capable
of
circumferentially coating a carbon sacrificial layer of substantially uniform
thickness of
between 10 and 200 Angstroms onto the substrate.
The substrate temperature is controlled to achieve a substrate temperature
between
about 300 and 1100 degrees Centigrade. The deposition chamber is evacuated to
a pressure
less than or equal to 2 x 10-~ Torr. A pre-cleaning of the substrate is
conducted under
vacuum by glow discharge. The substrate is rotated to ensure uniform cleaning
and
subsequent uniform deposition thickness. After cleaning the substrate is moved
into the
magnetron and coated with the carbon layer. The substrate is then moved into
position to
receive the stmt-forming metal coating with simultaneous ion bombardment. One
electron
beam evaporation source contains titanium while the other source contains
nickel. The
evaporation rates of each of the titanium and nickel evaporation sources are
separately
controlled to form a nitinol alloy on the substrate as the stmt-forming metal.
Example 4: Planar Deposition of Stent.
The same operating conditions of Example 3 are followed, except that a planar
substrate is used. The deposition source is a single electron beam evaporation
source
containing platinum and is used with simultaneous argon ion impingement onto
the substrate
from a controlled ion beam source.
The substrate temperature is controlled to achieve a substrate temperature
between
about 300 and 1100 degrees Centigrade. The deposition chamber is evacuated to
a pressure
less than or equal to 2 x 10-~ Torr. A pre-cleaning of the substrate is
conducted under
vacuum by glow discharge. After cleaning the substrate is moved into position
within the
deposition chamber and coated with platinum from the electron beam evaporation
source
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with simultaneous argon ion bombardment, with the electron beam evaporation
source
passing platinum through a pattern mask corresponding to a stmt pattern which
is interposed
between the source and the substrate to pass a pattern of platinum onto the
substrate.
After deposition, the patterned stmt is removed from the substrate and rolled
about a
forming substrate to a cylindrical shape and opposing ends of the planar stmt
material are
brought into juxtaposition with one another and may be attached by laser
welding or left
uncoupled.
Example 5: Thin-Film Deposition with Stent-Graft Etch
The same conditions are employed as in Example 4, except that a uniform layer
of
stmt-forming material is deposited having a thickness of 150 microns without
patterning of
the stmt onto the deposited layer. Rather, a negative mask is applied to the
deposited stent-
forming material, and a chemical etchant is introduced to etch a pattern of
structural elements
into the stmt-forming metal. The etchant is permitted to react with the metal
until a thinner
film web having a thickness of between 2 -75 microns, is present between
adjacent structural
elements. After the thinner film web is formed, the etching is, stopped, and
the resultant
stmt-graft is removed and formed into a tubular shape.
Example 6: Dry Etching Method
The same conditions as in Example 5 are followed, except that reactive ion
etching is
employed to form the thinner film web.
Example 7: Stent-Graft Formation
The same conditions are followed as in Example 5, except that the structural
elements
are defined in an intermediate region of a tubular substrate, and interstitial
regions between
adjacent structural elements are etched by chemical etching until interstitial
openings are
formed between adjacent structural elements while masking the structural
elements and
proximal and distal regions of the tubular substrate. Proximal and distal
graft regions are
formed adjacent the intermediate region of the tubular substrate and
contiguous with the
plurality of structural elements, by masking the structural elements and
interstitial openings
and chemical etching the proximal and distal regions of the tubular substrate
to yield a
thinner film of material in the proximal and distal regions of the tubular
substrate. The
proximal and distal graft regions are then evened, with the proximal graft
region being
inverted luminally through the lumen of the structural members and the distal
graft region
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being everted abluminally over the structural members. The proximal graft
region is
mechanically joined to the distal terminal end of the plurality of structural
members, while
the distal graft region is mechanically joined to the proximal terminal end of
the plurality of
structural members, thereby encapsulating the plurality of structural members
between.the
5' everted proximal and distal graft regions.
Example 8: Stent-Graft Formation - Discrete Graft and Discrete Stent
A pre-fabricated self expanding superelastic shape memory alloy stmt is
provided.
Two cylindrical hypotubes of a superelastic shape memory material similar to
that of the stmt
are chemically etched to a substantially uniform thickness of 10 pm, with a
first hypotube
having an inner diameter which is of sufficient size to accommodate the outer
diameter of the
stmt, and a second hypotube having an outer diameter dimensioned to
accommodate the
inner diameter of the stmt. The etched hypotubes are then placed into a vacuum
chamber and
a cylindrical pattern mask having a regular array of circular openings, each
circular opening
having a diameter of about 25 pm, is positioned concentrically about each of
the cylindrical
hypotubes. The etched hypotubes are reactive ion etched to transfer the masked
pattern to the
etched hypotube and impart a pattern of circular openings that pass through
the wall thickness
of the etched hypotubes corresponding to the mask pattern. The stmt, and first
and second
etched and reactive ion etched hypotubes are concentrically engaged upon one
and other,
with the second hypotube being concentrically positioned within the lumen of
the stmt and
the first hypotube being concentrically positioned about the abluminal surface
of the stmt.
Proximal and distal ends of the stmt, the first hypotube and the second
hypotube are
mechanically joined by welding and then trimmed by laser cutting to ensure
that the proximal
and distal ends are co-terminus.
Example 9: Graft Formation
A cylindrical mandrel is provided which is coated with a sacrificial layer. A
plurality
of patterned recesses is defined in the sacrificial layer. The mandrel is
introduced into a
deposition chamber and a nickel-titanium alloy is vacuum deposited onto the
mandrel, while
rotating the mandrel, until a uniform adherent layer of the deposited nickel-
titanium alloy
covers the cylindrical mandrel. After deposition, the sacrificial layer is
removed, and the
uniform adherent layer disengaged from the cylindrical mandrel, yielding the
inventive graft,
with openings corresponding to the plurality of patterned recesses in the
graft material.
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Example 10: Planar Laminated Film
A vacuum chamber capable of being pumped to 5 x 10-' Torr is provided with and
installed within industry standard thin-film deposition equipment described as
follows. An
electron beam gun capable of evaporating metals is placed at the base of the
chamber. The
gun crucible is filled with a charge of high purity aluminum. A film thickness
and deposition
rate control and monitoring device is installed above and to the side of the
gun, capable of
monitoring and controlling incident.power to the gun crucible in order to
control deposition
rate. A fixture to hold a planar substrate is installed fifty cm above and
centered over the
gun. A moveable shutter is placed between the gun and the substrate fixture,
such that at a
given and appropriate time the shutter can be removed from the deposition path
to allow
deposition onto a substrate. Infrared heaters are installed in the chamber in
a position that
allows controlled heating of the substrate to 200 degrees C. An ion beam gun
is installed in
the chamber in such a position that a formed and controlled Ar ion beam can be
directed onto
a substrate held in the substrate fixture.
The following steps are taken to form a laminate / multilayer film on a
substrate. A
section of 316L stainless steel sheet metal, 36" square and .016" thick is
attached to the
substrate holding fixture to serve as the deposition substrate. The chamber is
pumped to a
base pressure of 5 x 10-~ Torr. The infrared heaters are engaged to heat and
maintain the
substrate at 200 degrees C. With the shutter in the deposition path, the
electron beam gun
power is ramped up which heats and outgases the aluminum charge. The aluminum
charge is
heated to obtain a vapor pressure compatible with a deposition rate equivalent
to 75
angstroms per second. Simultaneous with this, the ion beam gun is started and
a stable 200
volt Ar ion beam with the current density of 0.5 mA/cm2 is formed, at a
chamber pressure of
3 x 10-5 Torr.
When these conditions are reached and stabilized, the shutter is opened. An
aluminum film of 5000 angstroms thickness is deposited onto the substrate. At
this point the
shutter is closed and the electron beam gun power is reduced to zero. The ion
beam gun
remains running. The chamber is baclcfilled with oxygen to a pressure of 8 x
10 -4 Torr.
The shutter reopens allowing Ar ion impingement of the substrate in the oxygen
environment
for three minutes. At this point the shutter is closed and the oxygen flow is
ceased. The
chamber is allowed to pump back down to 3 x 10 -5 Torr. The electron beam gun
is
restarted, which again outgases the aluminum charge and brings it to the
appropriate
deposition vapor pressure. The shutter reopens and a second aluminum layer of
5000
angstrom thickness is deposited onto the substrate. Again the shutter is
closed and the
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electron beam gun power reduced to zero. This layer is then Ar ion impinged in
an oxygen
baclcfilled environment as before. This cycle is repeated to form multiple
successive layers
as are required for form a multilayer film of 50 micron total thickness.
While the invention has been described with reference to its preferred
embodiments,
those of ordinary skill in the relevant arts will understand and appreciate
that the present
invention is not limited to the recited preferred embodiments, but that
various modifications
in material selection, deposition methodology, manner of controlling the
material
heterogeneities of the deposited stmt material, and deposition process
parameters may be
employed without departing from the invention, which is to be limited only by
the claims
appended hereto.
