Prosthetic heart valve leaflet

Abstract

Disclosed herein are leaflets for prosthetic heart valves, and methods of forming such leaflets. As one example, a prosthetic heart valve can include a frame that is radially expandable from a radially collapsed configuration to a radially expanded configuration, and a plurality of leaflets mounted on an inside of the frame. Each leaflet is a composite leaflet comprising at least one polymeric layer and at least one mesh layer, where at least an outer portion of the at least one polymeric layer has a porosity of 3-80 µm.

Description

PROSTHETIC HEART VALVE LEAFLET CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. Patent Application No.63 / 556,315, filed February 21, 2024, the entire disclosure which is incorporated by reference for all purposes. FIELD

[0002] The present disclosure relates to prosthetic heart valves, and in particular to leaflets for prosthetic heart valves. BACKGROUND

[0003] The human heart can suffer from various valvular diseases. These valvular diseases can result in significant malfunctioning of the heart and ultimately require repair of the native valve or replacement of the native valve with an artificial valve. There are a number of known repair devices (for example, stents) and artificial valves, as well as a number of known methods of implanting these devices and valves in humans. Percutaneous and minimally-invasive surgical approaches are used in various procedures to deliver prosthetic medical devices to locations inside the body that are not readily accessible by surgery or where access without surgery is desirable. In one specific example, a prosthetic heart valve can be mounted in a crimped state on the distal end of a delivery apparatus and advanced through the patient’s vasculature (for example, through a femoral artery and the aorta) until the prosthetic valve reaches the implantation site in the heart. The prosthetic valve is then expanded to its functional size, for example, by inflating a balloon on which the prosthetic valve is mounted, actuating a mechanical actuator that applies an expansion force to the prosthetic valve, or by deploying the prosthetic valve from a sheath of the delivery apparatus so that the prosthetic valve can self-expand to its functional size.

[0004] Most expandable, prosthetic heart valves comprise a cylindrical metal frame or stent and prosthetic leaflets mounted inside the frame. When implanted in a patient’s body, the leaflets of the prosthetic heart valve are configured to open and close (during systole and diastole, for example), in order to regulate a flow of blood through the prosthetic heart valve. SUMMARY

[0005] Described herein are prosthetic heart valves, delivery apparatuses, and methods for implanting prosthetic heart valves. Also described herein are composite leaflets configured to be mounted inside a frame of a prosthetic heart valve, and methods for forming the leaflets. In some examples, a composite leaflet can comprise a mesh layer that provides structure to the leaflet and a polymeric layer that increases the biocompatibility of the leaflet. For example, the composite leaflet can comprise a mesh layer comprising a metalor metal alloy (such as nitinol) that has a structure that allows the leaflet to bend but not elongate. The mesh layer can be covered by one or more polymeric layers that are configured to enhance the biocompatibility of the leaflet. In some examples, the one or more polymeric layers can comprise a microporous polymer layer having a porosity in a range that promotes growth of a relatively thin layer of tissue (for example, comprising healthy endothelial cells) over the leaflet when implanted in a patient. As such, the devices and methods disclosed herein can, among other things, overcome one or more of the deficiencies of typical prosthetic heart valves and their delivery apparatus.

[0006] A prosthetic heart valve can comprise a frame and a valvular structure coupled to the frame. In addition to these components, a prosthetic heart valve can further comprise one or more of the components disclosed herein.

[0007] In some examples, the prosthetic heart valve can comprise a sealing member configured to reduce paravalvular leakage.

[0008] In some examples, the valvular structure can comprise a plurality of composite leaflets mounted inside the frame.

[0009] In some examples, each composite leaflet can comprise at least one polymeric layer and at least one mesh layer.

[0010] In some examples, the mesh layer comprises a plurality of interconnected struts forming openings or gaps therebetween.

[0011] In some examples, the at least one polymeric layer comprises a first polymeric layer surrounding the struts of the mesh layer.

[0012] In some examples, the at least one polymeric layer comprises a second polymeric layer disposed around the first polymeric layer, where the second polymeric layer is a microporous polymer layer comprising a plurality of filaments.

[0013] In some examples, the second polymeric layer is thicker than the first polymeric layer.

[0014] In some examples, the mesh layer comprises a shape memory material.

[0015] In some examples, the composite leaflets can be three-dimensional.

[0016] In some examples, a prosthetic heart valve comprises a frame that is radially expandable from a radially collapsed configuration to a radially expanded configuration, and a plurality of leaflets mounted on an inside of the frame, where each leaflet is a composite leaflet comprising at least one polymeric layer and at least one mesh layer. At least an outer portion of the at least one polymeric layer has a porosity of 3–80 µm.

[0017] In some examples, a prosthetic heart valve comprises a frame that is radially expandable from a radially collapsed configuration to a radially expanded configuration, and a plurality of leaflets mounted on an inside of the frame. Each leaflet is a composite leaflet comprising a mesh layer comprising interconnected struts, a first polymeric layer surrounding the struts of the mesh layer, and a second polymeric layer disposed around the first polymeric layer, where the second polymeric layer is a microporous polymer layer having a porosity of 3–80 µm, and where the second polymeric layer is thicker than the first polymeric layer.

[0018] In some examples, a prosthetic heart valve comprises a frame and a plurality of leaflets mounted inside of the frame. Each leaflet is a composite leaflet comprising at least one microporous polymeric layer and at least one mesh layer. The microporous polymeric layer is configured to induce a layer of tissue having a predetermined maximum thickness to form on the microporous polymer layer.

[0019] In some examples, a prosthetic heart valve comprises one or more of the components recited in Examples 1–15, 29, 40–48, and 51–59 below.

[0020] A composite leaflet for a prosthetic heart valve can comprise at least one mesh layer and at least one polymeric layer.

[0021] In some examples, the at least one mesh layer comprises a plurality of interconnected struts forming openings or gaps therebetween.

[0022] In some examples, the mesh layer comprises a shape memory material.

[0023] In some examples, the at least one polymeric layer comprises a first polymeric layer surrounding the struts of the mesh layer.

[0024] In some examples, the at least one polymeric layer comprises a second polymeric layer disposed around the first polymeric layer, where the second polymeric layer comprises a plurality of filaments forming a microporous polymer layer.

[0025] In some examples, the second polymeric layer is thicker than the first polymeric layer.

[0026] In some examples, the composite leaflet can be three-dimensional.

[0027] In some examples, a composite leaflet for a prosthetic heart valve comprises a mesh layer comprising a plurality of interconnected struts that is configured to enable bending without elongation of the leaflet, wherein the plurality of interconnected struts forms a plurality of openings in the mesh layer. The composite leaflet further comprises at least one polymeric layer surrounding the mesh layer and disposed within the plurality of openings in the mesh layer, between the plurality of interconnected struts.

[0028] In some examples, a composite leaflet for a prosthetic heart valve comprises one or more of the components recited in Examples 18–28 below.

[0029] A method for forming a composite leaflet for a prosthetic heart valve can comprise forming a mesh layer and coating the mesh layer with a polymer.

[0030] In some examples, the method can comprise coating the mesh layer with the polymer to form a first polymeric layer around the mesh layer, and further comprising electrospinning a polymer over the first polymeric layer to form a second polymeric layer.

[0031] In some examples, a method for forming a composite leaflet for a prosthetic heart valve comprises forming a mesh layer comprising interconnected struts, the interconnected struts defining openings in the mesh layer. The method further comprises coating the mesh layer with a polymer to form a first polymeric layer around the interconnected struts of the mesh layer, and electrospinning a polymer over the first polymeric layer to form a second polymeric layer.

[0032] In some examples, the second polymeric layer has a porosity of 3–80 µm.

[0033] In some examples, the composite leaflet is three-dimensional.

[0034] In some examples, a method comprises one or more of the features recited in Examples 16–17, 30–39, 49–50, and 60 below.

[0035] The various innovations of this disclosure can be used in combination or separately. This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. The foregoing and other objects, features, and advantages of the disclosure will become more apparent from the following detailed description, claims, and accompanying figures. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] FIG.1 is a side view of a prosthetic heart valve, according to one example.

[0037] FIG.2 is a side view of an example of a delivery apparatus configured to deliver and implant a radially expandable prosthetic heart valve at an implantation site.

[0038] FIG.3 is a perspective view of a prosthetic heart valve, according to an example.

[0039] FIG.4 is a plan view of an exemplary composite leaflet for a prosthetic heart valve.

[0040] FIG.5 is an example of a mesh layer for a composite leaflet, where the mesh layer has cells arranged in a grid structure.

[0041] FIG.6 is a cross-sectional view of the mesh layer of FIG.5.

[0042] FIG.7 is a detail view of a portion of the mesh layer of FIG.6 with a polymeric layer coating the mesh layer.

[0043] FIG.8 is a detail view of a portion of the mesh layer of FIG.6 with a thinner, inner polymeric layer covering the mesh layer and a thicker, outer microporous polymeric layer covering the inner polymeric layer.

[0044] FIG.9 is an example of a mesh layer for a composite leaflet, where the mesh layer has cells with a hexagonal shape.

[0045] FIG.10 is an example of a unit or cell of a mesh layer for a composite leaflet, where the mesh layer comprises a network of interconnected struts forming a zigzag pattern.

[0046] FIG.11 is an example of a unit or cell of a mesh layer for a composite leaflet, where the mesh layer unit comprises a plurality of interconnected struts with varying sized gaps therebetween.

[0047] FIG.12A is an example of a unit or cell of a mesh layer for a composite leaflet, where the mesh layer unit comprises a plurality of interconnected struts forming a triangular zigzag pattern with minimal gaps between struts in the x and y directions.

[0048] FIG.12B is an example of a unit or cell of a mesh layer for a composite leaflet, where the mesh layer unit comprises a plurality of interconnected struts forming a triangular zigzag pattern with minimal gaps between struts in the x and y directions, and with struts and gaps oriented in the y direction disposed adjacent to one another.

[0049] FIG.13A is an example of a mesh layer for a composite leaflet, where the mesh layer comprises a plurality of interconnected struts arranged to provide increased bending flexibility without elongation of the struts.

[0050] FIG.13B is a detail view of a portion of the mesh layer of FIG.13A.

[0051] FIG.14 is a schematic of a portion of a composite leaflet comprising the mesh structure of FIG.13A arranged along a cusp edge portion of the leaflet.

[0052] FIG.15A is a detail view of a portion of the mesh layer of FIG.13A with a thinner, inner polymeric layer covering the mesh layer, a thicker, outer microporous polymeric layer covering the inner polymeric layer, and a thin layer of tissue growth over the outer microporous polymeric layer.

[0053] FIG.15B is a detail view of a portion of the mesh layer of FIG.13A with a microporous polymeric layer covering the mesh layer and a thin layer of tissue growth over the microporous polymeric layer.DETAILED DESCRIPTION General Considerations

[0054] For purposes of this description, certain aspects, advantages, and novel features of examples of this disclosure are described herein. The disclosed methods, apparatus, and systems should not be construed as being limiting in any way. Instead, the present disclosure is directed toward all novel and nonobvious features and aspects of the various disclosed examples, alone and in various combinations and sub-combinations with one another. The methods, apparatus, and systems are not limited to any specific aspect or feature or combination thereof, nor do the disclosed examples require that any one or more specific advantages be present or problems be solved.

[0055] Although the operations of some of the disclosed examples are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language set forth below. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed methods can be used in conjunction with other methods. Additionally, the description sometimes uses terms like “provide” or “achieve” to describe the disclosed methods. These terms are high-level abstractions of the actual operations that are performed. The actual operations that correspond to these terms may vary depending on the particular implementation and are readily discernible by one of ordinary skill in the art.

[0056] As used in this application and in the claims, the singular forms “a,” “an,” and “the” include the plural forms unless the context clearly dictates otherwise. Additionally, the term “includes” means “comprises.” Further, the term “coupled” generally means physically, mechanically, chemically, magnetically, and / or electrically coupled or linked and does not exclude the presence of intermediate elements between the coupled or associated items absent specific contrary language.

[0057] As used herein, the term “proximal” refers to a position, direction, or portion of a device that is closer to the user and further away from the implantation site. As used herein, the term “distal” refers to a position, direction, or portion of a device that is further away from the user and closer to the implantation site. Thus, for example, proximal motion of a device is motion of the device away from the implantation site and toward the user (for example, out of the patient’s body), while distal motion of the device is motion of the device away from the user and toward the implantation site (for example, into the patient’s body). The terms “longitudinal” and “axial” refer to an axis extending in the proximal and distal directions, unless otherwise expressly defined.

[0058] As used herein, “e.g.” means “for example,” and “i.e.” means “that is.” Overview of the Disclosed Technology

[0059] As introduced above, prosthetic heart valves comprise a frame that is radially expandable and collapsible, and prosthetic leaflets mounted inside the frame. When implanted in a patient’s body, the leaflets of the prosthetic heart valve are configured to open and close (during systole and diastole, for example), in order to regulate a flow of blood through the prosthetic heart valve. Most commercially available prosthetic valves have leaflets made of natural tissue, such as pericardial tissue from a cow or other sources. Synthetic leaflets, such as made from various polymers, have been described in the prior art but have not been proven to be suitable for human implantation for various reasons. For example, some such synthetic leaflets may lack sufficient structural integrity to prevent degradation under pressure (during opening and closing of the leaflets), may not produce sufficient hemodynamics comparable to tissue leaflets, and / or may trigger an undesirable inflammatory response that prevents proper functioning of the leaflets.

[0060] Described herein are composite leaflets that can comprise at least one mesh layer and at least one polymeric layer. The mesh layer has a structure that is configured to enable bending of the leaflet during operation of the prosthetic heart valve in which it is mounted, while also providing adequate structure and reducing wear. The at least one polymeric layer can comprise a biocompatible polymer (or combination of polymers) and can be configured to promote a thin layer of tissue overgrowth (for example, healthy endothelial cells) that reduces a likelihood of fibrotic tissue overgrowth or clot formation on the prosthetic leaflets, when implanted in vivo. As a result, the composite leaflets can have increased biocompatibility, increased longevity and resistance to wear, and flexibility for opening and closing during operation of a prosthetic heart valve when implanted in a patient’s body.

[0061] Prosthetic valves disclosed herein can be radially compressible and expandable between a radially compressed state and a radially expanded state. Thus, the prosthetic valves can be crimped on or retained by an implant delivery apparatus in the radially compressed state while being advanced through a patient’s vasculature on the delivery apparatus. The prosthetic valve can be expanded to the radially expanded state once the prosthetic valve reaches the implantation site. It is understood that the prosthetic valves disclosed herein may be used with a variety of implant delivery apparatuses and can be implanted via various delivery procedures, examples of which will be discussed in more detail later. In some examples, the composite leaflets disclosed herein can be used in prosthetic heart valves that are not radially expandable and compressible (such as, so-called surgical heart valves, which typically have non-expandable frames, implanted via open-heart surgery).

[0062] FIG.1 illustrates an exemplary prosthetic device (for example, prosthetic heart valve) comprising a frame, leaflets secured on an inside of the frame, and an outer skirt disposed around an outer surface of the frame. In some examples, the frame can comprise commissure windows configured to receive adjacent sides of adjacent leaflets, thereby forming commissures that are secured to the frame. The prosthetic device can be advanced through a patient’s vasculature, such as to a native heart valve, by a delivery apparatus, such as the exemplary delivery apparatus shown in FIG.2. FIG.3 shows an example of an exemplary prosthetic device (for example, prosthetic heart valve) that comprises a plurality of leaflets and can be delivered using the delivery apparatus of FIG.2.

[0063] An exemplary composite leaflet for a prosthetic valve (such as the prosthetic valves shown in FIGS.1 or 3) is shown in FIG.4. The leaflet can comprise a mesh layer, or mesh core, that comprises a plurality of interconnected struts with gaps, void spaces, or openings formed between adjacent struts. In some examples, the mesh layer can comprise a metal and / or shape memory material. FIGS.5–8 show an exemplary structure for the mesh layer comprising a grid-like structure.

[0064] In some examples, the mesh layer can be formed by physical vapor deposition (PVD) followed by laser cutting (for example, femto laser cutting). In some examples, the mesh layer can be formed by photolithography.

[0065] In some examples, a thinner polymeric layer can coat and / or surround the mesh layer (around the struts), as shown in FIG.7. In some examples, an additional, thicker microporous polymeric layer can cover and / or be disposed over the thinner polymeric layer. In some examples, the microporous polymeric layer can comprise an electrospun polymer (or formed by electrospinning). The thicker microporous polymeric layer can comprise a plurality of polymer filaments or fibers, which results in the microporous polymeric layer having a porosity that promotes a thin layer of tissue growth (for example, healthy endothelial cells and / or neointima covered by healthy endothelial cells) on the leaflet when implanted in a patient’s body, as depicted schematically in FIGS.15A and 15B, thereby reducing or preventing a foreign body reaction and fibrotic tissue overgrowth on the leaflets following implantation and during valve operation in vivo.

[0066] FIGS.9–13B show additional exemplary structures for the mesh layer which comprise different arrangements of struts. In some examples, the arrangement of struts of the mesh layer can be configured to reduce elongation in the x- and y-directions, in a plane of the mesh layer when laid flat (such as the structures shown in FIGS.10–13B).

[0067] FIG.14 shows an exemplary arrangement of the mesh structure of FIGS.13A and 13B arranged along a cusp edge portion of a leaflet, where the mesh structure can include orserve as sewing anchors for attaching the leaflet to a frame and / or skirt of a prosthetic heart valve. Examples of the Disclosed Technology

[0068] FIG.1 shows an exemplary prosthetic valve 10, according to one example. Any of the prosthetic valves disclosed herein are adapted to be implanted in the native aortic annulus, although in some examples they can be adapted to be implanted in the other native annuluses of the heart (the pulmonary, mitral, and tricuspid valves). The disclosed prosthetic valves also can be implanted within vessels communicating with the heart, including a pulmonary artery (for replacing the function of a diseased pulmonary valve, or the superior vena cava or the inferior vena cava (for replacing the function of a diseased tricuspid valve) or various other veins, arteries and vessels of a patient. The disclosed prosthetic valves also can be implanted within a previously implanted prosthetic valve (which can be a prosthetic surgical valve or a prosthetic transcatheter heart valve) in a valve-in-valve procedure.

[0069] In some examples, the disclosed prosthetic valves can be implanted within a docking or anchoring device that is implanted within a native heart valve or a vessel. For example, in one example, the disclosed prosthetic valves can be implanted within a docking device implanted within the pulmonary artery for replacing the function of a diseased pulmonary valve, such as disclosed in U.S. Patent Application Publication No. 2017 / 0231756, which is incorporated by reference herein. In some examples, the disclosed prosthetic valves can be implanted within a docking device implanted within or at the native mitral valve, such as disclosed in International Patent Application Publication No. WO2020 / 247907, which is incorporated herein by reference. In some examples, the disclosed prosthetic valves can be implanted within a docking device implanted within the superior or inferior vena cava for replacing the function of a diseased tricuspid valve, such as disclosed in U.S. Patent Application Publication No.2019 / 0000615, which is incorporated herein by reference.

[0070] The prosthetic valve 10 can have four main components: a stent or frame 12, a valvular structure 14, an inner skirt 16, and a perivalvular outer sealing member or outer skirt 18. The prosthetic valve 10 can have an inflow end portion 15, an intermediate portion 17, and an outflow end portion 19.

[0071] The valvular structure 14 can comprise three leaflets 40, collectively forming a leaflet structure, which can be arranged to collapse in a tricuspid arrangement, although in some examples there can be greater or fewer number of leaflets (for example, one or more leaflets 40). The leaflets 40 can be secured to one another at their adjacent sides to form commissures 22 of the valvular (or leaflet) structure 14. The lower edge of valvular structure 14 can have an undulating, curved scalloped shape and can be secured to the inner skirt 16 bysutures (not shown). In some examples, the leaflets 40 can be formed of pericardial tissue (for example, bovine pericardial tissue), biocompatible synthetic materials, or various other suitable natural or synthetic materials as known in the art and described in U.S. Patent No. 6,730,118, which is incorporated by reference herein.

[0072] The frame 12 can be formed with a plurality of circumferentially spaced slots, or commissure windows 20 that are adapted to mount the commissures 22 of the valvular structure 14 to the frame. The frame 12 can be made of any of various suitable plastically- expandable materials (for example, stainless steel, etc.) or self-expanding materials (for example, nitinol), as known in the art. When constructed of a plastically-expandable material, the frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed (or compressed) configuration on a delivery catheter and then expanded inside a patient by an inflatable balloon or equivalent expansion mechanism to a radially expanded configuration. When constructed of a self-expandable material, the frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed configuration and restrained in the collapsed configuration by insertion into a sheath or equivalent mechanism of a delivery catheter. Once inside the body, the prosthetic valve can be advanced from the delivery sheath, which allows the prosthetic valve to expand to its functional size.

[0073] Suitable plastically-expandable materials that can be used to form the frame 12 include, metal alloys, polymers, or combinations thereof. Example metal alloys can comprise one or more of the following: nickel, cobalt, chromium, molybdenum, titanium, or other biocompatible metal. In some examples, the frame 12 can comprise stainless steel. In some examples, the frame 12 can comprise cobalt-chromium. In some examples, the frame 12 can comprise nickel-cobalt-chromium. In some examples, the frame^12 comprises a nickel- cobalt-chromium-molybdenum alloy, such as MP35N® alloy (tradename of SPS Technologies), which is equivalent to UNS R30035 (covered by ASTM F562-02). MP35N® / UNS R30035 alloy comprises 35% nickel, 35% cobalt, 20% chromium, and 10% molybdenum, by weight.

[0074] The frame 12 can comprise a plurality of interconnected struts 32 that form cells (or openings or void spaces) in the frame.

[0075] In some examples, as shown in FIG.1 an upper edge portion 28 (also referred to as an outflow edge portion) of the outer skirt 18 can be secured to the frame 12 by stitches 24 and a lower edge portion 30 (also referred to as an inflow edge portion) of the outer skirt 18 can be secured to the frame 12 by stitches 26 extending along the inflow end portion 15 of the prosthetic valve 10. For example, the stitches 24 can wrap around struts 32 of the frame 12 forming a row of circumferentially extending struts 32 at the intermediate portion 17 of the prosthetic valve 10. Further, in some examples, the stitches 26 can wrap around struts 32 ofthe frame 12 forming a row of circumferentially extending struts 32 at the inflow end portion 15 of the prosthetic valve 10. In some instances, the upper edge portion 28 can be secured to struts 32 that are closer to the outflow end portion 19 of the frame 12 (such as the row of circumferentially extending struts 32 forming inflow ends of the row of cells disposed at the outflow end portion 19.

[0076] FIG.2 shows a delivery apparatus 100, according to an example, that can be used to implant an expandable prosthetic heart valve (for example, the prosthetic heart valve 10 of FIG.1 and / or any of the other prosthetic heart valves described herein). In some examples, the delivery apparatus 100 is specifically usable or adapted for use in introducing a prosthetic valve into a heart.

[0077] The delivery apparatus 100 in the illustrated example of FIG.2 is a balloon catheter comprising a handle 102 and a steerable, outer shaft 104 extending distally from the handle 102. The delivery apparatus 100 can further comprise an intermediate shaft 106 (which also may be referred to as a balloon shaft) that extends proximally from the handle 102 and distally from the handle 102, the portion extending distally from the handle 102 also extending coaxially through the outer shaft 104. Additionally, the delivery apparatus 100 can further comprise an inner shaft 108 extending distally from the handle 102 coaxially through the intermediate shaft 106 and the outer shaft 104 and proximally from the handle 102 coaxially through the intermediate shaft 106.

[0078] The outer shaft 104 and the intermediate shaft 106 can be configured to translate (move) longitudinally, along a central longitudinal axis 120 of the delivery apparatus 100, relative to one another to facilitate delivery and positioning of a prosthetic valve at an implantation site in a patient’s body.

[0079] The intermediate shaft 106 can include a proximal end portion 110 that extends proximally from a proximal end of the handle 102, to an adaptor 112. A rotatable knob 114 can be mounted on the proximal end portion 110 and can be configured to rotate the intermediate shaft 106 around the central longitudinal axis 120 and relative to the outer shaft 104.

[0080] The adaptor 112 can include a first port 138 configured to receive a guidewire therethrough and a second port 140 configured to receive fluid (for example, inflation fluid) from a fluid source. The second port 140 can be fluidly coupled to an inner lumen of the intermediate shaft 106.

[0081] The intermediate shaft 106 can further include a distal end portion that extends distally beyond a distal end of the outer shaft 104 when a distal end of the outer shaft 104 is positioned away from an inflatable balloon 118 of the delivery apparatus 100. A distal endportion of the inner shaft 108 can extend distally beyond the distal end portion of the intermediate shaft 106.

[0082] The balloon 118 can be coupled to the distal end portion of the intermediate shaft 106.

[0083] In some examples, a distal end of the balloon 118 can be coupled to a distal end of the delivery apparatus 100, such as to a nose cone 122 (as shown in FIG.2), or to an alternate component at the distal end of the delivery apparatus 100 (for example, a distal shoulder). An intermediate portion of the balloon 118 can overlay a valve mounting portion 124 of a distal end portion of the delivery apparatus 100 and a distal end portion of the balloon 118 can overly a distal shoulder 126 of the delivery apparatus 100. The valve mounting portion 124 and the intermediate portion of the balloon 118 can be configured to receive a prosthetic heart valve in a radially compressed state. For example, as shown schematically in FIG.2, a prosthetic heart valve 150 (which can be one of the prosthetic valves described herein) can be mounted around the balloon 118, at the valve mounting portion 124 of the delivery apparatus 100.

[0084] The balloon shoulder assembly, including the distal shoulder 126, is configured to maintain the prosthetic heart valve 150 (or other medical device) at a fixed position on the balloon 118 during delivery through the patient’s vasculature.

[0085] The outer shaft 104 can include a distal tip portion 128 mounted on its distal end. The outer shaft 104 and the intermediate shaft 106 can be translated axially relative to one another to position the distal tip portion 128 adjacent to a proximal end of the valve mounting portion 124, when the prosthetic valve 150 is mounted in the radially compressed state on the valve mounting portion 124 (as shown in FIG.2) and during delivery of the prosthetic valve to the target implantation site. As such, the distal tip portion 128 can be configured to resist movement of the prosthetic valve 150 relative to the balloon 118 proximally, in the axial direction, relative to the balloon 118, when the distal tip portion 128 is arranged adjacent to a proximal side of the valve mounting portion 124.

[0086] An annular space can be defined between an outer surface of the inner shaft 108 and an inner surface of the intermediate shaft 106 and can be configured to receive fluid from a fluid source via the second port 140 of the adaptor 112. The annular space can be fluidly coupled to a fluid passageway formed between the outer surface of the distal end portion of the inner shaft 108 and an inner surface of the balloon 118. As such, fluid from the fluid source can flow to the fluid passageway from the annular space to inflate the balloon 118 and radially expand and deploy the prosthetic valve 150.

[0087] An inner lumen of the inner shaft can be configured to receive a guidewire therethrough, for navigating the distal end portion of the delivery apparatus 100 to the target implantation site.

[0088] The handle 102 can include a steering mechanism configured to adjust the curvature of the distal end portion of the delivery apparatus 100. In the illustrated example, for example, the handle 102 includes an adjustment member, such as the illustrated rotatable knob 160, which in turn is operatively coupled to the proximal end portion of a pull wire. The pull wire can extend distally from the handle 102 through the outer shaft 104 and has a distal end portion affixed to the outer shaft 104 at or near the distal end of the outer shaft 104. Rotating the knob 160 can increase or decrease the tension in the pull wire, thereby adjusting the curvature of the distal end portion of the delivery apparatus 100. Further details on steering or flex mechanisms for the delivery apparatus can be found in U.S. Patent No.9,339,384, which is incorporated by reference herein.

[0089] The handle 102 can further include an adjustment mechanism 161 including an adjustment member, such as the illustrated rotatable knob 162, and an associated locking mechanism including another adjustment member, configured as a rotatable knob 178. The adjustment mechanism 161 is configured to adjust the axial position of the intermediate shaft 106 relative to the outer shaft 104 (for example, for fine positioning at the implantation site). Further details on the delivery apparatus 100 can be found in International Patent Application No. PCT / US2021 / 047056, which is incorporated by reference herein.

[0090] FIG.3 shows a prosthetic valve 200 comprising a radially expandable and / or compressible annular frame 202, a plurality of leaflets 204 mounted within the frame 202, and an outer skirt 206 secured to and around an outer surface of the frame 202. The frame 202 can comprise a plurality of interconnected struts 214 and a plurality of apices 208 that are spaced circumferentially apart around an inflow end 216 and an outflow end 218 of the frame 202 (only the apices 208 at the outflow end portion 218 are visible in FIG.3). Each apex 208 is formed at a junction between two angled struts 214 at either the inflow end 216 or the outflow end 218. The frame 202 comprises a plurality of axially extending posts 210, some of which define commissure windows therein. For example, the axially extending posts 210 that define commissure windows therein can comprise axially extending window struts 220 (which can also be referred to herein as commissure supports or commissure support posts) that define a commissure window 222 therebetween. Commissure tabs of adjacent leaflets 204 can be paired together and extend through the commissure windows 222, thereby forming commissures 212 secured to the frame 202 which can protrude radially outward from the frame 202. In some examples, the prosthetic valve 200 can be a balloon expandable valve and can be used with the delivery apparatus 100 of FIG.2. Additionaldetails on the prosthetic valve 200 can be found in International Patent Application Publication No. WO / 2022 / 226147, which is incorporated by reference herein.

[0091] FIG.4 is a plan view of an exemplary leaflet 300, which can be a composite leaflet 300 comprising at least one inner mesh layer (which can also be referred to herein as a mesh core) and at least one polymeric layer 312 covering (or coating) the mesh layer. Since the polymeric layer (or layers) cover the inner mesh layer, only the outermost polymeric layer 312 is shown in FIG.4 (and is referred to as the second polymeric layer 312 in the description below). Various exemplary structures for the inner mesh layer are shown in FIGS.5–14, as described further below.

[0092] In some examples, as shown in FIG.4, the leaflet 300 can comprise a main body 302 with a cusp edge portion 304, an outflow edge portion 306, and two commissure tabs 308 (or sides or tab portions) extending from the main body 302 on opposite sides of the main body 302 of the leaflet 300. It should be noted that the shape and size of the leaflet 300 shown in FIG.4 is exemplary, and the methods and structures of the composite leaflet described here can be applied to leaflets having various shapes and / or sizes.

[0093] FIG.5 depicts an exemplary structure for the mesh layer 310 of the leaflet 300. It should be noted that the mesh layer 310 shown in FIG.5, as well as the additional mesh layers shown in FIGS.9–13B and described herein, can be depicted having a certain overall geometry (such as square) for ease of illustration only. However, the overall geometry (or shape of the outer perimeter) of the mesh layer 310, and the additional mesh layers depicted in FIGS.9–13B can have a variety of shapes and / or sizes, which may match or closely follow the shape and / or size of the intended leaflet to be formed with the mesh layer (for example, as shown partially in FIG.14). For example, the mesh layer 310 can have an overall shape that matches or closely follows the shape of the leaflet 300 in FIG.4.

[0094] Further, although the mesh layers depicted in FIGS.5 and 9–14 may be depicted as relatively two-dimensional, in some examples, the mesh layers shown and described herein can be three-dimensional, such as having curves or one or more dome-shapes. For example, as described in International Patent Application Publication No. WO 2022 / 260979, which is incorporated by reference herein, three-dimensional leaflets can refer to leaflets that are not flattenable or are not planar and cannot be flattened out. In some examples, the leaflets can be configured with various curves, parabolic shapes, or the like that result in concave surfaces, convex surfaces, folds, or the like, that give the leaflet a three- dimensional shape. Utilization of non-flattenable or three-dimensional leaflets can enable the leaflets to have a longer arc length at their free edges, thereby resulting in a lower center of coaptation such that the leaflets properly coapt in the closed position, without the risk of contacting the frame in the open position, even when the prosthetic valve is under expanded.

[0095] As shown in FIG.5, the mesh layer 310 can have a grid-like structure. For example, the mesh layer 310 can comprise a plurality of interconnected struts 314 which form a plurality of rows and columns of cells 316 (which can also be referred to herein as openings, gaps, or void spaces). In some examples, as shown in FIG.5, each cell 316 (or sub- structure of the mesh layer 310) can have a square or rectangular shape formed by four connected struts 314.

[0096] In some examples, a width 318 (and / or height) of the cells 316 (or openings) can be in a range of 0.3 – 3 mm. For example, when the cells 316 are square-shaped, as shown in FIG.5, both the width 318 (in the x-direction) and height (in the y-direction) can be in a range of 0.3 – 3 mm. In some examples, when the cells 316 have a rectangular shape, the width 318 and height can both be in a range of 0.3 – 3 mm, with the longer dimension (width or height) being a larger value within the range than the smaller dimension (the height or width).

[0097] In some examples, the struts 314 can have a diameter or width (which can also be referred to as a thickness) that is in a range of 10–50 µm or 10–40 µm. In some examples, the diameter or width of the struts 314 can be 10–30 µm, 15–25 µm, or about 20 µm. The struts of the additional mesh structures or layers described herein with reference to FIGS.9– 15B can have the same or similar widths to those of struts 314, as described above and further below.

[0098] In some examples, the diameter or width of the struts 314 and / or a size or width 318 of the cells 316 can be specified based on a desired degree of flexibility (for bending during opening and closing of the leaflets) of the leaflet comprising the mesh layer 310, while also reducing a likelihood of degradation of the leaflet under pressure (for example, during opening and closing of the leaflets when the prosthetic valve is implanted in a patient). For example, thinner struts 314 (or struts having a smaller diameter or width) can have more flexibility that thicker or wider struts 314. At the same time, thicker struts 314 can have increased resistance to tearing or degradation than thinner struts 314.

[0099] Further, in some examples, the size of the cells 316, or void spaces or gaps between struts for the additional mesh layers described herein, can be minimized to reduce elongation of the mesh layer, and thus the leaflet 300, in x and y directions of the leaflet 300 (as shown by coordinate axes in FIGS.4 and 5). The x and y directions can be referred to herein as vertical and horizontal directions which define a plane of the leaflet (or mesh layer), for example when the leaflet is lying flat as shown in FIG.4.

[0100] For example, the struts 314 may not elongate under stress (when implanted and operating within a patient’s body), but the gaps, openings, or cells 316 may elongate understress. Thus, reducing the gaps between struts or the size of the cells 316 can reduce overall elongation of the leaflet 300 during operation of a prosthetic valve.

[0101] In some examples, a diameter or width of the struts 314 can be limited or defined by the chosen manufacturing method for forming the mesh layer 310.

[0102] In some examples, the mesh layer 310 (as well as the additional mesh layers described herein, such as mesh layers 410, 510, 610, 710, 750, or 800) can be formed by photolithography.

[0103] In some examples, the mesh layer 310 (as well as the additional mesh layers described herein, such as mesh layers 410, 510, 610, 710, 750, or 800) can be formed by forming a thin sheet by physical vapor deposition (PVD), and then laser cutting (for example, femto laser cutting) the thin sheet to form the struts 314 and cells 316 (or structure of the interconnected struts of any of the other mesh layers described herein).

[0104] In some examples, the metallurgical condition for forming the mesh layer 310 can have a minimum of 5 grains per thickness.

[0105] In some examples, heating may be utilized to close any cracks that may have been formed during the formation of the mesh layer 310.

[0106] In some examples, the mesh layer 310 (before or after laser cutting when using PVD, in some examples) can be strengthened by utilizing suitable techniques, such as compression (for example, between dies) or bombardment with particles (for example, shot peening).

[0107] In some examples, abrasive sand blasting can be also utilized to polish and remove any sharp edges that may be present along the mesh layer 310.

[0108] In some examples, the mesh layer 310 can be electropolished to achieve a macro- level surface smoothness. In some examples, bead blasting can be applied to the mesh layer 310, which may obviate the need for electropolishing.

[0109] Any of the above-described methods for forming the mesh layer 310 can be applied to the additional mesh layers described herein, such as any one of mesh layers 410, 510, 610, 710, 750, or 800.

[0110] The mesh layer 310 (as well as the additional mesh layers described herein) can comprise a metal or metal alloy. In some examples, the mesh layer 310 (as well as the additional mesh layers described herein) can comprise a shape memory material (or shape memory metal or metal alloy). In some examples, the shape memory material is nitinol.

[0111] In some examples, the shape memory metal (such as nitinol) can comprise 50– 52% nickel. In some examples, the shape memory metal (such as nitinol) can comprise 50– 51 %, 50–50.7 %, 50–50.6%, or about 50.5 % nickel.

[0112] In some examples, a nickel concentration of about 50.5 %, or 50–50.7 % can be lower than that of standard medical devices (such as a frame of a prosthetic valve, which may comprise about 50.8 % nickel). When the shape memory metal of the mesh layer (for example, mesh layer 310 or the additional mesh layers described herein) comprises a lower nickel concentration (for example, 50.5 % or 50–50.7 %), the material of the mesh layer can achieve a higher transformation temperature.

[0113] In some examples, the leaflet 300 including the mesh layer 310 (or any of the additional mesh layers described herein, such as mesh layers 410, 510, 610, 710, 750, or 800) can be heated to a temperature that is above body temperature (for example, above 98.6 °F) such that a predictable (or predetermined) folding behavior during crimping (or radially compressing or collapsing) of the prosthetic valve is achieved. In this way, the shape memory properties of the material of the mesh layer can be selected such that a predictable folding behavior for the leaflets is achieved, thereby preventing crumpling, or pinching of the leaflets within a frame of the prosthetic valve.

[0114] In some examples, the material condition of the nitinol of the mesh layer 310 (or any of the additional mesh layers described herein) can be R-phase or martensite. As a result, the mesh layer has an increased fatigue resistance (as compared to a nitinol mesh is the austenite phase).

[0115] FIG.6 shows a cross-sectional view of the mesh layer 310 and FIG.7 shows a detail view of a portion of the cross-section of FIG.6. In particular, FIG.7 shows a cross- section of a strut of the mesh layer 310.

[0116] The mesh layer 310 can be coated or covered with at least one, or one or more, polymeric layers. In some examples, as shown in FIG.7, the struts 314 of the mesh layer 310 can be covered with at least a first polymeric layer 320.

[0117] In some examples, the first polymeric layer 320 is a relatively thin layer formed by dipping the mesh layer 310 in a polymer or combination of polymers.

[0118] In some examples, the first polymeric layer 320 can be formed by dipping the mesh layer 310 in a diluted polymer solution (such as a diluted thermoplastic polyurethane (TPU) solution) to create a bonding layer around the struts 314 of the mesh layer 310.

[0119] In some examples, the first polymeric layer 320 has a first thickness of about 1–10 µm, as shown in FIG.7.

[0120] To allow proper polymer adhesion to the struts 314 of the mesh layer 310, in some examples, the mesh layer 310 can be etched (by using plasma or any other suitable etching procedure) prior to being dipped in the diluted polymer (for example, TPU). In some examples, etching or surface activation of the mesh layer 310 can facilitate adhesiveness over the surface of the mesh layer 310, as well as modifying the surface's electro-negative charge. By having an etched, or not fully smoothed surface, the one or more polymer layers can better adhere to the mesh layer.

[0121] The leaflet 300 can comprise a second polymeric layer 312, as shown in the detail view of FIG.8. As introduced above, the second polymeric layer 312 can be an outermost layer of the leaflet 300. In some examples, the second polymeric layer 312 can be formed over (and coat) the first polymeric layer 320 (as shown in FIG.8).

[0122] In some examples, the leaflet 300 can include only the second polymeric layer 312 and not the first polymeric layer 320 (for example, as shown in FIG.15B).

[0123] The second polymeric layer 312 can be thicker than the first polymeric layer 320. As such, the second polymeric layer 312 can form a majority of a total thickness of the polymeric coating or one or more polymeric layers covering the mesh layer 310 of the leaflet 300.

[0124] In some examples, the second polymeric layer 312 has a second thickness in a range of 4–120 µm or at least 30 µm on each side of the mesh layer 310, which is thicker than the first thickness of the first polymeric layer 320.

[0125] In some examples, the second polymeric layer 312 comprises a polymer, such as TPU.

[0126] The second polymeric layer 312 is a microporous polymeric layer (or microporous polymer layer) that comprises a plurality of fibers or filaments 322. In some examples, the second polymeric layer 312 can be formed by various methods that result in a fibrous, microporous structure that is not woven or knit together. In this way, the second polymeric layer 312 in such examples can be referred to as a non-woven fibrous layer (for example, a textile without interlaced yarns or fibers, or having randomly interlaced yarns or fibers). The microporous filament (or fibrous) structure of the second polymeric layer 312 can be configured to encourage overgrowth of a thin layer of tissue, which can advantageously inhibit clot formation when the resulting leaflets 300 are mounted in a prosthetic valve and implanted in a patient.

[0127] In some examples, the second polymeric layer 312 is formed by electrospinning. As such, the second polymeric layer 312 can be referred to herein as an electrospun polymeric layer.

[0128] In some examples, the second polymeric layer 312 is formed by melt blown spinning or air jet spinning.

[0129] As introduced above, the second polymeric layer 312 can comprise a plurality of filaments 322 (as depicted schematically in FIG.8). In some examples, a filament diameter of the filaments 322 can be in a range of 1–30 µm. In some examples, the filament diameter of the filaments 322 can be in a range of 3–20 µm, 4–10 µm, or about 5 µm.

[0130] In some examples, the second polymeric layer 312 is at least two times thicker than the filament diameter. In some examples, the second polymeric layer 312 can be formed to include up to 4 layers of filaments 322. Thus, for a maximum filament diameter of 30 µm, for example, the second polymeric layer 312 can have a thickness of up to 120 µm.

[0131] The second polymeric layer 312 can have a porosity (or pore size), formed by the filaments (for example, electrospun filaments), in a range of 3–80 µm. As described further below with reference to FIGS.15A and 15B, the porosity of the microporous polymer layer can be specifically tailored to promote a thin layer of tissue growth over the composite leaflet when implanted in a patient (in a prosthetic heart valve). The thin layer of tissue can comprise healthy endothelial cells that prevent a foreign body reaction and fibrotic tissue overgrowth on the composite leaflets, thereby increasing the biocompatibility, mobility, and longevity of the composite leaflets of the prosthetic heart valve.

[0132] In some examples, at least an outer portion of the second polymeric layer 312 has a porosity of 3–80 µm (for example, at least half or a majority portion of the second polymeric layer 312 that is disposed farthest away from the mesh layer). In some examples, the entirety of the second polymeric layer 312 has the porosity in a range of 3–80 µm.

[0133] As shown in FIG.8, in some examples, after forming the second polymeric layer 312 by electrospinning or other, similar techniques (as noted above), the gaps between struts 314, or cells 316, can be filed by the second polymeric layer 312.

[0134] In some examples, the first polymeric layer 320 can have thickness in a range of 3–50 µm or 5–40 µm and be configured as a relatively thick polymeric film (for example, a thin TPU film). For example, in such examples, the first polymeric layer 320 can be formed by dipping the mesh layer 310 in a diluted polymer (for example, TPU) to create a primer layer, while the mesh layer 310 is placed on or over a nonstick surface or film (such as a PTFE film, or other suitable film that will allow easy removal of the formed first polymeric layer 320 therefrom, without sticking to each other). In some examples, this can be repeated for both sides of the mesh layer 310. After creating the first polymeric layer 320, the nonstick surface or film is removed. In some examples, the second polymeric layer 312 can be formed over (or on top of) the polymeric film of the first polymeric layer 320.

[0135] In some examples, the first polymeric layer 320 can be formed by casting on a TPU surface.

[0136] In some examples, the leaflet 300 can comprise additional polymeric layers. For example, the first polymeric layer 320 could comprise two sub-layers, where a first sub-layer is formed by dipping the mesh layer 310 in diluted polymer and then a second sub-layer is formed by positioning the dipped mesh layer 310 against a nonstick surface and further dipping or casting in polymer (for example, TPU) to form a thicker polymeric layer prior to electrospinning. The second polymeric layer 312 can then be formed over the two sub-layers of the first polymeric layer 320. Such a combination of layers can be referred to as three polymeric layers of the leaflet 300.

[0137] When using PVD to form any of the mesh layers described herein, such as mesh layer 310, the laser cut patterns can be designed such that they provide a desired directional strength and flexibility to the final leaflet 300.

[0138] Similarly, when using photolithography to form any of the mesh layers described herein, such as mesh layer 310, the printed patterns can be designed such that they provide a desired directional strength and flexibility to the final leaflet 300.

[0139] For example, FIGS.9–13B show additional examples of mesh layers for prosthetic leaflets. In some examples, the mesh layers shown in FIGS.9–13B can replace the mesh layer 310 in the leaflet 300. In some examples, the mesh layers shown in FIGS.9–13B can comprise one or more of, or all, the polymeric layers described above and shown in FIGS.7 and 8. In some examples, the mesh layers shown in FIGS.9–13B can comprise similar materials, strut thickness, and be formed using the same or similar methods as those described above with reference to FIGS.5–8.

[0140] It should be noted that FIGS.10–12B show a portion of their respective mesh layers, such as a single unit, and do not include cut lines for the sake of clarity. However, these mesh layers can include additional units (for example, to the left, right, and or bottom of the depicted images) that are continuous with the depicted unit.

[0141] Turning first to FIG.9, a mesh layer 410 of a composite leaflet, such as leaflet 300, is shown. The mesh layer 410 can comprise a plurality of interconnected struts 414 which form a plurality of cells 416 (or gaps, openings, or void spaces). In some examples, as shown in FIG.9, each cell 416 (or sub-structure of the mesh layer 410) can have a hexagonal shape formed by six connected struts 414. As such, the mesh layer 410 can have a honeycomb structure.

[0142] In some examples, similar mesh layers can be formed with interconnected struts forming cells of different shapes, such as octagonal cells, triangular cells, or the like.

[0143] In some examples, a width 418 and / or height 419 of the cells 416 can be in a range of 0.3 – 3 mm.

[0144] FIG.10 shows a portion (or cell, for example) of an exemplary mesh layer 510 of a composite leaflet, such as leaflet 300. The mesh layer 510 can comprise a plurality of interconnected struts 514 which form a plurality of void spaces or openings 516 (which can also be referred to herein as cells).

[0145] The unit of the mesh layer 510 can have a zigzag patten that is configured to provide structural flexibility (specifically, bending flexibility without tension flexibility or elongation) to the leaflet, without needing to thin the material of the struts 514 too much. For example, the struts 514 may have a thickness that is on the higher end of the range of 10–40 µm (as defined above for the struts 314), such as 20–30 µm.

[0146] It should be noted that FIG.10 shows a single unit or cell of a mesh layer 510 for a leaflet, and the unit shown in FIG.10 can be repeated (for example, to the left, right, and / or bottom of the unit shown in FIG.10) to form a complete mesh layer that is shaped to form the leaflet (for example, leaflet 300).

[0147] The spacing or gaps 518 between adjacent struts 514, or the size of the openings 516 formed therebetween, can vary for the mesh layer 510. For example, the gaps 518 can be larger between struts around the periphery of the cell shown in FIG.10, and smaller between struts 514 in a more central region of the cell.

[0148] FIG.11 shows a portion (or cell, for example) of an exemplary mesh layer 610 of a composite leaflet, such as leaflet 300. The mesh layer 610 can comprise a plurality of interconnected struts 614 which form a plurality of void spaces or openings 616.

[0149] It should be noted that FIG.11 shows a single unit or cell of a mesh layer 610 for a leaflet, and the unit shown in FIG.11 can be repeated (for example, to the left, right, and / or bottom of the unit shown in FIG.11) to form a complete mesh layer that is shaped to form the leaflet (for example, leaflet 300).

[0150] The spacing or gaps 618 between adjacent struts 614, or the size of the openings 616 formed therebetween, can vary for the mesh layer 610.

[0151] It should be noted that although the struts 614 are depicted as thin lines in FIG. 11, the struts 614 can have a thickness that is the same or similar to the struts 314 of mesh layer 310, as described above.

[0152] FIG.12A shows a portion (a unit or cell, for example) of an exemplary mesh layer 710 of a composite leaflet, such as leaflet 300. The mesh layer 710 can comprise a plurality of interconnected struts 714 which form a plurality of void spaces or openings 716, 718.

[0153] It should be noted that FIG.12A shows a single unit or cell (which can be referred to herein as a mesh layer unit) of a mesh layer 710 for a leaflet, and the unit shown in FIG. 12A can be repeated (for example, to the left, right, and / or bottom of the unit shown in FIG. 12A) to form the complete mesh layer that is shaped to form the leaflet (for example, leaflet 300).

[0154] The struts 714 are arranged in a triangular zigzag type of pattern which results in triangular openings 716 which are configured as open cells with a gap 720 between two of the three struts 714 forming each triangular opening 716. A larger, central opening 718 is formed in a central region of the cell.

[0155] In some examples, a widest dimension of each triangular opening 716 can be less than 1 mm.

[0156] As shown in FIG.12A, the gaps 720 are arranged in the x and y directions and are very small. For example, the gaps 720 can be as small as possible for manufacturing tolerances when forming the mesh layer 710 by PVD and laser cutting or by photolithography.

[0157] In some examples, the gaps 720 can be in a range of 0.05 to 0.3 mm.

[0158] As a result of minimizing a size of the gaps 720 that are arranged in the x and y directions, when the leaflet, and thus the mesh layer 710, is pulled in the x and / or y directions, elongation of the leaflet in those directions will be minimized. This can prevent the leaflet from elongating or deforming during radially expanding the prosthetic valve and / or during operation of the prosthetic valve when implanted in a body of a patient. In this way, the structure of the mesh layer 710 can allow the leaflet (for example, leaflet 300) to bend (for example, about a z axis), while also reducing or preventing elongation in the x and y directions.

[0159] It should be noted that although the struts 714 are depicted as thin lines in FIGS. 12A and 12B, the struts 714 can have a thickness that is the same or similar to the struts 314 of mesh layer 310, as described above.

[0160] In some examples, the intersection points between two struts 714 (such as the edges of the triangle) can be rounded or made less sharp than shown in FIG.12A (and similarly FIG.12B).

[0161] In some examples, the struts 714 (or any of the other struts described herein) can be rounded or cylindrical (for example, having a round cross-section having a diameter).

[0162] FIG.12B shows a variation of the mesh layer 710. For example, FIG.12B shows a portion (a unit or cell, for example) of an exemplary mesh layer 750 of a composite leaflet,such as leaflet 300. The unit of the mesh layer 750 comprises the plurality of interconnected struts 714 which form a plurality of void spaces or openings 716, 722. The mesh layer 750 is the same as the mesh layer 710, except it includes two additional, opposing rows of zigzagging struts 714 inside the central opening 718, thereby creating a smaller opening 722 between the two rows.

[0163] This results in a strut 714 disposed in parallel with, and adjacent to, a gap 720, as indicated in FIG.12A by the dashed circled regions 724. As a result, elongation of the mesh layer 760 in the y direction is further prevented. This can increase and integrity of the leaflet in which the mesh layer 750 is arranged.

[0164] FIG.13A shows an exemplary mesh layer 800 of a composite leaflet, such as leaflet 300. The mesh layer 800 can comprise a plurality of interconnected struts 814 which form a plurality of void spaces or openings 816, 818. The interconnected struts 814 can be arranged to form vertically and horizontally oriented struts (vertical struts 810 and horizontal struts 812, as shown in the detail view of FIG.13B) that are configured for bending and curved struts 820 that are interconnected with small gaps 822 therebetween such that elongation of the mesh layer 800 in the vertical and horizontal directions (or y and x direction, as depicted in FIG.13A) is prevented or reduced.

[0165] For example, the mesh layer 800 can comprise a plurality of repeating mesh layer units 802 (one unit 802, as well as a portion of connecting units, are shown in FIG.13B) that each comprise two opposing vertical struts 810, two opposing horizontal struts 812, and eight curved struts 820 which form a cross-shaped structure having an opening 818 shaped as a four-pointed flower-type shape. As shown in FIG.13B, each curved strut 820 connects to one vertical strut 810 or horizontal strut 812 and an end of an adjacent curved strut 820. The gaps 822 are formed between ends of two adjacent curved struts 820 that connect to the same vertical strut 810 or horizontal strut 812.

[0166] Four adjacent and interconnected units 802 can form an opening 816 therebetween.

[0167] In some examples, a width or diameter of the struts 814 can be in a range of 10– 50 µm, 10–40 µm, 15–25 µm, 20–30 µm, or about 20 µm.

[0168] In some examples, a length of the vertical struts 810 and horizontal struts 812 can be in a range of 0.3 – 0.5 mm, 0.35 – 0.45 mm, or about 0.4 mm.

[0169] Thus, the gaps 822 can be relatively small such that elongation in the x and y directions (or horizontal and vertical directions, or the directions that the horizontal struts 812 and vertical struts 810 extend, respectively) is reduced or prevented. For example, once the mesh layer 800 is embedded in TPU (by the one or more polymeric layers describedherein), the gaps 822 will be filed with polymer (for examples, filaments of the polymer) and will not elongate (or increase in size) easily. Thus, when forces in the x or y directions are applied on the composite leaflet when implanted in a patient’s body, the leaflet can be prevented from elongating in these directions.

[0170] Instead, the composite leaflet comprising the mesh layer 800 can be configured to bend, thereby allowing the leaflet to open and close during operating of the prosthetic valve. For example, bending is facilitated by the vertical struts 810 and horizontal struts 812 being exposed to twisting (or torque). For example, the vertical struts 810 and horizontal struts 812 can allow bending of adjacent curved struts 820 about an axis defined along the vertical struts 810 or horizontal struts 812.

[0171] FIG.14 shows an exemplary arrangement of the mesh layer 800 of FIGS.13A and 13B in a composite leaflet 850 (partial leaflet shown in FIG.14). In some examples, the leaflet 850 can be shaped the same or similar to the leaflet 300 of FIG.4. It should be noted that the shape and size of the leaflet 850 shown in FIG.850 is exemplary, and the methods and structures of the composite leaflet 850 described herein can be applied to leaflets having various shapes and / or sizes.

[0172] The leaflet 850 comprises a main body 852 with a cusp edge portion 854, an outflow edge portion 856, and two commissure tabs 858 (or sides or tab portions) extending from the main body 852 on opposite sides of the main body 852 of the leaflet 850.

[0173] In some examples, the mesh layer units 802 can be arranged, end-to-end, along the cusp edge portion 854 of the leaflet 850. As such, the mesh layer 800 in the leaflet 850 can form a curved pattern along at least the cusp edge portion 854. In some examples, one strut 810 of each mesh layer unit 802 along the cusp edge portion 854 can be disposed adjacent to the cusp edge of the cusp edge portion 854.

[0174] In some examples, the one strut 810 of each mesh layer unit 802 can be arranged parallel to a line tangent to the portion of the cusp edge disposed adjacent to the one strut 810.

[0175] In some examples, the one strut 810 of the mesh layer unit 802 arranged at the commissure tab 858 can be aligned with an end of the commissure tab 858 that connects to the main body 852.

[0176] In some examples, each mesh layer unit 802 can comprise one or more apertures 860 configured as stitching points for receiving a suture or other fastener for attaching the cusp edge portion 854 of the leaflet 850 to a frame and / or connecting skirt (for example, inner skirt 16) sof a prosthetic valve.

[0177] In some examples, the one or more apertures can be disposed in a strut 810 of each mesh layer unit 802. In some examples, the one or more apertures can be disposed in a junction between a strut 810 and strut 820 of each mesh layer unit 802.

[0178] In some examples, each mesh layer unit 802 can comprise two apertures 860 that are spaced apart from one another.

[0179] In some examples, the struts of the mesh layer units 802 may not include apertures, but the interior corners between the strut 810 and struts 820 that are disposed adjacent to the cusp edge can form anchors for sutures or other fasteners for attaching the cusp edge portion 854 of the leaflet 850 to a frame and / or connecting skirt of a prosthetic valve.

[0180] In this way, the mesh layer units 802 of the leaflet 850 can form anchoring points for sutures or fasteners along the cusp edge portion 854 of the leaflet 850. As such, the mesh layer 800 of the leaflet 850 can provide reinforced anchoring points for attaching the leaflet 850 to the remainder of the prosthetic valve (for example, the frame).

[0181] The mesh layer units 802 can continue in a similar fashion (as those along the cusp edge portion 854) across the main body 852 of the leaflet 850. In some examples, the line of mesh layer units 802 can continue along the outflow edge portion 856.

[0182] FIGS.15A and 15B show exemplary cross-sectional views of a portion of the mesh layer 800 of FIG.13B in the composite leaflet 850 which has been implanted in a patient, and thus a resulting tissue layer 862 is formed over the second polymeric layer 312. As such, FIGS.15A and 15B show cross-sectional views of two struts 820 of a mesh layer unit 802 surrounded by various polymeric layers of the leaflet 850 and a thin tissue layer 862.

[0183] In some examples, as shown in FIG.15A, the struts 820 (and the rest of the struts of the mesh layer until 802 of the mesh layer 800) can be surrounded by a first polymeric layer 320 (as described above). The first polymeric layer is surrounded by a second polymeric layer, or the microporous polymeric layer 312 which comprises a plurality of filaments 322 (as described above). The second polymeric layer 312 fills the gaps (for example, openings 816 and 818 shown in FIG.13A) between struts of the mesh layer 800 and forms a layer on both sides of the mesh layer 800.

[0184] In some examples, as shown in FIG.15B, the leaflet may not include the first polymeric layer 320, and instead the microporous polymeric layer 312 can surround the struts of the mesh layer 800 and be disposed in the gaps between the struts (for example, openings 816 and 818 shown in FIG.13A).

[0185] As introduced above, the microporous polymeric layer 312 can be configured (or structured or formed) to encourage overgrowth of a thin layer of healthy tissue (tissue layer 862), which can advantageously inhibit a foreign body response and fibrotic tissue overgrowth when the resulting leaflets 850 are mounted in a prosthetic valve and implanted and operating in a patient. The tissue layer 862 can comprise healthy endothelial cells (or neointima with healthy endothelial cells over top) that minimize or prevent fibrotic tissue overgrowth. As a result, a thickness of the tissue layer 862 can remain relatively thin (for example, 10 µm, 20 µm, 30 µm, 40 µm, 50 µm, 60 µm, 70 µm, 80 µm, 90 µm, 100 µm, or in a range of 10–60 µm or 10–100 µm) such that the leaflets can bend and open and close during operation in the body with little to no resistance.

[0186] The tissue layer 862 can grow or form over (and, in some examples, within) the microporous polymeric layer after a predetermined period of time following implantation of the prosthetic valve including the leaflets in a subject (for example, a human or animal).

[0187] To achieve such a tissue layer 862 of healthy endothelial cells, the microporous polymeric layer 312 can have a porosity (or pore size), formed by the filaments 322, in a range of 3–80 µm. In this way, the microporous polymeric layer 312 can serve as a scaffold for healthy tissue growth within the pores of the microporous polymeric layer 312 and on an outside of the microporous polymeric layer 312. The porosity of the microporous polymeric layer 312 can be specifically tailored to promote a relatively thin, healthy layer of tissue growth (tissue layer 862) over the composite leaflet when implanted in a patient (in a prosthetic heart valve), thereby increasing the biocompatibility, mobility, and longevity of the composite leaflets of the prosthetic heart valve.

[0188] For example, the microporous polymeric layer 312 can promote healthy endothelialization and / or reduce foreign body reaction with a prosthetic valve including the composite leaflets (for example, leaflets 850) is implanted in the body. The microporous polymeric layer 312 can improve endothelial cell adhesion, migration, and / or proliferation. Endothelialization can reduce hemolysis, reduce thrombosis and / or promote anticoagulation, reduce inflammation, or any combination thereof.

[0189] In some examples, to allow for neovascularization of the microporous polymeric layer 312, the porosity of the microporous polymeric layer 312 can be in a range of 30–80 µm.

[0190] In some examples, to allow for cell migration but not neovascularization within the microporous polymeric layer 312, the porosity of the microporous polymeric layer 312 can be in a range of 3–20 µm.

[0191] In some examples, to allow for formation of the tissue layer 862 but without cell migration within the microporous polymeric layer 312, the porosity of the microporous polymeric layer 312 can be in a range of 2–3 µm.

[0192] In some examples, the porosity of the microporous polymeric layer 312 can be in a range of 2–80 µm, 3–80 µm, 3–60 µm, 5–20 µm, 50–80 µm, or 3–30 µm to achieve the tissue layer 862.

[0193] As a result, the microporous polymeric layer 312, having the porosity described above, can allow for a controlled amount of tissue growth (tissue layer 862) over the composite leaflets (for example, leaflets 850).

[0194] The composite leaflets described herein provide prosthetic leaflets for prosthetic heart valves that are robust and have increased longevity, are flexible, and are biocompatible. For example, the mesh layer of the composite leaflets provide flexibility to the leaflets such that they can bend when radially compressing and expanding the prosthetic valve, and during operation when implanted in a patient’s body, while also providing increased resistance to elongation in x and y directions in a plane of the leaflet (and increased longevity). Further, the microporous polymeric layer(s) of the composite leaflets can provide the leaflets with a surface texture that encourages a thin layer of tissue growth (without fibrotic tissue overgrowth), thereby resulting in a synthetic, composite leaflet that can be both structurally and biologically viable. Delivery Techniques

[0195] For implanting a prosthetic valve within the native aortic valve via a transfemoral delivery approach, the prosthetic valve is mounted in a radially compressed state along the distal end portion of a delivery apparatus. The prosthetic valve and the distal end portion of the delivery apparatus are inserted into a femoral artery and are advanced into and through the descending aorta, around the aortic arch, and through the ascending aorta. The prosthetic valve is positioned within the native aortic valve and radially expanded (for example, by inflating a balloon, actuating one or more actuators of the delivery apparatus, or deploying the prosthetic valve from a sheath to allow the prosthetic valve to self-expand). Additionally and / or alternatively, a prosthetic valve can be implanted within the native aortic valve in a transapical procedure, whereby the prosthetic valve (on the distal end portion of the delivery apparatus) is introduced into the left ventricle through a surgical opening in the chest and the apex of the heart and the prosthetic valve is positioned within the native aortic valve. Additionally and / or alternatively, in a transaortic procedure, a prosthetic valve (on the distal end portion of the delivery apparatus) is introduced into the aorta through a surgical incision in the ascending aorta, such as through a partial J-sternotomy or right parasternal mini-thoracotomy, and then advanced through the ascending aorta toward the native aortic valve.

[0196] For implanting a prosthetic valve within the native mitral valve via a transseptal delivery approach, the prosthetic valve is mounted in a radially compressed state along the distal end portion of a delivery apparatus. The prosthetic valve and the distal end portion of the delivery apparatus are inserted into a femoral vein and are advanced into and through the inferior vena cava, into the right atrium, across the atrial septum (through a puncture made in the atrial septum), into the left atrium, and toward the native mitral valve. Additionally and / or alternatively, a prosthetic valve can be implanted within the native mitral valve in a transapical procedure, whereby the prosthetic valve (on the distal end portion of the delivery apparatus) is introduced into the left ventricle through a surgical opening in the chest and the apex of the heart and the prosthetic valve is positioned within the native mitral valve.

[0197] For implanting a prosthetic valve within the native tricuspid valve, the prosthetic valve is mounted in a radially compressed state along the distal end portion of a delivery apparatus. The prosthetic valve and the distal end portion of the delivery apparatus are inserted into a femoral vein and are advanced into and through the inferior vena cava, and into the right atrium, and the prosthetic valve is positioned within the native tricuspid valve. A similar approach can be used for implanting the prosthetic valve within the native pulmonary valve or the pulmonary artery, except that the prosthetic valve is advanced through the native tricuspid valve into the right ventricle and toward the pulmonary valve / pulmonary artery.

[0198] Another delivery approach is a transatrial approach whereby a prosthetic valve (on the distal end portion of the delivery apparatus) is inserted through an incision in the chest and an incision made through an atrial wall (of the right or left atrium) for accessing any of the native heart valves. Atrial delivery can also be made intravascularly, such as from a pulmonary vein. Still another delivery approach is a transventricular approach whereby a prosthetic valve (on the distal end portion of the delivery apparatus) is inserted through an incision in the chest and an incision made through the wall of the right ventricle (typically at or near the base of the heart) for implanting the prosthetic valve within the native tricuspid valve, the native pulmonary valve, or the pulmonary artery.

[0199] In all delivery approaches, the delivery apparatus can be advanced over a guidewire previously inserted into a patient’s vasculature. Moreover, the disclosed delivery approaches are not intended to be limited. Any of the prosthetic valves disclosed herein can be implanted using any of various delivery procedures and delivery devices known in the art.

[0200] Any of the systems, devices, apparatuses, etc. herein can be sterilized (for example, with heat / thermal, pressure, steam, radiation, and / or chemicals, etc.) to ensure they are safe for use with patients, and any of the methods herein can include sterilization of the associated system, device, apparatus, etc. as one of the steps of the method. Examples of heat / thermal sterilization include steam sterilization and autoclaving. Examples of radiation for use in sterilization include, without limitation, gamma radiation, ultra-violet radiation, and electron beam. Examples of chemicals for use in sterilization include, without limitation, ethylene oxide, hydrogen peroxide, peracetic acid, formaldehyde, and glutaraldehyde. Sterilization with hydrogen peroxide may be accomplished using hydrogen peroxide plasma, for example. Additional Examples of the Disclosed Technology

[0201] In view of the above-described implementations of the disclosed subject matter, this application discloses the additional examples enumerated below. It should be noted that one feature of an example in isolation or more than one feature of the example taken in combination and, optionally, in combination with one or more features of one or more further examples are further examples also falling within the disclosure of this application.

[0202] Example 1. A prosthetic heart valve comprising: a frame; and a plurality of leaflets mounted inside of the frame, wherein each leaflet is a composite leaflet comprising at least one polymeric layer and at least one mesh layer, wherein at least an outer portion of the at least one polymeric layer has a porosity of 3–80 µm.

[0203] Example 2. The prosthetic heart valve of any example herein, particularly example 1, wherein the at least one mesh layer comprises a metal alloy.

[0204] Example 3. The prosthetic heart valve of any example herein, particularly either example 1 or example 2, wherein the at least one mesh layer comprises a shape memory material.

[0205] Example 4. The prosthetic heart valve of any example herein, particularly example 3, wherein the shape memory material is nitinol, and wherein the nitinol comprises 50–50.7% nickel.

[0206] Example 5. The prosthetic heart valve of any example herein, particularly any one of examples 1–4, wherein the at least one polymeric layer comprises TPU.

[0207] Example 6. The prosthetic heart valve of any example herein, particularly any one of examples 1–5, wherein the at least one polymeric layer includes one or more polymeric layers disposed over a first side of the at least one mesh layer, a second side of the at least one mesh layer, and within void spaces formed by struts of the at least one mesh layer.

[0208] Example 7. The prosthetic heart valve of any example herein, particularly any one of examples 1–5, wherein the at least one mesh layer comprises a plurality of interconnected struts, and wherein the at least one polymeric layer comprises a first polymeric layer disposed around and covering each strut of the plurality of interconnected struts.

[0209] Example 8. The prosthetic heart valve of any example herein, particularly example 7, wherein the at least one polymeric layer comprises a second polymeric layer disposed over the first polymeric layer, the second polymeric layer comprising a plurality of polymeric filaments formed into a microporous polymer layer, and wherein the second polymeric layer has the porosity of 3–80 µm.

[0210] Example 9. The prosthetic heart valve of any example herein, particularly example 8, wherein the plurality of polymeric filaments has a filament diameter in a range of 1–30 µm, and wherein the second polymeric layer comprises at least four layers of polymeric filaments.

[0211] Example 10. The prosthetic heart valve of any example herein, particularly either example 8 or example 9, wherein the second polymeric layer is thicker than the first polymeric layer.

[0212] Example 11. The prosthetic heart valve of any example herein, particularly any one of examples 1–10, wherein the at least one mesh layer comprises a plurality of interconnected struts forming a plurality of openings in the mesh layer.

[0213] Example 12. The prosthetic heart valve of any example herein, particularly example 11, wherein the plurality of interconnected struts is arranged into a plurality of mesh layer units, wherein each mesh layer unit comprises two opposing vertical struts, two opposing horizontal struts, and eight curved struts which form an opening shaped as a four- pointed flower-type shape.

[0214] Example 13. The prosthetic heart valve of any example herein, particularly example 12, wherein each curved strut connects to one vertical strut or horizontal strut and an end of an adjacent curved strut.

[0215] Example 14. The prosthetic heart valve of any example herein, particularly example 13, wherein a gap is formed between ends of two adjacent curved struts that connect to the same vertical strut or horizontal strut.

[0216] Example 15. The prosthetic heart valve of any example herein, particularly any one of examples 11–14, wherein the largest dimension of each opening of the plurality of openings is 0.3 – 3 mm.

[0217] Example 16. A method of implanting the prosthetic heart valve of any example herein, particularly any one of examples 1–15, wherein the method includes, after a predetermined period of time following implantation in a subject, growing a tissue layer over the outer portion of the at least one polymeric layer, wherein the tissue layer comprises healthy endothelial cells.

[0218] Example 17. The method of any example herein, particularly example 16, wherein the tissue layer has a thickness in a range of 10–100 µm.

[0219] Example 18. A composite leaflet for a prosthetic heart valve, comprising: a mesh layer comprising a plurality of interconnected struts that is configured to enable bending without elongation of the leaflet, wherein the plurality of interconnected struts forms a plurality of openings in the mesh layer; and at least one polymeric layer surrounding the mesh layer and occupying the plurality of openings in the mesh layer, between the plurality of interconnected struts.

[0220] Example 19. The composite leaflet of any example herein, particularly example 18, wherein the plurality of interconnected struts of the mesh layer comprises a shape memory material.

[0221] Example 20. The composite leaflet of any example herein, particularly example 19, wherein the shape memory material is nitinol, and wherein the nitinol comprises 50– 50.6% nickel.

[0222] Example 21. The compositive leaflet of any example herein, particularly any one of examples 18–20, wherein at least an outer portion of the at least one polymeric layer has a porosity in a range of 3–80 µm.

[0223] Example 22. The composite leaflet of any example herein, particularly any one of examples 18–21, where the at least polymeric layer comprises a first polymeric layer surrounding the plurality of interconnected struts and a second polymeric layer covering the first polymeric layer, wherein the second polymeric layer is thicker than the first polymeric layer, and wherein at least the second polymeric layer is disposed within the plurality of openings.

[0224] Example 23. The composite leaflet of any example herein, particularly example 22, wherein the first polymeric layer comprises a thin film of a polymer, and wherein the second polymeric layer comprises a plurality of filaments of the polymer.

[0225] Example 24. The composite leaflet of any example herein, particularly example 23, wherein the second polymeric layer comprises a plurality of electrospun filaments and has a porosity of 3–80 µm.

[0226] Example 25. The composite leaflet of any example herein, particularly either example 23 or example 24, wherein the polymer is TPU.

[0227] Example 26. The composite leaflet of any example herein, particularly any one of examples 18–25, wherein the plurality of interconnected struts is arranged in a zigzag pattern that is configured to reduce elongation of the leaflet in x and y directions that define a plane of the leaflet.

[0228] Example 27. The composite leaflet of any example herein, particularly any one of examples 18–25, wherein the plurality of interconnected struts is arranged into a plurality of mesh layer units, each mesh layer unit comprising two opposing vertical struts, two opposing horizontal struts, and eight curved struts which form an opening shaped as a four- pointed flower-type shape.

[0229] Example 28. The composite leaflet of any example herein, particularly example 27, wherein each curved strut connects to one vertical strut or horizontal strut and an end of an adjacent curved strut.

[0230] Example 29. A prosthetic heart valve, comprising: a frame; and at least one leaflet mounted on an inside of the frame, wherein the at least one leaflet is the leaflet of any example herein, particularly any one of examples 18–28.

[0231] Example 30. A method for forming a composite leaflet for a prosthetic heart valve, comprising: forming a mesh layer comprising interconnected struts, the interconnected struts defining openings in the mesh layer; coating the mesh layer with a polymer to form a first polymeric layer around the interconnected struts of the mesh layer; and electrospinning a polymer over the first polymeric layer to form a second polymeric layer, wherein the second polymeric layer has a porosity of 3–80 µm.

[0232] Example 31. The method of any example herein, particularly example 30, wherein forming the mesh layer comprises forming a thin sheet by physical vapor deposition (PVD) and laser cutting the thin sheet to form the interconnected struts and openings.

[0233] Example 32. The method of any example herein, particularly example 30, wherein forming the mesh layer comprises forming the interconnected struts using photolithography.

[0234] Example 33. The method of any example herein, particularly any one of examples 30–32, wherein the interconnected struts comprise a shape memory metal.

[0235] Example 34. The method of any example herein, particularly example 33, further comprising heat treating the mesh layer to a temperature that is above bodytemperature such that the composite leaflet folds in a predetermined way during radially collapsing the prosthetic valve into a radially collapsed configuration.

[0236] Example 35. The method of any example herein, particularly any one of examples 30–34, wherein coating the mesh layer with a polymer to form the first polymeric layer includes dipping the mesh layer in the polymer to form a thin film around the interconnected struts.

[0237] Example 36. The method of any example herein, particularly any one of examples 30–35, further comprising, prior to electrospinning, coating the first polymeric layer with a third polymeric layer, wherein the third polymeric layer is thicker than the first polymeric layer.

[0238] Example 37. The method of any example herein, particularly any one of examples 30–36, wherein the second polymeric layer is thicker than the first polymeric layer.

[0239] Example 38. The method of any example herein, particularly any one of examples 30–37, wherein electrospinning the polymer over the first polymeric layer to form the second polymeric layer includes electrospinning the polymer into four layers of filaments to form the second polymeric layer, and wherein the second polymeric layer is disposed within the openings in the mesh layer.

[0240] Example 39. The method of any example herein, particularly any one of examples 30–38, wherein the polymer of the first polymeric layer is TPU, and wherein the polymer of the second polymeric layer is TPU.

[0241] Example 40. A prosthetic heart valve comprising: a frame; and a plurality of leaflets mounted inside of the frame, wherein each leaflet is a composite leaflet comprising: a mesh layer comprising interconnected struts; a first polymeric layer surrounding the struts of the mesh layer; and a second polymeric layer disposed around the first polymeric layer, wherein the second polymeric layer is a microporous polymer layer having a porosity of 3– 80 µm, and wherein the second polymeric layer is thicker than the first polymeric layer.

[0242] Example 41. The prosthetic heart valve of any example herein, particularly example 40, wherein the second polymeric comprises a plurality of filaments having a filament diameter of 1–30 µm.

[0243] Example 42. The prosthetic heart valve of any example herein, particularly either example 40 or example 41, wherein the mesh layer comprises a shape memory metal.

[0244] Example 43. The prosthetic heart valve of any example herein, particularly any one of examples 40–42, wherein the interconnected struts are arranged to form openingstherebetween, and wherein a polymer of one or more of the first polymeric layer and the second polymeric layer is disposed within the openings.

[0245] Example 44. The prosthetic heart valve of any example herein, particularly any one of examples 40–43, wherein the first and second polymeric layers comprise TPU.

[0246] Example 45. The prosthetic heart valve of any example herein, particularly any one of examples 40–44, wherein the interconnected struts are arranged to form vertically and horizontally oriented struts that are configured for bending and curved struts that are interconnected with small gaps therebetween such that elongation of the mesh layer in the vertical and horizontal directions is prevented.

[0247] Example 46. The prosthetic heart valve of any example herein, particularly any one of examples 40–45, wherein the second polymeric layer has a porosity of 3–20 µm.

[0248] Example 47. The prosthetic heart valve of any example herein, particularly any one of examples 40–45, wherein the second polymeric layer has a porosity of 5–20 µm.

[0249] Example 48. The prosthetic heart valve of any example herein, particularly any one of examples 40–45, wherein the second polymeric layer has a porosity of 30–80 µm.

[0250] Example 49. A method of implanting the prosthetic heart valve of any example herein, particularly any one of examples 40–48, wherein the method includes, after a predetermined period of time following implantation in a subject, growing a tissue layer over the outer portion of the at least one polymeric layer, wherein the tissue layer comprises healthy endothelial cells.

[0251] Example 50. The method of any example herein, particularly example 49, wherein, after the predetermined period of time, the tissue layer has a thickness in a range of 10–100 µm.

[0252] Example 51. A prosthetic heart valve comprising: a frame; and a plurality of leaflets mounted inside of the frame, wherein each leaflet is a composite leaflet comprising at least one microporous polymeric layer and at least one mesh layer, wherein the microporous polymeric layer is configured to induce a layer of tissue having a predetermined maximum thickness to form on the microporous polymer layer.

[0253] Example 52. The prosthetic heart valve of any example herein, particularly example 51, wherein the layer of tissue comprises endothelial cells.

[0254] Example 53. The prosthetic heart valve of any example herein, particularly either example 51 or example 52, wherein the at least one microporous polymeric layer has a porosity of 3–80 µm.

[0255] Example 54. The prosthetic heart valve of any example herein, particularly any one of examples 51–53, wherein the mesh layer comprises nitinol.

[0256] Example 55. The prosthetic heart valve of any example herein, particularly example 54, wherein the nitinol comprises 50–50.6% nickel.

[0257] Example 56. The prosthetic heart valve of any example herein, particularly any one of examples 51–55, wherein the at least one microporous polymeric layer comprises TPU.

[0258] Example 57. The prosthetic heart valve of any example herein, particularly any one of examples 51–56, wherein the at least one microporous polymeric layer includes one or more polymeric layers disposed over a first side of the at least one mesh layer, a second side of the at least one mesh layer, and within void spaces formed by struts of the at least one mesh layer.

[0259] Example 58. The prosthetic heart valve of any example herein, particularly any one of examples 51–57, wherein the predetermined maximum thickness is 100 µm.

[0260] Example 59. A prosthetic heart valve or leaflet of any one of examples 1–58, wherein the prosthetic heart valve or leaflet is sterilized.

[0261] Example 60. A method comprising sterilizing the prosthetic heart valve, apparatus, and / or assembly of any example.

[0262] The features described herein with regard to any example can be combined with other features described in any one or more of the other examples, unless otherwise stated. For example, any one or more of the features of one leaflet can be combined with any one or more features of another leaflet. As another example, any one or more features of one mesh layer can be combined with any one or more features of another mesh layer.

[0263] In view of the many possible ways in which the principles of the disclosure may be applied, it should be recognized that the illustrated configurations depict examples of the disclosed technology and should not be taken as limiting the scope of the disclosure nor the claims. Rather, the scope of the claimed subject matter is defined by the following claims and their equivalents.

Claims

WE CLAIM:

1. A prosthetic heart valve comprising: a frame; and a plurality of leaflets mounted inside of the frame, wherein each leaflet is a composite leaflet comprising at least one polymeric layer and at least one mesh layer, wherein at least an outer portion of the at least one polymeric layer has a porosity of 3–80 µm.

2. The prosthetic heart valve of claim 1, wherein the at least one mesh layer comprises a metal alloy.

3. The prosthetic heart valve of either claim 1 or claim 2, wherein the at least one mesh layer comprises a shape memory material.

4. The prosthetic heart valve of claim 3, wherein the shape memory material is nitinol, and wherein the nitinol comprises 50–50.7% nickel.

5. The prosthetic heart valve of any one of claims 1–4, wherein the at least one polymeric layer comprises TPU.

6. The prosthetic heart valve of any one of claims 1–5, wherein the at least one polymeric layer includes one or more polymeric layers disposed over a first side of the at least one mesh layer, a second side of the at least one mesh layer, and within void spaces formed by struts of the at least one mesh layer.

7. The prosthetic heart valve of any one of claims 1–5, wherein the at least one mesh layer comprises a plurality of interconnected struts, and wherein the at least one polymeric layer comprises a first polymeric layer disposed around and covering each strut of the plurality of interconnected struts.

8. The prosthetic heart valve of claim 7, wherein the at least one polymeric layer comprises a second polymeric layer disposed over the first polymeric layer, the second polymeric layer comprising a plurality of polymeric filaments formed into a microporous polymer layer, and wherein the second polymeric layer has the porosity of 3–80 µm.

9. A method of implanting the prosthetic heart valve of any one of claims 1–8, wherein the method includes, after a predetermined period of time following implantation in a subject, growing a tissue layer over the outer portion of the at least one polymeric layer, wherein the tissue layer comprises healthy endothelial cells.

10. The method of claim 9, wherein the tissue layer has a thickness in a range of 10–100 µm.

11. A composite leaflet for a prosthetic heart valve, comprising:a mesh layer comprising a plurality of interconnected struts that is configured to enable bending without elongation of the leaflet, wherein the plurality of interconnected struts forms a plurality of openings in the mesh layer; and at least one polymeric layer surrounding the mesh layer and occupying the plurality of openings in the mesh layer, between the plurality of interconnected struts.

12. The composite leaflet of claim 11, wherein the plurality of interconnected struts of the mesh layer comprises a shape memory material.

13. The compositive leaflet of either claim 11 or claim 12, wherein at least an outer portion of the at least one polymeric layer has a porosity in a range of 3–80 µm.

14. The composite leaflet of any one of claims 11–13, wherein the plurality of interconnected struts is arranged into a plurality of mesh layer units, each mesh layer unit comprising two opposing vertical struts, two opposing horizontal struts, and eight curved struts which form an opening shaped as a four-pointed flower-type shape.

15. A method for forming a composite leaflet for a prosthetic heart valve, comprising: forming a mesh layer comprising interconnected struts, the interconnected struts defining openings in the mesh layer; coating the mesh layer with a polymer to form a first polymeric layer around the interconnected struts of the mesh layer; and electrospinning a polymer over the first polymeric layer to form a second polymeric layer.

16. The method of claim 15, wherein the second polymeric layer has a porosity of 3–80 µm.

17. The method of either claim 15 or claim 16, wherein forming the mesh layer comprises forming a thin sheet by physical vapor deposition (PVD) and laser cutting the thin sheet to form the interconnected struts and openings.

18. The method of either claim 15 or claim 16, wherein forming the mesh layer comprises forming the interconnected struts using photolithography.

19. The method of any one of claims 15–18, wherein the interconnected struts comprise a shape memory metal, and further comprising heat treating the mesh layer to a temperature that is above body temperature such that the composite leaflet folds in a predetermined way during radially collapsing the prosthetic valve into a radially collapsed configuration.

20. The method of any one of claims 15–19, wherein the second polymeric layer is thicker than the first polymeric layer.

21. The method of any one of claims 15–20, wherein electrospinning the polymer over the first polymeric layer to form the second polymeric layer includes electrospinning the polymer into four layers of filaments to form the second polymeric layer, and wherein the second polymeric layer is disposed within the openings in the mesh layer.

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