Patent Description:
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.

<CIT> discloses a heart valve prosthesis and method of manufacture. <CIT> discloses a heart valve prosthesis with a shape of the leaflets in neutral state having a hyperbolic component in a plane perpendicular to the blood flow.

The invention relates to an artificial valve according to independent claim <NUM>.

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.

This aspect of the invention can have a variety of embodiments. The extensions can have a length along the z-axis between about <NUM> and about <NUM>.

The coaptation regions have a substantially hyperbolic profile. Each of the plurality of leaflets has 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.

Adjacent leaflets are 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 <NUM> and about <NUM>.

The stent can include metal or plastic. The metal can be selected from the group consisting of: stainless steel, <NUM> stainless steel, cobalt-chromium alloys, and nickel-titanium alloys.

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.

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.

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 <NUM> of the frame of the stent.

The stent can include one or more anchor points. The anchor points can contain a radio-opaque material.

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.

Another aspect 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.

This aspect can have a variety of embodiments. The leaflets include extensions beyond the commissure lines along a z-axis. The extensions can have a length along the z-axis between about <NUM> and about <NUM>.

Each of the plurality of leaflets has a substantially elliptical leaflet-stent attachment line. The stent has an expandable, optionally 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.

The stent includes metal or according to a configuration not covered by the invention, plastic. The metal can be selected from the group consisting of: stainless steel, <NUM> stainless steel, cobalt-chromium alloys, and nickel-titanium alloys.

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.

According to an aspect not covered by the invention, 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.

Another aspect 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 are coupled to a relatively wide post of the stent.

The leaflets further include extensions beyond the commissure lines along a z-axis. The extensions can have a length along the z-axis between about <NUM> and about <NUM>.

The coaptation regions have a substantially hyperbolic profile. Each of the plurality of leaflets has 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.

The relatively wide post can include one or more windows. The relatively wide post can have a width between about <NUM> and about <NUM>.

The stent includes metal, according to a configuration not covered by the invention, the stent includes plastic. The metal can be selected from the group consisting of: stainless steel, <NUM> stainless steel, cobalt-chromium alloys, and nickel-titanium alloys.

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. According to a configuration not covered by the invention, 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.

Another aspect 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 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.

This aspect 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.

Another aspect 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.

Another aspect 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.

This aspect 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.

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:.

The instant invention is most clearly understood with reference to the following definitions.

As used herein, the singular form "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

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 <NUM> standard deviations of the mean. "About" can be understood as within <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term about.

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. patent law and can mean "includes," "including," and the like.

Unless specifically stated or obvious from context, the term "or," as used herein, is understood to be inclusive.

Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of <NUM> to <NUM> is understood to include any number, combination of numbers, or sub-range from the group consisting <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (as well as fractions thereof unless the context clearly dictates otherwise).

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.

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.

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.

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.

Referring now to <FIG>, one aspect of the invention provides an artificial, flexible valve <NUM>. The valve includes an expandable, cylindrical stent <NUM> defining a wall <NUM>. Valve <NUM> further includes a plurality of leaflets 106a-106c. Wall <NUM> can be formed by dip coating stent <NUM> in a polymer as further described herein. Leaflets <NUM> can be coupled to wall <NUM> along seams <NUM> using a variety of approaches (e.g., glue) as discussed further herein. Stent <NUM> includes one or more vertical posts <NUM>, <NUM>, which are relatively narrow posts <NUM>, according to a configuration not covered by the invention, or relatively wide posts <NUM>, according to the invention. Preferably leaflet joints between adjacent leaflets <NUM> are positioned on or close to a vertical post <NUM>, <NUM> of the stent <NUM>.

The valve <NUM> will now be described in the context of its components and methods of fabrication.

Referring now to <FIG>, stent <NUM> is a metallic stent having a plurality of wires, according to the invention (or strips and the like, according to configurations not covered by the invention), defining a plurality of cells <NUM>, <NUM> of various sizes. Stent <NUM> can be fabricated from a variety of malleable materials such as stainless steel, <NUM> stainless steel, cobalt-chromium alloys, nickel-titanium alloys (colloquially known as "nitinol"), and the like. Stent <NUM> can also be formed from various non-metallic materials, according to configurations not covered by the invention, such as plastics such as polyethylene, polyurethane, polytetrafluoroethylene (PTFE), silicone, poly(propylene) (PP), polyethylene terephthalate (PET), and the like.

Stent <NUM> can be completely enveloped by a polymer dip coating. Stent <NUM> and/or wall <NUM> can also be fabricated from a biocompatible material.

The stent <NUM> 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 <NUM>, <NUM> of the stent can be covered as the bare <NUM> stent is dipped into the polymer solution.

<FIG> depicts a stent <NUM> prior to expansion, dip coating, and leaflet installation. Stents <NUM> typically have a diameter of between about <NUM> and <NUM> prior to expansion and can be expanded to between about <NUM> and about <NUM> for implantation into a subject.

The components of stent <NUM> 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 <NUM> can be between about <NUM> and about <NUM>.

As discussed above, stent <NUM> includes one or more vertical posts 110a-110c to enhance bonding with leaflets <NUM>.

Stent <NUM> can include a plurality of vertical posts <NUM> that can serve a variety of functions. Some vertical posts <NUM> can include additional structure and are referred to herein as wide posts <NUM>. Wide posts <NUM> are preferably located at leaflet joints where two leaflets <NUM> meet. For example, in a valve <NUM> having a three leaflets <NUM>, wide posts <NUM> can be positioned at <NUM>° intervals within cylindrical stent <NUM>.

Wide posts <NUM> provide mechanical support to leaflets and prevent or substantially limit inward deformation of wall <NUM> due to tensile forces applied to leaflets <NUM> transferred to wall <NUM>. Without being bound by theory, it is believed that the wide posts <NUM> provide increased strength and resiliency due to formation of polymer wall <NUM> through windows <NUM> and around wide posts <NUM>, thus providing cohesive holding of the polymer to itself around the stent <NUM> instead of relying solely on adhesive bonding of the polymer wall <NUM> to the stent <NUM>.

Wide posts <NUM> advantageously allow for relaxed tolerances in positioning leaflets <NUM> relative to wide posts <NUM>. For example, window <NUM> can have a width of between about <NUM> and about <NUM> (e.g., about <NUM>) and a height of between about <NUM> and about <NUM> (e.g., about <NUM>).

A variety of additional wide post geometries are depicts in <FIG>. In <FIG>, the wide posts have a solid architecture without any windows. In <FIG>, the wide posts have a substantially rectangular architecture defining a single, long window as in <FIG>, and <FIG>. In <FIG>, the wide posts define a plurality of coaxial substantially rectangular windows. In <FIG>, the wide posts define a plurality of coaxial, substantially parallel windows. In <FIG>, the wide posts define a plurality of coaxial, substantially rectangular windows in a <NUM>×<NUM> arrangement. In <FIG>, the wide posts include a plurality of circular windows. These wide post architectures are further depicted in <FIG>. 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.

Referring now to <FIG>, the positioning of a leaflet joint <NUM> (formed, e.g., on mandrel <NUM> as discussed herein) adjacent to window <NUM> of wide post <NUM> is depicted. (The polymer dip-coated wall <NUM> is completely transparent for ease and clarity in viewing, but can be transparent, translucent, or opaque. ) <FIG> further depict how a geometry of the stent <NUM> can be selected to substantially approximate the leaflet-stent attachment seam <NUM> discussed herein in order to provide added mechanical support and resiliency.

Referring now to <FIG>, stent <NUM> can include one or more anchor points <NUM>. Anchor points <NUM> advantageously facilitate holding, dipping, and rotation of the stent <NUM> during the dip coating process without interfering with the dip coating of the remainder of the stent architecture. Accordingly, the entire stent <NUM> can be dip coated in a single dipping, although multiple dippings can be utilized to control coating density, thickness, and the like. Anchor points <NUM> can also receive one or more radio-opaque materials such as platinum to aid in placement and visualization of the valve.

In one embodiments depicted in <FIG>, stent <NUM> can be engaged with a holder <NUM> (e.g., by posts <NUM>) for dipping and rotation. Once the polymer (again depicted as, but not necessarily, transparent) is wet on the stent <NUM>, the stent can be positioned horizontally and rotated axially.

Leaflets <NUM> can be formed using a variety of techniques including dip coating, 3D-printing (also known as additive manufacturing), molding, and the like.

Referring now to <FIG>, leaflets <NUM> can be fabricated by dip coating a mandrel <NUM> with a polymer. The mandrel <NUM> 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 <NUM> will be removed from the mandrel <NUM> after the polymer dries, roughness of mandrel surface can be controlled using known machining and other manufacturing techniques. The mandrel <NUM> can be made from a cylinder. Preferably, the diameter of the mandrel <NUM> is a slightly (e.g., between about <NUM> and about <NUM>) smaller than inner diameter of stent <NUM> after expansion.

The mandrel <NUM> for the leaflets <NUM> 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 <NUM> can be dimensioned to produce leaflets <NUM> 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 <NUM>.

Mandrel <NUM> can be designed to have a complementary geometry to the desired leaflet shape and permits easier viewing of leaflet geometry. Although mandrel <NUM> is utilized to describe the geometry of the leaflet <NUM>, 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) <NUM> can be produced using techniques other than dip coating. Mandrel <NUM> is preferably cylindrical and can have an outer profile substantially approximating an inner profile of stent <NUM>. Mandrel <NUM> can define a plurality of pockets <NUM> that each define a leaflet <NUM> as it hangs from wall <NUM> via attachment line <NUM>. Each leaflet <NUM> terminates in a commissure line <NUM> 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 <NUM> can extend beyond the commissure line <NUM> to an extended commissure line <NUM> for improved sealing as will be discussed herein.

Referring now to <FIG>, mandrel can be cast, machined, printed, or otherwise fabricated so that pockets <NUM> have a desired geometry. The commissure line <NUM> and the coaptation region <NUM> and optionally the extended commissure line <NUM> have a substantially hyperbolic profile when viewed in the x-y plane. Leaflet-stent attachment line <NUM> and optionally a leaflet valley line <NUM> (formed by taking a cross-section in a z plane) 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 <NUM> to the contour of the cylindrical mandrel <NUM>. A comparison of elliptical vs. parabolic leaflet valley lines is provided in <FIG>. A comparison of elliptical vs. parabolic leaflet-stent attachment lines is provided in <FIG>.

Referring now to <FIG>, mandrel <NUM> can define a gap <NUM> between adjacent leaflets. Advantageously, leaflets <NUM> with a hyperbolic profile can produce smaller gaps than leaflets with parabolic profiles. For example, gaps <NUM> can be less than <NUM> or between about <NUM> and about <NUM> (e.g., between about <NUM> and about <NUM>, between about <NUM> and about <NUM>, between about <NUM> and about <NUM>, between about <NUM> and about <NUM>, between about <NUM> and about <NUM>, between about <NUM> and about <NUM>, between about <NUM> and about <NUM>, about <NUM> and about <NUM>, about <NUM> and about <NUM>, and the like).

As seen in <FIG>, the length of hyperbolic commissure line <NUM> is about twice the radius of the stent or mandrel. The positioning of a hyperbolic commissure line <NUM> relative to defined asymptotes is depicted in <FIG>.

Referring now to <FIG>, coaptation region can have minimal height in the z-axis so as to consist only of the commissure line <NUM>. Alternatively, coaptation region <NUM> can have a vertical extension in the z-axis to an extended commissure line <NUM> as depicted in <FIG>. The height of the coaptation region <NUM> can be selected to reduce the amount of regurgitation, while still allowing the valve to open. For example the coaptation region <NUM> can have a height between about <NUM> and about <NUM> (e.g., about <NUM>). Although <FIG> depict extensions of coaptation region <NUM> 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 lealets hanging therebetween) approach and/or contact each other to form an extended coaptation region.

The zone of coaptation is affected by the pressure placed upon the closed valve <NUM>. The higher the pressure, the more downward tension is placed on the leaflets <NUM>, possibly leading to a failure of coaptation with consequent regurgitation. Proper coaptation also allows the leaflets <NUM> to support each other, so there is less stress placed on any individual leaflet <NUM>. Another benefit of enhancing height of the coaptation zone is that this allows the valve <NUM> 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 <NUM>.

Options for enhancing the height of the coaptation zone, according to the invention, 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>. 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 <NUM> axes.

Referring now to <FIG>, coaptation regions <NUM> can have varying heights in the z-axis between the commissure line <NUM> and extended commissure line <NUM>. For example, the height of coaptation region <NUM> can increase toward the outside of the mandrel as depicted in <FIG>. According to the invention, the height of the coaptation region <NUM> dips to form a trough between the outside and the center of the mandrel <NUM> as depicted in <FIG>.

Referring now to <FIG>, the same profiles can be applied to commissure line <NUM> without any coaptation region <NUM>.

Referring now to <FIG>, the commissure lines <NUM>, coaptation regions <NUM> and/or extended commissure lines <NUM> 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 <NUM>, coaptation region <NUM>, and/or extended commissure line <NUM>. For example, the mandrel <NUM> can be thicker between the perimeter and the center as depicted in <FIG> to produce one or more scallops. In <FIG>, the mandrel <NUM> can have either a single curve or multiple curves.

In order to increase tear-resistance of the leaflets <NUM> and enhance bonding strength between leaflets <NUM> and stent <NUM>, the thickness of the leaflets <NUM> can be controlled regionally. Because the most common failure points are at the outer edges of the leaflets <NUM> (such as commissure line <NUM> or extended commissure line <NUM> and leaflet-stent attachment line <NUM>), increased thickness at outer areas of the leaflets <NUM> 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 <NUM> can be large enough to cover the glued area for bonding the leaflets <NUM> and the covered stent <NUM>. In some embodiments, the thickness of thickened areas of the leaflets is between about <NUM> and about <NUM>.

Multiple dippings can be performed to produce leaflets with a desired thickness. In some embodiments, the thickness of the leaflets is between about <NUM> and about <NUM>.

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.

Referring now to <FIG>, a photograph of a mandrel <NUM> is provided. Referring now to <FIG>, a reinforcing zone <NUM> can be formed on the mandrel <NUM> prior either by removing mandrel material to allow for additional thickness in certain (e.g., outer) regions of leaflets <NUM> 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 <NUM>.

After dipping the mandrel <NUM> into the polymer solution, the coated polymer dries in order to form the leaflet(s) <NUM>. Because the formed leaflets <NUM> 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.

Referring now to <FIG>, the gap portion <NUM> 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 <NUM>. For example, the gap portion <NUM> can have a grooved profile as depicted in <FIG>, a concave profile as depicted in <FIG>, or an angled profile as depicted in <FIG>. 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 <NUM>.

The stent-mounted valve <NUM> can be implanted with smaller diameter than its manufactured diameter for reducing leakage and improving durability.

Referring now to <FIG>, <FIG>, and <FIG>, a method for fabricating a valve is depicted. A bare stent <NUM> and a bare mandrel <NUM> are provided.

The stent <NUM> can be first coated with a polymer such as PEEK or other metal surface modifier prior to further dip coating of the stent <NUM> in another polymer in order to improve adhesion of the leaflet polymer <NUM> to the metal stent <NUM>.

The bare mandrel <NUM> can optionally be coated with a release agent to promote separation of the polymer leaflets from the mandrel <NUM>.

Both the bare stent <NUM> and the mandrel <NUM> are dip coated separately in a polymer, which may be the same or different for the bare stent <NUM> and the mandrel <NUM>.

The leaflets <NUM> formed on the mandrel <NUM> can be removed prior to introduction to the coated stent. Alternatively, the coated mandrel <NUM> can be introduced into the coated stent, the leaflets <NUM> can be bonded to the coated stent, and the mandrel <NUM> can be then be removed to leave the assembled valve <NUM>.

Leaflets <NUM> 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 <NUM> and/or mandrel <NUM> can be applied to bond the leaflets <NUM> to the dip-coated stent.

Although separate fabrication of the polymer-coated stent and the leaflets <NUM> 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.

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.

Referring now to <FIG>, stent <NUM> and leaflets <NUM> can be fabricated based on a diameter that is slightly larger than the placement location as depicted in <FIG>. When deployed to a location having a smaller diameter than the manufactured diameter, the leaflets <NUM> will be held in tight contact with each other as seen in <FIG> 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.

As can be seen in <FIG>, the coaptation regions of leaflets <NUM> have a substantially hyperbolic profile both at the manufactured diameter and the deployed diameter.

Referring now to <FIG>, a high-speed photograph of a closed valve under pressure during in vitro testing in a hemodynamic pulse duplicator is provided.

The leaflets <NUM> can be formed from the same or different polymer with which the stent <NUM> is coated to form wall <NUM>. For example, the leaflets <NUM> can be formed from polymers such as polyethylene, polyurethane, silicone, and the like. Wall <NUM> can be formed from polyethylene, polyurethane, silicone, and the like.

Supplementary materials such as directional fibers can mixed into the polymer solution or applied to the leaflets between coatings in order to increase durability.

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.

Referring now to <FIG>, a method <NUM> of implanting an artificial valve is provided. The valve to be implanted can be a valve <NUM> as described herein.

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).

In step S1804, the sheath (containing the valve and the expander) is introduced into a vessel of the subject.

In step S1806, the valve and the expander are advanced from the sheath and positioned in the desired location.

In step S1808, the desired positioning can be verified using various imaging techniques such as fiber optics, ultrasound, X-ray, and the like.

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.

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.

In step S1814, the expander and sheath can be retracted according to standard surgical techniques.

Referring now to <FIG>, a method <NUM> of expanding an implanted valve is provided. The implanted valve can be a valve <NUM> as described herein.

In step S1902, an expander is introduced into the implanted valve.

In step S1904, the expander is actuated within the implanted valve to increase the diameter of the implanted valve.

In step S1906, the desired expansion can be verified using various imaging techniques.

In step S1908, the expander can be retracted according to standard surgical techniques.

Claim 1:
An artificial, flexible valve (<NUM>) to be implanted within a patient's heart, the valve comprising:
a stent (<NUM>) defining a wall (<NUM>), the stent (<NUM>) being serially expandable to accompany a child's growth,
wherein the stent comprises metal and a plurality of wires (<NUM>) defining a plurality of cells (<NUM>; <NUM>) of various sizes; and
a plurality of leaflets (<NUM>) extending from the wall (<NUM>) of the stent (<NUM>), the plurality of leaflets (<NUM>) forming a plurality of coaptation regions (<NUM>) between two adjacent leaflets (<NUM>), the coaptation regions (<NUM>) each having a substantially hyperbolic profile formed in an x-y plane and including extensions along a z-axis beyond a commissure line and adapted and configured to form a releasable, but substantially complete seal when the leaflets (<NUM>) are in a closed position, each of the plurality of leaflets (<NUM>) having a leaflet-stent attachment line (<NUM>) that is substantially elliptical, the height of the coaptation region being enhanced by creating excess length of the leaflet free edges, so that the free edge length is greater than twice the radius of the stent,
wherein the height of each of the plurality of coaptation regions (<NUM>) dips to form a trough between the outside and the center of the stent,
wherein adjacent leaflets are coupled to a wide post of the stent.