U.S. patent application number 10/452954 was filed with the patent office on 2003-10-23 for expandable stent with sliding and locking radial elements.
Invention is credited to Koenig, Donald H., Steinke, Thomas A., Zeltinger, Joan.
Application Number | 20030199969 10/452954 |
Document ID | / |
Family ID | 24972826 |
Filed Date | 2003-10-23 |
United States Patent
Application |
20030199969 |
Kind Code |
A1 |
Steinke, Thomas A. ; et
al. |
October 23, 2003 |
Expandable stent with sliding and locking radial elements
Abstract
The present invention provides a lumen support stent with a
clear through-lumen for use in a body lumen. The stent is formed
from at least one series of sliding and locking radial elements and
at least one ratcheting mechanism comprising an articulating
element and a plurality of stops. The ratcheting mechanism permits
one-way sliding of the radial elements from a collapsed diameter to
an expanded diameter, but inhibits radial recoil from the expanded
diameter.
Inventors: |
Steinke, Thomas A.; (San
Diego, CA) ; Koenig, Donald H.; (San Diego, CA)
; Zeltinger, Joan; (Encinitas, CA) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE
CA
92614
US
|
Family ID: |
24972826 |
Appl. No.: |
10/452954 |
Filed: |
June 3, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10452954 |
Jun 3, 2003 |
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09739552 |
Dec 14, 2000 |
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09739552 |
Dec 14, 2000 |
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09283800 |
Apr 1, 1999 |
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6224626 |
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09283800 |
Apr 1, 1999 |
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09024571 |
Feb 17, 1998 |
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6033436 |
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Current U.S.
Class: |
623/1.16 ;
623/1.15 |
Current CPC
Class: |
A61F 2/07 20130101; A61F
2002/91533 20130101; A61L 31/16 20130101; A61F 2/92 20130101; A61F
2/915 20130101; A61L 2300/416 20130101; B33Y 80/00 20141201; A61F
2/93 20130101; A61F 2220/0058 20130101; A61F 2250/0098 20130101;
A61F 2/91 20130101; A61F 2002/072 20130101; A61F 2/94 20130101;
A61F 2002/9155 20130101; A61F 2220/005 20130101; A61F 2002/075
20130101; A61F 2250/0067 20130101; A61F 2002/91591 20130101 |
Class at
Publication: |
623/1.16 ;
623/1.15 |
International
Class: |
A61F 002/06 |
Claims
What is claimed is:
1. An expandable stent, comprising: a tubular member comprising a
series of slideably engaged radial elements; and at least one
articulating mechanism which permits one-way sliding of the radial
elements from a first collapsed diameter to a second expanded
diameter, wherein said at least one articulating mechanism does not
comprise paired slots, and wherein no radial element overlaps with
itself in the second expanded diameter.
2. The expandable stent of claim 1, wherein each radial element
comprises at least one elongated rib disposed between first and
second end portions.
3. The expandable stent of claim 2, wherein the radial elements
that comprise the series alternate between radial elements having
an odd number of elongated ribs and radial elements having an even
number of elongated ribs.
4. The expandable stent of claim 2, wherein the radial elements
that comprise the series alternate between radial elements having
one elongated rib and radial elements having two elongated
ribs.
5. The expandable stent of claim 1, wherein the tubular member
comprises at least series which are coupled to one another by at
least one linkage element.
6. The expandable stent of claim 5, wherein the at least one
linkage element is made from a degradable material.
7. The expandable stent of claim 1, wherein radial recoil of the
tubular member in the second expanded diameter is less than about
5%.
8. The expandable stent of claim 1, wherein the tubular member has
a stiffness of less than about 0.1 Newtons force/millimeter
deflection.
9. The expandable stent of claim 1, wherein the tubular member
provides a surface area coverage of greater than about 20%.
10. The expandable stent of claim 1, wherein the tubular member is
at least partially radiopaque.
11. The expandable stent of claim 1, wherein the radial elements
are made substantially from a material which is work hardened to
between about 25% and 95%.
12. The expandable stent of claim 1, wherein the radial elements
are made from a material selected from the group consisting of a
polymer, a metal, a ceramic, and combinations thereof.
13. The expandable stent of claim 12, wherein said material further
comprises a bioactive agent.
14. The expandable stent of claim 13, wherein the radial elements
are adapted to release the bioactive agent during stent deployment
when the tubular member is adjusted from the first collapsed
diameter to the second expanded diameter.
15. The expandable stent of claim 13, wherein the bioactive agent
is selected from the group consisting of antiplatelet agents,
antithrombin agents, antiproliferative agents and antiinflammatory
agents.
16. The expandable stent of claim 1, wherein the radial elements
are made from a degradable material.
17. The expandable stent of claim 16, wherein said degradable
material is selected from the group consisting of polyarylates
(L-tyrosine-derived), free acid polyarylates, polycarbonates
(L-tyrosine-derived), poly(ester-amides), poly(propylene
fumarate-co-ethylene glycol) copolymer, polyanhydride esters,
polyanhydrides, polyorthoesters, silk-elastin polymers, calcium
phosphate and magnesium alloys.
18. The expandable stent of claim 16, wherein said degradable
material further comprises a bioactive agent, which is released as
the material degrades.
19. The expandable stent of claim 18, wherein said degradable
material is adapted to deliver an amount of the bioactive agent
which is sufficient to inhibit restenosis at a site of stent
deployment.
20. The expandable stent of claim 18, wherein the bioactive agent
is selected from the group consisting of antiplatelet agents,
antithrombin agents, antiproliferative agents and antiinflammatory
agents.
21. The expandable stent of claim 1, comprising at least two
series, wherein the expanded diameters of the first and second
series are different.
22. The expandable stent of claim 1, wherein each articulating
mechanism comprises a slot and a tab on one radial element and at
least one stop on an adjacent radial element which is slideably
engaged in the slot, wherein the tab is adapted to engage the at
least one stop.
23. The expandable stent of claim 22, wherein the at least one stop
comprises a hole with a chamfered edge.
24. The expandable stent of claim 22, wherein the least one
articulating mechanism further comprises an expansion resistor on
the slideably engaged radial element, wherein the expansion
resistor resists passing through the slot during expansion until
further force is applied, such that the radial elements in the
module expand in a substantially uniform manner.
25. The expandable stent of claim 1, wherein the articulating
mechanism further comprises a release, such that actuation of the
release permits sliding of the radial elements from the second
expanded diameter back to the first collapsed diameter.
26. The expandable stent of claim 1, further comprising a floating
coupling element with an articulating mechanism.
27. The expandable stent of claim 1, further comprising a frame
element which surrounds at least one radial element in each
series.
28. The expandable stent of claim 27, wherein the tubular member
comprises at least two series, and wherein the frame elements from
adjacent series are coupled.
29. The expandable stent of claim 28, wherein the frame elements
from adjacent series are coupled by a linkage element extending
between the frame elements.
30. The expandable stent of claim 28, wherein the frame elements
from adjacent series are coupled by interlinking of the frame
elements.
31. An expandable stent, comprising: a tubular member comprising a
longitudinal length and a diameter which is adjustable between at
least a first collapsed diameter and at least a second expanded
diameter, said tubular member comprising: at least two series of
slideably engaged radial elements, wherein no radial element
overlaps with itself in the second expanded diameter; at least one
articulating mechanism which permits one-way sliding of the radial
elements from the first collapsed diameter to the second expanded
diameter; and at least one linkage element connecting adjacent
series of radial elements, wherein no linkage element or radial
element extends the longitudinal length of said tubular member.
Description
RELATED APPLICATIONS
[0001] This is a continuation of U.S. patent application Ser. No.
09/739,552, filed Dec. 14, 2000, which is a continuation-in-part of
U.S. patent application Ser. No. 09/283,800 filed on Apr. 1, 1999,
now U.S. Pat. No. 6,224,626, which is a continuation-in-part of
U.S. patent application Ser. No. 09/024,571 filed on Feb. 17, 1998,
now U.S. Pat. No. 6,033,436.
BACKGROUND OF THE INVENTION
[0002] This invention relates to expandable medical implants for
maintaining support of a body lumen.
[0003] An important use of stents is found in situations where part
of the vessel wall or stenotic plaque blocks or occludes fluid flow
in the vessel. Often, a balloon catheter is utilized in a
percutaneous transluminal coronary angioplasty procedure to enlarge
the occluded portion of the vessel. However, the dilation of the
occlusion can cause fissuring of atherosclerotic plaque and damage
to the endothelium and underlying smooth muscle cell layer,
potentially leading to immediate problems from flap formation or
perforations in the vessel wall, as well as long-term problems with
restenosis of the dilated vessel. Implantation of stents can
provide support for such problems and prevent re-closure of the
vessel or provide patch repair for a perforated vessel. Further,
the stent may overcome the tendency of diseased vessel walls to
collapse, thereby maintaining a more normal flow of blood through
that vessel.
[0004] Significant difficulties have been encountered with all
prior art stents. Each has its percentage of thrombosis, restenosis
and tissue in-growth, as well as various design-specific
disadvantages.
[0005] Examples of prior developed stents have been described by
Balcon et al., "Recommendations on Stent Manufacture, Implantation
and Utilization," European Heart Journal (1997), vol. 18, pages
1536-1547, and Phillips, et al., "The Stenter's Notebook,"
Physician's Press (1998), Birmingham, Mich. The first stent used
clinically was the self-expanding "Wallstent" which comprised a
metallic mesh in the form of a Chinese fingercuff. This design
concept serves as the basis for many stents used today. These
stents were cut from elongated tubes of wire braid and,
accordingly, had the disadvantage that metal prongs from the
cutting process remained at the longitudinal ends thereof. A second
disadvantage is the inherent rigidity of the cobalt based alloy
with a platinum core used to form the stent, which together with
the terminal prongs, makes navigation of the blood vessels to the
locus of the lesion difficult as well as risky from the standpoint
of injury to healthy tissue along the passage to the target vessel.
Another disadvantage is that the continuous stresses from blood
flow and cardiac muscle activity create significant risks of
thrombosis and damage to the vessel walls adjacent to the lesion,
leading to restenosis. A major disadvantage of these types of
stents is that their radial expansion is associated with
significant shortening in their length, resulting in unpredictable
longitudinal coverage when fully deployed.
[0006] Among subsequent designs, some of the most popular have been
the Palmaz-Schatz slotted tube stents. Originally, the
Palmaz-Schatz stents consisted of slotted stainless steel tubes
comprising separate segments connected with articulations. Later
designs incorporated spiral articulation for improved flexibility.
These stents are delivered to the affected area by means of a
balloon catheter, and are then expanded to the proper size. The
disadvantage of the Palmaz-Schatz designs and similar variations is
that they exhibit moderate longitudinal shortening upon expansion,
with some decrease in diameter, or recoil, after deployment.
Furthermore, the expanded metal mesh is associated with relatively
jagged terminal prongs, which increase the risk of thrombosis
and/or restenosis. This design is considered current state of the
art, even though their thickness is 0.004 to 0.006 inches.
[0007] Another type of stent involves a tube formed of a single
strand of tantalum wire, wound in a sinusoidal helix; these are
known as coil stents. They exhibit increased flexibility compared
to the Palmaz-Schatz stents. However, they have the disadvantage of
not providing sufficient scaffolding support for many applications,
including calcified or bulky vascular lesions. Further, the coil
stents also exhibit recoil after radial expansion.
[0008] One stent design described by Fordenbacher, employs a
plurality of elongated parallel stent components, each having a
longitudinal backbone with a plurality of opposing circumferential
elements or fingers. The circumferential elements from one stent
component weave into paired slots in the longitudinal backbone of
an adjacent stent component. By incorporating locking means within
the slotted articulation, the Fordenbacher stent may minimize
recoil after radial expansion. In addition, sufficient numbers of
circumferential elements in the Fordenbacher stent may provide
adequate scaffolding. Unfortunately, the free ends of the
circumferential elements, protruding through the paired slots, may
pose significant risks of thrombosis and/or restenosis. Moreover,
this stent design would tend to be rather inflexible as a result of
the plurality of longitudinal backbones.
[0009] Some stents employ "jelly roll" designs, wherein a sheet is
rolled upon itself with a high degree of overlap in the collapsed
state and a decreasing overlap as the stent unrolls to an expanded
state. Examples of such designs are described in U.S. Pat. No.
5,421,955 to Lau, U.S. Pat. Nos. 5,441,515 and 5,618,299 to
Khosravi, and U.S. Pat. No. 5,443,500 to Sigwart. The disadvantage
of these designs is that they tend to exhibit very poor
longitudinal flexibility. In a modified design that exhibits
improved longitudinal flexibility, multiple short rolls are coupled
longitudinally. See e.g., U.S. Pat. No. 5,649,977 to Campbell and
U.S. Pat. Nos. 5,643,314 and 5,735,872 to Carpenter. However, these
coupled rolls lack vessel support between adjacent rolls.
[0010] Another form of metal stent is a heat expandable device
using Nitinol or a tin-coated, heat expandable coil. This type of
stent is delivered to the affected area on a catheter capable of
receiving heated fluids. Once properly situated, heated saline is
passed through the portion of the catheter on which the stent is
located, causing the stent to expand. The disadvantages associated
with this stent design are numerous. Difficulties that have been
encountered with this device include difficulty in obtaining
reliable expansion, and difficulties in maintaining the stent in
its expanded state.
[0011] Self-expanding stents are also available. These are
delivered while restrained within a sleeve (or other restraining
mechanism), that when removed allows the stent to expand.
Self-expanding stents are problematic in that exact sizing, within
0.1 to 0.2 mm expanded diameter, is necessary to adequately reduce
restenosis. However, self-expanding stents are currently available
only in 0.5 mm increments. Thus, greater selection and adaptability
in expanded size is needed.
[0012] In summary, there remains a need for an improved stent: one
that has smoother marginal edges, to minimize restenosis; one that
is small enough and flexible enough when collapsed to permit
uncomplicated delivery to the affected area; one that is
sufficiently flexible upon deployment to conform to the shape of
the affected body lumen; one that expands uniformly to a desired
diameter, without change in length; one that maintains the expanded
size, without significant recoil; one that has sufficient
scaffolding to provide a clear through-lumen; one that employs a
thinner-walled design, which can be made smaller and more flexible
to reach smaller diameter vessels; and one that has a
thinner-walled design to permit faster endothelialization or
covering of the stent with vessel lining, which in turn minimizes
the risk of thrombosis from exposed stent materials.
SUMMARY OF THE INVENTION
[0013] The present invention relates to an expandable intraluminal
stent, comprising a tubular member with a clear through-lumen. The
tubular member has proximal and distal ends and a longitudinal
length defined therebetween, and a circumference, and a diameter
which is adjustable between at least a first collapsed diameter and
at least a second expanded diameter. In a preferred mode, the
longitudinal length remains substantially unchanged when the
tubular member is adjusted between the first collapsed diameter and
the second expanded diameter. The tubular member includes at least
one module comprising a series of sliding and locking radial
elements, wherein each radial element defines a portion of the
circumference of the tubular member and wherein no radial element
overlaps with itself in either the first collapsed diameter or the
second expanded diameter.
[0014] In one aspect, each radial element may comprise at least one
elongated rib disposed between first and second end portions.
Preferably, the radial elements that comprise a module alternate
between radial elements having an odd number of elongated ribs and
radial elements having an even number of elongated ribs. In one
preferred mode, the radial elements alternate between radial
elements having one elongated rib and radial elements having two
elongated ribs.
[0015] The stent also includes at least one articulating mechanism
comprising a tab and at least one stop. The articulating mechanism
permits one-way sliding of the radial elements from the first
collapsed diameter to the second expanded diameter, but inhibits
radial recoil from the second expanded diameter.
[0016] In variations to the stent, the tubular member may comprise
at least two modules which are coupled to one another by at least
one linkage element. In one variation, the tubular member may
further comprise a frame element that surrounds at least one radial
element in each module. In stents in which the tubular member
comprises at least two modules, such frame elements from adjacent
modules may be coupled. The coupling may include a linkage element
extending between the frame elements. In addition or in the
alternative, the frame elements from adjacent modules may be
coupled by interlinking of the frame elements. In another aspect,
the intermodular coupling may be degradable allowing for the
independent modules to adapt to the vessel curvature.
[0017] In another variation to the stent of the present invention,
any amount of overlap among the radial elements within in a module
remains constant as the tubular member is adjusted from the first
collapsed diameter to the second expanded diameter. This amount of
overlap is preferably less than about 15%.
[0018] The radial recoil of the tubular member in accordance with
one preferred embodiment is less than about 5%. The stiffness of
the stent is preferably less than about 0.1 Newtons
force/millimeter deflection. The tubular member also preferably
provides a surface area coverage of greater than about 20%.
[0019] In accordance with another variation of the present stent,
the tubular member is at least partially radiopaque. The radial
elements may be made substantially from a material which is work
hardened to between about 80% and 95%. In one preferred variation,
the radial elements in the expandable intraluminal stent are made
from a material selected from the group consisting of a polymer, a
metal, a ceramic, and combinations thereof. In one mode, the
material may be degradable.
[0020] In another mode of the invention, the material may also
include a bioactive agent. The material is preferable adapted to
deliver an amount of the bioactive agent which is sufficient to
inhibit restenosis at the site of stent deployment. In one
variation, the radial elements are adapted to release the bioactive
agent during stent deployment when the tubular member is adjusted
from the first collapsed diameter to the second expanded diameter.
The bioactive agent(s) is preferably selected from the group
consisting of antiplatelet agents, antithrombin agents,
antiproliferative agents, and antiinflammatory agents.
[0021] In another variation, the tubular member further comprises a
sheath, such as for example in a vessel graft.
[0022] In one aspect, the expandable intraluminal stent comprises
at least two modules, wherein the expanded diameters of the first
and second modules are different.
[0023] The articulating mechanism(s) of the present invention which
allow the stent to expand but inhibit stent recoil, may comprise a
slot and a tab on one radial element and at least one stop on an
adjacent radial element which is slideably engaged in the slot,
wherein the tab is adapted to engage the at least one stop. The
articulating mechanism(s) may also include an expansion resistor on
the slideably engaged radial element, wherein the expansion
resistor resists passing through the slot during expansion until
further force is applied, such that the radial elements in the
module expand in a substantially uniform manner. In another
variation, the articulating mechanism may include a release, such
that actuation of the release permits sliding of the radial
elements from the second expanded diameter back to the first
collapsed diameter for possible removal of the stent. In another
variation, the stent may comprise a floating coupling element
having an articulating mechanism.
[0024] In another variation, the expandable intraluminal stent
comprises a tubular member with a clear through-lumen and a
diameter which is adjustable between at least a first collapsed
diameter and at least a second expanded diameter. The tubular
member comprises a series of sliding and locking radial elements
made from a degradable material, wherein each radial element in the
series defines a portion of the circumference of the tubular member
and wherein no radial element overlaps itself. This stent also has
at least one articulating mechanism that permits one-way sliding of
the radial elements from the first collapsed diameter to the second
expanded diameter, but inhibits radial recoil from the second
expanded diameter. The degradable material may be selected from the
group consisting of polyarylates (L-tyrosine-derived), free acid
polyarylates, polycarbonates (L-tyrosine-derived),
poly(ester-amides), poly(propylene fumarate-co-ethylene glycol)
copolymer, polyanhydride esters, polyanhydrides, polyorthoesters,
and silk-elastin polymers, calcium phosphate, magnesium alloys or
blends thereof.
[0025] In a variation to the degradable stent, the degradable
polymer may further comprise at least one bioactive agent, which is
released as the material degrades. The at least one bioactive agent
may be selected from the group consisting of antiplatelet agents,
antithrombin agents, antiproliferative agents and antiinflammatory
agents.
[0026] In another variation, the stent material may be
fiber-reinforced. The reinforcing material may be a degradable
material such as calcium phosphate (e.g., BIOGLASS). Alternatively,
the fibers may be fiberglass, graphite, or other non-degradable
material.
[0027] In another mode, the stent of the present invention
comprises a tubular member having a wall and a clear through-lumen.
The tubular member comprises a series of sliding and locking radial
elements which do not overlap with themselves. The radial elements
further comprise a ratcheting mechanism that permits one-way
sliding of the radial elements from a first collapsed diameter to a
second expanded diameter. The tubular member in this embodiment has
a stiffness of less than about 0.1 Newtons force/millimeter
deflection, and the wall of the tubular member has a thickness of
less than about 0.005 inches.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIGS. 1A-C are plan views of one module of an expandable
stent in accordance with the present invention, illustrating a
series of radial elements. The assembled module is shown in various
states, from a collapsed state (FIG. 1A), to a partially expanded
state (FIG. 1B), to an expanded state (FIG. 1C).
[0029] FIGS. 2A and 2B are schematic views of the individual radial
elements from FIGS. 1A-C. A one-rib radial element is shown in FIG.
2A and a two-rib radial element is shown in FIG. 2B.
[0030] FIG. 3 is a perspective view of a tubular member formed from
one module comprising a series of one-rib and two-rib sliding and
locking radial elements.
[0031] FIGS. 4A and 4B are plan views of another embodiment of a
module having a floating coupling element, wherein the one-rib
radial elements further comprise a frame element. The module is
shown in a collapsed state (FIG. 4A) and an expanded state (FIG.
4B).
[0032] FIG. 4C is a perspective view of a tubular member comprising
a plurality of modules shown in FIGS. 4A and 4B.
[0033] FIG. 4D is a perspective view of a tubular member comprising
a plurality of the modules shown in FIGS. 4A and 4B, wherein the
expanded diameter of adjacent modules is not the same.
[0034] FIG. 5 is a plan view of another embodiment of a module
comprising sliding and locking radial elements having two ribs each
and a frame element.
[0035] FIG. 6 is a plan view of a variation of the stent showing
the linkage of adjacent modules, each comprising alternating
one-rib and a two-rib radial elements, wherein the one-rib elements
have a frame element adapted to facilitate linkage of adjacent
modules in the circumferential axis.
[0036] FIG. 7 is a plan view of a variation of the stent showing
intermodule coupling through inter-linking of adjacent frame
elements.
[0037] FIG. 8 is a plan view of a variation of the stent showing
intermodule coupling through direct attachment of adjacent frame
elements to one another.
[0038] FIG. 9 is a perspective view of a tubular member comprising
one module in accordance with one aspect of the present
invention.
[0039] FIG. 10 is a perspective view of a tubular member comprising
a plurality of modules.
[0040] FIG. 11 is a plan view of a snap-together variation of the
module design, having a floating coupling element and frame
elements on the one-rib radial elements.
[0041] FIGS. 12A-C are perspective views showing the steps in
forming a biased or chamfered stop.
[0042] FIGS. 13A and 13B show a releasable articulating mechanism
in accordance with a collapsible variation of the present stent. An
exploded view of the components of the releasable articulating
mechanism is shown in FIG. 13A. A perspective view of several
releasable articulating mechanisms positioned on a module are shown
in FIG. 13B.
[0043] FIGS. 14A and 14B show comparative longitudinal flexibility
data for undeployed mounted (collapsed diameter) stents (FIG. 14A)
and for deployed (expanded diameter) stents (FIG. 14B).
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0044] Stent Design
[0045] The present invention relates to a radially expandable stent
used to open, or to expand a targeted area in a body lumen. In one
preferred embodiment of the present invention, the assembled stent
comprises a tubular member having a length in the longitudinal axis
and a diameter in the radial axis, of appropriate size to be
inserted into the body lumen. The length and diameter of the
tubular member may vary considerably for deployment in different
selected target lumens depending on the number and configuration of
the structural components, described below. The tubular member is
adjustable from at least a first collapsed diameter to at least a
second expanded diameter. One or more stops and engaging elements
or tabs are incorporated into the structural components of the
tubular member whereby recoil (i.e., collapse from an expanded
diameter to a more collapsed diameter) is minimized to less than
about 5%.
[0046] The tubular member in accordance with the present invention
has a "clear through-lumen," which is defined as having no
structural elements protruding into the lumen in either the
collapsed or expanded diameters. Further, the tubular member has
smooth marginal edges to minimize the trauma of edge effects. The
tubular member is preferably thin-walled (wall thickness depending
on the selected materials ranging from less than about 0.006 inches
for plastic and degradable materials to less than about 0.002
inches for metal materials) and flexible to facilitate delivery to
small vessels and through tortuous vasculature. The thin walled
design will also minimize blood turbulence and thus risk of
thrombosis. The thin profile of the deployed tubular member in
accordance with the present invention also facilitates more rapid
endothelialization of the stent.
[0047] The wall of the tubular member comprises at least one
module, which consists of a series of sliding and locking radial
elements. Preferably, a plurality of modules are connected in the
longitudinal axis via linkage elements which couple at least some
of the radial elements between adjacent modules. The radial
elements are configured within each module so as to define the
circumference of the tubular member. Each radial element within a
module is preferably a discrete, unitary structure, comprising one
or more circumferential ribs bowed in the radial axis to form a
fraction of the total circumference of the tubular member. The
radial elements within a module are preferably assembled so that
all of the circumferential ribs are substantially parallel to one
another. At least one of the ribs in each radial element has one or
more stops disposed along the length of the rib. At least some of
the radial elements also have at least one articulating mechanism
for slideably engaging the rib(s) from adjacent, circumferentially
offset radial elements. In one aspect of the present invention, the
articulating mechanism includes a tab for engaging the stops
disposed along the slideably engaged adjacent rib. The articulation
between the tab from one radial element and the stops from an
adjacent radial element is such that a locking or ratcheting
mechanism is formed, whereby the adjacent radial elements may slide
circumferentially apart from one another, but are substantially
prevented from sliding circumferentially toward one another.
Accordingly, the tubular member may be radially expanded from a
smaller diameter to a larger diameter, but recoil to a smaller
diameter is minimized by the locking mechanism. The amount of
recoil can be customized for the application by adjusting the size
and the spacing between the stops along the ribs. Preferably, the
recoil is less than about 5%.
[0048] Some aspects of the present stents are disclosed in U.S.
Pat. No. 6,033,436 issued to Steinke, and co-pending U.S.
application Ser. No. 09/283,800. The disclosures of which are
hereby incorporated in their entirety by reference thereto.
[0049] Referring to FIGS. 1A-C, a plan view of one module 10 is
illustrated comprising a series of sliding and locking radial
elements 20 in accordance with one embodiment of the present
invention. The pictured module is shown in a two-dimensional, flat
plane. Each radial element has one or more elongated ribs 22 (in
the vertical axis) with a generally perpendicular end portion 24
(in the horizontal axis), permanently affixed to each end of each
rib. Each rib has at least one stop 30. The radial elements in the
module alternate from a one-rib configuration 20' to a two-rib
configuration 20". The illustrated one-rib configuration 20' has a
single rib 22 with a plurality of stops 30, whereas the illustrated
two-rib configuration 20" has two ribs, each with a plurality of
stops 30. The radial elements in accordance with the invention
could have different numbers of circumferential ribs 22, however,
vertically adjacent radial elements preferably alternate between an
odd-numbered rib configuration and an even-numbered rib
configuration, as illustrated in FIGS. 1A-C.
[0050] The odd-even alternation in adjacent radial elements
facilitates nesting of the circumferential ribs 22 within a module,
while maintaining a constant width (w). However, if the radial
elements are configured differently, e.g., in a parallelogram shape
as opposed to a rectangular shape, wherein the ribs exhibit a
non-circumferential orientation, then changes in the longitudinal
length of the module would be expected upon expansion of the
tubular member. Such variations are encompassed within the present
invention.
[0051] With reference to FIGS. 1A-C, some of the end portions 24 of
the radial elements 20 in the illustrated design are depicted with
articulating mechanisms 34 each comprising a slot 36 for slidably
engaging a rib from a vertically adjacent radial element and a tab
32 for engaging the stops 30 in the slidably engaged rib. The end
portions 24 of the one-rib radial elements 20' are generally
adapted to articulate with each rib 22 from the slideably engaged,
vertically adjacent two-rib radial element 20". The end portions 24
of the two-rib radial elements 20" are generally adapted to
articulate with the single rib 22 of the slideably engaged,
vertically adjacent one-rib radial element 20'. The articulating
mechanism is shown in greater detail in FIGS. 2A and 2B. The stops
30 may be evenly distributed along the entire length (as shown on
the second radial element from the bottom), or the stops may be
distributed unevenly along the ribs (as shown in the upper most
radial element).
[0052] The articulation between the tab 32 from one radial element
and the stops 30 from an adjacent radial element creates a locking
or ratcheting mechanism, such that only one-way sliding (expansion)
can take place. Accordingly, the series of radial elements in plan
view, as shown in FIGS. 1A-C, is adjustable from a collapsed state,
as shown in FIG. 1A, to a partially expanded state, as shown in
FIG. 1B, to a fully expanded state, as shown in FIG. 1C. Expansion
of the module 10 in plan view may be accomplished by application of
opposing forces (arrows). The nested, sliding and locking radial
elements 20 slide apart from one another, thereby increasing the
height (h) of the series in the vertical axis, with no change in
the width (w) of the series in the horizontal axis. The locking
mechanism formed by the articulation between the tab 32 and the
individual stops 30 prevents the expanded series from recoiling
back to a more collapsed height.
[0053] When the module 10 is rolled to form a tubular member, a
slideable articulation may be made between the end portion on the
radial element on top of the module and the rib from the radial
element on the bottom of the module. Likewise, a slideable
articulation may also be made between the end portion on the radial
element on the bottom of the module and the two ribs from the
radial element on top of the module. In a variation, after rolling
to form a tubular member, the top and bottom end portions can be
connected to one another by a variety of fastening means known in
the art, including welding, adhesive bonding, mechanical or snap
fit mechanism, etc. In other modes, specialized structural elements
may be included to facilitate coupling of the top and bottom
portions of the rolled module. Examples, of specialized
circumferential coupling elements are detailed below with reference
to FIGS. 4A and 4B.
[0054] With reference to FIGS. 2A and 2B, individual one-rib 20'
and two-rib 20" radial elements, respectively, are shown
unassembled in greater detail. Both the one-rib radial element 20'
in FIG. 2A and the two-rib 20" radial element in FIG. 2B have at
least one circumferential rib 22 and an end portion 24 on each end
of the rib. The rib has one or more stops 30 disposed along the
length of the rib 22. One end of each of the illustrated radial
elements includes an articulating mechanism 34 comprising a tab 32
and a slot 36. Also illustrated in FIGS. 2A and 2B are linkage
elements 40, which extend laterally from an end portion 24 of a
radial element. These linkage elements 40 are used to couple radial
elements between adjacent modules. The linkage elements may extend
from either or both end portions 24 of either the one-rib 20' or
two-rib 20" radial elements. In one preferred mode (as
illustrated), the linkage elements 40 extend off of both end
portions 24 of a one-rib radial element 20'. The configuration and
angle of the linkage elements may vary substantially depending on
the desired linkage distance between modules and the desired
flexibility and surface area coverage of the stent.
[0055] A tubular member formed from a single module 10 comprising
four one-rib radial elements 20' and four two-rib radial elements
20", similar to the plan view described with reference to FIGS.
1A-D and FIGS. 2A-B, is shown in FIG. 3. The radial elements that
form the wall of the tubular member alternate between radial
elements having odd and even-numbers of circumferential ribs 22.
Each rib in the illustrated module has one or more stops 30. An
articulating mechanism (shown in greater detail in FIGS. 2A and
2B), has a tab 32 that engages the stops and prevents the tubular
member from collapsing to a smaller diameter. Each radial element
forms a portion of the total circumference of the tubular member
(in this case 1/8 of the circumference). Preferably, the total
number of radial elements that comprise a module varies between
about 2 and 12. More preferably, the number of radial elements is
between 4 and 8 radial elements. Linkage elements 40 are shown
extending laterally away from the module on both sides. The linkage
elements 40 are for coupling the module to similar modules to
create a tubular member with a greater longitudinal length.
[0056] A variation of the basic module design described above with
reference to FIGS. 1A-D and FIGS. 2A-B is shown in FIGS. 4A and 4B.
The module is illustrated in plan view in both a collapsed state
(FIG. 4A) and an expanded state (FIG. 4B). In this variation of the
stent, similar to the earlier design, a module 110 comprises a
series of sliding and locking radial elements 120. Each radial
element has one or more elongated ribs 122 (in the vertical axis)
with a substantially perpendicular end portion 124 (in the
horizontal axis), permanently affixed to each end of each rib. Each
rib has one or more stops 130. The radial elements in the module
alternate from a one-rib configuration 120' to a two-rib
configuration 120". The one-rib configuration 120' has a single rib
122 with one or more stops 130, whereas the two-rib configuration
120" has two ribs, each with one or more stops 130.
[0057] Like the previously described module, the odd-even
alternation in adjacent radial elements facilitates nesting of the
circumferential ribs 122 within a module, while maintaining a
constant width (w). Some of the end portions 124 of the radial
elements 120 in the illustrated design are depicted with
articulating mechanisms 134 each comprising a slot 136 for slidably
engaging a rib from a vertically adjacent radial element and a tab
132 for engaging the stops 130 in the slidably engaged rib. The
feathered edges 138 of the articulating mechanisms 134 shown in
FIGS. 4A and 4B indicate where the articulating mechanism has been
welded onto the end portions 124 of the respective radial elements,
thereby creating the slot 136 through which the engaged rib can
slide. The end portions 124 of the one-rib radial elements 120' are
generally adapted to articulate with each rib 122 from the
slideably engaged, vertically adjacent two-rib radial element 120".
The end portions 124 of the two-rib radial elements 120" are
generally adapted to articulate with the single rib 122 of the
slideably engaged, vertically adjacent one-rib radial element 120'.
The stops 130 may be evenly distributed along the entire length (as
shown), or the stops may be distributed unevenly along the ribs, or
there may be only a single stop.
[0058] In FIGS. 4A and 4B, a bump 161 is also shown on the one-rib
radial elements 120". These bumps can be incorporated along the
length of the rib(s) in order to provide a temporary stop. During
expansion, the rib with the bump 161 temporarily stops sliding when
the bump 161 enters the slot 136 of the articulating mechanism 138.
This temporary stop allows other elements to fully expand before
the temporary stop is overcome by additional radial expansion
force. The incorporation of one or more of these bumps in a module
facilitates uniform expansion of the radial elements within the
module. In addition or in the alternative to the temporary stop
created by the bump 161, some elements may have only one stop so
that this element is expanded first to the stop, with the other
elements having multiple stops providing preferred expansion
steps.
[0059] The articulation between the tab 132 from one radial element
and the stops 130 from an adjacent radial element creates a locking
or ratcheting mechanism, such that only one-way sliding (expansion)
can take place. The nested, sliding and locking radial elements 120
slide apart from one another, thereby increasing the height of the
series in the vertical axis, with no change in the width of the
series in the horizontal axis. The locking mechanism formed by the
articulation between the tab 132 and the individual stop(s) 130
prevents the expanded series from recoiling back to a more
collapsed height.
[0060] The module 110 shown in FIGS. 4A and 4B includes a floating
coupling element 150 which is shaped like the end portion 124 of a
two-rib radial element 120", having one articulating mechanism 134
adapted to slideably engage the circumferential rib 122 of a
one-rib radial element 120'. In variations to the depicted
embodiment, the floating coupling element may be adapted to float
over more than one rib in radial elements having two or more
circumferential ribs. The coupling element 150 is also adapted to
couple with the end portion 124 of the top radial element 121 in
the series. Both the coupling element 150 and the end portion 124
on the top radial element 121 are configured so as to have coupling
arms 152 and 154, and 152' and 154', which may exhibit a
complimentary configuration as illustrated.
[0061] Another specialization illustrated in FIGS. 4A and 4B, are
frame elements 160 from which linkage elements 140 extend laterally
away from the frame elements 160. In the module depicted in FIGS.
4A and 4B, the frame elements 160 are only employed on the one-rib
radial elements 120'. The frame elements are shown attached to and
extending between the end portions 124 of the one-rib radial
elements 120', so that the circumferential rib 122 is surrounded,
or framed, by the end portions 124 and frame elements 160. The use
of frame elements to facilitate coupling between adjacent modules
has several advantages. The frame elements contribute additional
physical support to the vessel wall. Larger surface area of the
individual elements may be desirable in some instances, first to
provide greater support for the surrounding lumen, and second the
larger surface area provides a larger carrier for site-directed
introduction of biologically active agents (discussed below).
Alternatively, a smaller surface can be configured to minimize
impact of the stent material on the vessel wall, for example, by
using narrower ribs and frame elements. By suspending the linkage
elements 140 laterally outward from the radial elements, the frame
elements minimize the length of the linkage elements 140 that will
be necessary to couple adjacent modules, while separating the
sliding ribs from one module from those of the adjacent module.
Coupling of the linkage elements 140 in adjacent modules provides
for a very flexible stent. The flexure is also carried to the frame
element 160, allowing much larger movement, and thus, increased
flexibility. In variations to this mode, the frame elements can be
employed in radial elements have more than one rib. See e.g., FIG.
5, showing a module design comprising a series of two-rib radial
elements, each having frame elements.
[0062] With reference to FIG. 5, a variation of odd-even radial
elements is shown, wherein each of the two illustrated radial
elements 220 have two circumferential ribs 222 and two articulating
mechanisms 234 disposed on at least one of the end portions 224 of
the radial elements and comprising a tab 232 and a slot 236. As in
previous modes of the present invention, the circumferential ribs
may have a plurality of stops 230 disposed along the length of the
rib. Each of the radial elements has a frame element 260, which is
substantially rectangular in shape (linkage elements are not
shown). The frame element may be any shape consistent with the
function of surrounding the ribs and providing a connection point
for coupling the radial elements from one module to those from an
adjacent module. Preferably the frame elements permit nesting of
the ribs in both collapsed and expanded states, without overlapping
stent components, which would increase the thickness of the
stent.
[0063] The shape of the frame elements can be varied to cause
circumferential off-setting of the different radial elements having
odd and even-numbers of ribs. For example, with reference to FIG.
6, the lateral coupling of one pair of radial elements (a one-rib
320' and a two-rib 320" radial element) from one module are
connected by the linkage element 340 to another pair of radial
elements from an adjacent module. The frame elements 360 are shown
in this embodiment surrounding only the one-rib radial elements
320'. The frame elements 360 are configured so as to promote
nesting (and not overlap) of ribs 322 and frame elements 360,
minimize the lateral space between the modules, and facilitate
linkage by a circumferentially, rather than longitudinally,
oriented linkage element 340, thereby maximizing the
circumferential scaffolding and radial support.
[0064] With reference to FIG. 7, there is illustrated a variation
in the coupling mechanism between adjacent modules. No separate
linking elements are employed. Instead, the frame elements 360 from
adjacent modules may be assembled by weaving so as to inter-link
with one another as shown. This coupling between adjacent modules
allows much greater stent flexibility.
[0065] With reference to FIG. 8, there is illustrated another
variation in the coupling mechanism between adjacent modules. No
separate linking elements are employed. Instead, the frame elements
360 from adjacent modules are directly joined to one another as
shown. The frame elements from adjacent modules may attached by any
means suitable for the material, e.g., welding, etc. In one
embodiment, frame elements from adjacent modules may be constructed
(e.g., cut out) from a single piece of material. This direct
coupling of frame elements from adjacent modules tends to produce a
stent with greater axial strength.
[0066] A variety of different articulating mechanisms and stops are
encompassed within the present invention; including but not limited
to the slot and tab designs disclosed herein and illustrated in
FIGS. 1-8, as well as those disclosed in the parent case, now U.S.
Pat. No. 6,033,436 to Steinke, which is incorporated herein in its
entirety by reference thereto.
[0067] It will be appreciated by those skilled in the art that the
basic module design of a series of sliding and locking radial
elements provides the manufacturer with a great deal of flexibility
with regard to the collapsed and expanded diameters of the stent as
well as the longitudinal length. Increased expanded diameter and
expansion ratio can be achieved by increasing the number of radial
elements within each module. Increased longitudinal length can be
achieved by increasing the number of modules that are linked to
form the tubular member (from one module as shown in FIG. 9 to six
modules as shown in FIG. 10).
[0068] With reference to FIG. 9, a tubular member having only one
module 410 comprising a series of four radial elements (two one-rib
radial elements 420' and two two-rib radial elements 420"). In the
pictured module 410, no specialized coupling element, like the
floating coupling element described with respect to FIGS. 4A and 4B
is employed, although such a coupling element could be used in this
module without departing from the basic design. The illustrated
frame elements 460 have a rectangular shape and surround only the
one-rib radial elements 420'. The module shown in FIG. 9 is in an
expanded state and is subject to only minimum recoil or collapse
(<about 5%) because of the ratcheting effect created by the
articulation between a tab 432 on the articulating mechanism 434 of
one radial element and a stop 430 on the slideably engaged rib 422
from the adjacent radial element. The articulating mechanism is
shown as a separate structural element that has been affixed, e.g.,
by welding, to the end portion 424 of the respective radial
element, thereby entrapping and slideably engaging the rib(s) from
the adjacent radial element.
[0069] In FIG. 10, a stent in accordance with the present invention
is shown, comprising a tubular member 500 having six modules 510
which are linked in the longitudinal axis (for clarity, linkage
elements extending between the frame elements in adjacent modules
are not shown).
[0070] In another variation of the present invention, a series of
radial elements are illustrated in FIG. 11, wherein the
articulating mechanism is formed by a tab 632 in a one-way locking
slot 633. This design eliminates the need to attach an overlapping
articulating mechanism, e.g., by welding, to entrap and slideably
engage a circumferential rib from an adjacent radial element. As
shown in FIG. 11, an entry slot 631 is provided at one end of the
central locking slot 633, which is disposed along at least a
portion of the length of each rib in each radial element. The entry
slot 631 is adapted to permit a tab 632 on the end portion 624 of
one radial element 620 to fit into and engage the locking slot 633
in the rib. Once the tab(s) 632 is placed through the entry slot(s)
631 the radial elements 620 can be slid apart enough to prevent the
tab 632 from coming back out of the entry slot 631. The locking
slot 633 is adapted to allow the tab to slide through the slot in
only one direction (to a more expanded configuration). For example,
as illustrated, the locking slot 633 has a series of serrated
notches or stops 630, which are offset on both sides of the slot
and which permit the tab 632 to move through the slot 633 in one
direction, but which are shaped so as to engage the tab and prevent
it from moving through the slot in the opposite direction, i.e.,
prevent collapse of the expanded stent. Any of a variety of locking
slot and stop configurations are encompassed within this
snap-together design. Some alternative locking slot and stop
configurations are disclosed in the parent application, now U.S.
Pat. No. 6,033,436 to Steinke.
[0071] The weldless design module illustrated in FIG. 11 is shown
with framing elements 660 with linkage elements 640 around the
one-rib radial elements and a floating coupling element 650 with
coupling arms 652 and 654 for mating with complementary coupling
arms 652' and 654' on the end portion 624 of the top radial element
in the series. Because the intermodule coupling can be made to the
frame elements this increased length allows the stent to be very
flexible both in the collapsed and expanded states.
[0072] Another variation of the present invention includes varying
the articulating mechanism and rib configurations so as to produce
increasing friction with progressive expansion. This variation may
facilitate uniform expansion of all radial elements within a
module.
[0073] In another variation of the present stent, different modules
within the stent may exhibit different expanded diameters, such
that the stent may be adjustable to different luminal states along
the length of the stent. Accordingly, the stent may exhibit a
tapered configuration in its deployed state, having a larger
diameter at one end with progressive or step-wise decreases in
modular expanded diameter moving toward the other end of the
stent.
[0074] It will be appreciated by those of skill in the art that the
interlocking and sliding radial element design of the present
invention provides the manufacturer with substantial flexibility in
customizing the stent for different applications. Because overlap
of stent components is minimized by the nesting of ribs and frame
elements, the collapsed profile can be very thin without
compromising radial strength. Moreover, the degree of overlap does
not change substantially during expansion, unlike jelly-roll
designs which expand by unraveling of a rolled sheet. Furthermore,
the deployment flexibility of the present stent can be customized
by changing the length, configuration and number of lateral linkage
elements employed. Thus, a very flexible and ultra-thin embodiment
of the present stent is deemed to be uniquely suited for deployment
in small and difficult to reach vessels, such as the intercranial
vessels distal to the carotids and the remote coronary vessels.
[0075] In another variation, the stent may be used in combination
with a covering or sheath to provide a vessel graft, for example,
in the treatment of an aneurysm. Materials and methods of making
vessel grafts (stent and sheath) incorporating the present stent
design are described in detail below.
[0076] In another variation of the present invention, the stops
that are disposed along an elongate rib may be shaped so as to
facilitate locking of the tab from the articulating member within
the stop, wherein the shape of the hole is adapted to provide a
channel which will have a bias for capturing parts (i.e., a tab)
sliding past it. With reference to FIGS. 12A-C, there are
illustrated the steps in forming one embodiment of such a stop. In
FIG. 12A, the stent component 700 can be etched from the top 700'
and bottom 700" surfaces. The top and bottom surfaces are coated or
masked in some areas 702' and 702", respectively, with a layer that
resists etching (e.g., by chemical, laser, etc.), leaving uncoated
areas 704' and 704" on the top and bottom, respectively,
susceptible to etching. The uncoated areas are offset by a distance
706, which allows some overlap 708 between the top and bottom
uncoated areas 704' and 704". As illustrated in FIG. 12B, during
the etching process wherein stent material is removed, the uncoated
areas 704' and 704" become cavities 710 extending through the stent
material. At some point during the etching process, as shown in
FIG. 12C, the cavities meet in the overlap area 708 and create a
through hole or channel 712. The stop thus formed has a chamfered
edge that is biased for capturing a tab as it slides over the
stop.
[0077] In another embodiment of the present stent, the locking
mechanism may be designed to be releasable, wherein the stent may
be collapsed for removal from the body lumen. Whereas the other
configurations in this disclosure are designed for permanent
locking of the members in the expanded state, there may be a need
for a reversible, or unlocking mechanism. The components of one
possible release mechanism are illustrated in exploded view in FIG.
13A. Most aspects of the stent in accordance with the present
invention remain as described in preceding sections. However, the
articulating mechanism 1034 is altered to be releasable. The tab
1032 is preformed or biased (as a result of its springy material
and/or angle of deployment) not to lockably engage the individual
stops 1030. Instead, a moveable slider 1080 and retainer plate 1090
are positioned over the tab 1032 to deflect the tab downward into
the individual stops. The shape of tab 1032 which is deflected
against the rib 1022 by the slider 1080 and retainer plate 1090
provides locking of rib 1022 against one direction of travel
(collapse) while allowing travel in the opposite direction
(expansion). The slider 1080 has a wide area 1082 that provides the
structural interference to flex tab 1032 into the locking position.
When the wide region 1082 is positioned between retainer 1090 and
tab 1032 the tab is forced against the slideably engaged rib 1022
and into the passing stops 1030 as the rib slides through the
articulating mechanism. The slider 1080 also has a narrow region
1084 that will permit tab 1032 to relax and pull out of the stop
1030. By pulling the slider 1080 outward from the perpendicular
plane of the ribs 1020 the narrow region 1084 is repositioned over
the tab 1032, thereby allowing the tab to disengage from the stop
1030 and spring back upward against the retainer plate 1090.
[0078] With reference to FIG. 13B there is illustrated a partial
view of a module having one-rib and two-rib radial elements and
releasable articulating mechanisms 1034. The releasable
articulating mechanisms on the one-rib radial element are shown
engaging the two ribs from the adjacent two-rib radial element. The
slider may be modified on this releasable articulating mechanism to
have two narrow regions for releasing both tabs by pulling the one
side of the slider.
[0079] Stent Manufacture
[0080] Preferred materials for the making the stents of the present
invention include 316 stainless steel, tantalum, titanium,
tungsten, gold, platium, iridium, rhodium and alloys thereof. Also
shape memory alloys such as Nitinol may be used in accordance with
the present invention. Preferably, sheets are work-hardened prior
to forming of the individual stent elements to increase strength.
Methods of work hardening are well known in the art. Sheets are
rolled under tension, annealed under heat and then re-worked. This
may be continued until the desired modulus of hardness is obtained.
Most stents in commercial use today employ 0% to 10% work hardened
material in order to allow for "softer" material to deform to a
larger diameter. In contrast, because expansion of the sliding and
locking radial elements in accordance with the present invention
depends on sliding rather than material deformation, it is
preferred to use harder materials, preferably in the range of about
25-95% work hardened material to allow for thinner stent thickness.
More preferably, the stent materials are 50-90% work hardened and
most preferably, the materials are 80-85% work hardened.
[0081] Preferred methods of forming the individual elements from
the metal sheets may be laser cutting, laser ablation, die-cutting,
chemical etching, plasma etching or other methods known in the art
which are capable of producing high-resolution components. The
method of manufacture, in some embodiments, depends on the material
used to form the stent. Chemical etching provides high-resolution
components at relatively low price, particularly in comparison to
high cost of competitive product laser cutting. Tack-welding,
adhesives, mechanical attachment (snap-together), and other
art-recognized methods of attachment, may be used to fasten the
individual elements. Some methods allow for different front and
back etch artwork, which could result in chamfered edges, which may
be desirable to help improve engagements of lockouts.
[0082] In one preferred mode of the present invention, the stent is
made, at least in part, from a polymeric material, which may be
degradable. The motivation for using a degradable stent is that the
mechanical support of a stent may only be necessary for several
weeks after angioplasty, particularly if it also controls
restenosis and thrombosis by delivering pharmacologic agents.
Degradable polymeric stent materials are well suited for drug
delivery.
[0083] It is believed that there is a need for short-term
intervention since the majority of cardiac events occur in the
first 6 months, including in-stent restenosis. The permanency of
metal stents presents long-term risks and complications. With long
lesions and full coverage, metal stents can also preclude surgical
re-intervention. The ideal implant: (1) mimics the tissue it is
designed to replace in size, shape, and material consistency; (2)
neither is disposed to infection nor evokes a foreign body
response; (3) is a temporary prosthesis that takes on
characteristics of the natural tissue as it disappears; and (4) is
a biocompatible implant that has a smooth surface to minimize the
risk for thrombus formation and macrophage enzyme activity.
[0084] Degradable stents have the potential to perform more like an
ideal implant. Degradable stents that integrate seamlessly with the
living host tissue may improve tissue biocompatibility due to their
temporary residence. With the initial strength to secure the
diseased tissue, such stents may eliminate the concern for product
migration over time and long-term product failure. They may also
minimize time, costs, and complications associated with
re-intervention of specific and neighboring sites. Degradable
stents have a clear advantage over metal stents in that they can
dose the diseased tissue with a drug; compared to drug coated metal
stents, degradable stents can dose the tissue over a longer period
of time.
[0085] Unlike restenosis after angioplasty, in-stent restenosis is
a consequence almost entirely of tissue hyperplasia, occurring
principally at the points where the stent's struts impinge upon the
artery wall. Placement of an excessively stiff stent against the
compliant vessel creates a mismatch in mechanical behavior that
results in continuous lateral expansile stress on the arterial
wall. This stress can promote thrombosis, arterial wall thinning,
or excessive cellular proliferation. Hence, polymeric biomaterials,
which are more flexible, may minimize the pathology and are more
likely to approximate the mechanical profile of the native
tissue.
[0086] The intact internal elastic lamina (IEL) of a healthy artery
serves as an effective barrier to (1) protect the underlying smooth
muscle cells (SMC) from exposure to mitogens that induce
hyperplasia, and (2) prevent exposure to monocytes or lipid-filled
macrophages and circulating elastin peptides that promote hard
plaque formation and narrowing of the artery. A biomaterial stent
may minimize progression of disease states by mimicking the barrier
functions of the IEL: (1) by delivering a cell-cycle inhibitor to
counteract the affects of mitogens, and (2) by serving as a
temporary physical barrier to the trafficking immune cells.
[0087] In the natural disease states, arteriostenosis and
atherosclerosis, arteries can have a compromised or structurally
discontinuous IEL. The cause of the discontinuity is largely
unknown. Elastases, circulating elastin peptides, and elastin
receptors may play a pivotal role along with denudation of the
endothelium. A biomaterial stent that does not grossly over expand
the vessel wall may minimize the risk for further perforation of
the IEL. In addition the stent surface can serve as an anchorage
site for formation of an endothelial lining, the gatekeeper to
blood elements and circulating molecules.
[0088] In one mode of the degradable stent of the present
invention, the stent matrix may be formulated so as to release a
pharmacologic agent. Mechanical treatment of diseased vessels by
angioplasty and stenting can further damage the arterial wall.
Ironically, each of these practices can promote thrombus formation
and restenosis associated with reocclusion within 6- to 24-months
post-operatively. These inadequate clinical outcomes are the
impetus for development of many counteractive therapies. Some new
treatments for restenosis are use of radioisotopes, Paclitaxel and
Rapamycin all of which inhibit vascular cell proliferation.
[0089] It is estimated that pharmacological interventions for
restenosis need to occur continuously for 2-4 weeks following
angioplasty or stent implantation. It is also estimated that a
polymer stent can deliver a drug dose that is ten times higher than
systemic delivery. If a cell cycle inhibitor was released from a
degradable stent, we may achieve optimal long-term patency in the
diseased vessel.
[0090] Degradable biomaterial stents may improve the long-term
product safety and efficacy for the patients. We believe that a
completely degradable, drug-eluting stent that resides in the
vessel for several weeks after deployment will be effective in
controlling restenosis. Accordingly, the present invention
encompasses stents having the sliding and locking geometry
described above, wherein the stent components are made from a
functional biomaterial.
[0091] The mechanical properties of the degradable biomaterial are
selected in accordance with the present invention to exhibit at
least one, and preferably more, of the following characteristics:
(1) resist failure due to the multiaxial stress-strain behavior of
native arteries and exceeds that of annealed metals, which are
known to fail for stent applications; (2) retain mechanical
strength during several weeks or months post-deployment; (3)
degrade via hydrolytic or enzymatic degradation preferably with
surface erosion whereby the implant degrades uniformly and
maintains its original shape as it degrades; (4) maintains
favorable hemodynamics; (5) exhibits a hydrophilic, negatively
charged, smooth and uniform surface with a low critical surface
tension; (6) supports endothelialization; (7) is nontoxic and
eliminated from the body safely, i.e., no systemic effects; and (8)
includes an anti-restenosis pharmacological agent. The
pharmacologic agent may be a cell-cycle inhibitor that inhibits SMC
proliferation, allows for favorable early and late remodeling, and
that is stable in the biomaterial. The degradable biomaterial and
pharmacologic agent preferably provide dosing of the lesion for
about three to four weeks or through the degradation cycle of
stent.
[0092] Degradable plastic or natural (animal, plant or microbial)
or recombinant materials in accordance with one aspect of the
present invention may include polydepsipeptides, nylon copolymides,
conventional poly(amino acid) synthetic polymers, pseudo-poly(amino
acids), aliphatic polyesters, such as polyglycolic acid (PGA),
polylactic acid (PLA), polyalkylene succinates, polyhydroxybutyrate
(PHB), polybutylene diglycolate, and poly epsilon-caprolactone
(PCL), polydihydropyrans, polyphosphazenes, polyorthoesters,
polycyanoacrylates, polyanhydrides, polyketals, polyacetals,
poly(.alpha.-hydroxy-esters), poly(carbonates),
poly(imino-carbonates), poly(.beta.-hydroxy-esters), polypeptides,
and their chemical modifications and combinations (blends and
copolymers) and many other degradable materials known in the art.
(See e.g., Atala, A., Mooney, D. Synthetic Biodegradable Polymer
Scaffolds. 1997 Birkhauser, Boston; incorporated herein by
reference).
[0093] In one preferred mode, the degradable materials are selected
from the group consisting of poly(alkylene oxalates),
polyalkanotes, polyamides, polyaspartimic acid, polyglutarunic acid
polymer, poly-p-diaxanone (e.g., PDS from Ethicon),
polyphosphazene, and polyurethane.
[0094] In a more preferred mode, the degradable materials are
selected from the group consisting of poly(glycolide-trimethylene
carbonate); terpolymer (copolymers of glycolide, lactide or
dimethyltrimethylene carbonate); polyhydroxyalkanoates (PHA);
polyhydroxybutyrate (PHB) and poly(hydroxybutyrate-co-valerate)
(PHB-co-HV) and copolymer of same; poly(epsilon-caprolactone) and
copolymers (e.g., lactide or glycolide);
poly(epsilon-caprolactone-dimethyltrimethylene carbonate);
polyglycolic acid (PGA); and poly-L and poly-D(lactic acid) and
copolymers and additives (e.g., calcium phosphate glass) and lactic
acid/ethylene glycol copolymers.
[0095] In a most preferred mode, the degradable materials are
selected from the group consisting of polyarylates
(L-tyrosine-derived) or free acid polyarylates, polycarbonates
(L-tyrosine-derived), poly(ester-amides), poly(propylene
fumarate-co-ethylene glycol) copolymer (i.e., fumarate anhydrides),
polyanhydride esters (mechanically stronger) and polyanhydrides
(mechanically weaker), polyorthoesters, ProLastin or silk-elastin
polymers (SELP), calcium phosphate (BIOGLASS), magnesium alloys,
and a composition of PLA, PCL, PGA ester commercial polymers used
sigularly or in any mixture.
[0096] Natural polymers (biopolymers) include any protein or
peptide. These can be used in a blend or copolymer with any of the
other aforementioned degradable materials, as well as with
pharmacologic substances, or with hydrogels, or alone. Typically,
these biopolymers degrade upon the action of enzymes. Preferred
biopolymers may be selected from the group consisting of aliginate,
cellulose and ester, chitosan (NOCC and NOOC-G), collagen, cotton,
dextran, elastin, fibrin, gelatin, hyaluronic acid, hydroxyapatite,
spider silk, other polypeptides and proteins, and any combinations
thereof.
[0097] Coatings for degradable and metal stent materials may be
selected from the group consisting of hydrogels, such as:
NO-carboxymethyl chitosan (NOCC), PEG diacrylate with drug (intimal
layer) with second layer without drug (blood flow contact),
polyethylene oxide, polyvinylalcohol (PVA), PE-oxide,
polyvinylpyrolidone (PVP), polyglutarunic acid polymers, DMSO or
alcohols and any combinations thereof.
[0098] Where plastic and/or degradable materials are used, the
elements may be made using hot-stamp embossing to generate the
parts and heat-staking to attach the linkage elements and coupling
arms. Other preferred methods comprise laser ablation using a
screen, stencil or mask; solvent casting; forming by stamping,
embossing, compression molding, centripital spin casting and
molding; extrusion and cutting, three-dimensional rapid prototyping
using solid free-form fabrication technology, stereolithography,
selective laser sintering, or the like; etching techniques
comprising plasma etching; textile manufacturing methods comprising
felting, knitting, or weaving; molding techniques comprising fused
deposition modeling, injection molding, room temperature vulcanized
(RTV) molding, or silicone rubber molding; casting techniques
comprising casting with solvents, direct shell production casting,
investment casting, pressure die casting, resin injection, resin
processing electroforming, or reaction injection molding (RIM).
These parts may be connected or attached by solvent or thermal
bonding, or by mechanical attachment. Preferred methods of bonding
comprise the use of ultrasonic radiofrequency or other thermal
methods, and by solvents or adhesives or ultraviolet curing
processes or photoreactive processes. The elements may be rolled by
thermal forming, cold forming, solvent weakening forming and
evaporation, or by preforming parts before linking. Soluble
materials such as hydrogels which are hydrolized by water in blood
could also be used, for example, cross-linked poly 2-hydroxyethyl
methacrylate (PHEMA) and its copolymers, e.g., polyacrylamide, and
polyvinyl alcohol.
[0099] The addition of radiopacifiers (i.e., radiopaque materials)
to facilitate tracking and positioning of the stent could be added
in any fabrication method or absorbed into or sprayed onto the
surface of part or all of the implant. The degree of radiopacity
contrast can be altered by implant content. Radiopacity may be
imparted by covalently binding iodine to the polymer monomeric
building blocks of the elements of the implant. Common radiopaque
materials include barium sulfate, bismuth subcarbonate, and
zirconium dioxide. Other radiopaque elements include: cadmium,
tungsten, gold, tantalum, bismuth, platium, iridium, and rhodium.
In one preferred embodiment, iodine may be employed for its
radiopacity and antimicrobial properties. Radiopacity is typically
determined by fluoroscope or x-ray film.
[0100] The stents in accordance with the present invention, may
also be useful in vessel grafts, wherein the stent is covered with
a sheath formed from either a polymeric material, such as expanded
PTFE, degradable polymers, or a natural material, such as fibrin,
pericardial tissue, or their derivatives, as will be known to those
of skill in the art. The covering may be attached to the inner or
outer surface of the stent. Alternatively, the stent may be
embedded within layers of the covering material.
[0101] Once the stent components have been cut out and assembled
into flat modules (see plan views described with respect to FIGS.
1, 2, 4-8, and 11), and linkage elements between adjacent modules
have been connected (e.g., by welding, inter-weaving frame
elements, etc.), the flat sheets of material are rolled to form a
tubular member. Coupling arms from floating coupling elements and
end portions are joined (e.g., by welding) to maintain the tubular
shape. In embodiments that do not include coupling elements, the
end portions of the top and bottom radial elements in a module may
be joined. Alternatively, where sliding is desired throughout the
entire circumference, a sliding and locking articulation can be
made between the end portion of the top radial element and the
rib(s) of the bottom radial element (e.g., by tack-welding,
heat-staking or snap-together). Similarly, a corresponding
articulation can be made between the end portion of the bottom
radial element and the rib(s) of the top radial element.
[0102] Rolling of the module(s) to form a tubular member can be
accomplished by any means known in the art, including rolling
between two plates, which are each padded on the side in contact
with the stent elements. One plate is held immobile and the other
can move laterally with respect to the other. Thus, the stent
elements sandwiched between the plates may be rolled about a
mandrel by the movement of the plates relative to one another.
Alternatively, 3-way spindle methods known in the art may also be
used to roll the tubular member. Other rolling methods that may be
used in accordance with the present invention include those used
for "jelly-roll" designs, as disclosed for example, in U.S. Pat.
Nos. 5,421,955, 5,441,515, 5,618,299, 5,443,500, 5,649,977,
5,643,314 and 5,735,872; the disclosures of which are incorporated
herein in their entireties by reference thereto.
[0103] The construction of the stent in this fashion provides a
great deal of benefit over the prior art. The construction of the
locking mechanism is largely material-independent. This allows the
structure of the stent to comprise high strength materials, not
possible with designs that require deformation of the material to
complete the locking mechanism. The incorporation of these
materials will allow the thickness required of the material to
decrease, while retaining the strength characteristics of thicker
stents. In preferred embodiments, the frequency of locking holes or
stops present on selected circumferential ribs prevents unnecessary
recoil of the stent subsequent to expansion.
[0104] Drugs Incorporated into Stents
[0105] Drugs and other bioactive compounds can be incorporated into
the degradable matrices themselves or coated on the non-degradable
stent materials, thereby providing sustained release of such
compounds at the site of the stent. In addition, degradable
biomaterial can be fabricated in a various forms and processed into
the stent components. Preferred biomaterials would incorporate a
pharmaceutical agent blended with the degradable polymer prior to
fabricating the stent. The preferred pharmaceutical agent(s)
control restenosis (including neointimal thickening, intimal
hyperplasia and in-stent restenosis or limits vascular smooth
muscle cell overgrowth in the lumen of a stented vessel. Other body
applications may require different drugs.
[0106] In a another aspect of the present invention, the stent
biomaterial may also incorporate a hydrogel that acts to prevent
adhesions of blood cells, extracellular matrix or other cell types.
For instance, NOCC and NOCC-G chitosan. In another aspect, the
pharmaceutical agents or hydrogels can be coated onto the surface
of the biomaterial singularly or in mixtures or in combination with
other binders required to adhere or absorb the pharmaceutical or
hydrogel to the biomaterial surface. In addition or in the
alternative, the pharmaceutical or hydrogel or genetic material may
be incorporated with the biomaterial polymer, microspheres, or
hydrogel.
[0107] Use of synthetic, natural (plant, microbial, viral or
animal-derived) and recombinant forms having selected functions or
chemical properties can be mixed with complementary substances
(e.g., anti-thrombotic and anti-restenosis substances; nucleic
acids and lipid complexes). Pharmacologic agents may also
incorporate use of vitamins or minerals. For instance, those that
function directly or indirectly through interactions or mechanisms
involving amino acids, nucleic acids (DNA, RNA), proteins or
peptides (e.g., RGD peptides), carbohydrate moieties,
polysaccharides, liposomes, or other cellular components or
organelles for instance receptors and ligands.
[0108] Pharmaceutical agents may be polar or possess a net negative
or positive or neutral charge; they may be hydrophobic, hydrophilic
or zwitterionic or have a great affinity for water. Release may
occur by controlled release mechanisms, diffusion, interaction with
another agent(s) delivered by intravenous injection,
aerosolization, or orally. Release may also occur by application of
a magnetic field, an electrical field, or use of ultrasound.
[0109] The variety of compounds which may be used for coating
metallic stents or for incorporating into degradable stent
materials have been disclosed by Tanguay et al. Cardio Clin (1994)
and Nikol et al. Atherosclerosis (1996); these references are
herein incorporated in their entirety by reference thereto. These
compounds include antiplatelet agents (Table 1), antithrombin
agents (Table 2), and antiproliferative agents (Table 3). Some
preferred agents that fall within these classes of compounds are
presented in Tables 1-3 (below).
1TABLE 1 Antiplatelet Agents Compound Action Aspirin
Cyclo-oxygenase inhibition Dipyridamole Phosphodiesterase
inhibition Ticlopidine Blocks interaction between platelet
receptors, fibrinogen, and von Willebrand factors C7E3 Monoclonal
antibody to the glycoprotein IIb/IIIa receptor Integrelin
Competitive glycoprotein Iib/IIIa receptor inhibition MK-852,
MK-383 Glycoprotein IIb/IIIa receptor inhibition RO-44-9883
Glycoprotein IIb/IIIa receptor inhibition
[0110]
2TABLE 2 Antithrombin Agents Compound Action Heparin Antithrombin
III cofactor Low molecular weight Inhibition of factor Xa by
antithrombin III heparin (LMWH) R-Hirudin Selective thrombin
inhibition Hirulog Synthetic direct thrombin inhibition Argatroban,
efegatran Synthetic competitive thrombin inhibition Tick
anticoagulant Specific thrombin inhibition peptide Ppack
Irreversible thrombin inhibition
[0111] Additional anti-thrombogenic substances and formulations
include endothelium-derived relaxing factor, prostaglandin I.sub.2,
plasminogen activator inhibitor, tissue-type plasminogen activator
(tPA), ReoPro: anti-platelet glycoprotein IIb/IIIa integrin
receptor, heparin, polyamine to which dextran sulfate and heparin
are covalently bonded, heparin-containing polymer coating for
indwelling implants (MEDI-COAT by STS Biopolymers),
polyurethaneurea/heparin, hirudin/prostacyclin and analogues,
fibrin and fibrin peptide A, lipid-lowering drugs, e.g., Omega-3
fatty acids, and chrysalin (aka TRAP-508) by Chrysalis Vascular
Technologies (which is a synthetically manufactured peptide portion
of the human enzyme thrombin, responsible for blood clotting and
initiating cellular/tissue repair). Chrysalin mimics specific
attributes of thrombin by interacting with receptors on cells
involved in tissue repair.
[0112] Other anti-restenosis substances in accordance with the
present invention include INTEGRILIN.RTM. (eptifibatide) by COR
Therapeutics (blocks platelet clumping), Resten-NG (NeuGene) by AVI
BioPharma (synthetic version of C-MYC oncogene), and Implant
Sciences Corp., BiodivYsio (phosphorylcholine (PC)) by Abbott
Laboratories Inc. and Biocompatibles International PLC, Liposomal
Prostaglandin E1 by Endovasc Ltd. and Collaborative BioAlliance,
Adenovirus vectors to carry genes to vascular smooth muscle cells
(Boston Scientific Corp and CardioGene Therapeutics Inc.), TAXOL
(paclitaxel) by Bristol-Myers Squibb (prevents cell division by
promoting the assembly of and inhibiting the disassembly of
microtubules), and Rapamycin or nitric oxide. Other drugs include
ceramide, tranilast, probucol, statins, cilostazol, and low
molecular weight variations of heparin.
[0113] A variety of compounds are considered to be useful in
controlling vascular restenosis and in-stent restenosis. Some of
these preferred antiproliferative agents are presented in Table 3
(below).
3TABLE 3 Antiproliferative Agents Compound Action Angiopeptin
Somatostatin analog which inhibits IGF-I Ciprostene Prostacyclin
analog Calcium blockers Inhibition of slow calcium channels
Colchicine Antiproliferative and migration inhibition Cyclosporine
Immunosuppressive, intracellular growth signal inhibition
Cytorabine Antineoplastic, DNA synthesis inhibition Fusion proteins
Toxin-bounded growth factor Lioprost Prostacyclin analog Ketaserine
Serotonin antagonist Prednisone Steroid hormone Trapidil
Platelet-derived growth factor inhibitor (inhibitor of
thromboxane-A2 and/or PDGF receptor antagonist)
[0114] Specific therapeutic agents have also been identified which
may modulate smooth muscle cell (SMC) proliferation. Since SMC cell
proliferation has been implicated in atherosclerotic stenosis as
well as post-operative restenosis, incorporation of such agents may
be particularly useful. These include without limitation,
regulators of SMC mitosis (e.g., TAXOL, Rapamycin, or ceramide) and
stimulators and triggers for extracellular matrix production, such
as anti-FGF and TGF-.beta..sub.1 strategies, tissue inhibitor
metalloproteinases (TIMPs), and matrix metaloproteinases
(MMPs).
[0115] Various compounds address specific pathologic events and/or
vascular diseases. Some of these therapeutic target compounds are
summarized in Table 4 (below).
4TABLE 4 Specific Therapeutic Target Compounds Pathologic Event
Therapeutic Target Endothelial dysfunction Nitric oxide inducer or
antioxidants Endothelial injury Administer VEGF; FGF's Cell
activation & MEF-2 & Gax modulators; NFKB antagonists;
phenotypic modulation cell cycle inhibitors Dysregulated cell
growth E2F decoys; RB mutants; cell cycle inhibitors Dysregulated
apoptosis Bax or CPP32 inducers; Bcl-2 inhibitors; integrin
antagonists Thrombosis IIb/IIIa blockers; tissue factor inhibitors;
anti- thrombin agents Plaque rupture Metalloproteinase inhibitors;
leukocyte adhesion blockers Abnormal cell migration Integrin
antagonists: PDGF blockers; plasminogen activator inhibitors Matrix
modification Metalloproteinase inhibitors, plasminogen antagonists;
matrix protein cross-linking modifiers
[0116] The therapeutic agents to be bonded to or incorporated
within the stent materials of the present invention may be
classified in terms of their sites of action in the host. The
following agents are believed to exert their actions
extracellularly or at specific membrane receptor sites. These
include corticoids and other ion channel blockers, growth factors,
antibodies, receptor blockers, fusion toxins, extracellular matrix
proteins, peptides, or other biomolecules (e.g., hormones, lipids,
matrix metalloproteinases, and the like), radiation,
anti-inflammatory agents including cytokines such as interleukin-1
(IL-1), and tumor necrosis factor alpha (TNF-.alpha.), gamma
interferon (interferon-.gamma.), and Tranilast, which modulate the
inflammatory response.
[0117] Other groups of agents exert their effects at the plasma
membrane. These include those involved in the signal transduction
cascade, such as coupling proteins, membrane associated and
cytoplasmic protein kinases and effectors, tyrosine kinases, growth
factor receptors, and adhesion molecules (selectins and
integrins).
[0118] Some compounds are active within the cytoplasm, including
for example, heparin, ribozymes, cytoxins, antisense
oligonucleotides, and expression vectors. Other therapeutic
approaches are directed at the nucleus. These include gene
integration, proto-oncogenes, particularly those important for cell
division, nuclear proteins, cell cycle genes, and transcription
factors.
[0119] Genetic approaches to control restenosis include without
limitation: use of antisense oligonucleotides to PDGFR-.beta..beta.
mRNA to control PDGF expression; use of antisense oligonucleotides
for nuclear antigens c-myb or c-myc oncogenes (Bauters et al.,
1997, Trends CV Med); use of antisense phosphorothioate
oligodeoxynucleotides (ODN) against cdk 2 kinase (cyclin dependent
kinase) to control the cell cycle of vascular SMC (Morishita et al,
1993, Hypertension); use of VEGF gene (or VEGF itself) to stimulate
reconstructive wound healing such as endothelialization and
decrease neointima growth (Asahara et al 1995); delivery of the
nitric oxide synthetase gene (eNOS) to reduce vascular SMC
proliferation (Von Der Leyen et al., 1995, Proc Natl Acad Sci); use
of adenovirus expressing plasminogen activator inhibitor-1 (PAI-1)
to reduce vascular SMC migration and thereby diminish restenosis
(Carmeliet et al., 1997, Circulation); stimulation of
apolipoprotein A-1 (ApoA1) over-expression to rebalance serum
levels of LDL and HDL; use of apoptosis gene products to promote
cell death (of SMC) and cytotactic gene products to that regulate
cell division (tumor suppressor protein p53 and Gax homeobox gene
product to suppress ras; p21 over expression); and inhibition of
NFKB activation (e.g., p65) to control SMC proliferation (Autieri
et al., 1994, Biochem Biophys Res Commun).
[0120] Other therapeutic substances that may be useful as stent
coatings and/or depot formulations incorporated within degradable
stents include: antibodies to ICAM-1 for inhibition of monocyte
chemotactic recruitment and adhesion, macrophage adhesion and
associated events (Yasukawa et al, 1996, Circulation); toxin based
therapies such as chimeric toxins or single toxins to control
vascular SMC proliferation (Epstein et al., 1991, Circulation);
bFGF-saporin to selectively stop SMC proliferation among those
cells with a large number of FGF-2 receptors (Chen et al, 1995,
Circulation), suramin inhibits migration and proliferation by
blocking PDGF-induced and/or mitogen activated protein kinase
(MAPK-AP-1)-induced signaling (Hu et al., Circulation, 1999);
Beraprost Sodium, a chemically stable prostacyclin analogue (PG
I.sub.2), suppresses intimal thickening and lumenal narrowing of
coronary arteries. (Kurisu et al., Hiroshima J. Med Sci, 1997);
Verapamil inhibits neointimal smooth muscle cell proliferation
(Brauner et al., J Thorac Cardiovasc Surg 1997), agents that block
the CD154 or CD40 receptor may limit the progression of
atherosclerosis (E Lutgens et al., Nature Medicine 1999), agents
that control responses of shear stress response elements or
mechanical stress or strain elements or heat shock genes; and
anti-chemoattractants for SMC and inflammatory cells.
[0121] In addition or in the alternative, cells could be
encapsulated in a degradable microsphere, or mixed directly with
polymer, or hydrogel and serve as vehicle for pharmaceutical
delivery. Living cells could be used to continuously deliver
pharmaceutical type molecules, for instance, cytokines and growth
factors. Nonliving cells could also serve as a limited or timed
release system. Cells or any origin may be used in accordance with
this aspect of the present invention. Further, preserved or
dehydrated cells which retain their viability when rehydrated may
be used. Native, chemically modified (processed), and/or
genetically engineered cells may be used.
[0122] Stent Deployment
[0123] Stents can be deployed in a body lumen by means appropriate
to their design. One such method would be to fit the collapsed
stent over an inflatable element of a balloon catheter and expand
the balloon to force the stent into contact with the body lumen. As
the balloon is inflated, the problem material in the vessel is
compressed in a direction generally perpendicular to the wall of
the vessel which, consequently, dilates the vessel to facilitate
blood flow therethrough. Radial expansion of the coronary artery
occurs in several different dimensions and is related to the nature
of the plaque. Soft, fatty plaque deposits are flattened by the
balloon and hardened deposits are cracked and split to enlarge the
lumen. It is desirable to have the stent radially expand in a
uniform manner.
[0124] Alternatively, the stent may be mounted onto a catheter that
holds the stent as it is delivered through the body lumen and then
releases the stent and allows it to self-expand into contact with
the body lumen. This deployment is effected after the stent has
been introduced percutaneously, transported transluminally and
positioned at a desired location by means of the catheter. The
retaining means may comprise a removable sheath.
[0125] The popular stents in use today are stiffer than desired.
Their relative flexibility is shown in FIGS. 14A and 14B. The
flexibility of undeployed/mounted stents is shown in FIG. 14A. All
deflection tests were conducted in saline at body temperature as
defined in the ASTM standards for stent measurements. The S540
(2.5.times.18 mm) and S670 (3.0.times.18 mm) stents are produced by
Medtronic, the TRISTAR.RTM. (2.5.times.18 mm) is made by Guidant,
VELOCITY (2.5.times.13 mm) is produced by J&J, and the Nir
(2.5.times.32 mm) is marketed by Boston Scientific. The results
shown in FIG. 14A (undeployed on a delivery catheter) indicate that
the other stents tested are more than 2-fold stiffer than the stent
(MD3) made in accordance with the present invention. The difference
in flexibility of the deployed (expanded) stents is even more
pronounced, as illustrated in FIG. 14B.
[0126] Because of the very low profile, small collapsed diameter
and great flexibility, stents made in accordance with the present
invention may be able to navigate small or torturous paths. Thus,
the low-profile stent of the present invention may be useful in
coronary arteries, carotid arteries, vascular aneurysms (when
covered with a sheath), and peripheral arteries and veins (e.g.,
renal, iliac, femoral, popliteal, sublavian, aorta, intercranial,
etc.). Other nonvascular applications include gastrointestinal,
duodenum, biliary ducts, esophagus, urethra, reproductive tracts,
trachea, and repiratory (e.g., bronchial) ducts. These applications
may or may not require a sheath covering the stent.
[0127] The stents of the present invention are adapted for
deployment using conventional methods known in the art and
employing percutaneous transluminal catheter devices. The stents
are designed for deployment by any of a variety of in situ
expansion means, such as an inflatable balloon or a polymeric plug
that expands upon application of pressure. For example, the tubular
body of the stent is first positioned to surround a portion of an
inflatable balloon catheter. The stent, with the balloon catheter
inside is configured at a first, collapsed diameter. The stent and
the inflatable balloon are percutaneously introduced into a body
lumen, following a previously positioned guidewire in an
over-the-wire angioplasty catheter system, and tracked by a
fluoroscope, until the balloon portion and associated stent are
positioned within the body passageway at the point where the stent
is to be placed. Thereafter, the balloon is inflated and the stent
is expanded by the balloon portion from the collapsed diameter to a
second expanded diameter. After the stent has been expanded to the
desired final expanded diameter, the balloon is deflated and the
catheter is withdrawn, leaving the stent in place. The stent may be
covered by a removable sheath during delivery to protect both the
stent and the vessels.
[0128] The expanded diameter is variable and determined by the
desired expanded internal diameter of the body passageway.
Accordingly, the controlled expansion of the stent is not likely to
cause a rupture of the body passageway. Furthermore, the stent will
resist recoil because the locking means resist sliding of the
elongated ribs within the articulating mechanism on the end
portions of the radial elements. Thus, the expanded intraluminal
stent will continue to exert radial pressure outward against the
wall of the body passageway and will therefore, not migrate away
from the desired location.
[0129] While a number of preferred embodiments of the invention and
variations thereof have been described in detail, other
modifications and methods of using and medical applications for the
same will be apparent to those of skill in the art. Accordingly, it
should be understood that various applications, modifications, and
substitutions may be made of equivalents without departing from the
spirit of the invention or the scope of the claims.
* * * * *