U.S. patent application number 14/821777 was filed with the patent office on 2015-12-03 for composite stent.
This patent application is currently assigned to BRS Holdings, LLC. The applicant listed for this patent is BRS Holdings, LLC. Invention is credited to James R Johnson, Anita Tavakley.
Application Number | 20150343119 14/821777 |
Document ID | / |
Family ID | 40342522 |
Filed Date | 2015-12-03 |
United States Patent
Application |
20150343119 |
Kind Code |
A1 |
Johnson; James R ; et
al. |
December 3, 2015 |
COMPOSITE STENT
Abstract
A bioremovable composite stent includes bioremovable polymer and
bioremovable ceramic flakes generally coupled with adjacent layers
of bioremovable polymer so as to make a resilient composite stent
configured to move between a contracted configuration to an
expanded configuration. In one embodiment, the composite stent may
have a helical shape.
Inventors: |
Johnson; James R;
(Stillwater, MN) ; Tavakley; Anita; (Plymouth,
MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BRS Holdings, LLC |
Rosemount |
MN |
US |
|
|
Assignee: |
BRS Holdings, LLC
Rosemount
MN
|
Family ID: |
40342522 |
Appl. No.: |
14/821777 |
Filed: |
August 9, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11932531 |
Oct 31, 2007 |
9101505 |
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14821777 |
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11380572 |
Apr 27, 2006 |
9155646 |
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11932531 |
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Current U.S.
Class: |
156/308.2 ;
264/173.16 |
Current CPC
Class: |
B32B 2264/102 20130101;
B32B 2535/00 20130101; B29C 48/21 20190201; B29L 2031/7546
20130101; B29C 65/02 20130101; A61L 31/14 20130101; A61L 31/005
20130101; B29K 2067/043 20130101; A61L 31/10 20130101; B29K 2509/00
20130101; A61L 31/127 20130101; B32B 2367/00 20130101; B32B 27/18
20130101; A61F 2240/001 20130101; A61F 2230/0091 20130101; A61F
2/92 20130101; B32B 2264/104 20130101; A61F 2210/0076 20130101;
A61L 31/148 20130101; B29K 2067/046 20130101; A61L 31/06 20130101;
A61L 31/10 20130101; A61F 2/82 20130101; A61L 31/128 20130101; B29K
2505/08 20130101; B32B 27/36 20130101; B32B 37/06 20130101; C08L
67/04 20130101 |
International
Class: |
A61L 31/14 20060101
A61L031/14; B29C 47/06 20060101 B29C047/06; A61L 31/06 20060101
A61L031/06; B32B 27/36 20060101 B32B027/36; B32B 37/06 20060101
B32B037/06; A61L 31/12 20060101 A61L031/12; B29C 65/02 20060101
B29C065/02; B32B 27/18 20060101 B32B027/18 |
Claims
1. A method of making bioremovable composite material comprising,
coupling a first layer of bioremovable polymer that is
substantially free or completely free of bioremovable ceramic
material to a second layer of bioremovable polymer that includes
flakes of bioremovable ceramic material embedded therein, wherein
the bioremovable composite material is formed into a bioremovable
stent.
2. The method according to claim 1, comprising heating the first
layer and the second layer to couple the first layer and the second
layer together.
3. The method according to claim 1, comprising solvating a surface
of the first layer and coupling the second layer to the solvated
surface of the first layer.
4. The method of claim 1, further comprising a plurality of fibers
of bioremovable ceramic material embedded in the second layer of
bioremovable polymer.
5. The method according to claim 4, wherein the plurality of fibers
of bioremovable ceramic material are directionally aligned.
6. The method according to claim 1, comprising controlling a
degradation rate of the bioremovable stent by selecting one or more
of (i) a bioremovable polymer composition, (ii) a thickness of the
first layer or the second layer, (iii) a thickness of the flakes of
bioremovable ceramic material, or (iv) a porosity of the flakes of
bioremovable ceramic material.
7. The method of claim 1, wherein the first layer of bioremovable
polymer or the second layer of bioremovable polymer comprises
polyesters, polyols, polycarbonates, polyamides, polyethers,
polysaccharides, polyhydroxyalkanoates, polylactides,
polyglycolides, polycaprolactones, albumin, or copolymers
thereof.
8. The method according to claim 1, wherein the flakes of
bioremovable ceramic material comprise calcium phosphate, bioactive
glass or combinations thereof.
9. The method according to claim 4, wherein the fibers of
bioremovable ceramic material comprise calcium phosphate, bioactive
glass or combinations thereof.
10. The method according to claim 1, wherein the flakes of
bioremovable ceramic material have pores and a bioactive agent is
positioned in the pores.
11. The method according to claim 1, comprising extruding the first
layer, the second layer, or both.
12. The method according to claim 1, comprising coextruding the
first layer and the second layer.
13. A method comprising extruding a plurality of flakes of
bioremovable ceramic material in a bioremovable polymer to form an
extrudate, and forming a bioremovable stent from the extrudate.
14. A method according to claim 13, wherein the flakes of
bioremovable ceramic material comprise calcium phosphate, bioactive
glass or combinations thereof and the bioremovable polymer
comprises polyesters, polyols, polycarbonates, polyamides,
polyethers, polysaccharides, polyhydroxyalkanoates, polylactides,
polyglycolides, polycaprolactones, albumin, or copolymers
thereof.
15. The method according to claim 13, wherein the plurality of
flakes of bioremovable ceramic material have pores and a bioactive
agent is positioned in the pores.
Description
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This patent application is a divisional application of U.S.
patent Ser. No. 11/932,531, entitled "Composite Stent" filed on
Oct. 31, 2007 which is a continuation-in-part of U.S. patent
application Ser. No. 11/380,572, entitled "Composite Stent," filed
on 27 Apr. 2006, both of which are hereby incorporated herein by
reference in their entirety. In the event of a conflict, the
subject matter explicitly recited or shown herein controls over any
subject matter incorporated by reference. All definitions of a term
(express or implied) contained in any of the subject matter
incorporated by reference herein are hereby disclaimed. The
paragraphs shortly before the claims dictate the meaning to be
given to any term explicitly recited herein subject to the
disclaimer in the preceding sentence.
BACKGROUND
[0002] Blood vessels, the esophagus, intestines, endocrine gland
ducts, the urethra and other lumens are all subject to strictures
i.e., a narrowing or occlusion of the lumen. Strictures can be
caused by a variety of traumatic or organic disorders and symptoms
can range from mild irritation and discomfort to paralysis and
death.
[0003] Most life threatening stenoses are associated with the
cardiovascular system and are often treated by performing a
percutaneous coronary intervention (PCI) such as balloon
angioplasty (also referred to as percutaneous transluminal coronary
angioplasty or PTCA). Balloon angioplasty is performed by threading
a slender balloon-tipped catheter from an artery in the groin to a
trouble spot in an artery of the heart. Once in position, the
balloon is inflated to thereby dilate (widen) the narrowed coronary
artery so that blood can flow more easily. Unfortunately,
experience has shown that three to six months after PCI, many
patients experience restenosis (some estimates place the number at
between a third and half of all patients experience restenosis).
Injury to the arterial wall during PCI is believed to be the
initiating event that causes restenosis. The resulting stricture is
often formed from vascular smooth muscle cell proliferation and
extracellular matrix secretion at the injured site. Restenosis is
also a major problem in non-coronary artery disease including the
carotid, femoral, iliac, popliteal and renal arteries.
[0004] Other non-vascular tubular structures can also suffer from
stenosis due to a variety of causes such as inflammation, neoplasm,
and benign intimal hyperplasia. Some strictures such as those in
the esophagus or intestines, may be surgically removed and the
lumen repaired by anastomosis. The smaller transluminal spaces
associated with ducts and vessels may also be repaired in this
fashion. Unfortunately, restenosis caused by intimal hyperplasia is
common in these situations.
[0005] Aging men often suffer from stenosis of the urethra that
results in diminished urine flow rates. The most frequent cause is
enlargement of the prostate gland (e.g., benign prostatic
hypertrophy or BPH). In this disease, the internal lobes of the
prostate slowly enlarge and progressively occlude the urethral
lumen. A number of therapeutic options are available for treating
an enlarged prostrate. These include watchful waiting (no
treatment), several drugs, a variety of so-called "less invasive"
therapies, and transurethral resection of the prostate (TURP)--long
considered the gold standard.
[0006] In the urethra, a circumferential band of fibrous scar
tissue may progressively contract and narrow the lumen thereby
reducing the urine flow rate. A stricture of this type may be
congenital or may result from urethral trauma or disease. These
strictures were traditionally treated by dilation with sounds or
bougies. More recently, balloon catheters have been used to
mechanically dilate the lumen. Surgical urethrotomy is currently
the preferred treatment, but restenosis remains a significant
problem.
[0007] Stents were developed, at least in part, to attempt to
minimize the occurrence of restenosis. Stents can generally be
thought of as a form of mechanical scaffolding that holds the
occluded lumen open. There are two general types of stents:
permanent and temporary. Temporary stents can be further subdivided
into removable and absorbable.
[0008] Permanent stents are used where long term structural support
or restenosis prevention is required, or in cases where surgical
removal of the implanted stent is impractical. Permanent stents are
usually made from metals such as Phynox, 316 stainless steel, MP35N
alloy, and superelastic Nitinol (nickel-titanium).
[0009] Although stents are used primarily in the vasculature,
stents may also be used to hold any bodily lumen open. For example,
stents may be used as temporary devices to prevent closure of a
recently opened urethra following minimally invasive procedures to
treat an occlusion due to an enlarged prostate. These procedures
often result in a post treatment edema and urethral obstruction. In
these cases, the stent is typically not covered with tissue
(epithelialized) prior to removal.
[0010] Temporary absorbable stents can be made from a wide range of
synthetic biocompatible polymers depending on the physical
qualities desired. Representative biocompatible polymers include
polyanhydrides, polycaprolactone, polyglycolides, polylactides, and
polyphosphate esters.
[0011] Recently, a number of biocompatible, bioresorbable materials
have been used in stent development and in situ drug delivery
development. These stents are designed and made from copolymers
which unfortunately may not provide the desired physical properties
required to hold the lumen open for a sufficient time period for
healing to occur. Accordingly, it would be desirable to provide an
improved biocompatible, bioresorbable stent that has the desired
physical properties necessary to hold the lumen open for a time
sufficient to promote healing. Also, it would be desirable to
provide a stent that has a substrate that facilitates the growth or
regeneration of tissue as the substrate is removed by or
incorporated into the patient's body.
SUMMARY
[0012] Various embodiments of a composite stent are described
herein. The composite stent is used to support and/or dilate an
occluded bodily lumen or vessel. The composite stent may be sized
and/or otherwise configured to support and/or dilate any tubular
passages in the body such as blood vessels, urethra, intestines,
endocrine gland ducts, esophagus, and so forth. The composite stent
is configured to move between a contracted configuration where the
composite stent is sized to be inserted into and transported
through the bodily lumen and an expanded configuration where the
composite stent is sized to support and/or dilate the bodily
lumen.
[0013] The composite stent is bioremovable. After the composite
stent is implanted, it slowly degrades. The composite stent is
designed to degrade at a rate that keeps the stent in place long
enough to allow the lumen to remain open without the assistance of
the composite stent. Due to its bioremovability, the composite
stent reduces long-term complications associated with permanent
stents and/or eliminates the need to surgically remove the stent at
a later time. The degradation rate of the composite stent can be
altered by changing the composition of the materials that are used
to make the composite stent. The composite stent may also degrade
in a way that prevents chunks from spalling off of the stent and
causing clots or other blockages. In one embodiment, the composite
stent includes bioremovable polymer and bioremovable ceramic
material. The bioremovable ceramic material may be provided as a
plurality of fibers or flakes. Preferably, the bioremovable polymer
includes polylactide, polyglycolide, and/or polycaprolactone and
the bioremovable ceramic material includes calcium phosphate
material such as tricalcium phosphate.
[0014] It should be appreciated that the term "bioremovable" is
used herein to refer to biocompatible materials that are capable of
being broken down, gradually absorbed, and/or otherwise used by or
eliminated from the body by processes such as bioabsorbtion (i.e.,
they are absorbed by the body and moved within the body to be
used), biodegradation (i.e., chemically fall apart into non-toxic
components that are carried away by material moving through the
lumen), and the like. Thus, the term "bioremovable" is intended to
encompass both bioabsorbtion and biodegradation processes.
[0015] The inclusion of the bioremovable ceramic material provides
a number of advantages to the composite stent. For example, the
inclusion of flakes or fibers of bioremovable ceramic material
provides additional stiffness and/or strength to the composite
stent. The increased strength may prevent the composite stent from
being compressed or otherwise deformed by the force of the walls of
the lumen pressing against it. The bioremovable ceramic material
may also function as a source of calcium (e.g., bioremovable
ceramic material includes tricalcium phosphate) to facilitate
tissue regeneration and/or repair. In some embodiments, the
bioremovable ceramic material may be porous. The pores may provide
a number of advantages such as providing a substrate structure that
promotes rapid cell growth to occur. The pores may also be loaded
with a bioactive agent such as drugs, stem cells, and the like. As
the composite stent slowly degrades and exposes the bioremovable
ceramic material, the bioactive agents may be slowly released to
provide a therapeutic effect.
[0016] It should be appreciated that the composite stent may have
any of a number of suitable configurations. In one embodiment, the
composite stent may include a loose network of fibrous material
that is configured to expand in a bodily lumen. The fibrous
material may include a plurality of composite yams that are woven
together. The composite yams may include a core of bioremovable
ceramic fibers encased in one or more coatings of bioremovable
polymers. The outer coating of bioremovable polymer may be selected
to provide a slightly tacky surface. As the composite stent is
expanded in the bodily lumen, the surface forces between the
bioremovable polymer coatings on adjacent yams holds the composite
stent in an expanded position.
[0017] In another embodiment, the composite stent may include a
plurality of layers of different materials. For example, the
composite stent may include two or more layers that have different
physical properties and/or compositions. The composite stent may
include alternating layers of bioremovable polymer that have a high
concentration of bioremovable ceramic material and a low
concentration of bioremovable ceramic material. The high
concentration layers may include bioremovable ceramic material
dispersed or embedded in bioremovable polymer. The low
concentration layers may include very small amounts of bioremovable
ceramic material or may be completely free of bioremovable ceramic
material.
[0018] In one embodiment, the composite stent may include a
plurality of flakes of bioremovable ceramic material. The flakes
may be dispersed or embedded in bioremovable polymer. In one
embodiment, the flakes may be embedded in a layer of bioremovable
polymer so that the flakes are approximately parallel to each other
and/or the surface of the layer. Orienting the flakes in parallel
acts to enhance the physical properties of the composite stent such
as elastic modulus, strength, resiliency, and so forth. The flakes
strengthen the layer of bioremovable composite material along both
the width and length of the layer. Chopped fibers of bioremovable
ceramic material may also be embedded or dispersed in the composite
stent. In one embodiment, the chopped fibers may be oriented
parallel to each other. For example, the chopped fibers may be
oriented parallel to a lengthwise direction of the layer. In this
configuration, the chopped fibers increase the stiffness of the
layer in a lengthwise direction, but may not provide any increase
or may provide a small increase in the stiffness in the crosswise
direction.
[0019] The composite stent has a shape that allows it to move
between a contracted configuration where the composite stent is
sized to be inserted into the lumen of the patient and an expanded
configuration where the composite stent is sized to support and/or
dilate the lumen. In one embodiment, the composite stent may have a
helical shape. The composite material used to make the composite
stent may be resilient in nature. The resilient properties of the
composite material may cause the composite stent to move from the
contracted configuration where the composite stent is wound and in
a state of tension to the expanded configuration where the
composite stent is substantially unwound. It should be appreciated
that when the composite stent is deployed in the lumen, the
composite stent is not fully at a state of rest, but is still under
enough tension to hold the composite stent in place and to support
and/or dilate the lumen. In another embodiment, the composite stent
may take the form of a coiled sheet that can be expanded radially
in the lumen.
[0020] The bioremovable composite material used to make many of the
embodiments of the composite stent can be prepared using any
suitable process. In one embodiment, the different layers of
material may be prepared individually and coupled together to form
the layered bioremovable composite material. For example the
different layers of bioremovable polymer having high and low
concentrations of bioremovable ceramic material may be extruded or
molded individually. The individual layers may be coupled together
by heating a sandwich of layers or slightly solvating the surface
of each layer before applying the next layer. In the extrusion
process, the high concentration layers may be made by extruding a
mixture of bioremovable polymer and bioremovable ceramic material
into a ribbon or strip of bioremovable composite material. The low
concentration layers may be made by extruding bioremovable polymer
into a ribbon. In the cast and mold process, ribbons of
bioremovable polymer and ribbons of a combination of bioremovable
polymer and bioremovable ceramic material may be made by casting
the liquid bioremovable polymer and the mixture of bioremovable
polymer and bioremovable ceramic material into molds. Once the
ribbons have dried, the ribbons may be removed from the mold and
coupled together to form a layered bioremovable composite material.
The bioremovable composite material made using either process can
then be used to make the finished composite stent.
[0021] In another embodiment, the bioremovable composite material
may be prepared by extruding a mixture of bioremovable polymer and
bioremovable ceramic material in the shape of a tube. The tube may
be cut to have a resilient helical shape as described above. The
bioremovable composite material may also be prepared using an
integrated process where the different layers of material are
simultaneously extruded and immediately coupled together.
[0022] The foregoing and other features, utilities, and advantages
of the subject matter described herein will be apparent from the
following more particular description of certain embodiments as
illustrated in the accompanying drawings.
DRAWINGS
[0023] FIG. 1 shows a side view of a composite stent in a
contracted configuration to allow the stent to be inserted into a
lumen.
[0024] FIG. 2 shows a side view of the composite stent of FIG. 1 in
an expanded configuration to hold a lumen open.
[0025] FIG. 3 shows a perspective and cross-sectional view of one
embodiment of a composite yam or fiber that may be used to form at
least a part of the composite stent of FIG. 1.
[0026] FIG. 4 shows a side view of a plurality of ceramic fibers
which may be used in the composite yam of FIG. 3.
[0027] FIG. 5 shows a perspective view of another embodiment of a
composite stent in a contracted configuration to allow the stent to
be inserted into a lumen.
[0028] FIG. 6 shows a perspective view of one embodiment of the
composite stent from FIG. 5 in an expanded configuration.
[0029] FIG. 7 shows a perspective view of one embodiment of a
layered composite material that may be used to form at least part
of the composite stent from FIG. 5.
[0030] FIG. 8 shows a perspective view of the layered composite
material of FIG. 7 as holes are being made in the layered composite
material.
[0031] FIG. 9 shows one of a number of embodiments of the
geometrical shapes that the holes in the layered composite material
of FIG. 8 may have.
[0032] FIGS. 10 and 11 show a side view and a top view of another
embodiment of a composite material that may be used to make another
embodiment of the composite stent. The ceramic material is depicted
as being oriented roughly parallel to the top surface of the
composite material.
[0033] FIG. 12 shows a side view of another embodiment of a layered
composite material that may be used to make another embodiment of
the composite stent.
[0034] FIGS. 13 and 14 show a top view of a ribbon of composite
material (FIG. 13) that may be wound into a helical shape to make
another embodiment of a composite stent (FIG. 14).
[0035] FIG. 15 is a photograph of another embodiment of a composite
stent having a helical shape.
DETAILED DESCRIPTION
[0036] Although the subject matter described herein is provided in
the context of stents generally, it should be appreciated that
certain embodiments may be more suitable for a particular
application than other embodiments. For example the stent shown in
FIG. 1 may be more suited for intravascular use than for use in
other lumens. Also, the stent shown in FIG. 5 may be more suited
for use in the intestines or in other relatively larger lumens.
That being said, it should be appreciated that any of the stents
described herein may be configured to be used in any suitable lumen
in the body. Also, it should be appreciated, that the features,
advantages, characteristics, etc. of one embodiment may be applied
to any other embodiment to form an additional embodiment unless
noted otherwise.
Embodiments of Composite Stents that Use Fibrous Bioremovable
Composite Material
[0037] Referring to FIG. 1, a composite stent 10 is shown in a
contracted configuration or first configuration where the diameter
or size of the stent 10 is reduced to allow the stent 10 to be
inserted into a lumen or vessel. The stent 10 is formed from a
loose woven network of fibrous composite material. The stent 10 has
a generally cylindrical or tubular shape that is configured to fit
within a lumen. The stent 10 is bioremovable to allow the stent 10
to be safely and effectively removed over time from the lumen.
[0038] In order to facilitate insertion into the lumen, the stent
10 may be releasably coupled to a catheter or guide wire 12. The
catheter 12 is configured to allow the catheter 12 and stent 10 to
pass through the lumen to the occluded site. Once the stent 10 is
in position, the stent 10 can be expanded to open the occluded
lumen and hold it open. In one embodiment, as the stent 10 is
expanded, it may become shorter in length and larger in diameter as
illustrated in FIG. 2. The catheter 12 may then be withdrawn from
the lumen leaving the stent 10 in place.
[0039] It should be noted that for purposes of this disclosure, the
term "coupled" means the joining of two members directly or
indirectly to one another. Such joining may be stationary in nature
or movable in nature. Such joining may be achieved with the two
members or the two members and any additional intermediate members
being integrally formed as a single unitary body with one another
or with the two members or the two members and any additional
intermediate member being attached to one another. Such joining may
be permanent in nature or alternatively may be removable or
releasable in nature.
[0040] It should be appreciated that numerous methods may be used
to expand the stent 10. In one embodiment, the catheter 12 may be a
balloon catheter having a balloon positioned between the stent 10
and the main body of the catheter 12. The balloon can be inflated
using a fluid such as saline solution. As the balloon is inflated,
the stent 10 expands outward radially until the stent 10 is
positioned to hold the lumen open. In general, the stent 10 is
configured to expand in a lumen without substantial rotational
movement relative to the longitudinal axis of the stent 10 (see
stent 30 for an example where the stent expands by rotating about
the longitudinal axis of the stent 30).
[0041] It should be appreciated that any suitable bioremovable
fibrous material may be used to form the stent 10 (e.g., inorganic
fibrous material). Referring to FIG. 3, the fibrous material may
include a loose network of composite yams or composite fibers 14.
The composite yams 14 may be woven together in a loose weave such
as that shown in FIG. 3, or the composite yams 14 may be assembled
in other ways besides weaving (e.g., using a suitable rubbery
biodegradable polymer to engage the fibers to resist the movement
of the fibers so as to enhance the structural integrity of the
composite). It should be appreciated that the composite yams 14 may
be assembled together in a manner that allows the composite yams 14
to expand so that the stent 10 can likewise expand to fill the
lumen. At the same time, the composite yams 14 should be configured
so that upon expansion of the stent 10, the stent 10 has sufficient
strength to remain in position in the lumen and keep the occluded
site open.
[0042] FIG. 3 also shows a cross-sectional view of one of the
composite yams 14. Each composite yam 14 includes a plurality of
ceramic fibers 16 encased in or coated with a first or inner
polymer layer or coating 18 which is in turn coated with a second
or outer polymer layer or coating 20. It should be appreciated that
the ceramic fibers 16 may be soaked with the first polymer coating
18 to completely fill in the interstices between the ceramic fibers
16, or the ceramic fibers 16 may be individually coated with the
first polymer coating 18. The first polymer coating 18 may be
provided to give resiliency and toughness to the composite yam 14
by distributing the load on the ceramic fibers. The second polymer
coating 20, a more rubbery bioremovable polymer than the first
polymer coating 18, may engage the fibers 16/yam 14 to make firm
the structural integrity of the expanded stent 10. Thus, the first
polymer coating 18 may have a different modulus of elasticity than
the second polymer coating 20. In one embodiment, the first polymer
coating 18 has a higher modulus of elasticity than the second
polymer coating 20. Also, the first polymer coating 18 may have a
different molecular weight than the second polymer coating 20. In
one embodiment, the first polymer coating 18 may have a lower
molecular weight than the second polymer coating 20.
[0043] The higher friction property of the second polymer coating
20 holds the composite yams 14 in the expanded state by friction
forces and prevents the stent 10 from collapsing. It should be
appreciated that the composite yams 14 may include more than one
polymer coating 18, 20. For example, the composite yams 14 may be
prepared by forming multiple resilient coatings over the ceramic
fibers 16 with the final coating being a low modulus coating. The
thickness of the first polymer coating 18 and the second polymer
coating 20 may be about 0.1 to 5 microns.
[0044] It should be appreciated that in other embodiments of the
stent 10 a single polymer coating may be used or more than one
polymer coating (e.g., three or more) may be used. For example, a
single polymer coating may suffice so long as the polymer coating
has the requisite stiffness to support the integrity of the stent
10 and the friction properties sufficient to hold the stent 10 in
the expanded position. Also, bodily fluids (e.g., blood, etc.) may
soften the surface of the polymer so that the polymer provides
sufficient friction to hold the stent 10 open.
[0045] The stent 10 may be configured to gradually and uniformly
erode in the lumen (e.g., in the bloodstream of a patient) rather
than erode by periodically cleaving off large chunks. In one
embodiment, each layer may be selected to provide protection
against nonuniform erosion of the layer beneath it. The materials
used in the stent 10 may be selected to provide sufficient support
for the lumen at all times as the stent 10 is replaced by natural
tissues.
[0046] The first polymer coating 18 and the second polymer coating
20 for the stent 10 may include biocompatible, bioremovable
polymers. That is, the polymers will be removed by in-vivo
processes such that the polymers and their products are not toxic
or inhibit the purpose of the stent 10 and the products will be
either eliminated from the body or assimilated by the body.
Suitable examples of such polymers may be found among polyesters,
polyols, polycarbonates, polyamides, polyethers, polysaccharides,
and/or polyhydroxyalkanoates. Preferred examples include
polylactides (PLA), polyglycolides (PGA), polycaprolactones (PCL),
albumin, collagen, copolymers of any of these polymers, and/or
mixtures thereof. PLA is used to refer to poly-L-lactide (PLLA)
and/or poly-DL-lactide (PDLLA). In one embodiment, the first
polymer coating 18 and the second polymer coating 20 each includes
PLA, PGA, PCL and/or copolymers thereof.
[0047] The first polymer coating 18 is intended to provide a
protective load-distributing layer on the ceramic fibers to inhibit
fracture when the fibers are moved upon expanding the stent 10. It
may also have additional advantages such as modulating the rate of
bioremoval and providing some inter-surface friction between
fibers. The polymer should have sufficient molecular entanglement
to provide some toughness as well as the above features.
[0048] The second polymer coating 20 is designed to have a glass
transition temperature below body temperature. Its function is to
further stabilize the open stent from retracting by increased
friction, fiber on fiber, yam on yam, akin to locking the fibers in
place. For example, the second polymer coating 20 may be a
bioremovable polymer or copolymer of albumin having a modulus of
less than 1.times.10.sup.7 pascals. Further it is contemplated that
the weave of the yam that forms the stent 10 may provide some
mechanical resistance to retracting when open.
[0049] FIG. 4 shows the ceramic fibers 16 prior to being coated
with the first polymer coating 18. The ceramic fibers 16 are
generally positioned parallel to each other prior to being coated
with the first polymer coating 18. The ceramic fibers 16 may be any
suitable size. In one embodiment, the ceramic fibers 16 may be
about 0.5 microns to 10 microns in diameter or may be about 1
micron to 5 microns in diameter.
[0050] The ceramic fibers 16 may be made of any suitable
bioremovable ceramic material(s). Suitable examples of bioremovable
ceramic material include calcium phosphate material such as
tricalcium phosphate and/or other similar materials. Although a
number of ceramic materials have been referred to in the literature
as "resorbable," many of these compounds, such as hydroxyapatite,
are in fact only weakly resorbable. Calcium phosphate compounds
such as tricalcium phosphate, on the other hand, are much more
resorbable in comparison and are therefore preferred for use in the
composite stent. In one embodiment, the tricalcium phosphate is
amorphous. It should be noted that calcium phosphate materials are
generally bioabsorbed (i.e., incorporated into the body) rather
than biodegraded (i.e., removed by the body).
[0051] In one embodiment, the bioremovable ceramic material may be
substantially entirely made up of tricalcium phosphate. It should
be appreciated that in other embodiments, the bioremovable ceramic
material may include a mixture of tricalcium phosphate and another
bioremovable ceramic material or may be made up entirely of
bioremovable ceramic materials other than tricalcium phosphate. In
another embodiment, the bioremovable ceramic material may be
calcium phosphate material that has been fired to a temperature
that makes it strong enough to endure the bending movements which
occur during emplacement of the composite stent 10.
[0052] Although calcium phosphate materials are preferred for use
as the bioremovable ceramic material, other suitable bioremovable
ceramic materials may also be used. Additional bioremovable ceramic
materials include bioactive glasses such as BIOGLASS as well as
other similar materials. Unlike tricalcium phosphate, bioglass
typically biodegrades and exits the body. In one embodiment, each
composite yam 14 may include multiple different types of
bioremovable ceramic fibers 16. For example, the composite yam 14
may include a mixture of bioactive glass fibers, tricalcium
phosphate fibers, and/or other bioremovable ceramic fibers.
[0053] The ceramic fibers 16 may be prepared using any suitable
process. One suitable process for preparing tricalcium phosphate
fibers (beta tricalcium phosphate) is the sol gel process described
in U.S. Pat. Nos. 3,795,524, 4,801,562, 4,929,578, all of which are
incorporated by reference herein in their entireties. The process
includes mixing a source of calcium such as calcium acetate,
calcium citrate, calcium formamide, other organic and inorganic
compounds of calcium, with a source of phosphorous such as
phosphoric acid, phosphorous pentoxide, and the like, to yield
calcium phosphate. The purity of these materials are expected to
meet ASTM F1088-04a specifications for implantable products. The
salts are made in aqueous solutions and concentrated in a rotovapor
device. The viscosity may be increased to about 1000 to 20000
poises by adding glucose, corn syrup, or polyvinyl pyrrolidone
(PVP) up to or more than 2/3 of the total volume. Since fibers are
being made, the viscous material is drawn through a spinerette. The
resulting fibers are fired at varying temperatures depending on the
desired porosity of the ceramic material. To form fully dense
ceramic material, the fibers 16 are fired at about 1100 to
1200.degree. C. To form nano porous ceramic material, the fibers
are fibers 16 are fired at 750 to 850.degree. C.
[0054] The composite yam 14 may have any suitable size depending on
the application. The diameter of the composite yam 14 depends on
the number and size of ceramic fibers 16 used in the composite yam
14. In one embodiment, each composite yam 14 is about 20 microns to
150 microns in diameter or 50 microns to 100 microns in diameter.
The rate at which the bioremovable inorganic ceramic in the stent
10 is bioremoved may be controlled by altering the porosity,
thickness, and compositions of the materials being used. The ratio
of the amount of the different polymers and/or copolymers (e.g.,
PLA, PGA, PCL polymers and/or copolymers thereof) used in a
particular polymer coating may be altered to change the rate that
the polymer coating degrades to meet the requirements for the
coating. The ratio of the various polymers and/or copolymers may be
determined for each application to provide the desired degradation
rate. Also, other biocompatible chemicals such as plasticizers may
be used to control the rate of bioremoval.
[0055] Embodiments of Composite Stents that Use Sheets or Ribbons
of Bioremovable Composite Material
[0056] Referring to FIG. 5, another embodiment of a composite stent
30 is shown. In this embodiment, the stent 30 includes a sheet 32
having a plurality of holes or openings 34 in it. The stent 30
shown in FIG. 5 is wound or coiled so that it can be inserted into
a lumen. Since the stent 30 is not as flexible as the stent 10, the
stent 30 may be used in larger lumens such as the intestines or in
situations where the stent 30 is implanted directly (often
temporarily) into the lumen without passing it through long
sections of curved lumen. The stent 30 may be expanded in any
suitable manner such as, for example, using a balloon.
[0057] As shown in FIG. 6, the stent 30 may be held in the expanded
position using a belt and buckle type configuration. The sheet 32
includes a first end 36 which has a plurality of teeth 38 thereon
and a second end 40 which includes a buckle shaped opening 42 which
is sized to receive the first end 36. When the stent 30 is in the
expanded configuration, the teeth 38 engage the top and bottom of
the opening 42 to prevent the stent 30 from collapsing. The use of
the belt and buckle type configuration allows the stent 30 to be
mechanically locked in position. It is also contemplated that the
stent 30 may be held open due to the adhesiveness from a low
modulus bioremovable polymer coating, for example. The stent 30 may
also be held open using a mechanical fastener system such as a slot
insert system.
[0058] Another embodiment of a composite stent 70 is illustrated in
FIG. 14 and shown in a photograph in FIG. 15. The stent 70 includes
a ribbon or strip 72 of bioremovable composite material that has a
helical shape. In one embodiment, the ribbon 72 may have a
plurality of holes 74 in it that expose the interior wall of the
lumen as shown in FIG. 14.
[0059] The stent 70 may be configured to move from a contracted
configuration where the stent 70 is sized to be inserted and moved
through the lumen to an expanded configuration where the stent 70
is configured to support and/or dilate the lumen. In one
embodiment, the stent 70 may be resilient so that the resilient
properties of the stent 70 cause it to move from the contracted
configuration to the expanded configuration. For example, the stent
70 may be wound and in a state of tension when the stent 70 is in
the contracted configuration. When the stent 70 is wound, the stent
70 becomes longer and the diameter decreases thereby allowing the
stent 70 to be inserted into the lumen. A catheter or guidewire may
be used to guide the stent 70 to the appropriate location in the
lumen while maintaining the stent 70 in the contracted
configuration. Once the stent 70 is in place, the tension on the
stent 70 may be released (e.g., using a release trigger or other
appropriate system on the catheter) to allow the stent 70 to move
resiliently to the expanded configuration. In the expanded
configuration, the stent 70 contacts the inner surface of the lumen
and remains in a state of tension, albeit a lower state of tension
than when the stent 70 is in the contracted configuration, to hold
the stent 70 in place. The amount of tension that the stent 70
applies to the inner wall of the lumen can be adjusted to meet the
patient's requirements (e.g., pediatric uses may require less
tension between the stent and the lumen walls).
[0060] The stents 30, 70 may each include a plurality of layers of
different materials as shown in FIGS. 7 and 10-12. In one
embodiment, the stents 30, 70 may include alternating layers of
ceramic material and polymeric material as illustrated in FIG. 7.
In another embodiment, the stents 30, 70 may include alternating
layers of polymeric material having a high concentration of ceramic
material and a low concentration of ceramic material. The high
concentration layers may comprise ceramic material embedded or
dispersed in polymeric material. The low concentration layers may
be substantially free or completely free of ceramic material. It
should also be appreciated that one layer of polymeric material may
have a different composition than another layer of polymeric
material. Also, the thickness of the layers may be uniform or may
vary.
[0061] In one embodiment, the stents 30, 70 may include at least
two layers of material, or suitably, at least three layers of
material. In another embodiment, the stents 30, 70 may include up
to no more than twenty one layers of material or up to no more than
fifteen layers of material. The layers of material may be coupled
together to form a relatively resilient structure. The polymeric
material imparts resiliency to the sheet 32 and ribbon 72 of
composite material by distributing the load on bending of the stent
30. The resilient properties of the composite material allow the
stent 70 to move from the contracted configuration to the expanded
configuration as explained above. The thickness of the sheet 32 may
be about 10 to 200 microns, desirably about 30 to 150 microns, or
suitably 40 to 100 microns.
[0062] The composite material used to form the sheet 32 and/or the
ribbon 72 may be bioremovable. For example, the sheet 32 and/or the
ribbon 72 may include bioremovable polymer and bioremovable ceramic
material in the alternating layers. In one embodiment, the outer
two layers of the sheet 32 and/or the ribbon 72 may be bioremovable
polymer layers that are substantially free or completely free of
bioremovable ceramic material. Thus, the bioremovable ceramic
material is included in the interior layers of the sheet 32 and/or
ribbon 72. In another embodiment, the outer two layers of the sheet
32 and/or the ribbon 72 may include bioremovable ceramic material.
In this configuration, the layers of bioremovable polymer may be on
the inside of the sheet 32 and/or the ribbon 72. The layers that
include bioremovable ceramic material may be about 1 to 20 microns
thick or about 2 to 10 microns thick. Each layer of bioremovable
polymer may be about 0.1 to 10 microns thick, 0.5 to 8 microns
thick, or 1 to 5 microns thick. The bioremovable polymer and
bioremovable ceramic material may be any of the materials described
in connection with the stent 10. It should also be appreciated that
the bioremovable polymer used in any of the layers need not include
only a single polymer or copolymer. Rather, the bioremovable
polymer may include mixtures of one or more bioremovable polymers
and/or copolymers.
[0063] In one embodiment, the bioremovable ceramic material may be
fully dense. In another embodiment, the bioremovable ceramic
material may be porous to allow it to function as a carrier for
bioactive agents or to provide the desired bioremoval rate to the
stents 30, 70. For example, the bioremovable ceramic material may
have pore sizes from 1 nanometer to 0.1 microns. The methods used
to prepare the bioremovable ceramic material may be altered to
impart the desired amount of porosity as described in greater
detail as follows.
[0064] In one embodiment, the bioremovable ceramic material may
include a plurality of flakes dispersed within or deposited on an
underlying layer of bioremovable polymer. In one embodiment, the
flakes may be embedded in the bioremovable polymer so that the
flakes are approximately parallel to each other and/or to the
surface of the layer. Orienting the flakes in this manner enhances
the physical properties of the composite material by increasing its
stiffness and/or strength. The parallel orientation of the flakes
serves to strengthen the layer of bioremovable composite material
in a lengthwise direction and widthwise direction. In another
embodiment, chopped fibers of ceramic material may also be added to
the sheet 32 and/or ribbon 72, either alone or in combination with
flakes of ceramic material. In one embodiment, the chopped fibers
may be oriented parallel to each other in a lengthwise direction.
In this configuration, the chopped fibers increase the stiffness of
the layer in a lengthwise direction, but may not provide any
increase or may provide a small increase in stiffness in the
crosswise direction.
[0065] It should be appreciated that the flakes of ceramic material
may be any suitable size. It is preferred, however, to use flakes
having an aspect ratio of approximately 5 to 50, approximately 7 to
30, or approximately 10 to 20. The aspect ratio is the ratio of the
length (i.e., the longest dimension of its flat side) to its
thickness. The flakes may also be approximately 1 to 50 microns
thick and up to 300 microns or, desirably, 200 microns wide.
[0066] The flakes may be prepared using any suitable process. In
one embodiment, the flakes are prepared using the sol method
described above except that instead of forming fibers, the sol, for
example of tricalcium phosphate, is cast as a solution onto a plate
where after drying it is broken into small pieces and screened to
get uniform sized flakes. The flakes are then sintered at various
temperatures to finish the process and impart the desired porosity
to the flakes. The flakes may be fired at about 1100 to
1200.degree. C. to achieve full density or at 750 to 850.degree. C.
to provide nano-porous flakes, i.e., flakes that have a mean pore
size of approximately 1 nanometer to 0.1 nanometer. The flakes may
be fired in a drop furnace to prevent the flakes from sticking
together. Openings may be cut in the sheet 32 and/or ribbon 72 as
shown in FIGS. 8-9 and 13-14.
[0067] In another embodiment, very thin flakes of ceramic material
(1 to 10 microns thick) can be made by preparing a very dilute
solution of the ceramic material. A very thin coating of this
solution is made on an alumina plate or setter after which it is
dried at approximately 60 to 70.degree. C. The flakes are then held
at this temperature before being loaded into a furnace that is
heated to the desired sintering temperature as discussed above.
After sintering, the flakes are removed from the alumina setter.
The aspect ratio range of these flakes is on the order of 10 to 50.
It should be appreciated that this method may be modified to use
flash drying techniques to allow for timely production of larger
quantities of flakes.
[0068] The flakes may also be made using a water dispersion of nano
particles of ceramic material (e.g., amorphous calcium phosphate).
This dispersion is coated onto an alumina setter plate using a
Mayer rod. The coating is then dried and sintered at the desired
temperature as described above. The thickness of flakes made by
this method is somewhat greater than flakes made by the solution
method--on the order of 10 to 30 microns thick. The aspect ratio of
these flakes was approximately 5 to 20. Both this technique and the
solution technique when applied to amorphous calcium phosphate
produced flakes of tricalcium phosphate. It should be appreciated
that larger scale production methods may be obtained by coating the
water dispersion or the solution onto suitable polymer films. The
flakes may be removed by bending or stretching the film to crack
and pop the flakes off.
[0069] Referring to FIG. 7, one embodiment of the sheet 32 is shown
having five layers of material. More specifically, the sheet 32
includes a top layer of bioremovable polymer material 44, an
intermediate layer of bioremovable polymer material 46, and a
bottom layer of bioremovable polymer material 48. In between the
top layer 44 and the intermediate layer 46 is a first layer of
bioremovable ceramic material 50, and in between the intermediate
layer 46 and the bottom layer 48 is a second layer of bioremovable
ceramic material 52. It should be appreciated that the sheet 32 may
have more or less than five layers. For example, the sheet 32 may
have at least three layers, at least five layers, at least seven
layers, or at least nine layers. Also, it should be appreciated
that the ribbon 70 may also be configured to have a similar layer
structure as that shown for the sheet 32.
[0070] Referring to FIGS. 8 and 9, the sheet 32 may include
openings 34 having any of a number of suitable shapes. For example,
as shown in FIG. 9, the openings 34 may include hexagonal openings,
or, in other embodiments, square, circular, oval, or other shaped
openings. The openings 34 may be provided to allow the lumen tissue
to still be in contact with the material moving through the
lumen.
[0071] The sheet 32 may be a continuous sheet of, for example,
sintered tricalcium phosphate on the order of 10 microns thick. The
sheet 32 may be made using the process described in U.S. Pat. Nos.
3,436,307 and 3,444,929, both of which are hereby incorporated by
reference herein in their entireties. In this process, a dispersion
of submicron to micron size particles of ceramic material is
dispersed with a binder in a liquid, e.g., about 10%
methylcellulose in water or alternatively polyvinyl butyral in
toluene or other suitable solvent. The dispersion is tape-cast onto
a plastic sheet and dried. The sheet may then be sintered to keep
it flat. Such sheets can have a thickness of about 10 to 20
microns. Sintering to achieve flat sheets may require placing
alumina microspheres under and over the sheets. The particles of
tricalcium phosphate in this example are expected to meet ASTM
purity standards F1088-04a for use as implants. The stent sheets
are then used to construct an alternating layer structure,
bioremovable polymer/ceramic as described above for the flake
construction. It should be appreciated that this method may also be
used to make flakes of ceramic material if the sheet is broken into
appropriately sized flakes (e.g., sheet broken and screened to
separate out appropriate sized flakes).
[0072] The sheet 32 may be prepared by coating a ceramic material
sheet with a solution of 0.1 grams of PLA/PGA copolymer (90/10 to
10/90) in 5 cc of a suitable solvent such as methylene chloride or
acetone. Once the ceramic material sheet has been completely
coated, another ceramic material sheet is positioned over the
coated side of the first ceramic material sheet. The coating
process may then be repeated on this new composite ceramic polymer
material sheet. This process is used to provide the desired number
of layers in the sheet 32. It should also be appreciated that this
process may be used to prepare a ribbon shaped composite material
having the layer characteristics shown in FIG. 7.
[0073] FIGS. 10 and 11 show side and top views, respectively, of
one embodiment of a ribbon or layer 80 that is used as one of the
layers in the ribbon 72 of composite material. These FIGS. show the
flakes 78 oriented parallel to the flat planar side of the ribbon
70 and to each other. FIG. 12 shows one embodiment of the ribbon 72
having five layers of material. Specifically, the ribbon 72
includes a top layer 84 of bioremovable polymer material, an
intermediate layer 86 of bioremovable polymer material, and a
bottom layer 88 of bioremovable polymer material. In between the
top layer 84 and the intermediate layer 86 is a first layer 90 of
bioremovable polymer embedded with bioremovable ceramic material,
and in between the intermediate layer 86 and the bottom layer 88 is
a second layer 92 of bioremovable polymer embedded with
bioremovable ceramic material. It should be appreciated that the
ribbon 70 may have more or less than five layers. For example, the
ribbon may have at least three layers, at least five layers, at
least seven layers, or at least nine layers of material. Also, it
should be appreciated that the sheet 32 may also be configured to
have a similar layer structure as that shown for the ribbon 70.
[0074] The ribbon may be prepared using any suitable process. In
one embodiment, the different layers of material may be prepared
individually and coupled together to form the layered bioremovable
composite material. For example the different layers of
bioremovable polymer having high and low concentrations of
bioremovable ceramic material may be extruded as a viscous polymer
or molded individually (e.g., liquid polymer with dispersion of
ceramic material is placed in an appropriately sized mold until
dry). The individual layers may be coupled together by heating a
sandwich of layers or slightly solvating the surface of each layer
before applying the next layer. In the extrusion process, the high
concentration layers may be made by extruding a mixture of
bioremovable polymer and bioremovable ceramic material into a
ribbon or strip of bioremovable composite material. The low
concentration layers may be made by extruding bioremovable polymer
into a ribbon. In the cast and mold process, ribbons of
bioremovable polymer and ribbons of a combination of bioremovable
polymer and bioremovable ceramic material may be made by casting
the liquid bioremovable polymer and the mixture of bioremovable
polymer and bioremovable ceramic material into molds. Once the
ribbons have dried, the ribbons may be removed from the mold and
coupled together to form a layered bioremovable composite material.
The bioremovable composite material made using either process can
then be used to make the finished composite stent.
[0075] In another embodiment, the bioremovable composite material
may be prepared by extruding a mixture of bioremovable polymer and
bioremovable ceramic material in the shape of a tube. The tube may
be cut to have a resilient helical shape. The bioremovable
composite material may also be prepared using an integrated process
where the different layers of material are simultaneously extruded
and immediately coupled together.
[0076] One or more bioactive agents (also referred to herein as
therapeutic agents) may be coated onto the stents 10, 30 or
embedded inside the stents 10, 30. For example, bioactive agents
may be embedded in the bioremovable polymer so that as the stents
10, 30 degrade, the bioactive agent is slowly released. In another
embodiment, the bioremovable ceramic material may be porous and
impregnated with the bioactive agent. As the bioremovable ceramic
material is exposed and removed, the bioactive agents may be
released. The concentration of bioactive agents in the stents 10,
30 may be selected based on the rate at which the stents 10, 30 are
removed so that the appropriate dose of bioactive agent is
continually being released until the stents 10, 30 have fully
degraded.
[0077] It should be appreciated that anyone or combination of a
wide variety of bioactive agents may be suitable to be used with
the stents 10, 30 depending on the application and the particular
pathology. The term "bioactive agent" includes pharmacologically
active substances that produce a local or systemic effect in a
patient. The term thus means any pharmacological substance intended
for use in the diagnosis, cure, mitigation, treatment or prevention
of disease or in the enhancement of desirable physical or mental
development and conditions in a patient. Bioactive agents that may
be used in connection with a vascular stent include drugs such as
heparin, prostacyclin, angiopeptin, and/or methotrexate. Other
bioactive agents that may be used include, without limitation:
antiinfectives such as antibiotics and antiviral agents;
chemotherapeutic agents (i.e. anticancer agents); anti-rejection
agents; analgesics and analgesic combinations; anti-inflammatory
agents; hormones such as steroids; growth factors such as vascular
endothelial growth factor (VEGF); stem cells, and other naturally
derived or genetically engineered proteins, polysaccharides,
glycoproteins, or lipoproteins. In one embodiment, the stent may be
coated with stem cells to facilitate tissue repair at the site of
the occlusion in the lumen. The outside surface of the stent may
also be coated with ceramic material (e.g., flakes of bioremovable
ceramic material) to provide a suitable surface structure for the
stem cells to grow on.
EXAMPLES
[0078] The following examples are provided to further illustrate
the subject matter disclosed herein. The following examples should
not be considered as being limiting in any way.
Example 1
Preparation of Layered Polymer/Ceramic Composite
[0079] In this example, a multi-layer composite ribbon was prepared
using high aspect ratio thin flakes as follows. It should be
appreciated that although the ceramic material is not bioremovable,
this example demonstrates the feasibility of making the polymer
ceramic composite material. Other bioremovable ceramic materials
may be substituted for the titania.
[0080] Two polymer solutions were initially prepared. The first
solution ("Solution A") contained 20 wt. % of bioremovable polymer
(50/50 PLA/PGA copolymer available from Lakeshore Biomaterials as
5050DL High IV) in acetone. The second solution ("Solution B") was
the same as Solution A with titania flakes added (approximately 1/3
of the volume was titania flakes). The titania flakes were prepared
using the sol-gel process described in U.S. Pat. No. 3,709,706
issued to Sowman, which is hereby incorporated by reference in its
entirety.
[0081] The solutions were used to prepare a seven layer ribbon by
applying alternating coats of each solution on top of each other
starting with Solution A. Each layer was allowed to dry before the
next layer was added. When each coating was applied to the dried
layer, the solvent/polymer material from the coating acted to
slightly solvate the very top of the dried layer thereby adhering
the layers together. Each coating of Solution B was thin enough
that the flat surfaces of the flakes in the coating were oriented
parallel to the flat surface of the ribbon.
Example 2
Preparation of Calcium Phosphate Flakes from Solution
[0082] In this example, tricalcium phosphate flakes were prepared
from solution as follows. A solution was formed by adding 2 grams
of amorphous calcium phosphate powder (available from
Plasma-Biotal, Ltd. as Captal A.C.P.) to 80 ml of an 11.1 wt. %
solution of citric acid (Aldrich) in water. The mixture was stirred
for one hour at room temperature to form a slightly cloudy liquid.
The slightly cloudy liquid was passed through a 0.2 micron syringe
filter to remove undissolved debris, resulting in a clear solution.
Several flat alumina plates were coated with this solution by
spreading the solution over the surface with a glass rod. The
plates were placed in an oven that was heated at 65.degree. C.
until the coating dried. The dried coating was clear in appearance.
Once the coating had dried, the plates were transferred from the
oven to a furnace where the coating was sintered at 650.degree. C.
in air. The sintered coating was white in appearance. The thin
white coating was scraped off the alumina plates with a razor blade
to produce flakes.
Example 3
Preparation of Calcium Phosphate Flakes from Dispersion
[0083] In this example, tricalcium phosphate flakes were prepared
from a aqueous dispersion as follows. A flat smooth alumina plate
was cleaned with acetone and coated with an aqueous dispersion of
amorphous calcium phosphate nanoparticles (available from
Plasma-Biotal as Tri Calcium Orthophosphate Ca.sub.3P0.sub.4 water
suspension) using a #20 Mayer rod. The plate was placed in an oven
heated at 65.degree. C. until the coating dried. Once the coating
had dried, the plate was transferred to a kiln and fired at
1150.degree. C. in air. The resulting ceramic flakes were thin and
strong.
Example 4
Preparation of a Helical Ribbon of Composite Material Using PCL
[0084] In this example, a helical shaped composite material was
prepared as follows. Initially two solutions were prepared. The
first solution ("Solution C") was prepared by adding PCL (available
from Solvay as CAPA 6500) to methylene chloride to form a 7.7 wt. %
solution of PCL. The second solution ("Solution D") was formed by
adding 1.0 wt. % tricalcium phosphate flakes prepared in Example 3
to Solution C. Solutions C and D were loaded into separate
rectangular templates (each template was approximately 6.4 mm wide,
200 mm long, and 0.44 mm deep) to dry at room temperature in air.
Once the ribbons dried, the ribbons were cut from the templates.
This method was used to make three strips from Solution C and two
ribbons from Solution D.
[0085] The dried ribbons were stacked on top of each other in
alternating fashion with the ribbons of Solution D positioned
between the ribbons of Solution C. The stack was then clamped
between two flat metal plates and placed in an oven heated at
60.degree. C. overnight to adhere the layers together. Once the
layers were adhered together, the composite material was coiled
around a glass rod. Tape and a wire mesh sleeve were used to hold
the composite material in place. This assembly was heated overnight
at 60.degree. C. to set the helical shape. The result was a helical
ribbon of composite material that had an internal diameter that was
approximately the same size as the diameter of the glass rod.
Example 5
Preparation of a Helical Ribbon of Composite Material Using
PLA/PGA
[0086] In this example, the method from Example 4 was repeated
except that a solution of PLA/PGA polymer (50/50 PLA/PGA available
from Lakeshore Biomaterials as 5050DL High IV) was substituted for
the PCL. The composite material stack was not heated since the
individual ribbons of material adhered strongly to each other in
air at room temperature. The composite material was coiled around
the glass rod and left overnight at room temperature to create the
coil shape. The result was a helical ribbon of composite material
that had an internal diameter that was approximately the same size
as the diameter of the glass rod.
Example 6
Preparation of a Narrow Helical Ribbon of Composite Material
[0087] In this example, a stack of alternating ribbons of material
was made as described in Example 4. After the stack was heat
pressed to seal the layers together, approximately 1.6 mm of
material was trimmed from each long edge. The composite material
was coiled and heated as previously described to produce a smaller,
finer helical structure.
Example 7
Preparation of Bioremovable Polymer Material Using PLA/PGA/PCL
[0088] In this example, a bioremovable polymer was prepared using
PLA/PGA/PCL. A flexible ribbon of polymer material was prepared by
coating a 15.9 wt. % solution of PLA/PGA/PCL copolymer (38/12/50
PLA/PGA/PCL, available from Lakeshore Biomaterials as 381250 DLGCL
2E) in methylene chloride (Aldrich) onto a glass sheet and allowing
it to dry at room temperature. The resulting flexible ribbon of
polymer material was easily peeled from the glass surface.
Illustrative Embodiments
[0089] Reference is made in the following to a number of
illustrative embodiments of the subject matter described herein.
The following embodiments illustrate only a few selected
embodiments that may include the various features, characteristics,
and advantages of the subject matter as presently described.
Accordingly, the following embodiments should not be considered as
being comprehensive of all of the possible embodiments. Also,
features and characteristics of one embodiment may and should be
interpreted to equally apply to other embodiments or be used in
combination with any number of other features from the various
embodiments to provide further additional embodiments, which may
describe subject matter having a scope that varies (e.g., broader,
etc.) from the particular embodiments explained below. Accordingly,
any combination of any of the subject matter described herein is
contemplated.
[0090] According to one embodiment, a composite stent comprises: a
loose network of woven fibrous material configured to expand in a
lumen, the fibrous material including bioremovable ceramic
material; and a bioremovable polymer which coats the fibrous
material. The bioremovable ceramic material may include calcium
phosphate material and/or bioactive glass. The bioremovable ceramic
material may include tricalcium phosphate. The bioremovable polymer
may be a first bioremovable polymer and wherein the bioremovable
ceramic material may be coated with the first bioremovable polymer
and the first bioremovable polymer may be coated with a second
bioremovable polymer. The second bioremovable polymer may have a
modulus of elasticity that is lower than the first bioremovable
polymer. The bioremovable polymer may have elastomeric properties
such that the fibrous materials resist sliding past one another
when the stent is expanded.
[0091] According to another embodiment, a composite stent
comprises: a plurality of composite yams woven together to form a
network configured to expand in a lumen, each of the plurality of
composite yams including a plurality of bioremovable ceramic fibers
coated with a bioremovable polymer; wherein at least substantially
all of the plurality of bioremovable ceramic fibers are positioned
substantially parallel to each other. The bioremovable polymer may
be a first bioremovable polymer and wherein the composite stent
comprises a second bioremovable polymer which forms a coating over
the first bioremovable polymer. The first bioremovable polymer may
provide resiliency to the composite stent and the first
bioremovable polymer and/or the second bioremovable polymer may
provide sufficient friction to hold the network in place upon
expansion in the lumen. The first bioremovable polymer may comprise
polylactide and/or polyglycolide. The bioremovable ceramic fibers
may include tricalcium phosphate.
[0092] According to another embodiment, a composite stent
comprises: a continuous cylindrical network of woven fibrous
material configured to expand in a lumen, the fibrous material
including bioremovable ceramic material; and a bioremovable polymer
which coats the fibrous material.
[0093] According to another embodiment, a composite stent
comprises: a network of woven fibrous material configured to expand
in a lumen without substantial rotational movement of the fibrous
material relative to a longitudinal axis of the composite stent,
the fibrous material including bioremovable ceramic material; and a
bioremovable polymer which coats the fibrous material.
[0094] According to another embodiment, a composite stent
comprises: a plurality of substantially cylindrical composite yams
woven together to form a network which is configured to expand in a
lumen, each of the plurality of composite yams including a
plurality of bioremovable ceramic fibers coated with a bioremovable
polymer.
[0095] According to another embodiment, a composite stent
comprises: a plurality of composite yams which form a loose, woven,
continuous, cylindrical network configured to expand in a lumen,
each of the plurality of composite yams including a plurality of
bioremovable ceramic fibers oriented substantially parallel to each
other; wherein the plurality of bioremovable ceramic fibers are
coated with a first bioremovable polymer and the first bioremovable
polymer is coated with a second bioremovable polymer.
[0096] According to another embodiment, a composite stent
comprises: a first layer comprising bioremovable ceramic material;
a second layer comprising a bioremovable polymer, the second layer
being coupled to the first layer to form a sheet; wherein the sheet
is coiled and configured to expand in a lumen. The bioremovable
ceramic material may include calcium phosphate material and/or
bioactive glass. The bioremovable ceramic material may include
tricalcium phosphate. The bioremovable polymer may comprise
polylactide and/or polyglycolide. The composite stent may comprise
a third layer which includes bioremovable polymer, the third layer
being coupled to the first layer so that the first layer is
positioned between the first layer and the third layer. The
composite stent may comprise a fourth layer which includes a
bioremovable ceramic material and a fifth layer which includes
bioremovable polymer, the fourth layer being coupled to the third
layer and the fifth layer being coupled to the fourth layer so that
the fourth layer is positioned between the third layer and the
fifth layer. The sheet may include a plurality of openings. The
openings may have any suitable geometrical shape such as hexagonal,
circular, triangular, and the like. The sheet may be about 10
microns to 200 microns thick. The first layer may include a
plurality of flakes of bioremovable ceramic material.
[0097] According to another embodiment, a composite stent
comprises: a first layer comprising bioremovable ceramic flakes; a
second layer comprising a bioremovable polymer, the second layer
being coupled to the first layer to form a sheet; wherein the sheet
is wound and configured to expand in a lumen.
[0098] According to another embodiment, a composite stent
comprises: a plurality of layers comprising a layer which includes
a bioremovable ceramic material which is coupled to another layer
which includes a bioremovable polymer; wherein the plurality of
layers is wound and configured to expand in a lumen.
[0099] According to another embodiment, a composite stent
comprises: a multi layer sandwich which includes a layer of
bioremovable ceramic material coupled to a layer which includes a
bioremovable polymer which provides resilience to the sandwich;
wherein the sandwich includes plurality of holes therethrough;
wherein the sandwich is configured to be wound and inserted into a
lumen; and wherein the sandwich is configured to unwind and expand
to a fixed position in the lumen. The layer of ceramic material may
include bioremovable ceramic material.
[0100] According to another embodiment, a composite stent
comprises: a plurality of layers that include bioremovable polymer;
and a plurality of flakes of bioremovable ceramic material; wherein
the plurality of layers alternate between having a high
concentration of the plurality of flakes and having a low
concentration of the plurality of flakes; and wherein the composite
stent is expandable. The bioremovable ceramic material may include
tricalcium phosphate. The bioremovable polymer may include
polylactide, polyglycolide, polycaprolactone, and/or copolymers
thereof. The layers that have a low concentration of bioremovable
ceramic material may be substantially free or completely free of
any of the plurality of flakes. The plurality of layers may include
at least three layers that have a low concentration of the
plurality of flakes. The composite stent may be resilient and the
resilient properties of the composite stent may cause it to move
from a contracted configuration where the composite stent is sized
to be positioned in a bodily lumen to an expanded configuration
where the composite stent is sized to hold the bodily lumen open.
Each of the plurality of flakes may be porous. The composite stent
may comprise a bioactive agent positioned in the pores of the
plurality of flakes. The bioactive agent may include heparin,
prostacyclin, angiopeptin, and/or methotrexate.
[0101] According to another embodiment, a composite stent
comprises: a layer of bioremovable polymer that includes a
plurality of flakes of bioremovable ceramic material dispersed in
the bioremovable polymer; wherein the plurality of flakes of
bioremovable ceramic material are oriented parallel to each other
and to the surfaces of the layer. The bioremovable ceramic material
may include tricalcium phosphate. The bioremovable polymer may
include polylactide, polyglycolide, polycaprolactone, and/or
copolymers thereof. The average aspect ratio of the plurality of
flakes may be approximately 10 to 20. Each of the plurality of
flakes may be porous. The layer may be a first layer and wherein
the composite stent includes a second layer of bioremovable polymer
coupled to the first layer, the second layer being substantially
free or completely free of any bioremovable ceramic material.
[0102] According to another embodiment, a composite stent comprises
a plurality of flakes of bioremovable ceramic material embedded in
bioremovable polymer. The bioremovable ceramic material may include
tricalcium phosphate. The bioremovable polymer may include
polylactide, polyglycolide, polycaprolactone, and/or copolymers
thereof. The composite stent may be coated with stem cells. The
average aspect ratio of the plurality of flakes may be
approximately 5 to 30. The average aspect ratio of the plurality of
flakes may be approximately 10 to 20. The composite stent may
comprise a first layer that includes the plurality of flakes and a
second layer of bioremovable polymer coupled to the first layer,
the second layer being substantially free or completely free of any
bioremovable ceramic material. Each of the plurality of flakes may
be porous. The composite stent may comprise a bioactive agent
positioned in the pores of the plurality of flakes. The bioactive
agent may include heparin, prostacyclin, angiopeptin, and/or
methotrexate.
[0103] According to another embodiment, a composite stent
comprises: bioremovable polymer; and bioremovable ceramic material;
wherein the composite stent has a helical shape; and wherein the
composite stent is resilient and resilient properties of the stent
cause it to move from a contracted configuration to an expanded
configuration. The composite stent may be wound and in a state of
tension in the contracted configuration and the composite stent is
at least substantially unwound and not in a state of tension in the
expanded configuration. The composite stent may have a plurality of
openings in it. The composite stent may comprise a first layer that
includes the bioremovable ceramic material embedded in the
bioremovable polymer and a second layer of bioremovable polymer
coupled to the first layer, the second layer being substantially
free or completely free of any bioremovable ceramic material.
[0104] According to another embodiment, a composite stent
comprises: a ribbon of bioremovable polymer; and a plurality of
flakes of bioremovable ceramic material embedded in the
bioremovable polymer; and a plurality of chopped fibers of
bioremovable ceramic material embedded in the bioremovable polymer;
wherein the flakes are parallel to a surface of the ribbon and the
fibers are parallel to a longitudinal direction of the ribbon. The
composite stent may be expandable. The mean length of the plurality
of fibers may be approximately 50 to 200 microns and the mean
diameter of the plurality of fibers may be approximately 5 to 20
microns. The composite stent may have a plurality of openings in
it. The composite stent may be resilient and the resilient
properties of the composite stent may cause it to move from a
contracted configuration where the composite stent is sized to be
inserted into a lumen to an expanded configuration where the
composite stent supports and/or dilates the lumen. The composite
stent may comprise a plurality of layers of bioremovable polymer
that alternate between having a high concentration of the plurality
of flakes and/or the plurality of fibers and having a low
concentration of the plurality of flakes and/or the plurality of
fibers.
[0105] According to another embodiment, a method of making
bioremovable composite material comprises: extruding a mixture of
bioremovable polymer and bioremovable ceramic material to form the
bioremovable composite material. The bioremovable composite
material may include a plurality of flakes of bioremovable ceramic
material. The method may comprise heating the mixture as the
mixture is extruded. The method may comprise making openings in the
bioremovable composite material. The bioremovable composite
material may have alternating layers that have a high concentration
of bioremovable ceramic material and a low concentration of
bioremovable ceramic material. The method may comprise coupling the
bioremovable composite material to bioremovable polymer. The method
may comprise using the bioremovable composite material to make a
composite stent that is configured to move from a contracted
configuration where the composite stent is sized to be positioned
in a bodily lumen to an expanded configuration where the composite
stent is sized to hold the bodily lumen open.
[0106] According to another embodiment, a method of making
bioremovable composite material comprises: coupling a first layer
of bioremovable polymer that is substantially free or completely
free of bioremovable ceramic material to a second layer of
bioremovable polymer that includes bioremovable ceramic material
embedded therein. The method may comprise coupling the second layer
to a third layer of bioremovable polymer that is substantially free
or completely free of bioremovable ceramic material and coupling
the third layer to a fourth layer of bioremovable polymer that
includes bioremovable ceramic material embedded therein. The method
may comprise heating the first layer and the second layer to couple
the first layer and the second layer together. The method may
comprise solvating a surface of the first layer and coupling the
second layer to the solvated surface of the first layer. The
bioremovable ceramic material embedded in the second layer may
include a plurality of flakes of bioremovable ceramic material.
[0107] According to another embodiment, a method of making
bioremovable composite material comprises: mixing bioremovable
ceramic material with bioremovable polymer to form a first mixture;
solidifying the first mixture in a mold to form a first ribbon;
coupling the first ribbon and a second ribbon together to form a
bioremovable composite material, the second ribbon including
bioremovable polymer. A plurality of flakes of bioremovable ceramic
material may be mixed with the bioremovable polymer to form the
first mixture. The bioremovable ceramic material may be mixed with
the bioremovable polymer to form the first mixture includes
tricalcium phosphate. The method may comprise solidifying
bioremovable polymer in a mold to form the second ribbon. The
method may comprise heating the first ribbon and the second ribbon
to couple the first ribbon and the second ribbon together. The
method may comprise coiling the bioremovable composite material to
form a composite stent. The second ribbon may be substantially free
or completely free of bioremovable ceramic material.
[0108] According to another embodiment, a method of using a
composite stent comprises: positioning the composite stent in a
bodily lumen, the composite stent including bioremovable polymer
and bioremovable ceramic material, the composite stent being in a
contracted configuration where the composite stent is coiled in a
state of tension; and releasing the composite stent so that the
resilient properties of the composite stent cause the composite
stent to expand in the bodily lumen.
[0109] The terms recited in the claims should be given their
ordinary and customary meaning as determined by reference to
relevant entries (e.g., definition of "plane" as a carpenter's tool
would not be relevant to the use of the term "plane" when used to
refer to an airplane, etc.) in dictionaries (e.g., consensus
definitions from widely used general reference dictionaries and/or
relevant technical dictionaries), commonly understood meanings by
those in the art, etc., with the understanding that the broadest
meaning imparted by any one or combination of these sources should
be given to the claim terms (e.g., two or more relevant dictionary
entries should be combined to provide the broadest meaning of the
combination of entries, etc.) subject only to the following
exceptions: (a) if a term is used herein in a manner more expansive
than its ordinary and customary meaning, the term should be given
its ordinary and customary meaning plus the additional expansive
meaning, or (b) if a term has been explicitly defined to have a
different meaning by reciting the term followed by the phrase "as
used herein shall mean" or similar language (e.g., "herein this
term means," "as defined herein," "for the purposes of this
disclosure [the term] shall mean," etc.). References to specific
examples, use of "i.e.," use of the word "invention," etc., are not
meant to invoke exception (b) or otherwise restrict the scope of
the recited claim terms. Accordingly, the subject matter recited in
the claims is not coextensive with and should not be interpreted to
be coextensive with any particular embodiment, feature, or
combination of features shown herein. This is true even if only a
single embodiment of the particular feature or combination of
features is illustrated and described herein. Thus, the appended
claims should be read to be given their broadest interpretation in
view of the prior art and the ordinary meaning of the claim
terms.
[0110] As used herein, spatial or directional terms, such as
"left," "right," "front," "back." and the like, relate to the
subject matter as it is shown in the drawing FIGS. However, it is
to be understood that the subject matter described herein may
assume various alternative orientations and, accordingly, such
terms are not to be considered as limiting. Furthermore, as used
herein (i.e., in the claims and the specification), articles such
as "the," "a," and "an" can connote the singular or plural. Also,
as used herein, the word "or" when used without a preceding
"either" (or other similar language indicating that "or" is
unequivocally meant to be exclusive--e.g., only one of x or y,
etc.) shall be interpreted to be inclusive (e.g., "x or y" means
one or both x or y). Likewise, as used herein, the term "and/or"
shall also be interpreted to be inclusive (e.g., "x and/or y" means
one or both x or y). In situations where "and/or" or "or" are used
as a conjunction for a group of three or more items, the group
should be interpreted to include one item alone, all of the items
together, or any combination or number of the items. Moreover,
terms used in the specification and claims such as have, having,
include, and including should be construed to be synonymous with
the terms comprise and comprising.
[0111] Unless otherwise indicated, all numbers or expressions, such
as those expressing dimensions, physical characteristics, etc. used
in the specification are understood as modified in all instances by
the term "about." At the very least, and not as an attempt to limit
the application of the doctrine of equivalents to the claims, each
numerical parameter recited in the specification or claims which is
modified by the term "about" should at least be construed in light
of the number of recited significant digits and by applying
ordinary rounding techniques. Moreover, all ranges disclosed herein
are to be understood to encompass any and all subranges subsumed
therein. For example, a stated range of 1 to 10 should be
considered to include any and all subranges between and inclusive
of the minimum value of 1 and the maximum value of 10; that is, all
subranges beginning with a minimum value of 1 or more and ending
with a maximum value of 10 or less (e.g., 5.5 to 10).
* * * * *