U.S. patent application number 15/308667 was filed with the patent office on 2017-07-06 for artificial, flexible valves and methods of fabricating and serially expanding the same.
This patent application is currently assigned to Baylor College of Medicine. The applicant listed for this patent is Baylor College of Medicine, William Marsh Rice University. Invention is credited to Kwonsoo Chun, Daniel Harrington, Henri Justino.
Application Number | 20170189175 15/308667 |
Document ID | / |
Family ID | 54393140 |
Filed Date | 2017-07-06 |
United States Patent
Application |
20170189175 |
Kind Code |
A1 |
Justino; Henri ; et
al. |
July 6, 2017 |
ARTIFICIAL, FLEXIBLE VALVES AND METHODS OF FABRICATING AND SERIALLY
EXPANDING THE SAME
Abstract
One aspect of the invention provides an artificial, flexible
valve including: a stent defining a wall and a plurality of
leaflets extending from the wall of the stent. The plurality of
leaflets form a plurality of coaptation regions between two
adjacent leaflets. The coaptation regions include extensions along
a z-axis and adapted and are configured to form a releasable, but
substantially complete seal when the leaflets are in a closed
position. Another aspect of the invention provides an artificial,
flexible valve including: a stent defining a wall and a plurality
of leaflets extending from the wall of the stent. Each of the
plurality of leaflets terminates in a commissure line. The
commissure lines deviate from a hyperbola formed in the x-y plane
by at least one deviation selected from the group consisting of: a
deviation in the z-direction and one or more curves relative to the
hyperbola.
Inventors: |
Justino; Henri; (Houston,
TX) ; Harrington; Daniel; (Houston, TX) ;
Chun; Kwonsoo; (Katy, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Baylor College of Medicine
William Marsh Rice University |
Houston
Houston |
TX
TX |
US
US |
|
|
Assignee: |
Baylor College of Medicine
Houston
TX
William Marsh Rice University
Houston
TX
|
Family ID: |
54393140 |
Appl. No.: |
15/308667 |
Filed: |
May 6, 2015 |
PCT Filed: |
May 6, 2015 |
PCT NO: |
PCT/US15/29442 |
371 Date: |
November 3, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61989820 |
May 7, 2014 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 2230/0008 20130101;
A61F 2250/0098 20130101; A61F 2/2418 20130101; A61F 2220/0008
20130101; A61F 2230/0069 20130101; A61F 2/2415 20130101 |
International
Class: |
A61F 2/24 20060101
A61F002/24 |
Claims
1. An artificial, flexible valve comprising: a stent defining a
wall; and a plurality of leaflets extending from the wall of the
stent, the plurality of leaflets forming a plurality of coaptation
regions between two adjacent leaflets, the coaptation regions each
having a substantially hyperbolic profile including extensions
along a z-axis and adapted and configured to form a releasable, but
substantially complete seal when the leaflets are in a closed
position.
2. The valve of claim 1, wherein the extensions have a length along
the z-axis between about 1 mm and about 10 mm.
3. The valve of claim 1, wherein the extensions have a curved
profile.
4. The valve of claim 3, wherein the curved profile lies in an x-y
plane.
5. The valve of claim 3, wherein the curved profile is a variance
in extension length along the z-axis.
6. (canceled)
7. The valve of claim 1, wherein each of the plurality of leaflets
has a substantially elliptical leaflet-stent attachment line.
8. (canceled)
9. The valve of claim 1, wherein one or more from the group
consisting of: the leaflets, the coaptation regions, and the
leaflet stent attachment lines are reinforced with one or more
selected from the group consisting of: reinforcing materials and
directional fibers.
10. (canceled)
11. The valve of claim 1, wherein adjacent leaflets are coupled to
a wide post of the stent.
12. The valve of claim 11, wherein the wide post includes one or
more windows.
13.-15. (canceled)
16. The valve of claim 1, wherein: the leaflets are formed from a
first polymer; and the stent is dip-coated in a second polymer; and
the leaflets are coupled to the second polymer mechanically,
chemically, or by one or more techniques selected from the group
consisting of: gluing, chemical fusing, thermal fusing, sonic
welding, stitching, and mechanical fastening.
17.-23. (canceled)
24. The valve of claim 1, wherein: a leaflet-stent attachment line
for each of the plurality of leaflets substantially approximates a
frame of the stent; and the leaflet-stent attachment line lies
within about 3 mm of the frame of the stent.
25. (canceled)
26. The valve of claim 1, wherein the stent includes one or more
anchor points.
27. (canceled)
28. The valve of claim 1, wherein the valve is adapted and
configured for replacement of one or more cardiac valves selected
from the group consisting of: aortic, mitral, tricuspid, and
pulmonary or insertion in a subject's veins in order to treat
venous insufficiency.
29. (canceled)
30. (canceled)
31. An artificial, flexible valve comprising: a stent defining a
wall; and a plurality of leaflets extending from the wall of the
stent, each of the plurality of leaflets terminating in a
commissure line, the commissure lines deviating from a hyperbola
formed in the x-y plane by at least one deviation selected from the
group consisting of: a deviation in the z-direction and one or more
curves relative to the hyperbola.
32.-60. (canceled)
61. An artificial, flexible valve comprising: an expandable,
cylindrical stent defining a wall; and a plurality of leaflets
extending from the wall of the stent, wherein adjacent leaflets are
coupled to a relatively wide post of the stent.
62.-90. (canceled)
91. A mandrel comprising: a cylindrical profile; and a plurality of
recesses adapted and configured to define a plurality of leaflets
forming a plurality of coaptation regions between two adjacent
leaflets, the coaptation regions including extensions along a
z-axis and adapted and configured to form a releasable, but
substantially complete seal when the leaflets are in a closed
position.
92. The mandrel of claim 91, further comprising: one more cutting
guides located between the plurality of recesses.
93. The mandrel of claim 91, further comprising: one or more
heating elements.
94. A mandrel comprising: a cylindrical profile; and a plurality of
recesses adapted and configured to define a plurality of leaflets,
each of the plurality of leaflets terminating in a commissure line,
the commissure lines deviating from a hyperbola formed in the x-y
plane by at least one deviation selected from the group consisting
of: a deviation in the z-direction and one or more curves relative
to the hyperbola.
95. (canceled)
96. (canceled)
97. A method for fabricating an artificial, flexible valve, the
method comprising: dip coating a cylindrical mandrel having a
plurality of recesses each approximating a profile of a leaflet;
and coupling the leaflets to an inner wall of a stent; wherein the
stent and the mandrel have larger diameters than a target location
for the valve.
98.-100. (canceled)
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to U.S. Provisional Patent
Application Ser. No. 61/989,820, filed May 7, 2014. The entire
content of this application is hereby incorporated by reference
herein.
BACKGROUND OF THE INVENTION
[0002] Valves exist in the body (e.g., in the heart and the
systemic veins) to allow unidirectional blood flow. A variety of
congenital conditions, infectious diseases (e.g., rheumatic heart
disease), endocarditis, and age-related impairments (e.g., senile
stenosis) can necessitate implantation of an artificial valve.
SUMMARY OF THE INVENTION
[0003] One aspect of the invention provides an artificial, flexible
valve including: a stent defining a wall and a plurality of
leaflets extending from the wall of the stent. The plurality of
leaflets form a plurality of coaptation regions between two
adjacent leaflets. The coaptation regions include extensions along
a z-axis and adapted and are configured to form a releasable, but
substantially complete seal when the leaflets are in a closed
position.
[0004] This aspect of the invention can have a variety of
embodiments. The extensions can have a length along the z-axis
between about 1 mm and about 10 mm. The extensions can have a
curved profile. The curved profile can lie in an x-y plane. The
curved profile can be a variance in extension length along the
z-axis.
[0005] The coaptation regions can have a substantially hyperbolic
profile. Each of the plurality of leaflets can have a substantially
elliptical leaflet-stent attachment line. The stent can be an
expandable, cylindrical stent. The leaflets can be reinforced with
one or more selected from the group consisting of: reinforcing
materials and directional fibers. One or more selected from the
group consisting of: coaptation regions and leaflet-stent
attachment lines can be reinforced with one or more selected from
the group consisting of: additional polymer thickness, reinforcing
materials, and directional fibers.
[0006] Adjacent leaflets can be coupled to a wide post of the
stent. The wide post can include one or more windows. The wide post
can have a width between about 0.5 mm and about 3 mm.
[0007] The stent can include metal or plastic. The metal can be
selected from the group consisting of: stainless steel, 316L
stainless steel, cobalt-chromium alloys, and nickel-titanium
alloys.
[0008] The leaflets can be formed from a first polymer. The first
polymer can be selected from the group consisting of:
polytetrafluoroethylene, polyethylene, polyurethane, silicone, and
copolymers thereof.
[0009] The stent can be dip-coated in a second polymer. The second
polymer can be selected from the group consisting of:
polytetrafluoroethylene, polyethylene, polyurethane, silicone, and
copolymers thereof. The leaflets can be coupled to the second
polymer. The leaflets can be mechanically coupled to the second
polymer. The leaflets can be chemically coupled to the second
polymer. The leaflets can be coupled to the second polymer by one
or more techniques selected from the group consisting of: gluing,
chemical fusing, thermal fusing, sonic welding, stitching, and
mechanical fastening.
[0010] A leaflet-stent attachment line for each of the plurality of
leaflets can substantially approximate a frame of the stent. The
leaflet-stent attachment line can lie within about 3 mm of the
frame of the stent.
[0011] The stent can include one or more anchor points. The anchor
points can contain a radio-opaque material.
[0012] The valve can be adapted and configured for replacement of
one or more cardiac valves selected from the group consisting of:
aortic, mitral, tricuspid, and pulmonary.
[0013] The valve can be adapted and configured for insertion in a
subject's veins in order to treat venous insufficiency. The valve
can be adapted and configured for serial expansion as the subject
ages.
[0014] Another aspect of the invention provides an artificial,
flexible valve including: a stent defining a wall and a plurality
of leaflets extending from the wall of the stent. Each of the
plurality of leaflets terminates in a commissure line. The
commissure lines deviate from a hyperbola formed in the x-y plane
by at least one deviation selected from the group consisting of: a
deviation in the z-direction and one or more curves relative to the
hyperbola.
[0015] This aspect of the invention can have a variety of
embodiments. The leaflets can further include extensions beyond the
commissure lines along a z-axis. The extensions can have a length
along the z-axis between about 1 mm and about 10 mm. The extensions
can have a curved profile. The curved profile can lie in an x-y
plane. The curved profile can be a variance in extension length
along the z-axis.
[0016] Each of the plurality of leaflets can have a substantially
elliptical leaflet-stent attachment line. The stent can have an
expandable, cylindrical stent. The leaflets can be reinforced with
one or more selected from the group consisting of: reinforcing
materials and directional fibers.
[0017] One or more selected from the group consisting of:
coaptation regions and leaflet-stent attachment lines can be
reinforced with one or more selected from the group consisting of:
additional polymer thickness, reinforcing materials, and
directional fibers.
[0018] Adjacent leaflets can be coupled to a wide post of the
stent. The wide post can include one or more windows. The wide post
can have a width between about 0.5 mm and about 3 mm.
[0019] The stent can include metal or plastic. The metal can be
selected from the group consisting of: stainless steel, 316L
stainless steel, cobalt-chromium alloys, and nickel-titanium
alloys.
[0020] The leaflets can be formed from a first polymer. The first
polymer can be selected from the group consisting of:
polytetrafluoroethylene, polyethylene, polyurethane, silicone, and
copolymers thereof.
[0021] The stent can be dip-coated in a second polymer. The second
polymer can be selected from the group consisting of:
polytetrafluoroethylene, polyethylene, polyurethane, silicone, and
copolymers thereof. The leaflets can be coupled to the second
polymer. The leaflets can be mechanically coupled to the second
polymer. The leaflets can be chemically coupled to the second
polymer. The leaflets can be coupled to the second polymer by one
or more techniques selected from the group consisting of: gluing,
chemical fusing, thermal fusing, sonic welding, stitching, and
mechanical fastening.
[0022] A leaflet-stent attachment line for each of the plurality of
leaflets can substantially approximate a frame of the stent. The
leaflet-stent attachment line can lie within about 3 mm of the
frame of the stent.
[0023] The stent can include one or more anchor points. The anchor
points can contain a radio-opaque material.
[0024] The valve can be adapted and configured for replacement of
one or more cardiac valves selected from the group consisting of:
aortic, mitral, tricuspid, and pulmonary.
[0025] The valve can be adapted and configured for insertion in a
subject's veins in order to treat venous insufficiency. The valve
can be adapted and configured for serial expansion as the subject
ages.
[0026] Another aspect of the invention provides an artificial,
flexible valve including: an expandable, cylindrical stent defining
a wall and a plurality of leaflets extending from the wall of the
stent. Adjacent leaflets can be coupled to a relatively wide post
of the stent.
[0027] The leaflets can further include extensions beyond the
commissure lines along a z-axis. The extensions can have a length
along the z-axis between about 1 mm and about 10 mm. The extensions
can have a curved profile. The curved profile can lie in an x-y
plane. The curved profile can be a variance in extension length
along the z-axis.
[0028] The coaptation regions can have a substantially hyperbolic
profile. Each of the plurality of leaflets can have a substantially
elliptical leaflet-stent attachment line. The leaflets can be
reinforced with one or more selected from the group consisting of:
reinforcing materials and directional fibers.
[0029] One or more selected from the group consisting of:
coaptation regions and leaflet-stent attachment lines can be
reinforced with one or more selected from the group consisting of:
additional polymer thickness, reinforcing materials, and
directional fibers.
[0030] The relatively wide post can include one or more windows.
The relatively wide post can have a width between about 0.5 mm and
about 3 mm.
[0031] The stent can include metal or plastic. The metal can be
selected from the group consisting of: stainless steel, 316L
stainless steel, cobalt-chromium alloys, and nickel-titanium
alloys.
[0032] The leaflets can be formed from a first polymer. The first
polymer can be selected from the group consisting of:
polytetrafluoroethylene, polyethylene, polyurethane, silicone, and
copolymers thereof.
[0033] The stent can be dip-coated in a second polymer. The second
polymer can be selected from the group consisting of:
polytetrafluoroethylene, polyethylene, polyurethane, silicone, and
copolymers thereof. The leaflets can be coupled to the second
polymer. The leaflets can be mechanically coupled to the second
polymer. The leaflets can be chemically coupled to the second
polymer. The leaflets can be coupled to the second polymer by one
or more techniques selected from the group consisting of: gluing,
chemical fusing, thermal fusing, sonic welding, stitching, and
mechanical fastening.
[0034] A leaflet-stent attachment line for each of the plurality of
leaflets can substantially approximate a frame of the stent. The
leaflet-stent attachment line can lie within about 3 mm of the
frame of the stent.
[0035] The stent can include one or more anchor points. The anchor
points can contain a radio-opaque material.
[0036] The valve can be adapted and configured for replacement of
one or more cardiac valves selected from the group consisting of:
aortic, mitral, tricuspid, and pulmonary. The valve can be adapted
and configured for insertion in a subject's veins in order to treat
venous insufficiency. The valve can be adapted and configured for
serial expansion as the subject ages. The valve may not contain any
animal-derived materials.
[0037] Another aspect of the invention provides a mandrel
including: a cylindrical profile and a plurality of recesses
adapted and configured to define a plurality of leaflets forming a
plurality of coaptation regions between two adjacent leaflets. The
coaptation regions can include extensions along a z-axis and be
adapted and configured to form a releasable, but substantially
complete seal when the leaflets are in a closed position.
[0038] This aspect of the invention can have a variety of
embodiments. The mandrel can include one more cutting guides
located between the plurality of recesses. The mandrel can include
one or more heating elements.
[0039] Another aspect of the invention provides a mandrel
including: a cylindrical profile and a plurality of recesses
adapted and configured to define a plurality of leaflets. Each of
the plurality of leaflets terminate in a commissure line. The
commissure lines deviate from a hyperbola formed in the x-y plane
by at least one deviation selected from the group consisting of: a
deviation in the z-direction and one or more curves relative to the
hyperbola.
[0040] This aspect of the invention can have a variety of
embodiments. The mandrel can include one more cutting guides
located between the plurality of recesses. The mandrel can include
one or more heating elements.
[0041] Another aspect of the invention provides a method for
fabricating an artificial, flexible valve. The method includes: dip
coating a cylindrical mandrel having a plurality of recesses each
approximating a profile of a leaflet and coupling the leaflets to
an inner wall of a stent.
[0042] This aspect of the invention can have a variety of
embodiments. The method can further include dip coating the stent
prior to coupling the leaflets to the inner wall of the stent. The
stent and the mandrel can have larger diameters than a target
location for the valve. The method can further include separating
adjacent leaflets from each other.
BRIEF DESCRIPTION OF THE DRAWINGS
[0043] For a fuller understanding of the nature and desired objects
of the present invention, reference is made to the following
detailed description taken in conjunction with the accompanying
drawing figures wherein like reference characters denote
corresponding parts throughout the several views and wherein:
[0044] FIGS. 1A and 1B provide perspective (in which fluid flows
from the bottom of the stent toward the top of the stent) and top
(in which fluid flows out of the page when the valve is open and
flows down into the page to close the valve) views of a valve
according to an embodiment of the invention;
[0045] FIG. 2 depicts a stent according to an embodiment of the
invention;
[0046] FIGS. 3A-3F depict various stent geometries according to
embodiments of the invention;
[0047] FIG. 4 depicts various vertical post geometries according to
embodiments of the invention;
[0048] FIGS. 5A-5D depict the positioning of a leaflet joint
adjacent to a window of a vertical post according to an embodiment
of the invention;
[0049] FIG. 6 depicts a stent prior to expansion, dip coating, and
leaflet installation according to an embodiment of the
invention;
[0050] FIG. 7 depicts a stent including one or more anchor points
according to an embodiment of the invention;
[0051] FIG. 8 depicts the engagement of a stent with a holder for
dipping and rotation according to an embodiment of the
invention;
[0052] FIGS. 9A-9E depict a mandrel according to an embodiment of
the invention;
[0053] FIG. 9F depicts the positioning of a hyperbolic commissure
line relative to defined asymptotes according to embodiments of the
invention;
[0054] FIG. 10A depicts a comparison of elliptical vs. parabolic
geometries leaflet valley lines according to embodiments of the
invention;
[0055] FIGS. 10B and 10C depict a comparison of elliptical vs.
parabolic leaflet stent attachment lines according to embodiments
of the invention;
[0056] FIGS. 11A-11D depict mandrels for forming coaptation regions
of varying height according to embodiments of the invention;
[0057] FIGS. 12A-12D depict mandrels for forming coaptation regions
of varying radial length according to embodiments of the
invention;
[0058] FIGS. 12E-12H depict mandrels for forming commissure lines
having variable depths along the z-axis according to embodiments of
the invention;
[0059] FIGS. 12I-12K depict mandrels for forming coaptation regions
having curved profiles in an x-y plane, resulting in increased
coaptation length, according to embodiments of the invention;
[0060] FIGS. 12L-12N depict mandrels for forming commissure lines
having curved profiles in an x-y plane, resulting in increased
coaptation length, according to embodiments of the invention;
[0061] FIG. 13A depicts a mandrel according to an embodiment of the
invention;
[0062] FIGS. 13B and 13C depict the positioning of reinforcing
zones on a mandrel according to an embodiment of the invention;
[0063] FIGS. 14A-14C depict various top profiles according to an
embodiment of the invention;
[0064] FIGS. 15A and 15B depict the fabrication of valves according
to embodiments of the invention;
[0065] FIG. 16 depict the fabrication of valves according to an
embodiment of the invention;
[0066] FIGS. 17A and 17B depict the compression of a valve after
assembly in order to bring leaflets into contact with each other
according to embodiments of the invention;
[0067] FIG. 17C is a high-speed photograph of a closed valve under
pressure according to embodiments of the invention;
[0068] FIG. 18 depicts a method of implanting a valve according to
embodiments of the invention; and
[0069] FIG. 19 depicts a method of expanding an implanted valve
according to embodiments of the invention.
DEFINITIONS
[0070] The instant invention is most clearly understood with
reference to the following definitions.
[0071] As used herein, the singular form "a," "an," and "the"
include plural references unless the context clearly dictates
otherwise.
[0072] Unless specifically stated or obvious from context, as used
herein, the term "about" is understood as within a range of normal
tolerance in the art, for example within 2 standard deviations of
the mean. "About" can be understood as within 10%, 9%, 8%, 7%, 6%,
5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated
value. Unless otherwise clear from context, all numerical values
provided herein are modified by the term about.
[0073] As used in the specification and claims, the terms
"comprises," "comprising," "containing," "having," and the like can
have the meaning ascribed to them in U.S. patent law and can mean
"includes," "including," and the like.
[0074] Unless specifically stated or obvious from context, the term
"or," as used herein, is understood to be inclusive.
[0075] Ranges provided herein are understood to be shorthand for
all of the values within the range. For example, a range of 1 to 50
is understood to include any number, combination of numbers, or
sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27,
28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,
45, 46, 47, 48, 49, or 50 (as well as fractions thereof unless the
context clearly dictates otherwise).
DETAILED DESCRIPTION OF THE INVENTION
[0076] Aspects of the invention provide a novel platform that
allows development of polymeric valves of any size and shape.
Aspects of the invention can be applied to valves designed for
surgical implantation (e.g., through a sternotomy or thoracotomy)
or valves designed for percutaneous, transcatheter implantation.
Additionally, embodiments of the invention allow for possible
percutaneous replacement of a dysfunctional valve, whether in
adults or in small children. In addition, if implanted in a child,
embodiments of the invention allow the valve to be serially
expanded to accompany the child's growth.
Cardiac Applications
[0077] Multiple types of congenital heart defects require heart
valve replacement surgery in infancy or childhood. In adults, the
most commonly replaced valves are aortic and mitral, whereas in
children, the pulmonary valve is the most commonly replaced valve.
Heart valves are currently replaced using tissue valves (homograft
or xenograft) or mechanical metal valves, each having their
shortcomings. Homograft valves are in short supply, particularly in
sizes suitable for use in children, and biologic tissue-based
valves (whether bovine, porcine, or homograft) tend to induce an
immunologic reaction which leads to failure of these valves.
Mechanical valves generally require anticoagulation, and are almost
never used in the pulmonary position due to an increased risk of
thrombosis.
[0078] Furthermore, none of the surgically implanted valves can
adapt to growing patients. The rapid growth of pediatric patients
leads them to outgrow their implanted valves within a few years and
induces a cycle of frequent surgical valve replacements during
childhood. Aspects of the invention provide valves having improved
biocompatibility, durability, and hemodynamic performance and would
reduce the frequency of recurrent open heart surgeries for valve
replacement.
Venous Applications
[0079] Additionally, aspects of the invention can be used for
venous valve replacement in patients having venous disease such as
chronic venous insufficiency (leading to leg swelling). Because the
polymer leaflets can be made extremely thin, the valves can even
open under extremely low venous pressure gradients.
Artificial, Flexible Valves
[0080] Referring now to FIGS. 1A and 1B, one aspect of the
invention provides an artificial, flexible valve 100. The valve
includes an expandable, cylindrical stent 102 defining a wall 104.
Valve 100 further includes a plurality of leaflets 106a-106c. Wall
104 can be formed by dip coating stent 102 in a polymer as further
described herein. Leaflets 106 can be coupled to wall 104 along
seams 108 using a variety of approaches (e.g., glue) as discussed
further herein. Stent 102 can include one or more vertical posts
110, 112, which can be relatively narrow posts 110 or relatively
wide posts 112. Preferably leaflet joints between adjacent leaflets
106 are positioned on or close to a vertical post 110, 112 of the
stent 102.
[0081] The valve 100 will now be described in the context of its
components and methods of fabrication.
Stents
[0082] Referring now to FIG. 2, stent 102 can be a metallic stent
having plurality of wires, strips, and the like 202 defining a
plurality of cells 204, 206 of various sizes. Stent 102 can be
fabricated from a variety of malleable materials such as stainless
steel, 316L stainless steel, cobalt-chromium alloys,
nickel-titanium alloys (colloquially known as "nitinol"), and the
like. Stent 102 can also be formed from various non-metallic
materials such as plastics such as polyethylene, polyurethane,
polytetrafluoroethylene (PTFE), silicone, poly(propylene) (PP),
polyethylene terephthalate (PET), and the like.
[0083] Stent 102 can be completely enveloped by a polymer dip
coating. Stent 102 and/or wall 104 can also be fabricated from a
biocompatible material.
[0084] The stent 102 can be manufactured by laser cutting or wire
forming. To increase bonding strength between metal and polymer,
roughness of stent surface can be controlled. Some or all open
cells 204, 206 of the stent can be covered as the bare 102 stent is
dipped into the polymer solution.
[0085] FIG. 6 depicts a stent 102 prior to expansion, dip coating,
and leaflet installation. Stents 102 typically have a diameter of
between about 2 mm and 6 mm prior to expansion and can be expanded
to between about 5 mm and about 30 mm for implantation into a
subject.
[0086] The components of stent 102 can have a variety of dimensions
that can be selected to achieve a desired flexibility, rigidity,
resilience, and the like. For example, the thickness and width of
components of the stent 102 can be between about 0.1 mm and about 2
mm.
[0087] As discussed above, stent 102 can include one or more
vertical posts 110a-110c to enhance bonding with leaflets 106.
[0088] Stent 102 can include a plurality of vertical posts 110 that
can serve a variety of functions. Some vertical posts 110 can
include additional structure and are referred to herein as wide
posts 112. Wide posts 112 are preferably located at leaflet joints
where two leaflets 106 meet. For example, in a valve 100 having a
three leaflets 106, wide posts 112 can be positioned at 120.degree.
intervals within cylindrical stent 102.
[0089] Wide posts 112 provide mechanical support to leaflets and
prevent or substantially limit inward deformation of wall 104 due
to tensile forces applied to leaflets 106 transferred to wall 104.
Without being bound by theory, it is believed that the wide posts
112 provide increased strength and resiliency due to formation of
polymer wall 104 through windows 206 and around wide posts 112,
thus providing cohesive holding of the polymer to itself around the
stent 102 instead of relying solely on adhesive bonding of the
polymer wall 104 to the stent 102.
[0090] Wide posts 112 advantageously allow for relaxed tolerances
in positioning leaflets 106 relative to wide posts 112. For
example, window 208 can have a width of between about 0.5 mm and
about 3 mm (e.g., about 1 mm) and a height of between about 1 mm
and about 10 mm (e.g., about 5 mm).
[0091] A variety of additional wide post geometries are depicts in
FIGS. 3A-3F. In FIG. 3A, the wide posts have a solid architecture
without any windows. In FIG. 3B, the wide posts have a
substantially rectangular architecture defining a single, long
window as in FIGS. 1A, 1B, and 2. In FIG. 3C, the wide posts define
a plurality of coaxial substantially rectangular windows. In FIG.
3D, the wide posts define a plurality of coaxial, substantially
parallel windows. In FIG. 3E, the wide posts define a plurality of
coaxial, substantially rectangular windows in a 2.times.3
arrangement. In FIG. 3F, the wide posts include a plurality of
circular windows. These wide post architectures are further
depicted in FIG. 4. Although substantially circular and rectangular
window geometries are depicted, any geometry can be utilized
including windows having a profile approximating a triangle, a
square, an n-gon (e.g., a hexagon, an octagon, and the like), and
the like.
[0092] Referring now to FIGS. 5A-5D, the positioning of a leaflet
joint 502 (formed, e.g., on mandrel 900 as discussed herein)
adjacent to window 206 of wide post 112 is depicted. (The polymer
dip-coated wall 104 is completely transparent for ease and clarity
in viewing, but can be transparent, translucent, or opaque.) FIG.
5B-5D further depict how a geometry of the stent 102 can be
selected to substantially approximate the leaflet-stent attachment
seam 108 discussed herein in order to provide added mechanical
support and resiliency.
[0093] Referring now to FIG. 7, stent 102 can include one or more
anchor points 702. Anchor points 702 advantageously facilitate
holding, dipping, and rotation of the stent 102 during the dip
coating process without interfering with the dip coating of the
remainder of the stent architecture. Accordingly, the entire stent
102 can be dip coated in a single dipping, although multiple
dippings can be utilized to control coating density, thickness, and
the like. Anchor points 702 can also receive one or more
radio-opaque materials such as platinum to aid in placement and
visualization of the valve.
[0094] In one embodiments depicted in FIG. 8, stent 102 can be
engaged with a holder 802 (e.g., by posts 804) for dipping and
rotation. Once the polymer (again depicted as, but not necessarily,
transparent) is wet on the stent 102, the stent can be positioned
horizontally and rotated axially.
Leaflets
[0095] Leaflets 106 can be formed using a variety of techniques
including dip coating, 3D-printing (also known as additive
manufacturing), molding, and the like.
[0096] Referring now to FIG. 9A, leaflets 106 can be fabricated by
dip coating a mandrel 900 with a polymer. The mandrel 900 can be
made with a solid such as a metal (e.g., stainless steel, titanium,
aluminum, and the like), a plastic (e.g., polyethylene,
polypropylene, polyvinyl chloride, polytetrafluoroethylene,
polyoxymethylene, and the like), and the like. Since the coated
polymer leaflets 106 will be removed from the mandrel 900 after the
polymer dries, roughness of mandrel surface can be controlled using
known machining and other manufacturing techniques. The mandrel 900
can be made from a cylinder. Preferably, the diameter of the
mandrel 900 is a slightly (e.g., between about 0.05 and about 0.4
mm) smaller than inner diameter of stent 102 after expansion.
[0097] The mandrel 900 for the leaflets 106 can have novel
features, including edges representing the leaflet attachment
points that are mathematically defined and leaflet tips that are
extended in order to increase the coaptation length of the
leaflets. The mandrel 900 can be dimensioned to produce leaflets
106 having different regional thickness and supplementary materials
such as directional fibers or reinforcing particles inserted
between layers or mixed into the polymer solution in order to
increase durability. For example, polymer interaction with
particles on the nanoscale or microscale can greatly improve the
physical properties or tear resistance of the polymer leaflets
106.
[0098] Mandrel 900 can be designed to have a complementary geometry
to the desired leaflet shape and permits easier viewing of leaflet
geometry. Although mandrel 900 is utilized to describe the geometry
of the leaflet 106, it should be recognized that the upstream
surface of the resulting leaflets will have this geometry when
formed by dip coating and that the complementary geometry of the
leaflet(s) 106 can be produced using techniques other than dip
coating. Mandrel 900 is preferably cylindrical and can have an
outer profile substantially approximating an inner profile of stent
102. Mandrel 900 can define a plurality of pockets 902 that each
define a leaflet 106 as it hangs from wall 104 via attachment line
108. Each leaflet 106 terminates in a commissure line 904 often,
but not necessarily lying in a plane at the point where the
elliptical or parabolic curve ends and where the leaflet often
contacts the other leaflets. A substantially vertical coaptation
region 906 can extend beyond the commissure line 904 to an extended
commissure line 912 for improved sealing as will be discussed
herein.
[0099] Referring now to FIGS. 9B and 9C, mandrel can be cast,
machined, printed, or otherwise fabricated so that pockets 902 have
a desired geometry. In one embodiment of the invention, the
commissure line 904 (and optionally the coaptation region 906 and
extended commissure line 912) has a substantially hyperbolic
profile when viewed in the x-y plane. Additionally or
alternatively, leaflet-stent attachment line 108 and/or a leaflet
valley line 908 (formed by taking a cross-section in a z plane) can
have substantially elliptical profiles. Although other quadratic
profiles (e.g., parabolic) could be used, elliptical profiles
better promote a secure pocket shape and the closure of the
leaflet-stent attachment line 108 to the contour of the cylindrical
mandrel 900. A comparison of elliptical vs. parabolic leaflet
valley lines is provided in FIG. 10A. A comparison of elliptical
vs. parabolic leaflet-stent attachment lines is provided in FIGS.
10B and 10C.
[0100] Referring now to FIG. 9D, mandrel 900 can define a gap 910
between adjacent leaflets. Advantageously, leaflets 106 with a
hyperbolic profile can produce smaller gaps than leaflets with
parabolic profiles. For example, gaps 910 can be less than 1 mm or
between about 0.1 mm and about 1 mm (e.g., between about 0.1 mm and
about 0.2 mm, between about 0.2 mm and about 0.3 mm, between about
0.3 mm and about 0.4 mm, between about 0.4 mm and about 0.5 mm,
between about 0.5 mm and about 0.6 mm, between about 0.6 mm and
about 0.7 mm, between about 0.7 mm and about 0.8 mm, about 0.8 mm
and about 0.9 mm, about 0.9 mm and about 1 mm, and the like).
[0101] As seen in FIG. 9E, the length of hyperbolic commissure line
904 is about twice the radius of the stent or mandrel. The
positioning of a hyperbolic commissure line 904 relative to defined
asymptotes is depicted in FIG. 9F.
[0102] Referring now to FIG. 11A, coaptation region can have
minimal height in the z-axis so as to consist only of the
commissure line 904. Alternatively, coaptation region 906 can have
a vertical extension in the z-axis to an extended commissure line
912 as depicted in FIGS. 11B-11D. The height of the coaptation
region 906 can be selected to reduce the amount of regurgitation,
while still allowing the valve to open. For example the coaptation
region 906 can have a height between about 1 mm and about 10 mm
(e.g., about 3 mm). Although FIGS. 11B-11D depict extensions of
coaptation region 904 that extend solely in the z-axis, the same
effect can be achieved using a smooth leaflet-stent attachment line
that extends in the z-axis so that the adjacent leaflet-stent
attachment lines (and/or the regions of leaflets hanging
therebetween) approach and/or contact each other to form an
extended coaptation region.
[0103] The zone of coaptation is affected by the pressure placed
upon the closed valve 100. The higher the pressure, the more
downward tension is placed on the leaflets 106, possibly leading to
a failure of coaptation with consequent regurgitation. Proper
coaptation also allows the leaflets 106 to support each other, so
there is less stress placed on any individual leaflet 106. Another
benefit of enhancing height of the coaptation zone is that this
allows the valve 100 to be re-dilated to a larger diameter late
after implantation (such as to accommodate growth of a pediatric
patient), while still maintaining competence of the valve 100.
[0104] Options for enhancing the height of the coaptation zone
include creating excess length of the leaflet free edges, so that
the free edge length is greater than twice the radius of the stent
or mandrel depicted in FIG. 9E. Lengthening of the leaflet free
edges can be accomplished by curved edges in the x-y plane, or in
the z-axis, or in all 3 axes.
[0105] Referring now to FIGS. 12A-12D, coaptation regions 906 can
have varying heights in the z-axis between the commissure line 904
and extended commissure line 912. For example, the height of
coaptation region 906 can increase toward the outside of the
mandrel as depicted in FIG. 12B. In another embodiment, the height
of the coaptation region 906 can dip to form a trough between the
outside and the center of the mandrel 900 as depicted in FIG.
12C.
[0106] Referring now to FIGS. 12E-12H, the same profiles can be
applied to commissure line 904 without any coaptation region
906.
[0107] Referring now to FIGS. 12I-12K, the commissure lines 904,
coaptation regions 906 and/or extended commissure lines 912 can
have curved profiles in an x-y plane (as opposed to a substantially
hyperbolic profile) in order to increase the length of the
commissure line 904, coaptation region 906, and/or extended
commissure line 912. For example, the mandrel 900 can be thicker
between the perimeter and the center as depicted in FIG. 12I to
produce one or more scallops. In FIGS. 12J and 12K, the mandrel 900
can have either a single curve or multiple curves.
[0108] Referring now to FIGS. 12L-12N, the same profiles can be
applied to commissure line 904 without any coaptation region
906.
[0109] In order to increase tear-resistance of the leaflets 106 and
enhance bonding strength between leaflets 106 and stent 102, the
thickness of the leaflets 106 can be controlled regionally. Because
the most common failure points are at the outer edges of the
leaflets 106 (such as commissure line 904 or extended commissure
line 912 and leaflet-stent attachment line 108), increased
thickness at outer areas of the leaflets 106 can improve the
strength and durability. Also, if local areas are expected to have
concentrated stress, the areas can be locally reinforced (e.g.,
made thicker than other areas). The thickness can be smoothly
increased. The width of thickened area along leaflet-stent
attachment line 108 can be large enough to cover the glued area for
bonding the leaflets 106 and the covered stent 102. In some
embodiments, the thickness of thickened areas of the leaflets is
between about 0.1 mm and about 1 mm.
[0110] Multiple dippings can be performed to produce leaflets with
a desired thickness. In some embodiments, the thickness of the
leaflets is between about 0.01 mm and about 0.2 mm.
[0111] Different reinforcing materials such as strips, fibers and
particles can be placed between the layers, or directly mixed into
the polymer solution. The inserted material(s) can prevent tearing
and reduce propagation of the tear if it occurs. The materials can
have directional properties and can be layered onto, or embedded
into, the leaflets in an optimal direction to prevent or limit
tears.
[0112] Referring now to FIG. 13A, a photograph of a mandrel 900 is
provided. Referring now to FIG. 13B, a reinforcing zone 1302 can be
formed on the mandrel 900 prior either by removing mandrel material
to allow for additional thickness in certain (e.g., outer) regions
of leaflets 106 or by introducing one or more reinforcing fibers
prior to, during, or after dip coating. Suitable reinforcing
materials include fibers (e.g., polymers, nanotubules, aramids,
para-aramids, and the like), wires, and the like. Transitions
between reinforced and non-reinforced areas can be smooth in order
to minimize any turbulence in the implanted valve 100.
[0113] After dipping the mandrel 900 into the polymer solution, the
coated polymer dries in order to form the leaflet(s) 106. Because
the formed leaflets 106 are connected, they need to be separated
from each other. These can be cut by a sharp cutter (e.g., a knife,
a scalpel, a razor blade, a utility knife, and the like), a heated
iron, a laser, a rotary tool, and the like. A guide on the top
surface of the mandrel for cutting provides a clear, easy, and safe
cutting path. The guide can be grooved/concave or convex. Also, the
commissure edges of the mandrel can be sharp like a blade to
facilitate leaflet separation and to improve on the quality of the
cut edges.
[0114] Referring now to FIG. 14A-14C, the gap portion 910 of the
mandrel can have various top profiles to facilitate sealing of the
leaflets and/or separation of the leaflets prior to removal from
mandrel 900. For example, the gap portion 910 can have a grooved
profile as depicted in FIG. 14A, a concave profile as depicted in
FIG. 14B, or an angled profile as depicted in FIG. 14C.
Additionally or alternatively, a heating element (e.g., an Ohmic or
resistive heating element such as a wire) can be included in the
mandrel and can be actuated to melt the polymer to separate the
leaflets and/or relax the polymer to facilitate removal of the
leaflets from the mandrel 900.
[0115] The stent-mounted valve 100 can be implanted with smaller
diameter than its manufactured diameter for reducing leakage and
improving durability.
Methods of Fabricating Valves
[0116] Referring now to FIGS. 15A, 15B, and 16, a method for
fabricating a valve is depicted. A bare stent 102 and a bare
mandrel 900 are provided.
[0117] In some embodiments, the stent 102 can be first coated with
a polymer such as PEEK or other metal surface modifier prior to
further dip coating of the stent 102 in another polymer in order to
improve adhesion of the leaflet polymer 106 to the metal stent
102.
[0118] The bare mandrel 900 can optionally be coated with a release
agent to promote separation of the polymer leaflets from the
mandrel 900.
[0119] Both the bare stent 102 and the mandrel 900 are dip coated
separately in a polymer, which may be the same or different for the
bare stent 102 and the mandrel 900.
[0120] The leaflets 106 formed on the mandrel 900 can be removed
prior to introduction to the coated stent. Alternatively, the
coated mandrel 900 can be introduced into the coated stent, the
leaflets 106 can be bonded to the coated stent, and the mandrel 900
can be then be removed to leave the assembled valve 100.
[0121] Leaflets 106 can be bonded to the dip-coated stent using a
variety of techniques including gluing, chemical fusing (i.e.,
dissolving the polymers) thermal fusing, sonic welding, stitching,
mechanical fastening, and the like. For example, the same polymer
solution used to coat either bare stent 102 and/or mandrel 900 can
be applied to bond the leaflets 106 to the dip-coated stent.
[0122] Although separate fabrication of the polymer-coated stent
and the leaflets 106 are currently preferred as a means of avoiding
or minimizing air bubbles, the entire valve could be formed in a
single dip coating (or series of dip coatings) through use of
production-grade manufacturing techniques and other
optimizations.
[0123] Although dipcoating was successfully used to fabricate
prototypes of the valves described herein, any other manufacturing
technique capable of producing flexible leaflets can be utilized.
Exemplary techniques include injection molding and additive
manufacturing or 3D printing.
[0124] Referring now to FIGS. 17A and 17B, stent 102 and leaflets
106 can be fabricated based on a diameter that is slightly larger
than the placement location as depicted in FIG. 17A. When deployed
to a location having a smaller diameter than the manufactured
diameter, the leaflets 106 will be held in tight contact with each
other as seen in FIG. 17B to form a tight seal. (In order to form a
press fit with the vessel wall, the deployed diameter will be
greater than the vessel diameter, but less than the manufactured
diameter.)
[0125] As can be seen in FIGS. 17A and 17B, the coaptation regions
of leaflets 106 have a substantially hyperbolic profile both at the
manufactured diameter and the deployed diameter.
[0126] Referring now to FIG. 17C, a high-speed photograph of a
closed valve under pressure during in vitro testing in a
hemodynamic pulse duplicator is provided.
Polymers
[0127] The leaflets 106 can be formed from the same or different
polymer with which the stent 102 is coated to form wall 104. For
example, the leaflets 106 can be formed from polymers such as
polyethylene, polyurethane, silicone, and the like. Wall 104 can be
formed from polyethylene, polyurethane, silicone, and the like.
[0128] Supplementary materials such as directional fibers can mixed
into the polymer solution or applied to the leaflets between
coatings in order to increase durability
[0129] The selected polymer can be dissolved by a solvent such as
tetrahydrofuran or dimethylacetamide. The thickness of the coated
polymer can be controlled as a function of the density of the
polymer solution and total number of dippings. When the polymer
becomes dry after dipping, the coated stent and mandrel can be
placed horizontally and axially rotated in order to produce a
constant thickness and prevent the polymer from dripping.
Implantation of Valves
[0130] Referring now to FIG. 18, a method 1800 of implanting an
artificial valve is provided. The valve to be implanted can be a
valve 100 as described herein.
[0131] In step S1802, the valve is placed over an expander and
within a sheath. Various surgical expanders and access devices
exist in the cardiac surgery field. For example, a balloon catheter
could be introduced into a patient's femoral artery and guided to
the location of the implanted valve (e.g., within the patient's
heart or systemic veins).
[0132] In step S1804, the sheath (containing the valve and the
expander) is introduced into a vessel of the subject.
[0133] In step S1806, the valve and the expander are advanced from
the sheath and positioned in the desired location.
[0134] In step S1808, the desired positioning can be verified using
various imaging techniques such as fiber optics, ultrasound, X-ray,
and the like.
[0135] In step S1810, the expander is actuated within the valve to
expand the valve to form a press fit against the vessel in which
the valve is implanted. For example, a balloon catheter can be
expanded by introducing gas or a liquid into the balloon.
[0136] In step S1812, the desired positioning and expansion can be
verified using various imaging techniques such as fiber optics,
ultrasound, X-ray, and the like.
[0137] In step S1814, the expander and sheath can be retracted
according to standard surgical techniques.
Expansion of Implanted Valves
[0138] Referring now to FIG. 19, a method 1900 of expanding an
implanted valve is provided. The implanted valve can be a valve 100
as described herein.
[0139] In step S1902, an expander is introduced into the implanted
valve.
[0140] In step S1904, the expander is actuated within the implanted
valve to increase the diameter of the implanted valve.
[0141] In step S1906, the desired expansion can be verified using
various imaging techniques.
[0142] In step S1908, the expander can be retracted according to
standard surgical techniques.
Surgically-Implanted Valves
[0143] Although embodiments of the invention are described and
depicted in the context of percutaneous, transcatheter valves
having expandable, cylindrical stents, embodiments of the invention
described herein can be applied to surgically-implanted valves that
generally include anchors having fixed-diameter anchors supporting
a plurality of leaflets (e.g., the CARPENTIER-EDWARDS.TM. series of
valves available from Edwards Lifesciences Corporation of Irvine,
Calif.). In such embodiments, the anchor replaces the expandable,
cylindrical stents described herein.
EQUIVALENTS
[0144] Although preferred embodiments of the invention have been
described using specific terms, such description is for
illustrative purposes only, and it is to be understood that changes
and variations may be made without departing from the spirit or
scope of the following claims.
INCORPORATION BY REFERENCE
[0145] The entire contents of all patents, published patent
applications, and other references cited herein are hereby
expressly incorporated herein in their entireties by reference.
* * * * *