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Medical Patent Abstract
Implantable medical grafts fabricated of metallic or pseudometallic
films of biocompatible materials having a plurality of microperforations
passing through the film in a pattern that imparts fabric-like qualities
to the graft or permits the geometric deformation of the graft.
The implantable graft is preferably fabricated by vacuum deposition
of metallic and/or pseudometallic materials into either single or
multi-layered structures with the plurality of microperforations
either being formed during deposition or after deposition by selective
removal of sections of the deposited film. The implantable medical
grafts are suitable for use as endoluminal or surgical grafts and
may be used as vascular grafts, stent-grafts, skin grafts, shunts,
bone grafts, surgical patches, non-vascular conduits, valvular leaflets,
filters, occlusion membranes, artificial sphincters, tendons and
ligaments.
Medical Patent Claims
What is claimed is:
1. An implantable medical graft, comprising: a. a tubular graft
member comprising a vacuum deposited metal film having a first surface,
a second surface and a thickness intermediate the first surface
and the second surface wherein said thickness is less than 75 .mu.m;
and b. a plurality of microperforations formed in and passing through
the thickness of the vacuum deposited metal film and communicating
between the first surface and the second surface.
2. The implantable medical graft according to claim 1, wherein
the vacuum deposited metal film is made of a metallic material selected
from the group consisting of titanium, vanadium, aluminum, nickel,
tantalum, zirconium, chromium, silver, gold, silicon, magnesium,
niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum
and alloys thereof.
3. The implantable graft according to claim 1, wherein the each
of the plurality of microperforations is capable of undergoing geometric
deformation.
4. The implantable graft according to claim 1, wherein the plurality
of microperforations are arrayed in at least one pattern that imparts
at least one of compliance and pliability to the body member.
5. The implantable graft according to claim 1, wherein the plurality
of microperforations is arrayed in at least one pattern sufficient
to permit dimensional change of at least a portion of the device.
6. The implantable graft according to claim 5, wherein the dimensional
change comprises at elastic one of elastic, plastic, shape memory
and superelastic compliance.
7. The implantable medical graft according to claim 1, wherein
the tubular graft member further comprises a first surface including
a luminal surface and a second surface including an abluminal surface.
8. The implantable medical graft according to claim 1, wherein
the tubular graft member further comprises a generally planar member.
9. The implantable medical graft according to claim 1, wherein
the plurality of microperforations each further comprise a generally
co-planar tri-leg configuration.
10. An implantable medical device, comprising a generally tubular,
non-coiled, graft member consisting essentially of: a. a vacuum
deposited metal film having a first surface, a second surface and
a thickness intermediate the first surface and the second surface
wherein said thickness is less than 75 .mu.m; and b. a plurality
of microperforations formed in and passing through the thickness
of the vacuum deposited metal film and communication between the
first surface and the second surface, each of the plurality of microperforations
having an open surface area less than about 2 mm.sup.2 when the
graft member is in a non-diametrically enlarged state.
11. The implantable medical graft according to claim 10, wherein
the vacuum deposited metal film is made of a metallic material selected
from the group consisting of titanium, vanadium, aluminum, nickel,
tantalum, zirconium, chromium, silver, gold, silicon, magnesium,
niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum
and alloys thereof.
12. The implantable graft according to claim 10, wherein the each
of the plurality of microperforations is capable of undergoing geometric
deformation.
13. The implantable graft according to claim 10, wherein the plurality
of microperforations are arrayed in at least one pattern that imparts
at least one of compliance and pliability to the body member.
14. The implantable graft according to claim 10, wherein the plurality
of microperforations is arrayed in at least one pattern sufficient
to permit dimensional change of at least a portion of the device.
15. The implantable graft according to claim 14, wherein the dimensional
change comprises at elastic one of elastic, plastic, shape memory
and superelastic compliance.
16. The implantable medical graft according to claim 10, wherein
the tubular graft member further comprises a first surface including
a luminal surface and a second surface including an abluminal surface.
17. The implantable medical graft according to claim 10, wherein
the tubular graft member further comprises a generally planar member.
18. The implantable medical graft according to claim 10, wherein
the plurality of microperforations each further comprise a generally
co-planar tri-leg configuration.
Medical Patent Description
BACKGROUND OF THE INVENTION
The present invention relates generally to implantable metallic
medical devices. More specifically, the present invention relates
to implantable medical devices, including, for example, surgical
and endoluminal vascular grafts, stent grafts, skin grafts, shunts,
bone grafts, surgical patches, non-vascular conduits, valvular leaflets,
filters, occlusion membranes, sphincters, artificial tendons and
ligaments. More specifically, the present invention relates to implantable
medical grafts fabricated of metallic or pseudometallic films of
biocompatible materials having a plurality of microperforations
passing through the film. The plurality of microperforations may
serve multiple purposes, including, for example, permitting geometric
deformation of the film, imparting a fabric-like quality to the
film, and imparting flexibility to the film. The term "fabric-like"
is intended to mean a quality of being pliable and/or compliant
in a manner similar to that found with natural or synthetic woven
fabrics.
The inventive implantable grafts are fabricated entirely of self-supporting
films made of biocompatible metals or biocompatible pseudometals.
Heretofore in the field of implantable medical devices, it is unknown
to fabricate an implantable medical device that comprises a graft
at least as one of its elements, such as a stent graft, entirely
of self-supporting metal or pseudometal materials. As used herein
the term "graft" is intended to indicate any type of device
or part of a device that comprises essentially a material delimited
by two surfaces where the distance between said surfaces is the
thickness of the graft and that exhibits integral dimensional strength
and that has microperforations that pass through the thickness of
the graft. The inventive grafts may be formed in planar sheets,
toroids, and in other shapes as particular applications may warrant.
However, for purposes of illustration only, the present application
will refer to tubular grafts. For purposes of this application,
the terms "pseudometal" and "pseudometallic"
are intended to mean a biocompatible material which exhibits biological
response and material characteristics substantially the same as
biocompatible metals. Examples of pseudometallic materials include,
for example, composite materials and ceramics. Composite materials
are composed of a matrix material reinforced with any of a variety
of fibers made from ceramics, metals, carbon, or polymers.
When implanted into the body, metals are generally considered to
have superior biocompatibility than that exhibited by polymers used
to fabricate commercially available polymeric grafts. It has been
found that when prosthetic materials are implanted, integrin receptors
on cell surfaces interact with the prosthetic surface. The integrin
receptors are specific for certain ligands in vivo. If a specific
protein is adsorbed on a prosthetic surface and the ligand exposed,
cellular binding to the prosthetic surface may occur by integrin-ligand
docking. It has also been observed that proteins bind to metals
in a more permanent fashion than they do to polymers, thereby providing
a more stable adhesive surface. The conformation of proteins coupled
to surfaces of most medical metals and alloys appears to expose
greater numbers of ligands and preferentially attract endothelial
cells having surface integrin clusters to the metal or alloy surface
relative to leukocytes. Finally, metals and metal alloys exhibit
greater resistance to degradation of metals relative to polymers,
thereby providing greater long-term structural integrity and stable
interface conditions.
Because of their relatively greater adhesive surface profiles,
metals are also susceptible to short-term platelet activity and/or
thrombogenicity. These deleterious properties may be offset by administration
of pharmacologically active antithrombogenic agents in routine use
today. Surface thrombogenicity usually disappears 1-3 weeks after
initial exposure. Antithrombotic coverage is routinely provided
during this period of time for coronary stenting. In non-vascular
applications such as musculoskeletal and dental, metals have also
greater tissue compatibility than polymers because of similar molecular
considerations. The best article to demonstrate the fact that all
polymers are inferior to metals is van der Giessen, W J. et al.
Marked inflammatory sequelae to implantation of biodegradable and
non-biodegradable polymers in porcine coronary arteries, Circulation,
1996:94(7):1690-7.
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 .mu.m/hr or 2.5 times the diameter of an
EC, which is nominally 10 .mu.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. 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. Clin. Invest.
1993; 91:2640-2652, Davies, P. F., Robotewski, A., Griem, M. L.,
Qualitative studies of endothelial cell adhesion, J. Clin. Invest.
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 .mu.m.sup.2,
with the majority of them being about 1 .mu.m.sup.2, 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, availability of attachment sites will
favorably influence attachment and migration. It is known that materials
commonly used as medical grafts, such as polymers, do not become
covered with EC and therefore do not heal after they are placed
in the arteries. It is therefore an object of this invention to
replace polymer grafts with metal grafts that can potentially become
covered with EC and can heal completely. Furthermore, heterogeneities
of materials in contact with blood flow are preferably controlled
by using vacuum deposited materials.
There have been numerous attempts to increase endothelialization
of implanted medical devices such as stents, including covering
the stent with a polymeric material (U.S. Pat. No. 5,897,911), imparting
a diamond-like carbon coating onto the stent (U.S. Pat. No. 5,725,573),
covalently binding hydrophobic moieties to a heparin molecule (U.S.
Pat. No. 5,955,588), coating a stent with a layer of blue to black
zirconium oxide or zirconium nitride (U.S. Pat. No. 5,649,951),
coating a stent with a layer of turbostratic carbon (U.S. Pat. No.
5,387,247), coating the tissue-contacting surface of a stent with
a thin layer of a Group VB metal (U.S. Pat. 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 stent (U.S. Pat. No. 5,690,670), coating
the stent, 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. Pat. No. 5,891,507), coating a stent with a silane compound
with vinyl functionality, then forming a graft polymer by polymerization
with the vinyl groups of the silane compound (U.S. Pat. No. 5,782,908),
grafting monomers, oligomers or polymers onto the surface of a stent
using infrared radiation, microwave radiation or high voltage polymerization
to impart the property of the monomer, oligomer or polymer to the
stent (U.S. Pat. No. 5,932,299). However, all these approaches do
not address the lack of endothelialization of polymer grafts.
It is, therefore, desirable to fabricate the inventive graft of
metallic and/or pseudometallic materials. The inventive metal devices
may be fabricated of pre-existing conventional wrought metallic
materials, such as stainless steel or nitinol hypotubes, or may
be fabricated by thin film vacuum deposition techniques. In accordance
with the present invention, it is preferable to fabricate the inventive
implantable devices by vacuum deposition. Vacuum deposition permits
greater control over many material characteristics and properties
of the resulting formed device. For example, vacuum deposition permits
control over grain size, grain phase, grain material composition,
bulk material composition, surface topography, mechanical properties,
such as transition temperatures in the case of a shape memory alloy.
Moreover, vacuum deposition processes will permit creation of devices
with greater material purity without the introduction of large quantities
of contaminants that adversely affect the material, mechanical or
biological properties of the implanted device. Vacuum deposition
techniques also lend themselves to fabrication of more complex devices
than those susceptible of manufacture by conventional cold-working
techniques. For example, multi-layer structures, complex geometrical
configurations, extremely fine control over material tolerances,
such as thickness or surface uniformity, are all advantages of vacuum
deposition processing.
In vacuum deposition technologies, materials are formed directly
in the desired geometry, e.g., planar, tubular, etc. The common
principle of vacuum deposition processes is to take a material in
a minimally processed form, such as pellets or thick foils, known
as the source material and atomize them. Atomization may be carried
out using heat, as is the 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 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 and/or 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.
A first advantage of vacuum deposition processing is that vacuum
deposition of the metallic and/or pseudometallic films permits tight
process control and films may be deposited that have regular, homogeneous
atomic and molecular pattern of distribution along their fluid-contacting
surfaces. 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.
Secondly, in addition to materials and devices that are made of
a single metal or metal alloy, henceforth termed a layer, the inventive
grafts may be comprised of a layer of biocompatible material or
of a plurality of layers of biocompatible materials formed upon
one another into a self-supporting multilayer structure because
multilayer structures are generally known to increase the mechanical
strength of sheet materials, or to provide special qualities by
including layers that have special properties such as superelasticity,
shape memory, radio-opacity, corrosion resistance etc. A special
advantage of vacuum deposition technologies is that it is possible
to deposit layered materials and thus films possessing exceptional
qualities may be produced (cf., H. Holleck, V. Schier: Multilayer
PVD coatings for wear protection, Surface and Coatings Technology,
Vol. 76-77 (1995) pp. 328-336). 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.
Multilayers are also used in the field of thin film fabrication
to increase the mechanical properties of the thin film, specifically
hardness and toughness.
Thirdly, the design possibilities for possible configurations and
applications of the inventive graft are greatly enhanced by employing
vacuum deposition technologies. Specifically, vacuum deposition
is an additive technique that lends itself toward fabrication of
substantially uniformly thin materials with potentially complex
three dimensional geometries and structures that cannot be cost-effectively
achieved, or in some cases achieved at all, by employing conventional
wrought fabrication techniques. Conventional wrought metal fabrication
techniques may entail smelting, hot working, cold working, heat
treatment, high temperature annealing, precipitation annealing,
grinding, ablation, wet etching, dry etching, cutting and welding.
All of these processing steps have disadvantages including contamination,
material property degradation, ultimate achievable configurations,
dimensions and tolerances, biocompatibility and cost. For example
conventional wrought processes are not suitable for fabricating
tubes having diameters greater than about 20 mm diameter, nor are
such processes suitable for fabricating materials having wall thicknesses
down to about 5 .mu.m with sub-.mu.m tolerances.
While the inventive self-supporting metal or pseudometal graft
may be fabricated of conventionally fabricated wrought materials,
in accordance with the best mode contemplated for the present invention,
the inventive graft is preferably fabricated by vacuum deposition
techniques. By vacuum depositing the metal and/or pseudometallic
film as the precursor material for the inventive graft, it is possible
to more stringently control the material, biocompatibility and mechanical
properties of the resulting film material and graft than is possible
with conventionally fabricated graft-forming materials. The inventive
self-supporting graft may be used alone, i.e., the whole implantable
device may be made of a single graft, or it may be a part of a structure
where the graft is used in conjunction either with other grafts,
or in conjunction with other structural elements, such as scaffolds,
stents, and other devices. The term "in conjunction" may
mean actual connection, such as that made by welding, fusing, or
other joining methods, as well as being made from the same piece
of material by forming some area of the piece into a graft and some
other area of the piece into another member or part of the device.
SUMMARY OF THE INVENTION
In accordance with a preferred embodiment of the invention, there
is provided a self-supporting graft member having a plurality of
microperforations passing through the wall thickness of the graft.
The graft member may assume virtually any geometric configuration,
including sheets, tubes or rings. The plurality of microperforations
may serve to impart geometric compliance to the graft, geometric
distendability to the graft and/or limit or permit the passage of
body fluids or biological matter through the graft, such as facilitating
transmural endothelialization while preventing fluid flow through
the wall of the graft under normal physiological conditions. The
plurality of microperforations may also impart a fabric-like quality
to the graft by imparting pliability and/or elastic, plastic or
superelastic compliance to the graft, such as that required for
longitudinal flexibility in the case of a vascular graft.
In a first embodiment, the graft may be made from plastically deformable
materials such that upon application of a force, the microperforations
geometrically deform to impart permanent enlargement of one or more
axes of the graft, such as length in the case of a planar graft,
e.g., a surgical patch graft, or diameter, such as in the case of
a tubular graft, e.g., a vascular graft. In a second embodiment,
the graft may be fabricated of elastic or superelastic materials.
Elastic and/or superelastic materials will permit the microperforations
to geometrically deform under an applied force in a manner that
allows for a recoverable change in one or more axes of the graft.
In each of the first and second embodiments of the invention, the
graft may be fabricated in such a manner as to have fabric-like
qualities by controlling the film thickness, material properties
and geometry of the plurality of microperforations. Furthermore,
in such cases where minimally invasive delivery is required, such
as for endoluminal delivery of vascular grafts, the first and second
embodiments allow for delivery using balloon expansion and self-expansion,
respectively, or a combination of both. Minimally invasive delivery
may also be accomplished by folding the graft for delivery similar
to the manner in which an angioplasty balloon is creased and fluted
or folded. The graft may be delivered by unfolding the device in
vivo either by assistance such as by using a balloon, or by the
graft material's plastic, elastic or superelastic properties or
by a combination thereof. After delivery, the plurality of microperforations
may be patterned in such a manner as to allow for additional dimensional
enlargement of the graft member by elastic or plastic deformation
such as a radially expansive positive pressure.
For some applications it is preferable that the size of each of
the plurality of microperforations be such as to permit cellular
migration through each opening, without permitting fluid flow there
through. In this manner, for example, blood cannot flow through
the plurality of microperforations (in their deformed or un-deformed
state), but various cells or proteins may freely pass through the
plurality of microperforations to promote graft healing in vivo.
For other applications, moderate amounts of fluid flow through the
plurality of deformed or un-deformed microperforations may be acceptable.
For example, endoluminal saphenous vein grafts may be fabricated
with microperforations that serve the dual function of permitting
transmural endothelialization while also excluding biological debris,
such as thrombus from passing through the wall thickness of the
graft, effectively excluding detrimental matter from entering the
circulation. In this example, each of the plurality of microperforations
in either their deformed or undeformed state, may exceed several
hundred microns.
Those skilled in the art will understand that a direct relationship
exists between the size of pores and the overall ratio of expansion
or deformability of an implantable graft. Generally, therefore,
it is appreciated that pore sizes must increase in order to increase
the effective attainable degree of expansion or deformation of the
graft.
For applications where large deformation and small pore size are
both requirements, in accordance with another aspect of the inventive
graft embodiment, it is contemplated that two or more graft members
are employed such as diametrically concentric grafts for tubular
configurations. The two or more graft members have a pattern of
a plurality of microperforations passing there through, with the
plurality of patterned microperforations 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 as well as a smaller effective pore
size. In order to facilitate cellular migration through and healing
of the first and second graft members in vivo, it may be preferable
to provide additional cellular migration pathways that communicate
between the plurality of microperforations in the first and second
graft members. These additional cellular migration pathways, if
necessary, 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 microperforations in the first and second
graft members, 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, the microgrooves serve as cellular migration conduits
between the plurality of microperforations in the first and second
graft members, or 3) where the microperforations are designed to
impart an out of plane motion of the graft material upon deformation,
thereby keeping a well defined space between the planes originally
defining the facing surfaces of the grafts.
The graft member or members may be formed as a monolayer film,
or may be formed from a plurality of film layers formed one upon
another. The particular material used to form each layer of biocompatible
metal and/or pseudometal is chosen for its biocompatibility, corrosion-fatigue
resistance and mechanical properties, i.e., tensile strength, yield
strength. The metals include, without limitation, the following:
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. Additionally, each layer of
material used to form the graft may be doped with another material
for purposes of improving properties of the material, such as radiopacity
or radioactivity, by doping with tantalum, gold, or radioactive
isotopes.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the inventive graft.
FIG. 2A is a fragmentary plan view depicting a first pattern of
microperforations useful in the present invention.
FIG. 2B is a fragmentary plan view depicting a second pattern of
microperforations useful in the present invention.
FIG. 2C is a fragmentary plan view depicting a third pattern of
microperforations useful in the present invention.
FIG. 2D is a fragmentary plan view depicting a fourth pattern of
microperforations useful in the present invention.
FIG. 3A is photomicrograph depicting the inventive graft having
the first pattern of microperforation depicted in FIG. 2A in a geometrically
undeformed state.
FIG. 3B is a photomicrograph of the inventive graft illustrated
in FIG. 3A showing the microperforations in a geometrically deformed
state.
FIG. 4 is a diagrammatic illustration depicting geometric deformation
of the fourth pattern of microperforations in FIG. 2D.
FIG. 5 is a diagrammatic cross-sectional view illustration depicting
the inventive graft assuming a folded condition suitable for endoluminal
delivery.
FIG. 6 is a photographic illustration of the inventive graft used
as a stent covering.
FIG. 7 is a photographic illustration of the inventive graft deformed
approximately 180 degrees along its longitudinal axis illustrating
the fabric-like quality of the graft.
FIG. 8A is a photographic illustration of the inventive graft circumferentially
covering a braided expansion member and mounted on an expansion
jig that exerts a compressive force along the longitudinal axis
of the braided expansion member and which radially expands the braided
expansion member.
FIG. 8B is a photographic illustration of the inventive graft radially
exhibiting radial compliance under the influence of a radially expansive
force.
FIG. 9 is a flow diagram depicting alternate embodiments of making
the inventive graft.
FIG. 10A is a histology slide, stained with hematoxylin and eosin,
from a 28 day explanted swine carotid artery having the inventive
graft implanted therein.
FIG. 10B is a histology slide, stained with hematoxylin and eosin,
from a 28 day explanted swine carotid artery having the inventive
graft implanted therein.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
With the foregoing as background, we turn now to a description
of the present invention with reference the preferred embodiments
thereof and with reference to the accompanying figures. As noted
above, the inventive microporous metallic implantable devices may
assume a wide number of geometric configurations, including, for
example, planar sheets, tubes or toroids. For ease of reference,
however, the accompanying figures and the following description
of the invention will refer to tubular implantable graft members.
Those skilled in the art, however, will understand that this is
merely an exemplary geometric configuration and is not intended
to limit the scope of the invention to tubular members or be limited
in application to graft members.
With particular reference to FIG. 1, the inventive implantable
medical device is illustrated as a graft 10. Graft 10 consists generally
of a body member 12 having a first surface 14 and a second surface
16 and a thickness 18 intermediate the first surface 14 and the
second surface 16. A plurality of microperforations 20 is provided
and pass through the thickness 18 of the body member 12 with interperforation
regions 22 of the body member 12 between adjacent microperforation
20. The plurality of microperforations 20 each preferably have a
geometric configuration that is susceptible of geometric change,
such that the open surface area of each microperforation 20 may
change under an externally applied load. Each of the plurality of
microperforations 20 in the undeformed state preferably has an open
surface area less than about 2 mm.sup.2, with the total open surface
area of the graft in the undeformed state being between 0.001 to
99%. The open surface area of the plurality of microperforations
and the open surface area of the graft may change considerably upon
deformation of the plurality of microperforations 20. Both the size
of the microperforations 20 in the deformed and undeformed state
and the total open area of the graft 12 in the deformed and undeformed
state may be selected in view of the following non-exclusive factors
based on the graft application: 1) the desired compliance of the
graft 10, 2) the desired strength of the graft 10, 3) desired stiffness
of the graft 10, 4) the desired degree of geometric enlargement
of the microperforations 20 upon deformation and 5) in some cases,
such as with vascular grafts, the desired delivery profile and post
delivery profile.
In accordance with a preferred embodiment of the present invention,
the plurality of microperforations 20 is patterned in such a manner
as to define deformation regions of the body member 12. The thickness
18 is between 0.1 .mu.m and 75 .mu.m, preferably between 1 .mu.m
and 50 .mu.m. When fabricated within these thickness ranges, the
graft 10 has a thickness 18 which is thinner than the wall thickness
of conventional non-metallic implantable grafts and that of conventional
metal endoluminal stents.
The plurality of microperforations is patterned in a regular array
forming a regular array of microperforations 20 in both the longitudinal
and circumferential axes of the body member 12. For purposes of
reference, the pattern of microperforations 20 will, hereinafter,
be described with reference to a planar X-Y axes, which in a tubular
member will correspond to the longitudinal or circumferential axes
of the tubular member. Those of ordinary skill in the art will understand
that reference to X-axis or Y-axis when applied to a tubular member
may be used such that the term "X-axis" may correspond
to either the longitudinal axis or circumferential direction of
the tubular member and the term "Y-axis" may refer to
the corresponding circumferential direction or longitudinal axis
or the tubular member.
It will be appreciated by those of ordinary skill in the art that
individual different geometric patterns may have associated intended
uses, function or mechanical requirements of a particular device.
Thus, the particular intended use of the implantable member 12 will
be a consideration in the selection of the particular geometric
pattern for the plurality of microperforations 20. For example,
where the implantable member 12 has an intended use as a free-standing
implantable endoluminal vascular graft, a large circumferential
expansion ratio and longitudinal flexibility may be desirable. Thus,
a particular geometry of the plurality of microperforations 20 that
offers these properties will be selected. The plurality of microperforations
20 also affect the material properties of the implantable member
10. For example, the geometry each microperforation 20 may be altered
so that each microperforation 20 exhibits stress-strain relief capabilities
or the microperforations 20 may control whether geometric deformation
of the microperforations 20 are plastic, elastic or superelastic
deformation. Thus, both the geometry of the individual microperforations
20, the orientation of the microperforations 20 relative to the
X-Y axis of the implantable member 10 and the pattern of the microperforations
20 may be selected to directly impart, affect or control the mechanical
and material properties of the implantable member 10.
Different geometric patterns for the plurality of microperforations
20 in accordance with the preferred embodiments of the invention
are illustrated in FIGS. 2A-2C. FIG. 2A illustrates a first geometry
for each of the plurality of microperforations 30. In accordance
with this first geometry, each of the plurality of microperforations
30 consist of generally elongated slots 32a, 32b. Each of the generally
elongated slots 32a, 32b preferably include terminal fillets 34
on opposing ends of each elongated slot 32a, 32b. The terminal fillets
34 serve a strain relief function that aids in strain distribution
through the interperforation regions 22 between adjacent slots 32.
FIG. 2A further illustrates a first geometric pattern for the plurality
of microperforations 32a, 32b, wherein a first row of a plurality
of microperforations 32a is provided with adjacent microperforations
32a being arrayed in end-to-end fashion along a common axis, and
a second row of a plurality of microperforations 32b is provided
with adjacent microperforations 32b being arrayed in end-to-end
fashion along a common axis with one another and with the microperforations
32a. The first row of microperforations 32a and the second row of
microperforations 32b are offset or staggered from one another,
with an end of a microperforation 32a being laterally adjacent to
an intermediate section of a microperforation 32b, and an end of
microperforation 32b being laterally adjacent an intermediate section
of a microperforation 32a.
The first geometry 30 of the plurality of microperforations 32a,
32b illustrated in FIG. 2A permits a large deformation along an
axis perpendicular to a longitudinal axis of the slots. Thus, where
the longitudinal axis of slots 32a, 32b is co-axial with the longitudinal
axis of the implantable member 10, deformation of the slots 32a,
32b will permit circumferential compliance and/or expansion of the
implantable member 10. Alternatively, where the longitudinal axis
of the slots 32a, 32b is parallel to the circumferential axis of
the implantable member 10, the slots 32a, 32b permit longitudinal
compliance, flexibility and expansion of the implantable member
10.
FIG. 2B illustrates a second geometry 40 for the plurality of microperforations
20 and consists of a plurality of microperforations 42a, 44b, again
having a generally elongate slot-like configuration like those of
the first geometry 30. In accordance with this second geometry 40,
individual microperforations 42a and 44b are oriented orthogonal
relative to one another. Specifically, a first microperforation
42a is oriented parallel to an X-axis of the implantable member
10, while a first microperforation 44b is positioned adjacent to
the first microperforation 44a along the X-axis, but the first microperforation
44b is oriented perpendicular to the X-axis of the implantable member
10 and parallel to the Y-axis of the implantable member 10. Like
the first geometry, each of the plurality of microperforations 42a,
44b may include a terminal fillet 44 at opposing ends of the slot
of each microperforation in order to serve a strain relief function
and transmit strain to the interperforation region 22 between adjacent
microperforations. This second geometry 40 offers a balance in both
compliance and degree of expansion in both the X and Y-axes of the
implantable device 12
In each of FIGS. 2A and 2B, each of the microperforations 32a,
32b, 42a, 44b has a generally longitudinal slot configuration. Each
of the generally longitudinal slots may be configured as a generally
linear or curvilinear slot. In accordance with the preferred embodiments
of the invention, however, it is preferred to employ generally linear
slots.
FIG. 2C illustrates a third preferred geometry 50 for the plurality
of microperforations. In accordance with this third geometry 50,
each of the plurality of microperforations 52 has a generally trapezoidal
or diamond-like shape with interperforation graft regions 56 between
adjacent pairs of microperforations 52. It will be appreciated that
the third geometry 50 may be achieved by geometrically deforming
the first geometry 30 along an axis perpendicular to the longitudinal
axis of the plurality of microperforations 32a, 32b. Similarly,
the first geometry 30 may be achieved by deforming microperforations
52 in the third geometry 50 along either an X-axis or a Y-axis of
the implantable member 10.
FIGS. 3A and 3B are photomicrographs illustrating the inventive
implantable device 12 having a plurality of microperforations formed
as generally longitudinal slots 32a, 32b in accordance with the
first geometry depicted in FIG. 2A. Each of the plurality of microperforations
were formed with an orientation parallel to the longitudinal axis
of the implantable device 12. The implantable device 12 consists
of a 6 mm inner diameter NiTi shape memory tubular graft member
having a wall thickness of 5 .mu.m. FIG. 3A depicts the plurality
of microperforations 32a and 32b in their undeformed state, while
FIG. 3B depicts the plurality of microperforations 32a and 32b in
their geometrically deformed state under the influence of stain
applied perpendicular to the longitudinal axis of the implantable
graft 12. It may be clearly understood that geometric deformation
of the plurality of microperforations 32a, 32b permitted circumferential
expansion of the inventive graft. The dimensions of each of the
plurality of microperforations in their undeformed state depicted
in FIGS. 3A and 3B was 430 .mu.m in length, 50 .mu.m width, with
the terminal fillets having a 50 .mu.m diameter.
In accordance with a fourth geometry of the plurality of microperforations
20 illustrated in FIGS. 2D and 4, each of the plurality of microperforations
20 have a generally tri-legged or Y-shaped configuration. The Y-shaped
configuration of each of the plurality of microperforations 20 has
three co-planar radially projecting legs 31a, 31b, 31e, each offset
from the other by an angle of about 120 degrees thereby forming
a generally Y-shape. Each of the three co-planar radially projecting
legs 31a, 31b, 31c may be symmetrical or asymmetrical relative to
one another. However, in order to achieve uniform geometric deformation
across the entire graft body member 12, it is preferable that each
of the plurality of microperforations 20 has geometric symmetry.
Those skilled in the art will recognize that beyond the two particular
patterns described here any number of different patterns may be
used without significantly departing from the inventive graft concept
described in the present patent.
Those skilled in the art will understand that each of the microperforations
20 are capable of undergoing deformation upon application of a sufficient
force. In a tubular geometry, the graft 12 may deform both circumferentially
and longitudinally. As is illustrated in FIG. 3a, each of the plurality
of elongated slots may deform into opened microperforations which
assume a generally rhomboidal shape. Similarly, Y-shaped microperforations
20 shown in 4 are capable of deformation into generally circular
or oval open microperforations 21. The deformation regions 22 between
adjacent microperforations 20 facilitate deformation of each of
the plurality of microperforations 20 by deforming to accommodate
opening of each of the plurality of microperforations 20.
As depicted in FIG. 5, the inventive graft 12 may be folded to
assume a smaller diametric profile for endoluminal delivery. In
order to facilitate folding, the pattern of the plurality of microperforations
20 may be fashioned to create a plurality of folding regions 23,
that constitute relatively weakened regions of the graft 12, to
permit folding the graft 12 along folding regions 23.
FIG. 6 is a photographic illustration of the inventive microporous
graft 12 circumferentially mounted onto an endoluminal stent 5.
It may be readily seen that the microporous graft 12 exhibits mechanical
properties of high longitudinal flexibility and both radial and
circumferential compliance.
FIG. 7 is a photographic illustration of the inventive microporous
graft 12 mounted onto mandrel and flexed approximately 180 degrees
along its longitudinal axis. Upon longitudinal flexion, the inventive
graft 12 undergoes a high degree of folding with a plurality of
circumferentially oriented folds 7, characteristic of its fabric-like
qualities.
FIGS. 8A and 8B are photographic reproductions illustrating the
high degree of circumferential compliance of the inventive microporous
graft 12. A 6 mm microporous graft having a 5 .mu.m wall thickness
was mounted concentrically over a braided pseudostent. An axial
force was applied along the longitudinal axis of the braided pseudostent
causing the pseudostent to radially expand and exert a circumferentially
expansive force to the inventive graft 12. As is clearly depicted
in FIGS. 8A and 8B the plurality of micropores in the inventive
graft 12 geometrically deform thereby permitting circumferential
expansion of the graft 12.
Thus, one embodiment of the present invention provides a new metallic
and/or pseudometallic implantable graft that is biocompatible, geometrically
changeable either by folding and unfolding or by application of
a plastically, elastically or superelastically deforming force,
and capable of endoluminal delivery with a suitably small delivery
profile. Suitable metal materials to fabricate the inventive graft
are chosen for their biocompatibility, mechanical properties, i.e.,
tensile strength, yield strength, and their ease of fabrication.
The compliant nature of the inventive graft material may be employed
to form the graft into complex shapes by deforming the inventive
graft over a mandrel or fixture of the appropriate design. Plastic
deformation and shape setting heat treatments may be employed to
ensure the inventive implantable members 10 retain a desired conformation.
According to a first preferred method of making the graft of the
present invention, the graft is fabricated of vacuum deposited metallic
and/or pseudometallic films. With particular reference to FIG. 9,
the fabrication method 100 of the present invention is illustrated.
A precursor blank of a conventionally fabricated biocompatible metal
or pseudometallic material may be employed at step 102. Alternatively,
a precursor blank of a vacuum deposited metal or pseudometallic
film may be employed at step 104. The precursor blank material obtained
either from step 102 or step 104 is then preferably masked at step
108 leaving exposed only those regions defining the plurality of
microperforations. The exposed regions from step 108 are then subjected
to removal either by etching at step 110, such as by wet or dry
chemical etching processing, with the etchant being selected based
upon the material of the precursor blank, or by machining at step
112, such as by laser ablation or EDM. Alternatively, when employing
the vacuum deposition step 104, a pattern mask corresponding to
the plurality of microperforations may be interposed at step 106
between the target and the source and the metal or pseudometal deposited
through the pattern mask to form the patterned microperforations.
Further, when employing the vacuum deposition step 104, plural film
layers maybe deposited to form a multilayer film structure of the
film prior to or concurrently with forming the plurality of microperforations.
Thus, the present invention provides a new metallic and/or pseudometallic
implantable graft that is biocompatible, compliant, geometrically
changeable either by folding and unfolding or by application of
a plastically, elastically or superelastically deforming force,
and, in some cases, capable of endoluminal delivery with a suitably
small delivery profile and suitably low post-delivery profile. Suitable
metal materials to fabricate the inventive graft are chosen for
their biocompatibility, mechanical properties, i.e., tensile strength,
yield strength, and in the case where vapor deposition is deployed,
their ease of deposition include, without limitation, the following:
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. Examples of pseudometallic
materials potentially useful with the present invention include,
for example, composite materials and ceramics.
The present invention also provides a method of making the inventive
expandable metallic graft by vacuum deposition of a graft-forming
metal or pseudometal and formation of the microperforations either
by removing sections of deposited material, such as by etching,
EDM, ablation, or other similar methods, or by interposing a pattern
mask, corresponding to the microperforations, between the target
and the source during deposition processing. Alternatively, a pre-existing
metal and/or pseudometallic film manufactured by conventional non-vacuum
deposition methodologies, such as wrought hypotube or sheet, may
be obtained, and the microperforations formed in the pre-existing
metal and/or pseudometallic film by removing sections of the film,
such as by etching, EDM, ablation, or other similar methods. An
advantage of employing multilayer film structures to form the inventive
graft is that differential functionalities may be imparted in the
discrete layers. For example, a radiopaque material such as tantalum
may form one layer of a structure while other layers are chosen
to provide the graft with its desired mechanical and structural
properties.
In accordance with the preferred embodiment of fabricating the
inventive microporous metallic implantable device in which the device
is fabricated from vacuum deposited nitinol tube, a cylindrical
deoxygenated copper substrate is provided. The substrate is mechanically
and/or electropolished to provide a substantially uniform surface
topography for accommodating metal deposition thereupon. A cylindrical
hollow cathode magnetron sputtering deposition device was employed,
in which the cathode was on the outside and the substrate was positioned
along the longitudinal axis of the cathode. A cylindrical target
consisting either of a nickel-titanium alloy having an atomic ratio
of nickel to titanium of about 50-50% and which can be adjusted
by spot welding nickel or titanium wires to the target, or a nickel
cylinder having a plurality of titanium strips spot welded to the
inner surface of the nickel cylinder, or a titanium cylinder having
a plurality of nickel strips spot welded to the inner surface of
the titanium cylinder is provided. It is known in the sputter deposition
arts to cool a target within the deposition chamber by maintaining
a thermal contact between the target and a cooling jacket within
the cathode. In accordance with the present invention, it has been
found useful to reduce the thermal cooling by thermally insulating
the target from the cooling jacket within the cathode while still
providing electrical contact to it. By insulating the target from
the cooling jacket, the target is allowed to become hot within the
reaction chamber. Two methods of thermally isolating the cylindrical
target from the cooling jacket of the cathode were employed. First,
a plurality of wires having a diameter of 0.0381 mm were spot welded
around the outer circumference of the target to provide an equivalent
spacing between the target and the cathode cooling jacket. Second,
a tubular ceramic insulating sleeve was interposed between the outer
circumference of the target and the cathode cooling jacket. Further,
because the Ni--Ti sputtering yields can be dependant on target
temperature, methods which allow the target to become uniformly
hot are preferred.
The deposition chamber was evacuated to a pressure less than or
about 2-5.times.10.sup.-7 Torr and pre-cleaning of the substrate
is conducted under vacuum. During the deposition, substrate temperature
is preferably maintained within the range of 300 and 700 degrees
Centigrade. It is preferable to apply a negative bias voltage between
0 and -1000 volts to the substrate, and preferably between -50 and
-150 volts, which is sufficient to cause energetic species arriving
at the surface of the substrate. During deposition, the gas pressure
is maintained between 0.1 and 40 mTorr but preferably between 1
and 20 mTorr. Sputtering preferably occurs in the presence of an
Argon atmosphere. The argon gas must be of high purity and special
pumps may be employed to reduce oxygen partial pressure. Deposition
times will vary depending upon the desired thickness of the deposited
tubular film. After deposition, the plurality of microperforations
are formed in the tube by removing regions of the deposited film
by etching, such as chemical etching, ablation, such as by excimer
laser or by electric discharge machining (EDM), or the like. After
the plurality of microperforations are formed, the formed microporous
film is removed from the copper substrate by exposing the substrate
and film to a nitric acid bath for a period of time sufficient to
remove dissolve the copper substrate.
EXAMPLE
A 5 .mu.m thick NiTi graft having a pattern of microperforations
consisting of parallel staggered longitudinally oriented linear
slots, each slot being 430 .mu.m length, 25 .mu.m width, and having
50 .mu.m diameter fillets on each end of each linear slot, was mounted
onto a 6 mm NiTi stent and delivered endoluminally to the left carotid
artery of a swine. After 28 days, the swine was euthanized, and
the graft explanted from the left carotid artery. Samples were prepared
using standard hematoxylin and eosin staining procedures, and microscope
slides prepared. As illustrated in FIG. 10A histology of the explanted
samples revealed complete endothelialization around the graft 12,
negligible neointimal proliferation with the absence of trauma to
the internal elastic lamina. FIG. 10B is a sample indicating cross-talk
between the arterial superficial and deep layers with the transmural
formation of small capillaries.
While the present invention has been described with reference to
its preferred embodiments, those of ordinary skill in the art will
understand and appreciate that variations in materials, dimensions,
geometries, and fabrication methods may be or become known in the
art, yet still remain within the scope of the present invention
which is limited only by the claims appended hereto.
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