U.S. patent application number 10/159836 was filed with the patent office on 2003-12-04 for implantable product with improved aqueous interface characteristics and method for making and using same.
Invention is credited to Cook, Alonzo D., Cutright, Warren J., Krall, Robert C., Montgomery, William D..
Application Number | 20030225439 10/159836 |
Document ID | / |
Family ID | 29583039 |
Filed Date | 2003-12-04 |
United States Patent
Application |
20030225439 |
Kind Code |
A1 |
Cook, Alonzo D. ; et
al. |
December 4, 2003 |
Implantable product with improved aqueous interface characteristics
and method for making and using same
Abstract
An implantable medical device including a porous membrane that
is treated with a hydrophilic substance to obtain rapid optimum
visualization using technology for viewing inside of a mammalian
body. These technologies include ultrasound echocardiography and
video imaging such as that used during laparoscopic procedures.
Inventors: |
Cook, Alonzo D.; (Flagstaff,
AZ) ; Cutright, Warren J.; (Flagstaff, AZ) ;
Krall, Robert C.; (Flagstaff, AZ) ; Montgomery,
William D.; (Flagstaff, AZ) |
Correspondence
Address: |
W. L. Gore & Associates, Inc.
551 Paper Mill Road
P.O. Box 9206
Newark
DE
19714-9206
US
|
Family ID: |
29583039 |
Appl. No.: |
10/159836 |
Filed: |
May 31, 2002 |
Current U.S.
Class: |
607/2 ;
607/11 |
Current CPC
Class: |
A61F 2/82 20130101; A61F
2/01 20130101; A61B 8/0833 20130101; A61L 31/10 20130101; A61F
2250/0097 20130101; A61B 17/0057 20130101; A61B 6/12 20130101; A61L
31/146 20130101; A61L 31/18 20130101; A61L 31/048 20130101 |
Class at
Publication: |
607/2 ;
607/11 |
International
Class: |
A61F 002/00 |
Claims
The invention claimed is:
1. A device for implantation comprising a porous membrane supported
by a support frame forming an implantable device; the porous
membrane containing a hydrophilic substance adapted to rapidly
wet-out the porous membrane upon contact with an aqueous
solution.
2. The device of claim 1 wherein the device is configured for
cardiovascular implantation.
3. The device of claim 1 wherein wet-out occurs within 5 seconds of
immersion in an aqueous solution.
4. The device of claim 3 wherein the aqueous solution comprises DI
water.
5. The device of claim 3 wherein the aqueous solution comprises
human blood.
6. The device of claim 1 wherein the porous membrane comprises an
expanded polytetrafluoroethylene.
7. The device of claim 6 wherein the hydrophilic substance
comprises polyvinyl alcohol (PVA).
8. The device of claim 7 wherein the PVA is cross-linked in
place.
9. The device of claim 7 wherein wet-out occurs within 5 seconds of
immersion in an aqueous solution.
10. The device of claim 1 wherein the hydrophilic substance
comprises polyvinyl alcohol (PVA).
11. The device of claim 1 wherein the PVA is cross-linked in
place.
12. The device of claim 10 wherein wet-out occurs within 5 seconds
of immersion in an aqueous solution.
13. The device of claim 1 wherein the device is configured to serve
as a septal defect closure device.
14. The device of claim 1 wherein the device is configured to serve
as a stent-graft.
15. The device of claim 1 wherein the device is configured to serve
as an embolic filter.
16. The device of claim 1 wherein the device is effectively
transparent to ultrasound imaging.
17. An implantable device comprising a porous membrane of expanded
polytetrafluoroethylene; a dry hydrophilic treatment applied to the
porous membrane comprising a polyvinyl alcohol that is cross-linked
in situ; wherein the porous membrane wets-out within 5 seconds of
exposure to an aqueous solution of DI water so that the porous
expanded polytetrafluoroethylene membrane becomes entirely
translucent.
18. The device of claim 17 wherein the membrane is attached to a
frame.
19. The device of claim 18 wherein the device is configured for
cardiovascular implantation.
20. The device of claim 19 wherein the device is configured to
serve as a septal defect closure device.
21. The device of claim 17 wherein the membrane contains a barrier
layer.
22. The device of claim 21 wherein the barrier layer is impervious
to fluid transmission.
23. The device of claim 21 wherein the barrier layer allows
transmission of ultrasound.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to implantable medical devices
and more particularly to medical devices that are designed to be
surgically or endoluminally placed in a body.
[0003] 2. Description of Related Art
[0004] Medical devices designed to be introduced through
catheter-based delivery systems or through trocars are often
deployed using various remote visualization techniques, such as
x-ray imaging, fluoroscopy, ultrasound, and/or video imaging.
[0005] It has been determined that devices made from certain
microporous polymers, such as expanded polytetrafluoroethylene
(PTFE), sometimes are difficult to properly visualize using certain
remote visualization techniques because air trapped in the
microporous polymer can distort remote images. Most porous
materials will eventually wet-out with body fluids following
implantation, although this process may take time. In the case of
expanded PTFE, its hydrophobic nature can vastly slow the process
of replacing air with fluid following implantation--which can lead
to poor initial visualization following implantation.
[0006] Expanded PTFE is now a preferred material for use with many
implantable surgical and interventional devices, such as vascular
grafts, implantable sheet materials, stent-grafts, embolic filters,
and various occluders including septal occluders. As use of this
material has increased, it has become evident that these devices
often do not provide optimal initial visual clarity under
ultrasound, video imaging, and direct visualization.
[0007] Ultrasonic imaging is a somewhat vexing problem for
implantable porous materials. "Sound" is generally defined as a
periodic disturbance in fluid density, or inelastic strain of a
solid, generated by a vibrating object. In the case of
"ultrasound," it is generally defined as sound with a frequency of
over about 20,000 Hz. The velocity of ultrasound waves depends on
the medium through which they propagate. The velocity of sound
through air is about 330 m/sec; the velocity of sound through water
is about 1480 m/sec; the velocity of sound through muscle is about
1580 m/sec. While liquids tend to transmit ultrasound waves, air
tends to absorb such waves. As a result, the presence of air in an
implantable membrane introduces a disruptive layer that will
interfere with normal ultrasound wave transmission. While it is
recognized that these problems can be corrected by replacing the
air in the porous material with liquid, this process has generally
been addressed through the slow wetting-out of the porous material
over time following implantation.
[0008] For some applications, this process of slow wetting-out may
be undesirable. With the growing advent of remotely delivered
devices, more and more comprising a membrane attached to an
expanding frame, there is a need for instantaneous exact
visualization of the device prior to and immediately following
implantation. Devices such as fluoroscopes and x-rays can provide
such visualization, but the harmful radiation these devices deliver
to patients and medical personnel make them less desirable for
daily use. Due to its very low side-effect risks, ultrasound
visualization would be a preferred method of visualization, but
only if the remotely deployed devices can be instantly visualized
without interference. To date, no entirely suitable method of
instantly ultrasonically visualizing a device incorporating a
porous membrane has yet been developed.
[0009] Visualization and wet-out issues are discussed in a number
of existing patents. For instance, in Japanese Patent Application
No. 96480 to Oga it is recognized that expanded PTFE implantable
sheet material has a number of problems, including that: it cannot
be seen through; it reflects light, causing glare problems for
surgical staff; and it cannot be effectively probed with
ultrasound. The patent teaches that these problems can be corrected
by providing an expanded PTFE center layer that is pre-impregnated
with an aqueous liquid and two outer layers sealing the liquid
impregnated layer. Liquid polyvinyl alcohol (PVA) may be included
in the liquid impregnated layer. While this approach may solve
visualization problems, it presents a number of other problems,
including vastly increased manufacturing, packaging, shipping, and
handling problems while dealing with a pre-wetted material.
[0010] In PCT Patent Application WO 96/40305 to Hubbard, it is
again recognized that expanded PTFE cannot be seen through, it
reflects light, and it is not suitable for ultrasound imaging.
Hubbard teaches that the expanded PTFE can be pre-impregnated with
saline, polysaccharides, gums and gels, glycerol/gum xanthan,
sera/lipids, or the like, and then shipped wet. Again, this concept
requires increased expense and effort in dealing with the
manufacturing, packaging, and handling of a "wet" product.
[0011] Separate from visualization issues, a number of other
patents suggest incorporating wet or wettable materials within
implantable devices for various reasons of improved device
performance. For instance, U.S. Pat. No. 4,193,138 to Okita teaches
use of an expanded PTFE vascular graft with a water-soluble polymer
in its pores. The polymer in the pores forms a bonded film of
water, preventing adsorption of plasma protein, which is claimed to
improve patency. Multiple types of cross-linked PVA are disclosed
as a "swollen gel" in the pores of the expanded PTFE.
[0012] Similarly, U.S. Pat. No. 5,041,225 to Norman teaches an
expanded PTFE membrane coated with a combination of a hydrophilic
polymer and a complexing agent. The polymer is rendered water
insoluble by the complexing agent, which also provides good protein
bonding. PVA is taught as the hydrophilic polymer and various
inorganic compounds, such as boric acid, sodium borate, etc., are
taught as the complexing agents.
[0013] In U.S. Pat. No. 5,049,275 to Gillberg-LaForce et al., it is
taught that a microporous membrane, such as expanded PTFE, can be
changed from hydrophobic to hydrophilic by incorporating a vinyl
monomer, such as PVA, polymerized within the pores of the membrane.
This patent teaches that the membrane should be rendered
hydrophilic to be used as a separation membrane in rechargable
batteries, or in blood oxygenators, in bioreactors or for use in
blood dialysis, or to support a liquid membrane, wherein a liquid
which is imbibed in the pores of the microporous membrane is the
medium through which transport takes place.
[0014] In U.S. Pat. No. 4,525,374 to Vaillancourt it is taught that
an expanded PTFE membrane can be coated to render it hydrophilic by
treating it with triethanolamine dodecylbenzene sulfonate and then
dried. The patent teaches that the membrane should be rendered
hydrophilic to maintain the existing (inert characteristics)
surface properties of hydrophobic membrane filters and yet render
these filters hydrophilic such that they can be used for fluid
filtration, particularly for pharmaceutical processes.
[0015] In U.S. Pat. No. 5,755,762 to Bush it is taught that
electrical conductivity can be improved by treating an expanded
PTFE jacketed pacing or defibrillation lead with a wet-out agent,
such as DSS, TDMAC, surfactants, or hydrogels. Likewise in U.S.
Pat. No. 5,090,422 to Dahl et al., it is taught that an expanded
PTFE pacing lead jacket can be treated with a "wetting agent, or
surface modified" to allow wet-out and improve initial electrical
performance.
[0016] U.S. Pat. No. 5,897,955 to Drumheller et al. teaches that a
PVA coating can be provided on an expanded PTFE surface to aid in
attaching various biological entities. U.S. Pat. No. 5,902,745 to
Butler et al. teaches that a PVA treatment can be provided in the
wall of an expanded PTFE cell containment device to aid in seeing
the cells inside.
[0017] In summary, numerous concepts have been previously proposed
for rendering a porous membrane wet or wettable for a number of
functional reasons. However, particularly with regard to
endoscopically deployed devices that mount porous membranes on some
form of support frame, none of these previous concepts has taught
or suggested an ideal solution to aid in the instant visualization
of an implanted device that is highly effective, simple to
implement, and does not burden the manufacturing, packaging,
shipping, or handling of the implantable device.
SUMMARY OF THE INVENTION
[0018] The present invention employs treatment of an implantable
medical device, comprising a microporous membrane supported by a
frame, that allows the device to be rapidly and accurately
visualized by ultrasound and video imaging, and renders the device
transparent under direct visualization. The present invention
eliminates air-interference issues with porous membrane devices,
such as those incorporating expanded PTFE, by modifying the porous
membrane with a dried hydrophilic substance, such as polyvinyl
alcohol (PVA), to allow the membrane to rapidly displace air with
liquid once introduced into the body or otherwise contacted with an
aqueous liquid. The presence of dried hydrophilic substance on
and/or in the pores of the membrane vastly increases the rate at
which air is displaced by aqueous liquids and improves the rapid
and precise visualization of the device.
[0019] The preferred device of the present invention comprises an
expandable frame attached to a porous expanded PTFE membrane that
includes a cross-linked PVA material bound to the membrane. This
construction is suitable for use with a wide variety of remotely
deployed devices, such as septal and other occlusion devices,
embolic filters, certain stent-graft devices, implantable sheets,
and the like. In addition to allowing for very rapid accurate
visualization of the implanted device, the present invention is
believed to also provide a number of other benefits, including
improved biological performance and better ingrowth.
[0020] Another benefit of the present invention is its ability to
absorb aqueous solution, which may contribute to a significant
decrease in the abrasion type injuries seen when membranes come in
contact with tissue. In those instances where a membrane that is
impervious to fluid transmission is required, a barrier membrane
can be inserted between layers of expanded PTFE, thus allowing
ultrasound transmission and ingrowth.
[0021] These and other benefits of the present invention will be
appreciated from review of the following description.
DESCRIPTION OF THE DRAWINGS
[0022] The operation of the present invention should become
apparent from the following description when considered in
conjunction with the accompanying drawings, in which:
[0023] FIG. 1 is a three-quarter perspective view of a septal
defect closure device of the present invention, including a frame
and a porous membrane;
[0024] FIG. 2 is a cross-section view of a heart, including a
septal defect therein, showing initial deployment of the septal
defect closure device of FIG. 1;
[0025] FIG. 3 is a cross-section view of the heart showing second
stage deployment of the septal defect closure device;
[0026] FIG. 4 is a cross-section view of the heart showing final
deployment of the septal defect closure device;
[0027] FIG. 5 is an ultrasound image of a heart having been sealed
with a conventional septal defect closure device, including a
"shadow effect" caused by air trapped in the membrane portion of
the device;
[0028] FIG. 6 is an ultrasound image of a heart having been sealed
with a septal defect closure device of the present invention,
illustrating no shadow effect;
[0029] FIG. 7 is a three-quarter isometric view of an embolic
filter of the present invention, including a frame and a porous
membrane;
[0030] FIG. 8 is a three-quarter isometric view of a stent-graft of
the present invention, including a frame and a porous membrane;
[0031] FIG. 9 is a three-quarter isometric view of the stent-graft
of FIG. 8 following exposure to an aqueous liquid, the membrane
component having been wetted-out so as to render visible the frame
elements underneath;
[0032] FIG. 10 is a three-quarter isometric view of a porous
implantable membrane of the present invention;
[0033] FIG. 11 is a three-quarter isometric view of the porous
implantable membrane of FIG. 10 following initial implantation over
a tissue defect, the membrane having been rendered transparent by
contact with aqueous media at the surgical site;
[0034] FIG. 12 is a three-quarter perspective view of another
embodiment of the present invention comprising an artificial cornea
having a porous membrane attached around a transparent lens member,
said lens serving in part as the frame supporting the porous
membrane; and
[0035] FIG. 13 is a cross-section view along line 13-13 of FIG.
12.
DETAILED DESCRIPTION OF THE INVENTION
[0036] The present invention is directed to the modification of
implantable devices that employ a porous membrane mounted on one or
more frame elements so as to allow the device to be deployed
remotely in a medical procedure. The porous membrane of the present
invention is loaded with a hydrophilic substance that is dried on
and/or within the membrane. In its pre-implanted state the device
of the present invention is visually and tactilely
indistinguishable from conventional membrane and frame devices, but
when exposed to an aqueous liquid the membrane portion wets-out
rapidly so that the device becomes translucent or transparent to
light and ultrasonic imaging.
[0037] One embodiment of the present invention is illustrated in
FIG. 1. In this embodiment, the device comprises a septal defect
closure device 20 comprising a porous membrane 22 and a helical
support frame 24. The device is delivered to a treatment site in a
body using a series of concentrically mounted catheter tubes 26a
and 26b mounted on a mandrel 28. This device is similar to those
disclosed in U.S. Pat. Nos. 5,879,366, 6,080,182, and 6,171,329,
all to Shaw et al., and currently available for investigational
purposes from W.L. Gore & Associates, Inc., Flagstaff, Ariz.,
under the trademark HELEX.TM..
[0038] The device illustrated in FIG. 1 differs from the devices
described in the Shaw patents and available under the HELEX
trademark in that the membrane has been treated in accordance with
the present invention to render it hydrophilic. When treated in the
manner described in detail below, the septal defect closure device
will rapidly absorb aqueous solution so as to become transparent
upon introduction into the blood system of a patient. This
modification provides a number of important benefits.
[0039] The process for deploying a septal defect closure device 20
of the present invention is illustrated in FIGS. 2 through 4. As
shown, the defect closure device 20 is guided into a heart 30 using
the catheter tube 26 so as to position the device through a septal
defect 32. Shown in FIG. 2, a first portion 34 of the device is
then deployed on one side of the septal defect 32 by releasing part
of the frame 24 and attached membrane 22 from the catheter tube 26.
A second portion 36 of the device is subsequently deployed on an
opposite side of the septal defect, as is shown in FIG. 3. Once
imaging assures the medical staff that the device is properly
positioned, as is shown in FIG. 4, a final latch 38 is deployed to
lock the device in the septal defect and the catheter tube 26 is
removed.
[0040] Although the conventional device functions very well, its
membrane component is constructed from a porous expanded
polytetrafluoroethylene (PTFE) membrane, which is hydrophobic. As a
result, the membrane may take many days or weeks to fully absorb
surrounding solution and become visually and sonically transparent.
FIG. 5 is an ultrasonic image of a conventional septal defect
closure device shown immediately following implantation. The image
shows a distinct shadow (marked "Shadow Effect") caused by air
trapped in the membrane portion of the device. Until wet-out
occurs, this shadow effect makes it difficult to determine the
precise location of the device and the structure of surrounding
tissue using ultrasonic imaging.
[0041] FIG. 6 is an ultrasonic image of a device of the present
invention of comparable orientation and dimensions of the device
shown in FIG. 5. This device is shown as imaged by ultrasound
immediately after implantation, but as can be seen, no shadow
effect is evident in the image. This is because the provision of a
dried hydrophilic substance within the pores of the membrane 22
causes the membrane to rapidly wet-out once exposed to an aqueous
medium, such as blood. As a result, both the device and the
surrounding tissues can be clearly viewed using ultrasonic imaging
almost instantaneously following implantation.
[0042] As the terms "rapid" and "rapidly" are used to describe the
wet-out process of the present invention, they mean that most if
not all of the air normally trapped in the porous structure of the
membrane has been displaced by liquid within 30 seconds following
contact with an aqueous medium, and more preferably within 5 to 10
seconds following aqueous medium contact. The effective evacuation
of air can be confirmed in a porous expanded PTFE material once the
membrane becomes translucent to visual light.
[0043] To construct a device of the present invention, a
hydrophilic layer is formed on a membrane by applying a polymeric
hydrophilic surfactant, such as but not limited to polyvinyl
alcohol (PVA) or polyvinyl pyrrolidone (PVP), to the surface of the
membrane. The hydrophilic substance may then be bound in place,
such as through cross-linking the surfactant to itself in situ. For
a porous frame member, the hydrophilic layer may optionally be
adsorbed within the porous void spaces of the frame member as
well.
[0044] When using a hydrophobic membrane, and if the polymer chosen
for the hydrophilic layer dissolves in only high surface tension
solvents, the hydrophobic membrane should be pre-wetted with a
miscible solvent having a low surface tension to enhance adsorption
of the polymer onto the membrane. Examples of appropriate
pre-wetting agents can be, but are not limited to, isopropyl
alcohol (IPA), ethanol, or methanol in a concentration of about 25%
to 100%, preferably 50% to 100%, and most preferably 70% to 100%.
The membrane should be immersed in the miscible solvent for about 1
second to one hour, preferably 5 seconds to five minutes, and most
preferably for about 30 to 60 seconds.
[0045] The membrane is then immediately transferred into a solution
of the polymeric surfactant in an appropriate solvent. For example,
a solution comprising a polymeric surfactant dissolved in a
suitable solvent (such as water), at a concentration of about
0.001% to about 99.9%, preferably about 0.25% to about 5%, and most
preferably 1.5% to 2.5%, is initially adsorbed onto the surfaces
and optionally into the porous spaces of a porous membrane simply
by dipping the membrane in the solution for about 0.05 minutes to
about 24 hours, preferably 5 to 180 minutes, and most preferably
for about 10 to 30 minutes. This treatment step permits
physisorption of the surfactant to the surface of the membrane. The
membrane is then rinsed to wash off any excess polymeric surfactant
and then the polymeric surfactant may be cross-linked in place.
[0046] Suitable materials for the hydrophilic layer include, but
are not limited to, polyvinyl alcohol, polyethylene glycol,
polypropylene glycol, dextran, agarose, alginate, polyacrylamide,
polyglycidol, poly(vinyl alcohol-co-ethylene),
poly(ethyleneglycol-co-propyleneglycol), poly (vinyl
acetate-co-vinyl alcohol), poly(tetrafluoroethylene co-vinyl
alcohol), poly(acrylonitrile-co-acrylamide), poly
(acrylonitrile-co-acryl- ic acid-co-acrylamide), polyacrylic acid,
poly-lysine, polyethyleneimine, polyvinyl pyrrolidone,
polyhydroxyethylmethacrylate, and polysulfone, and their
copolymers, either alone or in combination.
[0047] Preferred copolymers for formation of the hydrophilic layer
are copolymers comprising at least one moiety capable of
physiochemically adsorbing to the membrane, at least one moiety
capable of chemical modification with a suitable agent, and at
least one moiety capable of interacting with high surface tension
fluids. These moieties may be selected such that one moiety
fulfills all of these three roles simultaneously, fulfills two
roles, or fulfills only one role.
[0048] Suitable solvents for this purpose include, but are not
limited to, methanol, ethanol, isopropanol, tetrahydrofuran,
trifluoroacetic acid, acetone, water, dimethyl formamide (DMF),
dimethyl sulfoxide (DMSO), acetonitrile, benzene, hexane,
chloroform, and supercritical carbon dioxide.
[0049] The polymeric surfactant of the layer is covalently
cross-linked to itself in situ using a suitable cross-linking agent
to produce surface-bound planar molecules of extremely high
molecular weight. These very high molecular weight molecules serve
to greatly reduce or eliminate the potential for desorption or
migration of the surfactant.
[0050] Suitable reagents for use in cross-linking the polymeric
surfactant in situ are compounds comprising at least two chemically
functional groups, either homofunctional or heterofunctional, that
include, but are not limited to, aldehydes, epoxides, acyl halides,
aryl halides, isocyanates, amines, anhydrides, acids, alcohols,
haloacetals, arylcarbonates, thiols, esters, imides, vinyls,
azides, nitros, peroxides, sulfones, and maleimides.
[0051] The reagents should be dissolved in solvents that wet the
adsorbed layer. Solvents suitable for dissolving the cross-linking
reagent include, but are not limited to, acetone, water, alcohols,
tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dimethyl
formamide (DMF), benzene, acetonitrile, and dioxane. Other possible
reagents include, but are not limited to, free radicals, anions,
cations, plasma irradiation, electron irradiation, and photon
irradiation. One preferred cross-linking agent is glutaraldehyde,
preferably using a catalyst of hydrochloric acid (HCl), preferably
dissolved in water. The membrane with the surfactant is then
submersed into a solution of, but not limited to,
glutaraldehyde/HCl in a water concentration of about 0.001%/0.001%
to 99.9%/99.9%, preferably 0.1%/0.1% to 5%/5%, and most preferably
1%/1% to 3%/3%. The membrane should be submersed for anywhere from
1 second to 3 hours, but preferably 1 minute to one hour, and most
preferably 10 to 20 minutes followed by a final rinse to wash off
any excess glutaraldehyde/HCl uncrosslinked residual.
[0052] When treated in this manner, the membrane will rapidly
absorb liquid and will render the device translucent to light and
relatively transparent to sound. As such, the present invention has
numerous applications for all kinds of endoluminally and surgically
delivered devices, including: implantable closure devices;
implantable filter devices; various graft and stent-graft devices;
various implantable sheets, including sheets that include support
frames; implantable devices with impermeable barrier layers, and
implantable devices with incorporating skirts or other elements of
porous material. Examples of such other applications for devices of
the present invention are illustrated in FIGS. 7 through 13.
[0053] FIG. 7 illustrates one form of an embolic filter device 40
of the present invention. In this embodiment, the device 40
includes a porous membrane 42, having multiple macroscopic openings
44 therein, attached to a guidewire 46 by a frame 48. By treating
the porous membrane 42 in the manner described above, the membrane
will rapidly wet-out so as to allow clear ultrasonic imaging of the
device 40 following deployment. Additionally, it is believed that
rapid wet-out of the membrane may also provide improved filtration
performance for the membrane 42.
[0054] FIGS. 8 and 9 illustrate a stent-graft device 50 of the
present invention. In this instance, the device 50 includes a frame
52, comprising a series of undulating stent elements 52a, 52b, 52c,
52d, 52e, and a membrane 54 mounted around the outside of the frame
52. Although wet-out of many blood-deployed graft elements is not
desired since such wet-out can lead to serum leakage, for some
applications where such seepage is not an issue, a device of the
present invention can be used to enhance visual and ultrasonic
imaging. Even in instances where serum leakage may be undesirable,
the benefits of the present invention can still be achieved by
providing a barrier layer within the device to resist serum
leakage. As is shown in FIG. 8, prior to exposure to an aqueous
medium, the membrane 54 completely obscures the frame elements 52
mounted therein. Once exposed to blood or other aqueous liquid, as
is shown in FIG. 9, the membrane 54 becomes translucent or even
transparent so as to allow visualization of the frame 52 and the
interior of the device. This kind of device is believed beneficial
for certain stent-graft applications, such as carotid stenting,
peripheral vascular stenting, or as a transjugular intrahepatic
portacaval shunt (TIPS). This device may also be of use in the
revision of the venous anastomosis of a vascular graft used for
hemodialysis access, in coronary artery bypass graft revisions, or
in stenting coronary arteries. Additionally, the rapid wet-out of
the membrane may also provide additional benefits, such as
presenting a better blood contact surface within the device, and
allowing more rapid cell ingrowth into the device.
[0055] Still another application for the present invention
comprises an implantable sheet device 56 as illustrated in FIGS. 10
and 11. In this embodiment, the device 56 comprises a porous
membrane, such as one constructed from expanded PTFE and
commercially available from W.L. Gore & Associates, Inc., in a
variety of forms such as those sold under the trademarks
GORE-TEX.RTM., PRECLUDE.RTM., MYCROMESH.RTM., or DUALMESH.RTM..
Although all of these membranes have been engineered for different
implantation applications, each shares the common property of being
constructed at least in part from a hydrophobic porous expanded
PTFE material. This material is highly light reflective and can
result in some glaring when implanted under bright surgical light
in the surgical site. This may likewise be a problem when implanted
endoscopically and the physician must view the surgical site
through remote video imaging. For some such applications it is
believed that allowing the membrane to be rapidly rendered
translucent or transparent, as is shown in FIG. 11, may aid the
physician in placing and anchoring the sheet in place.
Additionally, as is also shown in FIG. 11, a translucent sheet 56
may also allow visualization of underlying tissue 58 and
confirmation of proper sheet placement over areas requiring repair,
such as a tissue tear 60. Again, additional benefits that a
wetted-out sheet could provide may include improved blood or other
body fluid contact, and/or improved tissue ingrowth.
[0056] In instances where serum leakage is undesirable, a barrier
membrane can be placed within the device construct to prevent serum
leakage. One such device is available from W.L. Gore &
Associates, Inc., as the GORE-TEX.RTM. ACUSEAL Cardiovascular
Patch. This device comprises two layers of expanded PTFE and a
middle barrier layer of thermoplastic fluoropolymer elastomer. This
middle barrier layer can serve in part as a support frame for the
two layers of expanded PTFE. When the outer layers of expanded PTFE
are treated with PVA, this embodiment of the invention is
particularly useful as a surgical membrane for use in carotid
artery endarterectomy repair, where it is desirable to check the
patency of the repaired vessel immediately following the surgery
using ultrasound.
[0057] As the term "membrane" is used herein it is intended to
include any porous material that may be incorporated into an
implantable device in any suitable shape and configuration.
Suitable configurations contemplated by the present invention
include sheets, tubes, fibers, rods, etc. Configurations may also
include other shapes, such as the folded-over strips of material
illustrated in the septal defect closure device of FIG. 1. The
porous material may include any of, or any combination of, the
following materials: expanded PTFE, polypropylene, polyolefin
hollow fiber, polyvinylidene fluoride, PTFE,, fluorinated ethylene
propylene (FEP), hexafluoropropylene, polyethylene, polypropylene,
polyamide (nylon), polyethyleneterephthalate, polyurethane,
silicone rubber, polystyrene, polysulfone, polyester,
polyhydroxyacid, polycarbonate, polyimide, polyamino acid,
regenerated cellulose, or proteins, such as silk, wool, and
leather. Particularly preferred for use with the present invention
is a porous expanded PTFE material, such as that employed in
various medical products available from W.L. Gore & Associates,
Inc.
[0058] As the term "frame" is used herein it is intended to include
any support structure that may be incorporated into or used with an
implantable device. Suitable configurations may include defect
closure frame configurations, any of a wide variety of stent frame
configurations, filter frame configurations, occluder
configurations, or any frame designed to aid in the positioning of
a porous material in a body. Suitable materials include metals,
such as stainless steel, nitinol, MP35N, titanium, or other metals
used in biomedical applications; plastics, such as PTFE, expanded
PTFE, polypropylene, fluorinated ethylene propylene,
hexafluoropropylene, polyethylene, polypropylene, nylon,
polyethyleneterephthalate, polyurethane, silicone rubber,
polystyrene, polysulfone, polyester, polyhydroxyacids,
polycarbonate, thermoplastic fluoropolymer elastomer, or other
plastics used in biomedical applications; as well as other
materials suitable for use in biomedical applications. The frame
may be internal, external or both with respect to the porous
membrane.
[0059] Without intending to limit the present invention to the
specifics described hereinafter, the following examples illustrate
how the present invention may be made and used.
EXAMPLE 1
Process for Coating a Septal Occluder
[0060] A HELEX.TM. Septal Occluder (SO) is acquired from W.L. Gore
& Associates, Inc., Flagstaff, Ariz. This device, illustrated
in FIGS. 1 through 4, comprises a nitinol metal frame and a porous
expanded PTFE sheet wrapped around the metal frame.
[0061] The entire SO is immersed in 100% isopropyl alcohol for 30
seconds. The SO is then transferred to a 2% PVA/DI Water solution
for 30 minutes. The SO is rinsed in DI water for 10 minutes and
then placed in a 2% glutaraldehyde/1% hydrochloric acid-DI water
solution for 15 minutes. The SO is then rinsed in DI water for 15
minutes and allowed to air dry.
[0062] This final treated SO wetted-out rapidly when exposed to an
aqueous solution, the membrane becoming completely translucent
within 5 seconds after submersion in a water bath.
EXAMPLE 2
Process for Coating Stent-Graft
[0063] A VIATORR.TM. Stent-Graft is acquired from W.L. Gore &
Associates, Inc., Flagstaff, Ariz. This device, designed for
establishing a shunt through a patient's liver in a transjugular
intrahepatic portacaval shunt (T.I.P.S.) procedure, comprises a
nitinol metal stent-element that is partially covered with a
tubular expanded PTFE graft element.
[0064] The stent-graft is placed in 100% IPA for 30 seconds and
then immediately transferred into a 2% PVA/DI Water solution for 20
minutes. The stent-graft is then transferred into a DI water rinse
for 15 minutes. The stent-graft is then placed in the 2%
glutaraldehyde/1% hydrochloric acid-DI water solution for 15
minutes. The stent-graft is then transferred into a final DI rinse
for 15 minutes.
[0065] The final stent-graft device wet out rapidly when exposed to
DI water, becoming completely translucent within 5 seconds after
submersion in the water.
EXAMPLE 3
Process for Coating Embolic Filter
[0066] The filtering membrane was made by laser perforating one
layer of a thin (total thickness about 0.0005 cm (0.0002 in))
polytetrafluoroethylene (PTFE) membrane from W.L. Gore &
Associates, Elkton, Md. A hole pattern of uniform size and spacing
was created. The perforated membrane was then folded on itself and
heat-sealed using a soldering iron to create a conical shape. The
conical flat pattern was then trimmed with scissors, inverted, and
mounted on a tapered mandrel.
[0067] The conical filter membrane was attached to a nitinol metal
frame using a fluorinated ethylene propylene (FEP) powder coated
adhesive (FEP 5101, available from E.I duPont de Nemours & Co.,
Wilmington, Del.) and localized heat application.
[0068] Following embolic filter construction, the embolic filter
was placed in 100% IPA for 30 seconds. The device was then
immediately transferred into a 2% PVA/DI Water solution for 20
minutes. Then the device was transferred into a DI water rinse for
15 minutes. Following the rinse, the device was placed in a 2%
glutaraldehyde/1% hydrochloric acid-DI water solution for 15
minutes. The device was then transferred into a final DI rinse for
15 minutes.
[0069] Without the PVA treatment the device would not pass any
fluid. After PVA treatment, the device was very effective at
passing fluid while stopping the 100 micron and larger particles
with over 98% efficiency.
EXAMPLE 4
Process for Coating a Pericardial Membrane
[0070] A PRECLUDE.RTM. Pericardial Membrane (PCM) was acquired from
W.L. Gore & Associates, Inc., Flagstaff, Ariz., and treated as
follows. The PCM was immersed in IPA for 30 seconds. The PCM was
immediately transferred into a 2% PVA/DI Water solution for 30
minutes. The PCM was transferred into a DI water rinse for 10
minutes. The PCM was placed in a 2% glutaraldehyde/1% hydrochloric
acid-DI water solution for 15 minutes.
[0071] The PCM was then transferred into a final DI rinse for 15
minutes.
EXAMPLE 5
Use of Pericardial Membrane in an Animal Model
[0072] The PCM made as described in Example 4, above, was implanted
into an animal model. Immediately following implant the PCM
material became visually transparent and presented no noticeable
glare.
EXAMPLE 6
Use of Septal Occluder in an Animal--Visualization by
Ultrasound
[0073] An ultrasound machine (Sequoia C256, Acuson Corporation,
Mountain View, Calif.) with an Intracardiac Probe (Acunav, Acuson
Corporation, Mountain View, Calif.) was used to assess the clarity
of visualization of the HELEX Septal Occluder treated according to
Example 1. The treated device was immersed in heparinized saline
and then deployed into a canine acutely. The edges of the device
were clearly seen. The differences between the inventive device and
a control are illustrated in FIGS. 5 and 6 and have been previously
described.
EXAMPLE 7
Testing for Hydroxyl Groups
[0074] This example describes an assay by which uniformity of
coverage of devices with cross-linked polyvinyl alcohol (PVA) can
be qualitatively assessed by visual inspection and quantitatively
assessed by removal of the dye and spectrophotometric measurement
of the dye concentration. The assay employs a blue dye, Cibachron
Blue 3GA, which binds to free hydroxyl groups that are present on
the surface of immobilized PVA. One molecule of Cibachron Blue
binds to one free hydroxyl, so one can quantify free hydroxyl
availability by removal of the attached dye with strong acid.
[0075] Binding of Cibachron Blue 3GA was accomplished using a
modification of the method described in Hermanson, G. T., Mallia,
A. K., and Smith, P. K., Immobilized Affinity Ligand Techniques,
1992, Academic Press, p. 176, as follows:
[0076] 1. A piece of PVA-coated Septal Occluder made in accordance
with Example 1 is cut, weighed and measured;
[0077] 2. Add10 ml deionized water to the membrane and heat to
60.degree. C. in a tube block heater;
[0078] 3. Add 0.1 gm of Cibachron Blue 3GA in 3 ml water, and heat
at 60.degree. C. for 30 min;
[0079] 4. Add 1.5 gm NaCl and heat at 60.degree. C. for 1 hr;
[0080] 5. Raise the temperature to 80.degree. C.;
[0081] 6. Add 0.15 gm Na.sub.2CO.sub.3 and heat at 80.degree. C.
for 2 hr;
[0082] 7. Cool, remove dye and rinse with water until no more color
is removed.
[0083] Controls not treated with PVA are wetted with absolute
ethanol, then water-rinsed prior to the above regimen. Any residual
color on controls can be removed by a 15 min. treatment in absolute
ethanol after water rinsing, and followed by more water rinses.
Alcohol will not affect the dye on the PVA.
[0084] Removal of the dye for quantification is done according to a
modification of the procedure of Clonis, Y. D., Goldfinch, M. J.,
and Lowe, C. R. Biochem. J. 197, 1981, 203-11, "The interaction of
yeast hexokinase with Procion Green H-4G," as follows:
[0085] 1. The stained PVA-coated membrane is cut into small pieces
and placed in a vial containing 0.6 ml of 5N HCl. The vial is then
heated at 60.degree. C. for 3 hrs in a test tube block heater.
[0086] 2. Then, 2.4 ml of 2.5 M sodium phosphate buffer, pH 7.4, is
added, and the tubes are agitated for 5 min to extract the color
from the membrane pieces.
[0087] 3. The extract is removed, and the absorbances are read on a
Varian DMS300 UV/VIS spectrophotometer at 620 nm.
[0088] 4. The amount of dye in the extract is quantified from a
standard curve constructed by preparing a series of Cibachron Blue
solutions in the HCl/sodium phosphate mix ranging in concentration
from 20 to 200 .mu.g/ml.
[0089] 5. The membrane pieces from which the dye is extracted are
washed in water. These pieces should now be white.
[0090] The results are expressed as .mu.g Cibachron Blue/mg device.
Four samples were tested according to the protocol above. The
results were: 4.45+/-1.45 .mu.g dye/mg Helex, N=4. The untreated
(control) samples did not take up any dye.
EXAMPLE 8
FTIR Test for Hydroxyl Groups
[0091] The degree of cross-linking of the layer may be assessed by
Fourier Transform Infrared Spectroscopy (FTIR). For example, with
FTIR the free hydroxyl groups of polyvinyl alcohol (PVA) are
detectable before crosslinking at approximately 3349 cm.sup.-1.
After cross-linking, the peak shifts to approximately 3383
cm.sup.-1 and decreases in height. As a positive internal control,
an FTIR peak at approximately 2942 cm.sup.-1 due to the CH.sub.2
groups does not change position or height as a result of
cross-linking. A shift in the hydroxyl group (--OH) peak position
from approximately 3349 cm.sup.-1 to approximately 3383 cm.sup.-1
with a decrease in peak height is an indication of the amount of
PVA that has become cross-linked in the formation of the first
layer.
[0092] The detection of the broad hydroxyl peak at approximately
3383 cm.sup.-1 was confirmed on a HELEX Septal Occluder made
according to Example 1, using a Model 560ESP FTIR (NICOLET Corp.,
Madison, Wis.) and an ATR crystal apparatus (Zinc-Selenium 45 deg.,
Part#0050-603, SpectraTech, Stamford, Conn.). An untreated control
HELEX Septal Occluder demonstrated no peak between 3000 and 3600
cm.sup.-1.
EXAMPLE 9
Evaluation of Tissue Ingrowth of Large Hole GORE-TEX.RTM.
MYCROMESH.RTM. Biomaterial and GORE-TEX.RTM. DualMesh Biomaterial
Impregnated with PVA.
[0093] Six New Zealand White Rabbits were used in this study.
Samples of Large Hole GORE-TEX.RTM. MYCROMESH.RTM. Biomaterial and
GORE-TEX.RTM. DualMesh Biomaterial.RTM. were obtained from W.L.
Gore & Associates, Inc. (Flagstaff, Ariz.). The samples were
treated with PVA according to the method described in Example 4 to
create hydrophilic membranes. Four samples were implanted in each
of six animals. Two approximately 2.5 cm disks, one MYCROMESH
biomaterial and one DUALMESH biomaterial were implanted
subcutaneously on the rabbit dorsum. Two approximately 3.75 cm
disks, one MYCROMESH biomaterial and one DUALMESH biomaterial were
implanted intra-abdominally on the peritoneal wall in contact with
viscera.
[0094] One side of both materials has a textured appearance. The
MYCROMESH biomaterial was implanted with the textured side opposed
to muscle, the DUALMESH biomaterial was implanted with the textured
side adjacent to muscle. Animals were in-life for 7 and 30 days.
There were 3 animals per in-life period.
[0095] Explant Observations
[0096] 7 Day Explants: No adhesions were observed to both materials
in the intra-abdominal regions. Both materials were generally
covered by a thin translucent capsule within the subcutaneous
tissue. The surrounding soft tissue was unremarkable.
[0097] 30 Day Explants: No adhesions were observed to both
materials. The surrounding soft tissue in the intra-abdominal
region appeared unremarkable. A thin translucent capsule covered
both implants in the subcutaneous region.
[0098] Histological Analysis
[0099] 7 Day Explants: Large Hole GORE-TEX.RTM. MYCROMESH.RTM.
Biomaterial: The tissue response was a minimal foreign-body
reaction with mild inflammation consistent with wound healing. The
periimplant membrane consisted of early granulation tissue
containing numerous and scattered large and small blood vessels.
The cellular components, at the interface, consisted of histiocytes
and foreign body giant cells. The peripheral nerve bundles appeared
unremarkable with mild degeneration consistent with wound healing.
Numerous blood vessels were observed within the macropores. The
neomesothelium dipped down and covered the macropores in the
intraperitoneal region. Cellular migration into the interstices was
extensive and scattered throughout the implants.
[0100] Polarized light microscopy revealed the nodes of the
expanded PTFE to be aligned parallel and consistent through the
entire implant. The fiber lengths appeared large. Occasionally, the
implants appeared loosely adherent to the underlying muscle
tissue.
[0101] GORE-TEX.RTM. DUALMESH Biomaterial: The microstructure
appeared similar to the large hole MYCROMESH Biomaterial with
consistent parallel aligned nodes with large fibril lengths.
Cellular migration into the interstices was extensive and scattered
with numerous red blood cells and histiocytes. The periimplant
membrane consisted of granulation tissue with numerous blood
vessels. There was no evidence of bacteria or calcification.
[0102] 30 Day Explants: Large Hole MYCROMESH.RTM. Biomaterial: The
periimplant membrane appeared to have a bland fibrocollagenous
tissue with linearly aligned collagen fibers. The foreign-body
tissue response was minimal. There was no evidence of inflammation
in several of the implants. Cellular migration into the interstices
was extensive with considerable collagen deposition. Blood vessels
were numerous at the interface. The peripheral nerve bundles
appeared unremarkable. Capillaries were observed within the
interstices. Cellular migration was observed from both interfaces.
There was no evidence of bacteria. A few microfoci of calcification
were observed.
[0103] DUALMESH.RTM. Biomaterial: The periimplant membrane
consisted of a bland fibrocollagenous tissue with aligned parallel
collagen fibers to the interface. The neomesothelial-like membrane
appeared mature. Blood vessels were numerous at the interface
consisting predominantly of capillaries. Cellular migration into
the interstices was extensive and often scattered. Collagen
deposition was evident. Some of the sutures demonstrated occasional
microfoci of calcification. The foreign-body tissue response was
minimal. Several of the implants demonstrated no evidence of
inflammation. There was no evidence of bacteria.
[0104] Conclusion
[0105] There was extensive cellular migration with collagen
deposition into the interstices of both implants at the 30 day time
frame. The migration of cells into both implants at the 7 day time
frame was remarkable and considerable. The periimplant membrane
appeared to consist of a bland fibrocollagenous tissue. Small blood
vessels were numerous at the interface of both implants. The nerve
bundles in the subcutaneous site, at the 7 day time frame,
demonstrated degeneration consistent with wound healing, but
appeared unremarkable at the 30 day time frame. Cellular ingrowth
into the treated membrane spanned the entire membrane width
(>500 um).
[0106] Cellular migration into the interstices of the large hole
MYCROMESH.RTM. Biomaterial was evident from both interfaces. The
foreign-body tissue response was minimal. There was no evidence of
inflammation in many of the implants at the 30 day time frame.
There was no evidence of bacteria in all implants for all time
frames. Occasionally, microfoci of calcification was sparsely
observed in both implants and in the sutures.
EXAMPLE 10
Subcutaneous Study of PRECLUDE.RTM. Dura Membrane in a Rabbit
Model
[0107] Six adult New Zealand White Rabbits were used in this study.
Samples of PRECLUDE.RTM. Dura Substitute were obtained from W.L.
Gore & Associates, Inc. (Flagstaff, Ariz.) and treated
according to the method described in Example 4 to create
hydrophilic membranes. Two surfactants, Dioctyl Sodium
Sulfosuccinate (DSS) and Polyvinyl alcohol (PVA), were used to
render the material immediately wettable with water or saline,
allowing for vessel and tissue visibility during surgery, and to
help in postoperative evaluations.Two, approximately 2.5 cm
diameter disks were implanted subcutaneously on the dorsum of the
rabbit. One device was treated with DSS and one with PVA. There
were two in-life periods, of 7 days and 30 days, with 3 animals at
each in-life time period.
[0108] Explant Observations
[0109] 7 Day Explants: All of the implants appeared wet-out and
intact. The implants were loosely adherent to the underlying muscle
tissue. Occasional regions of hemorrhage were observed at the
suture site. The implants were covered by a thin, translucent
capsule along the anterior surface, toward the parietal region.
Blood vessels were occasionally observed in the posterior region,
along the muscle tissue.
[0110] 30 Day Explants: All of the implants were generally
encapsulated by a translucent to a slightly opaque capsule. Many of
the implants appeared to be firmly to loosely adherent to the
underlying muscle tissue. Suture sites still showed persistent
brownish/reddish granular regions.
[0111] Histological Evaluation
[0112] 7 Day Explants: A gradient effect was observed among all
three materials. Consistently, the Dura Membrane treated with PVA
revealed no adherence to the underlying soft tissue. The adipose
tissue, at the interface, appeared benign. The foreign-body tissue
response and histiocytic response were minimal.
[0113] The Dura Membrane implants treated with DSS demonstrated no
adherence to the underlying muscle tissue. However, within the
adipose tissue numerous foreign body giant cells and histiocytes
were observed with a few vacuoles. This adipose tissue appeared
mildly inflamed.
[0114] The Dura Membrane control demonstrated a marked inflammatory
effect characterized by a zone of fibrinous regions as well as
histiocytes and foreign body giant cells within the adipose tissue.
The periprosthetic tissue was generally in close proximity to the
Dura Membrane.
[0115] 30 Day Explants: The PRECLUDE.RTM. Dura Membrane implants
treated with PVA consistently revealed non-adherence to the
underlying soft tissue. The periprosthetic tissue appeared bland.
The underlying adipose tissue was unremarkable.
[0116] The Dura Membrane implants treated with DSS demonstrated
close proximity of the periprosthetic tissue to the surface of the
Dura Membrane. Occasional regions of focal attachment were observed
along one surface of the Dura Membrane. Generally, mild
inflammation with hypercellularity of the periprosthetic tissue was
observed. Occasional foreign body giant cells and histiocytes were
observed within the adipose tissue.
[0117] The Dura Membrane control implants consistently revealed
close proximity of the periprosthetic tissue to both surfaces of
the implants. Numerous regions of focal attachment of the
periprosthetic tissue to the Dura Membrane were observed.
Generally, inflammation with hypercellularity of the periprosthetic
tissue was observed. Foreign body giant cells and histiocytes were
observed within the adipose tissue. There was no evidence of
bacteria or calcification at all time periods in all the
implants.
[0118] Conclusion
[0119] The PRECLUDE.RTM. Dura Membrane treated with PVA
demonstrated non-adherence of the periimplant membrane. The tissue
response was bland.
[0120] The Dura Membrane treated with DSS demonstrated close
proximity of the periimplant membrane with focal regions of
attachment and mild inflammation of the adipose tissue.
[0121] The Dura Membrane control implants demonstrated an adverse
tissue response. This was characterized by close apposition of the
periimplant membrane to both surfaces. Numerous regions of focal
tissue attachment and persistent inflammation of the adipose tissue
were apparent.
EXAMPLE 11
Treatment of Corneal Prostheses
[0122] Corneal prostheses (or "keratoprostheses") were made,
treated with PVA, implanted and evaluated after explant. Shown in
FIG. 12 is an isometric view of an implantable corneal prosthesis.
Shown is a keratoprosthesis 70 having expanded PTFE peripheral
skirts 72, 74 attached to a fluoropolymer corneal substitute 76.
The expanded PTFE skirts were treated with PVA in accordance with
the procedure described in Example 4. Shown in FIG. 13 is a
cross-sectional view of an implantable keratoprosthesis 70, showing
a first expanded PTFE skirt layer 72, a second expanded PTFE skirt
layer 74 and an polymeric corneal substitute layer 76. The corneal
substitute layer 76 was shaped to conform to surrounding native
tissue and had a thickness and flexibility suitable for long term
ocular implantation. The corneal substitute layer 76 provided an
"internal" support frame for the expanded PTFE membranes.
[0123] Keratoprosthesis 70 was produced by providing a sheet of
expanded PTFE, commercially available from W.L. Gore &
Associates, Inc., as GORE-TEX.RTM. Soft Tissue Patch. The 2 mm
(0.04") thick expanded PTFE sheet was split into sheets
approximately 0.15 mm (0.006") thick. Holes having diameters of
about 5.5 mm (0.22") were laser cut into the sheets. A stacked
assembly was then prepared for a first lamination process, which
bonded a thermoplastic fluoropolymer elastomer to the laser cut
sheet. The stacked assembly was formed (from the top down) by
aligning the following layers: a first aluminum plate about 30 mm
(0.12") thick, a sheet of KAPTON.RTM., high temperature plastic
about 0.05 mm (0.002") thick available from E.I. duPont de Nemours,
Wilmington Del., a sheet of 2 mm thick GORE-TEX.RTM. Soft Tissue
Patch, a second sheet of KAPTON, a layer of thermoplastic
fluoropolymer elastomer about 0.2 mm (0.008") thick, the laser cut
expanded PTFE sheet, a third sheet of KAPTON, a second sheet of 2
mm thick GORE-TEX.RTM. Soft Tissue Patch, a fourth layer of KAPTON
and a second aluminum plate. All layers were about 10 cm (4"0)
square. This stacked assembly was placed into a heated platen press
and laminated at about 200.degree. C., under about 0.03 MPa (5 psi)
for about 2 minutes. This first lamination process bonded the
thermoplastic fluoropolymer elastomer to the first 0.15 mm thick
expanded PTFE sheet with the laser cut holes.
[0124] A second sheet of the 0.15 mm thick expanded PTFE with laser
cut holes was then aligned to and bonded to the thermoplastic
fluoropolymer elastomer. A stacked assembly was prepared for a
second lamination process which bonded the thermoplastic
fluoropolymer elastomer to the second laser cut sheet. The stacked
assembly was formed (from the top down) by aligning the following
layers: a first aluminum plate about 30 mm (0.12") thick, a sheet
of KAPTON, a sheet of 2 mm thick GORE-TEX.RTM. Soft Tissue Patch, a
second sheet of KAPTON, a sheet of the 0.15 mm thick expanded PTFE
with laser cut holes, the bonded thermoplastic fluoropolymer
elastomer/first laser cut expanded PTFE sheet, a third sheet of
KAPTON, a second sheet of 2 mm thick GORE-TEX.RTM. Soft Tissue
Patch, a fourth layer of KAPTON, and a second aluminum plate. All
layers were about 10 cm (4") square. The laser cut holes in the
first and second sheets were concentrically aligned to each other.
This stacked assembly was placed into a heated platen press and
laminated at about 200.degree. C., under about 0.03 MPa (5 psi) for
about 2 minutes. This second lamination process bonded the
thermoplastic fluoropolymer elastomer to the second 0.15 mm thick
expanded PTFE sheet with the laser cut holes, resulting in a three
layer laminate as depicted in FIG. 13.
[0125] The three layered laminate was then aligned onto a laser.
Disks approximately 9.7 mm (0.39") were concentrically cut relative
to the existing 5.5 mm holes. The disks were then formed into the
convex shape by compression forming and then heating to retain the
final shape. The resulting keratoprosthesis is depicted in FIGS. 12
and 13.
[0126] The keratoprosthesis was then treated with PVA using the
following process:
[0127] 1) The keratoprosthesis was placed into a 60 ml syringe
containing about 30 ml of 100% isopropyl alcohol. The air was
expelled from the syringe. The syringe plunger was then partially
withdrawn with the syringe port plugged, forming a partial vacuum
within the syringe. The vacuum was maintained for about 15 seconds
and then the plunger was allowed to relax. This vacuum application
was repeated five more times. The vacuum application forced the
residual air from the porous expanded PTFE, allowing the alcohol to
fully penetrate.
[0128] 2) The keratoprosthesis was then soaked in a 2% PVA/DI water
solution for about 2 hours, stirring at about 45 minute
intervals.
[0129] 3) The keratoprosthesis was then rinsed in DI water for
about 30 minutes with occasional stirring. p1 4) The
keratoprosthesis was then placed in a 2% glutaraldehyde/1%
hydrochloric acid-DI water solution for about 1.5 hours, with
occasional stirring.
[0130] 5) The keratoprosthesis was then rinsed in DI water for
about 30 minutes with occasional stirring.
[0131] 6) The treated keratoprosthesis was then sterilized prior to
implantation.
[0132] A study was performed to evaluate the healing process and
tissue response of keratoprosthesis prototypes in a New Zealand
White Rabbit. PVA treated e-PTFE keratoprostheses were compared
with untreated expandd PTFE prototypes in four animals each. The
groups were examined by gross and histological analysis after an
implant period of 90 days.
[0133] Prototypes treated with PVA had superior performance
compared to their untreated counterparts. One prototype in the
untreated group failed at 68 days. Two of the four of the untreated
group had skirt lifting, indicating poor device anchorage.
Additional gross observations of the untreated prototypes included
patchy areas of wet-out expanded PTFE compared with complete
wetting-out of the expanded PTFE in the PVA treated group. In
addition, there was glistening on the anterior expanded PTFE
surface of the PVA group, confirmed to be corneal epithelial
attachment with histology. This phenomenon did not appear in the
untreated group. Tissue attachment in both groups stopped at the
expanded PTFE/thermoplastic elastomer junction.
[0134] While particular embodiments of the present invention have
been illustrated and described herein, the present invention should
not be limited to such illustrations and descriptions. It should be
apparent that changes and modifications may be incorporated and
embodied as part of the present invention within the scope of the
following claims.
* * * * *