U.S. patent application number 13/295918 was filed with the patent office on 2012-05-10 for surface textured implants.
This patent application is currently assigned to Biosensors International Group, Ltd.. Invention is credited to Fuh-Sheng Chen, Debashis Dutta, Shih-Horng SU.
Application Number | 20120116502 13/295918 |
Document ID | / |
Family ID | 42132405 |
Filed Date | 2012-05-10 |
United States Patent
Application |
20120116502 |
Kind Code |
A1 |
SU; Shih-Horng ; et
al. |
May 10, 2012 |
SURFACE TEXTURED IMPLANTS
Abstract
Devices and methods for controlling the flaking of coating
fragments from medical implants and improving the delivery of
therapeutic agents from such coatings are described.
Inventors: |
SU; Shih-Horng; (Irvine,
CA) ; Chen; Fuh-Sheng; (San Diego, CA) ;
Dutta; Debashis; (Irvine, CA) |
Assignee: |
Biosensors International Group,
Ltd.
Hamilton
BM
|
Family ID: |
42132405 |
Appl. No.: |
13/295918 |
Filed: |
November 14, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12612175 |
Nov 4, 2009 |
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13295918 |
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61111833 |
Nov 6, 2008 |
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Current U.S.
Class: |
623/1.46 |
Current CPC
Class: |
A61F 2002/0081 20130101;
A61F 2230/0002 20130101; A61F 2250/0067 20130101; A61F 2/06
20130101; A61F 2/0077 20130101; A61F 2/04 20130101; A61F 2250/0071
20130101; A61L 2400/12 20130101; A61K 33/00 20130101; A61F
2250/0068 20130101; A61F 2/848 20130101; A61F 2/82 20130101 |
Class at
Publication: |
623/1.46 |
International
Class: |
A61F 2/82 20060101
A61F002/82 |
Claims
1. A radially expandable device for introducing into the body of a
subject to produce a beneficial effect, said device comprising: an
upper surface that contacts tissue at a treatment site; wherein
said upper surface comprises a coating and one or more texture
features designed to interact with said coating and control
fragments of said coating that flake off said upper surface as a
result of radial expansion of said device at said treatment
site.
2. The device of claim 1 wherein said texture features control the
size of said fragments.
3. The device of claim 1 wherein said texture features control the
shape of said fragments.
4. The device of claim 1 wherein said texture features control the
quantity of said fragments.
5. The device of claim 1 wherein said texture features comprise one
or more peaks.
6. The device of claim 1 wherein said texture features comprise one
or more valleys.
7. The device of claim 1 wherein said texture features comprise one
or more peaks and valleys.
8. The device of claim 5 wherein said peaks comprise stress
risers.
9. The device of claim 8 wherein said stress risers control the
initiation and propagation of stress fractures in said coating.
10. The device of claim 1 wherein said texture features comprise
one or more plateaus.
11. The device of claim 1 wherein said texture features comprise
one or more peaks, valleys and plateaus.
12. The device of claim 1 wherein said fragments are too small to
cause thrombi.
13. The device of claim 1 wherein said fragments are too small to
cause emboli.
14. The device of claim 1 wherein said coating contains a
therapeutic agent.
15. The device of claim 1 wherein said coating controls the size of
said fragments such that the fragments do not exceed a width of 1
mm.
16. The device of claim 1 wherein said coating controls the size of
said fragments such that the maximum width of fragments are from
0.1 to 50 microns.
17. The device of claim 1 wherein said coating controls the size of
said fragments such that the surface area of fragments are from 1
to 10,000 .mu.m.sup.2.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Application No. 61/111,833, filed on Nov. 6, 2008, entitled
"Surface Textured Implants," which is incorporated herein by
reference.
[0002] The following references and additional references cited,
herein, are hereby incorporated by reference in their entirety.
[0003] U.S. Pat. No. 6,805,898
[0004] U.S. Pat. No. 6,800,089
[0005] U.S. Pat. No. 6,913,617
[0006] U.S. Pat. No. 7,335,314
[0007] U.S. Pat. No. 6,764,505
[0008] U.S. Patent Publication No. 20080097591
[0009] U.S. Patent Publication No. 20080097568
[0010] U.S. Patent Publication No. 20050211680
[0011] International Patent Pub. No. WO/2008/027872
[0012] Stout, K. J. et al. (1994) The development of methods for
the characterization of roughness on three dimensions, Publication
No. EUR 15178 EN of the Commission of the European Communities,
Luxembourg.
[0013] Barbato, G. et al. (1995) Scanning tunneling microscopy
methods for roughness and micro hardness measurements, Synthesis
report for research contract with the European Union under its
programme for applied metrology, European Commission Catalogue
number: CD-NA-16145 EN-C, Brussels Luxemburg. 109 pages.
[0014] Jorgensen, K. et al. (1993) The Scanning Tunneling
Microscope and Surface Characterisation, Nanotechnology
4:152-158.
TECHNICAL FIELD
[0015] The present devices and methods are in the field of
implantable devices or prostheses, particularly devices that
include a therapeutic surface coating.
REFERENCE TO A "SEQUENCE LISTING," A TABLE, OR A COMPUTER PROGRAM
LISTING APPENDIX SUBMITTED ON A COMPACT DISK
[0016] NOT APPLICABLE
BACKGROUND OF THE INVENTION
[0017] Drug-eluting stents are commonly used in coronary
angioplasty procedures, after a diseased vessel has been opened by
balloon angioplasty, to maintain the opened diameter of the vessel
and to reduce the risk that the vessel will re-narrow by a process
known as restenosis. Stents of this type are typically composed of
a radially expandable stent body, e.g., a metal stent body, whose
outer surface is coated with a drug-containing polymer coating from
which the anti-restenosis drug is eluted over a period of a few
week to several months. The stent is carried to the target vascular
site in a contracted condition on the catheter balloon. As the
balloon is expanded to open a narrowed portion of a vessel, the
stent carried on the balloon is expanded against the vessel wall
for deployment in the vessel. During this stent expansion, the
stent coating is exposed to radial stresses and may fracture,
releasing flaked coating material into the bloodstream. Flaked
pieces of sufficient size can serve as sites for blood clotting,
posing a concern for embolism.
[0018] Previous efforts to address this problem have involved
increasing the adhesion of the coating to the implant, in an effort
to minimize flaking. One way to increase adhesion is to roughen or
texture the surface of the implant, as described in U.S. Pat. Nos.
6,805,898 and 7,335,314 (Wu et al.), U.S. Pat. No. 6,913,617
(Reiss), and WO 08/027,872. However, when medical implants
experience sufficient structural deformation, rigid and semi-rigid
coatings inevitably crack and flake off in fragments, fibers, or
strands, risking clinical complications such as embolism, blood
flow interruption/disruption, and blood clots. This problem is
observed, for example, in the case of coated filaments of vascular
stents, which are typically expanded following delivery to a
preselected site of implantation. A related problem is observed
when two stents are implanted in an overlapping or juxtaposed
configuration, wherein contact between the stents causes damage to
the coating of one or both stents.
[0019] It is, therefore, apparent that simply increasing the
adhesion of the coating to the surface of the medical implant does
not fully address the problems of flaking, dislodgement and coating
embolization.
BRIEF SUMMARY OF THE INVENTION
[0020] The following aspects and embodiments thereof described and
illustrated below are meant to be exemplary and illustrative, not
limiting in scope.
[0021] In one aspect, the invention provides a radially expandable
device for introducing into the body of a subject to produce a
beneficial effect. The device comprises a coating and an upper
surface that contacts tissue at a treatment site. The upper surface
comprises one or more texture features designed to interact with
the coating and cause fragments of the coating to flake off the
upper surface as a result of radial expansion of the device at the
treatment site. The resulting fragments are too small to cause
thrombi and/or emboli.
[0022] The texture features of the device of the present invention
control the size of the coating fragments. Further, the texture
features of the device control the shape of the fragments. In
addition, texture features also control the quantity of the
fragments.
[0023] In one embodiment, the texture features of the present
invention comprise one or more peaks, and/or one or more valleys
and/or one or more plateaus. Further, the peaks comprise stress
risers that control the initiation and propagation of stress
fractures in the coating.
[0024] These and other objects and features of the invention are
made more fully apparent in the following detailed description of
the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIGS. 1A and 1B show exemplary textured surfaces on a
filament.
[0026] FIG. 2A shows exemplary texture features having peaks
protruding above a coating. FIG. 2B shows the detachment of coating
fragments in response to surface deformation.
[0027] FIG. 3A shows exemplary texture features wherein a coating
covers peaks. FIG. 3B shows stress fractures that occur in response
to surface deformation. FIG. 3C shows the detachment of coating
fragments in response to surface deformation.
[0028] FIG. 4A shows exemplary texture features wherein a coating
covers valleys. FIG. 4B shows stress fractures that occur in
response to surface deformation. FIG. 4C shows the detachment of
coating fragments in response to surface deformation.
[0029] FIGS. 5A-5D show an exemplary texture feature having both
peaks and valleys.
[0030] FIGS. 6A and 6B show detachment of coating fragments from a
peak-and-valley texture feature in response to surface
deformation.
[0031] FIGS. 7A and 7B show the response of coating fragments
attached to a peak-and-valley texture feature in response to
surface deformation.
[0032] FIGS. 8A-8D show texture features that include elevated
plateaus between peaks, of peaks and valleys.
[0033] FIG. 9A shows penetration of cell membranes and cells by
texture features. FIG. 9B shows a detached coating fragment held
captive against a tissue by texture features.
DETAILED DESCRIPTION OF THE INVENTION
[0034] Before the inventive devices and methods are disclosed and
described, it is to be understood that this invention is not
limited to stents, or the like, as such may vary. It is also to be
understood that the terminology used herein is for the purpose of
describing particular embodiments only and is not intended to be
limiting.
[0035] The present devices and methods relate to a vascular
implant, such as a stent, having a surface texture that controls
the size and shape of fragments of coating material that may
separate from the implant, and methods for manufacturing such
devices. The devices and methods are particularly useful for
controlling the size and shape of coating fragments that originate
from rigid and semi-rigid coatings, which have the greatest
tendency to break and flake off the surface of a medical implant
following structural deformation.
[0036] The devices and methods may best be understood with
reference to the accompanying drawings. Similar features are
identified using the same reference numerals.
DEFINITIONS
[0037] As used herein, the term "medical implant" or `implant"
refers to a stent, pin, screw, plate, mesh structure, orthopedic
appliance, RFID tag, pacemaker, gastric band/collar, cosmetic
implant, or other devices suitable for implantation into the body
of a mammalian subject. An exemplary implant is an expandable
vascular stent.
[0038] As used herein, a "texture feature" or "texture element" is
a discrete surface region within a surface texture that can be
defined in terms of shape, volume, area and/or dimensions.
[0039] As used herein, the term "valley" refers to a depression,
indentation, trough or characteristic extending toward a device's
lower surface that forms a portion of a texture feature.
[0040] As used herein, the term "peak" refers to a protrusion,
projection, elevation or characteristic extending toward a device's
upper surface that forms a portion of a texture feature.
[0041] As used herein, the term "comparatively non-textured," as it
applies to the region for attachment of coating to the surface of a
medical implant, refers to a texture feature having less than 20%,
and preferably less than 10%, of the valley to peak height of a
textured region.
[0042] As used herein, the term "flake" or "flake off" refers to
the detachment, release or separation of a portion (i.e., a
fragment) of coating from the surface of a medical implant in
response, for example, to structural deformation or handling.
Depending on the particular medical implant and coating concerned,
such flaking off may be relied upon to produce an intended
therapeutic effect, or may be an unintended or unavoidable
consequence of the use of a particular coating material with a
particular medical implant.
[0043] As used herein, the terms "break," "crack" and "fracture"
are intended to refer to the process by which stress fractures
initiate and/or propagate in a rigid or semi-rigid coating of a
medical implant subjected to structural deformation or handling.
Breaks and cracks may be encouraged at a preselected location in a
coating by the use of stress risers.
[0044] As used herein, a "stress riser" is a feature associated
with the surface of a coated medical implant that concentrates the
stress of structural deformation at a particular location in the
coating, thereby causing breaks or cracks to initiate at, and
propagate from, that location.
[0045] As used herein, the term "structural deformation" refers to
distortion, bending, stretching, flexing or other physical changes
to the surface of a medical implant that can cause at least a
portion of a rigid or semi-rigid coating to separate from the
surface.
[0046] As used herein, the term "rigid or semi-rigid," as it refers
to coatings, is intended to broadly encompass coatings that are
relatively non-elastic, and which therefore may fracture and flake
during structural deformation, as when a coated stent is radially
expanded or deformed along its radial or longitudinal axis during
deployment.
Surface Textured Implants
[0047] A first aspect of the present invention is a surface
textured implant for introducing into the body of a subject to
produce a beneficial effect. In one embodiment, the implant is a
stent having a body formed of expandable, interconnected elements,
such as metal or polymer wires or filaments, according to
well-known construction of radially expandable stents. Such stents
are formed, for example, by laser cutting a cylindrical metal or
polymer tube. In the figures described below, the structures shown
are intended to represent portions of individual filaments or
elements making up the stent. Such a filament structure has an
upper surface that is in contact with the vessel wall when the
stent is deployed, side surfaces, and a lower surface that forms
part of the interior surface of the stent in the deployed
condition. It will be understood that the structures may also
illustrate other surface elements of implants.
[0048] With this background in mind, FIG. 1A shows a portion of a
stent filament 10 which, together with other interconnected
filaments, makes up the body of a stent. The filament has a first,
upper surface 12 forming part of the outer surface of a stent, a
second lower surface 15 (dotted arrow) that forms part of the inner
surface of the stent, and one or more side surfaces 14. As noted,
where the implant is a vascular stent, the second surface may be in
contact with blood present in the lumen of a blood vessel.
[0049] The first surface 12 of filament 10 has a texture that
includes one or more discrete texture features 16 designed to
interact with a coating (shown in subsequent figures) applied to
the filament. These texture features may cover all or only a
portion of the filament surface and may be arranged in the form of
a grid (FIG. 1A), honeycomb pattern (FIG. 1B) or other
configuration that preferably allows the texture features 16 to be
grouped together at high density on an upper surface 12 of a
filament 10. Exemplary regular shapes for texture features include,
but are not limited to, rectangles, hexagons, geometric shapes,
fishscales, archimedes, diamonds, crosshatching, mathematically
modeled shapes and the like. Irregular shapes for texture features,
including but not limited to shapes which can not be defined or
represented by mathematics, are also used with the present
invention. Additional texture features are further described,
below. For convenience, similar features are identified using the
same reference numerals.
Texture Features with Peaks or Valleys to Control Flaking
[0050] FIGS. 2A, 3A and 4A show cross-sectional side views of
several embodiments of texture features that include peaks and/or
valleys. In all these figures, an upper surface 22 of a filament 20
is in contact with a body tissue 24, generally represented by the
area above the diagrams. In FIGS. 2A and 3A, discrete texture
features 26, 27 having a width (W) are defined by peaks 28, 29
which protrude from the upper surface of the filament. In FIG. 4A,
texture features 30 having a width (W) are defined by valleys 32 in
the surface of the filament. Where the texture feature has an
irregular shape, the width (W) is defined as the widest dimension
between peaks or valleys. In both cases, the texture features may
further include a plateau region 34 between the peaks or valleys,
as appropriate. The plateau region may be substantially
non-textured or may have an additional texture to increase adhesion
of a coating 36, which is further illustrated in the figures.
[0051] As illustrated in FIGS. 2A, 3A and 4A, the height of the
peaks or depth of the valleys further defines height (H) of the
texture feature. Since a texture feature may be bounded by the
surface of the filament (i.e., the plateau) and peripheral peaks or
valleys, and is only required to be open to the body tissue that it
contacts once implanted, the texture feature also defines a volume
(V), some or all of which can be filled with coating material.
[0052] Where texture features 26, 27 are defined by peaks 28, at
least a portion of one or more peaks may protrude above the coating
(FIG. 2A) or be covered by the coating (FIG. 3A). Where texture
features 30 are defined by valleys 32, the coating may initially
cover the valleys (FIG. 4A).
[0053] Texture features defined by peaks and valleys provide
several advantages in terms of coating adhesion and flaking
control. First, the texture features may increase the adhesion of
the coating to the surface of the implant, thereby reducing flaking
of the coating in response to surface deformation. Second, the
texture features may introduce stress risers on the surface of the
implant, such that if or when the amount of structural deformation
to the implant surface becomes sufficient to overcome the adhesion
of at least a portion of the coating to the surface of the implant,
the texture features control the size, shape and quantity of
coating fragments that flake off the surface of the implant. Such
surface distortion commonly occurs as a result of radial expansion
of a vascular stent at the site of implantation.
[0054] The manner in which texture features control the size, shape
and quantity of coating fragments is illustrated in subsequent
figures, wherein similar structures are represented by the same
reference numerals used above. Where texture features 26 are
defined by peaks 28 that protrude above a coating 36, as shown in
FIG. 2A, the size, shape and quantity of released coating fragments
38 are predetermined by the dimensions of the texture features, as
shown in FIG. 2B. Where texture features 27 are defined by peaks 29
that are covered by a coating 36, as shown in FIG. 3A, the peaks
function as stress risers to control the initiation and propagation
of stress fractures 44 in the coating (FIG. 3B), which direct the
flaking of coating fragments 40 along the stress fractures 44
originating from the peaks (FIG. 3C).
[0055] Where texture features 30 are defined by valleys 32, as
shown in FIG. 4A, the valleys function as stress risers to control
the initiation and propagation of stress fractures 46 in the
coating (FIG. 4B), which direct the flaking of coating fragments 42
along the stress fractures (FIG. 4C). The coating may detach so as
to leave a small portion of the coating 48 in the valleys or detach
completely thereby including the portion of coating in the
valleys.
Texture Features with Peaks and Valleys to Control Flaking
[0056] A particular type of texture feature for use in controlling
coating flaking includes both peaks and valleys. As illustrated in
FIG. 5A, such a texture feature 52 is defined by peaks 54 that
flank valleys 56 in a first surface 58 of a filament 50. These
peaks and valleys serve as stress risers (dotted arrows) to control
coating flaking. As before, the texture feature includes a plateau
60, which may be comparatively non-textured or may include an
additional texture to increase adhesion of a coating. Each texture
feature can be described by a width (W), measured between the
peaks, and a height (H), measured between the tops of the peaks and
bottom of the valleys. As above, the first surface of the filament
may have one or a plurality of adjacent texture features on a
portion of the first surface or, alternatively, the first surface
may be substantially or completely covered by such features.
[0057] FIGS. 5C and 5D illustrate texture features 64, 66 on a
first surface 68 of a filament 70, following application of a rigid
or semi-rigid coating 72, 74. The coating contacts a plateau 76
between peaks 78 and valleys 80, fills or partially fills the
valleys, and contacts at least a portion of the inside surfaces of
the peaks. The thickness of the coating may be such that the peaks
are covered by the coating, as shown in FIG. 5C, or at least a
portion of one or more of the peaks protrude above the coating, as
shown in FIG. 5D. While isolated texture features 52, 64, 66 are
illustrated in FIGS. 5A and 5C, it will be apparent that the
surface of a filament may have a plurality of texture features, as
shown in the previous figures.
[0058] Using the same reference numerals as used in FIG. 5A to
indicate similar features, FIG. 5B illustrates the initiation and
propagation of stress fractures 82 in a coating 84, as a
consequence of the numerous stress risers introduced by a
peak-and-valley type of texture feature 52.
[0059] FIGS. 6A and 6B illustrate embodiments by which a fragment
of coating 86, 88 having a predetermined size and shape may detach
from a peak-and-valley type of texture feature 90, as generally
illustrated in FIG. 5A. It is to be understood that additional
embodiments by which a coating fragment may detach from a texture
feature not specifically illustrated herein are also included
within the scope of the present invention. Release occurs when
structural deformation of a first surface 92 of a filament 94
produces sufficient stress on the coating to overcome adhesion to
the surface 92. The coating may detach so as to leave a relatively
small portion of the coating 89 in all or a portion of one or more
valleys 96 of the texture feature (an example, of which, is shown
in FIG. 6A), or detach completely (as shown in FIG. 6B). The amount
of coating, if any, that remains in the valleys is relatively small
compared to the amount of coating that flakes off.
[0060] FIGS. 7A and 7B further illustrate embodiments of the
interactions between the coating 112 and the
peak-and-valley-texture features 102 in response to particular
forms of stress produced by deformation of a first surface 104 of a
filament 100. In FIG. 7A, the ends of the filament are drawn in a
downward direction, indicated by the arrows, pulling peaks 106 of
the texture feature away from the coating 112. As stress increases,
the coating becomes attached only to a plateau 110 portion of the
texture feature, and eventually detaches as shown in FIGS. 6A and
6B. This type of surface deformation, and the resulting stresses
caused by the deformation, can be found, for example, at the
surface of a stent following insertion into a blood vessel and
subsequent radial expansion at a vascular site.
[0061] In FIG. 7B, the ends of the filament 100 are drawn in an
upward direction, indicated by the arrows, pushing the peaks of the
texture feature toward (i.e., into) the coating 112. As the amount
of deformation at the first surface 104 of the filament increases,
the coating 112 may initially be clamped and retained by the
inwardly drawn peaks 106. However, as deformation increases, the
space (i.e., volume) defined by the texture feature becomes
insufficient to contain the amount of coating originally applied to
the surface of the filament, and a fragment of the coating
eventually detaches, as shown in FIGS. 6A and 6B. This type of
surface deformation, and the resulting stresses caused by the
deformation, can be found, for example, in the struts or ductile
hinges of a stent following insertion into a blood vessel and
subsequent radial expansion at a vascular site.
Texture Features with Elevated Plateau Regions
[0062] A further variation of the present texture features provides
a cross-sectional shape suitable for holding captive regions of
coating to further reduce flaking and detachment. Exemplary texture
features are illustrated in FIGS. 8A-8D. As illustrated in previous
drawings, the texture features 116, 118, 120 are shown arranged on
the surface of a vascular stent filament 122. As before, the
texture features include peaks or peaks and valleys flanking a
lower plateau region. However, the embodiments illustrated in FIGS.
8A-8D include peaks or peaks and valleys flanking a lower plateau
region and further being connected through an additional elevated
plateau region.
[0063] For example, FIG. 8A shows texture features 116 having peaks
124, 126 of height H flanking lower plateau regions 128, which
peaks are further connected through elevated plateau regions 130.
The resulting texture features have a cross-section that is wider
at the level of the lower plateau region 128 (i.e., W.sub.1) than
at the level of the elevated/upper plateau region 130 (i.e.,
W.sub.2), such that portions of coating 132 (shown filing at least
a portion of one or more of the texture features) are held in place
and cannot readily detach from the texture features.
[0064] The embodiment shown in FIG. 8B is similar to that shown in
FIG. 8A, except that the cross-section of the texture features have
a different shape. For example, in FIG. 8A, one side 134 of the
texture features is substantially vertical and the other side 136
is angled inwardly toward a portion of the coating 142. In
contrast, as shown in FIG. 8B, both sides 138, 140 of the texture
features 118 are angled inwardly toward a portion of the coating.
Note that features common to FIGS. 8A and 8B are identified using
the same reference numerals.
[0065] FIG. 8C shows a texture feature having an elevated plateau
region 142, similar to that shown in FIGS. 8A and 8B, but further
including valleys 144, 146 flanking a lower plateau region 148, as
described with reference to FIGS. 5A-7B. At least one side and
optionally both sides 150, 152 of the texture features may be
angled inwardly toward a portion of the coating 154 as shown in
FIGS. 8A and 8B, respectively. Further, one side may also be
vertical, as shown in FIG. 8A.
[0066] Where a texture feature includes elevated plateau regions,
at least a portion of the coating may be below the level of the
elevated plateaus, as shown in FIGS. 8A-C, or above the level of
the elevated plateaus, as shown in FIG. 8D. Note that the same
reference numerals are used in FIGS. 8C and 8D, except that in FIG.
8D the layer of coating 155 above the elevated plateaus 142 is
separately indicated. Flaking is maximally reduced where the level
of the coating is below the level of the elevated plateaus;
however, contact between a body tissue, such as a vascular wall, is
maximized when the level of the coating is above the level of the
elevated plateaus. Note that the portion of the coating above the
elevated plateaus is still subject to controlled flaking as a
result of the stress fractures that can propagate through the
coating from the various stress risers introduced by the texture
features (see, e.g., FIG. 5B).
Design of Texture Features
[0067] The texture features are designed to retain the coating when
the surface of the implant is not experiencing structural
deformation and release fragments of coating having a controlled
size and shape when the surface of the implant experiences
sufficient structural deformation to overcome the adhesion between
the coating and the textured surface of the implant. In particular,
structural deformation at the surface of the implant causes
fracture lines to promulgate at the site of the stress risers
created by the peaks and/or valleys in the texture feature,
directing the coating to break into fragments that follow the
fracture lines. The size and shape of the released coating
fragments are thereby controlled by the preselected dimensions,
particularly the width (W) of the texture features.
[0068] The following description relates to design parameters to be
considered in selecting a surface texture feature for a particular
application.
Design Parameters for Texture Features
[0069] Design parameters for texture features can generally be
categorized as amplitude parameters, spatial parameters or hybrid
parameters, although such categorization is intended to be
descriptive rather than limiting. Amplitude parameters mainly
involve the depth or height (H) of the texture features. Spatial
parameters mainly involve the arrangement (e.g., density and
proximity) of texture features on the surface of a filament. Hybrid
parameters involve both amplitude and spatial parameters. Some
parameters may be more important for maximizing the adhesion of a
coating to the surface of an implant, whereas other parameters may
be more important for controlling the number and/or size of flaked
off fragments.
[0070] Preferred design parameters for use in designing texture
features are listed in Table 1. The Table provides a brief
description of each parameter, its common symbol/abbreviation,
references or applicable standards in two or three-dimensional
space, and default units. The indicated surface roughness
parameters can be measured using any appropriate devices and
calculation can be made using any appropriate software. An
exemplary device is a microscope adapted for use with a Scanning
Probe Image Processor (SPIP.TM.), as marketed by Image Metrology
A/S (Horsholm, Denmark). The SPIP.TM. allows detailed surface
characterization using images from electron, interference and
optical microscopes. The SPIP.TM. parameters incorporate the
recommendations of the European 8CR Project Scanning tunneling
microscopy methods for roughness and micro hardness measurements
(Barbato et al. (1995)) and other standards.
TABLE-US-00001 TABLE 1 Parameters for selecting texture features
Default Symbol Description 2-D reference Unit 3-D reference
Amplitude parameters: Sa Roughness Average DIN 4768 nm ISO/DIS
25178-2; ASME B46.1 ASME B46.1 Sq Root Mean Square (RMS) ISO 4287/1
nm ISO/DIS 25178-2; ASME 846.1 ASME B46.1 Ssk Surface Skewness ISO
4287/1 ISO/DIS 25178-2; ASME 846.1 ASME B46.1 Sku Surface Kurtosis
ANSI B.46.1 ISO/DIS 25178-2; ASME B46.1 ASME B46.1 Sz Peak-Peak ISO
4287/1 nm ISO/DIS 25178-2 St Peak-Peak ASME B46.1 nm ASME B46.1 Sy
Peak-Peak (old SPIP term) nm Stout et al. (1994) Sv Largest pit
height ASME B46.1 ISO/DIS 25178-2; ASME B46.1 Sp Largest peak
height ASME B46.1 ISO/DIS 25178-2; ASME B46.1 Smean Mean Value
Hybrid Parameters Ssc Mean Summit Curvature 1/nm Stout et al.
(1994) Sdr Surface Area Ratio ISO/DIS 25178-2 S2A Projected Area
nm.sup.2 S3A Surface Area nm.sup.2 Spatial Parameters Sds Density
of Summits 1/.mu.m.sup.2 ASME B46.1; Stout et al. (1994) Std
Texture Direction degrees Stout et al. (1994) Stdi Texture
Direction Index Barbato et al. (1995) Srw Dominant Radial Wave
Length nm Barbato et al. (1995) Str20 Texture Aspect Ratio at 30%
Str37 Texture Aspect Ratio at 37%
[0071] Most parameters listed in the Table, and described in more
detail below, are valid for any rectangular surface feature having
the dimensions M.times.N. However, some parameters, particularly
those relating to Fourier transformation, assume that the texture
is quadrangular (i.e., M=N).
[0072] Some of the parameters depend on the definition of a local
minimum and a local maximum. As used herein, a local minimum is
defined as a pixel where all eight neighboring pixels are higher,
and a local maximum is defined as a pixel where all eight
neighboring pixels are lower. Where there are no pixels outside the
borders of an image there are no local minimums or local maximums
on the borders. In some cases, parameters based on local minimums
and/or local maximums may be more sensitive to noise than other
parameters.
[0073] Prior to making calculations relating to roughness
parameters, slope correction is recommended, e.g., using 2nd or 3rd
order polynomial plane fit. Scan range and sample density should
also be taken into account when reporting roughness data.
[0074] Exemplary surface texture parameters can be divided into
several categories, which are described in detail, below. The
skilled artisan will recognize variations and combinations of these
parameters, which, though not specifically described herein, are
also included within the scope of the present invention.
Amplitude Parameters
[0075] Amplitude is described by six parameters, which provide
information about average properties, extremes and shapes of height
(H) distribution histograms. The parameters are based on
two-dimensional standards that are extended to three
dimensions.
[0076] Roughness Average (i.e., Sa) is defined as:
S a = 1 MN k = 0 M - 1 l = 0 N - 1 z ( x k , y l ) Equation 1
##EQU00001##
[0077] The Root Mean Square (RMS) parameter (i.e., Sq) is defined
as:
S q = 1 MN k = 0 M - 1 l = 0 N - 1 [ z ( x k , y l ) ] 2 Equation 2
##EQU00002##
[0078] Surface Skewness (i.e., Ssk) describes the asymmetry of the
height distribution histogram, and is defined as:
S sk = 1 MNS q 3 k = 0 M - 1 l = 0 N - 1 [ z ( x k , y l ) ] 3
Equation 3 ##EQU00003##
[0079] A symmetrical height distribution is indicated by Ssk=0, and
may be Gaussian like. A surface texture primarily characterized by
valleys is indicated by Ssk <0. A surface texture primarily
characterized by peaks is indicated by Ssk >0. Values are
typically <1 although more extreme surface textures may have
values >1 greater than 1.0.
[0080] Surface Kurtosis (i.e., Sku) describes the "peakedness" of
the surface topography, and is defined as:
S ku = 1 MNS q 4 k = 0 M - 1 l = 0 N - 1 [ z ( x k , y l ) ] 4
Equation 4 ##EQU00004##
[0081] Sku values may approaches 3.0 for Gaussian height
distributions, while smaller values indicate a broader range of
height distributions.
[0082] Peak-Peak Height is defined by three parameter (i.e., Sz,
St, Sy) according to the indicated ISO and ASME standards and Stout
et al. (1994) (Table 1). These parameters relate to the height
difference between the highest and lowest pixel in the image.
S.sub.z=S.sub.t=S.sub.V=Z.sub.max-Z.sub.min Equation 5
[0083] Maximum pit height (i.e., Sv) is defined as the largest pit
height value.
[0084] Maximum peak height (i.e., Sp) is defined as the largest
peak height value.
Hybrid Parameters
[0085] Three hybrid parameters reflect slope gradients based on
local z-slopes.
[0086] The Mean Summit Curvature (i.e., Ssc) is the average of the
principal curvature of the local maximums on the surface, and is
defined as follows for all local maximums where .delta.x and
.delta.y are the pixel separation distances:
S SC = - 1 2 n i = 1 n ( ( .delta. 2 z ( x , y ) .delta. x 2 ) + (
.delta. 2 z ( x , y ) .delta. y 2 ) ) Equation 6 ##EQU00005##
[0087] The Area Root Mean Square Slope (i.e., Sdq6) is similar to
the Sdq but includes more neighbor pixels in the calculation of the
slope for each pixel as defined as (Equation 7):
S dq 6 = 1 ( N - 6 ) ( M - 6 ) k = 3 N - 3 l = 3 M - 3 .DELTA. 2 x
k , y l ##EQU00006## .DELTA. 2 x k , y l = ( { 1 60 .DELTA. x [ - z
( x k - 3 , y l ) + 9 z ( x k - 2 , y l ) - 45 z ( x k - 1 , y l )
+ 45 z ( x k + 1 , y l ) - 9 z ( x k + 2 , y l ) + z ( x k + 3 , y
l ) ] } 2 + { 1 60 .DELTA. y [ - z ( x k , y l - 3 ) + 9 z ( x k ,
y l - 2 ) - 45 z ( x k , y l - 1 ) + 45 z ( x k , y l - 1 ) - 9 z (
x k , y l - 2 ) + z ( x k , y l - 3 ) ] } 2 ) 1 / 2
##EQU00006.2##
[0088] The Surfaces Area Ratio (i.e., Sdr) expresses the increment
of the interfacial surface area relative to the area of the
projected (flat) x-y plane:
S dr = ( k = 0 m - 2 l = 0 x - 2 A k , l ) - ( M - 1 ) ( N - 1 )
.delta. x .delta. y ( M - 1 ) ( N - 1 ) .delta. x .delta. y 100 %
Equation 8 ##EQU00007##
where Akl is defined as (Equation 9):
A kl = 1 4 ( .delta. y 2 + ( z ( x k , y l ) - z ( x k , y l + 1 )
) 2 + .delta. y 2 + ( z ( x k + 1 , y l ) - Z ( x k + 1 , y l + 1 )
) 2 ) .times. ( .delta. x 2 + ( z ( x k , y l ) - z ( x k + 1 , y l
) ) 2 + .delta. x 2 + ( z ( x k , y l + 1 ) - z ( x k + 1 , y l + 1
) ) 2 ) ##EQU00008##
For a flat surface, the surface area and the area of the x-y plane
are the same and Sdr=0%.
[0089] The Projected Area (i.e., S2A) relates to the area of the
flat x-y plane as given in the denominator of Equation 7.
[0090] The Surface Area (i.e., S3A) expresses the area of the
surface area taking the z height into account as given in the
numerator of Equation 7.
Spatial Parameters
[0091] Spatial properties of surface textures are described by five
parameters, namely the density of summits, the texture direction,
the dominating wavelength, and two index parameters. The first
index parameter is calculated directly from the image, while the
other is based on the Fourier spectrum. For these parameters the
images must be quadratic.
[0092] The Density of Summits, Sds, is the number of local maximums
per area:
S ds = NumberoflocalMaximums ( M - 1 ) ( N - 1 ) .delta. x .delta.
y Equation 10 ##EQU00009##
[0093] The Texture Direction (i.e., Std) is defined as the angle of
the dominating texture feature in the image with respect to a
dominating structural feature of a particular implant, for example,
a filament of a vascular stent. In this manner, if the filaments
are arranged perpendicular to the X-scan direction, then Std=O. If
the filament is turned clockwise, the angle is positive, and if the
filament is turned counter-clockwise, the angle is negative. Note
that this parameter is meaningful only if the surface texture has a
dominating directional feature.
[0094] Std may be calculated from the Fourier spectrum. The
relative amplitudes for different angles relating to the filament
orientation are calculated by summation of the amplitudes along M
equiangularly separated radial lines, as described in Stout et al.
(1994). The Fourier spectrum is translated so that the DC component
is at (M/2, M/2). An angle .alpha. of the i-th line is equal to
.pi./M, where i=0, 1, . . . , M-1.
[0095] The angular spectrum is calculated by the following
formula:
A ( .alpha. ) = i = 1 M / 2 - 1 F ( u ( M / 2 + cos ( .alpha. ) , v
( M / 2 + sin ( .alpha. ) ) ) ) Equation 11 ##EQU00010##
[0096] For non-integer values of p=M/2+i cos(.alpha.) and q=M/2+i
sin(.alpha.), the value of F(u(p),v(q)) is found by linear
interpolation between the values of F(u(p), v(q)) in the 2.times.2
neighboring pixels. The line having the angle a with the highest
amplitude sum (i.e., Amax) is the dominating direction in the
Fourier transformed image and is perpendicular to the texture
direction on the image.
[0097] The Texture Direction Index (i.e., Stdi) is a measure of the
dominance of the dominating direction, and is defined as the
average amplitude sum divided by the amplitude sum of the
dominating direction:
S tdi = i = 0 M - 1 A ( .pi. / M ) MA max Equation 12
##EQU00011##
[0098] The Stdi value is between 0 and 1, where surfaces with a
dominant direction have low Stdi values and surfaces lacking a
dominant direction have high Stdi values.
[0099] The Radial Wavelength (i.e., Srw) is the dominating
wavelength found in the radial spectrum calculated by summation of
amplitude values around M/(2-1) equidistantly separated
semicircles. The radius r of the semicircles (measured in pixels)
is in the range r=1, 2, . . . , M/(2-1). The radial spectrum is
calculated by the following formula:
.beta. ( r ) = i = 1 M - 1 F ( u ( M / 2 + r cos ( .pi. / M ) , v (
M / 2 + r sin ( .pi. / M ) ) ) ) Equation 13 ##EQU00012##
[0100] The amplitude for non-integer values of p=M/2+r cos(i.pi./M)
and q=M/2+r sin(i.pi./M) is calculated by linear interpolation
between the values of F(u(p),v(q)) in the 2.times.2 neighboring
pixels.
[0101] The Dominating Radial Wavelength (i.e., Srw) corresponds to
the semicircle with radius, rmax, having the highest amplitude sum,
.beta.max:
S rw = .delta. x ( M - 1 ) r max Equation 14 ##EQU00013##
[0102] The Texture Aspect Ratio Parameters (i.e., Str20 and Str37)
are used to identify texture strength (uniformity of texture
aspect). It is defined as the ratio of the fastest to slowest decay
to correlation 20% and 37% of the autocorrelation function
respectively. In principle, the texture aspect ratio has a value
between 0 and 1, wherein a surface with a dominant lay has a
texture aspect ratio close to 0, while a more spatially isotropic
texture feature has a texture aspect ratio closer to 1.
Exemplary Ranges for Selected Parameters
[0103] The dimensions of the texture features are preferably
selected such that released coating fragments are too small to
cause thrombi or emboli. In particular, the dimensions of the
texture features are selected such that the width (i.e.,
side-to-side dimension) of the coating fragments do not exceed
about 1 mm (i.e., W is about 1 mm or less). Exemplary values for
the maximum width (W) of flaked off coating fragments are from
about 0.01 microns (.mu.m) to about 1 mm, and preferably from about
0.1 .mu.m to about 50 .mu.m, from about 5 .mu.m to about 25 .mu.m,
or from about 5 .mu.m to about 20 .mu.m. In some cases, the maximum
size of the coating fragments is selected to be no greater than the
maximum dimensions of naturally occurring particles present at the
site of implantation, such as red blood cells. Similarly, the
surface area of a texture feature is preferably from about 1 to
about 10,000 .mu.m.sup.2, from about 10 to about 2,500 .mu.m.sup.2,
from about 20 to about 2,000 .mu.m.sup.2, from about 25 to about
1,500 .mu.m.sup.2, from about 30 to about 1,000 .mu.m.sup.2, from
about 40 to about 500 .mu.m.sup.2, or the like.
[0104] The height (H) of the texture feature is preferably less
than about 50 .mu.m, 30 .mu.m, 25 .mu.m, 20 .mu.m, 15 .mu.m, 10
.mu.m, or even less than about 0.1 .mu.m. Naturally, thinner
coatings produce thinner fragments; however, since the thickness of
the coating is typically less than the maximum width (W) of the
texture feature, W is one of the most important dimensions in terms
of controlling the size of coating fragments. The ratio of the
thickness of the coating to height (H) is not as critical. The
thickness of the coating may be less than H or several times H,
depending on, for example, whether the coating covers the peaks of
the surface features.
[0105] With reference to the foregoing description of surface
texture feature design parameters and other parameters that will be
apparent to the skilled artisan, Table 2 identifies exemplary
ranges of values suitable for designing a surface textured
endovascular stent filament having the described features and
advantages.
TABLE-US-00002 TABLE 2 Exemplary Ranges for Selected Parameters
Parameters Units Exemplary Range Roughness Average (Sa) nm 200 to
1,100 Root Mean Square (RMS) (Sq) nm 300 to 2,400 The Surface
Skewness (Ssk) -0.04 to -8.25 Surface Kurtosis (Sku) 2.8 to 53.1
Peak-Peak (Sz, St, Sy) nm 2,000 to 19,000 Maximum pit height (Sv)
nm -1,000 to -16,000 Maximum peak height (Sp) nm 700 to 5,300 Mean
Summit Curvature (Ssc) 1/nm 0.0001 to 0.0013 Surface Area Ratio
(Sdr) % 12 to 430 Projected Area (S2A) nm.sup.2 2.5 .times.
10.sup.9 Surface Area (S3A) nm.sup.2 2.5 to 25 .times. 10.sup.9
Density of Summits (Sds) 1/.mu.m.sup.2 0.025 to 0.50 Texture
Direction (Std) deg 0 to 180 Texture Direction Index (Stdi) 0.576
to 0.895 Dominant Radial Wave Length (Srw ) nm 13,167 to 53,152
Texture Aspect Ratio at 20% (Str20) 0.08 to 0.94 Texture Aspect
Ratio at 37% (Str37) 0.08 to 0.96
Advantages of Surface Textured Implants
[0106] As discussed in the Background section, previous efforts to
address the problem of coatings flaking off a medical implant
subject to structural deformation have been aimed at increasing the
adhesion of the coating to the surface of the implant. However,
under less-than-optimal, real world conditions, the benefit of
prior art adhesion improvement is offset resulting in undesirable
and uncontrolled coating fragmentation and dislodgment that trigger
emboli.
[0107] Increasing the adhesion of an elastic coating to the surface
of an implant surface may be effective in reducing flaking,
particularly where the amount of surface distortion is within the
elastic limits of the coating. However, rigid and semi-rigid
coatings still have a tendency to break and crack in response to
stresses, such as those caused by distortion of the underlying
surface structure. The resulting stress fractures propagate
producing small coating fragments that can detach from the surface
of an implant despite efforts to increase coating adhesion.
[0108] The present invention involves surface textures that control
the size and shape of coating fragments that detach from the
surface of an implant. Controlling the size and shape of coating
fragments reduces the risk of embolism, particularly where the
implant is in contact with the blood stream, as in the case of a
coated stent. In addition to reducing the clinical risk of
thrombosis and embolism using conventional coatings, the present
invention further enables the use of rigid and semi-rigid coatings
that were heretofore unsuitable or undesirable for use as implant
coatings due to their tendency to brake and crack. Such coatings
include, but are not limited to, poly(d,l-lactic acid),
poly(l-lactic acid), poly(d-lactic acid), ethylene vinyl alcohol,
.epsilon.-caprolactone, glycolide, ethylvinyl hydroxylated acetate,
polyvinyl alcohol, polyethylene oxides, polyester amides,
poly(glycolic acid), polyethylene glycol hyaluronic acid, polyester
amide, poly(glycerol-sebacate), cellulose acetate, cellulose
nitrate, polyester, polyorthoester, polyanhydride,
polyhydroxybutyrate valerate, polycarbonates, tyrosine-derived
polycarbonates, and co-polymers and mixtures thereof.
[0109] While controlling the size and shape of coating fragments is
one aspect of the present invention, another relates to improving
the delivery of a therapeutic agent to tissues in contact with or
proximal to a coating on the surface of a medical implant. In the
case of a vascular stent, the tissue may be the wall of a blood
vessel. In the case of an orthopedic implant, the tissue may be
bone. With these and other implants, the peaks of the texture
features may protrude beyond the coating, or lie just beneath the
level of the coating, such that the peaks can contact the tissue
either upon implantation, or at some time thereafter, e.g., when
some of the coating has eroded or degraded. These peaks may be
selected to penetrate cell membranes or layers of cells in a
tissue, thereby improving the transport of a therapeutic agent
present in the coating due to increased access to the affected
tissue.
[0110] This feature of the present invention is illustrated in FIG.
9A, which shows a first surface 162 of an implant 160 positioned
adjacent to a tissue 164 including layers of cells 166, 168, 170.
In one embodiment of the invention, the implant may be a stent and
the tissue may be the wall of a blood vessel. A peak 172 of a
texture feature 180 may penetrate the membrane of a cell 166.
Alternatively, a peak 174 of a texture feature 180 may penetrate a
cell 168 to contact additional cells or layers of cells within the
tissue. Penetrating cell membranes or cells in the tissue adjacent
to the implant allows a drug optionally present in a coating 176 to
invade the surface layer cell membranes and/or contact cell
surfaces deeper within the tissue.
[0111] Yet a further advantage of the present invention is to
confine a region or fragments of a coating to a location adjacent
to an affected tissue. As illustrated in FIG. 9B, peaks 182 of a
texture feature 190 of an implant 184 may prevent a flaked off
fragment of coating 184 from leaving the site of implantation,
e.g., by holding the fragment captive against the surface 186 of a
tissue 188 in the body. While the fragment of coating may no longer
be adhered to a plateau 192, peak 182, and/or valley 194 (where
present) of the texture feature, and may, therefore, be free to
move with respect to the texture feature (indicated by the crossed
dotted arrows), the peaks preclude the movement of the coating
fragment from its original location adjacent to the surface of the
tissue. This feature ensures that a region of tissue adjacent to an
implant continues to receive the correct dosage of a beneficial
agent present in the coating, even when the corresponding fragment
of coating is no longer adhered to the implant.
[0112] Yet another advantage of the present invention is an
increase in the surface area of the device that is in contact with
the coating. In particular, the peaks, valleys and/or plateaus that
form the texture features actually increase the surface area of the
device. As a result, the coating contacts a larger amount of device
surface area, which may provide additional control over coating
adhesion, coating fragmentation and dislodgement and, ultimately,
drug delivery to the tissue. For example, the actual measured
surface area of a stent having texture features may be 1.5 to 10
times greater than the actual measured surface area of a stent
without texture features.
[0113] The skilled artisan will appreciate these and other features
of the present invention, one or more of which may be present in
different embodiments.
Coatings and Therapeutic Agents
[0114] The coating of the present invention is preferably a rigid
or semi-rigid coating, to be distinguished from an elastic coating.
While the present invention can be used in combination with an
elastic coating, such coatings are generally less prone to cracking
and flaking, and, therefore, benefit less from the presence of
texture features on the surface of an implant.
[0115] As previously described, exemplary rigid or semi-rigid
coatings include, but are not limited to, poly(d,l-lactic acid),
poly(l-lactic acid), poly(d-lactic acid), a co-polymer of
polylactic acid and polyethylene oxide, a co-polymer of polylactic
acid and poly(caprolactone), polybutylmethacrylate,
polymethyl(meth)acrylate, and other acrylic polymers,
polyethylene-co-vinylacetate/polybutylmethacrylate),
tyrosine-derived polycarbonates, poly-b-hydroxyalkanoic acids,
poly-b-hydroxybutyric acid, polyanhydride, and the like. The
coating may be cross-linked or non-cross-linked.
[0116] The coating typically includes at least one therapeutically
effective agent for delivery to the site of implantation. Exemplary
therapeutic agents include, but are not limited to, thrombolytics,
antirestenotic agents. vasodilators, antihypertensive agents,
antimicrobials, antibiotics, antimitotics, antiproliferatives,
antisecretory agents, non-steroidal anti-inflammatory drugs,
immunosuppressive agents, growth factors and growth factor
antagonists, antitumor and/or chemotherapeutic agents,
antipolymerases, antiviral agents, photodynamic therapy agents,
antibody targeted therapy agents, antithrombotic agents,
dexamethasone, dexamethasone acetate, dexamethasone sodium
phosphate, anti-inflammatory steroids, prodrugs, sex hormones, free
radical scavengers, antioxidants, biologic agents, radiotherapeutic
agents, radiopaque agents, and radiolabelled agents, cytotoxic or
cytostatic agents, and the like. Particular, antirestenotic agents
include taxol (paclitaxel), doxorubicin, cladribine, colchicines,
vinca alkaloids, heparin, hirudin, and their derivatives. In an
alternate embodiment, the drug or therapeutic agent may be
dispersed in a polymeric coating or covalently integrated into a
polymeric coating.
[0117] In some embodiments, the coating may be primarily composed
of the therapeutic agent, without benefit of an additional support
material such as a cross-linked polymer or other structural
support. Thus one additional advantage of the invention is the
possibility to create implants which do not use polymers as a
required element of the therapeutic coating for means of structural
support of the therapeutic agent. Polymers coated on the surface of
an implant are known to cause undesirable acute and chronic tissue
reactions. Undesirable responses can be avoided by reducing the
amount of carrier polymer used to deliver a drug, or by or
eliminating carrier polymer completely.
[0118] A particular class of antirestenotic agents is the
macrocyclic trienes, exemplified by rapamycin and other limus
drugs, such as sirolimus, everolimus, myolimus, novolimus,
pimecrolimus, tacrolimus, and zotarolimus, and the like. Further, a
particular limus drug is 40-O-(2-Ethoxyethyl) rapamycin or
42-O-(2-Ethoxyethyl) rapamycin (i.e., BA9TM). Macrocyclic triene
compounds, and their synthesis, are described, for example, in U.S.
Pat. Nos. 4,650,803, 5,288,711, 5,516,781, 5,665,772, 6,153,252,
and 6,273,913, PCT Publication No. WO 97/35575, and U.S. Patent
Application Nos. 2000021217, 2001002935, 20080097591, 20080097568,
and 20050211680, each of which is incorporated by reference
herein.
[0119] Because the present invention may increase adhesion of a
coating to the surface of an implant, underlayers or primers are
not required but may be used without defeating the purpose of the
invention. Exemplary undercoat materials include, but are not
limited to, poly(d,l-lactic acid), poly(l-lactic acid),
poly(d-lactic acid), ethylene vinyl alcohol, s-caprolactone,
ethylvinyl hydroxylated acetate, polyvinyl alcohol, polyethylene
oxides, poly(dichloro-para-xylylene), silane-based coatings
including organosilanes, aminosilane, vinyl silane, epoxy silane,
methacryl silanes, alkylsilane, phenyl silane, and chlorosilane,
polytetrafluoroethylene (TEFLON.RTM.) and other fluoropolymers, and
co-polymers thereof and mixtures thereof. The underlayer can be
deposited from a solvent-based solution, by plasma-coating, or by
other coating or deposition processes (see, e.g., U.S. Pat. No.
6,299,604). The underlayer typically has a thickness of between
about 0.5 micron and 5 microns, and should take up less than 20%,
less than 15%, or even less than 10% of the volume in a texture
feature.
Manufacturing Process
[0120] Another aspect of the present invention is a manufacturing
process for producing a surface textured implant. The process
involves removing and/or redistributing material on the surface of
an implant to produce one or more texturing features for
controlling the size and shape of pieces of coating that flake off
the surface of the implant. The surface texture can be created by
technologies such as chemical etching, photolithography,
micro/nano-abrasion, laser engraving, die transfer printing, water
jet cutting, electro-pitting gas plasma etching, corona process,
and other chemical-mechanical, chemical-photo, chemical-electrical,
and electrical-mechanical techniques.
[0121] Valleys (i.e., depressions relative to the surface) in a
texture feature are typically created by removing material but can
be created by forming or extrusion. Peaks may be created by adding
material to the surface of an implant or by forming or extrusion,
wherein the material that forms the peaks originates from another
(typically adjacent) location on the surface of the implant.
[0122] The present invention is not limited to a particular implant
material, and can utilize many materials commonly used for making
implants and medical devices. Exemplary materials include, but are
not limited to, metals, polymers, and ceramics. Metals further
include, but are not limited to, stainless steel, cobalt chromium,
nitinol, inconel, molybdenum, platinum, titanium, tantalum,
tungsten, gold, platinum, iridium, and other medical grade metals.
Polymers further include, but are not limited to, poly(d,l-lactic
acid), poly(l-lactic acid), poly(d-lactic acid), methacrylate
polymers, such as polybutyl methacrylate, polymethyl(meth)acrylate,
and the like, ethylene vinyl alcohol, s-caprolactone, glycolide,
ethylvinyl hydroxylated acetate, polyvinyl alcohol, polyethylene
oxides, polyester amides, poly(glycolic acid), polyethylene glycol
hyaluronic acid, polyester amide, poly(glycerol-sebacate),
nanoscale structures of carbon, acetal copolymer, acetal
homopolymer, acrylonitrile butadiene styrene, polycarbonate, nylon,
polyamide, polyacrylate, polyaryl sulfone, polycarbonate,
polyetherketone, polyetherimide, polyether sulfone, polyethylene
terephthalate, polyimide, polyphenylene oxide, polyphenylene
sulfide, polypropylene, polysulfone, polyurethane, polyvinyl
chloride, styrene acrylonitrile, carbon or carbon fiber; cellulose
acetate, cellulose nitrate, silicone, polyethylene teraphthalate,
polyurethane, polyamide, polyester, polyorthoester, polyanhydride,
high molecular weight polyethylene, polytetrafluoroethylene,
polyanhydride, polyhydroxybutyrate valerate, co-polymers and
mixtures thereof, and other polymers suitable for use in making
implants. Ceramic materials further include, but are not limited
to, hydroxyapatite, zirconia ceramics, and pyrocarbon ceramic-like
materials.
[0123] The foregoing description and examples are intended to be
illustrative and not limiting. Other features and embodiments of
the present devices and methods will be apparent in view of the
disclosure.
* * * * *