WO2025235591A1

WO2025235591A1 - Prosthetic valves and skirts thereof

Info

Publication number: WO2025235591A1
Application number: PCT/US2025/028116
Authority: WO
Inventors: Tamir S. LEVI
Original assignee: Edwards Lifesciences Corp
Current assignee: Edwards Lifesciences Corp
Priority date: 2024-05-08
Filing date: 2025-05-07
Publication date: 2025-11-13
Anticipated expiration: 2026-11-08

Abstract

The present disclosure relates to prosthetic valve and valvular structures thereof. In an example, a prosthetic valve comprises an annular frame movable between a radially compressed state and a radially expanded state, and a one-piece valvular structure mounted within the frame and comprising a plurality of leaflets and an engagement portion. The frame comprises an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end. The leaflets are integrally formed as regions of the one-piece valvular structure, and have a thickness T1. The engagement portion is connected to the plurality of leaflets and extending between a distal end thereof and the leaflets, the engagement portion having a thickness T2, wherein T1 is greater than T2.

Description

PROSTHETIC VALVES AND SKIRTS THEREOF

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/664,057, filed May 8, 2024, and U.S. Provisional Application No. 63/682,279, filed August 12, 2024, the contents of which are herein incorporated by reference in their entirety.

FIELD

[0002] The present disclosure relates to implantable, radially expandable prosthetic devices, such as prosthetic valves, and in particular, to skirts and valvular structures of prosthetic valves.

BACKGROUND

[0003] Native heart valves, such as the aortic, pulmonary and mitral valves, function to assure adequate directional flow from and to the heart, and between the heart's chambers, to supply blood to the whole cardiovascular system. Various valvular diseases can render the valves ineffective and require replacement with artificial valves. Surgical procedures can be performed to repair or replace a heart valve. Surgeries are prone to an abundance of clinical complications, hence alternative less invasive techniques of delivering a prosthetic heart valve over a catheter and implanting it over the native malfunctioning valve, have been developed over the years.

[0004] Different types of prosthetic heart valves are known to date, including balloon expandable valve, self-expandable valves and mechanically-expandable valves. Different methods of delivery and implantation are also known, and may vary according to the site of implantation and the type of prosthetic valve. One exemplary technique includes utilization of a delivery assembly for delivering a prosthetic valve in a crimped state, from an incision which can be located at the patient's femoral or iliac artery, towards the native malfunctioning valve. Once the prosthetic valve is properly positioned at the desired site of implantation, it can be expanded against the surrounding anatomy, such as an annulus of a native valve, and the delivery assembly can be retrieved thereafter.

SUMMARY

[0005] Described herein are prosthetic valves, sealing skirts thereof and valvular structures thereof. [0006] In one of its basic configurations, a prosthetic valve comprises an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end. This basic configuration can preferably be provided with any one or more of the features described elsewhere herein, in particular with those of the examples described hereafter. However, it should be understood that the basic configuration can preferably also be provided with any one or more of the features shown in the figures and/or described in conjunction with the figures, either in addition to or alternatively to the features of the examples described hereafter.

[0007] In some examples, the frame comprises plurality of intersecting struts, which form a plurality of cells.

[0008] In some examples, the frame comprises an inflow cell row comprising a plurality of inflow cells at the inflow end of the frame.

[0009] In some examples, the frame comprises an outflow cell row of outflow cells at the outflow end of the frame.

[0010] In some examples, the frame comprises one or more subsequent cell rows arranged between the inflow cell row and the outflow cell row, each comprising a plurality of subsequent cells.

[0011] In some examples, the frame comprises a fist cell row, which is one of the subsequent cell rows.

[0012] In some examples, the frame comprises a second cell row, which is the inflow cell row or one of the subsequent cell rows.

[0013] In some examples, the first cell row is positioned closer to the outflow end of the frame than the second cell row.

[0014] In some examples, each strut of the frame has a width Ws.

[0015] In some examples, two adjacent cells share one or more struts of the plurality of intersecting struts.

[0016] In some examples, the prosthetic valve comprises a one-piece valvular structure mounted within the frame and comprising a plurality of leaflets, which are integrally formed as regions of the one-piece valvular structure.

[0017] In some examples, the prosthetic valve comprises a plurality of leaflets, positioned at least partially within the frame.

[0018] In some examples, each leaflet comprises leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame;

[0019] In some examples, the leaflets have a thickness Tl.

[0020] In some examples, the one-piece valvular structure comprises an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets, the engagement portion.

[0021] In some examples, the engagement portion has a thickness T2.

[0022] In some examples, Tl is greater than T2.

[0023] In some examples, T2 is in the range of 50 micron to 200 micron.

[0024] In some examples, the prosthetic valve comprises a skirt which comprises: a base layer portion secured to an inner surface of the frame; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through corresponding cells defined between struts of the frame.

[0025] In some examples, two adjacent protruding extensions are defined as extending through corresponding adjacent cells.

[0026] In some examples, the base layer portion is at least partially overlapping axially with the engagement portion.

[0027] In some examples, the base layer portion has thickness T3, an overlapping potion between the base layer portion and the engagement portion has total thickness T2+T3, and Tl is greater or equal to T2+T3.

[0028] In some examples, each of the protruding extensions has an inner surface, which is in contact with the base layer portion, and an outer surface, which is spherical dome shaped and positioned radially away from the inner surface.

[0029] In some examples, the outer surfaces of the protruding extensions are porous.

[0030] In some examples, the outer surfaces of the protruding extensions have pore size in the range of 3 micron to 50 micron.

[0031] In some examples, the outer surfaces of the protruding extensions are laminated by a coating layer.

[0032] In some examples, the coating layer is perforated, and has an aperture size in the range of 3 micron to 50 micron.

[0033] In some examples, the coating layer is hydrophilic.

[0034] In some examples, the proximal edge of the base layer portion is positioned closer to the outflow end of the frame than the leaflet distal end. [0035] In some examples, the entire region between the cusp lines of adjacent leaflets is covered by the base layer portion.

[0036] In some examples, the skirt base layer portion is positioned radially away from the engagement portion, and entirely covers it.

[0037] In some examples, the prosthetic valve is devoid of protruding extensions extending from a surface of the base layer portion which is axially defined between the proximal edge thereof and the leaflet distal end.

[0038] In some examples, the skirt comprises a plurality of first protruding extensions, each extending radially outwards a from the base layer portion and through each of the cells of the first cell row.

[0039] In some examples, in an untensioned state thereof the first protruding extensions extend at radial dimension RDF.'.

[0040] In some examples, when compressed radially inward the first protruding extensions extend at radial dimension RDc'.

[0041] In some examples, the skirt comprises second plurality of protruding extensions, each extending radially outwards at a radial dimension RD” from the base layer portion and through each of the cells of the second cell row.

[0042] In some examples, in an untensioned state thereof the second protruding extensions extend at radial dimension RDE".

[0043] In some examples, when compressed radially inward the second protruding extensions extend at radial dimension RDc”.

[0044] In some examples, RDE" is greater than RDE'.

[0045] In some examples, RDc" is greater than RDc'.

[0046] In some examples, the leaflets are in contact with the base layer portion of the skirt along a portion of the first cell row.

[0047] In some examples, the leaflets have a thickness Tl, and RDE" is greater than or equal to the sum of RDE' and Tl.

[0048] In some examples, the leaflets have a thickness Tl, and RDc" is greater than or equal to the sum of RDc’ and T 1.

[0049] In some examples, a distance between two adjacent protruding extensions at a position adjacent to the strut, along which they both extend, and radially outwards thereto, is Wo, wherein Ws is greater than Wo.

[0050] In some examples, the skirt base layer portion is elastically deformable. [0051] In some examples, the skirt comprises a plurality of protruding extensions, which come in contact with adjacent protruding extensions, at positions, which are located radially away from the cells through which they extend.

[0052] In some examples, each extending protrusion comprises a flexible shell, which is connected to the base layer portion and enclosing a void within the extending protrusion.

[0053] In some examples, each extending protrusion has a radial dimension defined as the length between the base layer portion and the most radially outwards point of the flexible shell, wherein the radial dimension of each extending protrusion, when the frame is in the radially expanded state is greater than the radial dimension of the same extending protrusion, when the frame is in the radially compressed state.

[0054] In some examples, each extending protrusion has a proximal end defined as the point of the protrusion, which is closest to the inflow end of the frame, and a distal end defined as the point of the shell, which is closest to the outflow end of the frame; wherein each extending protrusion has an axial length defined as the distance between the proximal end and the distal end thereof; wherein the axial length of each extending protrusion, when the frame is in the radially expanded state is greater than the axial length of the same extending protrusion, when the frame is in the radially compressed state.

[0055] In some examples, each cell of the frame is axially extending along the frame from a proximal end, which is closer to the inflow end of the frame, and a distal end, which is closer to the outflow end of the frame, wherein an axial length of each cell is defined between the proximal end and the distal end; wherein the axial length of each cell, when the frame is in the radially compressed state is greater than the axial length of the same cell, when the frame is in the radially expanded state.

[0056] In some examples, each extending protrusion is mounted within a corresponding cell of the frame, wherein upon the mounting and transition of the frame from a radially compressed state to a radially expanded state, the axial length of each cell is increased together with the axial length of the extending protrusion mounted therein and the same extending protrusion flattens and the radial dimension thereof is decreased.

[0057] In some examples, a thickness of each one of the flexible shells is Tc, wherein a thickness of each one of the struts of the frame through which the plurality of extending protrusion extend, is Ts, and wherein Tc is in the range of 0.5Ts to 1.5Ts.

[0058] In some examples, a thickness of each one of the struts of the frame through which the plurality of extending protrusions extend, is Ts, wherein when the frame is in its radially compressed state, the flexible shells extend radially outward past the struts at a radial dimension, which is not greater than 3Ts.

[0059] In some examples, the prosthetic valve comprises a plurality of reinforcement lines positioned radially inwards to the protruding extensions, and configured to prevent collapse of the base layer portion radially inward upon application of pressure radially inward thereon, when the frame is in its radially expanded state.

[0060] In some examples, the plurality of reinforcement lines are positioned radially inwards to the base layer portion.

[0061] In some examples, at least some of the reinforcement lines extend between at least two struts of one cell on the frame.

[0062] In some examples, at least some of the reinforcement lines are formed as reinforcement portions of the base layer portion of the skirt.

[0063] In some examples, the reinforcement portions comprise a reinforcing material and nonreinforced portions of base layer portion comprise a base layer portion material; wherein the base layer portion material is different from the reinforcing material.

[0064] In some examples, the base layer portion material has lower tensile strength than the reinforcing material.

[0065] In some examples, at least some of the reinforcement lines are sutured threads, extending between two or more of the struts.

[0066] In some examples, the base layer portion comprises at least one layer which has at least one surface defining a non-uniform surface morphology.

[0067] In some examples, the at least one layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the at least one layer is facing the protruding extensions, and the inner surface of the at least one layer is facing radially inwards and defines the non-uniform surface morphology of the base layer portion.

[0068] In some examples, the at least one layer is porous.

[0069] In some examples, the at least one layer is electrospun.

[0070] In some examples, the base layer portion comprises at least two layers.

[0071] In some examples, the base layer portion comprises: an internal layer, which among the base layer portions, is located the most distally to the protruding extensions; and an external layer, which among the base layer portions, is located the most proximally to the protruding extensions; wherein the internal layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the internal layer is facing the protruding extensions, and the inner surface of the internal layer is facing radially inwards, and wherein the inner surface of the internal layer has a non-uniform surface morphology.

[0072] In one of its basic configurations, a method comprises providing a generally rectangular patch, comprising a moldable material and extending between a first side edge and a second side edge. This basic configuration can preferably be provided with any one or more of the features described elsewhere herein, in particular with those of the examples described hereafter. However, it should be understood that the basic configuration can preferably also be provided with any one or more of the features shown in the figures and/or described in conjunction with the figures, either in addition to or alternatively to the features of the examples described hereafter.

[0073] In some examples, the patch has thickness Tl.

[0074] In some examples, the method comprises inserting a 2D-shaped patch into a mold, forcing it to assume a 3D-shape and cross-linking the tissue material to maintain a 3D-shape. [0075] In some examples, the patch comprises a plurality of leaflets, each one of the plurality of leaflets comprises a corresponding belly that forms a 3D-shape of the patch, wherein each leaflet belly is defined between a lower cusp line and an upper free edge of the corresponding leaflet.

[0076] In some examples, the patch comprises an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets.

[0077] In some examples, the method comprises cutting a thickness portion of the engagement portion, so that the thickness of the engagement portion is reduced from Tl to T2, which is lower than Tl.

[0078] In some examples, the cutting is performed by laser milling or by mechanical skiving. [0079] In some examples, the method comprises rolling the 3D- shaped patch by bringing the first side edge and the second side edge together to assume a cylindrical configuration.

[0080] In some examples, the method comprises connecting the 3D-shaped patch to a frame of a prosthetic valve.

[0081] In one of its basic configurations, a method comprises providing a prosthetic valve which comprises an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end. This basic configuration can preferably be provided with any one or more of the features described elsewhere herein, in particular with those of the examples described hereafter. However, it should be understood that the basic configuration can preferably also be provided with any one or more of the features shown in the figures and/or described in conjunction with the figures, either in addition to or alternatively to the features of the examples described hereafter.

[0082] In some examples, the frame comprises a plurality of intersecting struts, each having a width Ws, wherein the struts form a plurality of cells, wherein two adjacent cells share one or more struts of the plurality of intersecting struts.

[0083] In some examples, an area of the cells of the frame is Ac.

[0084] In some examples, the method comprises providing a 3D-shaped elongated, optionally flattened, PVL skirt having two side portions extending between a proximal edge portion and a distal edge portion, wherein each of the proximal edge portion and distal edge portion is longer than the two side portions.

[0085] In some examples, the skirt comprises an optionally flat base layer portion having an inner surface and an outer surface, each defined between the two side portions, the proximal edge portion and a distal edge portion.

[0086] In some examples, wherein a distance between the two side portions in an untensioned state is Dsu.

[0087] In some examples, the skirt comprises a plurality of protruding extensions, each extending away from the outer surface of the base layer portion to define the 3D-shape of the skirt.

[0088] In some examples, each of the base layer portion and the protruding extensions is elastically stretchable.

[0089] In some examples, the method comprises stretching the skirt laterally to a stretched state, so that the distance between the two side portions in the stretched state is Dss, which is greater than Dsu.

[0090] In some examples, the method comprises rolling the stretched skirt by bringing the side potions thereof together to assume a cylindrical configuration.

[0091] In some examples, the method comprises connecting the stretched rolled skirt to the frame of the prosthetic valve, such that each of the protruding extensions extends radially outwards from the base layer portion and through corresponding cells thereof, wherein two adjacent protruding extensions are defined as extending through corresponding adjacent cells. [0092] In some examples, the method comprises relieving tension created by the stretching.

[0093] In some examples, upon the relief, a distance between the two adjacent protruding extensions in the relieved state is WGR, which is smaller than Ws.

[0094] In some examples, upon the relief, a distance between the two side portions in the relieved state is DSR, which is smaller than Dss and greater or equal to Dsu. [0095] In some examples, the method comprises providing an optionally flattened patch having two side portions extending between a proximal edge portion and a distal edge portion, wherein each of the proximal edge portion and distal edge portion is longer than the two side portions. [0096] In some examples, the patch comprises a stretchable, optionally flat, base layer portion having an inner surface and an outer surface, each defined between the two patch side portions, the proximal edge portion and a distal edge portion.

[0097] In some examples, the method comprises stretching the patch laterally to a stretched state.

[0098] In some examples, the method comprises connecting a plurality of protruding extensions to the outer surface of the patch, such that each protruding extension extends away from the outer surface of the base layer portion to form a 3D-shaped PVL skirt.

[0099] In some examples, each of the intersecting struts, has a width Ws, wherein a distance between the two side portions in an untensioned state of the patch is Dsu, wherein the protruding extensions are elastically stretchable, and wherein upon the step of relief, a distance between the two adjacent protruding extensions in the relieved state is WGR, which is smaller than Ws, and further upon the relief, a distance between the two side portions in the relieved state is DSR, which is smaller than Dss and greater or equal to Dsu.

[0100] In some examples a cross-sectional area of the protruding extensions in an untensioned state thereof is AGU-

[0101] In some examples, the protruding extensions are elastically stretchable, wherein a cross-sectional area of the protruding extensions upon the stretching of the patch state thereof is AGS, wherein AGU is greater than Ac and smaller than Acs-

[0102] In some examples, the protruding extensions are elastically compressible.

[0103] In some examples, the method comprises planarly compressing the protruding extensions, so that a cross-sectional area of the protruding extensions in a compressed untensioned state is AGC, which is smaller than AGU.

[0104] In some examples, the method comprises relieving tension created by the planarly compressing.

[0105] In some examples, upon the step of relieving, an area of the protruding extensions in the relieved state is AGR, which is greater than Ac.

[0106] The aspects 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 invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE FIGURES

[0107] Some examples of the invention are described herein with reference to the accompanying figures. The description, together with the figures, makes apparent to a person having ordinary skill in the art how some examples may be practiced. The figures are for the purpose of illustrative description and no attempt is made to show structural details of an example in more detail than is necessary for a fundamental understanding of the invention. For the sake of clarity, some objects depicted in the figures are not to scale.

In the Figures:

[0108] Fig. 1A shows a perspective view of an exemplary prosthetic valve, which includes skirt and a valvular structure.

[0109] Fig. IB shows a perspective view of the frame of the prosthetic valve of Fig. 1 A.

[0110] Fig. 2A shows a flattened view of an exemplary skirt of the prosthetic valve of Fig. 1 A. [0111] Fig. 2B is a cross-sectional view along line 2B-2B of Fig. 2A.

[0112] Figs. 3A-3C show some stages in a method of forming an exemplary one-piece valvular structure.

[0113] Fig. 4 shows a perspective flattened view of an exemplary valvular structure having a differential thickness surface.

[0114] Fig. 5A shows a perspective view of an exemplary prosthetic valve having a skirt with a proximal portion of the base layer devoid of protruding extensions.

[0115] Fig. 5B shows a perspective view of an exemplary prosthetic valve having a skirt with a base layer defining throughs and peaks along its proximal edge.

[0116] Fig. 6 shows a perspective view of an exemplary valvular structure comprising three leaflets.

[0117] Fig. 7 shows a perspective view of an exemplary prosthetic valve having a skirt that includes two types of protruding extensions.

[0118] Fig. 8 shows a top view of the prosthetic valve of Fig. 7.

[0119] Fig. 9 shows a perspective view of an exemplary prosthetic valve comprising comprises reinforcement lines.

[0120] Fig. 10A shows a flattened view of an exemplary skirt mountable within a frame of a prosthetic valve. [0121] Fig. 10B shows an enlarged view of a portion of the skirt of Fig. 10A.

[0122] Fig. 11A and 11B are cross-sectional views of an exemplary prosthetic valve having a skirt with protruding extensions comprising outwardly biased extending shells, shown in a radially compressed state and in a radially expanded state, respectively.

[0123] Fig. 12A shows a cross-sectional view of an exemplary skirt having an electrospun base layer portion.

[0124] Fig. 12B schematically shows a surface texture of an exemplary surface of the base layer portion of the skirt of Fig. 12A.

[0125] Fig. 13A shows a cross-sectional view of an exemplary skirt having a porous base layer portion.

[0126] Fig. 13B schematically shows a surface texture of an exemplary surface of the base layer portion of the skirt of Fig. 13 A.

[0127] Fig. 14A shows a cross-sectional view of an exemplary skirt having a bi-layered base layer portion with an electrospun first layer disposed over a porous second layer.

[0128] Fig. 14B schematically shows a surface texture of an exemplary surface of the first layer of the skirt of Fig. 14 A.

[0129] Fig. 14C schematically shows a surface texture of an exemplary surface of the second layer of the skirt of Fig. 14 A.

[0130] Fig. 15A shows a cross-sectional view of an exemplary skirt having a bi-layered base layer portion with an electrospun first layer disposed over an electrospun second layer.

[0131] Fig. 15B schematically shows a surface texture of an exemplary surface of the first layer of the skirt of Fig. 15 A.

[0132] Fig. 15C schematically shows a surface texture of an exemplary surface of the second layer of the skirt of Fig. 15 A.

[0133] Fig. 16A shows a cross-sectional view of an exemplary skirt having a bi-layered base layer portion with an electrospun first layer disposed over a nonporous second layer.

[0134] Fig. 16B schematically shows a surface texture of an exemplary surface of the first layer of the skirt of Fig. 16A.

[0135] Fig. 16C schematically shows a surface texture of an exemplary surface of the second layer of the skirt of Fig. 16 A.

DETAILED DESCRIPTION

[0136] For purposes of this description, certain aspects, advantages, and novel features of the 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. The technologies from any example can be combined with the technologies described in any one or more of the other examples. In view of the many possible examples to which the principles of the disclosed technology may be applied, it should be recognized that the illustrated examples are only preferred examples and should not be taken as limiting the scope of the disclosed technology.

[0137] 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.

[0138] All features described herein are independent of one another and, except where structurally impossible, can be used in combination with any other feature described herein.

[0139] 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 terms "have" or "includes” means "comprises”. Further, the terms "coupled”, "connected”, and "attached", as used herein, are interchangeable and generally mean 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. As used herein, "and/or” means "and” or "or”, as well as "and” and "or”.

[0140] Directions and other relative references may be used to facilitate discussion of the drawings and principles herein, but are not intended to be limiting. For example, certain terms may be used such as "inner,” "outer,” "upper,” "lower,” "inside,” "outside,”, "top,” "bottom,” "interior,” "exterior,” "left,” right,” and the like. Such terms are used, where applicable, to provide some clarity of description when dealing with relative relationships, particularly with respect to the illustrated examples. Such terms are not, however, intended to imply absolute relationships, positions, and/or orientations. For example, with respect to an object, an "upper” part can become a "lower” part simply by turning the object over. Nevertheless, it is still the same part and the object remains the same.

[0141] The term "plurality” or "plural” when used together with an element means two or more of the element. Directions and other relative references (e.g., inner and outer, upper and lower, above and below, left and right, and proximal and distal) may be used to facilitate discussion of the drawings and principles herein but are not intended to be limiting.

[0142] The term "proximal”, as used herein, generally refers to a position, direction, or portion of any device or a component of a device, which is closer to a user of a delivery apparatus that can be used to implant the device in the patient and farther away from the implantation site. The term "proximal” when used with two spatially separated positions or parts of an object can be understood to mean closer to or oriented towards the proximal end of the device. The term "distal”, as used herein, generally refers to a position, direction, or portion of any device or a component of a device, which is further away from the user and closer to the implantation site. The term "distal” when used with two spatially separated positions or parts of an object can be understood to mean closer to or oriented towards the distal end of the delivery apparatus. The terms "longitudinal” and "axial” are interchangeable, and refer to an axis extending in the proximal and distal directions, unless otherwise expressly defined.

[0143] Throughout the figures of the drawings, different superscripts for the same reference numerals are used to denote different examples of the same elements. Examples of the disclosed devices and systems may include any combination of different examples of the same elements. Specifically, any reference to an element without a superscript may refer to any alternative example of the same element denoted with a superscript. In order to avoid undue clutter from having too many reference numbers and lead lines on a particular drawing, some components will be introduced via one or more drawings and not explicitly identified in every subsequent drawing that contains that component.

[0144] Figs. 1A and IB show perspective views of an example of a prosthetic valve 100, with and without soft components (such as a skirt and a valvular structure), respectively. The term "prosthetic valve", as used herein, refers to any type of a prosthetic valve deliverable to a patient’s target site over a catheter, which is radially expandable and compressible between a radially compressed, or crimped, state, and a radially expanded state. Thus, the prosthetic valves can be crimped on or retained by an implant delivery apparatus (not shown) in the radially compressed state during delivery, and then expanded to the radially expanded state once the prosthetic valve reaches the implantation site. The expanded state may include a range of diameters to which the valve may expand, between the compressed state and a maximal diameter reached at a fully expanded state. Thus, a plurality of partially expanded states may relate to any expansion diameter between radially compressed or crimped state, and maximally expanded state. A prosthetic valve 100 of the current disclosure may include any prosthetic valve configured to be mounted within the native aortic valve, the native mitral valve, the native pulmonary valve, and the native tricuspid valve.

[0145] It is to be understood that the prosthetic valves disclosed herein may be used with a variety of implant delivery apparatuses. Balloon expandable valves generally involve a procedure of inflating a balloon within a prosthetic valve, thereby expanding the prosthetic valve within the desired implantation site. Once the valve is sufficiently expanded, the balloon is deflated and retrieved along with a delivery apparatus. Self-expandable valves include a frame that is shape-set to automatically expand as soon an outer retaining shaft or capsule (not shown) is withdrawn proximally relative to the prosthetic valve. Mechanically expandable valves are a category of prosthetic valves that rely on a mechanical actuation mechanism for expansion. The mechanical actuation mechanism usually includes a plurality of expansion and locking assemblies (such as the prosthetic valves described in U.S. Patent No. 10,603,165, International Application No. PCT/US2021/052745, and U.S. Provisional Application Nos. 63/085,947 and 63/209904, each of which is incorporated herein by reference in its entirety), releasably coupled to respective actuation assemblies of a delivery apparatus, controlled via a handle (not shown) for actuating the expansion and locking assemblies to expand the prosthetic valve to a desired diameter. The expansion and locking assemblies may optionally lock the valve's diameter to prevent undesired recompression thereof, and disconnection of the actuation assemblies from the expansion and locking assemblies, to enable retrieval of the delivery apparatus once the prosthetic valve is properly positioned at the desired site of implantation. [0146] The term "plurality", as used herein, means more than one.

[0147] The prosthetic valve 100 comprises an inflow end 104 and an outflow end 106. In some instances, the inflow end 104 is the distal end of the prosthetic valve 100, and the outflow end 106 is the proximal end of the prosthetic valve 100. Alternatively, depending for example on the delivery approach of the valve, the inflow end can be the proximal end of the prosthetic valve, and the outflow end can be the distal end of the prosthetic valve.

[0148] The term "outflow", as used herein, refers to a region of the prosthetic valve through which the blood flows through and out of the prosthetic valve 100. [0149] The term "inflow", as used herein, refers to a region of the prosthetic valve through which the blood flows into the prosthetic valve 100.

[0150] In the context of the present application, the terms "lower” and "upper” are used interchangeably with the terms "inflow” and "outflow”, respectively. Thus, for example, the lower end of the prosthetic valve is its inflow end and the upper end of the prosthetic valve is its outflow end.

[0151] The terms "longitudinal” and "axial”, as used herein, refer to an axis extending in the proximal and distal directions, unless otherwise expressly defined.

[0152] The valve 100 comprises an annular frame 102 movable between a radially compressed state and a radially expanded state, and a valvular structure 170 mounted within the frame 102. The frame 102 can be made of various suitable plastically-expandable materials (e.g., stainless steel, etc.) or self-expanding materials (e.g., Nitinol). When constructed of a plastically- expandable material, the frame 102 (and thus the valve 100) can be crimped to a radially compressed state on a delivery catheter (not shown) and then expanded inside a patient by an inflatable balloon or equivalent expansion mechanism. When constructed of a self-expandable material, the frame 102 (and thus the valve 100) can be crimped to a radially compressed state and restrained in the compressed state by insertion into a sheath or equivalent mechanism of a delivery catheter. Once inside the body, the valve can be advanced from the delivery sheath, which allows the valve to expand to its functional size.

[0153] Suitable plastically-expandable materials that can optionally be used to form the frames disclosed herein (e.g., the frame 102) include metal alloys, polymers, or combinations thereof. Example metal alloys can optionally comprise one or more of the following: nickel, cobalt, chromium, molybdenum, titanium, or other biocompatible metal. In some examples, the frame 102 comprises stainless steel. In some examples, the frame 102 comprises cobalt-chromium. In some examples, the frame 102 comprises nickel-cobalt-chromium. In some examples, the frame 102 comprises a nickel-cobalt-chromium-molybdenum alloy, such as MP35N™ (tradename of SPS technologies), which is equivalent to UNS R3OO35 (covered by ASTM F562-02). MP35N™/UNS R30035 comprises 35% nickel, 35% cobalt, 20% chromium, and 10% molybdenum, by weight.

[0154] In the example illustrated in Figs. 1A-1B, the frame 102 is an annular, stent-like structure comprising a plurality of intersecting struts 108. In this application, the term "strut" 108 encompasses vertical struts, angled or curved struts, support posts, commissure windows, and any similar structures described by U.S. Pat. Nos. 7,993,394 and 9,393,110, which are incorporated herein by reference. A strut 108 may be any elongated member or portion of the frame 102. The frame 102 can have a cylindrical or substantially cylindrical shape having a constant diameter from the inflow end 104 to the outflow end 106 as shown, or the frame can vary in diameter along the height of the frame, as disclosed in US Pat. No. 9,155,619, which is incorporated herein by reference.

[0155] Figs. 1A-1B show an exemplary prosthetic valve 100 that can be representative of, but is not limited to, a balloon expandable prosthetic valve. The interconnected struts 108 comprise a plurality of angled struts 110 arranged in a plurality of rungs 112 of circumferentially extending rungs of angled struts, with the strut rungs 112 being arrayed along the length of the frame 102 between the outflow end 106 and the inflow end 104. Struts 108 of the frame 102 can optionally further include a plurality of axially extending struts 114. The term "axially extending strut" refers to a strut or a component of the frame 102 that generally extends in an axial direction, while the term "angled strut" generally refers to a strut that can extend at an angle relative to an axial line intersecting therewith along a plane defined by the frame 102. It is to be understood that the term "angled strut" encompasses both linear angled struts and curved struts.

[0156] Two or more struts 108 can intersect at junctions 124, which can be equally or unequally spaced apart from each other. The struts 108 may be pivotable or bendable relative to each other, so as to permit frame expansion or compression. For example, the frame 102 can be formed from a single piece of material, such as a metal tube, via various processes such as, but not limited to, laser cutting, electroforming, and/or physical vapor deposition, while retaining the ability to collapse/expand radially in the absence of hinges and like.

[0157] In some examples, the frame 102 further comprises a plurality of outflow apices 122 at the outflow end 106 of the frame, and a plurality of inflow apices 120 at the inflow end 104 of the frame. A plurality of intermediate junctions 124 are disposed between the inflow end 104 and outflow end 106.

[0158] The frame 102 of a prosthetic valve 100 comprises an inflow rung 1121 of inflow angled struts 1101 at the inflow end 104 of the frame, an outflow rung 1120 of outflow angled struts 110O at the outflow end 106 of the frame, and a plurality of subsequent rungs 112S arranged between the inflow rung 1121 and the outflow rung 1120, each comprising a plurality of subsequent angled struts 110S.

[0159] The frame 102 further comprises an inflow cell row 1181 comprising a plurality of inflow cells 1161 at the inflow end 104 of the frame 102, an outflow cell row 1180 of outflow cells 1160 at the outflow end 106 of the frame 102, and optionally one or more subsequent cell rows 118S arranged between the inflow cell row 1181 and the outflow cell row 1180, each comprising a plurality of subsequent cells 116S.

[0160] An exemplary frame 102 illustrated in Figs. 1A-1B is shown to include a first subsequent rung 112S1 proximal to the inflow rung 1121 and comprising subsequent angled struts 110S1, a second subsequent rung 112S2 proximal to the first subsequent rung 112S1 and comprising subsequent angled struts 110S2, a third subsequent rung 112S3 proximal to the second subsequent rung 112S2 and comprising subsequent angled struts 110S3, a fourth subsequent rung 112S4 proximal to the third subsequent rung 1 12S3 and comprising subsequent angled struts 110S4, and an outflow rung 1120 proximal to the fourth subsequent rung 112S4 and comprising outflow angled struts 1100.

[0161] Similarly, the frame 102 is shown to include a first subsequent cell row 118S 1 proximal to the inflow cell row 1181 and comprising subsequent cells 116S1, a second subsequent cell row 118S2 proximal to the first subsequent cell row 118S1 and comprising subsequent cells 116S2, a third subsequent cell row 118S3 proximal to the second subsequent cell row 118S2 and comprising subsequent cells 116S3, and an outflow cell row 1181 proximal to the third subsequent cell row 118S3 and comprising inflow cells 1161.

[0162] A frame 102 of a prosthetic valve 100 can optionally include a plurality of axially extending struts 114 vertically extending between the outflow rung 1120 of angled struts 110O, and the fourth or proximal-most subsequent rung 112S4 of angled struts 110S4.

[0163] The upper end portions of the outflow angled struts 110O of the outflow rung 1120 can form outflow apices 122 at or proximate to the outflow end 106, and end portions of the inflow angled struts 1101 of the inflow rung 1121 can form inflow apices 120 at the inflow end 104. The struts of each of the inflow rung 1121, subsequent rungs 112S, and outflow rung 1120, can extend circumferentially in a zig-zagged formation as illustrated.

[0164] The valvular structure 170 can include a plurality of leaflets 172 (e.g., three leaflets), positioned at least partially within the frame 102, and configured to regulate flow of blood through the prosthetic valve 100 from the inflow end 104 to the outflow end 106. While three leaflets 172 arranged to collapse in a tricuspid arrangement, are shown in the example illustrated in Fig. 1 A, it will be clear that a prosthetic valve 100 can include any other number of leaflets 172. Adjacent leaflets 172 can be optionally arranged together to form commissures 186 that are coupled (directly or indirectly) to respective portions of the frame 102, thereby securing at least a portion of the valvular structure 170 to the frame 102. In some examples, the valvular structure 170 can be formed as a unitary component having dedicated regions thereof defining integrally formed leaflets 172 that can be continuously interconnected at commissure attachment regions 184 (indicated, for example, in Figs. 3A-3C). Such commissure attachment regions 184 can be secured to the frame 102 to form commissures 186. [0165] In some examples, the plurality of leaflets 172 can be integrally formed as regions of a one-piece valvular structure 170 (such as unitary valvular structure 170^s shown, for example, in Fig. 3C), meaning that all of the leaflets 172 are continuous with each other without the need to otherwise couple them to each other (such as by suturing, adhering, and the like) to form the valvular structure 170. In some examples, the plurality of leaflets 172 can be formed and provided as separate components, which can be in turn joined to each other and/or to the frame 102 (e.g., by suturing) to form the valvular structure 170 (such as valvular structure 170^d shown, for example, in Fig. 6).

[0166] The leaflets 172 can be made from, in whole or part, biological material (e.g., pericardium), bio-compatible synthetic materials, or other such materials. Further details regarding transcatheter prosthetic valves, including the manner in which the valvular structure 170 can be coupled to the frame 102 of the prosthetic valve 100, can be found, for example, in U.S. Patent Nos. 6,730,118, 7,393,360, 7,510,575, 7,993,394, 8,652,202, and 11,135,056, all of which are incorporated herein by reference in their entireties.

[0167] In some examples, the axially extending struts 114 comprise a plurality of axial struts 190 and a plurality of commissure support members 192. The axially extending struts 114, including axially extending struts 190 and commissure support members 192, can be parallel to each other and/or to a central longitudinal axis Ca of the prosthetic valve 100.

[0168] A commissure support member 192 can be an axially extending strut which is configured to support a commissure 186 attachable or attached thereto, and may optionally include a geometry or features configured to facilitate attachment of the commissure 186 thereto, such as grooves, protrusions, holes, window openings, and the like. An axial strut 190 can be an axially extending strut which is configured to remain unattached to the valvular structure 170. That is to say, an axial strut 190 is not configured to mount a commissure, and may be devoid of geometrical or other features included in a commissure support member 192 for that end.

[0169] In some examples, a commissure support member 192 can include at least one recess formed over at least one side of the commissure support member 192. In some examples, a commissure support member 192 can have wavy or otherwise-shaped edges that define a plurality of recesses on both sides of the commissure support member 192, as shown, for example, in Fig. IB. A leaflet 172 can optionally include a pair of opposite commissure attachment portions in the form of tabs 184 (see for example, Fig. 6). Tabs 184 of adjacent leaflets 172 can be sutured to each other to form a commissure 186, wherein the suture can be passed through or along recesses of a commissure support member 192 to improve securement and prevent the knot of the commissure 186 from axially sliding along the commissure support member 192.

[0170] The prosthetic valve 100 can further comprise at least one skirt or sealing member. In some examples, a prosthetic valve can include a skirt 130 having a base layer portion 132 (indicated, for example, in Figs. 2A-2B) secured to an inner surface 128 of the frame 102, and can optionally include a plurality of protruding extensions 150 extending radially outwards from the base layer portion 132 and through corresponding cells 116 and/or openings defined between angled struts 110 of the frame, the skirt 130 configured to function, for example, as a sealing member to prevent or decrease perivalvular leakage. In some examples, an engagement portion of a unitary valvular structure can be provided as an integrally formed region of the valvular structure 170, which can optionally also serve as a sealing member to prevent or decrease perivalvular leakage. In some examples, skirt 130 can be provided as a separate component that can further function as an anchoring region for the leaflets 172 to the frame 102, and/or function to protect at least some portions of the leaflets 172 against damage which may be caused by contact with the frame 102, for example during valve crimping or during working cycles of the prosthetic valve 100.

[0171] In some examples, outwardly protruding extensions 150 of the skirt 130 protrude radially away from the frame's outer surface 127, configure to function, for example, as sealing members extending between the frame 102 and the surrounding tissue of the native annulus against which the prosthetic valve is mounted, thereby reducing risk of paravalvular leakage (PVL) past the prosthetic valve 100.

[0172] Each cell row 118 of the frame 102 comprises a plurality of cells 116 extending circumferentially such that each cell 116 is directly coupled to two circumferentially adjacent cells 116 on both sides thereof within the same cell row 118. The term "cell", as used herein, refers to a closed cell, having an enclosed perimeter defined by at least four struts 108.

[0173] In some examples, the outflow cells 1160 are coupled to adjacent outflow cells 1160 within the outflow cell row 1180 via axially extending struts 114. The outflow cells 1160 of the exemplary valve 100 shown in Figs. 1A-1B can be generally hexagonal, each outflow cell 1160 defined between two outflow angled struts 110O of the outflow rung 1120, two fourth subsequent angled struts 110S4 of the fourth subsequent rung 112S4, and two axially extending struts 114 extending between the outflow rung 1120 and the fourth subsequent rung 112S4. [0174] Cells 1161 and 116S of the inflow cell row 1181 and subsequent cell rows 118S can be generally diamond-shaped cells. For example, the frame 102 illustrated in Figs. 1A-1B is shown to include inflow cells 1161 defined by two inflow struts 1101 and two first subsequent angled struts 110S 1 , first subsequent cells 116S1 defined by two first subsequent angled struts 110S 1 and two second subsequent angled struts 110S2, second subsequent cells 116S2 defined by two second subsequent angled struts 110S2 and two third subsequent angled struts 110S3, and third subsequent cells 116S3 defined by two third subsequent angled struts 110S3 and two fourth subsequent angled struts 110S4.

[0175] In some examples, the outflow cells 1160 of the prosthetic valve 100 can have a height (measured in the axial direction) which is greater than the height of cells 116S, 1161 of the subsequent cell rows 118S, 1181, due to the axially extending struts 114 interconnecting the outflow rung 1120 and the fourth subsequent rung 112S4.

[0176] While all cells 116 of the inflow cell row 1181 and the subsequent cell rows 118S are shown in the example illustrated in Figs. 1A-1B to have substantially the same size and shape, it is to be understood that in some examples, cells 116 of the inflow cell row 1181 and the subsequent cell rows 118S, as well as outflow cells 1160, can have different sizes and shapes. [0177] Each leaflet 172 includes a leaflet belly 174 which is the movable and unattached part of the leaflet, defined between a lower cusp line 176 and an upper free edge 178 of the leaflet 172. The cusp line 176 of each leaflet 172 can define a leaflet distal end 177, which can optionally be a midpoint of the cusp line 176, defining a distal-most (or lower-most) end of the leaflet 172. In some examples, leaflet bellies 174 described herein can have a three-dimensional and concave shape, thereby resulting in increased mobility of the leaflet when the prosthetic valve is implanted in a patient. As a result, the efficiency of the prosthetic valve including the valvular structure can be improved.

[0178] Various exemplary implementations for prosthetic valve 100 and/or components thereof can be referred to, throughout the specification, with superscripts, for ease of explanation of features that refer to such exemplary implementations. It is to be understood, however, that any reference to structural or functional features of any device, apparatus or component, without a superscript, refers to these features being commonly shared by all specific exemplary implementations that can be also indicated by superscripts. In contrast, features emphasized with respect to an exemplary implementation of any device, apparatus or component, referred to with a superscript, may be optionally shared by some but not necessarily all other exemplary implementations. For example, a prosthetic valve 100^a, illustrated in Fig. 1 A, is an exemplary implementation of a prosthetic valve 100, and thus can include any of the features described for a prosthetic valve 100 throughout the current disclosure, except that the skirt 130^a of the prosthetic valve 100^a terminates distal to the cusp lines 176 of the leaflets 172. [0179] The base layer portion 132 extends between a distal edge 136 which is closer to the inflow end 104 of the frame, and an opposite proximal edge 134 closer to the outflow end 106. Fig. 2A shows a flattened view of the exemplary skirt 130^a of prosthetic valve 100^a of Fig. 1 A. Fig. 2B is a cross-sectional view along line 2B-2B of Fig. 2A. The proximal edge 134 of the base layer portion 132 of skirt 130^a is distal to the leaflet distal ends 177, such that the skirt 130^a can be fully disposed below the leaflets 172, having both the base layer portion 132 and protruding extensions 150 distal to (or below) the leaflets 172 and their cusp lines 176. In some examples, the proximal edge 134 of the base layer portion 132 of skirt 130^a can be distal to engagement portion 180 (for example, distal to the distal end 182 of engagement portion 180). Such configuration can maintain a smaller crimped profile of the prosthetic valve 100^a, by separating between the leaflet 172 and the skirt 130 in a manner that can avoid overlaying one against the other, which would otherwise add the thickness of both to the crimped profile of the valve.

[0180] In some examples, the proximal edge 134 of the base layer portion 132 can have a generally zig-zagged pattern that tracks a corresponding zig-zagged pattern of angled struts 110 along a rung 112 to which the proximal edge 134 is coupled, such as the first subsequent rung 112S1 for the illustrated prosthetic valve 100^a. In some examples, the distal edge 136 of the base layer portion 132 can be relatively linear.

[0181] A skirt 130 of the current disclosure can optionally include at least one row of circumferentially arranged protruding extensions 150, shaped and sized to radially extend outwardly through corresponding cells 116 of at least one cell row 118. In some examples, a skirt 130 can include a row of circumferentially arranged inflow protruding extensions 1501, aligned with, and configured to protrude through, inflow cells 1161 of the inflow cell row 1181. In some examples, a skirt 130 can further comprise a row of circumferentially arranged distal protruding extensions 150D which are distal to the inflow protruding extensions 1501, and can be configured to extend radially outwards through spaces defined distal to (or below) the inflow struts 1101, optionally terminating at the level of the inflow end 104.

[0182] In some examples, protruding extensions 150 can have a shape that generally conforms to the shape of cells 116 through which they protrude, such as the diamond- shaped inflow protruding extensions 1501 of skirt 130^a shown in Figs. 1A and 2A. In some examples, protruding extensions 150 can have a shape that at least partially tracks the shape of strut 108 bounding some borders to the protruding extension 150, such as the generally triangularly- shaped distal protruding extensions 150D of skirt 130^a shown in Figs. 1A and 2A.

[0183] In some examples, the valvular structure 170 can comprise shaped tissue material. As mentioned above, in some examples, the valvular structure 170, including leaflet bellies 174 of leaflets 172 thereof, is a single-piece three-dimensional construct formed from a single patch 166 of tissue, as shown, for example, in Fig. 3 A. In some examples, leaflet bellies 174 disclosed herein are not flattenable. The term "not flattenable", as used herein, means that the leaflet belly 174 cannot be flattened. That is to say, if an attempt is made to straighten out the curve of a free edge 178 of leaflet 172, the curve will not be able to be completely straightened such that leaflet belly 174 becomes flat. This is in contrast to leaflets that are cut from a flat patch and are then attached (e.g., sutured) to a frame of a prosthetic valve, wherein upon removal of such leaflets from the frame they can be laid flat on a flattened surface, with their free edges being able to completely straighten in their free state. In some examples, a leaflet belly 174 which is not flattenable defines a non-developable surface. Further details regarding leaflets or leaflet bellies thereof, which are three-dimensional or not flattenable, are described in International Application No. PCT/US2022/032303, and U.S. Provisional Application No. 63/587,399, each of which is incorporated herein by reference in its entirety.

[0184] In some examples, the prosthetic valve 100^c can comprise eyelets 126. In some examples, the eyelets 126 can configure to serve as anchors for coupling the prosthetic valve 100, to a delivery apparatus. In some examples, the frame 102 can comprise one or more inflow eyelets 1261 at the inflow end 104. In some examples, the frame 102 can comprise one or more outflow eyelets 1260 at the outflow end 106.

[0185] Figs. 3A-3C show some stages in a method of forming an exemplary valvular structure 170^a. Fig. 3 A shows a 3D-shaped patch 166^a of material, which can be a tissue patch that can have, prior to 3D-shaping thereof, a generally rectangular patch extending between side edges 168a and 168b. A flat rectangular patch 166^a having a thickness T1 can be inserted into a mold assembly and pressed between upper and lower templates, forcing it to assume the shape defined by the various surfaces of such templates. Fig. 3A shows the patch 166 in a 3D-shaped configuration, after removal from such a mold assembly. When the patch is formed of a tissue material (e.g., bovine pericardium), cross-linking the tissue patch 166 can result in the tissue maintaining its shape after being removed or separated from the mold assembly.

[0186] Fig. 3B shows an optional subsequent step of forming a tubular valvular structure 170^a by rolling the 3D-shaped patch 166^a. For example, the side edges 168a and 168b can be brought together in a mating or otherwise abutting relationship. Once mated, both side edges 168a, 168b can be coupled to each other, such as by sewing, adhering, or otherwise attaching the side edges 168, thus resulting in a substantially cylindrical valvular structure 170^a as shown in Fig. 3C. When the valvular structure 170^a is rolled to assume its cylindrical configuration, as shown in Fig. 3C, each commissure attachment portion 184 can be folded so as to form a commissure region fold extending radially outwards.

[0187] Each leaflet 172 of the valvular structure 170^a, as shown in Fig. 3C, has a free edge 178 and a cusp line 176 that can have, in some examples, a curved shape, opposite to the free edge 178. The cusp line 176 of each leaflet 172 can form a single scallop that can be, for example, parabolic in shape. Commissure attachment portions 184 of the valvular structure 170^a can be defined between adjacent leaflets 172, as regions of the valvular structure 170^a that extend to a certain axial length from the level of the free edges 178. A leaf-shaped leaflet belly 174 of each leaflet 172 is defined between the cusp line 176 and the free edge 178, excluding the commissure attachment portions 184.

[0188] When the valvular structure 170^a is coupled to the frame 102, a line of attachment, also referred to as a scalloped line, can extend along the cusp line 176 of all leaflets 172, together forming a scalloped shaped attachment pattern that can be stitched or otherwise coupled to the frame, directly or indirectly. The scalloped line of attachment, following at least a portion of the cusp lines 176, such as parallel to and somewhat distal to the cusp lines, optionally without extending into the commissure attachment portions 184, can have an undulating, curved scalloped shape. By forming the leaflets of the valvular structure 170 with this scalloped geometry (such as along the cusp lines 176), stresses on the leaflets 172 are reduced which, in turn, improves durability of the valve 100. The leaflet belly 174 of each leaflet 172 is the part of the leaflet 172 remaining unattached to the frame or other components of the valve after assembly, configured to open and close (or coapt) during operation of the prosthetic valve 100, such as during systole and diastole.

[0189] Fig. 3C shows an exemplary valvular structure 170^a, which can be similar to any example of a valvular structure 170 disclosed herein, except that the valvular structure 170^a further comprises an engagement portion 180 extending between a distal end 182 thereof and the cusp lines 176, optionally including portions bound between cusp lines 176 of adjacent leaflets 172 and the commissure attachment portions 184 defined therebetween, wherein the distal end 182 of the engagement portion 180 can be circular in the cylindrical configuration of the valvular structure 170^a as shown in Fig. 3C, or substantially linear in a flattened configuration of the valvular structure 170^a as shown in Fig. 3A for example. In some examples, the engagement portion 180 can optionally be cylindrically disposed along the inner surface 128 of the frame 102, and coupled thereto, such as by sutures or other couplers that extend both through the scalloped line following at least a portion of the cusp lines 176, and optionally the distal end 182 of the engagement portion 180.

[0190] In contrast to the leaflets 172, the engagement portion 180 can remain flattenable after the 3D-shaping process of the leaflets 172. Having a flattenable engagement portion 180 can assist in attachment thereof to the frame 102, wherein a flattenable engagement portion 180 can be rolled into a cylindrical or semi-cylindrical shape that can conveniently cover the inner surface of the frame 102, while the leaflet bellies 174, which are movable portions that remain unattached to the frame, can be formed as portions which are not-flattenable to improve performance of the valvular structure 170.

[0191] In some examples, the distal end 182 of the engagement portion 180 can extend all the way towards, or terminate in close proximity to, the inflow end 104 of the frame 102. In some examples, the distal end 182 of the engagement portion 180 can extend all the way towards, or terminate in close proximity to, the distal edge 136 of the skirt 130. In some examples, the distal end 182 of the engagement portion 180 can extend all the way towards, or terminate in close proximity to, the proximal edge 134 of the skirt 130.

[0192] Fig. 4 shows a perspective flattened view of an exemplary valvular structure 170^b, which is an exemplary implementation of valvular structure 170^a, and thus can include any of the features described for a valvular structure 170^a throughout the current disclosure, except that the valvular structure 170^b can have a differential thickness surface, as detailed herein. Specifically, in some examples, the valvular structure 170^b can be a one-piece valvular structure, as detailed above. Thus, according to some examples, the valvular structure 170^b can comprise a plurality of leaflets 172^b, which can include any of the features described for leaflets 172 throughout the current disclosure. In some examples, the leaflets 172^b can be integrally formed as regions of the one-piece valvular structure 170^b. In some examples, the valvular structure 170^b can include an engagement portion 180^b, which can include any of the features described for engagement portion 180 throughout the current disclosure. In some examples, the engagement portion 180^b can be connected to the plurality of leaflets 172^b. In some examples, the engagement portion 180^b can extend between a distal end 182 thereof and the leaflets 172^b.

[0193] With respect to the differential thickness of the valvular structure 170^b, in some examples, the thickness of the leaflets 172^b can be different than the thickness of the engagement portion 180^b. In some examples, the plurality of leaflets 172^b can have a thickness Tl. In some examples, at least one of the plurality of leaflets 172^b can have a thickness Tl. In some examples, at least a portion of the plurality of leaflets 172^b can have a thickness Tl. In some examples, each one of the plurality of leaflets 172^b can have a thickness Tl. In some examples, the engagement portion 180^b can have a thickness T2. In some examples, at least some of the engagement portion 180^b can have a thickness T2. In some examples, the engagement portion 180^b can have a uniform thickness T2. In some examples, Tl can be different from T2. In some examples, Tl can be greater than T2. In some examples, Tl can be at least 5% greater than T2. In some examples, T 1 can be at least 10% greater than T2. In some examples, Tl can be at least 25% greater than T2. In some examples, Tl can be at least 50% greater than T2. In some examples, Tl can be at least 100% greater than T2.

[0194] In some examples, thickness T2 may be in the range of 50 to 200 micron. In some examples, thickness T2 may be in the range of 50 micron to 200 micron, including each value and sub-range within the specified range, for example 50 micron to 100 micron, 75 micron to 125 micron, 100 micron to 150 micron, 125 micron to 175 micron or 150 micron to 200 micron. [0195] Thus, in some examples, the valvular structure 170^b can be mounted on a frame 102, which is detailed herein.

[0196] In some examples, at least some of the plurality of leaflets 172^b that have thickness Tl can include a corresponding leaflet belly 174.

[0197] In some examples, engagement portion 180^b having a thickness T2 can extend between a distal end thereof 182 and the cusp lines 176 of the leaflets 172^b.

[0198] In some examples, the valvular structure 170^b can be formed from a unitary material. In some examples, the valvular structure 170^b can comprise a moldable material. In some examples, the valvular structure 170^b can comprise a moldable material. In some examples, the valvular structure 170^b can comprise a millable material. In some examples, the valvular structure 170^b can comprise a shaped tissue material. In some examples, the engagement portion 180 can comprise a moldable material. In some examples, the engagement portion 180 can be moldable. In some examples, the engagement portion 180 can comprise a millable material. In some examples, the engagement portion 180 can comprise a shaped tissue material. In some examples, the shaped tissue material may be pericardium.

[0199] In some examples, the prosthetic valve 100 can further comprise a skirt 130. In some examples, the prosthetic valve 100 can include the frame 102, the one-piece valvular structure mounted 170^b within the frame 102, which includes the leaflets that have thickness Tl and engagement portion 180 that has thickness T2, and a skirt 130.

[0200] In some examples, the skirt 130 can include 5-30 or 10-25 protruding extensions 150. The protruding extensions 150 are detailed herein. [0201] In some examples, the distal edge 136 of the base layer portion 132 can be closer to the inflow end 104 of the frame 102 than the proximal edge 134. In some examples, the proximal edge 134 of the base layer portion 132 can be closer to the outflow end 106 of the frame than the distal edge 136. In some examples, the distal edge 136 of the base layer portion 132 can be connected to the frame 102. In some examples, the distal edge 136 of the base layer portion 132 can be connected to the frame 102 adjacent to the inflow end 104 thereof. For example, the distal edge 136 of the base layer portion 132 can be connected to the frame 102 by one or more sutures. In some examples, the distal edge 136 of the base layer portion 132 can be connected to the frame 102 adjacent to the inflow end 104 thereof at a plurality of radially spaced positions along the circumference of the frame 102, using a plurality of sutures.

[0202] In some examples, the engagement portion 180 can extend from a distal end thereof 182. In some examples, the engagement portion 180 can extend between a distal end thereof 182 and the leaflets 172^b. In some examples, the engagement portion 180 can extend between a distal end thereof 182 and the cusp lines 176 leaflets 172^b. In some examples, the distal end 182 of the engagement portion 180 can be closer to the inflow end 104 of the frame 102 than the leaflets 172^b. In some examples, cusp lines 176 leaflets 172^b can be closer to the outflow end 106 of the frame 102 than the distal end 182 of the engagement portion 180.

[0203] In some examples, the distal edge 136 of the base layer portion 132 can be connected to the frame 102. In some examples, the distal edge 136 of the base layer portion 132 can be connected to the frame 102 adjacent to the inflow end 104 thereof.

[0204] In some examples, the base layer portion 132 can be at least partially overlapping axially with the engagement portion 180^b. In some cases, it may be advantageous for the engagement portion 180^b to have a thickness T2 that is smaller than a thickness T1 of the leaflets 172. In some examples, a thickness T1 of the engagement portion 180^b, which is smaller than the thickness T2, can enable axial overlap of the engagement portion 180^b with the skirt 130 without significantly increasing the valve's overall crimped profile. In some examples, a thickness T1 of the engagement portion 180^b, which is smaller than the thickness T2, can enable axial overlap of the engagement portion 180^b with the base layer portion 132 without significantly increasing the valve's overall crimped profile. In some examples, a thickness T1 of the engagement portion 180^b, which is smaller than the thickness T2, can lead to a relatively small combined thickness of the engagement portion 180^b and the base layer portion 132. In some examples, the relatively small combined thickness of the engagement portion 180^b and the base layer portion 132 can reduce the crimped profile of the prosthetic valve 100, which can facilitate passage of the prosthetic valve 100 through narrower curved portions of a patient's vasculature.

[0205] In some examples, the base layer portion 132 can have a thickness T3. In some examples, the base layer portion 132 can have a thickness T3 at a portion which axially overlaps with the engagement portion 180. In some examples, an overlapping potion between the base layer portion 132 and the engagement portion 180 has a combined thickness of T2+T3. In some examples, the thickness T1 of the leaflets can be greater than or equal to the combined thickness of the base layer portion and the engagement portions T2+T3.

[0206] In some examples, the cusp lines 176 of the leaflets 172 can be sewed to the frame 102. In some cases, the cusp line 176 can be the part of the valvular structure 170^b that can optionally experience relatively high mechanical stress during the operation of the prosthetic valve 100. Therefore, the thickness T1 along the cusp lines 176 may be kept sufficiently thick to withstand such stresses. In contrast, the engagement portion 180 is not meant to move during normal operation of the prosthetic valve 100, therefore subjected to significantly smaller stresses. Thus, in some examples, the thickness T2 of the engagement portion 180 can be relatively thin without increasing risk of tearing or other failure modes thereof.

[0207] In some examples, the protruding extensions 150 of the skirt 130, such as exemplary protruding extension 150^a of skirt 130^a shown in Fig. 2B, can comprise foam or foam-like material 148 which is compressible and is biased radially outwards in a free state of the protruding extension 150. In some examples, the foam material 148 can be selected from the group consisting of: polyethylene foam, polyethylene terephthalate mesh and a combination thereof. In some examples, the foam material 148 can be porous. In some examples, the foam material 148 can have pore size in the range of 3 micron to 50 micron, including each value and sub-range within the specified range.

[0208] In some examples, each of the protruding extensions 150 can have an inner surface 1502 and an outer surface 1501. In some examples, the inner surface 1502 can be in contact with the base layer portion 132. In some examples, the inner surface 1502 can be attached to the base layer portion 132. In some examples, the outer surface 1501 can be curved, such as being semi-spherical or dome shaped. In some examples, the outer surface 1501 can be positioned radially away from the inner surface 1502.

[0209] In some examples, the outer surfaces 1501 of the protruding extensions 150 can be porous. In some examples, the outer surfaces 1501 of the protruding extensions 150 can have pore size in the range of 3 micron to 50 micron, including each value and sub-range within the specified range. [0210] In some examples, the outer surfaces 1501 of the protruding extensions 150 can be laminated by a coating layer 1503 (indicated, for example, in Fig. 5A). In some examples, the coating layer 1503 can be perforated. In some examples, the coating layer 1503 can be hydrophilic. In some examples, the coating layer 1503 can have a high durometer. In some examples, the base layer portion 132 can have a high durometer.

[0211] In some examples, each one of the protruding extensions 150 of the skirt 130 can have a thickness in the range of 10 micron to 100 micron, including each value and sub-range within the specified range. The thickness of a protruding extension 150 is defined between the inner surface 1502 of the protruding extension 150 and the outermost point (i.e., the most radially away point) of the outer surface 1501, in a free or uncompressed state of the extension 150.

[0212] In some examples, there is provided a method of forming a valvular structure 170^b. In some examples, there is provided a method of forming a valvular structure 170^b of prosthetic valve 100. In some examples, the valvular structure 170^b can be the valvular structure 170^b described above with respect to Fig. 4. In some examples, there is provided a method of forming a prosthetic valve 100. In some examples, there is provided a method of forming the prosthetic valve 100 described above with respect to Fig. 4, optionally including the valvular structure 170^b. In some examples, the valvular structure 170^h of the method can include a plurality of leaflets 172^b that can have a thickness Tl. In some examples, the valvular structure 170^b formed by a method disclosed herein can include an engagement portion 180 that can optionally have a thickness T2. In some examples, Tl and/or T2 may be as described above with respect to Fig 4.

[0213] In some examples, the valvular structure 170^b formed by a method disclosed herein can be attached to the frame 102 of the prosthetic valve 100, optionally by sewing, adhering, glueing and the like of the valvular structure 170^b to the frame 102. In some examples, the attachment can be between the side edges 168 of the valvular structure 170^b and the frame 102. [0214] In some examples, the methods can include a step of providing a generally rectangular patch 166^b. In some examples, the patch 166^b can include a moldable material. In some examples, the patch 166^b can extend between a first side edge 168a and a second side edge 168b. In some examples, the first side edge 168a and the second side edge 168b can be substantially parallel.

[0215] In some examples, the patch 166^b provided by the step of the present method can have a thickness Tl. In some examples, the patch 166^b provided by the step of the present method can have a uniform thickness Tl. [0216] In some examples, the patch 166^b provided by the step of the present method can be 3D-shaped.

[0217] In some examples, the methods can include a step of inserting a 2D-shaped patch (e.g., a flattenable patch) into a mold. In some examples, the step can further include forcing the 2D- shaped patch to assume a three-dimensional shape. In some examples, the 2D-shaped patch can include a tissue material. In some examples, the step can further include cross-linking the tissue material to produce a 3D-shaped patch 166^b.

[0218] In some examples, the 3D-shaped patch 166^b can include a plurality of leaflets 172^b. In some examples, the bellies 174 can form a 3D-shape of the patch 166^b.

[0219] In some examples, the patch 166^b provided by the step of the present method can include an engagement portion 180. In some examples, the engagement portion 180 can be connected to the plurality of leaflets 172^b. In some examples, the engagement portion 180 can extend between a distal end thereof 182 and the leaflets 172^b.

[0220] In some examples, the methods can include a step of cutting a thickness portion of the engagement portion 180. In some examples, the cutting can include cutting through substantially the entire surface of the engagement portion 180. In some examples, cutting a thickness portion of the engagement portion 180 can be performed without cutting any thickness portion of the leaflets 172^b.

[0221] In some examples, the cutting step can result in thinning the cut thickness portion of the engagement portion 180. In some examples, the cutting step can comprise reducing the thickness of the cut portion of the engagement portion 180 from T1 to T2. In some examples, the cutting step can result in thinning engagement portion 180. In some examples, cutting step can comprise reducing the thickness of the engagement portion 180 from T1 to T2. In some examples, T1 can be greater than T2. In some examples, T1 can be in the range of 50-200 micron. Exemplary relations between T1 and T2 are presented herein.

[0222] In some examples, the cutting can be performed by laser milling or by mechanical skiving. In some examples, the cutting can be performed by laser milling. In some examples, the cutting can be performed by mechanical skiving.

[0223] In some examples, the patch 166^b can include a tissue material. In some examples, the patch 166^b can include a tissue material that can be easy to cut.

[0224] In some examples, the cutting step can precede the molding step. In some examples, the molding step can precede the cutting step.

[0225] In some examples, the methods can include a step of rolling the patch 166^b. In some examples, rolling the patch 166^b can be performed by bringing the first side edge 168a and the second side edge 168 together. In some examples, rolling the patch 166^b can be performed by bringing the first side edge 168a and the second side edge 168 together to assume a cylindrical configuration.

[0226] In some examples, the methods can include a step of connecting the patch 166^b to a frame 102 of a prosthetic valve 100.

[0227] Fig. 5A shows a perspective view of an exemplary prosthetic valve 100^c. Prosthetic valve 100^c is an exemplary implementation of a prosthetic valve 100, and thus can include any of the features described for a prosthetic valve 100 throughout the current disclosure, except that the skirt 130^c of prosthetic valve 100^c has a higher base layer portion 132^c that extends in the proximal direction (e.g., towards outflow end 106) past the protruding extensions 150, such that an upper (or proximal) portion of the skirt 130^c is devoid of protruding extensions 150.

[0228] In some examples, at least some of the protruding extensions 150 can extend radially outwards from the base layer portion 132. In some examples, at least some of the protruding extensions 150 can extend radially outwards from the base layer portion 132 and through corresponding cells 116. In some examples, each one of the protruding extensions 150 can extend radially outwards from the base layer portion 132. In some examples, each one of the protruding extensions 150 can extend radially outwards from the base layer portion 132 and through corresponding cells 116.

[0229] In some examples, as shown for example Figs. 3C and 5A, the cusp line 176 can have a cusp arched shape defining a leaflet distal end 177. In some examples, such as for a unitary valvular structure 170, the cusp lines 176 of adjacent leaflets can define inter-leaflet regions 179 therebetween, when the proximal edge 134 of the skirt 130 is positioned proximal to the leaflet distal end 177, at least a part of the inter-leaflet region 179 may be covered by the base layer portion 132. The higher extension of the skirt 130^c can result in a higher sealing length around the frame 102.

[0230] In some examples, at least part of the inter-leaflet regions 179 can be covered by portions of the base layer portion 132. In the example illustrated in Fig. 5A, the proximal edge 134 of base layer portion 132^c is positioned proximal to the leaflet distal end 177, such that the inter-leaflet regions 179 are partially covered by the base layer portion 132^c. When the valvular structure 170 is formed as a unitary piece of material, defining integrally formed inter-leaflet regions 179 between leaflets 172, a portion of an inter-leaflet region 179 that remains uncovered by the base layer portion 132^c can be directly attached to the frame 102 to seal thereagainst and prevent perivalvular leakage across the frame between the leaflet 172. [0231] In some examples, the proximal edge 134 of the base layer portion 132^c can be relatively linear, such that the height of the base layer portion 132^c, defined between the distal edge 136 and the proximal edge 134, can be optionally uniform along the circumference of the valve 100^c. In some examples, the proximal edge 134 of the base layer portion 132^c can have a generally straight pattern such that it can be substantially uniformly distanced from the inflow end 104 of the frame 102. In some examples, the proximal edge 134 of the base layer portion 132^c can have a generally straight pattern such that it can be substantially uniformly distanced from the outflow end 106 of the frame 102.

[0232] Increasing the height of a skirt 130 can improve PVL sealing across the prosthetic valve by increasing the sealing length, However, in the case of a skirt that includes protruding extensions 150, increasing the height of the skirt 130 such that protruding extensions are also present along regions proximal to the leaflet distal ends 177 will result in the thickness of the protruding extensions 150 added to the thickness of the leaflets 172 at such regions, which will eventually increase the overall crimped profile of the prosthetic valve 100. However, and as shown for prosthetic valve 100^c in Fig. 5 A, elongating solely the base layer portion 132^c such that its proximal edge 134 is proximal to the leaflet distal ends 177, while all protruding extensions 150 are positioned distal to the leaflet distal ends 177, will allow improvement of PVL sealing by having a longer sealing length of the skirt 130^c, without significant increase in the crimped profile as the regions of the leaflets 172 and the regions along which the protruding extensions 150 are disposed, are separated from each other.

[0233] Fig. 5B shows a perspective view of an exemplary prosthetic valve 100^d, which can be similar to any example of a prosthetic valve 100^c disclosed herein, except that the proximal edge 134 of the base layer portion 132^d of the skirt 130^d of prosthetic valve 100^d extends between throughs 142, which can be closer to the inflow end 104 of the frame 102, and peaks 140, which can be closer to the outflow end 106 of the frame 102. In some examples, to the base layer portion 132^d can extend towards peaks 140 in a manner that forms a plurality of outflow extensions 138 extending from the throughs 142.

[0234] In some examples, the prosthetic valve 100^d can include a valvular structure 170^d which can be similar to any example of a valvular structure 170 disclosed herein, except that the valvular structure 170^d includes separately formed leaflets 172^d instead of being formed as a one-piece material. The valvular structure 170^d can be devoid of an integral engagement portion 180, such that the cusp line 176^d of each leaflet 172^d can be a free end portion that does not extend further to any extension forming an engagement portion. [0235] An exemplary valvular structure 170^d is illustrated in Fig. 6, including three separately formed leaflets 172^d that can be joined together and mounted against the frame 102 by being coupled to the frame 102 directly or indirectly (such as via skirt 130) along their cusp lines 176^d. Each leaflet 172^d can include a pair of opposite commissure attachment portions in the form of tabs 184^d between their cusp line 176^d and the free edge 178. Tabs 184^d of adjacent leaflets can be joined to form commissures 186 secured to the frame 102.

[0236] When the leaflets 172^d are mounted inside the frame 102, the inter-leaflet regions 179 defined between cusp lines 176^d of adjacent leaflets 172^d do not include solid matter such as tissue or fabric. In such cases, utilization of a skirt 130^c having a base layer portion 132^c that optionally defines a relatively linear proximal edge 134 of the type described above with respect to Fig. 5A, positioned above the leaflet distal ends 177 but below (e.g., distal to) the tabs 184^d or upper ends of the cusp lines 176^d, can result in upper exposed portions of the interleaflet regions 179 (e.g., the portions of the inter-leaflet regions 179 proximal to the proximal edge 134 of a base layer portion 132^c) which are uncovered, posing a risk of perivalvular leakage of blood therethrough.

[0237] In some examples, a skirt 130^c having a base layer portion 132° defining a relatively linear proximal edge 134 can be utilized in combination with a valvular structure 170^d by further elongating the base layer portion 132^c such that the proximal edge 134 is proximate commissures 186 so as to cover the entire areas of the inter-leaflet regions 179, to prevent perivalvular leakage therethrough. However, uniformly elongating the base layer portion 132^c along the circumference of the prosthetic valve 100 will result in excess material of the 132^c laid in front of a larger portion of the leaflet bellies 174, which can further increase the overall crimped profile.

[0238] An exemplary base layer portion 132^d of a skirt 130^d shown in Fig. 5B is illustrated to include a proximal edge 134 extending between throughs 142 and peaks 140, thereby forming a plurality of outflow extensions 138 which are aligned with the inter-leaflet regions 179. In some examples, the outflow extensions 138 can be triangularly formed as illustrated, though it is to be understood that other shapes of the outflow extensions 138 are contemplated. In some examples, the outflow extensions 138 are shaped and dimensioned to entirely cover the interleaflet regions 179. Advantageously, a skirt 130^d equipped with a base layer portion 132^d having outflow extensions 138 as described herein and illustrated for example in Fig. 5B, can provide adequate PVL sealing, including over the inter-leaflet regions 179, without significantly increasing the overall crimped profile of the prosthetic valve 100^d. [0239] While an exemplary skirt 130^d is described herein for use with a valvular structure 170^d, it is to be understood that this is not meant to be limiting, and that an exemplary skirt 130^d that includes outflow extension 138 can be similarly used with any other type of valvular structure 170, including, for example, a one-piece valvular structure, such as any of the valvular structures 170^a or 170^b disclosed herein, in which case the outflow extension 138 can be aligned with and optionally coupled to (e.g., by stitching) the material (e.g., tissue material) forming the integral inter-leaflet regions 179.

[0240] Figs. 7 and 8 are perspective and top views, respectively, of an exemplary prosthetic valve 100^e. Prosthetic valve 100^e is an exemplary implementation of a prosthetic valve 100, and thus can include any of the features described for a prosthetic valve 100 throughout the current disclosure, except that the skirt 130^e of prosthetic valve 100^e includes at least two types of protruding extensions 150, such as first protruding extensions 150' and second protruding extensions 150", each type of protruding extensions 150 having a different radial dimension RD in a free or uncompressed state thereof.

[0241] A radial dimension RD of a protruding extensions 150 is defined as the maximal size or dimension thereof, protruding radially outwards from a corresponding cell 116 of the frame 102, in a free or uncompressed state of the protruding extensions 150. For example, and as shown in Fig. 2B, a radial dimension RD can be measured between its inner surface 1502 and the outermost point of its outer surface 1501. As shown in Figs. 7-8, A first protruding extensionl50' will have a radial dimension RD', which can be optionally greater than a radial dimension RD" of a second protruding extension 150". The radial dimension RD', can be optionally greater than the radial dimension RD" in an untensioned state of the first protruding extensions 150' and second protruding extensions 150" and/or the radial dimension RD', can be optionally greater than the radial dimension RD” when the first protruding extensions 150’ and second protruding extensions 150" are compressed radially inward.

[0242] The radial dimension of the first protruding extensions 150' in an untensioned or free state of the first protruding extensions 150'can be defined as RDE'. The radial dimension of the second protruding extensions 150” in an untensioned or free state of the second protruding extensions 150"can be defined as RDE".

[0243] As detailed herein, the protruding extensions 150, including the first protruding extensions 150' and/or the second protruding extensions 150" can be compressible, in some examples. Thus, in some examples, the protruding extensions 150 can further have a radial dimension in a compressed stated. Compressed state can include, in some examples, a radial inward compression of the protruding extensions 150. The protruding extensions 150 can experience a radial inward compression, optionally, when compressed by an external enclosure such as a delivery shaft or a capsule thereof. In some examples, the external enclosure is rigid and has a diameter of about 7.5mm.

[0244] A skirt 130^e can have a relatively elongated base layer portion 132^e having its proximal edge 134 positioned proximal to the leaflet distal ends 177, in a similar manner to that described herein for any example of skirt 130^c or 130^d. However, while the skirts 130^c and 130^d are illustrated in Figs. 5A and 5B, respectively, to be devoid of rows of protruding extensions 150 proximal to the leaflet distal ends 177, the skirt 130^e can include protruding extensions 150 extending through cell 116 of the frame 102 both above and below the leaflet distal ends 177. Since a valvular structure 170 can include leaflets 172 having a thickness (e.g., thickness Tl), the combination of the thickness Tl of the leaflets 172 and the radial dimension RD of protruding extensions 150 positioned in front of the leaflets 172, proximal to the leaflet distal ends 177, can increase the crimped profile of the valve. In some examples, one or more rows of first protruding extensions 150' having a radial dimension RD' can extend through corresponding cell row(s) 118 distal to the leaflet distal ends 177, and one or more rows of second protruding extensions 150” having a smaller radial dimension RD" can extend through corresponding cell row(s) 118 aligned with or proximal to the leaflet distal ends 177.

[0245] For example, Fig. 7 illustrates two rows of first protruding extensions 150' positioned below (or distal to) the leaflet distal ends 177, including inflow protruding extensions 150T extending radially outwards through inflow cells 1161 of the inflow cell row 1181, and distal protruding extensions 150'D extending radially outwards through spaces defined distal to the inflow struts 1101. The example shown in Fig. 7 further illustrates two rows of second protruding extensions 150" aligned with or positioned proximal to the leaflet distal ends 177, including first subsequent protruding extensions 150”Sl extending radially outwards through first subsequent cells 116S 1 of the first subsequent cell row 118S1, shown in this example to be axially aligned with the leaflet distal ends 177, and second subsequent protruding extensions 150"S2 extending radially outwards through second subsequent cells 116S2 of the second subsequent cell row 118S2, illustrated to be proximal to the leaflet distal ends 177. It is to be understood that two rows of first protruding extensions 150' and two rows of second protruding extensions 150" are shown in Fig. 7 by way of illustration and not limitation. Moreover, while the second subsequent protruding extensions 150"S2 are shown to be generally triangularly- shape, it is to be understood that this is shown by way of example only, and that any other shape is contemplated. [0246] By having smaller sized protruding extensions 150" in the radial direction, a longer PVL sealing length contributed by axial distribution of protruding extensions 150 along a larger length of the skirt 130^d can be achieved, without significantly increasing the crimped profile at the level of the leaflets 172. In some examples, the difference between the radial dimension RD' of the first protruding extensions 150' and the radial dimension RD" of the second protruding extensions 150" can be equal to or greater than the thickness T1 of the leaflets 172. In some examples, RD' can be at least 5% greater than RD”. In some examples, RD' can be at least 10% greater than RD". In some examples, RD' can be at least 15% greater than RD". In some examples, RD' can be at least 20% greater than RD". In some examples, RD' can be at least 25% greater than RD”. In some examples, RD' can be at least 33% greater than RD". In some examples, RD’ can be at least 50% greater than RD”. In some examples, RD' can be at least 75% greater than RD". In some examples, RD' can be at least 100% greater than RD".

[0247] In some examples, the difference between the radial dimension RDE' of the first protruding extensions 150' and the radial dimension RDE" of the second protruding extensions 150” when both in an untensioned state can be equal to or greater than the thickness T1 of the leaflets 172. In some examples, RDE' can be at least 5% greater than RDE". In some examples, RDE' can be at least 10% greater than RDE". In some examples, RDE' can be at least 15% greater than RDE". In some examples, RDE' can be at least 20% greater than RDE". In some examples, RDE' can be at least 25% greater than RDE". In some examples, RDE’ can be at least 33% greater than RDE". In some examples, RDE' can be at least 50% greater than RDE". In some examples, RDE' can be at least 75% greater than RDE". In some examples, RDE' can be at least 100% greater than RDE".

[0248] In some examples, the difference between the radial dimension RDe’ of the first protruding extensions 150’ and the radial dimension RDe” of the second protruding extensions 150" when both in a compressed state can be equal to or greater than the thickness T1 of the leaflets 172. In some examples, RDe' can be at least 5% greater than RDe". In some examples, RDe' can be at least 10% greater than RDc". In some examples, RDe' can be at least 15% greater than RDe”. In some examples, RDe' can be at least 20% greater than RDe”. In some examples, RDe' can be at least 25% greater than RDe". In some examples, RDE’ can be at least 33% greater than RDe". In some examples, RDe' can be at least 50% greater than RDe". In some examples, RDe' can be at least 75% greater than RDe". In some examples, RDe' can be at least 100% greater than RDe".

[0249] In some examples, the radial dimensions in the compressed state, RDe' and RDe” can be dictated by the amount of material (e.g., foam) within the corresponding protruding extensions 150. In some examples, the first protruding extensions 150' comprise filling material at a first amount and the second protruding extensions 150" comprise filling material at a second amount, which is greater than the first amount.

[0250] In some examples, the radial dimensions in the compressed state, RDc' and RDc" can be dictated by the type of material within the corresponding protruding extensions 150. In some examples, the first protruding extensions 150’ comprise a first filling material and the second protruding extensions 150" comprise a second filling material, which is different than the first filling material. In some examples, the first filling material is more compressible than the second filling material.

[0251] In some examples, the radial dimensions in the compressed state, RDc' and RDc" can be dictated by a geometrical design of the corresponding protruding extensions 150. In some examples, the first protruding extensions 150’ have a first geometrical design and the second protruding extensions 150" have a second geometrical design, which is different than the first geometrical design. In some examples, the first geometrical design is more flattenable than the second geometrical design.

[0252] While two types of differently sized protruding extensions 150' and 150" are described above and illustrated in Fig. 7, it is to be understood that, in some examples, a skirt 130^e of a prosthetic valve 100^e can include more than two types of differently sized protruding extensions 150, each having a different radial dimension RD. More than two types of differently sized protruding extensions 150 can optionally be arranged to achieve gradual change in radial depth of protrusion of a skirt 130 along a height of the valve.

[0253] As mentioned above, a protruding extension 150 can define an inner surface 1502 at the interface with the base layer portion 132, and an opposite outer surface 1501. In some examples, the outer surfaces 1501 of the protruding extensions 150 can be porous. In some examples, the outer surfaces 1501 of the protruding extensions 150 can have pore size in the range of 3 micron to 50 micron, including each value and sub-range within the specified range. In some examples, the outer surfaces 1501 of the protruding extensions 150 can be laminated by a coating layer 1503. In some examples, the coating layer 1503 can be perforated. In some examples, the coating layer 1503 can have aperture size in the range of 3 micron to 50 micron, including each value and sub-range within the specified range. The pore size of the outer surface 1501 and/or the coating layer 1503 is configured to be large enough to allow passage of fluids therethrough, so as to facilitate swelling and radial expansion of the protruding extension 150 upon exposure to the surrounding blood stream, while also being limited in size (e.g., small enough) to prevent loose or reticulated foam particles from being released from the protruding extension 150 into the blood stream. In some examples, the coating layer 1503 can be hydrophilic, which can advantageously increase smoothness of the outer surface of the protruding extension 150 and facilitate fluid absorbability into the protruding extension 150. In some examples, the coating layer 1503 can have a high durometer while also having a relatively high elasticity.

[0254] In some examples, the base layer portion 132 can have a high durometer, configured to prevent excessive undesired inwardly-oriented bending or protrusion thereof, and maintain it relatively taut against the inner surface of the frame 102. In some examples, base layer portion 132 can have a thickness in the range of 10 micron to 100 micron, including each value and sub-range within the specified range. In some examples, the coating layer 1503 can have a thickness in the range of 10 micron to 100 micron, including each value and sub-range within the specified range.

[0255] Fig. 9 shows a perspective view from a bottom view angle of an exemplary prosthetic valve 100^f. Prosthetic valve 100^f is an exemplary implementation of a prosthetic valve 100, and thus can include any of the features described for a prosthetic valve 100 throughout the current disclosure, except that the prosthetic valve 100^f further comprises reinforcement lines 146 configured to limit inwardly-oriented protrusion of the skirt 130^f.

[0256] During typical valve operation, the leaflets 172 transition between a closed state in diastole, with their free edges 178 coapting against each other, and an open state allowing blood to flow through the prosthetic valve 100. The outflow orifice through which the blood can flow determines the pressure gradient across the valve. An effective outflow orifice (EOA) is defined as the open space through which blood can flow when the valvular structure 170 is in the open configuration. When the prosthetic valve is expanded and implanted in a patient's body, the protruding extensions 150 are pressed against surrounding anatomical structures, such as the annulus and optionally calcified native leaflets, which can push against the protruding extensions 150 radially inwards. The pressure applied on the protruding extensions 150 can cause them to push, in turn, against the base layer portion 132, causing it to protrude radially inwards to some extent, relative to the frame 102. This optional inwardly-oriented extension of the base layer portion 132 can result in a narrower EOA, thereby producing a relatively high pressure gradient across the prosthetic valve.

[0257] As mentioned above, one way of mitigating such a risk involves providing a base layer portion having a relatively high durometer, configured to resist such inwardly-oriented protrusion of the base layer portion 132. In some examples, as schematically illustrated in Fig. 9, the skirt 130^f can include a plurality of reinforcement lines 146 configured to limit such inwardly -oriented protrusion of the base layer portion 132^f. In some examples, the reinforcement lines 146 can be positioned radially inwards to the protruding extensions 150. In some examples, the reinforcement lines 146 can be configured to prevent or limit inwardly- oriented extension of the base layer portion 132^f, such as by resisting a tendency of the base layer portion 132^f to extend radially inward when the protruding extensions 150 are inwardly pressed by the surrounding anatomy.

[0258] In some examples, at least some of the plurality of reinforcement lines 146 can be positioned radially inwards to the base layer portion 1 2^f. In some examples, each one of the plurality of reinforcement lines 146 can be positioned radially inwards to the base layer portion 132^f.

[0259] In some examples, at least some of the reinforcement lines 146 can extend between at least two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, at least some of the reinforcement lines 146 can extend between two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, at least some of the reinforcement lines 146 can extend between at least two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, at least some of the reinforcement lines 146 can extend between two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, at least some of the reinforcement lines 146 can extend between midpoints of at least two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, at least some of the reinforcement lines 146 can extend between midpoints of two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, at least some of the reinforcement lines 146 can extend between midpoints of at least two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, at least some of the reinforcement lines 146 can extend between midpoints of two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f. [0260] In some examples, each one of the reinforcement lines 146 can extend between at least two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, each one of the reinforcement lines 146 can extend between two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, each one of the reinforcement lines 146 can extend between at least two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, each one of the reinforcement lines 146 can extend between two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, each one of the reinforcement lines 146 can extend between midpoints of at least two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, each one of the reinforcement lines 146 can extend between midpoints of two struts 108 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, each one of the reinforcement lines 146 can extend between midpoints of at least two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f. In some examples, each one of the reinforcement lines 146 can extend between midpoints of two angled struts 110 of a cell 116 of the frame 102 of the prosthetic valve 100^f.

[0261] In some examples, the reinforcement lines 146 can extend between at least two struts 108 that do not share a common intermediate junction 124. In some examples, the reinforcement lines 146 can extend between two struts 108 that do not share a common intermediate junction 124. In some examples, the reinforcement lines 146 can extend between at least two angled struts 110 that do not share a common intermediate junction 124. In some examples, the reinforcement lines 146 can extend between two angled struts 110 that do not share a common intermediate junction 124. In some examples, the reinforcement lines 146 can extend between midpoints of at least two struts 108 that do not share a common intermediate junction 124. In some examples, the reinforcement lines 146 can extend between midpoints of two struts 108 that do not share a common intermediate junction 124. In some examples, the reinforcement lines 146 can extend between midpoints of at least two angled struts 110 that do not share a common intermediate junction 124. In some examples, the reinforcement lines 146 can extend between midpoints of two angled struts 110 that do not share a common intermediate junction 124.

[0262] In some examples, the reinforcement lines 146 can extend between at least two opposite struts 108. In some examples, the reinforcement lines 146 can extend between two opposite struts 108. In some examples, the reinforcement lines 146 can extend between at least two angled opposite struts 110. In some examples, the reinforcement lines 146 can extend between two angled opposite struts 110. In some examples, the reinforcement lines 146 can extend between midpoints of at least two opposite struts 108. In some examples, the reinforcement lines 146 can extend between midpoints of two opposite struts 108. In some examples, the reinforcement lines 146 can extend between midpoints of at least two angled opposite struts 110. In some examples, the reinforcement lines 146 can extend between midpoints of two angled opposite struts 110.

[0263] In some examples, the reinforcement lines 146 can extend between at least two substantially parallel struts 108. In some examples, the reinforcement lines 146 can extend between two substantially parallel struts 108. In some examples, the reinforcement lines 146 can extend between at least two angled substantially parallel struts 110. In some examples, the reinforcement lines 146 can extend between two angled substantially parallel struts 110. In some examples, the reinforcement lines 146 can extend between midpoints of at least two substantially parallel struts 108. In some examples, the reinforcement lines 146 can extend between midpoints of two substantially parallel struts 108. In some examples, the reinforcement lines 146 can extend between midpoints of at least two angled substantially parallel struts 110. In some examples, the reinforcement lines 146 can extend between midpoints of two angled substantially parallel struts 110.

[0264] In some examples, the midpoints of the struts 108 and/or angled struts 110 can be defined as any point within the central 50% of the length of the strut 108 and/or 110. In some examples, the midpoints of the struts 108 and/or angled struts 110 can be defined as any point within the central 40% of the length of the strut 108 and/or 110. In some examples, the midpoints of the struts 108 and/or angled struts 110 can be defined as any point within the central 30% of the length of the strut 108 and/or 110. In some examples, the midpoints of the struts 108 and/or angled struts 110 can be defined as any point within the central 20% of the length of the strut 108 and/or 110. In some examples, the midpoints of the struts 108 and/or angled struts 110 can be defined as any point within the central 10% of the length of the strut 108 and/or 110.

[0265] An exemplary illustration presented in Fig. 9 shows, inter alia, reinforcement lines 146 that extend between inflow angled struts 1101 and first subsequent angled struts 110S1 of inflow cells 1161. The illustration presented in Fig. 9 further shows, inter alia, reinforcement lines 146 that extend between first subsequent angled struts 110S1 and second subsequent angled struts 110S2 of first subsequent cells 116S1.

[0266] In some examples, at least some of the reinforcement lines 146 can be formed as reinforcement portions of the base layer portion 132^f of the skirt 130^f. In some examples, each one of the reinforcement lines 146 can be formed as reinforcement portions of the base layer portion 132^f of the skirt 130^f. In some examples, the thickness of the base layer portion 132^f at the reinforcement lines 146 can higher than the thickness of the base layer portion 132^f in nonreinforced portions thereof. In some examples, the increased thickness of the base layer portion 132^f at the reinforcement portions can provide the reinforcement of the reinforcement lines 146.

[0267] In some examples, the reinforcement lines 146 can be incorporated within the base layer portion 132^f. In some examples, the reinforcement lines 146 can be embedded within the base layer portion 132^f. [0268] In some examples, the reinforcement portions of the base layer portion 132^f can comprise a reinforcing material. In some examples, non-reinforced portions of the base layer portion 132^f can comprise a base layer portion material. In some examples, the base layer portion material can be different from the reinforcing material. In some examples, the base layer portion material can have lower tensile strength than the reinforcing material. In some examples, the base layer portion material can have lower durometer than the reinforcing material. In some examples, the reinforcing material can comprise a metal or a metal alloy. In some examples, the reinforcing material can consist of a metal.

[0269] In some examples, the at least some of the reinforcement lines 146 can be sutured threads, extending between two or more of the struts 108. In some examples, each one of the reinforcement lines 146 can be sutured threads, extending between two or more of the struts 108. In some examples, the at least some of the reinforcement lines 146 can be sutured threads, extending between two or more of the angled struts 110. In some examples, each one of the reinforcement lines 146 can be sutured threads, extending between two or more of the angled struts 110.

[0270] The suture-based reinforcement lines 146, in some examples, can be tied to two strut(s) 108 and/or angled stmt(s) 110, e.g., at the midpoints thereof, as detailed herein for any exemplary extension of reinforcement lines 146.

[0271] The suture-based reinforcement lines 146, in some examples, can be tied to two strut(s) 108 and/or angled struts 110 of the same cell 116, e.g., the suture-based reinforcement lines 146, can be tied to two strut(s) 108 and/or angled struts 110 that do not share a common intermediate junction 124 and/or are opposite and/or are substantially parallel struts 108, 110, as detailed herein for any exemplary extension of reinforcement lines 146.

[0272] In some examples, a suture-based reinforcement line 146 can be sutured to a strut 108. In some examples, a suture-based reinforcement line 146 can be sutured to the strut 108 at a midpoint of the strut 108. In some examples, a suture-based reinforcement line 146 that can be sutured to the strut 108 can optionally penetrate through the base layer portion 132^f radially inward. In some examples, a suture-based reinforcement line 146 that can be sutured to the strut 108 can optionally penetrate through the base layer portion 132^f radially inward in the vicinity of the strut 108. In some examples, a suture-based reinforcement line 146 that can be sutured to the strut 108 can optionally extend towards another strut 108.

[0273] In some examples, a suture-based reinforcement line 146 that can extend towards the other strut 108 can optionally penetrate through the base layer portion 132^f radially outwards. In some examples, a suture-based reinforcement line 146 that can extend towards the other strut 108 can optionally penetrate through the base layer portion 132^f radially outwards in the vicinity of the other strut 108. In some examples, a suture-based reinforcement line 146 that can penetrate through the base layer portion 132^f radially outwards can be optionally sutured to the other strut 108. In some examples, a suture-based reinforcement line 146 that can penetrate through the base layer portion 132^f radially outwards can be optionally sutured to the other strut 108 at a midpoint of the other strut 108.

[0274] In some examples, a suture-based reinforcement line 146 can be sutured to an angled strut 110. In some examples, a suture-based reinforcement line 146 can be sutured to the angled strut 110 at a midpoint of the angled strut 110. In some examples, a suture-based reinforcement line 146 that can be sutured to the angled strut 110 can optionally penetrate through the base layer portion 132^f radially inward. In some examples, a suture-based reinforcement line 146 that can be sutured to the angled strut 110 can optionally penetrate through the base layer portion 132^f radially inward in the vicinity of the angled strut 110. In some examples, a suturebased reinforcement line 146 that can be sutured to the angled strut 110 can optionally extend towards another angled strut 110.

[0275] In some examples, a suture-based reinforcement line 146 that can extend towards the other angled strut 110 can optionally penetrate through the base layer portion 132^f radially outwards. In some examples, a suture-based reinforcement line 146 that can extend towards the other angled strut 110 can optionally penetrate through the base layer portion 132^f radially outwards in the vicinity of the other angled strut 110. In some examples, a suture-based reinforcement line 146 that can penetrate through the base layer portion 132^f radially outwards can optionally be sutured to the other angled strut 110. In some examples, a suture-based reinforcement line 146 that can penetrate through the base layer portion 132^f radially outwards can optionally be sutured to the other angled strut 110 at a midpoint of the other angled strut 110.

[0276] In some examples, reinforcement line(s) 146, such as suture-based reinforcement line(s) 146, can extend between strut(s) 108 and/or angled strut(s) 110 that do not belong to the same cell 116. For example reinforcement line(s) 146 can extend between an inflow angled strut 1101 and a strut 108 or angled strut 110, which is in the vicinity of the proximal edge 134 of base layer portion 132^f. Such reinforcement line(s) 146 can reinforce a plurality of protruding extensions 150.

[0277] In some examples, reinforcement line(s) 146, such as suture-based reinforcement line(s) 146, can be untensionable. Tensionable or stretchable reinforcement line(s) 146 may be stretched upon the radial inward pressure applied by the protruding extensions 150, in some examples. In some examples, reinforcement line(s) 146, such as suture-based reinforcement line(s) 146, can have a high Young Modulus. In some examples, polyethylene terephthalate has high Young Modulus of about 2950 MPa, and may be used as a reinforcement line 146 forming material. In some examples, the reinforcement line(s) 146 are made of a material which has a Young Modulus of at least 1500MPa. In some examples, the reinforcement line(s) 146 are made of a material which has a Young Modulus of at least 2000MPa. In some examples, the reinforcement line(s) 146 are made of a material which has a Young Modulus of at least 2500MPa.

[0278] Fig. 10A shows a flattened view of an exemplary skirt 130, which can be mountable within a frame 102 of a prosthetic valve 100 as detailed herein, and can be implemented according to any of the examples described herein for a skirt 130 that includes protruding extensions 150 extending from the base layer portion 132. Fig. 10B is an enlarged view of a section of the exemplary skirt 130.

[0279] While the base layer portion 132 is shown in Fig. 10 A to have generally linear proximal edge 134 and distal edge 136, it is to be understood that any of the proximal edge 134 or distal edge 136 can have any other shape. While the skirt 130 is shown in Figs. 10A-10B to includes four rows of protruding extensions 150 covering substantially the entire height of the skirt 130, it is to be understood that this is shown by way of illustration and not limitation, and that the skirt 130 can include any number of rows of protruding extensions 150 spread in any desired arrangement of the base layer portion 132, wherein the protruding extensions 150 can include diamond- shaped cells, triangularly-shaped cells, or any other shape of cells.

[0280] In some examples, the base layer portion 132 can be positioned radially away from an engagement portion 180 of an exemplary valvular structure 170 when the skirt 130 is mounted on a prosthetic valve 100. In some examples, the engagement portion 180 of an exemplary valvular structure 170 can be at least partially covered by the base layer portion 132 of the skirt 130 when the skirt 130 is mounted on a prosthetic valve 100. In some examples, the engagement portion 180 of an exemplary valvular structure 170 can be entirely covered by the base layer portion 132 of the skirt 130. In some examples, the engagement portion 180 of an exemplary valvular structure 170 can be at least partially covered by the skirt 130. In some examples, the engagement portion 180 of an exemplary valvular structure 170 can be entirely covered by the skirt 130.

[0281] In some examples, the base layer portion 132 of the skirt 130 can extend between the distal edge 136 and the commissures 186 when the skirt 130 is mounted on a prosthetic valve 100. In some examples, upon extension between the distal edge 136 and the commissures 186, the base layer portion 132 can at least partially cover the engagement portion 180 of an exemplary valvular structure 170. In some examples, upon extension between the distal edge 136 and the commissures 186, the base layer portion 132 can fully cover the engagement portion 180 of an exemplary valvular structure 170.

[0282] In some examples, the skirt 130 can define a plurality of inter-extension gaps 144, as indicated in Figs. 10A-10B. An inter-extension gap 144 can be optionally defined between two adjacent protruding extensions 150 of the skirt 130. An inter-extension gap 144 can be optionally defined as a region dividing or separating between two adjacent protruding extensions 150.

[0283] The skirt 130 can include pairs of protruding extensions 150, wherein each pair of adjacent protruding extensions 150 can include two adjacent protruding extensions configured to extend through corresponding adjacent cells 116, when the skirt 130 is mounted on the frame 102. Two adjacent protruding extensions 150 can be defined as sharing a common interextension gap 144.

[0284] In some examples, the skirt 130 can be made of a stretchable material. In some examples, the base layer portion 132 of the skirt 130 can be made of a stretchable material. In some examples, protruding extensions 150 of the skirt 130 can comprise a stretchable material. In some examples, the base layer portion 132 along the inter-extension gaps 144 can be made of a stretchable material. In some examples, the skirt 130 can be stretchable. In some examples, the base layer portion 132 can be stretchable. In some examples, the protruding extensions 150 can be stretchable. In some examples, the inter-extension gaps 144 can be stretchable. In some examples, upon stretching the skirt 130, the dimensions of the base layer portion 132 can be altered. In some examples, upon stretching the skirt 130, the dimensions of the inter-extension gaps 144 can be altered. In some examples, upon stretching the skirt 130, the dimensions of the protruding extensions 150 can be altered.

[0285] As used herein, the term "stretchable” can refer to the ability of a material, structure, device or device component to be strained in tension (e.g., being made longer and/or wider) without undergoing permanent deformation or failure such as tear or fracture, e.g., the ability to elongate at least 5% or at least 10% of its length without permanently deforming, tearing, or breaking. The term can also be meant to encompass substrates that may be elastically and/or plastically deformable (i.e. after being stretched, the substrate may return to its original size when the stretching force is released or the substrate may not return to its original size and in some examples, may remain in the stretched form) and the deformation (i.e. stretching and optionally flexing) may occur during manufacture of the substrate (e.g. with the substrate being stretched and optionally flexed to form its final shape), during assembly of a device.

[0286] In some examples, the skirt 130 can be elastically deformable. In some examples, the base layer portion 132 of the skirt 130 can be elastically deformable. In some examples, the protruding extensions 150 of the skirt 130 can be elastically deformable. In some examples, the inter-extension gaps 144 of skirt 130 can be elastically deformable.

[0287] As used herein, the term "elastic deformation” can refer to a deformation caused to a material, structure, device or device component, wherein the deformation caused may be reversible, and the deformation disappears after the removal of applied forces. A classic example of elastic deformation is the stretching of a rubber band.

[0288] In some examples, the skirt 130 can have an elongation at break of at least 5%. In some examples, the skirt 130 can have an elongation at break of at least 10%. In some examples, the skirt 130 can have an elongation at break of at least 15%. In some examples, the skirt 130 can have an elongation at break of at least 20%. In some examples, the skirt 130 can have an elongation at break of at least 25%. In some examples, the base layer portion 132 of the skirt 130 can have an elongation at break of at least 5%. In some examples, the base layer portion 132 can have an elongation break of at least 10%. In some examples, the base layer portion 132 can have an elongation at break of at least 15%. In some examples, the base layer portion 132 can have an elongation at break of at least 20%. In some examples, the base layer portion 132 can have an elongation at break of at least 25%. In some examples, the protruding extensions 150 of the skirt 130 can have an elongation at break of at least 15%. In some examples, the protruding extensions 150 can have an elongation at break of at least 20%. In some examples, the protruding extensions 150 can have an elongation at break of at least 25%. [0289] As used herein, the term "elongation at break” can refer to a measure of a ductility and toughness of a material, structure, device or device component. The elongation at break can quantify the amount of deformation a material can withstand before breaking. Elongation can be a metric that is regularly employed in the testing and assessment of materials and components for engineering and manufacturing applications.

[0290] The inter-extension gaps 144 can have width WG, as indicated in Fig. 10B, which can be optionally defined between parallel edges of adjacent protruding extensions 150 in a free state of the skirt 130 (e.g., prior to mounting the skirt 130 against frame 102). The protruding extensions 150 can have width Wp, as indicated in Fig. 10B, which can be measured as the maximal width of a protruding extensions 150 in the lateral (or circumferential) direction in a free state of the skirt 130 (e.g., prior to mounting the skirt 130 against frame 102). [0291] In some examples, a distance between two adjacent protruding extensions 150 at a position adjacent to the strut 108, along which they both extend radially outwards, is WG. In some examples, a distance between two adjacent protruding extensions 150 at a position adjacent to the angled strut 110, along which they both extend radially outwards, is WG.

[0292] In some examples, the struts can have widths Ws, indicated, for example, in Figs. 1A- 1B. As used herein, a "width" of a strut is measured between opposing locations on opposing surfaces of a strut that extend between the radially facing inner 128 and outer 127 surfaces of the frame.

[0293] In some examples, Ws can be greater than WG. In some examples, Ws can be at least 5% greater than WG- In some examples, Ws can be at least 10% greater than WG. In some examples, Ws can be at least 20% greater than WG. In some examples, Ws can be at least 25% greater than WG.

[0294] In some examples, when the skirt 130 having pre-assembly inter-extension gap widths WG that are smaller than the strut widths Ws, the inter-extension gaps 144 can be stretched over the corresponding struts 108 when the skirt 130 is mounted against the frame 102, forcing the adjacent protruding extensions 150 to be tightly pressed (e.g., in the circumferential direction) against the corresponding struts 108 disposed therebetween. In this manner, the protruding extensions 150 can be more densely packed within the corresponding cells 116, which can advantageously improve retention of the skirt 130 against the frame 102.

[0295] An additional advantage of the dense packing of the protruding extensions 150 c within the corresponding cells 116, is that it can enable to reduce the number of stitches required in order to mount and fasten the skirt 130 to the frame 102.

[0296] In some examples, at least some of the plurality of protruding extensions 150 can be in contact with protruding extensions 150 adjacent thereto, at positions, which are located radially away from the cells 116 through which the protruding extensions 150 extend. In some examples, contact between adjacent protruding extensions 150 can create more uniform continuity in the external surface of the prosthetic valve.

[0297] The frame 102 can include pairs of adjacent cells 116, each pair including two adjacent cells 116 that can be defined as cells 116 through which two adjacent protruding extensions 150 of the skirt 130 extend, when the skirt 130 is mounted against the frame 102. Two adjacent cells 116 can be defined as sharing a strut 108 and/or angled strut 110.

[0298] In some examples, there is provided a method of assembling a prosthetic valve 100 by pre- stretching a paravalvular leakage (PVL) skirt 130 prior to mounting the skirt 130 against a frame 102 of the valve 100. In some examples, the method can include a step of providing a frame 102 that can be implemented according to any example of a frame 102 described herein. [0299] In some examples, the method can include a step of providing a PVL skirt 130, optionally in a flattened configuration of the skirt 130. In some examples, the PVL skirt 130 can be a 3D-shaped elongated and optionally flattened PVL skirt. In some examples, the flattened PVL skirt 130 can include two side portions, 1302a and 1302b extending between a proximal edge portion 134 and a distal edge portion 136. In some examples, each of the proximal edge 134 portion and a distal edge portion 136 can be longer than the two side portions. The terms "PVL skirt 130" and "skirt 130", as used herein, are interchangeable.

[0300] In some examples, the PVL skirt 130, when provided in a flattened configuration thereof, can include a flat base layer portion 132. In some examples, the base layer portion 132 can be elastically stretchable.

[0301] In some examples, the PVL skirt 130 can include a plurality of protruding extensions 150, each extending away from the base layer portion 132 to define a 3D-shape of the skirt 130. In some examples, the protruding extensions 150 can be elastically stretchable.

[0302] A distance between the two side portions of the skirt 130 in an untensioned state thereof can be defined as Dsu- In some examples, the method can include a step of laterally stretching the PVL skirt 130, optionally while in its flattened configuration, to a stretched state. Upon the stretching of the skirt 130, the distance between the two side portions in the stretched state of the skirt 130 can be defined as Dss, which can be greater than Dsu. In some examples, Dss can be at least 5% greater than Dsu. In some examples, Dss can be at least 10% greater than Dsu. In some examples, Dss can be at least 15% greater than Dsu- In some examples, Dss can be at least 20% greater than Dsu. In some examples, Dss can be at least 25% greater than Dsu.

[0303] In some examples, the method can include a step of rolling the flattened PVL skirt 130. In some examples, the rolling can include bringing the side potions of the skirt 130 together. In some examples, the rolling can include assuming a cylindrical configuration of the skirt 130. In some examples, the rolling can include bringing the side potions of skirt 130 together to assume a cylindrical configuration of the skirt. It is to be understood that upon assuming a cylindrical configuration, the skirt is no longer flattened. In some examples, the skirt 130 is stretched in its flattened configuration, and is maintained in a stretched state when rolled to assume a cylindrical configuration. In some examples, the skirt 130 can remain unstretched in its flattened configuration, and can be circumferentially stretched after rolling thereof to the cylindrical configuration. [0304] In some examples, the method can include a step of mounting the stretched rolled skirt 130 against the frame 102, such as by approximating the base layer portion 132 to the inner surface 128 of the frame and passing the protruding extensions 150 through corresponding cells 116, optionally until the base layer portion 132 contacts the inner surface 128 of the frame 102. As described above, two adjacent protruding extensions 150 can be defined as extending through corresponding adjacent cells 116. A distance between two adjacent protruding extensions 150 in the untensioned or unstretched state, prior to mounting against the frame 102, can be equal to the width Wc of inter-extension gaps 144, which can be equal to or smaller than the width Ws of angled struts 110, as described above. When the skirt is laterally or circumferentially stretched, the distance between two adjacent protruding extensions 150 will extend to a gap which is greater than WG, and can be optionally greater than the width Ws of corresponding angled struts 110.

[0305] In some examples, mounting the stretched rolled skirt 130 against the frame 102 can include axially positioning the skirt 130 such that the inflow end 104 of the frame 102 can be closer to the distal edge portion 136 than it is to the proximal edge portion 134.

[0306] In some examples, mounting the stretched rolled skirt 130 against the frame 102 can include axially positioning the skirt 130 such that the outflow end 106 of the frame 102 can be closer to the proximal edge portion 134 than it is to the distal edge portion 136.

[0307] In some examples, the method can include a step of relieving tension created by the stretching. In some examples, upon the relief, a distance between the two adjacent protruding extensions 150 in the relieved or unstretched state, subsequent to mounting against the frame 102, can be less than its size in the stretched state, striving to return to the original size WG- Since the two adjacent protruding extensions 150 are separated by a corresponding angled strut 110 extending therebetween upon reliving tension, the distance between the two adjacent protruding extensions 150 in the relieved or unstretched state, subsequent to mounting against the frame 102, can be substantially equal to the width Ws of the angled strut 110.

[0308] The distance between the two side portions of the skirt 130 in the relieved state can be defines as DSR, which can be optionally greater than or equal to Dsu- In some examples, Dss can be greater than DSR. In some examples, Dss can be at least 5% greater than DSR. In some examples, Dss can be at least 10% greater than DSR. In some examples, Dss can be at least 15% greater than DSR. In some examples, Dss can be at least 20% greater than DSR. In some examples, Dss can be at least 25% greater than DSR.

[0309] In some examples, the method can further include a step of attaching the skirt 130 to the frame 102, such as by suturing or using any other type of suitable couplers. Attaching the skirt 130 to the frame 102 can be performed after approximation of the base layer portion 132 to the inner surface 128 of the frame 102 and extending the protruding extensions 150 through the corresponding cells 116. Releasing tension to move the skirt 130 to an unstretched configuration can be performed prior to, during, or after attaching the skirt 130 to the frame 102. In some examples, the base layer portion 132 can be brought into contact with the inner surface 128 of the frame 102, after which tension can be released, prior to attachment of the skirt 130 to the frame 102 by suturing and the like. The pressure applied by adjacent protruding extensions 150 against corresponding struts 108 after releasing the tension can advantageously help in temporarily maintaining position of the skirt 130 over the frame 102, thereby simplifying the subsequent attachment procedure.

[0310] In some examples, there is provided a method of assembling a prosthetic valve 100 by planarly compressing the protruding extensions 150 of a PVL skirt 130. In some examples, the method can include a step of providing a frame 102 that can be implemented according to any example of a frame 102 described herein. An area of a cell 116 can be defined as Ac.

[0311] In some examples, the method can include a step of providing a PVL skirt 130, optionally in a flattened configuration of the skirt 130. In some examples, the flattened PVL skirt 130 can be a 3D-shaped elongated and optionally flattened PVL skirt.

[0312] A projected area of a protruding extension 150 in a free state thereof can be defined as AGU- In some examples, the protruding extensions 150 can be elastically compressible. The term "projected area", with respect to that of a protruding extension 150, refers to the area of the protruding extension 150 in a planar uncompressed state thereof, as projected over the plane of the base layer portion 132. The projected area of a protruding extension 150 can be defined along a base portion thereof (e.g., at or in close proximity to the inner surface 1502 of protruding extension 150), configured to extend substantially between the inner surface 128 and the outer surface 127 of the frame 102 when the protruding extension 150 extends through the corresponding cells 116. The term "planar compression", as used herein, refers to compression of the protruding extensions 150 along a plane that is substantially orthogonal to the radial direction, such as along the plane of, or parallel to the plane of, the base layer portion 132. Thus, in some examples, the protruding extensions 150 can be compressible both in the radial and in the planar directions.

[0313] In some examples, the method can include a step of planarly compressing the protruding extensions 150. Upon compression of the protruding extensions 150, a projected area of the protruding extensions 150 in a planar compressed state can be defined as AGC, which can be smaller than AGU. [0314] In some examples, AGU can be at least 2% greater than AGC- In some examples, AGU can be at least 5% greater than AGC. In some examples, AGU can be at least 10% greater than AGC. In some examples, AGU can be at least 15% greater than AGC. In some examples, AGU can be at least 20% greater than AGC-

[0315] In some examples, the method can include a step of rolling the flattened PVL skirt 130. In some examples, the rolling can include bringing the side potions of the skirt 130together. In some examples, the rolling can include assuming a cylindrical configuration of the skirt 130. In some examples, the rolling can include bringing the side potions of the skirt 130together to assume a cylindrical configuration of the skirt. It is to be understood that upon assuming a cylindrical configuration, the skirt is no longer flattened.

[0316] In some examples, the method can include a step of mounting the rolled skirt 130 against the frame 102, such as by approximating the base layer portion 132 to the inner surface 128 of the frame and passing the protruding extensions 150 through corresponding cells 116, optionally until the base layer portion 132 contacts the inner surface 128 of the frame 102. As described above, two adjacent protruding extensions 150 can be defined as extending through corresponding adjacent cells 116.

[0317] In some examples, the method can include a step of planarly compressing the protruding extensions 150 from a projected area AGU to a projected area AGC that can be optionally equal to or smaller than the area Ac of a cell 116, prior to or during passing of the protruding extensions 150 through the corresponding cells 116, and allowing the protruding extensions 150 to re-expand to inside the corresponding cells 116 to assume a projected area equal to the area Ac of the cells 116.

[0318] In some examples, Ac can be greater than AGC. In some examples, Ac can be at least 2% greater than AGC. In some examples, Ac can be at least 5% greater than AGC. In some examples, Ac can be at least 10% greater than AGC. In some examples, Ac can be at least 15% greater than AGC. In some examples, Ac can be at least 20% greater than AGC.

[0319] In some examples, the protruding extensions 150 are not necessarily actively compressed in the planar directions prior to mounting the skirt 130 against the frame 102, but can be rather forced to compress from their projected area AGU to the optionally smaller area Ac of the cells 116 during the mounting of the skirt 130, by virtue of forcibly pressing the protruding extensions 150 to radially pass them through the corresponding cells 116.

[0320] In some examples, AGU can be greater than Ac. In some examples, AGU can be at least 2% greater than Ac. In some examples, AGU can be at least 5% greater than Ac. In some examples, AGU can be at least 10% greater than Ac. In some examples, Ac can be at least 15% greater than Ac. In some examples, AGU can be at least 20% greater than Ac.

[0321] In some examples, the method can further include a step of attaching the skirt 130 to the frame 102, such as by suturing or using any other type of suitable couplers. Attaching the skirt 130 to the frame 102 can be performed after approximation of the base layer portion 132 to the inner surface 128 of the frame 102 and extending the protruding extensions 150 through the corresponding cells 116. In some examples, attachment of the skirt 130 to the frame 102 by suturing and the like, can be performed after allowing the protruding extensions 150 to planarly expand in the corresponding cells 116. The pressure applied by protruding extensions 150 striving to planarly expand against surrounding angled struts 110 can advantageously help in temporarily maintaining position of the skirt 130 over the frame 102, thereby simplifying the subsequent attachment procedure.

[0322] In some examples, there is provided a method of forming a prosthetic valve 100 which comprises a paravalvular leakage (PVL) skirt. The method can include stretching a patch of stretchable material and connecting the protruding extensions 150 thereto at the stretched state. [0323] In some examples, the method can include a step of providing a frame 102 that can be implemented according to any example of a frame 102 described herein.

[0324] In some examples, the method can include a step of providing an optionally flattened patch having two side portions extending between a proximal edge portion 134 and a distal edge portion 136, wherein each of the proximal edge portion 134 and distal edge portion 136 can be longer than two side portions 1302a and 1302b. In some examples, the patch can be flattened.

[0325] In some examples, the method comprises stretching the patch laterally to a stretched state. In some examples, the method can include a step of laterally stretching the patch, optionally while in its flattened configuration, to a stretched state. Upon the stretching of the skirt 130, the distance between the two side portions in the stretched state of the skirt 130 can be defined as Dss, which can be greater than Dsu, as detailed with respect to the various methods described herein.

[0326] In some examples, the method comprises connecting a plurality of protruding extensions 150 to the outer surface of the patch, such that each protruding extension 150 extends away from the outer surface of the patch to form a 3D-shaped PVL skirt 130.

[0327] In some examples, the method comprises optionally rolling the stretched PVL skirt 130 by bringing the side potions thereof 1302 and 1302b together to assume a cylindrical configuration. In some examples, the patch can be provided flattened and the method comprises optionally rolling the stretched PVL skirt 130 by bringing the side potions thereof 1302 and 1302b together to assume a cylindrical configuration.

[0328] In some examples, the patch can be provided in a rolled configuration.

[0329] In some examples, the method comprises connecting the stretched rolled skirt 130 to the frame 102 of the prosthetic valve 100. In some examples, the method comprises connecting the stretched rolled skirt 130 to the frame 102 of the prosthetic valve 100 such that each of the protruding extensions 150 extends radially outwards from the base layer portion 132. In some examples, upon the connection protruding extensions 150 extend through corresponding cells 116. In some examples, upon the connection protruding extensions 150 extend through corresponding cells 116.

[0330] In some examples, the method can include a step of relieving tension created by the stretching. The step of relieving may be as described for the different method herein

[0331] A cross-sectional area of the protruding extensions upon the stretching of the patch state thereof can be defined as AGS.

[0332] In some examples, AGU is greater than Ac. In some examples, AGU is at least 5% greater than Ac. In some examples, AGU is at least 10% greater than Ac. In some examples, AGU is at least 15% greater than Ac. In some examples, AGS is greater than Ac. In some examples, AGU is at least 5% greater than Ac. In some examples, AGS is at least 10% greater than Ac. In some examples, AGU is at least 15% greater than Ac. In some examples, AGS is greater than Ac. In some examples, AGU is at least 5% greater than AGU. In some examples, AGS is at least 10% greater than AGU In some examples, AGU is at least 15% greater than AGU

[0333] Advantageously, the method described herein can prevent wrinkles in the base layer portion 132, that may form upon the stretching thereof. Wrinkles in the inner surface of the base layer portion 132 can cause flow disturbances through the prosthetic valve 100, when it is employed.

[0334] Figs. 11A and 11B are schematic cross-sectional views of an exemplary prosthetic valve 100^g in a radially expanded state and in a radially compressed state, respectively. Prosthetic valve 100^g is an exemplary implementation of a prosthetic valve 100, and thus can include any of the features described for a prosthetic valve 100 throughout the current disclosure, except that the protruding extensions 150^g of the skirt 130^s of prosthetic valve 100^g are devoid of compressible foam-like material. Instead of being filled with compressible or foam-like material, each protruding extensions 150^g can comprise an outwardly biased extending shell 152 attached to the base layer portion 132, enclosing a void or cavity 154 between the extending shell 152 and the base layer portion 132. [0335] An axial length of each cell 116 can be defined between a proximal end of the cell and the distal end of the cell. The axial length of at least some of the cells 116 of the frame 102, when the frame 102 is in the radially compressed state (shown for example in Fig. 1 IB) can be greater than the axial length of the same cell 116, when the frame 102 is in the radially expanded state (shown for example in Fig. 11A). In some examples, the axial length of each cell 116, when the frame 102 is in the radially compressed state can be greater than the axial length of the same cell 116, when the frame 102 is in the radially expanded state.

[0336] In some examples, the cell axial length in the radially compressed state can he at least 10% greater than the cell axial length in the radially expanded state. In some examples, the cell axial length in the radially compressed state can be at least 25% greater than the cell axial length in the radially expanded state. In some examples, the cell axial length in the radially compressed state can be at least 50% greater than the cell axial length in the radially expanded state. In some examples, the cell axial length in the radially compressed state can be at least 100% greater than the cell axial length in the radially expanded state.

[0337] In some examples, at least some of the extending shells 152 can extend radially outwards from the base layer portion 132. In some examples, at least some of the extending shells 152 can extend radially outwards from the base layer portion 132 and through corresponding cells 116. In some examples, each one of the extending shells 152 can extend radially outwards from the base layer portion 132. In some examples, each one of the extending shells 152 can extend radially outwards from the base layer portion 132 and through corresponding cells 116. In some examples, at least some of the extending shells 152 can extend radially outwards from the base layer portion 132 and within or through corresponding cells 116. In some examples, each one of the extending shells 152 can extend radially outwards from the base layer portion 132. In some examples, each one of the extending shells 152 can extend radially outwards from the base layer portion 132 and within or through corresponding cells 116.

[0338] As detailed herein, the level of extension of the extending shells 152 within or through the corresponding cells 116 can be determined by the configuration of the frame 102 (i.e., whether the frame is in a radially expanded configuration or in a radially compressed configuration).

[0339] In some examples, each protruding extension 150^g can include a flexible shell 152. In some examples, the flexible shell 152 can be connected to the base layer portion 132. In some examples, the flexible shell 152 can enclose a void or cavity 154 within the protruding extension 150^s. [0340] The shell 152 can be formed of a pre-shaped material which is biased radially outwards to define the radial dimension RD of the protruding extension 150^s.

[0341] In some examples, the flexible shell 152 can be pre-shaped to a curved shape, such as semi-spherical dome shaped, in a radially uncompressed and an axially non-tensioned state of the skirt 130⁸. In some examples, the flexible shells 152 can be positioned radially away from the base layer portion 132.

[0342] In some examples, flexible shells 152 of the protruding extensions 150^s can be laminated by a coating layer, such as the coating layer 1503 described above. Tn some examples, the coating layer can be hydrophilic. In some examples, the shells 152 can be hydrophilic.

[0343] In some examples, the coating layer can have a high durometer. In some examples, the flexible shells 152 can have a high durometer. In some examples, the extending shells can have a high durometer.

[0344] In some examples, the shells 152 can be stretchable. In some examples, the flexible shells 152 can be elastically deformable. In some examples, the shells 152 can have elongation at break of at least 5%. In some examples, the shells 152 can have elongation at break of at least 10%. In some examples, the flexible shells 152 can have elongation at break of at least 15%.

[0345] In some examples, each one of the shells 152 of the skirt 130^s can have a thickness in the range of 10 micron to 100 micron, including each value and sub-range within the specified range.

[0346] In some examples, the radial dimension RDE defined by each extending shell, in a radially uncompressed and an axially non-tensioned state of the skirt 130^g, is greater than the radial dimension RDc defined by the same extending shell in an axially tensioned state of the skirt 130^s.

[0347] In some examples, RDE can be at least 10% greater than RDc. In some examples, RDE can be at least 25% greater than RDc. In some examples, RDE can be at least 50% greater than RDc. In some examples, RDE can be at least 100% greater than RDc. In some examples, RDE can be at least 200% greater than RDc. In some examples, RDE can be at least 300% greater than RDc. In some examples, RDE can be at least 500% greater than RDc.

[0348] As specified herein, prosthetic valve frames are movable between a radially compressed, or crimped, state, and a radially expanded state. Thus, the prosthetic valves can be crimped on or retained by an implant delivery apparatus (not shown) in the radially compressed state during delivery, and then expanded to the radially expanded state once the prosthetic valve reaches the implantation site. The expanded state may include a range of diameters to which the valve may expand, between the compressed state and a maximal diameter reached at a fully expanded state. Thus, a plurality of partially expanded states may relate to any expansion diameter between radially compressed or crimped state, and maximally expanded state.

[0349] Yet, in some examples, a large crimped profile can disturb the process of implantation due to limited space within the implant delivery apparatus. Therefore, in some examples, it can be beneficial to reduce the crimped profile of the prosthetic valve 100 as a whole.

[0350] In some examples, more condensed foam cells that are used as filler material configured to bias protruding extensions of a PVL skirt radially outwards, can improve PVL sealing. However, such filler materials may also increase the crimped profile of the prosthetic valve onto which they are mounted. Thus, in some examples, protruding extensions 150^s can include a shell 152 which is pre-shaped to bias radially outwards and encloses a cavity, wherein such shells 152 can assume a smaller profile when the prosthetic valve is crimped, axially tensioning the skirt 130⁸.

[0351] For that end, it may be desirable to design extending shells 152 configured to assume a relatively flattened configuration when the prosthetic valve 100^g is crimped.

[0352] In some examples, each extending shell 152 can extend axially along a corresponding cell 116. In some examples, each extending shell 152 can extend axially along a corresponding cell 116 between a proximal end 157 and a distal end 158 of the extending shell 152.

[0353] In some examples, the proximal end 157 of the extending shell 152 can be defined as the point of the shell 152, which is closest to the inflow end 104 of the frame 102. In some examples, the distal end 158 of the extending shell 152 can be defined as the point of the shell 152, which is closest to the outflow end 106 of the frame 102.

[0354] Each extending shell 152 has an axial height Hs, which can be defined as the distance between the proximal end 157 and the distal end 158 of the extending shell 152.

[0355] In some examples, each extending shell can be axially elongated when the frame is in the radially compressed state (see Fig. 1 IB, defining an elongated height Hsc that can be greater than the axial height HSE of the same extending shell 152, when the frame is in the radially expanded state (see Fig. HA).

[0356] In some examples, Hsc can be at least 10% greater than HSE- In some examples, Hsc can be at least 25% greater than HSE- In some examples, Hsc can be at least 50% greater than HSE- In some examples, Hsc can be at least 100% greater than HSE. [0357] In some examples, each extending shell 152 can be mounted within a corresponding cell 116 of the frame 102. In some examples, when the skirt 130^s is mounted against the frame 102 such that protruding extensions 150^s and shells 152 thereof are disposed inside corresponding cells 116, transitioning of the frame 102 from a radially expanded state to a radially compressed state serves to elongate the frame 102 and cells 116 thereof, and correspondingly increase the axial height Hs of the extending shell 152 therewith.

[0358] In some examples, upon crimping or compression of the frame 102 in a manner that elongates the frame 102 as well as the skirt 130^s and protruding extensions 150^s thereof, the axial elongation of extending shells 152 can also flatten them. In some examples, crimping or compression of the frame 102 from a radially expanded state to a radially compressed state can increase the axial height Hs and reduce the radial dimension RD of the extending shells 152.

[0359] In some examples, in order to prevent the extending shells 152 from extending substantially outward farther from the frame 102 in its crimped configuration, the thickness of the extending shells 152 can be comparable to that of the struts 108 and/or 110 of the frame 102, and the shells 152 can be designed to completely flatten over the base layer portion 132 in the crimped configuration of the frame 102, such that the shells 152 can be entirely concealed inside the thickness of the frame 102 in their compacted state. Thus, in some examples, the extending shells 152 can be configured not to substantially protrude radially away of the frame 102 in the crimped configuration of the frame 102.

[0360] A thickness of each one of the flexible shells 152 can be defined as Tc. In some examples, a thickness of each one of the struts 108 and/or 110 of the frame 102 through which the plurality of extending shells 152 extend, can be defined as Ts (measured in the radial direction between inner 128 and outer 127 surfaces of the frame).

[0361] In some examples, the thickness Tc of flexible shell 152 can be in the range of 0.5Ts to 1.5Ts, including each value and sub-range within the specified range. In some examples, Tc can be in the range of 0.75Ts to 1.25Ts. In some examples, Tc can be in the range of 0.9Ts to l.lTs.

[0362] In some examples, when the frame 102 is in its radially compressed state, the extending shells 152 can extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is not greater than 3Ts. In some examples, when the frame 102 is in its radially compressed state, the extending shells 152 can extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is not greater than 2Ts. In some examples, when the frame 102 is in its radially compressed state, the extending shells 152 can extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is not greater than Ts. In some examples, when the frame 102 is in its radially compressed state, the extending shells 152 can extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is not greater than 0.5Ts. In some examples, when the frame 102 is in its radially compressed state, the extending shells 152 can extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is not greater than 0.25Ts. In some examples, when the frame 102 is in its radially compressed state, the extending shells 152 may not extend radially outward past the outer surface 127 of the frame 102.

[0363] In some examples, upon expansion of the frame 102 from a radially compressed state to a radially expanded state, and releasing axial tension from the skirt 130^g to allow it to revert to its shorter height, the shells 152 revert to their pre-shaped biased configuration extending radially away from the base layer portion 132.

[0364] In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than Ts. In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than 2Ts. In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than 3Ts. In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than 5Ts. In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than 7Ts. In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than 10Ts. In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than 15Ts. In some examples, when the frame 102 is in its radially expanded state, the extending shells 152 extend radially outward past the outer surface 127 of the frame 102 to a radial distance which is greater than 2OTs.

[0365] In some examples, the flexible shell 152 can be reinforced so that it can bulge in radially outwards upon expansion of the frame 102 from a radially compressed state to a radially expanded state. [0366] Reference is made to Figs. 12A-16C. Figs. 12A and 13 A show cross-sectional views of exemplary skirts 130^h. Skirt 130^h which is an exemplary implementation of any skirt disclosed herein, and thus can include any of the features described for any one of skirts 130 throughout the current disclosure, except that the base layer portion 132^h of skirt 130^h has a non-uniform surface morphology, as detailed herein. Base layer portion 132 defines an outer surface 1321 facing the protruding extensions 150, and an inner surface 1322 facing radially inwards (for example, facing a longitudinal axis of the frame 102 when coupled to the frame 102), opposite to the outer surface 1321.

[0367] In some examples, the inner surface 1322 of the base layer portion 132^h can have a non- uniform surface morphology . In some examples , the outer surface 1321 can have a non-uniform surface morphology. In some examples, each one of the inner surface 1322 and the outer surface 1321, individually, can have a non-uniform surface morphology.

[0368] The term "surface morphology" is to be understood as referring to the different geometric characteristics (including, but not limited to, geometry, structure, height profile) of the surface of a substantially planar portion of a sheet, such as the base layer portion 132^h of the skirt 130^h disclosed herein. The surface morphology of a sheet structure can be “non- uniform”. A "non-uniform surface morphology" is intended to mean that the surface can be not smooth, and can comprise, e.g., pores and/or intermediate spaces/recesses and elevations in the surface, which can also be referred as rough surfaces. Thus, the term “surface morphology” refers also to a roughness property of at least one surface of the sheet.

[0369] In some examples, the inner surface 1322 can be a textured inner surface 1322. In some examples, the outer surface 1321 can be a textured outer surface 1321. In some examples, each one of the inner surface 1322 and the outer surface 1321, individually, can be a textured surface. [0370] The tern "textured surface", as used herein, refers to a surface having a topology with nano- to micron-sized surface variations formed by a texturing technique. While the characteristics of such a surface can be variable depending on the materials and techniques employed, such a surface can include micron-sized pores exposed to the external environment (such as blood in the vicinity of the textured surface), which have a depth that does not extend through the complete thickness of the base layer portion 132.

[0371] the skirt 130^h can be secured to the frame 102 of any exemplary prosthetic valve 100 disclosed herein, such that the base layer portion 132^h can be disposed around, and optionally inwardly to, the inner surface 128 of the frame 102.

[0372] In general, a smooth inner surface 1322 of the base layer portion 132 of a skirt 130^h to which protruding extensions 150 are attached can lead to embolization and thrombus detachment, upon implantation and implementation of the prosthetic valves 100 for an extended duration in a human anatomy. Without wishing to be bound by any theory of mechanism of action, smooth surfaces are non-adherent, and upon implantation, the inner surface 1322 of the base layer portion 132 of a skirt 130 can be exposed to the blood stream. Such exposure can result in biological response within the body, which favors the formation of thrombi. In the case of a smooth inner surface 1322, adhesion of such thrombotic formations to the base layer portion 132 is relatively loose, which is of critical concern because, if dislodged, such thrombi can create am embolus that may flow downstream and reach important systemic organs.

[0373] Therefore, a neointimal-formation encouraging surface, configured to encourage neointimal tissue development over the inner surface 1322, can advantageously prevent or reduce the likelihood of thrombus formation that can spontaneously detach into the blood stream.

[0374] The term "neointimal tissue" refers to a thin layer of tissue having an average thickness (in a direction perpendicular to the surface) of no more than 200pm (or another average thickness threshold). As used herein, the term "thrombus" or "blood clot" refers to a solid or semi-solid mass that can include the constituents of blood that is the product of blood coagulation. There are two components to a thrombus, aggregated platelets that form a platelet plug, and a mesh of cross-linked fibrin protein.

[0375] In some examples, the base layer portion 132 can have an inner surface 1322 which is a tissue-adherent surface. The term "tissue-adherent surface", as used herein, refers to a surface texture that causes or encourages adherence of tissue thereto. In some examples, a tissue adherent surface can be a thrombogenic surface, configured to cause or encourage development of a thrombus and coagulation of blood. In some examples, a tissue-adherent surface can be a surface that encourages formation of a neointimal tissue thereon. As exemplified herein, more textured or rough surfaces will have higher thrombogenicity and/or tissue adherence values compared to flatter smooth surfaces comprised of the same materials. Similarly two surfaces having the same structure may have different thrombogenicities and/or tissue adherence values depending on their chemical composition.

[0376] Relative thrombogenicity or tissue adherence values between articles that can include different materials, or include the same material but having different surface textures, can be determined, for example, according to the regulation (EU) 2017/745 of the European parliament and of the council on medical devices. The regulation refers to ISO 10993-4-2017, and includes measurements to be performed in order to determine three main parameters relating to thrombogenicity: (1) Thrombin generation, as measured by ELISA (Enzyme-Linked Immunosorbent Assay) for Thrombin-antithrombin complex and Prothrombin fragment Fl+2; (2) Fibrin generation as measured by ELISA for Fibrinopeptide A; and (3) Intrinsic pathway (FXII) as measured by PTT (Partial Thromboplastin Time) test.

[0377] In some examples, the inner surface 1322 of the base layer portion 132^h can be porous. In some examples, the base layer portion 132^h of skirt 130^h can be porous.

[0378] In some examples, the base layer portion 132 of the skirt 130^b can include a plurality of pores. In some examples, each pore can have a pore size in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. [0379] It is to be understood that the pore size can be measured as the pore diameter, which in such cases, the unit used is one-dimensional, e.g., micron. For example, a mean pore size of the plurality of pores can be in the range of 0.5 micron to 10 micron, which is a one-dimensional value, and therefore relates to the pore diameter.

[0380] In some examples, each pore can have a pore size in the range of 10 micron to 15 micron. In some examples, each pore can have a pore size in the range of 80 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 10 micron to 15 micron. In some examples, an average pore size of the plurality of pores can be in the range of 80 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 10 micron to 15 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 80 micron to 100 micron.

[0381] In some examples, the base layer portion 132^h can be perforated. In some examples, the base layer portion 132^h can include a plurality of perforations. In some examples, the base layer portion 132^h can be perforated, such that at least some of the plurality of the perforations extend through a thickness of the base layer portion 132^h and pierce through the inner surface 1322 and through the outer surface 1321. In some examples, the base layer portion 132^h can be perforated, such that each one of the plurality of the perforations extends through a thickness of the base layer portion 132^h and pierces through the inner surface 1322 and through the outer surface 1321.

[0382] In some examples, even a relatively very low threshold as low as 0.5 micron for the pose size can be considered, since cell migration or neovascularization is not required for the development of a neointimal tissue layer.

[0383] It is to be understood by the person having ordinary skill in the art that the terms “porous” and “perforated” can be partially overlapping. For example, a base layer portion 132, which has pores that extend from its inner surface 1322 to its outer surface 1321 , and pierce through both the inner surface 1322 and its outer surface 1321, can be considered to be both perforated and porous.

[0384] Fig. 12B schematically shows a surface texture of an exemplary inner surface 1322^hl of the base layer portion 132^h of Figure 12A. As can be seen in detail in Fig. 12B, the inner surface 1322^hl can optionally include a plurality of filaments. In some examples, the base layer portion 132^b can include a plurality of filaments. Base layer portions 132 that are porous and include a plurality of filaments can be formed by one or more of the methods as described herein in detail, for example electrospinning or air jet spinning.

[0385] Fig. 13A is similar to Fig. 12A and also portrays a cross-sectional view of an exemplary skirt 130^h comprising a base layer portion 132^h and a plurality of protruding extensions 150. However, Fig. 13B schematically shows a surface texture of an exemplary inner surface 1322^h2 of the base layer portion 132^h of Fig. 13 A, which can optionally be perforated. Examples related to perforated base layer portions 132^h and inner surfaces 1322^h2 thereof are detailed herein.

[0386] In some examples, the base layer portion 132^h can be selected from an electrospun base layer portion 132, melt blown spun base layer portion 132, air jet spun base layer portion 132 and a base layer portion 132 comprising a salt-leached inner surface 1322.

[0387] In some examples, the base layer portion 132^h can be an electrospun base layer portion 132. It is to be understood that “electrospun base layer portion” relates to a base layer 132 as disclosed herein, which was formed through a process of electrospinning.

[0388] In general, electrospinning is a method that produces fine fibers by charging and ejecting a polymer melt or solution through a spinneret under a high-voltage electric field, wherein the melt or solution is then solidified or coagulated to form a filament. The formed filaments are ultrafine, which can be in the hundreds of nanometers range in some examples. During the electrospinning process, electric force is applied to the polymer solution or melt to draw charged threads therefrom. When a sufficiently high voltage is applied to the droplet of the polymer melt or solution, the body of the liquid becomes charged, and electrostatic repulsion counteracts the surface tension and the droplet is stretched. At a critical point a stream of liquid erupts from the surface to form a charged liquid jet. As the jet dries in flight and deposited on a surface, the ultrafine filament is formed.

[0389] Advantageously, an electrospun layer, such as an electrospun base layer portion 132, can optionally lead to absence of signs of inflammation compared to smooth skirts. Also, an electrospun layer, such as an electrospun base layer portion 132, can optionally lead to absence of signs of growth of giant cells compared to smooth skirts.

[0390] In some examples, an electrospun base layer portion 132^h can optionally be electrospun from a melt. In some examples, the electrospun base layer portion 132^h can optionally be electrospun from a solution. In some examples, the solution can optionally include an organic solvent. In some examples, the organic solvent can optionally be selected from the group consisting of: l,l,l,3,3,3-hexafluoro-2-propanol (HFIP), tetrahydrofuran (THF), acetone, dimethylformamide (DMF) and any combination thereof.

[0391] In some examples, the base layer portion 132^h can be electrospun from a solution, wherein the solution can optionally include a polymeric material at a concentration in the range of 2% w/w to 12% w/w, including each value and sub-range within the specified range. It is to be understood to the person having ordinary skill in the art that the polymer within the electrospinning solution forms fine filaments upon the electrospinning process, wherein the product can optionally be the base layer portion 132^h. Therefore, in some examples, the dissolved polymer is the material forming the base layer portion 132^h. Thus, any example which applies to any polymer as the base layer portion 132 can similarly apply to the polymer in the electrospinning solution. Similarly, it is to be understood to the person having ordinary skill in the art that any example, which applies to any polymer as the polymer in the electrospinning solution, can similarly apply to the base layer portion 132^h.

[0392] In some examples, the base layer portion 132¹¹ can include a plurality of filaments. In some examples, the electrospun base layer portion 132^h can include a plurality of filaments. In some examples, upon electrospinning of the base layer portion 132 a plurality of filaments can form.

[0393] In some examples, each one of the plurality of filaments can have a diameter in the range of 0. 1 to 20 micron, including each value and sub-range within the specified range. In some examples, each one of the plurality of filaments can have a diameter in the range of 1 to 5 micron. In some examples, each one of the plurality of filaments can have a diameter in the range of 1 to 1.5 micron. In some examples, each one of the plurality of filaments can have a diameter in the range of 3 to 5 micron. In some examples, the plurality of filaments can have an average diameter in the range of 1 to 5 micron, including each value and sub-range within the specified range. In some examples, the plurality of filaments can have an average diameter in the range of 1 to 1.5 micron. In some examples, the plurality of filaments can have an average diameter in the range of 3 to 5 micron. In some examples, the plurality of filaments can have a mean diameter in the range of 1 to 5 micron, including each value and sub-range within the specified range. In some examples, the plurality of filaments can have a mean diameter in the range of 1 to 1.5 micron. In some examples, the plurality of filaments can have a mean diameter in the range of 3 to 5 micron.

[0394] In addition to forming a base layer portion 132, in some examples, through electrospinning, which can result in an electrospun base layer portion 132, it can be contemplated to provide an optionally smooth base layer portion and to electrospray a coating layer thereon, which can form a textured inner surface 1322 thereon.

[0395] In some examples, formation of a textured surface of a base layer portion 132^h can include electrospraying a polymer over the inner surface of the base layer portion 132 to form a textured inner surface 1322. In some examples, formation of a textured surface of a base layer portion 132^h can include providing a liquid polymer composition contained in an electrospray device and electrospraying the liquid polymer composition over the inner surface of the base layer portion 132 to form a textured inner surface 1322.

[0396] The electrospray device can optionally include a container and a spinneret, in fluid communication therewith, the liquid polymer composition is contained in the container at the beginning of a procedure for formation of the tissue-adherent surface.

[0397] In some examples, materials, such as polymers, which can be suitable for the purpose of promoting endothelization and/or neointimal growth, can include, but are not limited to, fluorinated polymers (e.g., TPU, ePTFE, FEP), as well as biomimetic collagen or hyaluronic acid-based materials.

[0398] Collagen is the main structural protein in the extracellular matrix found in the body's various connective tissue. Different forms of collagen typically have molecular weights in an order of magnitude of hundreds kilodaltons. In the context of the present disclosure, collagen can be considered to be under the definition of “polymer”. Moreover, electrospinning of collagen was reported.

[0399] Similarly, hyaluronic acid, a glycosaminoglycan polymer can be considered to be under the definition of “polymer” in the context of the present disclosure.

[0400] In some examples, the base layer portion 132^h can optionally include a polymer selected from the group consisting of: thermoplastic polyurethane (TPU), expanded poly tetrafluoroethylene (ePTFE), fluorinatedethylenepropylene polymer (FEP), biomimetic collagen, a hyaluronic acid derivative and a combination thereof.

[0401] In some examples, the electrospinning can be performed at a flow rate in the range of 0.1 ml pe hour to 8 ml per hour, including each value and sub-range within the specified range. [0402] In some examples, the electrospinning can be performed at a voltage in the range of 10 kV to 14 kV, including each value and sub-range within the specified range.

[0403] In some examples, the base layer portion 132^h can be a jet spun base layer portion 132. It is to be understood that "jet spun base layer portion" relates to a base layer 132 as disclosed herein, which was formed through a process of jet spinning.

[0404] Jet spinning, also known as air-jet spinning technology or air-jet spinning process, is a method used in the textile industry to produce yarn. It is a spinning technique that can utilize high-speed jets of air to twist and bind fibers together, and thereby can form continuous strands of yarn. It is a pneumatic method, which can include passing a drafted strand of fibers through one or two fluid nozzles located between the front roller of a drafting system and a take up device.

[0405] In some examples, the jet-spun base layer portion 132^h can optionally be jet-spun from a melt. In some examples, the jet-spun base layer portion 132^h can optionally be jet-spun from a solution. In some examples, the solution can optionally include an organic solvent. In some examples, the organic solvent can optionally be selected from the group consisting of: l,l,l,3,3,3-hexafluoro-2-propanol (HFIP), tetrahydrofuran (THF), acetone, dimethylformamide (DMF) and any combination thereof.

[0406] In some examples, the base layer portion 132^h can be jet-spun from a solution, wherein the solution can optionally include a polymeric material at a concentration in the range of 2% w/w to 12% w/w, including each value and sub-range within the specified range. It is to be understood to the person having ordinary skill in the art that the polymer within the jet-spinning solution forms fibers upon the jet-spinning process, wherein the product can optionally be the base layer portion 132^h. Therefore, in some examples, the dissolved polymer is the material forming the base layer portion 132^h. Thus, any example which applies to any polymer as the base layer portion 132^h, can similarly apply to the polymer in the jet-spinning solution. Similarly, it is to be understood to the person having ordinary skill in the art that any example which applies to any polymer as the polymer in the jet-spinning solution, can similarly apply to the base layer portion 132^h.

[0407] In addition to forming a base layer portion 132^h, in some examples, through jetspinning, which can result in a jet-spun base layer portion 132¹¹, it can be contemplated to provide an optionally smooth base layer portion and to jet-spray a coating layer thereon, which can form a textured inner surface 1322 thereon.

[0408] In some examples, formation of a textured surface of a base layer portion 132¹¹ can include jet- spraying a polymer over the inner surface of the base layer portion 132 to form a textured inner surface 1322. In some examples, formation of a textured surface of a base layer portion 132^h can include providing a liquid polymer composition contained in a jet-spray device and jet- spraying the liquid polymer composition over the inner surface of the base layer portion 132 to form a textured inner surface 1322.

[0409] In some examples, materials, such as polymers, which can be suitable for the purpose of promoting endothelization and/or neointimal growth, can include, but are not limited to, fluorinated polymers (e.g., TPU, ePTFE, FEP), as well as biomimetic collagen or hyaluronic acid-based materials.

[0410] In some examples, the base layer portion 132^h can comprise a salt- leached inner surface 1322. It is to be understood that "salt leached inner surface" relates to an inner surface 1322 of a base layer 132^h as disclosed herein, which was surface modified through a process of salt leaching.

[0411] In general, salt leaching is a method that produces porous media, including porous polymeric materials, and porous surfaces, including porous polymeric surfaces. When used to form porous polymers, salt leaching procedures involve production of a liquid mixture of a polymer melt or solution in its pre-casted form. The mixture further comprises a porogen, which is the compound that will eventually form the pores. As an organic material, the pre- casted polymer is soluble in organic solvents and insoluble in water. The porogen is selected such that it has the opposite solubility properties, i.e., it is a solid which is insoluble in organic solvents (and/or in the polymer melt) and is soluble in water. The mixture of the liquid (melted or solubilized) polymer and the porogen includes, therefore, liquid with solid particles of the porogen therein. In some examples, the liquid mixture can be made substantially homogeneous upon mixing, i.e., the solid particles a scattered substantially evenly in the liquid. The mixture is then casted or molded and hardened to form the desired shape of the product polymer. In this stage, the composition can be of a solid polymer mixed with particles of the porogen. The composition is then thoroughly washed with water to dissolve and leach the porogen, and leave the polymer with the remaining vacant pores.

[0412] The liquid composition of the polymer can be similar to any example described above for a liquid composition used in an electrospinning procedure. In some examples, formation of a porous base layer portion 132^h comprises providing a porogen, which can be solid at room temperature. In some examples, the porogen has melting point above 100°C or above 200°C. In some examples, the porogen is an inorganic compound. In some examples, the porogen has aqueous solubility of at least 1 gr/ml, at least 5 gr/ml or at least 10 gr/ml. In some examples, the porogen is in the form of a powder. In some examples, the porogen has particle size in the range of 0.4 micron to 4 micron, 2 micron to 20 micron, 10 micron to 100 micron, 50 micron to 500 micron, 100 micron to 1000 micron, or 200 micron to 2000 micron.

[0413] In some examples, formation of a salt-leached inner surface 1322 can include casting the mixture to form a solid casted layer that can include the porogen dispersed within the casted solid polymer. In some examples, formation of a salt- leached inner surface 1322 can include molding the mixture to form a solid molded layer that comprises the porogen dispersed within the molded solid polymer. In some examples, the porogen particles can be substantially evenly dispersed within the solid polymer.

[0414] In some examples, formation of a salt-leached inner surface 1322 can further comprise contacting the formed solid layer with water, thereby leaching at least some of the porogen from the solid layer to form vacated pores within the layer. In some examples, contact with water can be performed at a temperature of at least 20°C, at least 25°C, at least 30°C, at least 40°C, at least 60°C, or at least 80°C. In some examples, contact with water can be performed for a period of 1 to 120 minutes.

[0415] In some examples, the base layer portion 132^h can be a melt blown base layer portion 132^h. It is to be understood that "melt blown base layer portion" relates to a melt blown base layer portion 132 as disclosed herein, which went through a process of salt melt blowing.

[0416] Generally, melt blowing is a manufacturing process used to create nonwoven fabrics and materials. It is particularly known for its ability to produce fine fibers, which can be used in various applications. In some examples, the melt blowing can include a step of melt extrusion. In some examples, the melt extrusion can include melting a polymer resin. In some examples, the melt extrusion can include extrusion of the polymer through a spinneret. In some examples, the melt blowing can include a step of high-speed airflow. In some examples, the step of high-speed airflow step can include blowing hot air or gas onto the extruded polymer. In some examples, the step of high-speed airflow can be at least partially simultaneous with the step of melt extrusion. In some examples, the melt blowing can include a step of fiber formation. In some examples, the step of fiber formation can include stretching and/or elongating the molten polymer into very fine fibers.

[0417] As detailed herein it may be desirable, in some examples, to control biologic response in a manner that will promote only acute response of neointimal thin tissue growth (for example, no more than 200 micron) that will not proceed to become a thicker layer. In some examples, the base layer portion 132 can have an inner surface 1322, which is encouraging neointimal-formation, at a thickness in the range of 1 micron to 200 micron, including each value and sub-range within the specified range. In some examples, the base layer portion 132^h can encourage neointimal formation at a thickness in the range of 1 micron to 200 micron, including each value and sub-range within the specified range.

[0418] An optional means, according to the present disclosure of promoting endothelization or neointimal formation is by inclusion of a coating layer, which can optionally coat the inner surface of the base layer portion 132^h.

[0419] Thus, in some examples, the base layer portion 132^h can include a coating layer (not illustrated). In some examples, the coating layer can be coating the inner surface of the base layer portion 132^h, such that an inner surface of the coating layer can define the neointimal- formation encouraging inner surface 1322. In some examples, the coating can promote endothelization. In some examples, the coating can promote neointimal tissue formation. In some examples, the coating can promote endothelization. In some examples, the coating can promote neointimal formation at a thickness in the range of 1 micron to 200 micron, including each value and sub-range within the specified range.

[0420] In some examples, the coating can include at least one endothelium tissue promoting compound. In some examples, the endothelium tissue promoting compound can be selected from the group consisting of: collagen, chitosan hyaluronic acid and a combination thereof. In some examples, the endothelium tissue promoting compound can include collagen. In some examples, the endothelium tissue promoting compound can include collagen at a concentration of 0.1% w/w to 3% w/w. In some examples, the endothelium tissue promoting compound can include hyaluronic acid. In some examples, the endothelium tissue promoting compound can include hyaluronic acid at a concentration of 0.1% w/w to 3% w/w. In some examples, the endothelium tissue promoting compound can include chitosan. In some examples, the endothelium tissue promoting compound can include chitosan at a concentration of 0.1% w/w to 3% w/w.

[0421] In some examples, the endothelium tissue promoting compound can be non-toxic. In some examples, the endothelium tissue promoting compound can be non-inflammatory. In some examples, the endothelium tissue promoting compound can be bioresorbable. In some examples, the endothelium tissue promoting compound can be biodegradable. In some examples, the endothelium tissue promoting compound can be biodegradable over a period of one year to two years. Specifically, in some examples, endothelium tissue promoting compound can be configured to degrade over a period one year to two years while being replaced by native tissue.

[0422] Figs. 12A and 13A also present the value of T3, which, as detailed herein relates to the thickness of the base layer portion 132 of any exemplary skirt 130 disclosed herein, including exemplary base layer portion 132^h. The thickness can be measured from the outer surface 1321 to the inner surface 1322 of the base layer portion 132. In some examples, the thickness T3 can be in the range of 25 micron to 110 micron, including each value and sub-range within the specified range. In some examples, the thickness T3 can be in the range of 25 micron to 55 micron. In some examples, the thickness T3 can be in the range of 50 micron to 110 micron.

[0423] Figs. 12A and 13A graphically illustrated examples of a monolayered base layer portions 132^h (i.e., the base layer portions 132^h is illustrated to include a single layer). However, it is to be understood by the person having ordinary skill in the art that the term "base layer portion" is not limited to a monolayer. A base layer portion 132 can optionally include at least one layer, and in some examples, can optionally include two layers or more than two layers.

[0424] Reference is made to Figs. 14A-16C. Figs. 14A, 15A and 16A show cross-sectional views of exemplary skirts 130'. Skirt 130' is an exemplary implementation of any skirt disclosed herein, and thus can include any of the features described for any 130 throughout the current disclosure, except that the base layer portion 132' of skirt 130' includes more than one layer, e.g., two layers. In some examples, the base layer portion 132' comprises a first layer that can be also referred to as an internal layer 332, and a second layer which can be also referred to, in some cases, as an external layer 232. Optionally, the internal layer 332 of the base layer portion 132' can be textured or have a non-uniform surface morphology, as detailed herein, e.g., with respect to the base layer portion 132^h.

[0425] Fig. 14B schematically shows a surface texture of an exemplary inner surface 3322 of the internal layer 332 of the base layer portion 132' of Fig. 14A. As can be seen in detail in Fig. 14B, the inner surface 3322 can optionally include a plurality of filaments. In some examples, the internal layer 332 of the base layer portion 132' can include a plurality of filaments. Internal layers 332 that are porous and include a plurality of filaments can be formed by one or more of the methods as described herein in detail, for example electrospinning or air jet spinning. Figs. 15B and 16B schematically show similar surface textures of exemplary inner surfaces 3322 of base layers 132' of Figs. 15A and 16A, respectively, optionally including a plurality of filaments similar to those described herein with respect to Fig. 14B.

[0426] In some examples, the base layer portion 132' can include an external layer 232, which is proximal to the protruding extensions 150. In some examples, the base layer portion 132 of the skirt 130^c can have internal layer 332, which can be located more distally form the protruding extensions 150 compared to the external layer 232. In some examples, the external layer 232 can be located between the protruding extensions 150 and the internal layer 332. In some examples, the internal layer 332 can be proximal to the external layer 232. In some examples, the internal layer 332 can contact to the external layer 232. In some examples, the internal layer 332 can be attached or can be connected to the external layer 232.

[0427] In some examples, the external layer 232 of the base layer portion 132¹ defines an outer surface 2321 facing the protruding extensions 150. In some examples, the external layer 232 of base layer portion 132¹ defines an inner surface 2322 opposite to the outer surface 2321, oriented radially inwards towards internal layer 332 when the skirt 130¹ is mounted in the frame 102.

[0428] In some examples, the internal layer 332 of the base layer portion 132‘ defines an outer surface 3321 facing external layer 232. In some examples, the internal layer 332 of base layer portion 132¹ defines an inner surface 3322 opposite to the outer surface 3321, oriented radially inwards such as towards a longitudinal axis of the frame 102 when mounted in the frame 102. [0429] The internal or first layer 332 is positioned radially inwards to the second or external layer 232, and can define, in some examples, an innermost layer of the base layer portion 132 disposed radially inwards to any other layer of the base layer portion. The external or second layer 232 is radially outwards to the internal layer 332, and is closer to the protruding extensions 150. The external layer 232 extends between a distal edge 236 which is closer to the inflow end 104 of the frame, and an opposite proximal edge 234 which is closer to the outflow end 106. The internal layer 332 extends between a distal edge 336 which is closer to the inflow end 104 of the frame, and an opposite proximal edge 334 which is closer to the outflow end 106.

[0430] In some examples, the proximal edge 334 of the internal layer 332 defines the proximal edge 134 of the base layer portion 132. In some examples, the proximal edge 234 of the external layer 232 defines the proximal edge 134 of the base layer portion 132. In some examples, the proximal edge 334 of the internal layer 332 and the proximal edge 234 of the external layer 232 are aligned, together defining the proximal edge 134 of the base layer portion 132. In some examples, the distal edge 336 of the internal layer 332 defines the distal edge 136 of the base layer portion 132. In some examples, the distal edge 236 of the external layer 232 defines the distal edge 136 of the base layer portion 132. In some examples, the distal edge 336 of the internal layer 332 and the distal edge 236 of the external layer 232 are aligned, together defining the distal edge 136 of the base layer portion 132. [0431] In some examples, the inner surface 2322 can have a non-uniform surface morphology. In some examples, the outer surface 2321 can have a non-uniform surface morphology. In some examples, each one of the inner surface 2322 and the outer surface 2321, individually, can have a non-uniform surface morphology.

[0432] In some examples, the inner surface 3322 can have a non-uniform surface morphology. In some examples, the outer surface 3321 can have a non-uniform surface morphology. In some examples, each one of the inner surface 3322 and the outer surface 3321, individually, can have a non-uniform surface morphology.

[0433] In some examples, the inner surface 2322 can be a textured inner surface 2322. In some examples, the outer surface 2321 can be a textured outer surface 2321. In some examples, each one of the inner surface 2322 and the outer surface 2321, individually, can be a textured surface. [0434] In some examples, the inner surface 3322 can be a textured inner surface 3322. In some examples, the outer surface 3321 can be a textured outer surface 3321. In some examples, each one of the inner surface 3322 and the outer surface 3321, individually, can be a textured surface. [0435] In some examples, the external layer 232 can be disposed against, and in contact with, an inner surface 128 of the frame 102. In some examples, the skirt 130¹ can include a plurality of protruding extensions 150 extending radially outwards from the outer surface 2321 of the external layer 232.

[0436] A smooth inner surface 3322 of an internal layer 332 of the base layer portion 132can pose the same risk of thrombus detachment and embolization as described above with smooth inner surfaces of a skirt 130¹¹. In order to mitigate this risk, the internal layer 332 of the base layer portion 132¹ can have an inner surface 3322¹ configured to encourage neointimal tissue formation. In some examples, the internal layer 332 of the base layer portion 132¹ can have an inner surface 3322 configured to encourage endothelization. In some examples, the inner surface 3322 can be not smooth. In some examples, the inner surface 1322 can be rough.

[0437] In some examples, the inner surface 3322 of the internal layer 332 can be porous. In some examples, the internal layer 332 of base layer portion 132¹ can be porous.

[0438] Optionally, a porous internal layer 332 of base layer portion 132 of the skirt 130^c can be chosen to allow cell adherence. For example, a cell that can have a size similar to the pore size of internal layer 332. Typically, the diameter of a red blood cell is in the range of about 6 micron to about 8 micron. It is to be understood that the term “about”, as used herein refers to a ±20%, ±10% or ±5% difference in magnitude, and the term “similar” used herein refers to a ±30%, ±20% or ±10% difference in magnitude. [0439] In some examples, the inner surface 3322 of the internal layer 332 of the base layer portion 132 can include a plurality of pores. In some examples, the internal layer 332 of the base layer portion 132 can include a plurality of pores. In some examples, each pore can have a pore size in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron.

[0440] In some examples, a mean pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, each pore can have a pore size in the range of 20 micron to 100 micron. In some examples, each pore can have a pore size in the range of 80 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 20 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 80 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 20 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 80 micron to 100 micron.

[0441] In some examples, the internal layer 332 can be perforated. In some examples, the internal layer 332¹ can include a plurality of perforations. In some examples, the internal layer 332 can be perforated such that at least some of the plurality of the perforations extend through a thickness of internal layer 332 and pierce through the inner surface 3322 and through the outer surface 3321. In some examples, the internal layer 332 can be perforated such that each one of the plurality of the perforations extends through a thickness of internal layer 332 and pierces through the inner surface 3322 and through the outer surface 3321. In some examples, even a relatively very low threshold as low as 0.5 micron for the pose size can be considered, since cell migration or neovascularization is not required for the neointimal layer.

[0442] In some examples, the internal layer 332 of the base layer portion 132¹ can be selected from an electrospun internal layer 332, melt blown spun internal layer 332, air jet spun internal layer 332 and an internal layer 332 comprising a salt-leached inner surface 3322.

[0443] In some examples, the internal layer 332 of the base layer portion 132¹ can be an electrospun internal layer 332. [0444] Advantages of the electrospinning option are discussed with respect to the optionally electrospun base layer portion 132 herein. Advantageously, an electrospun layer, such as the internal layer 332, can optionally lead to absence of signs of inflammation compared to smooth skirts. In addition, an electrospun layer, such as the internal layer 332, can optionally lead to absence of signs of growth of giant cells compared to smooth skirts.

[0445] In some examples, the electrospun internal layer 332 of the base layer portion 132¹ can optionally be electrospun from a melt. In some examples, the electrospun internal layer 332 can optionally be electrospun from a solution. In some examples, the solution can optionally include an organic solvent. In some examples, the organic solvent can optionally be selected from the group consisting of: l,l,l,3,3,3-hexafhioro-2-propanol (HFIP), tetrahydrofuran (THF), acetone, dimethylformamide (DMF) and any combination thereof.

[0446] In some examples, the electrospun internal layer 332 can be electrospun from a solution, wherein the solution can optionally include a polymeric material at a concentration in the range of 2% w/w to 12% w/w, including each value and sub-range within the specified range. It is to be understood to the person having ordinary skill in the art that the polymer within the electrospinning solution forms fine filaments upon the electrospinning process, wherein the product can optionally be the internal layer 332. Therefore, in some examples, the dissolved polymer is the material forming the internal layer 332. Thus, any example, which applies to any polymer as the internal layer 332 can similarly apply to the polymer in the electrospinning solution. Similarly, it is to be understood to the person having ordinary skill in the art that any example, which applies to any polymer as the polymer in the electrospinning solution can similarly apply to the internal layer 332.

[0447] In some examples, the internal layer 332 of the base layer portion 132¹ can include a plurality of filaments. In some examples, the electrospun internal layer 332 can include a plurality of filaments. In some examples, upon electrospinning of the internal layer 332 of the base layer portion 132 a plurality of filaments can form.

[0448] In some examples, each one of the plurality of filaments can have a diameter in the range of 0.1 to 20 micron, including each value and sub-range within the specified range. In some examples, each one of the plurality of filaments can have a diameter in the range of 1 to 5 micron. In some examples, each one of the plurality of filaments can have a diameter in the range of 3 to 5 micron. In some examples, the plurality of filaments can have an average diameter in the range of 1 to 5 micron, including each value and sub-range within the specified range. In some examples, the plurality of filaments can have an average diameter in the range of 3 to 5 micron. In some examples, the plurality of filaments can have a mean diameter in the range of 1 to 5 micron, including each value and sub-range within the specified range. In some examples, the plurality of filaments can have a mean diameter in the range of 3 to 5 micron.

[0449] In some examples, formation of a textured surface of an internal layer 332 can include electrospraying a polymer over the inner surface of the internal layer 332 to form a textured inner surface 3322. In some examples, formation of a textured surface of an internal layer 332 can include providing a liquid polymer composition contained in an electrospray device and electrospraying the liquid polymer composition over the inner surface of the internal layer 332 to form a textured inner surface 3322.

[0450] The electrospray device can optionally be as defined for the electrospray device that can be utilized to form the textured surface of the base layer portion 132^h. In some examples, the internal layer 332 can optionally include a polymer selected from the group consisting of: thermoplastic polyurethane (TPU), expanded poly tetrafluoroethylene (ePTFE), fluorinatedethylenepropylene polymer (FEP), biomimetic collagen, a hyaluronic acid derivative and a combination thereof. In some examples, the electrospinning can be performed at a flow rate in the range of 0.1 ml pe hour to 8 ml per hour, including each value and subrange within the specified range. In some examples, the electrospinning can be performed at a voltage in the range of 10 kV to 14 kV, including each value and sub-range within the specified range.

[0451] In some examples, the internal layer 332 of the base layer portion 132' can be a jet spun internal layer 332. In some examples, the jet-spun internal layer 332 can optionally be jet-spun from a melt. In some examples, the jet-spun internal layer 332 can optionally be jet-spun from a solution. In some examples, the solution can optionally include an organic solvent. In some examples, the organic solvent can optionally be selected from the group consisting of: l,l,l,3,3,3-hexafluoro-2-propanol (HFIP), tetrahydrofuran (THF), acetone, dimethylformamide (DMF) and any combination thereof.

[0452] In some examples, the internal layer 332 can be jet-spun from a solution, wherein the solution can optionally include a polymeric material at a concentration in the range of 2% w/w to 12% w/w, including each value and sub-range within the specified range. It is to be understood to the person having ordinary skill in the art that the polymer within the jet-spinning solution forms fibers upon the jet-spinning process, wherein the product can optionally be the internal layer 332. Therefore, in some examples, the dissolved polymer is the material forming the internal layer 332. Thus, any example, which applies to any polymer as the internal layer 332 can similarly apply to the polymer in the jet-spinning solution. Similarly, it is to be understood to the person having ordinary skill in the art that any example, which applies to any polymer as the polymer in the jet-spinning solution can similarly apply to the internal layer 332.

[0453] In some examples, formation of a textured surface of an internal layer 332 can include jet-spraying a polymer over the inner surface of the internal layer 332 to form a textured inner surface 3322. In some examples, formation of a textured surface of an internal layer 332 can include providing a liquid polymer composition contained in a jet-spray device and jet-spraying the liquid polymer composition over the inner surface of the internal layer 332 to form a textured inner surface 3322.

[0454] In some examples, materials, such as polymers, which can be suitable for the purpose of promoting endothelization and/or neointimal growth, can include, but are not limited to, fluorinated polymers (e.g., TPU, ePTFE, FEP), as well as biomimetic collagen or hyaluronic acid-based materials.

[0455] In some examples, the internal layer 332 of the base layer portion 132¹ can comprise a salt-leached inner surface 3322. In some examples, formation of a porous internal layer 332 comprises providing a porogen, which can be solid at room temperature. In some examples, the porogen has melting point above 100°C or above 200°C. In some examples, the porogen is an inorganic compound. In some examples, the porogen has aqueous solubility of at least 1 gr/ml, at least 5 gr/ml or at least 10 gr/ml. In some examples, the porogen is in the form of a powder. In some examples, the porogen has particle size in the range of 0.4 micron to 4 micron, 2 micron to 20 micron, 10 micron to 100 micron, 50 micron to 500 micron, 100 micron to 1000 micron, or 200 micron to 2000 micron.

[0456] In some examples, formation of a salt-leached inner surface 3322 can include casting the mixture to form a solid casted layer that can include the porogen dispersed within the casted solid polymer. In some examples, formation of a salt-leached inner surface 3322 can include molding the mixture to form a solid molded layer that comprises the porogen dispersed within the molded solid polymer. In some examples, the porogen particles can be substantially evenly dispersed within the solid polymer.

[0457] In some examples, formation of a salt-leached inner surface 3322 can further comprise contacting the formed solid layer with water, thereby leaching at least some of the porogen from the solid layer to form vacated pores within the layer. In some examples, contact with water can be performed at a temperature of at least 20°C, at least 25°C, at least 30°C, at least 40°C, at least 60°C, or at least 80°C. In some examples, contact with water can be performed for a period of 1 to 120 minutes. [0458] In some examples, the internal layer 332 of the base layer portion 132¹ can be a melt blown internal layer 332.

[0459] In some examples, the internal layer 332 of the base layer portion 132 can have an inner surface 3322, which is encouraging neointimal-formation at a thickness in the range of 1 micron to 200 micron, including each value and sub-range within the specified range. In some examples, the internal layer 332 of the base layer portion 132 can encourage neointimal formation at a thickness in the range of 1 micron to 200 micron, including each value and subrange within the specified range.

[0460] In some examples, the internal layer 332 of the base layer portion 132 of the skirt 130^c can include a coating layer (not illustrated). In some examples, the coating layer can be coating the inner surface of the internal layer 332, such that an inner surface of the coating layer can define the neointimal-formation encouraging inner surface 3322. In some examples, the coating can promote endothelization. In some examples, the coating can promote neointimal tissue formation. In some examples, the coating can promote endothelization. In some examples, the coating can promote neointimal formation at a thickness in the range of 1 micron to 200 micron, including each value and sub-range within the specified range. In some examples, the coating can include at least one endothelium tissue promoting compound.

[0461] In some examples, the endothelium tissue promoting compound can be selected from the group consisting of: collagen, chitosan hyaluronic acid and a combination thereof. In some examples, the endothelium tissue promoting compound can include collagen. In some examples, the endothelium tissue promoting compound can include collagen at a concentration of 0.1% w/w to 3% w/w. In some examples, the endothelium tissue promoting compound can include hyaluronic acid. In some examples, the endothelium tissue promoting compound can include hyaluronic acid at a concentration of 0.1% w/w to 3% w/w. In some examples, the endothelium tissue promoting compound can include chitosan. In some examples, the endothelium tissue promoting compound can include chitosan at a concentration of 0.1% w/w to 3% w/w.

[0462] In some examples, the endothelium tissue promoting compound can be non-toxic. In some examples, the endothelium tissue promoting compound can be non-inflammatory. In some examples, the endothelium tissue promoting compound can be bioresorbable. In some examples, the endothelium tissue promoting compound can be biodegradable. In some examples, the endothelium tissue promoting compound can be biodegradable over a period of one year to two years. Specifically, in some examples, endothelium tissue promoting compound can be configured to degrade over a period one year to two years while being replaced by native tissue.

[0463] Figs. 14A, 15A and 16A also present the value of T3, which, as detailed herein relates to the thickness of the base layer portion 132 of any exemplary skirt 130 disclosed herein, including exemplary base layer portion 132¹. The thickness T3 of a multi-layered base layer portion 132¹ can be equal to the combined thicknesses of all layers comprised in base layer portion 132¹. For example, for a double-layered base layer portion 132¹ as illustrated in Fig. 14A, 15 A and 16A, the thickness T3 can be equal to the sum of a thickness T33 defined by the internal layer 332 and a thickness T32 defined by the external layer 232.

[0464] The thickness T33 of the internal layer 332 can be measured from the outer surface 3321 to the inner surface 3322 of the internal layer 332. In some examples, the thickness of the internal layer 332 can be in the range of 25 micron to 75 micron, including each value and subrange within the specified range. In some examples, the thickness of the internal layer 332 can be in the range of 25 micron to 65 micron. In some examples, the thickness of the internal layer 332 can be in the range of 50 micron to 60 micron.

[0465] Fig. 14C schematically shows a surface texture of an inner surface 2322¹¹ of an exemplary external layer 232¹¹ of the base layer portion 132¹ of Fig. 14A. As can be seen in detail in Fig. 14C, the inner surface 2322¹¹ can optionally be perforated. The perforated inner surface 2322¹¹ can optionally include a plurality of filaments. In some examples, the external layer 232¹¹ of the base layer portion 132¹ can be include a plurality of filaments. Internal layers 232 that are porous and include a plurality of filaments can be formed by one or more of the methods as described herein in detail, for example electrospinning or air jet spinning. As can also be seen when comparing Figure 14B and Figure 14C, the porosity of the external layer 232 and the porosity of the external layer 232 can be substantially different.

[0466] Figure 15C is an enlarged perspective view of the inner surface 2322 of the external layer 232 of the base layer portion of the skirt 130^c of Figure 15A. As can also be seen when comparing Figure 15B and Figure 15C, the porosity of the external layer 232 and the porosity of the external layer 232 can be different. In some examples, the pore size of the pores of the external layer 232 is smaller than the pore size of the pores of the external layer 232, as discussed herein. In some examples, the surface morphology of the inner surface 2322 has a more crowded texture than the surface morphology of the inner surface 3322.

[0467] Fig. 16C schematically shows a surface texture of an inner surface 2322¹³ of an exemplary external layer 232¹³ of the base layer portion 132¹ of Fig. 16A. As can be seen in detail in Fig. 14C, the inner surface 2322 can optionally be nonporous. In some examples, the inner surface 2322 can optionally have a flat surface morphology. In some examples, the inner surface 2322 can optionally be smooth. In some examples, the inner surface 2322 can optionally have a rough yet nonporous surface morphology.

[0468] An inner skirt 130 can be coupled to the frame 102 by one or more sutures (not shown) extending through the base layer portion 132, such as through exposed parts of the base layer 132 which are not covered by protruding extension 150, wherein the sutures can be optionally lopped around struts of the frame. In some examples, an internal layer 332 of a multi-layered base layer portion 132¹ is configured to promote neointimal tissue growth thereover, while the external layer 232 is configured to improve tissue adhesion to the skirt.

[0469] In some examples, the external layer 232¹³ is impermeable. In some examples, the external surface 2321¹³ of the external layer 232¹³ is impermeable. In some examples, the internal surface 2322¹³ of the external layer 232¹³ is impermeable.

[0470] In some examples, the external layer 232 of the base layer portion can be melt extruded. The term "melt extrusion", as used herein, refers to a process by which material, optionally a polymer, can be optionally mixed, at least partially melted and then forced through a mold or a cast under controlled conditions to a predetermined shape. Then upon colling, the material can assume the shape of the mold or the cast.

[0471] In some examples, the inner surface 2322 can be rough. It is to be understood that rough surfaces, textured surfaces and surfaces that have non-uniform surface morphologies can be either permeable or non-permeable.

[0472] In some examples, the inner surface 2322 of the external layer 232 can be porous. In some examples, the external layer 232 of base layer portion 132¹ can be porous.

[0473] While an internal layer 332 can includes a porous texture configured to encourage neointimal tissue growth over the inner surface 3322, an external or second layer 232 can be either nonporous or include smaller-sized pores. In some examples, a nonporous external layer 232 can include a rough surface 2322 that can enhance securement of an optionally electrospun internal layer 332. In some examples, a porous external layer 232 can include relatively smallsized pores that can be smaller than those of the internal layer 332, wherein the pores of the external layer 232 can be configured to enhance securement of an optionally electrospun internal layer 332 to the external layer 232, yet small enough to prevent loose or reticulated foam particles from being released from the protruding extension 150 through the surface 2321 of the external layer 232.

[0474] In some examples, the inner surface 2322 of the external layer 232 of the base layer portion 232 can include a plurality of pores. In some examples, the external layer 232 of the base layer portion 132 can include a plurality of pores. In some examples, each pore can have a pore size in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron.

[0475] In some examples, a mean pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, each pore can have a pore size in the range of 20 micron to 100 micron. In some examples, each pore can have a pore size in the range of 80 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 20 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 80 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 20 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 80 micron to 100 micron.

[0476] In some examples, the pore size of the internal layer 332 can be greater than the pore size the external layer 232. In some examples, the pore size of the internal layer 332 can be at least 10% greater than the pore size the external layer 232. In some examples, the pore size of the internal layer 332 can be at least 25% greater than the pore size the external layer 232. In some examples, the pore size of the internal layer 332 can be at least 50% greater than the pore size the external layer 232. In some examples, the pore size of the internal layer 332 can be at least 100% greater than the pore size the external layer 232. In some examples, the pore size of the internal layer 332 can be at least 250% greater than the pore size the external layer 232. In some examples, the pore size of the internal layer 332 can be at least 500% greater than the pore size the external layer 232.

[0477] In some examples, the average pore size of the plurality of pores of the internal layer 332 can be greater than the average pore size of the plurality of pores the external layer 232. In some examples, the average pore size of the plurality of pores of the internal layer 332 can be at least 10% greater than the average pore size of the plurality of pores the external layer 232. In some examples, the average pore size of the plurality of pores of the internal layer 332 can be at least 25% greater than the average pore size of the plurality of pores the external layer 232. In some examples, the average pore size of the plurality of pores of the internal layer 332 can be at least 50% greater than the average pore size of the plurality of pores the external layer 232. In some examples, the average pore size of the plurality of pores of the internal layer 332 can be at least 100% greater than the average pore size of the plurality of pores the external layer 232. In some examples, the average pore size of the plurality of pores of the internal layer 332 can be at least 250% greater than the average pore size of the plurality of pores the external layer 232. In some examples, the average pore size of the plurality of pores of the internal layer 332 can be at least 500% greater than the average pore size of the plurality of pores the external layer 232.

[0478] In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be greater than the mean pore size of the plurality of pores the external layer 232. In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be at least 10% greater than the mean pore size of the plurality of pores the external layer 232. In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be at least 25% greater than the mean pore size of the plurality of pores the external layer 232. In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be at least 50% greater than the mean pore size of the plurality of pores the external layer 232. In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be at least 100% greater than the mean pore size of the plurality of pores the external layer 232. In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be at least 250% greater than the mean pore size of the plurality of pores the external layer 232. In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be at least 500% greater than the mean pore size of the plurality of pores the external layer 232.

[0479] In some examples, the inner surface 2322 of the external layer 232 of the base layer portion 132 can include a plurality of pores. In some examples, the external layer 232 of the base layer portion 132 can include a plurality of pores. In some examples, each pore can have a pore size in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron.

[0480] In some examples, a mean pore size of the plurality of pores can be in the range of 0.5 micron to 100 micron, including each value and sub-range within the specified range, for example 0.5 micron to 1 micron, 1 micron to 5 micron, 5 micron to 25 micron or 25 micron to 100 micron. In some examples, each pore can have a pore size in the range of 20 micron to 100 micron. In some examples, each pore can have a pore size in the range of 80 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 20 micron to 100 micron. In some examples, an average pore size of the plurality of pores can be in the range of 80 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 20 micron to 100 micron. In some examples, a mean pore size of the plurality of pores can be in the range of 80 micron to 100 micron.

[0481] In some examples, the pore size of the internal layer 332 can be greater than the pore size the external layer 232. In some examples, the average pore size of the plurality of pores of the internal layer 332 can be greater than the average pore size of the plurality of pores the external layer 232. In some examples, the mean pore size of the plurality of pores of the internal layer 332 can be greater than the mean pore size of the plurality of pores the external layer 232. [0482] In some examples, the external layer 232 of the base layer portion 132¹ can be perforated. In some examples, the external layer 232 of the base layer portion 132¹ can include a plurality of perforations. In some examples, the external layer 232 of the base layer portion 132 of the skirt 130^c can be perforated, such that least some of the plurality of the perforations extend through a thickness of the external layer 232 and pierce through the inner surface 2322 and through the outer surface 2321. In some examples, the external layer 232 of the base layer portion 132 of the skirt 130^c can be perforated, such that each one of the plurality of the perforations extends through a thickness of the and pierces through the inner surface 2322 and through the outer surface 2321. In some examples, even a relatively very low threshold as low as 0.5 micron for the pose size can be considered, since cell migration or neovascularization is not required for the neointimal layer.

[0483] In some examples, the external layer 232 of the base layer portion 132¹ can be selected from a melt extruded external layer 232, an electrospun external layer 232, a melt blown spun external layer 232, an air jet spun external layer 232 and an external layer 232 comprising a salt-leached inner surface 2322.

[0484] In some examples, the external layer 232 of the base layer portion 132¹ can be an electrospun external layer 232.

[0485] In some examples, the electrospun external layer 232 of the base layer portion 132¹ can optionally be electrospun from a melt. In some examples, the electrospun external layer 232 can optionally be electrospun from a solution. In some examples, the solution can optionally include an organic solvent. In some examples, the organic solvent can optionally be selected from the group consisting of: l,l,l,3,3,3-hexafluoro-2-propanol (HFIP), tetrahydrofuran (THF), acetone, dimethylformamide (DMF) and any combination thereof.

[0486] In some examples, the electrospun external layer 232 can be electrospun from a solution, wherein the solution can optionally include a polymeric material at a concentration in the range of 2% w/w to 12% w/w, including each value and sub-range within the specified range. It is to be understood to the person having ordinary skill in the art that the polymer within the electrospinning solution forms fine filaments upon the electrospinning process, wherein the product can optionally be the external layer 232. Therefore, in some examples, the dissolved polymer is the material forming the external layer 232.

[0487] In some examples, the external layer 232 of the base layer portion 132¹ can include a plurality of filaments. In some examples, the external layer 232 can include a plurality of filaments. In some examples, upon electrospinning of the external layer 232 of the base layer portion 132 a plurality of filaments can form.

[0488] In some examples, each one of the plurality of filaments can have a diameter in the range of 0.1 to 20 micron, including each value and sub-range within the specified range. In some examples, each one of the plurality of filaments can have a diameter in the range of 1 to 5 micron. In some examples, each one of the plurality of filaments can have a diameter in the range of 1 to 1.5 micron. In some examples, the plurality of filaments can have an average diameter in the range of 1 to 5 micron, including each value and sub-range within the specified range. In some examples, the plurality of filaments can have an average diameter in the range of 1 to 1.5 micron. In some examples, the plurality of filaments can have a mean diameter in the range of 1 to 5 micron, including each value and sub-range within the specified range. In some examples, the plurality of filaments can have a mean diameter in the range of 1 to 1.5 micron.

[0489] In some examples, the plurality of filaments of the electrospun internal layer 332 can have a diameter, which is greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a diameter, which is at least 10% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a diameter, which is at least 25% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a diameter, which is at least 50% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a diameter, which is at least 100% greater than the diameter of the plurality of filaments of the electrospun external layer 232.

[0490] In some examples, the plurality of filaments of the electrospun internal layer 332 can have an average diameter, which is greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have an average diameter, which is at least 10% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have an average diameter, which is at least 25% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have an average diameter, which is at least 50% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have an average diameter, which is at least 100% greater than the diameter of the plurality of filaments of the electrospun external layer 232.

[0491] In some examples, the plurality of filaments of the electrospun internal layer 332 can have a mean diameter, which is greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a mean diameter, which is at least 10% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a mean diameter, which is at least 25% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a mean diameter, which is at least 50% greater than the diameter of the plurality of filaments of the electrospun external layer 232. In some examples, the plurality of filaments of the electrospun internal layer 332 can have a mean diameter, which is at least 100% greater than the diameter of the plurality of filaments of the electrospun external layer 232.

[0492] In some examples, the external layer 232 of the base layer portion 132¹ can be a jet spun external layer 232. In some examples, the external layer 232 of the base layer portion 132¹ can comprise a salt-leached inner surface 2322. In some examples, the external layer 232 of the base layer portion 132¹ can be a melt blown external layer 232.

[0493] The thickness of the external layer 232 can be measured from the outer surface 2321 to the inner surface 2322 of the external layer 232. In some examples, the thickness of the external layer 232 can be in the range of 25 micron to 55 micron, including each value and sub-range within the specified range. In some examples, the thickness of the external layer 232 can be in the range of 25 micron to 45 micron. In some examples, the thickness of the external layer 232 can be in the range of 35 micron to 45 micron.

[0494] It is to be understood that a double layered base layer portion 132‘ is shown in Figs. 14A-16C by way of illustration and not limitation, and that in some examples, a multi-layered base layer portion 132¹ can include more than two layers. For example, the internal layer 332 according to any example disclosed herein can be also referred to as a first layer 332 of a multilayered base layer portion 132¹, the external layer 232 according to any example disclosed herein can be also referred to as a second layer 232 of a multi-layered base layer portion 132¹, and at least one additional layer, such as a third layer (not shown) of the multi-layered base layer portion 132¹, can be disposed between the second layer 232 and the protruding extension

150, wherein the third layer can be implemented according to any of the examples disclosed herein of the external or second layer 232.

Some Examples of the Disclosed Implementations

[0495] Some examples of above-described implementations are 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 examples below are examples also falling within the disclosure of this application.

[0496] Example 1. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; and a one-piece valvular structure mounted within the frame and comprising: a plurality of leaflets, which are integrally formed as regions of the one-piece valvular structure, and have a thickness

T1 ; and an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets, the engagement portion having a thickness T2; wherein T1 is greater than T2.

[0497] Example 2. The prosthetic valve of any example herein, particularly of example 1, wherein T1 is at least 25% greater than T2.

[0498] Example 3. The prosthetic valve of any example herein, particularly of example 1, wherein T1 is at least 50% greater than T2.

[0499] Example 4. The prosthetic valve of any example herein, particularly of example 1, wherein T1 is at least 100% greater than T2.

[0500] Example 5. The prosthetic valve of any example herein, particularly of any one of examples 1 to 4, wherein the thickness T2 is in the range of 50 to 200 micron. [0501] Example 6. The prosthetic valve of any example herein, particularly of any one of examples 1 to 5, wherein each one of the plurality of leaflets comprises a corresponding belly, and wherein each leaflet belly is defined between a lower cusp line and an upper free edge of the corresponding leaflet.

[0502] Example 7. The prosthetic valve of any example herein, particularly of example 6 wherein the engagement portion is extending between a distal end thereof and the cusp lines of the leaflets.

[0503] Example 8. The prosthetic valve of any example herein, particularly of any one of examples 1 to 7, wherein the valvular structure is formed as a unitary component having dedicated regions thereof defining the integrally formed leaflet that are continuously interconnected at commissure attachment regions.

[0504] Example 9. The prosthetic valve of any example herein, particularly of example 8, wherein the commissure attachment regions are secured to the frame to form commissures.

[0505] Example 10. The prosthetic valve of any example herein, particularly of any one of examples 1 to 9, wherein the valvular structure comprises shaped tissue material.

[0506] Example 11. The prosthetic valve of any example herein, particularly of example 10, wherein the tissue material comprises pericardium.

[0507] Example 12. The prosthetic valve of any example herein, particularly of any one of examples 1 to 11, further comprising a skirt comprising: a base layer portion secured to an inner surface of the frame; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame.

[0508] Example 13. The prosthetic valve of any example herein, particularly of example 12, wherein the skirt base layer portion extends between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge closer to the outflow end of the frame.

[0509] Example 14. The prosthetic valve of any example herein, particularly of example 13, wherein the distal edge of the skirt base layer portion is connected to the inflow end of the frame.

[0510] Example 15. The prosthetic valve of any example herein, particularly of any one of examples 13 to 14, wherein the engagement portion is extending between a distal end thereof, which is closer to the inflow end of the frame, and cusp lines of the leaflets, which are closer to the outflow end of the frame. [0511] Example 16. The prosthetic valve of any example herein, particularly of example 15, wherein the distal edge of the skirt base layer portion is connected to the inflow end of the frame.

[0512] Example 17. The prosthetic valve of any example herein, particularly of any one of examples 12 to 16, wherein the base layer portion is at least partially overlapping axially with the engagement portion.

[0513] Example 18. The prosthetic valve of any example herein, particularly of example 17 wherein the base layer portion has thickness T3, wherein an overlapping potion between the base layer portion and the engagement portion has total thickness T2+T3, and wherein T1 is greater or equal to T2+T3.

[0514] Example 19. The prosthetic valve of any example herein, particularly of any one of examples 12 to 18, wherein the protruding extensions of the skirt comprise foam material.

[0515] Example 20. The prosthetic valve of any example herein, particularly of example 19, wherein the foam material is selected from the group consisting of: polyethylene foam, polyethylene terephthalate mesh and a combination thereof.

[0516] Example 21. The prosthetic valve of any example herein, particularly of any one of examples 19 to 20, wherein the foam material is porous, having pore size in the range of 3 micron to 50 micron.

[0517] Example 22. The prosthetic valve of any example herein, particularly of any one of examples 19 to 21, wherein each of the protruding extensions has an inner surface, which is in contact with the base layer portion, and an outer surface, which is spherical dome shaped and positioned radially away from the inner surface.

[0518] Example 23. The prosthetic valve of any example herein, particularly of example 22, wherein the outer surfaces of the protruding extensions are porous.

[0519] Example 24. The prosthetic valve of any example herein, particularly of example 23wherein the outer surfaces of the protruding extensions have pore size in the range of 3 micron to 50 micron.

[0520] Example 25. The prosthetic valve of any example herein, particularly of any one of examples 23 to 24, wherein the outer surfaces of the protruding extensions are laminated by a coating layer.

[0521] Example 26. The prosthetic valve of any example herein, particularly of example 25 wherein the coating layer is perforated, and has an aperture size in the range of 3 micron to 50 micron. [0522] Example 27. The prosthetic valve of any example herein, particularly of any one of examples 25 to 26, wherein the coating layer is hydrophilic.

[0523] Example 28. The prosthetic valve of any example herein, particularly of any one of examples 12 to 27, wherein each one of the protruding extensions of the skirt has a thickness in the range of 10 micron to 100 micron.

[0524] Example 29. A method of forming a prosthetic valve, the method comprising: providing a generally rectangular patch, comprising a moldable material and extending between a first side edge and a second side edge, wherein the patch has thickness T1 , the patch comprising: a plurality of leaflets, each one of the plurality of leaflets comprises a corresponding belly that forms a 3D-shape of the patch, wherein each leaflet belly is defined between a lower cusp line and an upper free edge of the corresponding leaflet; and an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets; cutting a thickness portion of the engagement portion, so that the thickness of the engagement portion is reduced from T1 to T2, which is lower than Tl; and rolling the 3D-shaped patch by bringing the first side edge and the second side edge together to assume a cylindrical configuration; and connecting the 3D-shaped patch to a frame of a prosthetic valve.

[0525] Example 30. The method of any example herein, particularly of example 29, wherein the cutting is performed by laser milling or by mechanical skiving.

[0526] Example 31. The method of any example herein, particularly of any one of examples 29 to 30, wherein Tl is in the range of 50-200 micron.

[0527] Example 32. The method of any example herein, particularly of any one of examples 29 to 31 , wherein the patch comprises a tissue material.

[0528] Example 33. The method of any example herein, particularly of example 32, further comprising inserting a 2D-shaped patch into a mold, forcing it to assume a 3D-shape and cross-linking the tissue material to maintain the 3D-shape.

[0529] Example 34. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; a plurality of leaflets, positioned at least partially within the frame, wherein each leaflet comprises: a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge, which is closer to the outflow end; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame; wherein the proximal edge of the base layer portion is positioned closer to the outflow end of the frame than the leaflet distal end.

[0530] Example 35. The prosthetic valve of any example herein, particularly example 34, wherein the entire region between the cusp lines of adjacent leaflets is covered by the base layer portion.

[0531] Example 36. The prosthetic valve of any example herein, particularly of any one of examples 34 to 35, wherein the proximal edge of the base layer portion has a generally straight pattern, such that it is substantially uniform in distance from the inflow end of the frame.

[0532] Example 37. The prosthetic valve of any example herein, particularly of any one of examples 34 to 35, wherein the base layer portion proximal edge extends between throughs, which are closer to an inflow end of the frame, and peaks, which are closer to the outflow end of the frame, to form a plurality of extensions extending from the throughs.

[0533] Example 38. The prosthetic valve of any example herein, particularly example 37, wherein the base layer portion and outflow extensions thereof are covering the entire region between adjacent leaflets.

[0534] Example 39. The prosthetic valve of any example herein, particularly of any one of examples 34 to 38, wherein the leaflet bellies are not flattenable.

[0535] Example 40. The prosthetic valve of any example herein, particularly of any one of examples 34 to 39, wherein adjacent leaflets are arranged together to form commissures that are coupled to respective portions of the frame, thereby securing the leaflets to the frame.

[0536] Example 41. The prosthetic valve of any example herein, particularly of any one of examples 34 to 40, wherein the leaflets comprise shaped tissue material.

[0537] Example 42. The prosthetic valve of any example herein, particularly example 41, wherein the tissue material comprises pericardium.

[0538] Example 43. The prosthetic valve of any example herein, particularly of any one of examples 34 to 42, wherein the distal edge of the skirt base layer portion is connected to the inflow end of the frame.

[0539] Example 44. The prosthetic valve of any example herein, particularly of any one of examples 34 to 43, wherein the leaflet distal end is at a midpoint of the cusp line.

[0540] Example 45. The prosthetic valve of any example herein, particularly of any one of examples 34 to 44, wherein the skirt is devoid of protruding extensions extending from a surface of the base layer portion which is axially defined between the proximal edge thereof and the leaflet distal end.

[0541] Example 46. The prosthetic valve of any example herein, particularly of any one of examples 34 to 35, wherein the leaflet bellies have a three-dimensional and concave shape.

[0542] Example 47. The prosthetic valve of any example herein, particularly of any one of examples 34 to 46, wherein the plurality of leaflets are configured to regulate flow of blood through the prosthetic valve from the inflow end to the outflow end of the frame.

[0543] Example 48. The prosthetic valve of any example herein, particularly of any one of examples 34 to 47, wherein the plurality of leaflets comprises three leaflets arranged to collapse in a tricuspid arrangement.

[0544] Example 49. The prosthetic valve of any example herein, particularly of any one of examples 34 to 48, wherein the protruding extensions of the skirt comprise foam material.

[0545] Example 50. The prosthetic valve of any example herein, particularly example 49, wherein the foam material is selected from the group consisting of: polyethylene foam, polyethylene terephthalate mesh and a combination thereof.

[0546] Example 51. The prosthetic valve of any example herein, particularly of any one of examples 49 to 50, wherein the foam material is porous, having pore size in the range of 3 micron to 50 micron.

[0547] Example 52. The prosthetic valve of any example herein, particularly of any one of examples 49 to 51 , wherein each of the protruding extensions has an inner surface, which is in contact with the base layer portion, and an outer surface, which is spherical dome shaped and positioned radially away from the inner surface.

[0548] Example 53. The prosthetic valve of any example herein, particularly example 52, wherein the outer surfaces of the protruding extensions are porous.

[0549] Example 54. The prosthetic valve of any example herein, particularly example 53, wherein the outer surfaces of the protruding extensions have pore size in the range of 3 micron to 50 micron.

[0550] Example 55. The prosthetic valve of any example herein, particularly of any one of examples 53 to 54, wherein the outer surfaces of the protruding extensions are laminated by a coating layer.

[0551] Example 56. The prosthetic valve of any example herein, particularly example 55, wherein the coating layer is perforated, and has an aperture size in the range of 3 micron to 50 micron. [0552] Example 57. The prosthetic valve of any example herein, particularly of any one of examples 55 to 56, wherein the coating layer is hydrophilic.

[0553] Example 58. The prosthetic valve of any example herein, particularly of any one of examples 34 to 57, wherein each one of the protruding extensions of the skirt has a thickness in the range of 10 micron to 100 micron.

[0554] Example 59. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; a one-piece valvular structure mounted within the frame and comprising: a plurality of leaflets, which are integrally formed as regions of the one-piece valvular structure; an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge, which is closer to the outflow end; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame; wherein the skirt base layer portion is positioned radially away from the engagement portion, and entirely covers it.

[0555] Example 60. The prosthetic valve of any example herein, particularly example 59, wherein the leaflets have thickness Tl, the engagement portion has a thickness T2, the base layer portion has thickness T3, so that the covered potion of the base layer portion and the engagement portion has total thickness T2+T3, and wherein Tl is greater or equal to T2+T3.

[0556] Example 61. The prosthetic valve of any example herein, particularly of any one of examples 59 to 60, wherein the valvular structure comprises shaped tissue material.

[0557] Example 62. The prosthetic valve of any example herein, particularly example 61, wherein the tissue material comprises pericardium.

[0558] Example 63. The prosthetic valve of any example herein, particularly of any one of examples 59 to 62, wherein adjacent leaflets of the plurality of leaflets are arranged together to form commissures, wherein the commissures are coupled to respective portions of the frame, thereby securing at least a portion of the valvular structure to the frame.

[0559] Example 64. The prosthetic valve of any example herein, particularly example 63, wherein the one-piece valvular structure has regions defining the integrally formed leaflets that are interconnected at commissure attachment regions. [0560] Example 65. The prosthetic valve of any example herein, particularly of any one of examples 63 to 64, wherein the base layer portion is extending between the distal edge and the commissures.

[0561] Example 66. The prosthetic valve of any example herein, particularly of any one of examples 59 to 65, wherein the proximal edge of the base layer portion has a generally straight pattern, such that it is substantially uniform in distance from the inflow end of the frame.

[0562] Example 67. The prosthetic valve of any example herein, particularly of any one of examples 48 to 55, wherein the base layer portion proximal edge extends between throughs, which are closer to an inflow end of the frame, and peaks, which are closer to the outflow end of the frame, to form a plurality of extensions extending from the throughs.

[0563] Example 68. The prosthetic valve of any example herein, particularly of any one of examples 59 to 67, wherein the skirt is devoid of protruding extensions extending from a surface of the base layer portion which is axially defined between the proximal edge thereof and the leaflet distal end.

[0564] Example 69. The prosthetic valve of any example herein, particularly of any one of examples 59 to 68, wherein the leaflet bellies are not flattenable.

[0565] Example 70. The prosthetic valve of any example herein, particularly of any one of examples 59 to 69, wherein the plurality of leaflets are configured to regulate flow of blood through the prosthetic valve from the inflow end to the outflow end of the frame.

[0566] Example 71. The prosthetic valve of any example herein, particularly of any one of examples 59 to 70, wherein the plurality of leaflets comprises three leaflets arranged to collapse in a tricuspid arrangement.

[0567] Example 72. The prosthetic valve of any example herein, particularly of any one of examples 59 to 71, wherein the engagement portion is extending between a distal end thereof, which is closer to the inflow end of the frame, and cusp lines of the leaflets, which are closer to the outflow end of the frame.

[0568] Example 73. The prosthetic valve of any example herein, particularly of any one of examples 59 to 72, wherein the distal edge of the skirt base layer portion is connected to the inflow end of the frame.

[0569] Example 74. The prosthetic valve of any example herein, particularly of any one of examples 59 to 73, wherein the protruding extensions of the skirt comprise foam material.

[0570] Example 75. The prosthetic valve of any example herein, particularly example 74, wherein the foam material is selected from the group consisting of: polyethylene foam, polyethylene terephthalate mesh and a combination thereof. [0571] Example 76. The prosthetic valve of any example herein, particularly of any one of examples 74 to 75, wherein the foam material is porous, having pore size in the range of 3 micron to 50 micron.

[0572] Example 77. The prosthetic valve of any example herein, particularly of any one of examples 74 to 76, wherein each of the protruding extensions has an inner surface, which is in contact with the base layer portion, and an outer surface, which is spherical dome shaped and positioned radially away from the inner surface.

[0573] Example 78. The prosthetic valve of any example herein, particularly example 77, wherein the outer surfaces of the protruding extensions are porous.

[0574] Example 79. The prosthetic valve of any example herein, particularly example 78, wherein the outer surfaces of the protruding extensions have pore size in the range of 3 micron to 50 micron.

[0575] Example 80. The prosthetic valve of any example herein, particularly of any one of examples 77 to 79, wherein the outer surfaces of the protruding extensions are laminated by a coating layer.

[0576] Example 81. The prosthetic valve of any example herein, particularly example 80, wherein the coating layer is perforated, and has an aperture size in the range of 3 micron to 50 micron.

[0577] Example 82. The prosthetic valve of any example herein, particularly of any one of examples 80 to 81, wherein the coating layer is hydrophilic.

[0578] Example 83. The prosthetic valve of any example herein, particularly of any one of examples 59 to 82, wherein each one of the protruding extensions of the skirt has a thickness in the range of 10 micron to 100 micron.

[0579] Example 84. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end, and comprises: plurality of intersecting struts, which form a plurality of cells; an inflow cell row comprising a plurality of inflow cells at the inflow end of the frame; an outflow cell row of outflow cells at the outflow end of the frame; one or more subsequent cell rows arranged between the inflow cell row and the outflow cell row, each comprising a plurality of subsequent cells; a fist cell row, which is one of the subsequent cell rows; and a second cell row, which is the inflow cell row or one of the subsequent cell rows; wherein the first cell row is positioned closer to the outflow end of the frame than the second cell row; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge, which is closer to the outflow end; and a plurality of first protruding extensions, each extending radially outwards a from the base layer portion and through each of the cells of the first cell row, wherein in an untensioned state thereof the first protruding extensions extend at radial dimension RDE', and when compressed radially inward the first protruding extensions extend at radial dimension RDc'; and a second plurality of protruding extensions, each extending radially outwards at a radial dimension RD" from the base layer portion and through each of the cells of the second cell row, wherein in an untensioned state thereof the second protruding extensions extend at radial dimension RDE", and when compressed radially inward the second protruding extensions extend at radial dimension RDc"; wherein RDE" is greater than RDE' and/or RDc” is greater than RDc'.

[0580] Example 85. The prosthetic valve of any example herein, particularly of example 84, further comprising a one-piece valvular structure mounted within the frame and, the valvular structure comprising: a plurality of leaflets, which are integrally formed as regions of the one- piece valvular structure; and an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets.

[0581] Example 86. The prosthetic valve of any example herein, particularly of example 85, wherein each leaflet comprises a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0582] Example 87. The prosthetic valve of any example herein, particularly of example 84, comprising a plurality of leaflets, positioned at least partially within the frame, wherein each leaflet comprises: a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal- most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0583] Example 88. The prosthetic valve of any example herein, particularly of any one of examples 86 to 87, wherein at least a portion of the first cell row is positioned closer to the outflow end of the frame than the lower cusp line.

[0584] Example 89. The prosthetic valve of any example herein, particularly of any one of examples 86 to 88, wherein the leaflets are in contact with the base layer portion of the skirt along a portion of the first cell row. [0585] Example 90. The prosthetic valve of any example herein, particularly of any one of examples 85 to 89, wherein the leaflets have a thickness Tl, wherein RDE" is greater than or equal to the sum of RDF.' and Tl .

[0586] Example 91. The prosthetic valve of any example herein, particularly of any one of examples 85 to 90, wherein the leaflets have a thickness Tl, wherein RDc" is greater than or equal to the sum of RDc’ and Tl.

[0587] Example 92. The prosthetic valve of any example herein, particularly of any one of examples 84 to 91 , wherein RDE" is at least 10% greater than RDE'.

[0588] Example 93. The prosthetic valve of any example herein, particularly of any one of examples 84 to 91, wherein RDE" is at least 20% greater than RDE'.

[0589] Example 94. The prosthetic valve of any example herein, particularly of any one of examples 84 to 93, wherein RDc" is at least 10% greater than RDc'.

[0590] Example 95. The prosthetic valve of any example herein, particularly of any one of examples 84 to 93, wherein RDc" is at least 20% greater than RDc'.

[0591] Example 96. The prosthetic valve of any example herein, particularly of any one of examples 85 to 91, comprising a plurality of inflow protruding extensions, each extending radially outwards a radial dimension RDE" from the base layer portion and through each of the cells of the inflow cell row in an untensioned state thereof, and at a radial dimension RDc" when compressed radially inward; and a first subsequent plurality of protruding extensions, each extending radially outwards at a radial dimension RDE' from the base layer portion and through each of the cells of a first subsequent cell row in an untensioned state thereof, and at a radial dimension RDc' when compressed radially inward.

[0592] Example 97. The prosthetic valve of any example herein, particularly of any one of examples 84 to 96, wherein a difference between the radial dimension RDE’ and the radial dimension RDE" is equal to or greater than a thickness Tl of the leaflets.

[0593] Example 98. The prosthetic valve of any example herein, particularly of any one of examples 84 to 97, wherein a difference between the radial dimension RDc' and the radial dimension RDc” is equal to or greater than a thickness Tl of the leaflets.

[0594] Example 99. The prosthetic valve of any example herein, particularly of example 97, wherein the sum of Tl and RDE' is greater than RDE".

[0595] Example 100. The prosthetic valve of any example herein, particularly of example 98, wherein the sum of Tl and RDc’ is at least 5% greater than RDc". [0596] Example 101. The prosthetic valve of any example herein, particularly of example 96, wherein at least a portion of the first subsequent cell row is positioned closer to the outflow end of the frame than the lower cusp line.

[0597] Example 102. The prosthetic valve of any example herein, particularly of any one of examples 96 or 101, wherein the leaflets are in contact with the base layer portion of the skirt along a portion of the first subsequent cell row.

[0598] Example 103. The prosthetic valve of any example herein, particularly of any one of examples 96 or 101 to 102, wherein the subsequent cell rows further comprising a second subsequent cell row proximal to the first subsequent cell row, the second subsequent cell row comprising plurality of second subsequent cells; and wherein the skirt comprises a second subsequent plurality of protruding extensions, each extending radially outwards at a radial dimension RDE'" from the base layer portion and through each of the cells of the second subsequent cell row in an untensioned state thereof, and at a radial dimension RDE'" when compresses radially inward.

[0599] Example 104. The prosthetic valve of any example herein, particularly of example 103 wherein RDE" is greater than RDE’".

[0600] Example 105. The prosthetic valve of any example herein, particularly of any one of examples 103 to 104, wherein RDE" is at least 10% greater than RDE'".

[0601] Example 106. The prosthetic valve of any example herein, particularly of any one of examples 103 to 105, wherein RDe” is greater than RDe'”.

[0602] Example 107. The prosthetic valve of any example herein, particularly of any one of examples 103 to 106, wherein RDe" is at least 10% greater than RDe'".

[0603] Example 108. The prosthetic valve of any example herein, particularly of any one of examples 103 to 107, wherein RDE' is greater than RDE"'.

[0604] Example 109. The prosthetic valve of any example herein, particularly of any one of examples 103 to 108, wherein RDE' is at least 10% greater than RDE'".

[0605] Example 110. The prosthetic valve of any example herein, particularly of any one of examples 103 to 109, wherein RDe' is greater than RDe"'.

[0606] Example 111. The prosthetic valve of any example herein, particularly of any one of examples 103 to 110, wherein RDe' is at least 10% greater than RDe'".

[0607] Example 112. The prosthetic valve of any example herein, particularly of any one of examples 86 to 111, wherein at least a portion of the second subsequent cell row is positioned closer to the outflow end of the frame than the lower cusp line. [0608] Example 113. The prosthetic valve of any example herein, particularly of any one of examples 103 to 112, wherein the leaflets are in contact with the base layer portion of the skirt along a portion of the second subsequent cell row.

[0609] Example 114. The prosthetic valve of any example herein, particularly of any one of examples 84 to 113, wherein each of the protruding extensions of the skirt comprise foam material.

[0610] Example 115. The prosthetic valve of any example herein, particularly of example 114, wherein the foam material is selected from the group consisting of: polyethylene foam, polyethylene terephthalate mesh and a combination thereof.

[0611] Example 116. The prosthetic valve of any example herein, particularly of any one of examples 114 to 115, wherein the foam material is porous, having pore size in the range of 3 micron to 50 micron.

[0612] Example 117. The prosthetic valve of any example herein, particularly of any one of examples 115 to 116, wherein each of the protruding extensions has an inner surface, which is in contact with the base layer portion, and an outer surface, which is spherical dome shaped and positioned radially away from the inner surface.

[0613] Example 118. The prosthetic valve of any example herein, particularly of example 117, wherein the outer surfaces of the protruding extensions are porous, having pore size in the range of 3 micron to 50 micron.

[0614] Example 119. The prosthetic valve of any example herein, particularly of any one of examples 117 to 118, wherein the outer surfaces of the protruding extensions are laminated by a perforated coating layer, which has an aperture size in the range of 3 micron to 50 micron.

[0615] Example 120. The prosthetic valve of any example herein, particularly of any one of examples 117 to 119, wherein the coating layer is hydrophilic.

[0616] Example 121. The prosthetic valve of any example herein, particularly of any one of examples 84 to 120, wherein each one of the protruding extensions of the skirt has a thickness in the range of 10 micron to 100 micron.

[0617] Example 122. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge, which is closer to the outflow end; a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame; and a plurality of reinforcement lines positioned radially inwards to the protruding extensions, and configured to prevent collapse of the base layer portion radially inward upon application of pressure radially inward thereon, when the frame is in its radially expanded state.

[0618] Example 123. The prosthetic valve of any example herein, particularly of example 123, further comprising a one-piece valvular structure mounted within the frame and, the valvular structure comprising: a plurality of leaflets, which are integrally formed as regions of the one- piece valvular structure; and an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets.

[0619] Example 124. The prosthetic valve of any example herein, particularly of example 123, wherein each leaflet comprises a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0620] Example 125. The prosthetic valve of any example herein, particularly of example 122, comprising a plurality of leaflets, positioned at least partially within the frame, wherein each leaflet comprises: a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal- most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0621] Example 126. The prosthetic valve of any example herein, particularly of any one of examples 122 to 125, wherein the plurality of reinforcement lines are positioned radially inwards to the base layer portion.

[0622] Example 127. The prosthetic valve of any example herein, particularly of any one of examples 122 to 126, wherein each cell of the frame is defined between at least three struts thereof; and wherein at least some of the reinforcement lines extend between at least two of the three struts.

[0623] Example 128. The prosthetic valve of any example herein, particularly of any one of examples 122 to 127, wherein at least some cells of the frame are defined between four struts thereof; and wherein at least some of the reinforcement lines extend between two opposite struts of the four struts.

[0624] Example 129. The prosthetic valve of any example herein, particularly of example 128, comprising reinforcement lines extending between each of the two opposite struts of the four struts. [0625] Example 130. The prosthetic valve of any example herein, particularly of any one of examples 122 to 129, wherein at least some cells of the frame are defined between six struts thereof; and wherein at least some of the reinforcement lines extend between two non-adjacent struts of the six stmts.

[0626] Example 131. The prosthetic valve of any example herein, particularly of example 130, comprising reinforcement lines extending between two opposite struts of the six struts.

[0627] Example 132. The prosthetic valve of any example herein, particularly of any one of examples 122 to 125 or 127 to 131 , wherein at least some of the reinforcement lines are formed as reinforcement portions of the base layer portion of the skirt.

[0628] Example 133. The prosthetic valve of any example herein, particularly of example 132, wherein the thickness of the base layer portion at the reinforcement portions is higher than the thickness of the base layer portion in non-reinforced portions.

[0629] Example 134. The prosthetic valve of any example herein, particularly of example 133, wherein the reinforcement portions are embedded within the base layer portion.

[0630] Example 135. The prosthetic valve of any example herein, particularly of any one of examples 132 to 134, wherein the reinforcement portions comprise a reinforcing material and non-reinforced portions of base layer portion comprise a base layer portion material; and wherein the base layer portion material is different from the reinforcing material.

[0631] Example 136. The prosthetic valve of any example herein, particularly of example 135, wherein the base layer portion material has lower tensile strength than the reinforcing material. [0632] Example 137. The prosthetic valve of any example herein, particularly of any one of examples 135 to 136, wherein the base layer portion material has lower durometer than the reinforcing material.

[0633] Example 138. The prosthetic valve of any example herein, particularly of any one of examples 135 to 137, wherein the reinforcing material comprises a metal or a metal alloy.

[0634] Example 139. The prosthetic valve of any example herein, particularly of any one of examples 126 to 131, wherein the at least some of the reinforcement lines are sutured threads, extending between two or more of the struts.

[0635] Example 140. The prosthetic valve of any example herein, particularly of example 139, wherein at least some sutured thread extends between two struts.

[0636] Example 141. The prosthetic valve of any example herein, particularly of any one of examples 139 to 140, wherein each thread is sutured to a strut, penetrates through the base layer portion radially inward in the vicinity of the strut, extends towards another strut, penetrates through the base layer portion radially outwards in the vicinity of the other strut and is sutured to the other strut.

[0637] Example 142. The prosthetic valve of any example herein, particularly of any one of examples 122 to 141, wherein the protruding extensions of the skirt comprise foam material.

[0638] Example 143. The prosthetic valve of any example herein, particularly of example 142, wherein the foam material is selected from the group consisting of: polyethylene foam, polyethylene terephthalate mesh and a combination thereof.

[0639] Example 144. The prosthetic valve of any example herein, particularly of any one of examples 142 to 143, wherein the foam material is porous, having pore size in the range of 3 micron to 50 micron.

[0640] Example 145. The prosthetic valve of any example herein, particularly of any one of examples 142 to 144, wherein each of the protruding extensions has an inner surface, which is in contact with the base layer portion, and an outer surface, which is spherical dome shaped and positioned radially away from the inner surface.

[0641] Example 146. The prosthetic valve of any example herein, particularly of example 145, wherein the outer surfaces of the protruding extensions are porous.

[0642] Example 147. The prosthetic valve of any example herein, particularly of example 145, wherein the outer surfaces of the protruding extensions have pore size in the range of 3 micron to 50 micron.

[0643] Example 148. The prosthetic valve of any example herein, particularly of any one of examples 146 to 147, wherein the outer surfaces of the protruding extensions are laminated by a coating layer.

[0644] Example 149. The prosthetic valve of any example herein, particularly of example 148, wherein the coating layer is perforated, and has an aperture size in the range of 3 micron to 50 micron.

[0645] Example 150. The prosthetic valve of any example herein, particularly of any one of examples 148 to 149, wherein the coating layer is hydrophilic.

[0646] Example 151. The prosthetic valve of any example herein, particularly of any one of examples 122 to 150, wherein each one of the protruding extensions of the skirt has a thickness in the range of 10 micron to 100 micron.

[0647] Example 152. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end, and comprises a plurality of intersecting struts, each having a width Ws, wherein the struts form a plurality of cells, wherein two adjacent cells share one or more struts of the plurality of intersecting struts; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge, which is closer to the outflow end; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between the struts of the frame, wherein two adjacent protruding extensions are defined as extending through corresponding adjacent cells; wherein a distance between two adjacent protruding extensions at a position adjacent to the strut, along which they both extend, and radially outwards thereto, is WG; and wherein Ws is greater than WG.

[0648] Example 153. The prosthetic valve of any example herein, particularly of example 152, further comprising a one-piece valvular structure mounted within the frame and, the valvular structure comprising: a plurality of leaflets, which are integrally formed as regions of the one- piece valvular structure; and an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets.

[0649] Example 154. The prosthetic valve of any example herein, particularly of example 153, wherein each leaflet comprises a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0650] Example 155. The prosthetic valve of any example herein, particularly of example 152, comprising a plurality of leaflets, positioned at least partially within the frame, wherein each leaflet comprises:

[0651] a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0652] Example 156. The prosthetic valve of any example herein, particularly of any one of examples 152 to 155, wherein Ws is at least 5% greater than WG.

[0653] Example 157. The prosthetic valve of any example herein, particularly of any one of examples 152 to 155wherein Ws is at least 10% greater than WG.

[0654] Example 158. The prosthetic valve of any example herein, particularly of any one of examples 152 to 155, wherein Ws is at least 15% greater than WG. [0655] Example 159. The prosthetic valve of any example herein, particularly of any one of examples 152 to 158, wherein each cell of the frame is defined between at least three struts thereof.

[0656] Example 160. The prosthetic valve of any example herein, particularly of any one of examples 152 to 159, wherein at least some cells of the frame are defined between four struts thereof.

[0657] Example 161. The prosthetic valve of any example herein, particularly of any one of examples 152 to 160, wherein at least some cells of the frame are defined between six struts thereof.

[0658] Example 162. The prosthetic valve of any example herein, particularly of any one of examples 152 to 161, wherein the skirt base layer portion is stretchable.

[0659] Example 163. The prosthetic valve of any example herein, particularly of any one of examples 152 to 162, wherein the skirt base layer portion is elastically deformable.

[0660] Example 164. The prosthetic valve of any example herein, particularly of any one of examples 152 to 163, wherein the skirt base layer portion has elongation at break of at least 5%.

[0661] Example 165. The prosthetic valve of any example herein, particularly of any one of examples 152 to 164, wherein the skirt base layer portion has elongation at break of at least 10%.

[0662] Example 166. The prosthetic valve of any example herein, particularly of any one of examples 152 to 165, wherein the skirt base layer portion has elongation at break of at least 15%.

[0663] Example 167. The prosthetic valve of any example herein, particularly of any one of examples 152 to 166, wherein the protruding extensions are stretchable.

[0664] Example 168. The prosthetic valve of any example herein, particularly of any one of examples 152 to 167, wherein the protruding extensions are elastically deformable.

[0665] Example 169. The prosthetic valve of any example herein, particularly of any one of examples 152 to 168, wherein the protruding extensions have elongation at break of at least 5%.

[0666] Example 170. The prosthetic valve of any example herein, particularly of any one of examples 152 to 169, wherein the protruding extensions have elongation at break of at least 10%.

[0667] Example 171. The prosthetic valve of any example herein, particularly of any one of examples 152 to 170, comprising a plurality of protruding extensions, which come in contact with adjacent protruding extensions, at positions, which are located radially away from the cells through which they extend.

[0668] Example 172. A method of forming a prosthetic valve which comprises a paravalvular leakage (PVL) skirt, the method comprising: providing a prosthetic valve which comprises an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end, and comprises a plurality of intersecting struts, each having a width Ws, wherein the struts form a plurality of cells, and wherein two adjacent cells share one or more struts of the plurality of intersecting struts; providing a 3D-shaped elongated, optionally flattened, PVL skirt having two side portions extending between a proximal edge portion and a distal edge portion, wherein each of the proximal edge portion and distal edge portion is longer than the two side portions, the skirt comprising: an optionally flat base layer portion having an inner surface and an outer surface, each defined between the two side portions, the proximal edge portion and a distal edge portion; and a plurality of protruding extensions, each extending away from the outer surface of the base layer portion to define the 3D-shape of the skirt; wherein a distance between the two side portions in an untensioned state is Dsu, wherein each of the base layer portion and the protruding extensions is elastically stretchable; stretching the PVL skirt laterally to a stretched state, so that the distance between the two side portions in the stretched state is Dss, which is greater than Dsu; rolling the stretched PVL skirt by bringing the side potions thereof together to assume a cylindrical configuration; connecting the stretched rolled skirt to the frame of the prosthetic valve, such that each of the protruding extensions extends radially outwards from the base layer portion and through corresponding cells thereof, wherein two adjacent protruding extensions are defined as extending through corresponding adjacent cells; and relieving tension created by the stretching; wherein upon the relief, a distance between the two adjacent protruding extensions in the relieved state is WGR, which is smaller than Ws, and further upon the relief, a distance between the two side portions in the relieved state is DSR, which is smaller than Dss and greater or equal to Dsu-

[0669] Example 173. The method of any example herein, particularly of example 172, wherein connecting the stretched rolled skirt to the frame of the prosthetic valve comprises attaching the skirt to the frame at a position, so that the inflow end of the frame is closer to the distal edge portion than it is to the proximal edge portion.

[0670] Example 174. The method of any example herein, particularly of any one of examples 172 to 173, wherein connecting the stretched rolled skirt to the frame of the prosthetic valve comprises attaching the skirt to the frame at a position, so that the outflow end of the frame is closer to the proximal edge portion than it is to the distal edge portion.

[0671] Example 175. The method of any example herein, particularly of any one of examples 172 to 174, wherein the proximal edge portion is a substantially linear edge.

[0672] Example 176. The method of any example herein, particularly of any one of examples 172 to 174, wherein the proximal edge portion defines a non-linear edge having an undulating shape.

[0673] Example 177. A method of forming a prosthetic valve which comprises a paravalvular leakage (PVL) skirt, the method comprising: providing a prosthetic valve which comprises an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end, and comprises a plurality of intersecting struts, wherein the struts form a plurality of cells, wherein two adjacent cells share one or more struts of the plurality of intersecting struts; providing an optionally flattened patch having two side portions extending between a proximal edge portion and a distal edge portion, wherein each of the proximal edge portion and distal edge portion is longer than the two side portions, the patch comprising: a stretchable, optionally flat, base layer portion having an inner surface and an outer surface, each defined between the two patch side portions, the proximal edge portion and a distal edge portion; stretching the patch laterally to a stretched state; connecting a plurality of protruding extensions to the outer surface of the patch, such that each protruding extension extends away from the outer surface of the base layer portion to form a 3D-shaped PVL skirt; optionally rolling the stretched PVL skirt by bringing the side potions thereof together to assume a cylindrical configuration; connecting the stretched rolled skirt to the frame of the prosthetic valve, such that each of the protruding extensions extends radially outwards from the base layer portion and through corresponding cells thereof, wherein two adj acent protruding extensions are defined as extending through corresponding adjacent cells; and relieving tension created by the stretching.

[0674] Example 178. The method of any example herein, particularly of example 177, wherein each of the intersecting struts, has a width Ws; wherein a distance between the two side portions in an untensioned state of the patch is Dsu, wherein the protruding extensions are elastically stretchable, and wherein upon the step of relief, a distance between the two adjacent protruding extensions in the relieved state is WGR, which is smaller than Ws, and further upon the relief, a distance between the two side portions in the relieved state is DSR, which is smaller than Dss and greater or equal to Dsu- [0675] Example 179. The method any one of claims 177 to 178, wherein connecting the stretched rolled skirt to the frame of the prosthetic valve comprises attaching the skirt to the frame at a position, so that the inflow end of the frame is closer to the distal edge portion than it is to the proximal edge portion.

[0676] Example 180. The method of any example herein, particularly of any one of examples 177 to 178, wherein connecting the stretched rolled skirt to the frame of the prosthetic valve comprises attaching the skirt to the frame at a position, so that the outflow end of the frame is closer to the proximal edge portion than it is to the distal edge portion.

[0677] Example 181. The method of any example herein, particularly of any one of examples 177 to 180, wherein the proximal edge portion is a substantially linear edge.

[0678] Example 182. The method of any example herein, particularly of any one of examples 177 to 181, wherein the proximal edge portion defines a non-linear edge having an undulating shape.

[0679] Example 183. The method of any example herein, particularly of any one of examples 177 to 182, wherein an area of the cells of the frame is Ac; wherein a cross-sectional area of the protruding extensions in an untensioned state thereof is AGU, wherein the protruding extensions are elastically stretchable, and wherein a cross-sectional area of the protruding extensions upon the stretching of the patch state thereof is AGS, wherein AGU is greater than Ac and smaller than AGS-

[0680] Example 184. A method of forming a prosthetic valve which comprises a paravalvular leakage (PVL) skirt, the method comprising: providing a prosthetic valve which comprises an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end, and comprises a plurality of intersecting struts, wherein the struts form a plurality of cells, wherein an area of the cells is AC; providing a 3D-shaped elongated, optionally flattened PVL skirt having two side portions extending between a skirt inflow end portion and a skirt outflow end portion, wherein each of the inflow end portion and outflow end portion is longer than the two side portions, the skirt comprising: an optionally flat base layer portion having an inner surface and an outer surface, each defined between the two side portions, the skirt inflow end portion and the skirt outflow end portion; and a plurality of protruding extensions, each extending away from the outer surface of the base layer portion to define the 3D-shape of the skirt; wherein a cross-sectional area of the protruding extensions in an untensioned state is AGU, wherein the protruding extensions are elastically compressible; planarly compressing the protruding extensions, so that a cross-sectional area of the protruding extensions in a compressed untensioned state is AGO, which is smaller than AGU; rolling the PVL skirt by bringing the side portions thereof together to assume a cylindrical configuration; mounting the rolled skirt to the frame of the prosthetic valve, such that each of the compressed extensions extends radially outwards from the base layer portion and through corresponding cells thereof; and relieving tension created by the planarly compressing; wherein upon the relief, an area of the protruding extensions in the relieved state is AGR, which is greater than Ac.

[0681] Example 185. The method of any example herein, particularly of example 184, wherein AGR is ±10% of AGU.

[0682] Example 186. The method of any example herein, particularly of any one of examples 184 to 185, wherein two adjacent cells share one or more struts of the plurality of intersecting struts, wherein two adjacent protruding extensions are defined as extending through corresponding adjacent cells, wherein each strut has a width Ws, wherein upon the relief a distance between the two adjacent protruding extensions in the relieved state is WGR, which is smaller than Ws.

[0683] Example 187. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge, which is closer to the outflow end; and a plurality of extending protrusions, each extending radially outwards from the base layer portion and within or through a corresponding cell or an opening defined between struts of the frame, wherein each extending protrusion comprises a flexible shell, which is connected to the base layer portion and enclosing a void within the extending protrusion.

[0684] Example 188. The prosthetic valve of any example herein, particularly of example 187, wherein each extending protrusion has a radial dimension defined as the length between the base layer portion and the most radially outwards point of the flexible shell; and wherein the radial dimension of each extending protrusion, when the frame is in the radially expanded state is greater than the radial dimension of the same extending protrusion, when the frame is in the radially compressed state.

[0685] Example 189. The prosthetic valve of any example herein, particularly of example 188, wherein each extending protrusion has a proximal end defined as the point of the protrusion, which is closest to the inflow end of the frame, and a distal end defined as the point of the shell, which is closest to the outflow end of the frame; wherein each extending protrusion has an axial length defined as the distance between the proximal end and the distal end thereof; and wherein the axial length of each extending protrusion, when the frame is in the radially expanded state is greater than the axial length of the same extending protrusion, when the frame is in the radially compressed state.

[0686] Example 190. The prosthetic valve of any example herein, particularly of any one of examples 188 to 189, wherein each cell of the frame is axially extending along the frame from a proximal end, which is closer to the inflow end of the frame, and a distal end, which is closer to the outflow end of the frame, wherein an axial length of each cell is defined between the proximal end and the distal end; and wherein the axial length of each cell, when the frame is in the radially compressed state is greater than the axial length of the same cell, when the frame is in the radially expanded state.

[0687] Example 191. The prosthetic valve of any example herein, particularly of example 190, wherein each extending protrusion is mounted within a corresponding cell of the frame, wherein upon the mounting and transition of the frame from a radially compressed state to a radially expanded state, the axial length of each cell is increased together with the axial length of the extending protrusion mounted therein.

[0688] Example 192. The prosthetic valve of any example herein, particularly of example 191, wherein upon the transition of the frame from a radially compressed state to a radially expanded state, and increase of the axial length of the extending protrusion, the same extending protrusion flattens and the radial dimension thereof is decreased.

[0689] Example 193. The prosthetic valve of any example herein, particularly of any one of examples 190 to 192, wherein each extending protrusion is mounted within a corresponding cell of the frame, wherein upon the mounting and transition of the frame from a radially expanded state to a radially compressed state, the axial length of each cell is decreased together with the axial length of the extending protrusion mounted therein.

[0690] Example 194. The prosthetic valve of any example herein, particularly of example 193, wherein upon the transition of the frame from a radially expanded state to a radially compressed state, and decrease of the axial length of the extending protrusion, the same extending protrusion extends radially away farther from the base layer portion and the radial dimension thereof is increased.

[0691] Example 195. The prosthetic valve of any example herein, particularly of example 194, wherein the flexible shell is reinforced so that it bulges in a radial outwards direction upon the transition of the frame from a radially expanded state to a radially compressed state. [0692] Example 196. The prosthetic valve of any example herein, particularly of any one of examples 187 to 195, wherein the flexible shells are stretchable.

[0693] Example 197. The prosthetic valve of any example herein, particularly of any one of examples 187 to 196, wherein the flexible shells are elastically deformable.

[0694] Example 198. The prosthetic valve of any example herein, particularly of any one of examples 187 to 197, wherein the flexible shells have elongation at break of at least 5%.

[0695] Example 199. The prosthetic valve of any example herein, particularly of any one of examples 187 to 197, wherein the flexible shells have elongation at break of at least 10%.

[0696] Example 200. The prosthetic valve of any example herein, particularly of any one of examples 187 to 197, wherein the flexible shells have elongation at break of at least 15%.

[0697] Example 201. The prosthetic valve of any example herein, particularly of any one of examples 187 to 200, wherein a thickness of each one of the flexible shells is To, wherein a thickness of each one of the struts of the frame through which the plurality of extending protrusion extend, is Ts, and wherein Tc is in the range of 0.5Ts to 1.5Ts.

[0698] Example 202. The prosthetic valve of any example herein, particularly of example 201, wherein Tc is in the range of 0.75Ts to 1.25Ts.

[0699] Example 203. The prosthetic valve of any example herein, particularly of example 201, wherein Tc is in the range of 0.9Ts to l.lTs.

[0700] Example 204. The prosthetic valve of any example herein, particularly of any one of examples 187 to 203, wherein a thickness of each one of the struts of the frame through which the plurality of extending protrusions extend, is Ts, wherein when the frame is in its radially compressed state, the flexible shells extend radially outward past the struts at a radial dimension, which is not greater than 3Ts.

[0701] Example 205. The prosthetic valve of any example herein, particularly of example 204, wherein when the frame is in its radially compressed state, the extending protrusion s extend radially outward past the struts at a radial dimension, which is not greater than 2Ts.

[0702] Example 206. The prosthetic valve of any example herein, particularly of example 204, wherein when the frame is in its radially compressed state, the extending protrusions extend radially outward past the struts at a radial dimension, which is not greater than Ts.

[0703] Example 207. The prosthetic valve of any example herein, particularly of example 204, wherein when the frame is in its radially compressed state, the extending protrusions extend radially outward past the struts at a radial dimension, which is not greater than 0.5Ts.

[0704] Example 208. The prosthetic valve of any example herein, particularly of any one of examples 187 to 207, wherein a thickness of each one of the struts of the frame through which the plurality of extending protrusions extend, is Ts, wherein when the frame is in its radially expanded state, the extending protrusions extend radially outward past the struts at a radial dimension, which is greater than 3Ts.

[0705] Example 209. The prosthetic valve of any example herein, particularly of example 208, wherein when the frame is in its radially expanded state, the extending protrusions extend radially outward past the struts at a radial dimension, which is greater than 5Ts.

[0706] Example 210. The prosthetic valve of any example herein, particularly of example 208, wherein when the frame is in its radially expanded state, the extending protrusions extend radially outward past the struts at a radial dimension, which is greater than 10Ts.

[0707] Example 211. The prosthetic valve of any example herein, particularly of any one of examples 208 to 210, further comprising a one-piece valvular structure mounted within the frame and, the valvular structure comprising: a plurality of leaflets, which are integrally formed as regions of the one-piece valvular structure; and an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets.

[0708] Example 212. The prosthetic valve of any example herein, particularly of example 211, wherein each leaflet comprises a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0709] Example 213. The prosthetic valve of any example herein, particularly of any one of examples 187 to 210, comprising a plurality of leaflets, positioned at least partially within the frame, wherein each leaflet comprises: a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame.

[0710] Example 214. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge which is closer to the inflow end of the frame, and an opposite proximal edge which is closer to the outflow end, wherein the base layer portion comprises at least one layer which has at least one surface defining a non-uniform surface morphology; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame. [0711] Example 215. The prosthetic valve of any example herein, particularly of example 214, wherein the at least one layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the at least one layer is facing the protruding extensions, and the inner surface of the at least one layer is facing radially inwards and defines the non- uniform surface morphology of the base layer portion.

[0712] Example 216. The prosthetic valve of any example herein, particularly of example 215, wherein the inner surface of the at least one layer is a neointimal-formation encouraging surface.

[0713] Example 217. The prosthetic valve of any example herein, particularly of any one of examples 214 to 216, wherein the at least one layer is porous.

[0714] Example 218. The prosthetic valve of any example herein, particularly of example 217, wherein the at least one porous layer comprises a plurality of pores, wherein a mean pore size of the plurality of pores is in the range of 0.5 micron to 200 micron.

[0715] Example 219. The prosthetic valve of any example herein, particularly of any one of examples 214 to 218, wherein the at least one layer is perforated.

[0716] Example 220. The prosthetic valve of any example herein, particularly of any one of examples 214 to 219, wherein the at least one layer comprises a plurality of filaments.

[0717] Example 221. The prosthetic valve of any example herein, particularly of example 220, wherein a mean diameter of the plurality of filaments is in the range of 0.1 to 20 micron.

[0718] Example 222. The prosthetic valve of any example herein, particularly of any one of examples 214 to 221, wherein the at least one layer of the base layer portion is selected from an electrospun layer, melt blown spun layer, air jet spun layer and a salt-leached layer.

[0719] Example 223. The prosthetic valve of any example herein, particularly of example 222, wherein the at least one layer of the base layer portion is electrospun.

[0720] Example 224. The prosthetic valve of any example herein, particularly of example 223, wherein the at least one layer of the base layer portion is electrospun from a solution comprising an organic solvent selected from the group consisting of: l,l,3,3,3-hexafluoro-2-propanol (HFIP), tetrahydrofuran (THF), acetone, dimethylformamide (DMF) and any combination thereof.

[0721] Example 225. The prosthetic valve of any example herein, particularly of any one of examples 223 to 224, wherein the comprises a polymeric material at a concentration in the range of 2% w/w to 12% w/w.

[0722] Example 226. The prosthetic valve of any example herein, particularly of any one of examples 214 to 225, wherein the at least one layer of the base layer portion comprises a polymer selected from the group consisting of: thermoplastic polyurethane (TPU), expanded poly tetrafluoroethylene (ePTFE), fluorinatedethylenepropylene polymer (FEP), biomimetic collagen, a hyaluronic acid derivative and a combination thereof.

[0723] Example 227. The prosthetic valve of any example herein, particularly of any one of examples 214 or 216 to 226, wherein the at least one layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the at least one layer is facing the protruding extensions, and the inner surface of the at least one layer is facing radially inwards; wherein the at least one layer of the base layer portion comprises a coating layer that is coating the inner surface thereof, and wherein the coating is configured to promote endothelization.

[0724] Example 228. The prosthetic valve of any example herein, particularly of example 227, wherein the coating comprises at least one endothelium tissue promoting compound selected from the group consisting of: collagen, chitosan hyaluronic acid and a combination thereof.

[0725] Example 229. The prosthetic valve of any example herein, particularly of any one of examples 214 to 228, wherein the base layer portion comprises at least two layers.

[0726] Example 230. The prosthetic valve of any example herein, particularly of any one of examples 214 to 228, wherein the base layer portion comprises exactly two layers.

[0727] Example 231. The prosthetic valve of any example herein, particularly of any one of examples 214 to 215 or 217 to 230, wherein the base layer portion comprises: an internal layer, which among the base layer portions, is located the most distally to the protruding extensions; and an external layer, which among the base layer portions, is located the most proximally to the protruding extensions; wherein the internal layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the internal layer is facing the protruding extensions, and the inner surface of the internal layer is facing radially inwards, and wherein the inner surface of the internal layer has a non-uniform surface morphology.

[0728] Example 232. The prosthetic valve of any example herein, particularly of example 231, wherein the inner surface of the internal layer is a neointimal-formation encouraging surface.

[0729] Example 233. The prosthetic valve of any example herein, particularly of any one of examples 231 to 232, wherein the internal layer is porous and comprises a plurality of pores, wherein a mean pores size of the plurality of pores is in the range of 80 micron to 100 micron. [0730] Example 234. The prosthetic valve of any example herein, particularly of any one of examples 231 to 233, wherein the internal layer is perforated. [0731] Example 235. The prosthetic valve of any example herein, particularly of any one of examples 231 to 234, wherein the internal layer comprises a plurality of filaments, wherein a mean diameter of the plurality of filaments is in the range of 1 micron to 5 micron.

[0732] Example 236. The prosthetic valve of any example herein, particularly of any one of examples 231 to 235, wherein the internal layer is selected from an electrospun layer, melt blown spun layer, air jet spun layer and a salt-leached layer.

[0733] Example 237. The prosthetic valve of any example herein, particularly of any one of examples 231 to 236, wherein the internal layer comprises a coating layer that is coating the inner surface thereof, wherein the coating is promoting endothelization, and comprises at least one endothelium tissue promoting compound selected from the group consisting of: collagen, chitosan hyaluronic acid and a combination thereof.

[0734] Example 238. The prosthetic valve of any example herein, particularly of any one of examples 231 to 237, wherein the internal layer has a thickness in the range of 55 micron to 75 micron.

[0735] Example 239. The prosthetic valve of any example herein, particularly of any one of examples 231 to 238, wherein the external layer has a thickness in the range of 30 micron to 50 micron.

[0736] Example 240. The prosthetic valve of any example herein, particularly of any one of examples 231 to 239, wherein each one of the internal layer and the external layer is porous, wherein each one of the internal layer and the external layer comprises a plurality of pores, and wherein a mean pore size of the plurality of pores of the internal layer is greater than the mean pore size of the plurality of pores of the external layer.

[0737] Example 241. The prosthetic valve of any example herein, particularly of any one of examples 231 to 239, wherein the external layer is non-porous.

[0738] Example 242. The prosthetic valve of any example herein, particularly of any one of examples 231 to 241, wherein the external layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the external layer is in contact with the protruding extensions, and the inner surface of the external layer is facing the internal layer, and wherein the external surface of the external layer has a uniform surface morphology.

[0739] Example 243. The prosthetic valve of any example herein, particularly of any one of examples 214 to 242, wherein the protruding extensions of the skirt comprise foam material.

[0740] It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate examples, may also be provided in combination in a single example. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single example, may also be provided separately or in any suitable sub-combination or as suitable in any other described example of the disclosure. No feature described in the context of an example is to be considered an essential feature of that example, unless explicitly specified as such.

[0741] In view of the many possible examples to which the principles of the disclosure may be applied, it should be recognized that the illustrated examples are only preferred examples and should not be taken as limiting the scope. Rather, the scope is defined by the following claims. We therefore claim all that comes within the scope and spirit of these claims.

Claims

1. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; and a one-piece valvular structure mounted within the frame and comprising: a plurality of leaflets, which are integrally formed as regions of the one- piece valvular structure, and have a thickness Tl; and an engagement portion connected to the plurality of leaflets and extending between a distal end thereof and the leaflets, the engagement portion having a thickness T2; wherein Tl is greater than T2.

2. The prosthetic valve of claim 1, further comprising a skirt which comprises: a base layer portion secured to an inner surface of the frame; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame.

3. The prosthetic valve of claim 2, wherein the skirt base layer portion extends between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge closer to the outflow end of the frame; wherein the engagement portion is extending between a distal end thereof, which is closer to the inflow end of the frame, and cusp lines of the leaflets, which are closer to the outflow end of the frame; and wherein the distal edge of the skirt base layer portion is connected to the inflow end of the frame.

4. The prosthetic valve of any one of claims 2-3, wherein the base layer portion is at least partially overlapping axially with the engagement portion, wherein the base layer portion has thickness T3, wherein an overlapping potion between the base layer portion and the engagement portion has total thickness T2+T3, and wherein Tl is greater or equal to T2+T3.

5. The prosthetic valve of any one of claims 2-4, wherein the protruding extensions of the skirt comprise foam material, wherein each of the protruding extensions has an inner surface, which is in contact with the base layer portion, and an outer surface, which is spherical dome shaped and positioned radially away from the inner surface, and wherein the outer surfaces of the protruding extensions are laminated by a coating layer.

6. The prosthetic valve of claim 5, wherein the coating layer is perforated, and has an aperture size in the range of 3 micron to 50 micron.

7. The prosthetic valve of any one of claims 5-6, wherein the coating layer is hydrophilic.

8. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; a plurality of leaflets, positioned at least partially within the frame, wherein each leaflet comprises: a leaflet belly, defined between a lower cusp line and an upper free edge of the leaflet, wherein the cusp line of each leaflet defines a leaflet distal end, defining a distal-most end of the leaflet, which is the part of the leaflet closest to the inflow end of the frame; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge, which is closer to the inflow end of the frame, and an opposite proximal edge, which is closer to the outflow end; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame; wherein the proximal edge of the base layer portion is positioned closer to the outflow end of the frame than the leaflet distal end.

9. The prosthetic valve of claim 8, wherein the entire region between the cusp lines of adjacent leaflets is covered by the base layer portion.

10. The prosthetic valve of any one of claims 8-9, wherein the base layer portion proximal edge extends between throughs, which are closer to an inflow end of the frame, and peaks, which are closer to the outflow end of the frame, to form a plurality of extensions extending from the throughs.

11. The prosthetic valve of claim 10, wherein the base layer portion and outflow extensions thereof are covering the entire region between adjacent leaflets.

12. The prosthetic valve of any one of claims 8-11, wherein the skirt is devoid of protruding extensions extending from a surface of the base layer portion which is axially defined between the proximal edge thereof and the leaflet distal end.

13. The prosthetic valve of any one of claims 8-12, wherein the protruding extensions of the skirt comprise foam material.

14. The prosthetic valve of claim 1 , wherein outer surfaces of the protruding extensions are porous.

15. A prosthetic valve comprising: an annular frame movable between a radially compressed state and a radially expanded state, wherein the frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end; and a skirt comprising: a base layer portion secured to an inner surface of the frame, and extending between a distal edge which is closer to the inflow end of the frame, and an opposite proximal edge which is closer to the outflow end, wherein the base layer portion comprises at least one layer which has at least one surface defining a non-uniform surface morphology; and a plurality of protruding extensions, each extending radially outwards from the base layer portion and through a corresponding cell or an opening defined between struts of the frame.

16. The prosthetic valve of claim 15, wherein the at least one layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the at least one layer is facing the protruding extensions, and the inner surface of the at least one layer is facing radially inwards and defines the non-uniform surface morphology of the base layer portion.

17. The prosthetic valve of claim 16, wherein the inner surface of the at least one layer is a neointimal-formation encouraging surface.

18. The prosthetic valve of any one of claims 15-17, wherein the at least one layer is perforated.

19. The prosthetic valve of any one of claims 15 or 17-18, wherein the at least one layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the at least one layer is facing the protruding extensions, and the inner surface of the at least one layer is facing radially inwards; wherein the at least one layer of the base layer portion comprises a coating layer that is coating the inner surface thereof; and wherein the coating is configured to promote endothelization.

20. The prosthetic valve of any one of claims 15-16 or 18-19, wherein the base layer portion comprises: an internal layer, which among the base layer portions, is located the most distally to the protruding extensions; and an external layer, which among the base layer portions, is located the most proximally to the protruding extensions; wherein the internal layer of the base layer portion defines an outer surface and an inner surface, wherein the outer surface of the internal layer is facing the protruding extensions, and the inner surface of the internal layer is facing radially inwards; and wherein the inner surface of the internal layer has a non-uniform surface morphology.

21. The prosthetic valve of claim 20, wherein the internal layer comprises a coating layer that is coating the inner surface thereof, wherein the coating is promoting endothelization, and comprises at least one endothelium tissue promoting compound selected from the group consisting of: collagen, chitosan hyaluronic acid and a combination thereof.