U.S. patent application number 17/231892 was filed with the patent office on 2021-07-29 for systems, devices, and methods relating to the manufacture of intravascularly implantable prosthetic valves.
The applicant listed for this patent is California Institute of Technology, Foldax, Inc.. Invention is credited to Manuel Bedrossian, Jason G. Beith, Morteza Gharib, Stephanie Rider.
Application Number | 20210228348 17/231892 |
Document ID | / |
Family ID | 1000005519916 |
Filed Date | 2021-07-29 |
United States Patent
Application |
20210228348 |
Kind Code |
A1 |
Beith; Jason G. ; et
al. |
July 29, 2021 |
SYSTEMS, DEVICES, AND METHODS RELATING TO THE MANUFACTURE OF
INTRAVASCULARLY IMPLANTABLE PROSTHETIC VALVES
Abstract
Improved prosthetic heart valves, their methods of manufacture,
and systems and devices for manufacturing the valves are described.
The prosthetic heart valves can be configured for transcatheter
implantation. The prosthetic heart valves can have artificial
leaflets. The prosthetic heart valves can be manufactured in
numerous ways, such as by polymeric dipping processes.
Inventors: |
Beith; Jason G.; (Santa Ana,
CA) ; Gharib; Morteza; (Altadena, CA) ; Rider;
Stephanie; (Los Angeles, CA) ; Bedrossian;
Manuel; (Tujunga, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Foldax, Inc.
California Institute of Technology |
Salt Lake City
Pasadena |
UT
CA |
US
US |
|
|
Family ID: |
1000005519916 |
Appl. No.: |
17/231892 |
Filed: |
April 15, 2021 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
16215376 |
Dec 10, 2018 |
11000369 |
|
|
17231892 |
|
|
|
|
62699467 |
Jul 17, 2018 |
|
|
|
62698749 |
Jul 16, 2018 |
|
|
|
62597099 |
Dec 11, 2017 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 2210/0014 20130101;
A61F 2/243 20130101; A61F 2250/006 20130101; A61F 2/2415 20130101;
A61F 2/2463 20130101; A61F 2/2418 20130101 |
International
Class: |
A61F 2/24 20060101
A61F002/24 |
Claims
1. A method of manufacturing an implantable valve, comprising:
dipping only one end of a stent in wet polymer; placing the dipped
stent on a mold, the mold comprising draft angle positions and a
contoured surface portion adjacent to draft angle positions,
wherein the dipped stent is placed on the mold such that draft
angle positions are aligned with commissure positions on the stent;
dipping the mold and dipped stent in wet polymer such that at least
the contoured surface portion of the mold and at least a portion of
the stent are covered in a polymer coating; and curing the polymer
coating.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 16/215,376, filed Dec. 10, 2018, which claims
the benefit of and priority to U.S. Provisional patent Application
Ser. No. 62/597,099, filed Dec. 11, 2017, U.S. Provisional patent
Application Ser. No. 62/698,749, filed Jul. 16, 2018, and U.S.
Provisional Patent Application Ser. No. 62/699,467, filed Jul. 17,
2018, all of which are incorporated by reference herein in their
entireties and for all purposes.
FIELD
[0002] The subject matter described herein relates generally to
improved replacement valves, and more particularly to improved
techniques for the manufacture and manufacturability of prosthetic
valves, such as implantable prosthetic heart valves having
artificial polymeric leaflets.
BACKGROUND
[0003] The human heart has a number of valves for maintaining the
flow of blood through the body in the proper direction. The major
valves of the heart are the atrioventricular (AV) valves, including
the bicuspid (mitral) and the tricuspid valves, and the semilunar
valves, including the aortic and the pulmonary valves. When
healthy, each of these valves operates in a similar manner. The
valve translates between an open state (that permits the flow of
blood) and a closed state (that prevents the flow of blood) in
response to pressure differentials that arise on opposite sides of
the valve.
[0004] A patient's health can be placed at serious risk if any of
these valves begin to malfunction. Although the malfunction can be
due to a variety of reasons, it typically results in either a blood
flow restricting stenosis or a regurgitation, where blood is
permitted to flow in the wrong direction. If the deficiency is
severe, then the heart valve may require replacement.
[0005] Substantial effort has been invested in the development of
replacement heart valves, most notably replacement aortic and
mitral valves. There is currently substantial interest in the
transcatheter implantation of prosthetic valves. Transcatheter
valve implementations often involve a bioprosthetic valve
integrated with an artificial arterial stent. This method offers
the advantages of a tissue based valve with the minimally invasive
catheter based implantation technique. Examples of such
transcatheter implantation techniques include aortic valve
replacement techniques, such as transcatheter aortic valve
implantation (TAVI) and transcatheter aortic valve replacement
(TAVR), and mitral valve replacement techniques such as
transcatheter mitral valve implantation (TMVI) and transcatheter
mitral valve replacement (TMVR). These techniques involve
introducing the valve prosthesis to the patient's body by way of a
catheter, and then expanding the prosthesis over the existing
damaged heart valve (as opposed to resecting the native valve
first). Transcatheter implantations of bioprosthetic valves suffer
from the finite life span of the biological tissue used to form the
valve leaflets, further exacerbated by the catheter based
implantation. In order to fit the valve into a catheter, the valve
must be reduced to a smaller cross-sectional size than the size
necessary for operation in the aortic or mitral valve position.
This size reduction can creases the tissue leaflets, and these
creases are susceptible to calcification at a higher rate than
uncreased tissue.
[0006] For these and other reasons, needs exist for improved
implantable valves, and for improved systems, devices, and methods
for manufacturing implantable valves.
SUMMARY
[0007] Provided herein are a number of example embodiments of
prosthetic heart valves configured for implantation through a
catheter or other intravascular delivery device. These embodiments
generally include a stent or support structure coupled with a
valvular body having two or more artificial polymeric leaflets. The
prosthetic valves can be contracted to a reduced radial dimension
that permits passage through the patient's vasculature or otherwise
introduced into the patient's body at a dimension smaller than that
required post-implantation. The prosthetic valves can expand, in
many embodiments autonomously, to an expanded configuration for
operation in regulating the patient's blood flow. The prosthetic
valves can be configured as aortic or mitral valve
replacements.
[0008] Systems, devices, and methods for manufacturing or use in
manufacturing a prosthetic heart valve are also provided. Many of
these embodiments utilize a dip casting or dipping process that
involves immersing some or all of an element of the prosthetic
valve (or used in formation of the prosthetic heart valve) into a
wet polymer to form a coating of polymer thereon. The polymer can
be then be cured to form a coating on a portion of the heart valve
or to form a component of the heart valve itself. Numerous
variations of method embodiments are disclosed, and these methods
themselves can be altered, rearranged, and supplemented with
additional steps.
[0009] Other systems, devices, methods, features and advantages of
the subject matter described herein will be or will become apparent
to one with skill in the art upon examination of the following
figures and detailed description. It is intended that all such
additional systems, methods, features and advantages be included
within this description, be within the scope of the subject matter
described herein, and be protected by the accompanying claims. In
no way should the features of the example embodiments be construed
as limiting the appended claims, absent express recitation of those
features in the claims.
BRIEF DESCRIPTION OF THE FIGURES
[0010] The details of the subject matter set forth herein, both as
to its structure and operation, may be apparent by study of the
accompanying figures, in which like reference numerals refer to
like parts. The components in the figures are not necessarily to
scale, emphasis instead being placed upon illustrating the
principles of the subject matter. Moreover, all illustrations are
intended to convey concepts, where relative sizes, shapes and other
detailed attributes may be illustrated schematically rather than
literally or precisely.
[0011] FIG. 1A is a perspective view depicting an example
embodiment of a prosthetic valve.
[0012] FIG. 1B is a top down view depicting an example embodiment
of a prosthetic valve.
[0013] FIGS. 1C-1D are side views depicting an example embodiment
of a prosthetic valve in expanded and contracted states,
respectively.
[0014] FIG. 1E is a photograph depicting an example embodiment of a
stent of a prosthetic valve.
[0015] FIGS. 2A-2B are side views depicting an example embodiment
of a prosthetic valve in expanded and contracted states,
respectively.
[0016] FIG. 2C is a side view depicting an example embodiment of a
prosthetic valve.
[0017] FIG. 3A is a perspective view of an example embodiment of a
stent of a prosthetic valve in an expanded state.
[0018] FIG. 3B is a side view of the front half of an example
embodiment of a stent of a prosthetic valve in an expanded
state.
[0019] FIGS. 3C-3D are perspective and side views, respectively, of
an example embodiment of a stent of a prosthetic valve in a
contracted state.
[0020] FIGS. 3E-3F are partial cross-sectional views depicting the
front half of an example embodiment of a valve within a
cross-section of the aortic anatomy when the valve is in the open
and closed states, respectively.
[0021] FIGS. 4A-4F are photographs of examples of various stages of
valve manufacturing processes.
[0022] FIG. 5A is a flow diagram depicting an example embodiment of
a method of manufacturing a valve.
[0023] FIGS. 5B-5C are perspective views of an example embodiment
of a mold before and after placement of an example stent thereon,
respectively.
[0024] FIG. 6A is a flow diagram depicting an example embodiment of
a method of manufacturing a valve.
[0025] FIGS. 6B-6C are perspective and top down views,
respectively, of an example embodiment of a stent of a valvular
body in an expanded state.
[0026] FIG. 6D is a photograph depicting an example stage of
manufacturing an example embodiment of a valve.
[0027] FIGS. 7-10A are flow diagrams depicting example embodiments
of methods of manufacturing valves.
[0028] FIG. 10B is a cross-sectional view depicting an example
embodiment of a valve during manufacturing.
[0029] FIGS. 11-13A are flow diagrams depicting example embodiments
of methods of manufacturing valves.
[0030] FIG. 13B is a cross-sectional view depicting an example
embodiment of a valve during manufacturing.
DETAILED DESCRIPTION
[0031] Before the present subject matter is described in detail, it
is to be understood that this disclosure is not limited to the
particular embodiments described, as such may, of course, vary. It
is also to be understood that the terminology used herein is for
the purpose of describing particular embodiments only, and is not
intended to be limiting, since the scope of the present disclosure
will be limited only by the appended claims.
[0032] The example embodiments described herein relate to improved
implantable prosthetic valves, such as prosthetic heart valves
having a support structure, stent, or frame coupled with two or
more leaflets, and techniques for the manufacture and
manufacturability of implantable valves. These embodiments are
particularly suited for artificial polymeric leaflets, and the
resulting artificial valves offer advantages comparable to current
approaches with the added benefit of a longer life span. Valves
with polymer-based leaflets are advantageous because polymers can
offer the same structural support as biological tissue, while being
much thinner and allowing the valve to be more easily contracted
for delivery. This in turn results in less stress on the polymer as
it is contracted which prevents long-term degradation of the valve
leaflets. In addition, the manufacturing methods described herein
permit fabrication of a valve without suturing leaflets to a
support structure or stent, thus promoting high quality repeatable
results.
Example Embodiments of Prosthetic Valves
[0033] FIG. 1A is a perspective view depicting an example
embodiment of an implantable prosthetic valve 100 having a support
structure or stent 102 and a valvular body 104. In this embodiment
the valvular body is configured as an aortic replacement valve and
has three valve leaflets 110-1, 110-2, and 110-3. Valve 100 is
configured to allow blood to flow from an upstream end 106
(sometimes referred to as the proximal end) to a downstream end 108
(sometimes referred to as the distal end) and valve 100 has a
longitudinal axis 112 extending between upstream end 106 and
downstream end 108 parallel to the primary direction of blood flow
through the valve.
[0034] All embodiments of valve 100 described herein can be
configured for transcatheter implantation, and thus can transition
between, on the one hand, an expanded or operative configuration
(having a relatively larger radial dimension) for regulating blood
flow and, on the other hand, a contracted or deliverable
configuration (having a relatively smaller radial dimension) that
permits intravascular delivery. FIG. 1B is an end view depicting
downstream end 108 of valve 100 in the expanded configuration (with
leaflets 110 in a partially open at-rest state) with the radial
dimension or width of valve 100 indicated by reference 114. FIGS.
1C and 1D are side views depicting valve 100 in the expanded and
contracted configurations, respectively. The longitudinal dimension
or length of valve 100 is indicated by reference 116. Valve 100 has
a relatively larger radial dimension 114 and a relatively smaller
longitudinal dimension 116 in the expanded configuration of FIG. 1C
than in the contracted configuration of FIG. 1D, where valve 100 is
longitudinally lengthened and radially shortened. FIG. 1E is a
photograph depicting an example embodiment of stent 102 in
isolation.
[0035] Stent 102 is coupled with valvular body 104 and provides
radial and longitudinal support for body 104. In the embodiment of
FIGS. 1A-1E, the body of stent 102 includes multiple struts 120
coupled together in a unitary or monolithic body. Each strut 120 is
coupled with another strut at a location 122 that is deformable for
transition of stent 102 between the expanded and contracted states.
In this embodiment, struts 120 are interconnected in a crossing
pattern, or lattice, such that multiple open regions 124 are
present. These open regions 124 have a four-sided diamond shape in
the configuration shown here. In the expanded state shown in FIG.
1C, each strut 120 is oriented at an angle with respect to
longitudinal axis 112, with the exception of strut 125, which is an
optional strut located parallel with longitudinal axis 112.
[0036] Strut 125 provides additional support (e.g., resistance to
tensile, compressive, and lateral force) at the position on stent
102 corresponding to the commissure position where leaflets 110-1
and 110-2 meet. These positions on stent 102 are indicated in FIG.
1B by reference numeral 111. Two triangular-shaped open regions 126
are present on each side of strut 125. Each set of struts 120 and
125 forming an individual open region 124 or 126 can be referred to
as a cell of stent 102, and the struts 120 and 125 can be part of
two or more cells. Struts 125 can provide resistance to deflection
of the downstream portion of valve 100 when in the closed state,
and can provide increased surface area for bonding or coupling the
polymer of valvular body 104 to stent 102.
[0037] In this embodiment there are two rows of cells indicated by
reference numerals 131 and 132, where each row includes nine cells,
although this is only an example and the rows can have other
numbers of cells as stated below. Leaflets 110 are located adjacent
the downstream row 131 of cells, generally in region 134. The
upstream terminus 135 of valvular body 104 can be at various
locations with respect to the upstream terminus 136 of stent 102.
In this embodiment, the upstream terminus 135 of valvular body 104
is in a position farther upstream (or proximal) to upstream
terminus 136 of stent 102 such that a length of valvular body 104
exists upstream to stent 102. This upstream portion of valvular
body 104 can be referred to as a skirt 140. Skirt 140 can prevent
or resist paravalvular leakage in some embodiments, and can also be
placed over stent 102 to cover any sharp or abrasive edges that can
otherwise introduce stress concentration to the valve as well as
traumatize the surrounding tissue. In addition to the manufacturing
techniques described herein (e.g., dipping and injection molding),
skirt 140 can be formed by electrospinning the polymer.
[0038] In the contracted configuration of FIG. 1D, stent 102 and
valvular body 104 are both radially contracted causing open regions
124 and 126 to become at least partially closed, and in most cases
substantially closed. In this contracted configuration, each strut
120 moves to an orientation that is closer to parallel to
longitudinal axis 112 than in the expanded configuration. Valve 100
can be configured such that the longitudinal axis of each of the
plurality of struts 120 are parallel to longitudinal axis 112 of
the valve or substantially parallel (e.g., about 5 degrees or less)
to longitudinal axis 112 when valve 100 is in the fully contracted
configuration. In the contracted configuration valvular body 104
can fold or collapse upon itself radially, and also elastically
deform longitudinally to permit longitudinal lengthening of stent
102. Upon expansion, valvular body 104 can elastically return to
its original shape.
[0039] FIGS. 2A and 2B are side views of another example embodiment
of valve 100 in the expanded and contracted states, respectively.
Here, valve 100 includes three rows of cells 201-203. A first
vertical strut 125-1 is present in the first row 201 of cells to
provide additional support at commissure position 111-1 where
leaflets 110-1 and 110-2 meet. A second strut 125-2 is present in
the third row of cells 203, directly upstream to first strut 125-2,
to provide additional support at location 111-1. Both first and
second struts 125-1 and 125-2 are optional, and each is preferably
elastic to permit longitudinal lengthening of stent 102 during
contraction. Although not shown, similar struts 125 are also
present at positions 111-2 and 111-3. Embodiments of valve 100 can
have zero, one, or more struts 125 at each of the locations 111
where leaflets 110 meet. Embodiments of valve 100 can also have
only one row of cells, or two or more rows of cells, and each row
can include any number of two or more cells. In many embodiments
each row includes a number of cells that is an integer multiple of
the number of leaflets.
[0040] FIG. 2C depicts a side view of another example embodiment of
valve 100 similar to that of FIGS. 2A and 2B, except skirt 140 has
been placed (e.g., rolled or inverted) over the upstream side of
stent 102. Such a configuration can resist paravalvular leakage
between valve 100 and the adjacent tissue, and also protect the
tissue against relative sharp or traumatic edges of stent 102.
Skirt 140 can be placed over any desired length of stent 102 (e.g.,
10%, 25%, 50%, 75%, 100%). If stent 102 is metallic and skirt 140
is placed over the entire length of stent 102, then skirt 140 can
also function to electrically insulate stent 102. Skirt 140 can be
bonded (e.g., through curing of the polymer or otherwise) to the
exterior of the upstream side or portion of stent 102, or can rest
on the exterior upstream side without being bonded thereto.
[0041] Valve 100 can be carried in the contracted configuration
within a lumen of a tubular, elongate delivery device (e.g., a
catheter) or restrained in the contracted configuration and carried
on the outer diameter of the delivery device, which in turn can be
tubular or non-tubular. Valve 100 can be biased to autonomously
expand from the contracted configuration to the expanded
configuration upon release from the constraint imposed by the
delivery device (sometimes referred to as a "self-expanding"
valve). Both stent 102 and valvular body 104 can be an elastic
material that returns to the expanded configuration after
contraction. Alternatively, stent 102 can be elastic and serve as
the primary or sole bias to return valve 100 to the expanded
configuration. Valve 100 can also be configured to require the
application of external force (such as from a balloon or other
mechanism) to cause expansion to the expanded configuration.
[0042] Another example embodiment of valve 100 is described with
respect to FIGS. 3A-3F, where valve 100 includes a contoured stent
302 coupled with valvular body 104. FIGS. 3A-3B are perspective and
side views, respectively, of stent 302 in the expanded state
(without valvular body 104), FIGS. 3C-3D are perspective and side
views, respectively, of stent 302 in the contracted state (without
valvular body 104), and FIGS. 3E-3F are cross-sections of the
aortic anatomy depicting side views of valve 100 within that
anatomy while in the open and closed states, respectively.
[0043] In this example embodiment, stent 302 is a self-expanding
frame of non-uniform radius having an upstream (proximal) end 306
and a downstream (distal) end 308. Downstream end 308 has a first
(or primary) crown 310 as well as a second (or secondary) crown 320
that can extend radially outward farther than primary crown 310.
Primary crown 310 extends farther distally than secondary crown
320. A third (or tertiary) crown 330 is located at upstream end 306
of stent 302. A necked down region (or waist) 340 is present
between crown 330, on the one hand, and crowns 310 and 320, on the
other hand. Waist 340 is where stent 302 has the relatively
smallest radial width. Each of crowns 310, 320, and 330 extends
radially outwards (e.g., flares) from waist 340.
[0044] Primary crown 310 is a continuation of the lattice
arrangement of stent 302 and includes three crown segments 311-1,
311-2, and 311-3 in locations where adjacent leaflets (not shown)
meet. Primary crown 310 mimics the tri-leaflet geometry of a
natural heart valve in order to provide optimal attachment of
artificial leaflets 110 (FIGS. 3E-3F). Bioprosthetic (natural
tissue) leaflets can alternatively be attached (e.g., sutured) onto
stent 302. The tri-leaflet geometry ensures a high effective
orifice area (EOA). By mimicking the natural shape of a heart
valve, the stresses associated with normal operating conditions of
the valve material are more evenly spread across stent 302,
increasing the overall longevity of the device. Primary crown 310
also mimics the compliance of natural heart valve attachment sites
by deflecting, which further distributes stress associated with
systolic cycle loading over valve 100. This deflection also allows
easier access for blood to flow through the aortic sinuses.
[0045] Secondary crown 320 is also a continuation of the regular
lattice of stent 302 and includes three crown segments 321-1,
321-2, and 321-3 that flare outwardly to a greater extent that
primary crown 310 (see FIG. 3B). Each secondary crown segment 321
assists in fixation of valve 100 within the anatomy. Segments 321
also include alignment holes 351 (e.g., in the distal most strut)
that can receive a thread, tether, or other portion of a delivery
device and can be used to physically manipulate the position of
valve 100 in three-dimensional space, as well as to radially rotate
or tilt valve 100 during implantation. Such control assists the
medical professional in achieving precise alignment. Alignment
holes 351 can also be used for device retrieval if the surgeon
should need to re-align the device after deployment.
[0046] Tertiary crown 330 located on the proximal end of the frame
has a slight outward expansion that assists in fixation. Stent 302
has the ability to self-locate within the anatomy when used as,
e.g., an aortic or mitral valve. For example, when configured as an
aortic replacement valve, waist 340 is receptive to placement
immediately adjacent the aortic annulus.
[0047] FIGS. 3E and 3F depict this embodiment of valve 100
configured as an aortic valve and deployed within the aortic
anatomy with valve 100 in the open and closed states, respectively.
Waist 340 of valve 100 is adjacent annulus 351 (which bulges into
the interior of the aorta) with primary crown 310 and secondary
crown 320 located downstream of annulus 351 in the ascending aorta
353, and tertiary crown 330 located upstream of annulus 351. Valve
100 is sized such that the radial dimension of the crowns 310, 320,
and 330, exceeds the radial dimension of annulus 351 and waist 340
when waist 340 is expanded in the anatomy. Valve 100 may be
slightly oversized to ensure adequate fixation, and may not expand
to the maximum radial dimension when implanted.
[0048] Valve 100 has a compliant nature. During flow conditions
(FIG. 3E) leaflets 110 are open and allowing flow, but when valve
100 closes (FIG. 3F) crown segments 311 of primary crown 310
deflect radially inwards allowing blood to flow easily into and
though aortic sinuses 352. Crown segments 321 of secondary crown
320 can also deflect inwards to a lesser degree without impacting
the fixation of valve 100.
[0049] The embodiments of valve 100 described herein are arrived at
by accounting for design considerations such as minimization of the
overall size of stent 102 and 302, prevention of interference with
the electrical conduction pathways of the heart, minimization of
the fluidic pressure gradient across valve 100, as well as the
prevention of blockage of any of the three aortic sinuses. By way
of non-limiting example, in the embodiment of FIGS. 3A-3F, the
overall aspect ratio (length and width) can be about 1:1 and the
ratio of primary crown height to overall length can be about 1:2.
These aspect ratios can be modulated as needed depending on various
factors related to the patient as well as whether valve 100 is
intended as an aortic or mitral replacement. The acute opening
angle of each crown segment of both the secondary and tertiary
crowns can be 50.degree. and can vary up to and including
60.degree. to promote the stents ability to be crimped and placed
inside a delivery device while at the same time providing enough
radial force to sufficiently fix valve 100 in the ventricular
outflow tract (VOT). Many embodiments of valve 100 can be
contracted such that the circumference is reduced by 84% or more.
Additional rows of cells may also be added for additional stability
in the VOT as well as to increase the radial force stent 102 or 302
exerts on the surrounding tissue.
[0050] The embodiment of valve 100 described with respect to FIGS.
3A-3F differs from the embodiments of FIGS. 1A-2C primarily in the
contoured profile and the presence of multiple downstream crowns,
but all other features and variations of valve 100 described with
respect to FIGS. 1A-2C can likewise be applied to the example
embodiment of FIGS. 3A-3F.
[0051] While the embodiments of valve 100 have a generally right
cylindrical upstream end, these embodiments can alternatively have
a curved or scalloped upstream end. Scalloped ends are known to
those of skill in the art (see, e.g., U.S. Pat. No. 9,301,837,
which is incorporated by reference herein in its entirety and for
all purposes.
[0052] In all of the embodiments of stent 302, secondary crown 320
and/or tertiary crown 330 can be omitted if desired. Alternatively,
either or both of crowns 320 and 330 can be included but can have a
constant radius along their length such that the sides of stent 302
where crowns 320 and/or 330 are present are parallel to the
longitudinal axis of stent 302.
[0053] While not required, stents 102 and 302 are preferably
fabricated in stages from one or more materials (e.g., a primary or
core structure of one material with a secondary structure or
coating of the same or another material). The material for the
primary structure is preferably elastic or superelastic. Examples
of such materials include titanium alloys (e.g., nitinol), elgiloy,
stainless steel, and various polymers. Materials for the secondary
coating can include polymeric materials such as polyether ether
ketones (PEEK), polyurethanes, a polyetherimides (PEI) such as
ULTEM, any of the artificial materials used to form leaflets 110,
and others. Leaflets 110 can be fabricated from polymeric
materials, including any biostable polyurethanes and polyurethane
compositions (e.g., polysiloxane-containing polyurethanes, etc.)
known in the art. Examples of polyurethane-containing leaflets are
described in U.S. Pat. Nos. 6,984,700, 7,262,260, 7,365,134, U.S.
Patent Publ. No. 2017/0119923 ("Polyurethane/urea Compositions"),
and Yilgor et al., "Silicone containing copolymers: Synthesis,
properties and applications," Prog. Polym. Sci. (2013), all of
which are incorporated by reference herein in their entirety for
all purposes. Materials that approach ideal isotropic non-creeping
characteristics are particularly suitable for use in many
embodiments. Leaflets 110 can also be fabricated from biological
tissue (e.g., a porcine valve).
Example Embodiments of Prosthetic Valve Manufacturing
[0054] Numerous embodiments of systems, devices, and methods of
manufacturing valves 100 having artificial polymeric leaflets 110
are described herein. These systems, devices, and methods can be
applied to any stent geometry or polymer, extending the valve's
possible applications to involve the treatment of multiple
conditions simultaneously, such as incorporating drug eluting
technologies to reduce inflammation due to the foreign body
response of the recipient's immune system. In addition, the
manufacturing methods described here can be automated and/or
robotized for inexpensive and repeatable manufacturing.
[0055] Generally, the manufacturing methods involve the fabrication
of stent 102 or 302 and then either coupling leaflets 110 or
valvular body 104 thereto, or integrally forming leaflets 110
thereon. For ease of discussion these systems, devices, and methods
are described herein with respect to fabrication of a valve 100
having stent 102, however it is stressed that all such systems,
devices, and methods can likewise be used to fabricate embodiments
of valve 100 having contoured stent 302. The manufacturing
embodiments described herein utilize a dip casting or dipping
process, however those of ordinary skill in the art will recognize
that other comparable formation processes (e.g., molding) can be
used instead. Dipping is used because the uniform effect of gravity
onto the polymer as it cures ensures that the resulting mold is
created at the lowest energy state of the polymer. This eliminates
stress concentrations in the macro and micro-structure of the
polymer that can result from other common molding techniques such
as injection molding, thus greatly extending the valve's
lifespan.
[0056] The use of these dipping techniques in addition to the use
of a contractable stent structure more readily allows valve 100 to
be implanted in a non-invasive catheter based procedure because the
stent will retain the ability to be contracted or crimped into a
smaller diameter than its resting size.
[0057] FIGS. 4A-4F are photographs of various stages of valve
manufacturing that will be referenced in conjunction with described
the present embodiments. FIGS. 4A-4F are examples of manufacturing
primarily by hand (manually), but these stages can be automated for
use in a higher volume manufacturing line. The manufacturing
embodiments described herein can utilize any of the approaches
described in Int'l Patent Application PCT/US18/45202 filed Aug. 3,
2018 and titled "Systems, Devices, and Methods Relating to the
Manufacture of Prosthetic Valves," which is incorporated by
reference herein in its entirety and for all purposes. These
approaches include, by way of non-limiting example: the use of a
two-stage polymer curing process and/or the use of an environmental
humidity chamber (EHC) for curing polymer for the stent and/or
valvular body of valve 100; and/or the application of an identifier
(e.g., a bar code) for improved traceability and/or automation.
[0058] FIG. 5A is a flow diagram depicting an example embodiment of
a method 500 of manufacturing valve 100. At 502, stent 102 is
dipped in a wet polymer 402 contained within a vessel 404 (FIG.
4A). In this and all dipping stages described herein, the actual
movement of the structure into the wet polymer can be automated
with a computer-controlled device. As used herein, "dipping" refers
to the acts of placing the element to be dipped (e.g., stent, mold,
valve) into the wet polymer and subsequently removing it. The
dipping can be performed such that at least one end, but preferably
all of stent 102 is coated or encapsulated in the polymer. Stent
102 can be partially cured to allow excess polymer to run off, or
stent 102 can proceed directly (without curing) to 504. At 504,
preferably while stent 102 is still wet (at least readily
deformable and removable upon touching), stent 102 can be placed
onto a mold 520 configured to form valvular body 104 and leaflets
110. Mold 520 can also be referred to as a former or mandrel and
can be shaped cylindrically or in any other desired fashion to
produce the components of valve 100. Mold 520 can have a contoured
surface for formation of valve leaflets 110, although such is not
required.
[0059] FIG. 5B is a perspective view depicting mold 520 and FIG. 5C
is a perspective view depicting mold 520 after coupling with stent
102, resulting in a mold and stent assembly 540. In the context of
dipping and curing, the terms "upward" (e.g., "facing upward") and
"downward" (e.g., "facing downward") are used in their normal sense
with respect to the force of gravity. Thus in FIGS. 5B and 5C,
upstream end 521 of mold 520 is facing downward and downstream end
522 is facing upward.
[0060] For dipping, in this embodiment, mold 520 is turned upside
down from the orientation depicted here, such that upstream end 521
of mold 520 is above downstream end 522 (upstream end 521 is facing
upward and downstream end 522 is facing downward). Mold 520
includes a base portion 523 with a geometry configured to form to
upstream portion of valvular body 104. Mold 520 also includes a
leaflet portion 524 with a surface that forms a negative image of
the interior geometry of leaflets 110 in a partially open at-rest
position. Above leaflet portion 524 is a run-off portion 526 that
allows excess polymer to run-off or drain away from leaflets 110
after dipping, if the curing process takes place with downstream
end 522 of mold facing downward (in some embodiments, curing can
take place while downstream end 522 faces upward). The polymer that
cures on run-off portion 526 can be removed during leaflet
finishing where, e.g., leaflets 110 are trimmed to their final
dimensions. In some embodiments, the trimming step can involve
removal of run-off portion 526 itself from mold 520.
[0061] In this embodiment, stent 102 is placed on mold 520 such
that the three draft angles 528 (located between each pair of
adjacent leaflets on mold 520) are aligned with the proper
respective positions on stent 102, which can be positions
corresponding to commissure positions where adjacent leaflets meet
(e.g., positions 111 of FIG. 1B). In this embodiment, these
positions are downstream termini of three crown segments 530.
Placement can be such that struts 120 forming crown segments 530
coincide with the draft angle 528, as shown in FIG. 5C. Alignment
of struts 120 with draft angle 528 allows even distribution of
stress to stent 102, and also allows the struts of each crown
segment 530 aligned with draft angle 528 to deflect radially inward
during operation of valve 100. This deflection can absorb strain
energy resulting from the closing of valve leaflets 110 that would
otherwise result in strain on leaflet 110 itself. Furthermore this
deflection increases the likelihood of clearance of all aortic
sinuses even if valve 100 is misaligned when implanted.
[0062] Coupling stent 102 to mold 520 while stent 102 is wet allows
stent 102 to adhere to mold 520 at thus remain in the proper
position during the dipping process, and also allows the
subsequently applied polymer to cure with a stronger bond to stent
102. At 506, mold and stent assembly 540 can be dipped into wet
polymer such that run-off portion 526 is submerged first. In this
and all embodiments described herein, mold 520 can be submerged
until at least leaflet portion 524 of mold 520 is covered. The
extent to which base portion 523 is submerged can vary. For
example, if valvular body 104 is configured with a skirt 140, then
submergence of mold 520 should continue at least far enough to form
skirt 140. Mold 520 can be submerged past the desired upstream
terminus of skirt 140 and any excess polymer can be trimmed to form
skirt 140.
[0063] This dipping at 506 preferably occurs with the same polymer
as used at 502, although a different batch may be used. In some
embodiments, the polymer used in 506 may have a different viscosity
or chemical composition from the polymer used at 502. Although the
methods disclosed herein are not limited to such, in some example
embodiments, the dipping steps (in this and all embodiments
described herein) can occur under both high temperature and
humidity, for example with a relative humidity (RH) in the range of
20-80% and a temperature in the range of 20-50 degrees C.
Furthermore, each dipping step (in this and all embodiments
described herein) can occur with one submergence or multiple
submergences of the mold and/or stent.
[0064] At 508, assembly 540 is allowed to cure such that downstream
end 522 is facing downward and the polymer can drain along run-off
portion 526. The curing recipe will vary depending on the type of
polymer used. After curing, stent 102 and valvular body 104 will be
securely fixed together to form valve 100.
[0065] In this and all embodiments herein, valve 100 can be
complete after curing, or valve 100 can be subjected to valve
finishing to finalize the valve structure. Examples of finishing
can include trimming or modifying the surface of leaflets 110 to
their final or near final state (e.g., through laser cutting,
ultrasonic trimming, water knife, a mechanical clam shell cutter,
and the like), applying additional coatings or surface treatments
to valve 100, moving skirt 140 (e.g., rolling skirt 140 over stent
102), attaching additional structures to valve 100 (such as bands
or tensioning elements as described herein), or others. Packaging
and sterilization of the finished valve can then occur.
[0066] In this embodiment, trimming of leaflets 110 can occur once
leaflets 110 are cured. In this and all other embodiments described
herein, trimming of leaflets 110 can occur once leaflets 110 are
cured, regardless of whether additional manufacturing steps (e.g.,
mating of valvular body 104 with stent 102) are still to be
performed.
[0067] FIG. 6A is a flow diagram depicting another example
embodiment of a method 600 of manufacturing valve 100. At 602 stent
102 is dipped in wet polymer such that at least a portion,
preferably all, of the stent body is encapsulated in polymer (FIG.
4A). Then at 604 stent 102 is allowed to completely cure to a dry
state or substantially cure to a substantially dry state. Coating
of stent 102 can be performed as part of method 600 or stent 102
can be precoated, or the coating can be omitted. Separately,
valvular body 104 is formed. This can occur at 606-610. At 606 mold
520 is dipped such that the downstream end 522 is submerged first
and continued until leaflet portion 524 and optionally at least a
portion of base portion 523 is submerged, after which mold 520 is
removed (FIG. 4D). At 608 mold 520 is also allowed to completely
cure to a dry state or substantially completely cure to a
substantially dry state to form valvular body 104 (FIG. 4E). FIGS.
6B and 6C are perspective and top down views of an example
embodiment of valvular body 104 (having upstream end 630 and
downstream end 632) after removal from mold 520.
[0068] At 610 the resulting valvular body 104 is removed from mold
520 and leaflets 110 can be trimmed, in either order. At 612
valvular body 104 is then positioned over stent 102 and aligned.
FIG. 6D is a photograph of an example embodiment of valvular body
104 partially positioned over a stent, in this instance stent 302.
At 614 the valvular body and stent assembly is then dipped in
polymer such that the upstream end is submerged first, preferably
over an upstream portion 634 of valvular body 104 (FIG. 6B), but
preferably stopping short of leaflets 110, to attach valvular body
104 to stent 102. This can be accomplished by grasping a portion of
the assembly that is not to be dipped (e.g., leaflets 110 and/or a
downstream portion of stent 102) and then dipping the assembly into
the polymer. At 616 valve 100 is then allowed to cure while
upstream end 106 is facing downward. Then valve 100 can be finished
as needed, including any necessary trimming to upstream end 106 and
rolling or inverting skirt 140 over stent 120 (FIG. 2C) if
desired.
[0069] FIG. 7 is a flow diagram depicting another example
embodiment of a method 700 of manufacturing valve 100. Valvular
body can be formed, e.g., at 702-704. At 702, mold 520 is dipped
into wet polymer such that downstream end 522 is submerged first
and continued until leaflet portion 524 and optionally at least a
portion of base portion 523 is submerged, after which mold 520 is
removed (FIG. 4D). At 704 mold 520 is then hung with downstream end
522 beneath upstream end 520 (such that excess polymer runs off
run-off portion 526) and the polymer is allowed to completely cure
to a dry state or substantially completely cure to a substantially
dry state to form valvular body 104 (FIG. 4E). After valvular body
104 is cured, at 706 stent 102 is dipped in order to at least
partially, and preferably entirely, encapsulate stent 102 in
polymer. At 708 stent 102, while in a wet state, is positioned over
valvular body 104 and mold 520 and properly aligned as needed (see
FIG. 4B). At 710 assembly 540 is then dipped again such that
upstream end 521 is submerged first (see FIG. 4C). Assembly 540 is
dipped to cover an upstream portion of valvular body 104 (like
portion 634 of FIG. 6B), but preferably stopping short of leaflets
110. The dipping at 710 can form skirt 140. At 712 valvular body
104 and stent 102 are allowed to cure with upstream end 106 facing
downward, to attach the two together and form valve 100. Valve 100
can then be finished as needed, including any necessary trimming to
upstream end 106 and rolling or inverting skirt 140 over stent 120
(FIG. 2C) if desired.
[0070] FIG. 8 is a flow diagram depicting another example
embodiment of a method 800 of manufacturing valve 100. At 802, mold
520 is dipped into wet polymer such that downstream end 522 is
submerged first, leaflet portion 524 is covered, and optionally at
least a portion of base portion 523 is covered. At 804, stent 102
is dipped in order to at least partially, and preferably entirely,
encapsulate stent 102 in polymer. 802 and 804 can be performed in
any order or concurrently. At 806, after dipping stent 102 and mold
520 and while both are still in an at least partially wet state
(e.g., immediately after dipping, or after one or both of stent 102
and body 104 have partially cured), stent 102 is positioned over
body 104 on mold 520 and aligned as needed. At 808, the assembly is
allowed to cure with downstream end 108 facing up. Curing the
assembly while in this orientation utilizes gravity to create skirt
140 out of excess polymer running over base portion 523 of mold
520. This excess polymer would otherwise drip off run-off portion
526 of mold 520. Valve 100 can then be removed from mold 520 and
finished as needed, including any necessary trimming to upstream
end 106 and rolling or inverting skirt 140 over stent 120 (FIG. 2C)
if desired.
[0071] FIG. 9 is a flow diagram depicting another example
embodiment of a method 900 of manufacturing valve 100. At 902, mold
520 is dipped into wet polymer such that downstream end 522 is
submerged first, leaflet portion 524 is covered, and optionally at
least a portion of base portion 523 is covered. At 904, mold 520 is
then hung with downstream end 522 beneath upstream end 521 (such
that excess polymer runs off run-off portion 526) and the polymer
is allowed to completely cure to a dry state or substantially
completely cure to a substantially dry state to form valvular body
104 (FIG. 4E). At 906, stent 102 is fixed around a mandrel (e.g., a
cylindrical mandrel). At 908, stent 102 and the mandrel are dipped
in order to at least partially, and preferably entirely,
encapsulate stent 102 in polymer (see FIG. 4F). Use of the mandrel
assists in forming a uniform and repeatable inner diameter to the
stent body as well as establishing skirt 140. At 909, stent 102 is
allowed to cure. At 910, after valvular body 104 and stent 102 are
cured, stent 102 is placed over valvular body 104 (e.g., while
still on mold 520) and stent 102 is bonded to body 104. If desired,
skirt 140 can be rolled or inverted over stent 120 (FIG. 2C) prior
to bonding. Many types of bonding methods can be used, and the
chosen method is preferably tailored to the polymer composition(s).
Examples of bonding methods include, but are not limited to,
polymeric bonding, solvent bonding, plasma bonding, and ultrasonic
welding. Valve 100 can then be finished as needed.
[0072] FIG. 10A is a flow diagram depicting another example
embodiment of a method 1000 for manufacturing valve 100. At 1002,
mold 520 is dipped into wet polymer such that downstream end 522 is
submerged first, leaflet portion 524 is covered, and optionally at
least a portion of base portion 523 is covered. At 1004, mold 520
is then hung with downstream end 522 beneath upstream end 520 (such
that excess polymer runs off run-off portion 526) and the polymer
is allowed to completely cure to a dry state or substantially
completely cure to a substantially dry state to form valvular body
104 (FIG. 4E). At 1006, leaflets 110 can optionally be trimmed
and/or otherwise finished while valvular body 104 is on mold 520.
At 1008, stent 102 is dipped in order to at least partially, and
preferably entirely, encapsulate stent 102 in polymer. At 1010,
while stent 102 is still wet, valvular body 104 is placed inside
stent 102, preferably while valvular body 104 is still on mold 520,
and aligned with stent 102. At 1012, if a skirt 140 is present in
valvular body 104, skirt 140 can be rolled, inverted, or otherwise
placed over the upstream side of stent 102 (see FIG. 2C).
[0073] At 1014, the valve assembly can be placed inside a lumen or
recess of an outer mold or mandrel and allowed to cure. FIG. 10B is
a cross-sectional view of mold 520 having valvular body 104 thereon
(after trimming of leaflets 110 and removal of run-off portion
526). Stent 102 is over valvular body 104 and skirt 140 has been
rolled over stent 102. The assembly is within an interior space
1005 of outer mandrel 1001. An optional tubular debonding shim 1003
can be placed between the exterior of stent 102 and the interior of
skirt 140 to prevent adhesion of the two. Outer mandrel 1001 exerts
force on valve 100 to assist in curing stent 102 to valvular body
104 and forming sufficient securement of the two elements together.
At 1016 valve 100 can be removed from outer mandrel 1001 and mold
520. Before or after removal from mold 520, any debonding shim 1003
can be removed from valve 100 and, also, an optional band or other
tensioning element (e.g., pre-stretched) can be placed around skirt
140 to hold skirt 140 in place around stent 102 if desired. The
tensioning element can be hydrophilic such that it swells within
the body, which can assist in the prevention of paravalvular
leakage. Valve 100 can then be finished as needed.
[0074] FIG. 11 is a flow diagram depicting another example
embodiment of a method 1100 for manufacturing valve 100. At 1102,
mold 520 is dipped into wet polymer such that downstream end 522 is
submerged first, leaflet portion 524 is covered, and optionally at
least a portion of base portion 523 is covered. At 1104, mold 520
is then hung with downstream end 522 beneath upstream end 520 (such
that excess polymer runs off run-off portion 526) and the polymer
is allowed to completely cure to a dry state or substantially
completely cure to a substantially dry state to form valvular body
104 (FIG. 4E). At 1106, leaflets 110 can optionally be trimmed
and/or otherwise finished while valvular body 104 is on mold 520.
At 1108, stent 102 is optionally dipped in polymer in order to at
least partially, and preferably entirely, encapsulate stent 102 in
polymer. At 1110, stent 102 (if dipped) can be allowed to cure to a
dry state.
[0075] At 1112, valvular body 104 can be placed inside and aligned
with stent 102, preferably after valvular body 104 has been removed
from mold 520. In this embodiment, 1112 is performed while stent
102 is dry, but in other embodiments stent 102 can be in a wet
state after dipping in wet polymer. At 1114, stent 102 is partially
contracted or crimped towards its contracted configuration using
outer mandrel 1001 or another crimping device. At 1116, while in
the partially contracted state, skirt 140 can be rolled, inverted,
or otherwise placed over the upstream side of stent 102. Skirt 104
is preferably of a radial dimension that is less than the fully
self-expanded radial dimension of stent 102, and thus stent 102 and
valvular body 104 are held together by the expansive force applied
by stent 102 against the interior of skirt 140. At 1118, stent 102
can be allowed to radially expand back to its expanded state, or
until the resistance applied by skirt 140 impedes further
expansion. This can be accomplished by removing stent 102 from
outer mandrel 1001. An optional band or other tensioning element
(e.g., pre-stretched) can be placed around skirt 140 to add further
securement. Again, the tensioning element can be hydrophilic such
that it swells within the body, which can assist in the prevention
of paravalvular leakage. Valve 100 can then be finished as
needed.
[0076] FIG. 12 is a flow diagram depicting another example
embodiment of a method 1200 for manufacturing valve 100. At 1202,
mold 520 is dipped into wet polymer such that downstream end 522 is
submerged first, leaflet portion 524 is covered, and optionally at
least a portion of base portion 523 is covered. At 1204, mold 520
is then hung with downstream end 522 beneath upstream end 520 (such
that excess polymer runs off run-off portion 526) and the polymer
is allowed to completely cure to a dry state or substantially
completely cure to a substantially dry state to form valvular body
104 (FIG. 4E). At 1206, leaflets 110 can optionally be trimmed
and/or otherwise finished while valvular body 104 is on mold 520.
At 1208, stent 102 is optionally dipped in order to at least
partially, and preferably entirely, encapsulate stent 102 in
polymer. At 1210, if dipped, then stent 102 can be allowed to
cure.
[0077] Valvular body 104 can then be removed from mold 520 and, at
1212, at least a portion of skirt 140 on an upstream side of
valvular body 104 can be placed over a portion of the exterior of
stent 102. In doing so, leaflets 110 of valvular body 104 are
aligned with stent 102, e.g., with struts or crown segments on
stent 102 configured for alignment with commissure locations
between leaflets 110. At 1214, the downstream end or side of
valvular body 104 is inverted or rolled into the interior (inner
lumen) of stent 102 such that leaflets 110 are positioned in the
within stent 102 in a manner that permits leaflets to operate to
regulate the flow of blood. An optional band or other tensioning
element (e.g., pre-stretched) can then be placed around skirt 140
to add further securement. Again, the tensioning element can be
hydrophilic such that it swells within the body, which can assist
in the prevention of paravalvular leakage. Valve 100 can then be
finished as needed.
[0078] FIG. 13A is a flow diagram depicting another example
embodiment of a method 1300 for manufacturing valve 100. At 1302,
upstream end 521 of mold 520 is inserted into stent 102 (which can
be previously dipped and cured if desired) such that at least a
portion of stent 102 is over on base portion 523 of mold 520, but
not extending over leaflet portion 524 of mold 520 (e.g., not as
far as depicted in FIG. 5C). Upstream end 521 of mold 520 can
include a taper to assist in insertion if desired. At 1304, a round
band or other tensioning element can optionally be placed over the
exterior of stent 102 to hold it to mold 520. FIG. 13B is a
cross-sectional view depicting an example of such an arrangement
with band 1305 placed over stent 102. As depicted here, upstream
end 521 of mold 520 includes a tapered portion 529.
[0079] At 1306, mold 520 is dipped into wet polymer such that
downstream end 522 is submerged first, leaflet portion 524 is
covered, and a portion of base portion 523 is covered, preferably
up to or near to the upstream terminus of band 1305. At 1308, mold
520 is then hung with downstream end 522 beneath upstream end 520
(such that excess polymer runs off run-off portion 526) and the
polymer is allowed to completely cure to a dry state or
substantially completely cure to a substantially dry state to form
valvular body 104. At 1310, leaflets 110 can optionally be trimmed
and/or otherwise finished while valvular body 104 is on mold 520.
At 1312, valvular body 104 and stent 102, which are held together
by the cured polymer, are removed from mold 520. At 1314, the
downstream side of valvular body 104 is inverted into the interior
of stent 102 to place leaflets 110 at the desired position within
stent 102. An additional exterior band or tensioning element (e.g.,
hydrophilic) can be applied around the exterior of valve 100, if
desired. Valve 100 can then be finished as needed.
[0080] Mold 520, in all of the embodiments described herein, can be
configured such that leaflet forming portion 524 does not include
an image of leaflets 110 but rather has a cylindrical or
substantially cylindrical shape, as is known to those of ordinary
skill in the art. Such a shape will result in a cylindrical or
substantially cylindrical portion of valvular body 104 where
leaflets 110 are to be positioned, and those leaflets 110 can then
be formed by trimming and/or shaping valvular body 104
accordingly.
[0081] In addition to the securement techniques already mentioned,
in all of the embodiments described herein, the commissure of
valvular body 104 between adjacent leaflets 110 can be bonded,
sewn, or otherwise secured to stent 102 thru additional methods to
provide additional support at that location.
[0082] In all of the embodiments of valve 100 described herein, one
or more anchors, barbs, abutments, or other structures that extend
radially outwards from valve 100 can be positioned on stent 102
and/or valvular body 104, such as near upstream end 106. Such
elements can act as fasteners that assist in lodging valve 100 to
the surrounding tissue after implantation.
[0083] In all of the embodiments described herein, mold 520 and/or
mandrel 1001 can be a material (or be coated with a material) that
resists cohesion with the polymer(s) used. Such a configuration can
make it easier to remove valvular body 104 and/or stent 102 from
mold 520 and/or mandrel 1001.
[0084] In all of the embodiments described herein, polymers having
different characteristics can be used. These characteristics can
include viscosity, chemical composition, the presence of additives,
and the like. For example, mold 520 and stent 102 can each be
dipped in a polymer having the same characteristics, or different
characteristics. If mold 520 and/or stent 102 is dipped multiple
times in an embodiment, then each dipping can be with a polymer
having the same or a different characteristic.
[0085] The embodiments of valve 100 described herein are trileaflet
(three leaflet) valves, although valve 100 can be implemented and
manufactured as a bileaflet (two leaflet) valve in the alternative.
Upon review of the present document, those of ordinary skill in the
art will readily recognize how to implement and manufacture valve
100 as a bileaflet valve without requiring such to be shown in a
figure.
[0086] Various aspects of the present subject matter are set forth
below, in review of, and/or in supplementation to, the embodiments
described thus far, with the emphasis here being on the
interrelation and interchangeability of the following embodiments.
In other words, an emphasis is on the fact that each feature of the
embodiments can be combined with each and every other feature
unless explicitly stated otherwise or logically implausible.
[0087] In many example embodiments, an implantable valve is
provided that includes: a stent including a plurality of
deflectable struts; and a polymeric valvular body coupled with the
stent, the polymeric valve body including a plurality of artificial
leaflets, where the implantable valve has a radial dimension and is
transitionable between a contracted state and an expanded state,
where the radial dimension is relatively smaller in the contracted
state than in the expanded state.
[0088] In these valve embodiments, the stent and valvular body can
be coupled together with cured polymer. The stent can be
encapsulated in the cured polymer. The polymeric valvular body can
be composed of the cured polymer.
[0089] In these valve embodiments, the implantable valve can have a
longitudinal axis and, when the implantable valve is in the
expanded state, the plurality of deflectable struts are transverse
to the longitudinal axis. When in a fully contracted state, the
plurality of deflectable struts can be parallel or substantially
parallel to the longitudinal axis. The valve can further include a
plurality of longitudinal struts, each of the plurality of
longitudinal struts positioned at a commissure between adjacent
leaflets. Each of the plurality of longitudinal struts can be
parallel to a longitudinal axis of the implantable valve when the
implantable valve is in the expanded and contracted configurations.
The plurality of deflectable struts can cross and form a plurality
of cells. The stent can include a first row of cells located
adjacent a downstream end of the stent, where the plurality of
longitudinal struts are in the first row of cells. The stent can
include a second row of cells located upstream of the first row of
cells, where no longitudinal strut is in the second row of
cells.
[0090] In these valve embodiments, the valvular body can include a
skirt located upstream from an upstream end of the stent. The skirt
can extend over the upstream end of the stent. The skirt can extend
over an exterior upstream portion of the stent. The skirt can
extend over the exterior upstream portion of the stent and can be
unconnected (not bonded) to the exterior upstream portion of the
stent.
[0091] In these valve embodiments, the stent can include a primary
crown and a secondary crown. The primary crown can include a
plurality of primary crown segments and the secondary crown can
include a plurality of secondary crown segments. A downstream
terminus of each of the plurality of primary crown segments can be
radially aligned with an interface between adjacent leaflets. Each
of the plurality of secondary crown segments can have a downstream
terminus that is upstream of the downstream terminus of each of the
plurality of primary crown segments. The stent can include a waist,
and where the primary and secondary crowns extend radially outwards
relatively farther than the waist when the implantable valve is in
the expanded configuration. The secondary crown can extend radially
outwards relatively farther than the primary crown when the
implantable valve is in the expanded configuration. The secondary
crown can be configured to deflect from a first position radially
outwards when the valve opens and deflect back to the first
position when the valve closes. The stent can include a tertiary
crown located upstream of the primary and secondary crowns. The
tertiary crown can include a plurality of tertiary crown segments.
An upstream terminus of the stent can be formed by an upstream
terminus of each of the plurality of tertiary crown segments. The
stent can include a waist, and the primary crown, secondary crown,
and tertiary crown can extend radially outwards relatively farther
than the waist when the implantable valve is in the expanded
configuration. The secondary crown can extend radially outwards
relatively farther than the primary crown and the tertiary crown
when the implantable valve is in the expanded configuration.
[0092] In these valve embodiments, the plurality of leaflets can be
two and only two leaflets, or the plurality of leaflets can be
three and only three leaflets. Other numbers of leaflets can also
be used. In these valve embodiments, the implantable valve can be
configured to replace an aortic valve of a human heart. In these
valve embodiments, the implantable valve can be configured to
replace a mitral valve of a human heart. In these valve
embodiments, the stent can include a primary structure with a
secondary structure coated over the primary structure.
[0093] In many example embodiments, methods of implanting a
prosthetic valve are provided, where the methods include: moving
the prosthetic valve, with an elongate delivery device while the
prosthetic valve is in a contracted state, through a body of a
recipient; and implanting the prosthetic valve in the body of the
recipient by, at least, deploying the prosthetic valve from the
delivery device, where the prosthetic valve is implanted in an
expanded configuration, and where the prosthetic valve is in
accordance with any of the aforementioned valve embodiments.
[0094] In many example embodiments, first methods of manufacturing
an implantable valve are provided, where the first methods include:
dipping a stent in wet polymer; placing the stent on a mold;
dipping the mold and stent into wet polymer such that at least a
portion of the mold and at least a portion of the stent are covered
in a polymer coating; and allowing the polymer coating to cure.
[0095] In these example embodiments of first methods, the mold can
include a contoured surface to form leaflets. The stent can be
placed on the mold such that the stent is aligned with the
contoured surface on the mold. The contoured surface of the mold
has a draft angle that is aligned with a commissure position on the
stent.
[0096] These example embodiments of first methods can include
trimming the polymer coating to form a plurality of leaflets. They
can include removing the stent and polymer coating from the
mold.
[0097] In these example embodiments of first methods, dipping the
stent in wet polymer can form a wet polymer coating on the stent,
and placing the stent on the mold can include placing the stent
with the wet polymer coating on the mold.
[0098] These example embodiments of first methods can include
finishing the polymer coating to form the implantable valve. The
implantable valve can be in accordance with any of the
aforementioned valve embodiments.
[0099] In many example embodiments, second methods of manufacturing
an implantable valve are provided, where the second methods
include: forming a polymeric valvular body; positioning the
polymeric valvular body over a stent; dipping an upstream portion
of the stent and polymeric valvular body in wet polymer such that a
polymer coating is placed on the upstream portion; and allowing the
polymer coating to cure.
[0100] In these example embodiments of second methods, forming the
polymeric valvular body can include: dipping a mold in wet polymer
to form a polymer coating on the mold; allowing the polymer coating
on the mold to cure; and trimming the valvular body to form a
plurality of leaflets. The mold can include a contoured surface to
form the plurality of leaflets.
[0101] These example embodiments of second methods can also
include: dipping the stent in wet polymer; and allowing the dipped
stent to cure, prior to positioning the polymeric valvular body
over the stent.
[0102] In these example embodiments of second methods, the
polymeric valvular body can be positioned over the stent such that
the stent is aligned with the plurality of leaflets. The polymeric
valvular body can be positioned over the stent such that commissure
positions between adjacent leaflets are aligned with corresponding
positions on the stent.
[0103] In these example embodiments of second methods, the valvular
body can include a plurality of leaflets, and the upstream portion
of the stent and polymeric valvular body can be dipped in wet
polymer such that the polymer coating is placed on the upstream
portion and not on the plurality of leaflets.
[0104] In these example embodiments of second methods, allowing the
polymer coating to cure can include allowing the polymer coating to
cure while an upstream end of the valvular body is facing
downward.
[0105] In these example embodiments of second methods, the
implantable valve can be formed after allowing the polymer coating
to cure or after performing valve finishing to the stent or
valvular body. The implantable valve can be in accordance with any
of the aforementioned valve embodiments.
[0106] In many example embodiments, third methods of manufacturing
an implantable valve are provided, where the third methods include:
forming a polymeric valvular body; dipping a stent in wet polymer;
positioning the stent having wet polymer thereon over the polymeric
valvular body; dipping an upstream portion of the stent and
polymeric valvular body in wet polymer such that a polymer coating
is placed on the upstream portion; and allowing the polymer coating
to cure.
[0107] In these example embodiments of third methods, forming the
polymeric valvular body can include: dipping a mold in wet polymer
to form a polymer coating on the mold; and allowing the polymer
coating on the mold to cure. The mold can include a contoured
surface to form the plurality of leaflets.
[0108] In these example embodiments of third methods, the stent can
be positioned over the valvular body such that the stent is aligned
with a plurality of leaflets of the valvular body. The stent can be
positioned over the polymeric valvular body such that commissure
positions between adjacent leaflets of the polymeric valvular body
are aligned with corresponding positions on the stent.
[0109] In these example embodiments of third methods, the valvular
body can include a plurality of leaflets, and the upstream portion
of the stent and polymeric valvular body are dipped in wet polymer
such that the polymer coating is placed on the upstream portion and
not on the plurality of leaflets.
[0110] In these example embodiments of third methods, allowing the
polymer coating to cure can include allowing the polymer coating to
cure while an upstream end of the valvular body is facing
downward.
[0111] In these example embodiments of third methods, the
implantable valve can be formed after allowing the polymer coating
to cure or after performing valve finishing to the stent or
valvular body. The implantable valve can be in accordance with any
of the aforementioned valve embodiments.
[0112] In many example embodiments, fourth methods of manufacturing
an implantable valve are provided, where the fourth methods
include: dipping a mold in wet polymer to form a polymer coating in
a wet state; dipping a stent in wet polymer; positioning the stent
having wet polymer thereon over the polymer coating in the wet
state; and allowing the stent and polymer coating to cure.
[0113] In these example embodiments of fourth methods, the mold can
include a contoured surface to form a plurality of leaflets. The
stent can be positioned over the polymer coating in the wet state
such that the stent is aligned with the contoured surface of the
mold.
[0114] In these example embodiments of fourth methods, allowing the
polymer coating to cure can include allowing the polymer coating to
cure while a downstream end of the mold is facing upward.
[0115] In these example embodiments of fourth methods, the
implantable valve can be formed after allowing the polymer coating
to cure or after performing valve finishing to the stent or
valvular body. The implantable valve can be in accordance with any
of the aforementioned valve embodiments.
[0116] In many example embodiments, fifth methods of manufacturing
an implantable valve are provided, where the fifth methods include:
positioning a stent over a polymeric valvular body; and bonding the
stent to the polymeric valvular body.
[0117] These example embodiments of fifth methods can further
include forming the polymeric valvular body prior to positioning
the stent over the polymeric valvular body. Forming the polymeric
valvular body can include: dipping a mold in wet polymer; and
allowing the wet polymer on the mold to cure. The mold can include
a contoured surface to form the plurality of leaflets.
[0118] These example embodiments of fifth methods can further
include: dipping the stent in wet polymer; and allowing the wet
polymer to cure prior to positioning the stent over the polymeric
valvular body.
[0119] In these example embodiments of fifth methods, the stent can
be positioned over the valvular body such that the stent is aligned
with a plurality of leaflets of the valvular body. The stent can be
positioned over the polymeric valvular body such that commissure
positions between adjacent leaflets of the polymeric valvular body
are aligned with corresponding positions on the stent.
[0120] In these example embodiments of fifth methods, bonding the
stent to the polymeric valvular body can be performed with one of
the following: polymeric bonding, solvent bonding, plasma bonding,
or ultrasonic welding.
[0121] In these example embodiments of fifth methods, the
implantable valve can be formed after allowing the polymer coating
to cure or after performing valve finishing to the stent or
valvular body. The implantable valve can be in accordance with any
of the aforementioned valve embodiments.
[0122] In many example embodiments, sixth methods of manufacturing
an implantable valve are provided, where the sixth methods include:
dipping a stent in wet polymer; positioning a polymeric valvular
body within the stent having wet polymer thereon; positioning a
skirt of the polymeric valvular body over the stent having wet
polymer thereon; and allowing the wet polymer to cure.
[0123] These example embodiments of sixth methods, can further
include forming the polymeric valvular body prior to dipping the
stent in wet polymer. Forming the polymeric valvular body can
include: dipping a mold in wet polymer; and allowing the wet
polymer on the mold to cure. These example embodiments of sixth
methods, can further include trimming a plurality of leaflets on
the valvular body. The polymeric valvular body can be positioned
within the stent having wet polymer thereon while the polymeric
valvular body is on the mold. The valvular body is positioned
within the stent such that the stent is aligned with a plurality of
leaflets of the valvular body. The polymeric valvular body can be
positioned within the stent such that commissure positions between
adjacent leaflets of the polymeric valvular body are aligned with
corresponding positions on the stent.
[0124] These example embodiments of sixth methods, can further
include placing a debonding shim between the skirt and the
stent.
[0125] In these example embodiments of sixth methods, allowing the
wet polymer to cure can include: placing the polymeric valvular
body and stent within an outer mandrel.
[0126] These example embodiments of sixth methods can further
include placing a tensioning element over the skirt after the skirt
is positioned over the stent. The tensioning element can be placed
over the skirt after the skirt is positioned over the stent and
prior to allowing the wet polymer to cure.
[0127] In these example embodiments of sixth methods, the
implantable valve can be formed after allowing the wet polymer to
cure or after performing valve finishing to the stent or valvular
body. The implantable valve can be in accordance with any of the
aforementioned valve embodiments.
[0128] In many example embodiments, seventh methods of
manufacturing an implantable valve are provided, where the seventh
methods include: positioning a polymeric valvular body within a
stent; at least partially radially contracting the stent;
positioning a skirt of the polymeric valvular body over the stent
while at least partially radially contracted; and allowing the
stent to expand.
[0129] These example embodiments of seventh methods can further
include forming the polymeric valvular body prior to positioning
the polymeric valvular body within the stent. Forming the polymeric
valvular body can include: dipping a mold in wet polymer; and
allowing the wet polymer on the mold to cure. These example
embodiments of seventh methods can further include trimming a
plurality of leaflets on the valvular body.
[0130] In these example embodiments of seventh methods, the
polymeric valvular body can be positioned within the stent while
the polymeric valvular body is on the mold. The valvular body can
be positioned within the stent such that the stent is aligned with
a plurality of leaflets of the valvular body. The polymeric
valvular body can be positioned within the stent such that
commissure positions between adjacent leaflets of the polymeric
valvular body are aligned with corresponding positions on the
stent.
[0131] These example embodiments of seventh methods can further
include coating the stent in polymer before positioning the
polymeric valvular body within the stent.
[0132] These example embodiments of seventh methods can further
include: dipping the stent in wet polymer; and allowing the wet
polymer to cure before positioning the polymeric valvular body
within the stent.
[0133] These example embodiments of seventh methods can further
include placing a debonding shim between the skirt and the
stent.
[0134] In these example embodiments of seventh methods, at least
partially radially contracting the stent can include placing the
polymeric valvular body and stent within an outer mandrel. Allowing
the stent to expand can include removing the stent from the outer
mandrel.
[0135] These example embodiments of seventh methods can further
include placing a tensioning element over the skirt after the skirt
is positioned over the stent.
[0136] In these example embodiments of seventh methods, the
implantable valve can be formed after allowing the stent to expand
or after performing valve finishing to the stent or valvular body.
The implantable valve can be in accordance with any of the
aforementioned valve embodiments.
[0137] In many example embodiments, eighth methods of manufacturing
an implantable valve are provided, where the eighth methods
include: positioning a polymeric valvular body over at least a
portion of a stent such that a portion of the polymeric valvular
body having a plurality of leaflets extends past the stent; and
inverting the portion of the polymeric valvular body such that the
plurality of leaflets are positioned within the stent.
[0138] These example embodiments of eighth methods can further
include forming the polymeric valvular body prior to positioning
the polymeric valvular body over the stent. Forming the polymeric
valvular body can include: dipping a mold in wet polymer; and
allowing the wet polymer on the mold to cure. These example
embodiments of eighth methods can further include trimming a
plurality of leaflets on the valvular body.
[0139] These example embodiments of eighth methods can further
include coating the stent in polymer before positioning the
polymeric valvular body over at least the portion of the stent.
[0140] These example embodiments of eighth methods can further
include: dipping the stent in wet polymer; and allowing the wet
polymer to cure before positioning the polymeric valvular body over
the at least the portion of the stent.
[0141] In these example embodiments of eighth methods, the
polymeric valvular body can be positioned over the at least the
portion of the stent such that the plurality of leaflets are
aligned with the stent. The polymeric valvular body can be
positioned over the at least the portion of the stent such that
commissure positions between adjacent ones of the plurality of
leaflets are aligned with corresponding positions on the stent.
[0142] These example embodiments of eighth methods can further
include placing a tensioning element over the polymeric valvular
body.
[0143] In these example embodiments of eighth methods, the
implantable valve is formed after inverting the portion of the
polymeric valvular body or after performing valve finishing to the
stent or valvular body. The implantable valve can be in accordance
with any of the aforementioned valve embodiments.
[0144] In many example embodiments, ninth methods of manufacturing
an implantable valve are provided, where the ninth methods include:
inserting an upstream end of a mold into a stent; dipping the mold
and stent into wet polymer to form a polymer coating; allowing the
polymer coating to cure to form a valvular body; removing the
valvular body and stent from the mold; and inverting a downstream
side of the valvular body into the stent.
[0145] These example embodiments of ninth methods can further
include applying a restraining band over an exterior of the stent
and mold prior to dipping the mold and stent into wet polymer.
[0146] In these example embodiments of ninth methods, allowing the
polymer coating to cure to form a valvular body can include
allowing the polymer coating to cure while a downstream end of the
mold is facing downward.
[0147] These example embodiments of ninth methods can further
include trimming a plurality of leaflets on the downstream side of
the valvular body prior to removing the valvular body and stent
from the mold.
[0148] These example embodiments of ninth methods can further
include coating the stent in polymer before inserting the upstream
end of the mold into the stent.
[0149] These example embodiments of ninth methods can further
include: dipping the stent in wet polymer; and allowing the wet
polymer to cure before inserting the upstream end of the mold into
the stent.
[0150] In these example embodiments of ninth methods, inserting the
upstream end of the mold into the stent can include aligning draft
angle positions on the mold with corresponding positions on the
stent.
[0151] In these example embodiments of ninth methods, the
implantable valve can be formed after inverting the downstream side
of the valvular body into the stent or after performing valve
finishing to the stent or valvular body. The implantable valve can
be in accordance with any of the aforementioned valve
embodiments.
[0152] Those of ordinary skill in the art will readily recognize,
in light of this description, the many variations of suitable dip
casting procedures, pressures, and temperatures that are not stated
here yet are suitable to fabricate the prosthetic heart valves
described herein. Likewise, those of ordinary skill in the art will
also recognize, in light of this description, the alternatives to
dip casting that can be used to fabricate the prosthetic heart
valves described herein.
[0153] As used herein and in the appended claims, the singular
forms "a", "an", and "the" include plural referents unless the
context clearly dictates otherwise.
[0154] Where a range of values is provided, each intervening value,
to the tenth of the unit of the lower limit unless the context
clearly dictates otherwise, between the upper and lower limit of
that range and any other stated or intervening value in that stated
range, is encompassed within the disclosure and can be claimed as a
sole value or as a smaller range. Where the stated range includes
one or both of the limits, ranges excluding either or both of those
included limits are also included in the disclosure.
[0155] Where a discrete value or range of values is provided, that
value or range of values may be claimed more broadly than as a
discrete number or range of numbers, unless indicated otherwise.
For example, each value or range of values provided herein may be
claimed as an approximation and this paragraph serves as antecedent
basis and written support for the introduction of claims, at any
time, that recite each such value or range of values as
"approximately" that value, "approximately" that range of values,
"about" that value, and/or "about" that range of values.
Conversely, if a value or range of values is stated as an
approximation or generalization, e.g., approximately X or about X,
then that value or range of values can be claimed discretely
without using such a broadening term.
[0156] However, in no way should this specification be interpreted
as implying that the subject matter disclosed herein is limited to
a particular value or range of values absent explicit recitation of
that value or range of values in the claims. Values and ranges of
values are provided herein merely as examples.
[0157] It should be noted that all features, elements, components,
functions, and steps described with respect to any embodiment
provided herein are intended to be freely combinable and
substitutable with those from any other embodiment. If a certain
feature, element, component, function, or step is described with
respect to only one embodiment, then it should be understood that
that feature, element, component, function, or step can be used
with every other embodiment described herein unless explicitly
stated otherwise. This paragraph therefore serves as antecedent
basis and written support for the introduction of claims, at any
time, that combine features, elements, components, functions, and
steps from different embodiments, or that substitute features,
elements, components, functions, and steps from one embodiment with
those of another, even if the following description does not
explicitly state, in a particular instance, that such combinations
or substitutions are possible. It is explicitly acknowledged that
express recitation of every possible combination and substitution
is overly burdensome, especially given that the permissibility of
each and every such combination and substitution will be readily
recognized by those of ordinary skill in the art.
[0158] While the embodiments are susceptible to various
modifications and alternative forms, specific examples thereof have
been shown in the drawings and are herein described in detail. It
should be understood, however, that these embodiments are not to be
limited to the particular form disclosed, but to the contrary,
these embodiments are to cover all modifications, equivalents, and
alternatives falling within the spirit of the disclosure.
Furthermore, any features, functions, steps, or elements of the
embodiments may be recited in or added to the claims, as well as
negative limitations that define the inventive scope of the claims
by features, functions, steps, or elements that are not within that
scope.
* * * * *