U.S. patent application number 14/158628 was filed with the patent office on 2014-05-15 for methods of manufacture of bioresorbable and durable stents with grooved lumenal surfaces for enhanced re-endothelialization.
This patent application is currently assigned to Abbott Cardiovascular Systems Inc.. The applicant listed for this patent is Abbott Cardiovascular Systems Inc.. Invention is credited to Stephen D. Pacetti.
Application Number | 20140134323 14/158628 |
Document ID | / |
Family ID | 46548815 |
Filed Date | 2014-05-15 |
United States Patent
Application |
20140134323 |
Kind Code |
A1 |
Pacetti; Stephen D. |
May 15, 2014 |
METHODS OF MANUFACTURE OF BIORESORBABLE AND DURABLE STENTS WITH
GROOVED LUMENAL SURFACES FOR ENHANCED RE-ENDOTHELIALIZATION
Abstract
Methods of making bioabsorbable stents with grooved lumenal
surfaces for enhanced re-endothelialization are disclosed. Methods
include molding grooves on the lumenal surface of coated
bioresorbable and durable stents. Methods further include molding
grooves on lumenal surfaces of a bioresorbable tube and forming a
scaffold from the tube.
Inventors: |
Pacetti; Stephen D.; (San
Jose, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Abbott Cardiovascular Systems Inc. |
Santa Clara |
CA |
US |
|
|
Assignee: |
Abbott Cardiovascular Systems
Inc.
Santa Clara
CA
|
Family ID: |
46548815 |
Appl. No.: |
14/158628 |
Filed: |
January 17, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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13182155 |
Jul 13, 2011 |
8632847 |
|
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14158628 |
|
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Current U.S.
Class: |
427/2.25 ;
264/171.12 |
Current CPC
Class: |
Y10T 29/49865 20150115;
Y10T 29/49885 20150115; A61L 31/06 20130101; B29C 48/09 20190201;
A61L 31/16 20130101; Y10T 29/49925 20150115; A61F 2/91 20130101;
A61L 31/10 20130101; B29L 2031/7542 20130101; A61F 2/82 20130101;
Y10T 29/49927 20150115 |
Class at
Publication: |
427/2.25 ;
264/171.12 |
International
Class: |
A61F 2/82 20060101
A61F002/82 |
Claims
1. A method of making a stent comprising: providing a bioresorbable
polymer tube having an original diameter; disposing the tube over a
tubular mandrel such that a lumenal surface of the tube faces a
surface of the mandrel, wherein the surface of the mandrel has a
plurality of grooves aligned longitudinally; radially compressing
the tube over the surface of the mandrel such that the grooves at
the surface of the mandrel form grooves on the lumenal surface of
the tube; and forming a stent scaffold from the tube after forming
the grooves, wherein the lumenal surface of the stent scaffold
includes grooves formed from the radial compression that are
aligned along a cylindrical axis of the stent scaffold.
2. The method of claim 1, further comprising forming a coating
comprising a bioresorbable polymer over at least the lumenal
surface of the scaffolding, wherein the coated lumenal surface
includes the grooves of the stent scaffold.
3. The method of claim 1, further comprising forming a coating
comprising a bioresorbable polymer over at least an ablumenal
surface of the scaffolding, wherein the luminal surface is free of
a coating.
4. The method of claim 1, further comprising disposing the tube
over the mandrel into a sliding wedge crimper, wherein the crimper
applies pressure to the tube to radially compress the tube over the
surface of the mandrel.
5. The method of claim 1, wherein the mandrel comprises a heating
element to heat the lumenal surface of the tube during the radial
compression.
6. The method of claim 1, further comprising heating the lumenal
surface of the tube during the radial compression to soften the
tube polymer to facilitate forming the grooves.
7. The method of claim 1, wherein the tube polymer at the lumenal
surface of the tube is softened by a solvent during the radial
compression to facilitate forming the grooves.
8. The method of claim 1, wherein a width of the grooves is 5 to 30
microns and a depth of the grooves is 0.5 to 20 microns.
9. A method of making a stent comprising: conveying a melted
polymer from an extruder barrel through an annulus of an annular
die to form a tube, wherein the annular die has a first surface
which forms an outer surface of the tube and an second surface that
forms an inner surface of the tube, wherein the second surface of
the annular die has grooves aligned longitudinally; allowing the
grooves on the second surface of the annular die to form grooves in
the inner surface of the tube formed as the polymer passes through
the annular die; radially expanding the tube to an expanded
diameter, wherein the radial expansion modifies a size of the
grooves; and fabricating a stent scaffold from the tube with the
expanded diameter, wherein a lumenal surface of the stent scaffold
has the modified grooves that are aligned longitudinally.
10. The method of claim 9, wherein a width of the modified grooves
is 5 to 30 microns and a depth of the modified grooves is 0.5 to 20
microns.
11. The method of claim 9, further comprising determining a groove
size of the mandrel that provides a desired modified grove size in
the expanded tube, wherein the desired modified groove size is a
width of 5 to 30 microns and a depth of 0.5 to 20 microns.
Description
[0001] This is a division of application Ser. No. 13/182,155 filed
Jul. 13, 2011 and is incorporated by reference herein.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to methods of manufacturing medical
devices, in particular, stents.
[0004] 2. Description of the State of the Art
[0005] This invention relates to manufacturing of implantable
medical devices. These devices include, but are not limited to,
radially expandable endoprostheses, that are adapted to be
implanted in a bodily lumen. An "endoprosthesis" corresponds to an
artificial device that is placed inside the body. A "lumen" refers
to a cavity of a tubular organ such as a blood vessel. A stent is
an example of such an endoprosthesis. Stents are generally
cylindrically shaped devices that function to hold open and
sometimes expand a segment of a blood vessel or other anatomical
lumen such as urinary tracts and bile ducts. Stents are often used
in the treatment of atherosclerotic stenosis in blood vessels.
"Stenosis" refers to a narrowing or constriction of a bodily
passage or orifice. In such treatments, stents reinforce body
vessels and prevent restenosis following angioplasty in the
vascular system. "Restenosis" refers to the reoccurrence of
stenosis in a blood vessel or heart valve after it has been treated
(as by balloon angioplasty, stenting, or valvuloplasty) with
apparent success.
[0006] Stents are typically composed of scaffold or scaffolding
that includes a pattern or network of interconnecting structural
elements or struts, formed from wires, tubes, or sheets of material
rolled into a cylindrical shape. This scaffolding gets its name
because it physically holds open and, if desired, expands the wall
of the passageway. Typically, stents are capable of being
compressed or crimped onto a catheter so that they can be delivered
to and deployed at a treatment site.
[0007] Delivery includes inserting the stent through small lumens
using a catheter and transporting it to the treatment site.
Deployment includes expanding the stent to a larger diameter once
it is at the desired location. Mechanical intervention with stents
has reduced the rate of restenosis as compared to balloon
angioplasty.
[0008] Stents are used not only for mechanical intervention but
also as vehicles for providing biological therapy. Medicated stents
provide biological therapy through local administration of a
therapeutic substance. A medicated stent may be fabricated by
coating the surface of either a metallic or polymeric scaffolding
with a polymeric carrier that includes an active or bioactive agent
or drug. A polymeric scaffolding may also serve as a carrier of an
active agent or drug.
[0009] These drug eluting stents (DES) are used in order to
revascularize occluded regions of the coronary vasculature. Current
DES work well yielding single digits of major adverse cardiac
events (MACE) and restenosis at one year for a majority of
patients. Ongoing issues are restenosis, an iatrogenic disease
caused by the intervention itself, and thrombosis. While the onset
of restenosis is gradual, stent thrombosis can occur suddenly and
the outcome is completely contrary to the intent of
revascularization. Stent thrombosis can occur at any time. However,
thrombosis which occurs in the first 30 days (subacute) is thought
to be due more to procedural issues, blood hypercoaguability, poor
stent placement and apposition, and perhaps drug effects. At longer
time points, the goal is for the vessel to heal and
re-endothelialize to avoid late stent thrombosis occurring beyond
30 days. The ongoing rates of late stent thrombosis have been
measured as 0.36 to 0.6% out to five years. Garg S, Serruys P.
Coronary Stents. J Amer Coll Cardiol 2010; 56(10): Suppl S. S1.
[0010] The only truly non-thrombogenic surface is healthy
endothelium. Consequently, rapid and complete re-endotheliazation
has always been a goal for metallic, drug eluting, and
bioresorbable stents in order to reduce and eliminate late stent
thrombosis. As all of the drugs presently used in DES inhibit the
proliferation of endothelial cells, the interest in promoting
endothelial cell growth remains high. After stenting,
re-endotheliatization is achieved primarily by migration of
endothelial cells from adjacent arterial areas of intact
endothelium. Haudenschild C C, Schartz S M. Lab Invest 1979;
41:407-418; Rogers C, Tseng D Y, et al. Circ Res 1999; 84:378-383.
Based on this mechanism, extensive work has been done to understand
factors which affect endothelial cell migration. For DES, a major
emphasis has been on how to achieve faster, or more complete,
endothelial cell migration onto stent struts.
INCORPORATION BY REFERENCE
[0011] All publications and patent applications mentioned in this
specification are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated to be incorporated by
reference, and as if each said individual publication or patent
application was fully set forth, including any figures, herein.
SUMMARY OF THE INVENTION
[0012] Various embodiments of the present invention include a
method of making a stent comprising: providing a stent including a
bioresorbable polymer scaffold and a bioresorbable polymer coating
over at least a portion of the scaffold; disposing the stent over a
tubular mandrel such that a lumenal surface of the stent faces a
surface of the mandrel, wherein the surface of the mandrel has a
plurality of grooves aligned longitudinally; and radially
compressing the stent over the surface of the mandrel such that the
grooves at the surface of the mandrel form grooves on the lumenal
surface of the stent, wherein the grooves on the luminal surface
are aligned along a cylindrical axis of the stent.
[0013] Further embodiments of the present include a method of
making a stent comprising: providing a bioresorbable polymer tube
having an original diameter; disposing the tube over a tubular
mandrel such that a lumenal surface of the tube faces a surface of
the mandrel, wherein the surface of the mandrel has a plurality of
grooves aligned longitudinally; radially compressing the tube over
the surface of the mandrel such that the grooves at the surface of
the mandrel form grooves on the lumenal surface of the tube; and
forming a stent scaffold from the tube after forming the grooves,
wherein the lumenal surface of the stent scaffold includes grooves
formed from the radial compression that are aligned along a
cylindrical axis of the stent scaffold.
[0014] Additional embodiments of the present invention include a
method of making a stent comprising: conveying a melted polymer
from an extruder barrel through an annulus of an annular die to
form a tube, wherein the annular die has a first surface which
forms an outer surface of the tube and an second surface that forms
an inner surface of the tube, wherein the second surface of the
annular die has grooves aligned longitudinally; allowing the
grooves on the second surface of the annular die to form grooves in
the inner surface of the tube formed as the polymer passes through
the annular die; radially expanding the tube to an expanded
diameter, wherein the radial expansion modifies a size of the
grooves; and fabricating a stent scaffold from the tube with the
expanded diameter, wherein a lumenal surface of the stent scaffold
has the modified grooves that are aligned longitudinally.
[0015] Other embodiments of the present invention include a method
of making a stent comprising: providing a stent having a metallic
scaffold and a polymer coating over the scaffold; disposing the
stent over a tubular mandrel such that a lumenal surface of the
stent faces a surface of the mandrel, wherein the surface of the
mandrel has a plurality of grooves aligned longitudinally; and
radially compressing the stent over the surface of the mandrel such
that the grooves at the surface of the mandrel form grooves on the
coating over the lumenal surface of the stent.
[0016] Further embodiments of the present invention include a
method of making a stent comprising: providing a stent having a
metallic scaffold; disposing the stent over a tubular mandrel such
that a lumenal surface of the scaffold faces a surface of the
mandrel, wherein the surface of the mandrel has a plurality of
grooves aligned longitudinally; and radially compressing the stent
over the surface of the mandrel such that the grooves at the
surface of the mandrel form grooves on the lumenal surface of the
metal of the scaffold.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 depicts a stent.
[0018] FIG. 2 depicts a portion of a grooved surface to illustrate
its features.
[0019] FIG. 3A depicts a grooved surface with rectangular
grooves.
[0020] FIG. 3B depicts a grooved surface with triangular
grooves.
[0021] FIG. 3C depicts a grooved surface with semicircular
grooves.
[0022] FIG. 4 depicts a radial cross-section of a scaffold 160 with
grooves in the lumenal surface.
[0023] FIG. 5 depicts a schematic illustration of a mandrel with
grooves in its surface aligned longitudinally or parallel along its
cylindrical axis.
[0024] FIG. 6A depicts a radial cross-section of struts of a stent
disposed over a mandrel with grooves on its surface that are
aligned longitudinally.
[0025] FIG. 6B depicts the stent and mandrel of FIG. 6A disposed
within the aperture of a sliding wedge crimper.
[0026] FIG. 6C illustrates the stent of FIG. 6B as shown by struts
after the crimping procedure showing the grooves formed in the
lumenal surface.
[0027] FIG. 7A depicts the radial cross-section of a polymer tube
disposed over a mandrel with grooves on its surface that are
aligned longitudinally.
[0028] FIG. 7B illustrates the tube and mandrel of FIG. 7A disposed
within the aperture of a sliding wedge crimper.
[0029] FIG. 7C illustrates the tube of FIG. 7B after the crimping
procedure showing the grooves formed in the lumenal surface.
[0030] FIG. 8A depicts a cross-section of a surface section that
has grooves.
[0031] FIG. 8B depicts the surface section of FIG. 8A with a
planarizing coating that fills in grooves and planarizes the
surface.
[0032] FIG. 8C depicts the surface section of FIG. 8A with a
conformal coating.
[0033] FIG. 9A shows a radial cross-section of a conventional
extrusion die.
[0034] FIG. 9B shows a radial cross-section of an extrusion die of
the present invention.
[0035] FIG. 10 depicts a section of a tube wall before and after
radial expansion.
DETAILED DESCRIPTION OF THE INVENTION
[0036] One example of early work directed to promoting
endothelialization was measurement of adhesion of endothelial cells
on 316L stainless steel surfaces with different etched grain sizes.
Choubey A, Marton O, Sprague E A. J Mater Sci: Mater Med 2009;
20:2105-2116. This work demonstrated that endothelial cells
attached better to the 16 micron grain size. That 16 micron
periodicity was advantageous, at least in cell culture.
[0037] In another study, the effect of grooves in a metal surface
was examined on endothelial cell migration rates in vitro. Palmaz J
C, Benson A, Sprague E A. JVIR 1999; 10:439-444. Grooves of various
sizes were made in nitinol with a silicon carbide-impregnated
cloth. The migration distances of human aortic endothelial cells on
the various surfaces shows faster endothelial cell migration on
unidirectional grooves of a certain size (15-22 microns). The cells
aligned with the grooves, elongated, and became more numerous on
grooved surfaces. More recent endothelial migration data in vitro
showed similar results. Sprague E A, Impact of Texture and Strut
Thickness: experimental and clinical evidence, TCT 2010,
Washington. While these in vitro results are intriguing, a
reasonable question is whether they can be repeated in vivo.
Sprague also presented in vivo endothelialization data which was
gathered in a porcine carotid model using a stent which
superficially resembles the Palmaz-Schatz. Groove size was 12-15
microns. A large, and statistically significant difference in
endothelial coverage was seen at 7 days, while at 3 weeks and
beyond there was no difference as the vessels were fully
endothelialized by then.
[0038] With results such as this, it is an open question why no
manufacturer has conducted clinical investigations into the utility
of a lumenally grooved stent. There are several reasons why this
concept has not made its way into a product. First, there are still
questions as to how to mass produce stents with grooves. Second,
there have been other, more attractive technologies to pursue for
stents such as drug delivery and better acute performance. Third,
determining benefit in a human clinical trial setting would be
expected to be challenging. For a DES, it would not be expected
that grooves would improve antirestenotic efficacy. It is
hypothesized that grooves would improve re-endothelialization which
occurs at 3-6 months in humans. However, there is no current method
to directly assess re-endothelialization in humans unless they
expire during the trial. Other clinical endpoints which may be
affected by re-endothelialization such as MACE, target vessel
failure (TVF), myocardial infarction (MI), death, and stent
thrombosis can be monitored, but are currently at low incidence
rates. It is statistically challenging to show improvement in these
endpoints with current generation DES and financially driven
pessimism usually wins out in deciding not to fund product
development or a trial. Still, as DES and BMS continue to evolve
and mature there is a need to improve these devices further, even
if by only an incremental amount. Therefore, constructs and
production techniques are needed to apply the grooved surface
concept to bioresorbable and to polymer coated metallic DES.
[0039] The methods described herein are generally applicable to a
variety of implantable medical device. In particular, the methods
can be applied to tubular implantable medical devices such as
self-expandable stents, balloon-expandable stents, and
stent-grafts.
[0040] A stent may include a pattern or network of interconnecting
structural elements or struts. FIG. 1 depicts a view of a stent
100. In some embodiments, a stent may include a body, backbone, or
scaffolding having a pattern or network of interconnecting
structural elements 105. Stent 100 may be formed from a tube (not
shown). The structural pattern of the device can be of virtually
any design. The embodiments disclosed herein are not limited to
stents or to the stent pattern illustrated in FIG. 1. The
embodiments are easily applicable to other patterns and other
devices. The variations in the structure of patterns are virtually
unlimited.
[0041] A stent such as stent 100 may be fabricated from a tube or a
sheet by rolling and bonding the sheet to form the tube. A polymer
tube or sheet can be formed by extrusion or injection molding while
a metallic tube can be made by extrusion or molten metal
casting.
[0042] A stent pattern, such as the one pictured in FIG. 1, can be
formed in a tube or sheet with a technique such as laser cutting or
chemical etching. The stent can then be crimped on to a balloon or
catheter for delivery into a bodily lumen.
[0043] An implantable medical device of the present invention can
be made partially or completely from a biodegradable,
bioresorbable, bioabsorbable, or biostable polymer. A polymer for
use in fabricating an implantable medical device can be biostable,
bioresorbable, bioabsorbable, biodegradable or bioerodable.
Biostable refers to polymers that are not biodegradable. The terms
biodegradable, bioresorbable, bioabsorbable, and bioerodable are
used interchangeably and refer to polymers that are capable of
being completely degraded and/or eroded into different degrees of
molecular levels when exposed to bodily fluids such as blood and
can be gradually resorbed, absorbed, and/or eliminated by the body.
The processes of breaking down and absorption of the polymer can be
caused by, for example, hydrolysis and metabolic processes.
[0044] A stent made from a bioresorbable polymer is intended to
remain in the body for a duration of time until its intended
function of, for example, maintaining vascular patency and/or drug
delivery is accomplished. After the process of degradation,
erosion, absorption, and/or resorption has been completed, no
portion of the biodegradable stent, or a biodegradable portion of
the stent will remain. In some embodiments, very negligible traces
or residue may be left behind.
[0045] A bioresorbable scaffolding can be made partially or
completely of polymers including poly(L-Lactide) (PLLA),
poly(L-lactide-co-D,L-lactide) (PLDLA), poly(D-lactide) (PDLA),
poly(D,L-lactide) (PDLLA), polyglycolide (PGA),
poly(D,L-lactide-co-glycolide) (PLGA), and
poly(L-lactide-co-glycolide) (PLLGA). PLLA is a suitable polymer
for a stent scaffold due to its high crystallinity and mechanical
strength. Greater flexibility for a bioresorbable scaffold can be
achieved by use of PLDLA. With respect to PLGA, the stent
scaffolding can be made from PLLGA with a mole % of GA between 5-15
mol %. The PLGA can have a mole % of (LA:GA) of 85:15 (or a range
of 82:18 to 88:12), 95:5 (or a range of 93:7 to 97:3), or
commercially available PLGA products identified as being 85:15 or
95:5 PLGA. Such polymers may also be used for a bioresorbable
coating on a bioresorbable scaffolding. The coating polymer may be
combined with a drug, such as an antiproliferative or
anti-inflammatory agent.
[0046] Detailed discussion of the manufacturing process of a
bioresorbable stent can be found elsewhere, e.g., US 2007/0283552.
The fabrication methods of a bioresorbable stent can include the
following steps:
[0047] (1) forming a polymeric tube from a bioresorbable polymer
resin using extrusion,
[0048] (2) radially expanding the formed tube to increase radial
strength,
[0049] (3) forming a stent scaffolding from the expanded tube by
laser machining a stent pattern in the expanded tube with laser
cutting (in exemplary embodiments, the strut thickness can be
100-200 microns, or more narrowly, 120-180, 130-170, or 140-160
microns),
[0050] (4) forming a therapeutic coating over the scaffolding,
[0051] (5) crimping the stent over a delivery balloon to a reduced
diameter for delivery, and
[0052] (6) sterilization with election-beam (E-beam) radiation.
[0053] With respect to step (1), an extruder generally includes a
barrel through which a polymer melt is conveyed from an entrance to
an exit port. A polymer resin is fed to the extruder barrel near
its proximal end from a hopper as a solid, for example, in the form
of a pellet. The polymer in the extruder barrel is heated to
temperatures above the melting temperature (Tm) of the polymer and
exposed to pressures that are generally far above ambient.
[0054] In the radial expansion step (2), the extruded polymer tube
may be expanded by blow molding. The tube is disposed in a mold.
The tube is expanded by increasing the pressure inside the mold and
heating the tube. The tube expands against the inner surface of the
mold so that the outer diameter of the expanded tube is at the
inner diameter of the tube. The tube may be heated to temperature
above the glass transition temperature (Tg) of the tubing polymer.
For example, PLLA has Tg of about 60 to 65 deg C. (Medical Plastics
and Biomaterials Magazine, March 1998), so the expansion
temperature may be 60 to 80 deg C. The percent radial expansion (%
RE) is defined as 100%.times.(Inside Diameter of Expanded
Tube/Original Inside Diameter of Tube-1). The % RE can be 100 to
200, 200 to 300, 300 to 400, or more than 400. The tube may also be
axially deformed during the radial expansion step.
[0055] In the coating step (4), a coating material is applied to
the surface of the scaffolding to form the coating. The coating
material is a solution including dissolved polymer (e.g., PDLLA)
mixed with a drug (e.g., everolimus). After application of the
coating material, the solvent is removed, leaving a coating of
polymer and drug. A coating of a desired thickness may be formed by
multiple coating material applications. In between coating
applications, solvent is removed or partially removed, followed by
application of additional coating material.
[0056] Certain embodiments of the present invention include methods
of making a bioabsorbable stent having a lumenal surface that has
grooves aligned longitudinally or parallel with the cylindrical
axis of the stent. The grooves promote re-endothelialization on the
lumenal suface when the stent is implanted. The stent may include a
bioresorbable stent scaffolding structure made of a polymer and a
coating over the scaffolding that is made of a different polymer
and a drug. In some embodiments, the luminal surface is free of
coating and the grooves are in the polymer of the scaffold on the
luminal surface. Such a scaffold can further include a coating on
the abluminal surface of the scaffold.
[0057] An exemplary bioresorbable stent can include a PLLA
scaffolding with coating including PDLLA. The coating can further
include an antiproliferative drug such as everolimus. The thickness
of the coating can be 1 to 3 microns.
[0058] Further embodiments of the invention include methods of
making a stent including a metallic stent scaffold with a polymer
coating on at least the lumenal surface of the stent scaffold with
grooves in the lumenal surface extending longitudinally or parallel
with the cylindrical axis of the stent. Other embodiments include a
metallic scaffolding with grooves in the metallic luminal surface
which is free of a coating and optionally, a coating on the
abluminal surface. An exemplary stent can include a metallic
scaffolding with a poly(vinylidene fluoride-co-hexafluoropropylene)
(PVDF-HFP) coating that is mixed with everolimus.
[0059] A groove may be defined as a long narrow furrow, channel, or
recess in a surface. FIG. 2 depicts a portion 120 of a grooved
surface. Portion 120 includes plateau surfaces 122, 124, and 126,
which are raised surfaces between grooves, and grooves 128 and 130.
Grooves 128 and 130 run along an axis or direction as shown by
arrows 132 and 134, respectively. A cross-section of the grooves
transverse to the axis of a groove can be rectangular, sinusoidal,
semicircular, triangular, or any other regular or irregular shape.
Exemplary cross-sections are shown in FIG. 3A-C. FIG. 3A depicts a
grooved surface 140 with rectangular grooves 142. FIG. 3B depicts a
grooved surface 144 with triangular grooves 146. FIG. 3C depicts a
grooved surface 148 with semicircular grooves 150.
[0060] The grooves may be characterized by depth of the grooves
(Dg) and width of the grooves (Wg) (or periodicity) and the width
of plateau (Wp), as shown in FIG. 3A. Dg may correspond to the
deepest point of the groove. Wg may correspond to the widest point
of the groove. W.sub.P may be 2 to 40 microns, or more narrowly 10
to 20 microns. Wg may be 5 to 30 microns, or more narrowly, 10 to
20 microns. Dg may be 0.5 to 20 microns or more narrowly, 1 to 10
microns.
[0061] In some embodiments of a bioabsorbable scaffold with or
without a coating, part or the entire lumenal surface of the
scaffold has grooves. The grooves may be aligned with the
longitudinal axis of the scaffold. However, in these and other
embodiments of the present invention, the grooves may be aligned
along any direction, for example, transverse to the cylindrical
axis, between 0 and 90 degrees to the cylindrical axis, which
includes spiral or helical grooves. Longitudinally aligned grooves
are preferred since they appear to be most favorable for promoting
re-endothelialization.
[0062] FIG. 4 depicts a radial cross-section of a scaffold 160 with
grooves in the lumenal surface. Strut cross-sections 162 have an
abluminal surface 164, a lumenal surface 166, and side wall
surfaces 168. Grooves 170 are shown in lumenal surfaces 166 with
the size of the grooves exaggerated for clarity. Additionally, the
coating is not shown for clarity.
[0063] In certain embodiments, grooves may be formed in a lumenal
surface of a stent that includes a bioresorbable polymer scaffold
and a bioresorbable polymer coating on or above at least the
lumenal surface of the scaffold. In another embodiment, grooves may
be formed in the luminal surface of a stent that includes a
bioresorbabale polymer scaffold with no coating on the luminal
surface of the coating and optionally a bioresorbable polymer
coating on at least the abluminal surface. Embodiments of methods
include molding grooves in the luminal surface of the stent. These
embodiments include disposing the stent over a tubular mandrel
having a plurality of longitudinal grooves in the surface of the
mandrel. For coronary applications, the inner diameter of the
scaffold can be 3 to 4 mm, or more narrowly, 3 to 3.5 mm. For
peripheral applications the diameter of the scaffold can be 4 to 6
mm, or more narrowly, 5 to 6 mm, or greater than 6 mm.
[0064] The inner diameter of the scaffolding may initially be
greater than diameter of the mandrel, for example, 0 to 1% greater,
1-5% greater, 5-10% greater, or more than 10% greater.
Alternatively, the diameter of the scaffold may be the same as the
diameter of the mandrel, and thus, initially has a tight fit over
the mandrel. The lumenal surface of the stent faces a surface of
the mandrel. The stent may then be radially compressed over the
surface of the mandrel such that the grooves at the surface of the
mandrel form or mold grooves on the coating of the lumenal surface
of the scaffold or on the scaffold. The formation and retention of
the grooves may be facilitated by softening the lumenal surface of
the scaffold.
[0065] In some embodiments, the stent may be radially compressed by
disposing the stent and the mandrel within a crimping device
adapted to apply radial pressure to a stent. The radial pressure
may reduce its diameter. In this, and in other embodiments, unless
otherwise noted, the pressure applied to the stent to form the
grooves may be between 10 and 500 psi. An exemplary crimping device
is a sliding wedge or iris crimper in which adjacent
pie-piece-shaped sections or wedges move inward and twist, much
like the leaves in a camera aperture. Other types of crimping
devices that may be used are described in US 2005/0119720.
[0066] FIG. 5 depicts a schematic illustration of a mandrel 180
with grooves 182 in its surface aligned longitudinally or parallel
to its cylindrical axis 184. Mandrel 180 has a diameter Dm and a
length Lm. The size of the grooves is exaggerated for clarity.
[0067] The mandrel can be hollow or solid. The mandrel can be made
of a metal or ceramic material. Exemplary metallic materials
include 300 series stainless steels, 316L stainless steel, tool
steels, chrome molybdenum steels, cobalt chromium based alloys such
as L-605, cobalt based satellite alloys, cobalt nickel alloys such
MP35N, and nickel-based alloys. The grooves in the surface of the
mandrel may be formed using a variety of techniques including
electrical discharge machining, laser machining, and ion beam
milling.
[0068] FIGS. 6A-6C illustrate a process of forming grooves in a
lumenal surface of a bioabsorbable stent. FIG. 6A depicts a radial
cross-section of struts 190 of a stent disposed over a mandrel 192
with grooves 194 on its surface that are aligned longitudinally.
FIG. 6B depicts the stent and mandrel disposed within the aperture
of a sliding wedge crimper 196 which includes a plurality of
sliding wedges 198 that form the aperture. Sliding wedges 198 slide
and rotate inward, decreasing the size of the aperture. As the
aperture size decreases, the surface of the wedges at the aperture
apply a radial pressure on struts 190. Struts 190 are pressed into
the grooved surface of mandrel 192 which forms or molds grooves in
the lumenal surface of the stent.
[0069] The aperture is of the crimper is then retracted and the
stent and mandrel are removed from the crimper. The diameter of the
stent may then increase back to or close to its original diameter.
FIG. 6C illustrates the stent as shown by struts 190 after the
crimping procedure showing the grooves in the lumenal surface 199
that are formed.
[0070] When forming grooves in a coated luminal surface, since both
the scaffold and coating are polymer, the grooves may be formed in
the coating polymer and the scaffold polymer. Therefore, the
grooves can have a depth greater depth than the thickness of the
coating. As discussed, the luminal surface of the scaffold may also
be free of coating polymer in which case the grooves are formed
only in the scaffold polymer.
[0071] As indicated, the formation of the grooves may be
facilitated by softening the polymer at the lumenal surface or
surface region. In some embodiments, the lumenal surface of the
stent may be heated to soften the polymer at the lumenal surface.
In such embodiments, the polymer surface may be heated by the
mandrel. The mandrel or the surface of the mandrel may be heated in
a number ways. The mandrel may be heated by an electrical heating
element or elements disposed within the mandrel. Additionally,
infra-red or microwave elements within the mandrel can heat the
mandrel. In other embodiments, the mandrel can be heated by using a
hollow mandrel and blowing a warm gas through the mandrel.
[0072] In some embodiments, the temperature of the mandrel surface
or the polymer surface during the radial compression may be above
ambient temperature to Tg of the polymer at the lumenal surface.
For example, between 30 degrees C. to Tg. In other embodiments, the
temperature during radial compression is above the Tg of the
polymer at the lumenal surface. For example, the temperature is Tg
to Tg+10 deg C., Tg+10 deg C. to Tg+20 deg C., or greater than
Tg+20 deg C. For example, Tg of PDLLA is 55 to 60 deg C. Medical
Plastics and Biomaterials Magazine, March 1998.
[0073] The temperature for heating a stent with a PDLLA coating
over a PLLA scaffold may be 55 to 70 deg C., or more narrowly, 55
to 60 deg C. In other embodiments, the temperature of the mandrel
or the polymer surface can be 30 to 40 deg C., 40 to 50 deg C., 50
to 60 deg C., 60 to 70 deg C., 70 to 80 deg C., or greater than 80
deg C. The temperature should be below a temperature or temperature
range at which a drug in the coating becomes unstable or is subject
to decomposition. Typical minimum stability temperatures for drugs
may be in the range of 60 to 100 deg C. For example, everolimus is
stable up to 60 deg C. and stable for short periods up to 80 deg
C., and unstable above 80 deg C.
[0074] In some embodiments, the polymer at the lumenal surface of
the stent may be softened by a solvent that swells or is capable of
dissolving the polymer at the lumenal surface. In such embodiments,
the solvent may be applied to the lumenal surface, for example, by
spraying, dipping, brushing, or some other way. After application
of the solvent to the lumenal surface, the stent may then be
radially compressed over the mandrel to form grooves in the
softened polymer surface. The solvent may then be removed from the
stent by a drying step, for example, by blowing a warm gas on the
lumenal surface or baking in a vacuum or convection oven.
[0075] As used herein, a "solvent" for a given polymer can be
defined as a substance capable of swelling the polymer or
dissolving or dispersing the polymer to form a uniformly dispersed
mixture at the molecular- or ionic-size level. Swelling of a
polymer occurs when a solvent in contact with a sample of the
polymer diffuses into the polymer. L. H. Sperling, Physical Polymer
Science, 3.sup.rd ed., Wiley (2001). Thus, a swollen polymer sample
includes solvent molecules dispersed within the bulk of the
polymer. Dissolution of the polymer occurs when polymer molecules
diffuse out of the swollen polymer into solution.
[0076] In other embodiments of softening with a solvent, the
solvent may be applied to the surface of the mandrel prior to
radially compressing the stent over the grooved mandrel surface. As
the stent is radially compressed over the mandrel, the solvent on
the mandrel softens the polymer at the lumenal surface of the
stent.
[0077] Representative examples of solvents that may be used in
accordance with the present invention include, but are not limited
to, acetone, 2-butanone, chloroform, hexafluoroisopropanol,
trifluoroethanol, 1,4-dioxane, tetrahydrofuran (THF),
dichloromethane, tetrachloroethylene, acetonitrile, dimethyl
sulfoxide (DMSO), and dimethylformamide (DMF), cyclohexane,
toluene, xylene, cyclohexanone, ethyl acetate, and methyl acetate.
Representative solvents that will dissolve a PDLLA polymer at a
lumenal surface include acetone, THF and chloroform. Representative
solvents that will swell a PDLLA polymer at a lumenal surface
include ethanol, acetonitrile, and n-butanol. As indicated above,
the coating on a scaffold is formed by applying a polymer solution
to a scaffold and then removing the solvent to form the polymer
coating. In some embodiments, the coating step is modified to
provide a polymer coating that includes residual solvent in the
coating sufficient to soften the coating. In such embodiments, the
drying step during the coating process is performed so that
residual solvent remains in the coating. The residual solvent
content in the coating may be 1 to 10 wt %, 1 to 5 wt %, 5 to 10 wt
%, or greater than 10 wt % of the total mass of the coating. After
the formation of the grooves in the lumenal surface, the residual
solvent can be removed in a drying step.
[0078] In further embodiments, a stent including a bioresorbable
polymer scaffold with a bioabsorbable polymer coating with a
grooved lumenal surface can be made by molding grooves into an
inner or lumenal surface of a polymeric tube. A scaffold pattern
may then be formed from the tube. The scaffold may then be coated
in a manner that the lumenal surface coating includes grooves. In
such embodiments, a polymeric tube may be disposed over a tubular
mandrel having a plurality of longitudinal grooves in the surface
of the mandrel. The diameter of the polymeric tube may the diameter
at which a scaffold is formed from the tube or the target diameter
of the fabricated stent. In some embodiments, the polymer tube is a
radially expanded tube, as descried above in the exemplary
fabrication process of a bioabsorbable stent.
[0079] The inner diameter of the tube may the same as the outer
diameter of the mandrel. Alternatively, the diameter of the tube
may be slightly larger than of the mandrel. For example, the tube
diameter may be less 0.05 mm greater, 0.5 to 0.1. mm greater, 0.1
to 0.3 mm greater, or more than 0.3 mm greater than the inner
diameter of the mandrel. The tube may then be radially compressed
over or into the surface of the mandrel such that the grooves at
the surface of the mandrel form or mold grooves in the lumenal
surface of the tube.
[0080] As above, the formation of the grooves may facilitated by
softening the lumenal surface of the scaffold. The mandrel may be
heated during the radial compression which heats the polymer at the
lumenal surface of the tube. Heating with a mandrel is described
above for heating the lumenal surface of a stent. The temperature
of the mandrel or the polymer surface can be 30 to 40 deg. C., 40
to 50 deg C., 50 to 60 deg C., 60 to 70 deg C., 70 to 80 deg C., or
greater than 80 deg C. Since there may be no drug at the tube
luminal surface, the temperature may be higher when molding grooves
in the tube than for the coating.
[0081] Additionally, the polymer at the lumenal surface of the tube
may be softened by a solvent that swells or is capable of
dissolving the polymer at the lumenal surface. The solvent may be
applied to the lumenal surface of the tube, for example, by
spraying, dipping, brushing, or some other way. After application
of the solvent to the lumenal surface of the tube, the tube may
then be radially compressed over the mandrel to form grooves in the
softened polymer surface. The solvent may then be removed from the
tube by a drying step, for example, by blowing a warm gas on the
lumenal surface or baking in a vacuum or convection oven.
[0082] Additionally, as discussed above, the solvent may be applied
to the surface of the mandrel prior to radially compressing the
stent over the grooved mandrel surface. As the stent is radially
compressed over the mandrel, the solvent on the mandrel softens the
polymer at the lumenal surface of the tube.
[0083] A solvent may be used that swells or dissolves the tube
polymer. Representative solvents that will dissolve a PLLA polymer
at a lumenal surface of a PLLA tube include chloroform,
hexafluoroisopropanol, and dichloromethane. Representative solvents
that will swell a PLLA polymer at a lumenal surface of a PLLA tube
include acetone, THF, and toluene.
[0084] FIGS. 7A-7C illustrate the process of forming grooves in a
lumenal surface of a tube. FIG. 7A depicts the radial cross-section
of a polymer tube 200 disposed over a mandrel 202 with grooves 204
on its surface that are aligned longitudinally. FIG. 7B illustrates
tube 200 and mandrel 202 disposed within the aperture of a sliding
wedge crimper 206. Sliding wedges 208 slide inward, decreasing the
size of the aperture and the surface of the sliding wedges at the
aperture apply a radial pressure on tube 200. Tube 200 is pressed
into the grooved surface of mandrel 202 which forms or molds
grooves in the lumenal surface of tube 200.
[0085] The aperture of the crimper is then retracted and the tube
and mandrel are removed from the crimper. FIG. 7C illustrates tube
200 after the crimping procedure showing the grooves in the lumenal
surface 209 that are formed.
[0086] A scaffold with a stent pattern may then be formed from the
tube having the lumenal surface with grooves. The scaffold may be
formed using exemplary laser cutting methods described in US
2007/0283552 and U.S. patent application Ser. No. 12/797,950. The
scaffold that is formed has grooves on the lumenal surface of the
struts.
[0087] A therapeutic coating may then be formed on the scaffold,
including on the lumenal surface with grooves. The coating may be
formed on the lumenal surface in a manner that results in a lumenal
surface with a coating that has grooves. The coating process is
performed in a manner that prevents filling in the grooves
resulting in a coating that planarizes the surface or a planarizing
coating. Therefore, the coating process is performed to provide a
conformal or close to a conformal coating on the surfaces inside of
the grooves, rather than filling in the grooves. A conformal
coating, as used herein, is a coating having a uniform thickness
over a particular portion of a surface or surfaces.
[0088] Alternatively, a coating can be formed on the abluminal
surface of the scaffold with no coating on the luminal surface with
grooves. FIGS. 8A-C illustrate the difference between a planarizing
and conformal coating.
[0089] FIG. 8A depicts a cross-section of a surface section 210
that has grooves 212. Surface section 210 include plateau surfaces
218 and grooves 212 which are defined by side wall surfaces 214 and
bottom surfaces 216. FIG. 8B depicts surface section 210 with a
planarizing coating that fills in grooves 212 and planarizes the
surface. FIG. 8C depicts surface section 210 with a conformal
coating 220. Coating 220 has a coating thickness that is uniform
across plateau surfaces 218, side wall surfaces 214 and bottom
surfaces 216. The width and depth of grooves 202 are decreased by
the conformal coating 220, however, conformal coating provides
maximum preservation of the grooved surfaces. The planarizing
coating and conformal coating are extreme cases of a coating of a
grooved surface. Different degrees of nonuniformity in coating
thickness in the grooves can lead to different degrees of
preservation of the depth and width of the grooves.
[0090] The coating process parameters can be modified to provide a
high degree of uniformity of coating thickness in the grooves
resulting in a coating that is conformal or close to it. Coating
parameters that favor conformal coating include the use of solvents
for coating solutions that are fast evaporating and coating
solutions that are relatively high viscosity. Representative
solvents that are fast evaporating include acetone and
dichloromethane. Increasing the percent solids of polymer in the
coating will raise the coating viscosity, tending towards a more
conformal coating. Applying the coating under conditions of
elevated temperature, or under with rapid drying such as by
directing warm air at the coating, will cause the coating to
solidify more rapidly, yielding a more conformal coating.
[0091] In further embodiments, a stent with longitudinally aligned
grooves in the lumenal surface can be formed from a tube having
grooves formed during the extrusion process that makes the tube. In
the tube extrusion process, a melted polymer is conveyed from an
extruder barrel through an annulus of an annular die to form a
tube. The annular die has a first surface which forms an outer
surface of the tube and a second surface that forms the inner
surface of the tube. Embodiments of the present invention include
an annular die having an second surface that has grooves aligned in
the longitudinal direction. As the polymer is conveyed through the
die the grooves on the first surface of the annular die form
grooves in the inner or lumenal surface of the tube.
[0092] FIG. 9A shows a radial cross-section of a conventional
extrusion die 220. Extrusion die 220 includes an outer hollow
tubular section 222 having an inner surface 223 and an inner hollow
tubular section 224 having an outer surface 225. The polymer
extrudate is conveyed through annular cavity 226 between inner
surface 223 and outer surface 225 to form a tube. The outer surface
of the tube is formed by inner surface 223 of tubular section 222
and the inner surface of the tube is formed by outer surface 225 of
inner tubular section 224. Nitrogen gas is passed through tubular
cavity 228 to facilitate control of the tube dimensions.
[0093] FIG. 9B shows a radial cross-section of an extrusion die 240
for use in the present invention. Extrusion die 240 includes an
outer hollow tubular section 242 having an inner surface 243 and an
inner hollow tubular section 244 having an outer surface 245. As
shown in FIG. 9B, outer surface 245 has longitudinally aligned
grooves 247. The polymer extrudate is conveyed through annular
cavity 246 between inner surface 243 and outer surface 245 to form
a tube. As the polymer extrudate is conveyed, grooves 247 on outer
surface 245 form grooves in the lumenal surface of the tube.
[0094] After forming the tube with lumenal grooves in the extrusion
step, the tube may then be radially expanded, as described above. A
scaffold may then be formed from the tube by laser machining The
radial expansion process increases the circumference and decreases
the thickness of the tube. Due to deformation of the tube, the
radial expansion step changes the width and depth of the grooves
formed during the extrusion process. Specifically, it is expected
that radial expansion increases the width and decreases the depth
of the grooves. FIG. 10 depicts a section of a tube wall before and
after radial expansion with the curvature omitted for the purpose
of simplification. FIG. 10 depicts a section 260 of a tube wall
that has an initial length L1, initial thickness W1, and initial
groove depth Dg1. After expansion the section has a larger length
L2, a smaller thickness W2. The final groove depth Dg2 is also
smaller than the initial groove depth Dg1. Thus, in order to obtain
grooves in the scaffolding of a target width and depth, the grooves
formed in the extrusion process should be narrower and deeper than
the target width and depth, respectively, in a scaffolding. The
groove size required at the extrusion process to obtain a target
groove size in a radial expanded tube can be determined
experimentally. Tubes with different groove sizes can be radially
expanded and the change in groove size observed.
[0095] Further embodiments include making a stent including a
metallic scaffold and a polymer coating on the scaffold with
grooves in the coating on the lumenal surface stent. In some
embodiments, a method includes disposing a coated metal stent over
a mandrel such that a lumenal surface of the stent faces a surface
of the mandrel. The surface of the mandrel has a plurality of
grooves aligned longitudinally. The stent is radially compressed
over the surface of the mandrel such that the grooves at the
surface of the mandrel form or mold grooves on the coating over the
lumenal surface of the stent.
[0096] In such embodiments, the stent can be radially compressed
using a crimper, as described above. The stent and mandrel may be
placed inside a sliding wedge crimper which applies pressure to the
stent and compresses the lumenal surface of the stent on the
surface of the mandrel and forms grooves in the coating at the
lumenal surface of stent. The coating may be softened to facilitate
formation of the grooves.
[0097] The coating may be softened by heating the coating during
compression through the use of a heated mandrel, which is described
above. The temperature of the mandrel or the polymer surface can be
less than 50 deg C., less than 60 deg C., less than 80 deg C., 30
to 40 deg C., 40 to 50 deg C., 50 to 60 deg C., 60 to 70 deg C., 70
to 80 deg C., or greater than 80 deg C. The temperature should
below a temperature that may cause damage to a drug that is within
the coating. A minimum decomposition temperature for drugs,
generally, may be in the range of 80 to 100 deg C.
[0098] A coating on a metallic scaffold can include more than one
layer. The layers can be made of different polymers. Also, one
layer may include a drug, while another layer may be free of drug,
except for incidental diffusion of drug from a drug containing
layer to an adjacent layer. Exemplary coatings can include a primer
layer that is directly in contact with the metal scaffolding. The
primer layer may be made of a polymer that has good adhesion to the
metal and may be free of drug. A drug layer may be disposed on the
primer layer. The drug layer may be made of a mixture of a polymer
and a drug. The polymer may be selected due to desirable release
properties for the drug.
[0099] The total thickness of the coating may be 2 to 20 microns,
or more narrowly, 2 to 10 microns, 3 to 10 microns, 3 to 8 microns,
or 3 to 5 microns. The thickness of a primer layer may be 1 to 15
microns, or more narrowly, 1 to 10 microns, or 1 to 5 microns. The
thickness of a therapeutic layer may be 2 to 15 microns, or more
narrowly, 2 to 10 microns, or 2 to 5 microns.
[0100] An exemplary primer layer is poly(n-butyl methacrylate)
(PBMA). A therapeutic layer that contains polymer and a drug may be
on the primer layer. An exemplary polymer for a drug layer may be
poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and an
exemplary drug is everolimus. PVDF-HFP melts at about 130-160 deg
C. and the everolimus drug is stable up to 60 deg C. and is stable
for short periods of time at temperatures between 60 and 80 deg C.
Heating the PVDF-HFP coating with applied pressure will cause the
PVDF-HFP coating to flow.
[0101] Additionally, as described above, the coating can be
softened by a solvent in the coating. The solvent may be applied to
the coating prior to radial compression or applied to the surface
of the mandrel. A softened coating can also be provided by
performing the coating operation in a manner that results in
residual solvent in the coating after the coating step, for
example, in the range of 1 to 10 wt % of the coating. Exemplary
solvents for PVDF-HFP include acetone, dimethyl acetamide, dimethyl
formamide, and dimethyl sulfoxide. Exemplary solvents that swell,
but do not dissolve PVDF-HFP include tetrahydrofuran, 1,4-dioxane,
and ethyl acetate.
[0102] In these embodiments of forming grooves in a coating on a
metallic scaffold, the radial compression that molds the grooves on
the coating will not deform or form grooves in the underlying
metallic scaffold. Thus, the groove depth is limited to the
thickness or approximately the thickness of coating. However, in a
multi-layer coating, the compression can deform two or more of the
layers. Therefore, the groove depth, for example, can be up to the
thickness of a therapeutic layer or up to the thickness of the
therapeutic layer and primer layer.
[0103] Additional embodiments of making a stent with a metallic
scaffold and a polymer coating with grooves in a coating of the
lumenal surface of the stent include forming grooves on the
metallic scaffold prior to coating. In such embodiments, an
uncoated metallic scaffold is placed over a mandrel with
longitudinally aligned grooves. The stent is radially compressed
over the surface of the mandrel to form grooves in the metallic
lumenal surface of the metallic scaffold. A crimping device such as
that described above may be used to apply the radial pressure.
[0104] The radial pressure applied and temperature of the mandrel
or stent surface is significantly higher than for forming grooves
in a polymer. The radial pressure may be 100 to 2000 psi, or more
narrowly, 200 to 1000, 300 to 1000, 500 to 1000, or 400 to 800 psi.
The temperature can be 800 to 1000 deg C., 200 to 500 deg C., 400
to 600 deg C., 400 to 1000 deg C., 500 to 1000 deg C., 600 to 1000
deg C., or 800 to 1000 deg C.
[0105] The mandrel is made of a material that has a strength and
hardness higher than the metallic scaffold. An exemplary metal for
a metallic scaffold is cobalt chromium. Suitable materials for a
mandrel for forming grooves in such a scaffold may include tungsten
carbide, titanium carbide, titanium nitride, aluminum nitride, and
boron nitride. Grooves in these very hard mandrel materials may be
formed by laser machining or ion beam milling.
[0106] After molding the grooves in the lumenal surface of the
scaffold, the scaffold may then be coated. The coating parameters
may be adjusted to preserve the grooves, as described above.
[0107] It was indicated above that a stent may be fabricated from a
sheet of polymer by rolling and bonding the sheet to form the tube.
The sheet or the rolled up sheet can be machined to form a stent
pattern. In further embodiments, a polymer stent with grooves on a
lumenal surface can be formed by molding grooves on a surface a
polymer sheet, forming a stent pattern in the sheet, and rolling
and bonding the sheet with the pattern to form a stent.
Alternatively, the grooves can be molded into the sheet after the
pattern is formed.
[0108] The grooves are formed on the sheet along a direction that
is parallel to the intended cylindrical axis of the rolled up
sheet. The sheet is rolled up about this axis with the surface with
grooves being the lumenal or inner surface.
[0109] The grooves on the polymer sheet, with or without the
pattern already formed, can be formed with a plate having a surface
with grooves. The grooved surface is pressed against the polymer
sheet. The plate may be softened by heating the plate and the
temperature of the plate or polymer surface can have the
temperature ranges described above. Alternatively, a solvent may be
used to soften the polymer surface.
[0110] An exemplary stent design made from a rolled up sheet is
described, for example, in US 2010/0244304 and US 2006/0136041. The
stent design includes opposing circumferentially adjacent modules
which have longitudinally adjacent slide-and-lock radial elements
which permit one-way sliding of the radial elements from a
collapsed diameter to an expanded or deployed diameter, but inhibit
radial recoil from the expanded diameter. The slide-and-lock
elements may flex or bend; however, unlike stents described above
that are compressed and expanded through flexing or bending of
elements, no substantial plastic deformation of the elements may be
necessary during expansion of the stent from a collapsed diameter
to an expanded diameter.
[0111] In addition to the polymers disclosed above, stents, such as
those made from rolled up sheets can be made from tyrosine-derived
polycarbonates. These degradable polymers are derived from the
polymerization of desaminotyrosyl-tyrosine alkyl esters. Exemplary
polymers include poly(DTE carbonate), poly(DTB carbonate), poly(DTH
carbonate), poly(DTO carbonate), and poly(DTBzI carbonate),
respectively, desamino-tyrosyltyrosine, referred to as "DT." The
pendent group (R) of the polycarbonates can also be, for example,
ethyl, butyl, hexyl, octyl, and benzyl esters.
[0112] For the purposes of the present invention, the following
terms and definitions apply:
[0113] The "glass transition temperature," Tg, is the temperature
at which the amorphous domains of a polymer change from a brittle
vitreous state to a solid deformable or ductile state at
atmospheric pressure. In other words, the Tg corresponds to the
temperature where the onset of segmental motion in the chains of
the polymer occurs. When an amorphous or semi-crystalline polymer
is exposed to an increasing temperature, the coefficient of
expansion and the heat capacity of the polymer both increase as the
temperature is raised, indicating increased molecular motion. As
the temperature is increased, the heat capacity increases. The
increasing heat capacity corresponds to an increase in heat
dissipation through molecular movement. Tg of a given polymer can
be dependent on the heating rate and can be influenced by the
thermal history of the polymer as well as its degree of
crystallinity. Furthermore, the chemical structure of the polymer
heavily influences the glass transition by affecting molecular
mobility.
[0114] The Tg can be determined as the approximate midpoint of a
temperature range over which the glass transition takes place.
[ASTM D883-90]. The most frequently used definition of Tg uses the
energy release on heating in differential scanning calorimetry
(DSC). As used herein, the Tg refers to a glass transition
temperature as measured by differential scanning calorimetry (DSC)
at a 20.degree. C./min heating rate.
[0115] While particular embodiments of the present invention have
been shown and described, it will be obvious to those skilled in
the art that changes and modifications can be made without
departing from this invention in its broader aspects. Therefore,
the appended claims are to encompass within their scope all such
changes and modifications as fall within the true spirit and scope
of this invention.
* * * * *