3D Shaped Skirt for Prosthetic Heart Valve

Abstract

The present invention relates to implantable prosthetic devices, and more particularly to 3D shaped skirts having various coatings and / or configurations.

Description

[Technical Field]

[0001] The present invention relates to the field of implantable prosthetic heart valves, and more particularly to a sealing member having a first layer with a variety of 3D shaped coatings on its upper surface, a method for manufacturing the same, and an implantable prosthetic heart valve including the same. [Background technology]

[0002] Natural heart valves, such as the aortic, pulmonary, and mitral valves, function to ensure proper directional flow of blood to and from the heart and between the atria and ventricles of the heart to supply the entire cardiovascular system. Various valvular diseases can cause the valves to fail, requiring replacement with prosthetic valves. Surgery can be performed to repair or replace heart valves. Because surgery is prone to numerous clinical complications, alternative, minimally invasive techniques have been developed over the years to deliver prosthetic heart valves over catheters and implant them over malfunctioning natural valves.

[0003] Various types of prosthetic heart valves are known, including balloon-expandable valves, self-expandable valves, and mechanically expandable valves. Various methods for delivery and implantation are also known and can vary depending on the implantation site and the type of prosthetic valve. One exemplary technique involves utilizing a delivery assembly to deliver a prosthetic valve in a crimped state through an incision, which may be located in the patient's femoral or iliac artery, toward the native, dysfunctional valve. After the prosthetic valve is properly positioned at the desired implantation site, it can be expanded against surrounding anatomical structures, such as the annulus of the native valve, and the delivery assembly can then be withdrawn. In some cases, valve explantation is required, in which the originally implanted valve is surgically removed from the patient's body.

[0004] Paravalvular leak (PVL) is a complication associated with prosthetic heart valve replacement that can occur when blood flows through a channel or gap located between the implanted prosthetic heart valve structure in its expanded state and the implantation site (e.g., surrounding cardiac or arterial tissue) without an adequate seal.

[0005] Thus, there remains a need to provide a prosthetic heart valve that allows for adequate sealing against surrounding tissue at the implantation site to substantially fill gaps or channels that could lead to PVL, and that allows for easy removal from the implantation site if necessary. Summary of the Invention

[0006] The present disclosure is directed to prosthetic heart valves and methods of making and / or using the same, particularly with respect to 3D shaped prosthetic heart valves that can adequately seal against surrounding tissue at the implantation site to substantially fill gaps or channels that could lead to PVL, and that can also be easily extracted from the implantation site during an extraction procedure.

[0007] According to a first aspect of the present invention, there is provided a prosthetic heart valve including a frame, a leaflet assembly mounted within the frame, and a seal member coupled to an outer surface of the frame. The frame includes a plurality of crossed struts and is movable between a radially compressed state and a radially expanded state. The seal member extends from an inflow edge toward an opposite outflow edge and includes a first layer and a second layer covering the first layer. The non-fibrous outer surface of the seal member is formed from a material that is essentially molded to define a plurality of raised portions having peaks and a plurality of non-raised portions. The first and second layers are disposed outwardly relative to the outer surface of the frame.

[0008] According to some embodiments, each of the plurality of non-raised portions is defined by an adjacent pair of the plurality of raised portions.

[0009] According to some embodiments, the raised portions are configured to deform when an external pressure exceeding a predefined threshold is applied to the raised portions in a direction configured to press the raised portions against the frame, and to return to a relaxed state when the external pressure is no longer applied to the raised portions, the distance of the peaks from the frame being greater compared to the distance of the non-raised portions from the frame in the relaxed state.

[0010] According to some embodiments, the predefined threshold for external pressure is 300 mmHg.

[0011] According to some embodiments, the distance of the peak from the frame is at least 1000% greater than the distance of the non-raised portion from the frame in the absence of an external force applied to press the raised portion against the frame (i.e., in a relaxed state). According to some embodiments, the distance of the peak from the frame is at least 2000% greater than the distance of the non-raised portion from the frame. According to some embodiments, the distance of the peak from the frame is at least 3000% greater than the distance of the non-raised portion from the frame.

[0012] According to some embodiments, the non-fibrous outer surface is a smooth surface.

[0013] According to some embodiments, the sealing member includes a third layer. According to some embodiments, the second layer and the third layer collectively form a coating over the first layer.

[0014] According to some embodiments, the first layer comprises at least one tear resistant fabric. According to some embodiments, the tear resistant fabric comprises a ripstop fabric. According to some embodiments, the first layer comprises a biocompatible material. According to some embodiments, the first layer comprises at least one elastic material. According to some embodiments, the first layer comprises a PET fabric. According to some embodiments, the first layer has a tear resistance of at least 5N. According to some embodiments, the first layer has a tear resistance of at least 15N.

[0015] According to some embodiments, the second layer comprises a biocompatible material. According to some embodiments, the second layer comprises at least one anti-thrombogenic material. According to some embodiments, the second layer is formed from a thermoplastic material. According to some embodiments, the second layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the second layer is formed from a thermoplastic elastomer. According to some embodiments, the second layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the second layer comprises TPU.

[0016] According to some embodiments, the third layer comprises a biocompatible material. According to some embodiments, the third layer comprises at least one anti-thrombogenic material. According to some embodiments, the third layer is formed from a thermoplastic material. According to some embodiments, the third layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the third layer is formed from a thermoplastic elastomer. According to some embodiments, the third layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the third layer comprises TPU.

[0017] According to some embodiments, the second and third layers are formed from the same material.

[0018] According to some embodiments, the raised portion of the seal member includes a plurality of ridges, the plurality of ridges being spaced apart from one another along the first surface of the seal member. According to some embodiments, the second layer forms the first surface of the seal member. According to some embodiments, each of the plurality of ridges extends outward from an outer surface of the frame. According to some embodiments, the plurality of ridges are compressible.

[0019] According to some embodiments, the seal member includes a plurality of internal channels, each channel formed in the second surface of the seal member. According to some embodiments, the number of channels is the same as the number of ridges, and each of the plurality of channels is formed by a respective one of the plurality of ridges on the opposite surface of the seal member. According to some embodiments, each of the plurality of channels faces inward.

[0020] According to some embodiments, the non-raised portion of the seal member includes a plurality of inter-ridge gaps formed on the surface of the first layer between two adjacent ridges of the seal member.

[0021] According to some embodiments, the plurality of ridges follow parallel path lines extending around and / or along the first surface of the seal member.

[0022] According to some embodiments, the plurality of ridges follow parallel path lines extending substantially parallel to at least one of the leading edge and / or the trailing edge.

[0023] According to some embodiments, the plurality of ridges follow parallel path lines extending substantially perpendicular to at least one of the inflow edge and the outflow edge.

[0024] According to some embodiments, the plurality of ridges follow parallel path lines that extend substantially obliquely relative to at least one of the leading edge and the trailing edge.

[0025] According to some embodiments, the seal member has a total layer thickness measured between the first and second surfaces of the seal member at one of the inter-ridge gaps and a seal member thickness measured by the height of the ridges of the seal member, the seal member thickness being at least 1000% greater than the total layer thickness. According to some embodiments, the seal member thickness is at least 2000% greater than the total layer thickness. According to some embodiments, the seal member thickness is at least 3000% greater than the total layer thickness.

[0026] According to some embodiments, a sealing member as disclosed herein above is prepared by a method including: (i) providing a tear-resistant flat sheet extending from a first lateral edge to a second lateral edge; (ii) treating the sheet with a thermal shaping process to form an elastic structure in an unfolded, relaxed state including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrical sealing member in a cylindrically folded state.

[0027] According to some embodiments, thermally shaping the sheet in step (ii) comprises thermoforming.

[0028] According to some embodiments, the sheet includes a tear-resistant first layer and a thermoplastic second layer.

[0029] According to some embodiments, the tear-resistant first layer comprises a ripstop fabric. According to some embodiments, the tear-resistant first layer comprises a biocompatible material. According to some embodiments, the tear-resistant first layer comprises at least one elastic material. According to some embodiments, the tear-resistant first layer comprises a PET fabric. According to some embodiments, the tear-resistant first layer has a tear resistance of at least 5N. According to some embodiments, the tear-resistant first layer has a tear resistance of at least 15N.

[0030] According to some embodiments, the thermoplastic second layer includes at least one anti-thrombogenic material. According to some embodiments, the thermoplastic second layer is formed from a biocompatible material. According to some embodiments, the thermoplastic second layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic second layer is formed from a thermoplastic elastomer. According to some embodiments, the thermoplastic second layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic second layer includes TPU.

[0031] According to some embodiments, the tear-resistant flat sheet in step (i) further comprises a thermoplastic third layer. According to some embodiments, the second and third layers are formed from the same material. According to some embodiments, the thermoplastic third layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic third layer comprises TPU.

[0032] According to some embodiments, step (ii) comprises placing the flat sheet onto a mold at an elevated temperature to form a plurality of ridges on the upper surface, and reducing the temperature to maintain the elastic structure of the thermoplastic second layer.

[0033] According to some embodiments, the thickness of the sealing member in the unfolded relaxed state is at least 1000% greater than the initial thickness of the sheet provided in step (i).

[0034] According to some embodiments, step (ii) comprises placing the flat sheet at an elevated temperature onto a mold and allowing the heated sheet to sink under gravity, thereby forming a plurality of ridges on the upper surface. According to some embodiments, the mold is selected from a plurality of rods, tubes, pipes, and combinations thereof.

[0035] According to some embodiments, the mold includes a base, a plurality of protrusions, and a vacuum source having openings. According to some embodiments, step (ii) includes placing a flat sheet at an elevated temperature over the plurality of protrusions and applying a vacuum using the vacuum source and openings to thermoform the sheet into an expanded, relaxed elastic structure.

[0036] According to some embodiments, step (ii) includes applying force using a mold onto two opposing edges of the flexible sheet. According to some embodiments, the mold includes a first mold and a second mold, the first mold including a first base and a plurality of first mold projections, and the second mold including a second base and a plurality of second mold projections. According to some embodiments, step (ii) includes placing the flat sheet between the plurality of first mold projections and the plurality of second mold projections, arranging the plurality of first mold projections and the plurality of second mold projections in a zipper-like configuration. According to some embodiments, step (ii) further includes pressing the second mold against the first mold at an elevated temperature to effectively engage the flat sheet between the first and second molds, thereby allowing the sheet to conform to said molds.

[0037] According to some embodiments, step (ii) comprises placing a flat sheet comprising a tear-resistant first layer as disclosed hereinabove on a mold at an elevated temperature, and coating the formed sheet with a second layer on the mold to form a plurality of ridges on the upper surface. According to some embodiments, the mold comprises a base and a plurality of protrusions. According to some embodiments, step (ii) comprises heat coating the formed sheet with the second layer at an elevated temperature that allows for thermoforming.

[0038] According to some embodiments, the second layer is formed from a thermoplastic material. According to some embodiments, the thermoplastic material is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic second layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic second layer comprises TPU.

[0039] According to some embodiments, the raised portion of the seal member of the present invention comprises a plurality of protrusions extending outwardly from and / or around the periphery of the first surface of the seal member. According to some embodiments, the plurality of protrusions are spaced apart from one another along the first surface. According to some embodiments, each of the plurality of protrusions is compressible. According to some embodiments, the seal member comprises a flat second surface opposite the first surface when in an expanded, relaxed state.

[0040] According to some embodiments, the non-raised portion of the seal member includes a plurality of inter-projection gaps, each gap being located between two adjacent projections, and according to some embodiments, the plurality of inter-projection gaps are oriented in the same direction as the projections.

[0041] According to some embodiments, each of the plurality of protrusions extends around and / or away from the first surface to form a 3D shape on the top surface, which according to some embodiments may be selected from the group consisting of an inverted U-shape, a hemisphere, a dome, a cylinder, a pyramid, a triangular prism, a pentagonal prism, a hexagonal prism, a flap, a polygon, and combinations thereof.

[0042] According to some embodiments, the plurality of protrusions form an elongated 3D shape and extend substantially parallel to at least one of the inflow edge and / or the outflow edge.

[0043] According to some embodiments, the plurality of protrusions form an elongated 3D shape and extend substantially perpendicular to at least one of the inflow edge and / or the outflow edge.

[0044] According to some embodiments, the plurality of protrusions form an elongated 3D shape and extend substantially obliquely relative to at least one of the leading edge and / or the leading edge.

[0045] According to some embodiments, the seal member has a total layer thickness measured between the first surface and the second surface at one of the inter-protrusion gaps and a seal member thickness defined as the distance between the protrusion and the second surface, the seal member thickness being at least 1000% greater than the total layer thickness. According to some embodiments, the seal member thickness is at least 2000% greater than the total layer thickness. According to some embodiments, the seal member thickness is at least 3000% greater than the total layer thickness.

[0046] According to some embodiments, the plurality of protrusions comprise the same material as the second layer. According to some embodiments, each protrusion is formed from a biocompatible material. According to some embodiments, each protrusion is formed from at least one anti-thrombogenic material. According to some embodiments, each protrusion is formed from a thermoplastic material. According to some embodiments, each protrusion is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, each protrusion is formed from a thermoplastic elastomer. According to some embodiments, each protrusion is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, each protrusion is formed from TPU.

[0047] According to some embodiments, each of the plurality of protrusions in the seal member of the present invention defines a solid structure, thereby forming a solid protrusion.

[0048] According to some embodiments, a sealing member as disclosed hereinabove including solid protrusions is prepared by a method including: (i) providing a tear-resistant flat sheet extending from a first lateral edge to a second lateral edge and from an inflow edge to an outflow edge; (ii) treating the sheet with a thermal shaping process to form an elastic structure in an unfolded, relaxed state including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrical sealing member in a cylindrically folded state. The tear-resistant flat sheet includes a tear-resistant first layer and a thermoplastic second layer as disclosed hereinabove.

[0049] According to some embodiments, step (ii) involves an extrusion-based shape-forming process that includes extruding a plurality of features onto the flat sheet of thermoplastic second layer, each feature comprising a molten composition at an elevated temperature and spaced apart from one another, and step (ii) further involves reducing the temperature, whereby each extruded feature transitions to an elastic state, thereby forming a plurality of protrusions on the upper surface.

[0050] According to some embodiments, the molten composition comprises at least one anti-thrombogenic and biocompatible material. According to some embodiments, the molten composition comprises at least one thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the molten composition comprises at least one thermoplastic elastomer material selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations and variations thereof. According to some embodiments, the molten composition comprises TPU.

[0051] According to some embodiments, step (ii) involves an injection molding process, which includes inserting a flat sheet into a mold at an elevated temperature and injecting a molten composition into said mold onto at least one side of the flat sheet. The molten composition is configured to conform to the shape of the mold when its temperature is reduced. The mold is configured to be removed after cooling, thereby forming the elastic structure of the sealing member in its expanded, relaxed state. The molten composition comprises a thermoplastic material as disclosed herein above.

[0052] According to some embodiments, step (ii) involves placing a mold including a plurality of spaced-apart mask members on the thermoplastic second layer of the flat sheet and depositing a thermoplastic material as disclosed hereinabove at an elevated temperature into spaces formed between adjacent mask members, and step (ii) further involves reducing the temperature to transition the thermoplastic material into an elastic state, thereby forming a plurality of protrusions on the flat sheet.

[0053] According to some embodiments, depositing the thermoplastic material in step (ii) is carried out by a technique selected from the group consisting of extrusion, brush coating, spray coating, chemical deposition, liquid deposition, vapor deposition, chemical vapor deposition, physical vapor deposition, roller printing, stencil printing, screen printing, inkjet printing, lithographic printing, 3D printing, and combinations thereof.

[0054] According to some embodiments, the thickness of the sealing member in its unfolded, relaxed state after step (ii) is at least 1000% greater than the initial thickness of the sheet provided in step (i).

[0055] According to some embodiments, each of the plurality of protrusions in the seal member of the present invention defines a hollow lumen therein, thereby forming a hollow protrusion. According to some embodiments, each hollow lumen includes two lumen edges, and each hollow lumen is open at one or both lumen edges.

[0056] According to some embodiments, each of the plurality of protrusions includes a plurality of apertures spaced apart along the protrusion, each aperture configured to provide fluid communication between the hollow lumen and an external environment outside the aperture.

[0057] According to some embodiments, each of the plurality of openings is sealed by a biodegradable membrane and configured to allow controlled release of a pharmaceutical composition from within each hollow lumen through the biodegradable membrane.

[0058] According to some embodiments, each of the hollow lumens contains a pharmaceutical composition disposed therein.

[0059] According to some embodiments, each of the hollow lumens includes a resilient porous member disposed therein. According to some embodiments, the resilient porous member includes a pharmaceutical composition disposed therein. According to some embodiments, the resilient porous member is a sponge.

[0060] According to some embodiments, the pharmaceutical composition comprises at least one pharmaceutically active ingredient selected from the group consisting of antibiotics, antivirals, antifungals, antiangiogenics, analgesics, anesthetics, anti-inflammatory drugs including steroidal anti-inflammatory drugs and non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antihistamines, mydriatics, antineoplastic drugs, immunosuppressants, anti-allergic drugs, metalloproteinase inhibitors, tissue inhibitors of metalloproteinases (TIMPs), vascular endothelial growth factor (VEGF) inhibitors or antagonists or intraceptors, receptor antagonists, RNA aptamers, antibodies, hydroxamic acids and macrocyclic antisuccinic hydroxamic acid derivatives, nucleic acids, plasmids, siRNAs, vaccines, DNA binding compounds, hormones, vitamins, proteins, peptides, polypeptides and peptide-like therapeutic agents, anesthetics, and combinations thereof.

[0061] According to some embodiments, each of the plurality of projections is a segmented projection, and each of the plurality of segmented projections defines an internal space between the segments. According to some embodiments, the internal space extends between an opening of each segmented projection and the first surface of the sealing member. According to some embodiments, the internal space extends between an opening of each segmented projection and the first surface of the first layer. According to some embodiments, the opening of each of the plurality of segmented projections is symmetrical with respect to an axis extending through the center of each segmented projection, thereby defining a symmetrical internal space. According to some embodiments, the opening of each of the plurality of segmented projections is obliquely offset with respect to the axis extending through the center of each segmented projection, thereby defining an asymmetrical internal space.

[0062] According to some embodiments, a sealing member as disclosed herein above, including hollow protrusions, is prepared by a method including: (i) providing a tear-resistant flat sheet extending from a first lateral edge to a second lateral edge and from an inflow edge to an outflow edge; and (ii) treating the sheet with a thermal shaping process, the process including disposing a plurality of elongated molding members on the tear-resistant flat sheet. Step (ii) further includes depositing a thermoplastic layer on the plurality of elongated molding members at an elevated temperature to form a plurality of protrusions (i.e., raised portions) on the upper surface, thereby forming the sheet into a 3D structure including a plurality of raised portions and a plurality of non-raised portions. Step (ii) further includes reducing the temperature to form the elastic 3D structure of the thermoplastic layer including the plurality of raised portions.

[0063] According to some embodiments, the method further comprises the step (iii) of joining two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0064] According to some embodiments, the thickness of the unfolded, relaxed sealing member after step (ii) is at least 1000% greater than the initial thickness of the sheet prepared in step (i).

[0065] According to some embodiments, the tear resistant flat sheet comprises a tear resistant first layer as disclosed hereinabove. According to some embodiments, the tear resistant flat sheet further comprises a thermoplastic second layer as disclosed hereinabove. According to some embodiments, the tear resistant flat sheet further comprises a thermoplastic third layer as disclosed hereinabove.

[0066] According to some embodiments, each elongate molding member is made from a heat-resistant metal or metal alloy.

[0067] According to some embodiments, step (ii) includes removing the plurality of elongated molding members from within the plurality of protrusions after the protrusions are formed.

[0068] According to some embodiments, removing the plurality of elongated molding members from the interior of the plurality of protrusions in step (ii) includes extracting each elongated molding member through at least one protruding edge located at the first lateral edge or the second lateral edge of the sheet, thereby forming a plurality of hollow cavities therein.

[0069] According to some embodiments, step (ii) further comprises drilling a plurality of apertures in the plurality of protrusions. According to some embodiments, step (ii) further comprises inserting a pharmaceutical composition into at least a portion of said hollow lumen.

[0070] According to some embodiments, the plurality of elongated shaped members are a plurality of elastic porous members. According to some embodiments, step (ii) further comprises impregnating the plurality of elastic porous members with the pharmaceutical composition.

[0071] According to some embodiments, each of the plurality of elongated molding members includes a sharp tip. According to some embodiments, depositing the thermoplastic layer onto the plurality of elongated molding members in step (ii) involves contacting the thermoplastic layer against the sharp tips of the elongated molding members. According to some embodiments, step (ii) further includes removing the plurality of elongated molding members through the plurality of protrusions to form a plurality of segmented protrusions.

[0072] According to some embodiments, step (ii) includes pulling the pointed tip of each elongated molding member through the thermoplastic layer. According to some embodiments, the pointed tip of each elongated molding member is pulled along an axis extending through the center of each segmented projection in a direction perpendicular to the flat sheet, thereby forming a symmetrical internal space. According to some embodiments, the pointed tip of each elongated molding member is pulled in the direction of a pulling arrow that is obliquely biased relative to the direction perpendicular to the flat sheet, thereby forming an asymmetrical internal space.

[0073] According to another aspect of the present invention, there is provided a prosthetic heart valve including a frame, a leaflet assembly mounted within the frame, and a seal member coupled to an outer surface of the frame. The frame includes a plurality of intersecting struts and is movable between a radially compressed state and a radially expanded state. The seal member is in a folded state. The seal member extends from an inflow edge toward an opposite outflow edge. The seal member includes a first layer and a second layer covering the first layer. The non-fibrous outer surface of the seal member is formed from an essentially molded material to define at least one helical projection extending radially outward in a helical configuration around the second layer between the inflow and outflow edges of the seal member. The first and second layers are disposed outwardly relative to the outer surface of the frame.

[0074] According to some embodiments, the at least one helical projection is configured to deform when an external pressure exceeding a predetermined threshold is applied to the helical projection in a direction configured to press the helical projection against the frame, and to return to a relaxed state when the external pressure is no longer applied to the helical projection. A distance of the at least one helical projection from the frame is greater than a distance of the second layer from the frame in the relaxed state. According to some embodiments, the predetermined external pressure threshold is 300 mmHg.

[0075] According to some embodiments, the distance of the at least one helical projection from the frame is at least 1000% greater than the distance of the second layer from the frame in the absence of an external force applied to press the helical projection against the frame (i.e., in a relaxed state). According to some embodiments, the distance of the helical projection from the frame is at least 2000% greater than the distance of the second layer from the frame. According to some embodiments, the distance of the helical projection from the frame is at least 3000% greater than the distance of the second layer from the frame.

[0076] According to some embodiments, the non-fibrous outer surface is a smooth surface.

[0077] According to some embodiments, the first layer comprises at least one tear resistant fabric. According to some embodiments, the tear resistant fabric comprises a ripstop fabric. According to some embodiments, the first layer comprises a biocompatible material. According to some embodiments, the first layer comprises at least one elastic material. According to some embodiments, the first layer comprises a PET fabric. According to some embodiments, the first layer has a tear resistance of at least 5N. According to some embodiments, the first layer has a tear resistance of at least 15N.

[0078] According to some embodiments, the second layer comprises a biocompatible material. According to some embodiments, the second layer comprises at least one anti-thrombogenic material. According to some embodiments, the second layer is formed from a thermoplastic material. According to some embodiments, the second layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the second layer is formed from a thermoplastic elastomer. According to some embodiments, the second layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the second layer comprises TPU.

[0079] According to some embodiments, the sealing member includes a third layer. According to some embodiments, the second layer and the third layer collectively form a coating over the first layer.

[0080] According to some embodiments, the third layer comprises a biocompatible material. According to some embodiments, the third layer comprises at least one anti-thrombogenic material. According to some embodiments, the third layer is formed from a thermoplastic material. According to some embodiments, the third layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the third layer is formed from a thermoplastic elastomer. According to some embodiments, the third layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the third layer comprises TPU.

[0081] According to some embodiments, the second and third layers are formed from the same material.

[0082] According to some embodiments, a sealing member as disclosed herein above, including at least one helical protrusion, is prepared by a method including: (i) providing a tear-resistant flat sheet in a folded cylindrical state extending from an inflow edge to an outflow edge; and (ii) disposing at least one helical mandrel around the tear-resistant flat sheet. Step (ii) further includes depositing a thermoplastic layer onto the at least one helical mandrel at an elevated temperature to form at least one helical protrusion on the upper surface, the at least one helical protrusion extending radially apart in a helical configuration around the periphery. Step (ii) further includes forming an elastic 3D structure in the thermoplastic layer by reducing the temperature. Step (ii) further includes removing the at least one helical mandrel from an interior of the at least one helical protrusion through at least one helical protruding edge located at the inflow edge or the outflow edge, thereby forming a helical hollow lumen therein.

[0083] According to some embodiments, the tear resistant flat sheet comprises a tear resistant first layer as disclosed hereinabove.

[0084] According to some embodiments, the thermoplastic layer in step (ii) comprises at least one antithrombogenic material. According to some embodiments, the thermoplastic layer is formed from a biocompatible material. According to some embodiments, the thermoplastic layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic layer is formed from a thermoplastic elastomer. According to some embodiments, the thermoplastic layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic layer comprises TPU.

[0085] According to some embodiments, the tear resistant flat sheet in step (i) further comprises a thermoplastic third layer. According to some embodiments, the second and third layers comprise the same material.

[0086] According to some embodiments, step (ii) further comprises drilling a plurality of openings in the helical projection. According to some embodiments, step (ii) further comprises inserting a pharmaceutical composition into at least a portion of the helical hollow lumen.

[0087] According to another aspect of the present invention, there is provided a prosthetic heart valve including a frame, a leaflet assembly mounted within the frame, and a seal member coupled to an outer surface of the frame. The frame includes a plurality of intersecting struts defining a plurality of coaptations and is movable between a radially compressed state and a radially expanded state. The seal member extends from an inflow edge toward an opposite outflow edge. The seal member includes a tear-resistant first layer and a thermoplastic second layer covering the first layer and defining a first surface of the seal member. The non-fibrous outer surface of the seal member is formed from a material that is essentially molded to define a single compressible projection extending around and away from the first surface of the seal member parallel to one of the outflow and inflow edges. The first and second layers are disposed outwardly relative to the outer surface of the frame.

[0088] The length of the single projection in a direction extending between the inlet and outlet edges of the seal member is at least as long as the distance between two joints on the frame, the joints being axially aligned and spaced apart along the frame of the valve.

[0089] According to some embodiments, the distance of the protrusion from the frame is greater than the distance of the first surface of the seal member from the frame when there is no external force applied to press the protrusion against the frame. According to some embodiments, the distance of the protrusion from the frame is greater than the distance of the first surface of the seal member from the frame by at least 1000%. According to some embodiments, the distance of the protrusion from the frame is greater than the distance of the first surface from the frame by at least 2000%. According to some embodiments, the distance of the protrusion from the frame is greater than the distance of the first surface from the frame by at least 3000%.

[0090] According to some embodiments, the non-fibrous outer surface is a smooth surface.

[0091] According to some embodiments, the tear-resistant first layer comprises a ripstop fabric. According to some embodiments, the first layer comprises a biocompatible material. According to some embodiments, the first layer comprises at least one elastic material. According to some embodiments, the first layer comprises a PET fabric. According to some embodiments, the first layer has a tear resistance of at least 5N. According to some embodiments, the first layer has a tear resistance of at least 15N.

[0092] According to some embodiments, the thermoplastic second layer comprises a biocompatible material. According to some embodiments, the second layer comprises at least one anti-thrombogenic material. According to some embodiments, the second layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the second layer is formed from a thermoplastic elastomer. According to some embodiments, the second layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the second layer comprises TPU.

[0093] According to some embodiments, the sealing member includes a thermoplastic third layer, and according to some embodiments, the thermoplastic second layer and the thermoplastic third layer collectively form a coating over the tear-resistant first layer.

[0094] According to some embodiments, the thermoplastic third layer comprises a biocompatible material. According to some embodiments, the third layer comprises at least one anti-thrombogenic material. According to some embodiments, the third layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the third layer is formed from a thermoplastic elastomer. According to some embodiments, the third layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the third layer comprises TPU.

[0095] According to some embodiments, the second thermoplastic layer and the third thermoplastic layer are formed from the same material.

[0096] According to some embodiments, the single compressible projection defines a single hollow lumen therein.

[0097] According to some embodiments, the single compressible projection includes a plurality of spaced-apart apertures therein. According to some embodiments, each of the plurality of apertures is sealed by a biodegradable membrane and configured to allow controlled release of a pharmaceutical composition from within the single hollow lumen through the biodegradable membrane. According to some embodiments, the single hollow lumen contains a pharmaceutical composition disposed therein. According to some embodiments, at least a portion of the apertures are sealed by a semi-permeable membrane.

[0098] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet; (ii) treating the sheet in a thermal shaping process to form an elastic structure in an unfolded, relaxed state, the elastic structure including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0099] According to some embodiments, the tear-resistant flat sheet in step (i) comprises a tear-resistant first layer and a thermoplastic second layer. The tear-resistant flat sheet extends between a first lateral edge and a second lateral edge and between an inflow edge and an outflow edge. According to some embodiments, the treating in step (ii) comprises contacting the flat sheet against a mold at an elevated temperature. Step (ii) further comprises reducing the temperature to maintain the elastic structure of the thermoplastic second layer, the second layer being distal to the mold. Step (ii) further comprises removing the mold from the sheet after the temperature has been reduced.

[0100] According to some embodiments, the flat sheet in step (i) comprises a tear-resistant first layer positioned between a thermoplastic second layer and a thermoplastic third layer of the flat sheet. According to some embodiments, step (ii) involves contacting the flat sheet against a mold, with the third layer contacting the mold.

[0101] According to some embodiments, step (ii) comprises contacting the flat sheet against a mold at an elevated temperature to form a plurality of ridges on the upper surface.

[0102] According to some embodiments, the second layer is thermoformable at elevated temperatures and elastic at reduced temperatures. According to some embodiments, the elevated temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0103] According to some embodiments, step (ii) involves placing a flat sheet on a mold, the second layer being distal to the mold. According to some embodiments, step (ii) involves placing a flat sheet on a mold, the third layer being in contact with the mold.

[0104] According to some embodiments, step (ii) comprises placing the flat sheet at an elevated temperature onto a mold and allowing the heated sheet to sink under gravity, thereby forming a plurality of ridges on the upper surface. According to some embodiments, the mold is selected from a plurality of rods, tubes, pipes, and combinations thereof.

[0105] According to some embodiments, the mold includes a base, a plurality of protrusions, and a vacuum source having a plurality of openings. According to some embodiments, the plurality of protrusions extend away from the base and are spaced apart along the base. According to some embodiments, the plurality of openings are formed in the base, the protrusions, or both.

[0106] According to some embodiments, step (ii) includes positioning a flat sheet above a mold. Step (ii) further includes heating the flat sheet to a thermoformable temperature. Step (ii) further includes driving the sheet toward the mold, thereby effectively engaging the flat sheet against the protrusions of the mold, thereby allowing the sheet to conform to the protrusions. Engagement of the sheet with the protrusions forms a plurality of ridges, and engagement of the sheet with the base forms a plurality of inter-ridge gaps of the seal member.

[0107] According to some embodiments, step (ii) includes applying force onto two opposing edges of the flexible sheet using a mold. According to some embodiments, the mold includes a first mold and a second mold. According to some embodiments, the first mold includes a first base and a plurality of first mold projections, and the second mold includes a second base and a plurality of second mold projections. According to some embodiments, step (ii) includes placing the flat sheet between the plurality of first mold projections and the plurality of second mold projections, arranging the plurality of first mold projections and the plurality of second mold projections in a zipper-like configuration. According to some embodiments, step (ii) further includes pressing the second mold against the first mold at an elevated temperature to effectively engage the flat sheet between the first and second molds, thereby allowing the sheet to conform to said molds.

[0108] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet including a tear-resistant first layer; (ii) treating the sheet in a thermal shaping process to form an elastic structure in an unfolded, relaxed state including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0109] The tear-resistant flat sheet extends between the first and second lateral edges and between the inflow and outflow edges. According to some embodiments, the treating in step (ii) includes placing the flat sheet over a mold to form a plurality of ridges on the upper surface above the mold, the mold including a base and a plurality of protrusions. Step (ii) further includes heat-coating the sheet with a thermoplastic material at an elevated thermoformable temperature to form a thermoplastic second layer on the upper surface. Step (ii) further includes reducing the temperature to form a resilient structure in the thermoplastic second layer.

[0110] According to some embodiments, the elevated thermoformable temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0111] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet; (ii) treating the sheet in a thermal shaping process to form an elastic structure in an unfolded, relaxed state, the elastic structure including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0112] According to some embodiments, the tear-resistant flat sheet in step (i) comprises a tear-resistant first layer and a thermoplastic second layer. The tear-resistant flat sheet extends between a first lateral edge and a second lateral edge and between an inflow edge and an outflow edge. According to some embodiments, the processing in step (ii) comprises extruding a plurality of spaced apart members onto the thermoplastic second layer of the flat sheet. Each member comprises a molten composition at a high temperature. Step (ii) further comprises reducing the temperature to transition each extruded member into an elastic state, thereby forming a plurality of protrusions on the upper surface.

[0113] According to some embodiments, the flat sheet in step (i) comprises a tear-resistant first layer positioned between a thermoplastic second layer and a thermoplastic third layer of the flat sheet.

[0114] According to some embodiments, the molten composition includes at least one antithrombogenic material. According to some embodiments, the molten composition is formed from a biocompatible thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the molten composition is formed from a thermoplastic elastomer. According to some embodiments, the molten composition is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the molten composition includes TPU.

[0115] According to some embodiments, the elevated temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0116] According to some embodiments, each of the plurality of protrusions formed in step (ii) is a 3D shape selected from the group consisting of an inverted U-shape, a hemisphere, a dome, a cylinder, a pyramid, a triangular prism, a pentagonal prism, a hexagonal prism, a flap, a polygon, and combinations thereof.

[0117] According to some embodiments, each of the plurality of protrusions formed in step (ii) is elongated and extends substantially parallel to at least one of the inflow and / or outflow edges of the sheet. According to some embodiments, each of the plurality of protrusions formed in step (ii) is elongated and extends substantially perpendicular to at least one of the inflow and outflow edges of the sheet. According to some embodiments, each of the plurality of protrusions formed in step (ii) is elongated and extends substantially obliquely to at least one of the inflow and outflow edges of the sheet.

[0118] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet; (ii) treating the sheet in a thermal shaping process to form an elastic structure in an unfolded, relaxed state, the elastic structure including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0119] According to some embodiments, the tear-resistant flat sheet in step (i) comprises a tear-resistant first layer and a thermoplastic second layer. The tear-resistant flat sheet extends between a first lateral edge and a second lateral edge and between an inflow edge and an outflow edge. According to some embodiments, the processing in step (ii) comprises placing a mold comprising a plurality of mask members spaced apart from one another on the thermoplastic second layer of the flat sheet. Step (ii) further comprises depositing a thermoplastic material at an elevated temperature into spaces formed between adjacent mask members. Step (ii) further comprises reducing the temperature to cause the thermoplastic material to transition to an elastic state, thereby forming a plurality of protrusions on the flat sheet.

[0120] According to some embodiments, the flat sheet in step (i) comprises a tear-resistant first layer positioned between a thermoplastic second layer and a thermoplastic third layer of the flat sheet.

[0121] According to some embodiments, the thermoplastic material in step (ii) is biocompatible. According to some embodiments, the thermoplastic material in step (ii) is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic material is anti-thrombogenic. According to some embodiments, the thermoplastic material is a thermoplastic elastomer. According to some embodiments, the thermoplastic elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic material comprises TPU.

[0122] According to some embodiments, each of the plurality of protrusions formed in step (ii) is a 3D shape selected from the group consisting of an inverted U-shape, a hemisphere, a dome, a cylinder, a pyramid, a triangular prism, a pentagonal prism, a hexagonal prism, a flap, a polygon, and combinations thereof.

[0123] According to some embodiments, each of the plurality of protrusions formed in step (ii) is elongated and extends substantially parallel to at least one of the inflow and / or outflow edges of the sheet. According to some embodiments, each of the plurality of protrusions formed in step (ii) is elongated and extends substantially perpendicular to at least one of the inflow and outflow edges of the sheet. According to some embodiments, each of the plurality of protrusions formed in step (ii) is elongated and extends substantially obliquely to at least one of the inflow and outflow edges of the sheet.

[0124] According to some embodiments, depositing the thermoplastic material in step (ii) is carried out by a technique selected from the group consisting of extrusion, brush coating, spray coating, chemical deposition, liquid deposition, vapor deposition, chemical vapor deposition, physical vapor deposition, roller printing, stencil printing, screen printing, inkjet printing, lithographic printing, 3D printing, and combinations thereof.

[0125] According to some embodiments, depositing the thermoplastic material in step (ii) includes depositing a monomer composition into the spaces formed between adjacent mask members and polymerizing the composition to transform the monomer composition into a polymerized elastic state, thereby forming a plurality of protrusions on the flat sheet.

[0126] According to some embodiments, the elevated temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0127] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet; (ii) treating the sheet in a thermal shaping process to form an elastic structure in an unfolded, relaxed state, the elastic structure including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0128] The tear-resistant flat sheet extends between the first and second lateral edges and between the inflow and outflow edges. According to some embodiments, the processing in step (ii) includes placing a plurality of elongated molding members on the tear-resistant flat sheet. Step (ii) further includes depositing a thermoplastic layer on the plurality of elongated molding members at an elevated temperature to form a plurality of protrusions on the upper surface. Step (ii) further includes forming an elastic 3D structure of the protrusions by reducing the temperature. Step (ii) further includes removing the plurality of elongated molding members from within the plurality of protrusions.

[0129] According to some embodiments, the flat sheet in step (i) comprises a single tear-resistant first layer. According to some embodiments, the flat sheet in step (i) further comprises a thermoplastic second layer. According to some embodiments, the flat sheet in step (i) comprises a tear-resistant first layer positioned between the thermoplastic second layer and the thermoplastic third layer of the flat sheet.

[0130] According to some embodiments, step (ii) includes placing a plurality of elongated molding members on a tear-resistant flat sheet and depositing a thermoplastic layer on the tear-resistant flat sheet at an elevated temperature, such that the plurality of elongated molding members are positioned between the tear-resistant flat sheet and the thermoplastic layer, thereby forming a plurality of 3D shaped protrusions.

[0131] According to some embodiments, the elevated temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0132] According to some embodiments, the thermoplastic layer in step (ii) is biocompatible. According to some embodiments, the thermoplastic layer in step (ii) is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic layer is anti-thrombogenic. According to some embodiments, the thermoplastic layer is a thermoplastic elastomer. According to some embodiments, the thermoplastic elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic layer comprises TPU.

[0133] According to some embodiments, the plurality of elongated molding members are made of a heat resistant metal or metal alloy. According to some embodiments, the plurality of elongated molding members are selected from rods, tubes, pipes, and combinations thereof.

[0134] According to some embodiments, removing the plurality of elongated molding members from the interior of the plurality of protrusions in step (ii) includes extracting each elongated molding member through at least one protruding edge located at the first lateral edge or the second lateral edge of the sheet, thereby forming a plurality of hollow cavities therein.

[0135] According to some embodiments, step (ii) further comprises drilling a plurality of apertures in the plurality of protrusions. According to some embodiments, step (ii) further comprises inserting a pharmaceutical composition into at least a portion of said hollow lumen.

[0136] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet; (ii) treating the sheet in a thermal shaping process to form an elastic structure in an unfolded, relaxed state, the elastic structure including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0137] The tear-resistant flat sheet extends between a first lateral edge and a second lateral edge and between an inflow edge and an outflow edge. According to some embodiments, the processing in step (ii) includes disposing a plurality of elastic porous members on the tear-resistant flat sheet. Step (ii) further includes depositing a thermoplastic layer on the plurality of elastic porous members at an elevated temperature to form a plurality of protrusions. Step (ii) further includes reducing the temperature to form the elastic 3D structure of protrusions.

[0138] According to some embodiments, the flat sheet in step (i) comprises a single tear-resistant first layer. According to some embodiments, the flat sheet in step (i) further comprises a thermoplastic second layer. According to some embodiments, the flat sheet in step (i) comprises a tear-resistant first layer positioned between the thermoplastic second layer and the thermoplastic third layer of the flat sheet.

[0139] According to some embodiments, step (ii) comprises placing a plurality of elastic porous members on a tear-resistant flat sheet and depositing a thermoplastic layer at an elevated temperature onto the tear-resistant flat sheet, such that the plurality of elastic porous members are positioned between the tear-resistant flat sheet and the thermoplastic layer, thereby forming a plurality of 3D shaped protrusions containing the elastic porous members therein.

[0140] According to some embodiments, the elevated temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0141] According to some embodiments, the thermoplastic layer in step (ii) is biocompatible. According to some embodiments, the thermoplastic layer in step (ii) is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic layer is anti-thrombogenic. According to some embodiments, the thermoplastic layer is a thermoplastic elastomer. According to some embodiments, the thermoplastic elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic layer comprises TPU.

[0142] According to some embodiments, each resilient porous member is formed from a heat-resistant biocompatible sponge.

[0143] According to some embodiments, step (ii) further comprises drilling a plurality of apertures in the plurality of protrusions.

[0144] According to some embodiments, step (ii) further comprises impregnating the plurality of elastic porous members with the pharmaceutical composition.

[0145] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet; (ii) treating the sheet in a thermal shaping process to form an elastic structure in an unfolded, relaxed state, the elastic structure including a plurality of raised portions and a plurality of non-raised portions; and (iii) connecting two opposite edges of the sheet to form a cylindrically folded cylindrical sealing member.

[0146] The tear-resistant flat sheet extends between the first and second lateral edges and between the inflow and outflow edges. According to some embodiments, the process in step (ii) includes placing a plurality of elongated molding members on the tear-resistant flat sheet, each of the plurality of elongated molding members including a sharp tip. Step (ii) further includes depositing a thermoplastic layer on the plurality of elongated molding members at an elevated temperature to form a plurality of protrusions. Step (ii) further includes forming an elastic 3D structure of the protrusions by reducing the temperature. Step (ii) further includes removing the plurality of elongated molding members through the plurality of protrusions to form a plurality of segmented protrusions.

[0147] According to some embodiments, the flat sheet in step (i) comprises a single tear-resistant first layer. According to some embodiments, the flat sheet in step (i) further comprises a thermoplastic second layer. According to some embodiments, the flat sheet in step (i) comprises a tear-resistant first layer positioned between the thermoplastic second layer and the thermoplastic third layer of the flat sheet.

[0148] According to some embodiments, depositing the thermoplastic layer onto the plurality of elongated molding members in step (ii) involves contacting the thermoplastic layer against sharp tips of the elongated molding members.

[0149] According to some embodiments, the plurality of elongated molding members and the sharp tip are formed from a heat-resistant metal or metal alloy.

[0150] According to some embodiments, step (ii) comprises pulling the sharp tip of each elongate molding member through the thermoplastic layer.

[0151] According to some embodiments, the pointed tip of each elongated molding member is pulled along an axis extending through the center of each divided projection in a direction perpendicular to the flat sheet, thereby forming a symmetrical internal space therein.

[0152] According to some embodiments, the pointed tip of each elongated molding member is pulled in the direction of the pulling arrow that is biased obliquely relative to the direction normal to the flat sheet, thereby forming an asymmetrical interior space therein.

[0153] According to some embodiments, the elevated temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0154] According to some embodiments, the thermoplastic layer in step (ii) is biocompatible. According to some embodiments, the thermoplastic layer in step (ii) is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic layer is anti-thrombogenic. According to some embodiments, the thermoplastic layer is a thermoplastic elastomer. According to some embodiments, the thermoplastic elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic layer comprises TPU.

[0155] According to another aspect of the present invention, there is provided a method for manufacturing a paravalvular leak (PVL) skirt, the method comprising: (i) providing a tear-resistant flat sheet in a folded cylindrical state extending from an inflow edge to an outflow edge; and (ii) treating the sheet in a thermal shaping process to form an elastic structure in the folded cylindrical state, the elastic structure including a plurality of raised portions and a plurality of non-raised portions.

[0156] According to some embodiments, the process in step (ii) includes placing at least one helical mandrel around the tear-resistant flat sheet. Step (ii) further includes depositing a thermoplastic layer onto the at least one helical mandrel at an elevated temperature to form at least one helical protrusion on the upper surface, the at least one helical protrusion extending radially apart in a helical configuration around the periphery. Step (ii) further includes maintaining the elastic structure of the thermoplastic layer by lowering the temperature. Step (ii) further includes removing the at least one helical mandrel from the interior of the at least one helical protrusion through at least one helical protruding edge located at the inflow edge or the outflow edge, thereby forming a helical hollow lumen therein.

[0157] According to some embodiments, the flat sheet in step (i) comprises a single tear-resistant first layer. According to some embodiments, the flat sheet in step (i) further comprises a thermoplastic second layer. According to some embodiments, the flat sheet in step (i) comprises a tear-resistant first layer positioned between the thermoplastic second layer and the thermoplastic third layer of the flat sheet.

[0158] According to some embodiments, step (ii) involves placing at least one helical mandrel around the thermoplastic second layer of the flat sheet.

[0159] According to some embodiments, the elevated temperature in step (ii) is at least 60° C. According to some embodiments, the reduced temperature in step (ii) is less than 40° C.

[0160] According to some embodiments, the thermoplastic layer in step (ii) is biocompatible. According to some embodiments, the thermoplastic layer in step (ii) is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic layer is anti-thrombogenic. According to some embodiments, the thermoplastic layer is a thermoplastic elastomer. According to some embodiments, the thermoplastic elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic layer comprises TPU.

[0161] According to some embodiments, step (ii) further comprises drilling a plurality of apertures in the helical projection.

[0162] According to some embodiments, step (ii) further comprises inserting a pharmaceutical composition into at least a portion of the helical hollow lumen.

[0163] According to some embodiments, in any of the above methods, the thickness of the sealing member after step (ii), optionally in an unfolded, relaxed state, is at least 1000% greater than the initial thickness of the sheet prepared in step (i). According to further embodiments, the thickness of the sealing member after step (ii) is at least 2000% greater than the initial thickness of the sheet prepared in step (i). According to yet further embodiments, the thickness of the sealing member after step (ii) is at least 3000% greater than the initial thickness of the sheet prepared in step (i).

[0164] According to some embodiments, in any of the above methods, the tear-resistant first layer of the flat sheet comprises a ripstop fabric. According to some embodiments, the tear-resistant first layer comprises a biocompatible material. According to some embodiments, the tear-resistant first layer comprises at least one elastic material. According to some embodiments, the tear-resistant first layer comprises a PET fabric. According to some embodiments, the tear-resistant first layer has a tear resistance of at least 5N. According to some embodiments, the tear-resistant first layer has a tear resistance of at least 15N.

[0165] According to some embodiments, in any of the above methods, the thermoplastic second layer of the flat sheet comprises at least one anti-thrombogenic material. According to some embodiments, the thermoplastic second layer is formed from a biocompatible material. According to some embodiments, the thermoplastic second layer is formed from a thermoplastic material selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic second layer is formed from a thermoplastic elastomer. According to some embodiments, the thermoplastic second layer is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic second layer comprises TPU.

[0166] According to some embodiments, in any of the above methods, the thermoplastic third layer of the flat sheet is formed from a thermoplastic elastomer selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations thereof. According to some embodiments, the thermoplastic third layer comprises TPU. According to some embodiments, the thermoplastic second layer and the thermoplastic third layer are formed from the same material.

[0167] According to another aspect of the present invention, there is provided a paravalvular leak (PVL) skirt produced by any of the methods disclosed hereinabove.

[0168] In accordance with another aspect of the present invention, there is provided a prosthetic heart valve including a frame, a leaflet assembly mounted within the frame, and a seal member coupled to an outer surface of the frame, the frame including a plurality of intersecting struts and movable between a radially compressed state and a radially expanded state, the seal member being manufactured according to any of the methods disclosed hereinabove.

[0169] Particular embodiments of the present invention may include some, all, or none of the above advantages. Additional advantages will be readily apparent to those skilled in the art from the figures, descriptions, and claims contained herein. Aspects and embodiments of the present invention are further described in the following specification and appended claims.

[0170] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of conflict, the present patent specification, including definitions, will control. As used herein, the indefinite articles "a" and "an" mean "at least one" or "one or more," unless the context clearly dictates otherwise.

[0171] The following embodiments and aspects thereof are described and illustrated in connection with systems, tools, and methods, which are intended for purposes of illustration and description, not limitation. In various embodiments, one or more of the above-mentioned problems are mitigated or resolved, while other embodiments are directed to other advantages or improvements. [Brief explanation of the drawings]

[0172] Some embodiments of the present invention will be described herein with reference to the accompanying drawings. This description, together with the drawings, will make clear to those skilled in the art how some embodiments may be implemented. The drawings are for illustrative purposes and do not attempt to show structural details of the embodiments in more detail than is necessary for a fundamental understanding of the present invention. For purposes of clarity, some objects shown in the drawings are not drawn to scale. In the drawings:

[0173] [Figure 1] FIG. 1 illustrates a prosthetic valve, including its various components, according to some embodiments. [Figure 2A] 2A-2B show a prosthetic valve in a crimped state (FIG. 2A) and in an expanded state disposed on an inflated balloon (FIG. 2B), according to some embodiments. [Figure 2B] Same as above. [Figure 3A] 3A-3B show side and top views, respectively, of a prosthetic valve positioned at a target implantation site, according to some embodiments. [Figure 3B] Same as above. [Figure 4A] FIG. 4A illustrates a perspective view of a seal member in an unfolded, relaxed state, according to some embodiments. [Figure 4B] 4B and 4C illustrate cross-sectional views of a seal member in an expanded, relaxed state, according to some embodiments. [Figure 4C] Same as above. [Figure 4D] 4D-4F illustrate perspective views of various configurations of a sealing member in a cylindrically folded state, according to some embodiments. [Figure 4E] Same as above. [Figure 4F] Same as above. [Figure 5A] 5A-5C illustrate various configurations for a seal member mounted on a frame of a prosthetic valve, according to some embodiments. [Figure 5B]Same as above. [Figure 5C] Same as above. [Figure 6A] 6A-6B illustrate exemplary thermal forming process steps using thermoforming for the manufacture of a seal member in an unfolded state, according to some embodiments. [Figure 6B] Same as above. [Figure 6C] 6C-6D illustrate the thermal processing steps of a flat flexible sheet using placement on a mold, heating, and vacuum thermoforming to produce a seal member in an unfolded state, according to some embodiments. [Figure 6D] Same as above. [Figure 6E] FIG. 6E illustrates a step of thermal processing a flat flexible sheet using thermoforming, which involves applying force using a mold on two opposing sides, to produce a seal member in an unfolded state, according to some embodiments. [Figure 7A] FIG. 7A illustrates a flexible sheet in an unfolded, relaxed state, according to some embodiments. [Figure 7B] FIG. 7B illustrates the flexible sheet of FIG. 7A placed over a mold, causing the flexible sheet to flexibly change shape to form the shape of the mold, according to some embodiments. [Figure 7C] FIG. 7C illustrates a coating process for the reshaped flexible sheet of FIG. 7B, according to some embodiments. [Figure 8A] FIG. 8A illustrates a perspective view of a seal member in an unfolded, relaxed state, according to some embodiments. [Figure 8B] 8B and 8C illustrate cross-sectional views of a seal member in an expanded, relaxed state, according to some embodiments. [Figure 8C] Same as above. [Figure 8D] 8D-8F illustrate perspective views of various configurations for a seal member in a cylindrically folded state, according to some embodiments. [Figure 8E] Same as above. [Figure 8F] Same as above. [Figure 9A] 9A-9C illustrate various configurations for a seal member mounted on a frame of a prosthetic valve, according to some embodiments. [Figure 9B] Same as above. [Figure 9C] Same as above. [Figure 10A] 10A-10C illustrate extrusion-based processing steps for the manufacture of a seal member, according to some embodiments. [Figure 10B] Same as above. [Figure 10C] Same as above. [Figure 11A] 11A-11E illustrate processing steps utilizing multiple molded members for the manufacture of a seal member, according to some embodiments. [Figure 11B] Same as above. [Figure 11C] Same as above. [Figure 11D] Same as above. [Figure 11E] Same as above. [Figure 12A] FIG. 12A illustrates a perspective view of a seal member in an unfolded, relaxed state, according to some embodiments. [Figure 12B] 12B-12E illustrate various cross-sectional views of a seal member in an expanded, relaxed state, according to some embodiments. [Figure 12C] Same as above. [Figure 12D] Same as above. [Figure 12E] Same as above. [Figure 12F] FIG. 12F illustrates a perspective view of a seal member in an expanded, relaxed state including multiple apertures, according to some embodiments. [Figure 12G] FIG. 12G illustrates a cross section of the seal member of FIG. 12F, according to some embodiments. [Figure 12H] FIG. 12H illustrates a perspective view of a seal member in an unfolded, relaxed state including multiple flaps, according to some embodiments. [Figure 13A]13A-13C show perspective views of various configurations for a sealing member in a cylindrically folded state, according to some embodiments. [Figure 13B] Same as above. [Figure 13C] Same as above. [Figure 13D] FIG. 13D illustrates a perspective view of a folded seal member, according to some embodiments. [Figure 14A] 14A-14C illustrate various configurations for a sealing member mounted on a prosthetic valve, according to some embodiments. [Figure 14B] Same as above. [Figure 14C] Same as above. [Figure 14D] FIG. 14D illustrates a folded seal member mounted on the frame of a prosthetic valve, according to some embodiments. [Figure 15] FIG. 15 illustrates a configuration for a sealing member including multiple apertures mounted on a frame of a prosthetic valve, according to some embodiments. [Figure 16A] 16A-16E illustrate various stages in the processing steps for manufacturing a seal member utilizing multiple mandrels, according to some embodiments. [Figure 16B] Same as above. [Figure 16C] Same as above. [Figure 16D] Same as above. [Figure 16E] Same as above. [Figure 17A] 17A-17F illustrate various stages in the processing steps for manufacturing a seal member utilizing multiple mandrels including sharp tips, according to some embodiments. [Figure 17B] Same as above. [Figure 17C] Same as above. [Figure 17D] Same as above. [Figure 17E] Same as above. [Figure 17F] Same as above. [Figure 18A]18A-18D illustrate various stages in the processing steps for manufacturing a seal member utilizing multiple mandrels, according to some embodiments. [Figure 18B] Same as above. [Figure 18C] Same as above. [Figure 18D] Same as above. [Figure 19A] 19A-19D illustrate various stages in the processing steps for manufacturing a seal member utilizing multiple mandrels including sharp tips, according to some embodiments. [Figure 19B] Same as above. [Figure 19C] Same as above. [Figure 19D] Same as above. [Figure 20] FIG. 20 illustrates perspective views of various configurations for the seal member of the present invention during a folding transition from an unfolded state to a cylindrically folded state, according to some embodiments. [Figure 21A] 21A-21B show side and top views, respectively, of a prosthetic valve including various sealing members in particular configurations positioned at a target implantation site, according to some embodiments. [Figure 21B] Same as above. [Figure 22A] 22A-22B show side and top views, respectively, of a prosthetic valve including various sealing members in particular configurations positioned at a target implantation site, according to some embodiments. [Figure 22B] Same as above. [Figure 23A] 23A-23B show additional configurations for a single-prong sealing element mounted on the frame of a prosthetic valve in an expanded state (FIG. 23A) and a crimped state (FIG. 23B), according to some embodiments. [Figure 23B] Same as above. [Figure 24] FIG. 24 illustrates an additional configuration for a seal member including a single protrusion with multiple apertures, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0174] In the following description, various aspects of the present disclosure are described. For purposes of explanation, specific configurations and details are set forth to provide a thorough understanding of various aspects of the present disclosure. However, it will be apparent to those skilled in the art that the present disclosure may be practiced without the specific details presented herein. Furthermore, well-known features may be omitted or simplified so as not to obscure the present disclosure.

[0175] Throughout the drawing figures, different superscripts for the same reference number are used to indicate different embodiments of the same component. The disclosed device and system embodiments may include any combination of different embodiments of the same component. Specifically, any reference to a component without a superscript may refer to any alternative embodiment of the same component shown with a superscript. To avoid undue confusion due to a plethora of reference numbers and callouts on a particular drawing, some components may be introduced through one or more drawings and not explicitly identified in all subsequent drawings that include that component.

[0176] Reference is now made to Figures 1-3B. Figure 1 illustrates a prosthetic heart valve 100, including its various components, according to some embodiments. Figure 2A illustrates the prosthetic heart valve 100 in a crimped state, according to some embodiments, and Figure 2B illustrates the prosthetic heart valve 100 in an expanded state disposed on an inflated balloon. Figures 3A-3B illustrate a side view and a top view, respectively, of the prosthetic heart valve 100 positioned at a target implantation site, according to some embodiments.

[0177] The prosthetic heart valve 100 is deliverable to a target site of interest via a catheter 50 (e.g., as shown in FIGS. 2A-2B ) and is radially expandable and compressible between a radially compressed or crimped state (e.g., as shown in FIG. 2A ) and a radially expanded state (e.g., as shown in FIGS. 1 and 2B ). Those skilled in the art will appreciate that target sites of interest for implantation of the prosthetic heart valve include the native aortic, mitral, pulmonary, and tricuspid valves of interest. The term “prosthetic valve,” as used herein, refers to any type of prosthetic valve that can be delivered to a target site of a patient via a catheter, and that is radially expandable and compressible between a radially compressed or crimped state and a radially expanded state.

[0178] The expanded state may include a range of diameters to which the valve 100 may expand between the compressed state and the maximum diameter reached at the fully expanded state. Thus, multiple partial expanded states may relate to any expanded diameter between the radially compressed or crimped state and the maximum expanded state. Thus, it will be understood that when the term "expanded state" is used herein, it refers to both the maximum expanded state and the partially expanded state. The prosthetic valve 100 of the present disclosure may include any prosthetic valve configured to be installed within a human subject's native aortic valve, native mitral valve, native pulmonary valve, and native tricuspid valve.

[0179] As used herein, the terms "compressed" and "crimped" are interchangeable and refer to the condition of the valve 100 as shown in FIG. 2A.

[0180] The term "plurality," as used herein, means two or more.

[0181] As described above, the prosthetic heart valve 100 can be delivered to an implantation site via a delivery assembly that carries the valve 100 toward the target site in a radially compressed or crimped state by expanding the valve 100 via various expansion mechanisms, and can be attached to the native anatomy. FIG. 1 shows an example of a balloon-expandable prosthetic valve 100. The process for implanting a balloon-expandable prosthetic valve generally involves inflating a balloon within the prosthetic valve, thereby expanding the prosthetic valve 100 within the desired implantation site. After the valve has been sufficiently expanded, the balloon is deflated and retrieved along with the delivery assembly.

[0182] Other types of valves may include other expansion mechanisms, such as mechanical expansion mechanisms or self-expanding mechanisms (not shown). Mechanically expandable valves are a category of prosthetic valves that rely on a mechanical drive mechanism for expansion. The mechanical drive mechanism typically includes multiple expansion and locking assemblies that are detachably coupled to respective drive assemblies of the delivery device and controlled via a handle for driving the drive assemblies to expand the prosthetic valve to a desired diameter. The expansion and locking assemblies may optionally lock the position of the valve to prevent undesired recompression after the prosthetic valve is properly positioned at the desired implantation site, and may be decoupled from the expansion and locking assemblies to allow retrieval of the delivery device.

[0183] A self-expanding valve includes a frame that is shaped to automatically expand as soon as an outer retaining structure, such as a capsule or a portion of a shaft, is pulled proximally relative to the prosthetic valve.

[0184] The prosthetic valve 100 may include an inflow end 104 and an outflow end 102. The prosthetic valve 100 may define a centerline 111 extending through the inflow end 104 and the outflow end 102. In some instances, the outflow end 102 is the distal end of the prosthetic valve 100, and the inflow end 104 is the proximal end of the prosthetic valve 100. Alternatively, the outflow end may be the proximal end of the prosthetic valve, and the inflow end may be the distal end of the prosthetic valve, depending, for example, on the valve delivery technique.

[0185] The term "proximal," as used herein, generally refers to a location, orientation, or portion of any device or of any device component that is closer to the user (e.g., a healthcare professional) and farther from the implantation site.

[0186] The term "distal," as used herein, generally refers to a location, orientation, or portion of any device or of any device component that is farther from the user (e.g., a healthcare professional) and closer to the implantation site.

[0187] The term "outflow," as used herein, refers to the area of ​​the prosthetic valve where blood flows through and out of the valve 100.

[0188] The term "inflow," as used herein, refers to the area of ​​the prosthetic valve where blood flows into the valve 100.

[0189] Thus, it will be appreciated that when the prosthetic heart valve 100 is implanted into a target implantation site, blood flows through the prosthetic heart valve 100 from the inflow end 104, where blood flows into the valve 100, toward the outflow end 102, where blood flows out of the valve 100.

[0190] Valve 100 includes an annular frame 106 movable between a radially compressed state and a radially expanded state, and a leaflet assembly 130 mounted within frame 106 .

[0191] The frame 106 can be formed from a variety of suitable materials, including, but not limited to, plastically deformable materials such as stainless steel, nickel-based alloys (e.g., cobalt-chromium alloys or nickel-cobalt-chromium alloys such as MP35N alloy), polymers, or combinations thereof. When constructed from a plastically deformable material, the frame 106 can be crimped into a radially compressed state onto a delivery shaft 50 (e.g., catheter 50) using, for example, a crimping device (not shown), and then expanded inside the patient by an inflatable balloon 52 (see FIGS. 2A-B) or equivalent expansion mechanism. Alternatively or additionally, the frame 106 can be formed from a shape memory material, such as, but not limited to, a nickel-titanium alloy (e.g., Nitinol). When constructed from a shape memory material, the frame 106 can be crimped into a radially compressed state and constrained in the compressed state by insertion into the shaft 50 or equivalent mechanism of a delivery device (not shown), as in the case of a self-expanding valve.

[0192] In the embodiment shown in FIG. 1 , the frame 106 is an annular, stent-like structure including a plurality of intersecting struts 110. The frame 106 can have one or more rows of openings or cells 108 defined by the intersecting struts, such as the angled struts 110 shown in FIG. 1 . The struts 110 can intersect at a junction 112; for example, the struts 110 can intersect at an upper junction that defines an outflow apex 114. The frame 106 can have a cylindrical or substantially cylindrical shape with a constant diameter from the inflow end 104 to the outflow end 102 of the frame, as shown, or the frame can have a varying diameter along its height, as disclosed in U.S. Pat. No. 9,155,619, incorporated herein by reference.

[0193] The struts 110 may be pivotable or bendable relative to one another to allow the frame to expand or contract. In some implementations, the frame 106 may be formed from a single piece of material, such as a metal tube, through various processes, including, but not limited to, laser cutting, electroforming, and / or physical vapor deposition, while retaining the ability to radially contract / expand.

[0194] The leaflet assembly 130 includes a plurality of leaflets 132 (e.g., three leaflets) positioned at least partially within the frame 106 and configured to regulate blood flow through the prosthetic valve 100 from the inflow end 104 to the outflow end 102. While the embodiment shown in FIG. 1 illustrates three leaflets 132 configured to fold in a tricuspid arrangement, it will be apparent that the prosthetic valve 100 may include any other number of leaflets 132. The lower edge 134 of the leaflet assembly 130 preferably has an undulating, curved, wavy shape. Forming the leaflets with such a wavy geometry reduces stress on the leaflets 130, thereby improving the durability of the valve 100. The wavy geometry also reduces the amount of tissue material used to form the leaflet assembly 130, thereby allowing for a smaller and more uniform crimp profile at the inflow end of the valve.

[0195] In the context of the prosthetic aortic valve 100 disclosed herein, the terms "inferior" and "upper" are used interchangeably with the terms "inflow" and "outflow," respectively, for convenience.

[0196] The valve leaflets 132 are formed from a flexible material derived from a biological material (e.g., bovine pericardium or pericardium from other sources), a biocompatible synthetic material, or other suitable material known in the art, for example, as described in U.S. Pat. Nos. 6,730,118, 6,767,362, and 6,908,481, which are incorporated herein by reference.

[0197] Each leaflet 132 may be coupled to the frame 106 along its inflow edge (the lower edge of the leaflet, also referred to as the "cusp edge") and / or at a joint 140 where adjacent portions of two leaflets 130 of the leaflet assembly 130 are connected to one another.

[0198] According to some embodiments, the prosthetic valve 100 further includes a sealing member 122 that may be mounted on an exterior surface of the frame 106. According to some embodiments, the sealing member 122 is configured to function, for example, as a sealing member retained between the frame 106 and the surrounding tissue of the native annulus to which the prosthetic valve 100 is attached. Advantageously, such incorporation of the sealing member 122 reduces the risk of paravalvular leakage (PVL) through the prosthetic valve 100. The sealing member 122 may be connected to the frame 106 using any suitable technique or mechanism. For example, the sealing member 122 may be sutured to the frame 106 utilizing sutures that may extend around the struts 110. Accordingly, sealing members such as the sealing member 122 are conventionally referred to as PVL skirts.

[0199] In some implementations, the inflow or pointed edges 134 of the leaflets 132 can be secured to the frame 106 using one or more connecting skirts 124. Each connecting skirt 124 can include a long, generally rectangular strip, which can have slits (not shown) formed therein to partially separate different portions thereof, and can be formed from a suitable synthetic material (e.g., PET) or natural tissue. The pointed edges 134 can be attached to the connecting skirts 124, which are secured to the frame 106 along a diagonal line extending along the curved surface of the frame 106 defined by a row of struts 110 extending diagonally from the inflow end 104 to the outflow end 102 of the frame. In alternative embodiments, the pointed edges 134 can be directly coupled to the struts 110 of the frame 106, for example, using a series of suture stitches, or can be directly coupled to other types of connecting members, such as an inner skirt, attached to the inner surface of the frame. Further examples and methods of attaching the seal member to the frame, as well as methods and techniques for coupling the valve leaflets 132 to the frame 106 with or without a connecting skirt, are disclosed in U.S. Patent Application Publication No. 2018 / 0028310, which is incorporated herein by reference.

[0200] Each leaflet 132 typically includes an oppositely located tab 136. Each tab 136 can be secured to an adjacent tab 136 of an adjacent leaflet 132, thereby forming a joint 140 that is secured to the frame 106.

[0201] During valve cycling, the leaflets 132 can articulate at the innermost edge of the tab layer, which helps move the leaflets away from the frame 106 during normal operation of the prosthetic valve. This can be advantageous if the prosthetic valve 100 is not fully expanded to its maximum nominal size when implanted into a patient, allowing the prosthetic valve 100 to be implanted into a wider range of patient annular sizes.

[0202] According to some embodiments, the prosthetic valve 100 further includes a plurality of support members 142, which may be formed from a relatively flexible and soft material, including a synthetic material (e.g., woven PET fabric) or natural tissue (e.g., bovine pericardium), attached to the struts 110 of the cells 108. The number of support members 142 may match the number of joints 140, where each joint 140 may be attached to the frame 106 by a plurality of sutures.

[0203] Each support member 142 can be sewn to a strut 110 that defines a cell 108. In some embodiments, each support member 142 is attached (e.g., sewn) to a respective strut of a set of struts 110 that form a cell 108 of the frame 106. In the embodiment shown in Figures 1 and 3A, for example, a support member 142 can be sewn to each strut of the cell 108, which includes four struts 110.

[0204] The joints 140 can be formed by folding the tabs 136 and then sewing them to each other and / or to additional components, such as reinforcement members, fabric, or the like, associated with the joints, according to various configurations disclosed in U.S. Patent Application Publication No. 2018 / 0028310, which is incorporated herein by reference. The joints 140 can then be attached to the respective support members 142, for example, by sewing them to the support members 142.

[0205] 2A-2B illustrate the transitions between states that a prosthetic valve 100 conventionally passes through before and / or during deployment into an implantation site. The prosthetic valve 100 may be assembled in a radially expanded state, as shown in FIG. 1. Prior to insertion into a patient's body, the prosthetic valve 100 can be crimped into a compressed configuration using a crimping device (not shown), and then stored in this compressed configuration until utilized for implantation into the patient's body. During the implantation procedure, the prosthetic valve 100 can be advanced through the patient's vasculature in the crimped or compressed state, as shown in FIG. 2A.

[0206] After the valve 100 is positioned at the target implantation site (e.g., the aortic annulus in the case of an aortic valve replacement), the balloon 52 can be inflated, expanding the valve 100 to its expanded state, as shown in Figures 2B, 3A, and 3B, thereby attaching the valve to surrounding tissue, such as the annular or arterial wall 105. After the valve is fully expanded, the balloon can be deflated and removed from within the patient's body, leaving the prosthetic valve in place.

[0207] In some cases, after the balloon 52 is deflated so that it no longer exerts an expansive force against the frame 106, the prosthetic valve 100 can contract radially inward to an expanded diameter slightly smaller than that defined by the inflated balloon 52. The contraction is preferably in the range of less than 5% compared to the diameter of the valve when expanded on the inflated balloon 52.

[0208] The leaflet assembly 130 constantly transitions between an open state (not shown) during systole and a closed state during diastole, as shown in FIG. 3B . The leaflets 132 define a non-planar coaptation surface (not shown) when their coaptation edges 138 coapt together to seal against blood flow through the prosthetic valve 100 in the closed state shown in FIG. 3B . Specifically, during diastole, the leaflets 132 fold radially inward to effectively seal against blood flow through the prosthetic valve 100 and, optionally, define a non-planar coaptation surface (not shown) when their coaptation edges 138 move toward each other. This folding exerts a radially inward pulling force on the coaptation regions 140. During diastole, after the pulling force on the leaflets 132 is released, the coaptation regions 140 resiliently return (radially outward) to their free-state position.

[0209] 3A-3B, the outer circumferential surface of the prosthetic valve 100 is shown to discontinuously engage the inner circumferential surface of the arterial wall 105, as indicated by gaps 107 (or voids or flow channels), which may result in a lack of a proper seal between the outer circumferential surface of the prosthetic valve and the inner circumferential surface of the arterial wall. These gaps 107 form because the outer surface of the frame 106 of the prosthetic heart valve 100 is typically circular, while the inner surface of the arterial wall 105 may have an irregular surface shape, and therefore, paravalvular leakage (PVL) may occur around the valve 100.

[0210] Paravalvular leak (PVL) is a complication associated with the implantation of prosthetic heart valves. It can occur when blood flows through a channel or gap between the expanded structure of the implanted prosthetic heart valve and the implantation site (e.g., surrounding cardiac or arterial tissue) without an adequate seal. PVL has previously been shown to significantly impact clinical outcomes in transcatheter aortic valve implantation, and the severity of PVL correlates with patient mortality.

[0211] To address this issue, adaptive sealing elements can be provided around the outer periphery of the prosthetic heart valve to improve sealing, as previously disclosed, for example, in U.S. Patent No. 10,722,316, which is incorporated herein by reference. Typically, these sealing components (also known as external skirts, or PVL skirts) can be configured to improve PVL sealing around the implanted prosthetic heart valve. In addition, some PVL skirts have been designed to promote tissue ingrowth (e.g., utilizing textured yarns on the outer surface of the skirt).

[0212] In some cases, valve explantation is required, in which a previously implanted valve is surgically removed from the patient's body. However, explantation of conventional implantable prosthetic heart valves can be a delicate and difficult procedure that can involve significant risks to the patient, as neointimal tissue may form between the sealing components and the surrounding anatomical structures, preventing removal of the valve from the implantation site without surgically cutting the surrounding tissue.

[0213] Advantageously, the present invention novelly discloses sealing elements (or PVL skirts) having three-dimensional (3D) shapes configured to enable a conformal fit or engagement between the prosthetic heart valve into which they are incorporated and the inner surface of the annular or arterial wall 105 at the implantation site, thereby improving the PVL seal around the implanted prosthetic heart valve. Moreover, the sealing elements of the present invention can be configured to prevent and / or reduce tissue ingrowth around the prosthetic heart valve, thereby allowing for easier and safer extraction of the prosthetic heart valve from surrounding tissue when needed. Advantageously, minimizing tissue ingrowth reduces the risks associated with complex surgical procedures required when ingrowth tissue connects the implant and anatomical structures.

[0214] A sealing member including a first tear-resistant layer and a second cushioning layer attached thereto and extending radially outward therefrom has been previously disclosed, for example, in U.S. Patent Application Publication No. 2019 / 0374337, which is incorporated herein by reference. U.S. Patent Application Publication No. 2019 / 0374337 discloses a second layer including pile strands or yarns woven or knitted into loops attached to the first layer. Such strands or yarns may be spaced apart in a manner that can promote tissue ingrowth. Thus, in applications where tissue ingrowth is to be avoided, it may be preferable to form the second layer from a continuous material that does not have spaced apart strands or yarns. However, forming the desired elastic 3D continuous layer different from such strands or yarns may prove difficult because it requires significant modifications to the manufacturing procedure to form such a layer in a manner that adheres to (or covers) the first layer. This specification provides several manufacturing procedures that can address these challenges, and the seal members resulting from such procedures.

[0215] Thus, according to certain aspects, the present invention provides a prosthetic heart valve 100 comprising a frame 106 and a leaflet assembly 130 mounted within the frame, the frame including a plurality of intersecting struts 110, the frame being movable between a radially compressed state and a radially expanded state as disclosed hereinabove, the valve 100 further comprising a sealing member 222 coupled to an outer surface of the frame 106, the sealing member 222 having a three-dimensional (3D) shape in its expanded, relaxed state.

[0216] The terms coupled, engaged, connected, and attached are interchangeable when used herein.

[0217] According to certain embodiments, the present invention provides a prosthetic heart valve 100 including a frame 106 and a leaflet assembly 130 mounted within the frame, the frame including a plurality of intersecting struts 110, the frame being movable between a radially compressed state and a radially expanded state as disclosed hereinabove, the valve 100 further including a sealing member 222 coupled to an outer surface of the frame 106, the sealing member 222 having a resilient three-dimensional (3D) shape in its expanded, relaxed state.

[0218] According to some embodiments, a prosthetic heart valve 100 is provided that includes a frame 106 and a leaflet assembly 130 mounted within the frame, the frame including a plurality of intersecting struts 110, the frame being movable between a radially compressed state and a radially expanded state, the valve 100 further including a seal member 222 bonded to an outer surface of the frame 106, the seal member 222 being formed by a process that includes at least one thermal shaping step.

[0219] The term "shape forming" refers to a process, procedure, or step in which an object forms a different shape compared to its original shape prior to shaping. Shape forming, as it relates to the processes and products of the present invention, is a process of forming a two-dimensional object into a three-dimensional object. The 3D shape is formed to elastically maintain its shape in the absence of applied heat or physical pressure (e.g., in a continuous shape forming process).

[0220] Thus, the term "thermal shaping" refers to a process, procedure, or step that assists in shaping an object to be shaped by heating the object to a temperature above ambient temperature. It is understood that thermal shaping processes and steps according to the present invention are shaping processes and steps that would be impossible or difficult to achieve at room temperature. Each possibility represents a separate embodiment. The 3D shape is formed to elastically maintain its shape in the absence of applied heat and physical pressure (e.g., in a continuous shaping process).

[0221] It will be appreciated that simply coating an object with a coating material does not, according to some embodiments, be considered shape forming unless steps are taken to shape the shape of the coated object during coating. In other words, a coating process in which the coated object has substantially the same shape before and after coating is not considered shape forming, according to some embodiments.

[0222] The term "unfolded," as used herein, refers to the state of a substantially flat, foldable sheet. For a rectangular object having four edges (e.g., a typical PVL skirt, according to some embodiments), an object is considered to be in the unfolded state when two opposing edges are separated from each other. For example, Figure 4A shows seal member 222 in the unfolded state.

[0223] Conversely, the term "folded," as used herein with respect to a PVL skirt, refers to the skirt's substantially cylindrical three-dimensional shape, and optionally, its state when coupled to an object (e.g., the frame of a prosthetic heart valve). For example, Figure 5A shows the sealing member (or PVL skirt) 222 in a folded state surrounding the prosthetic heart valve 100, and Figure 4D shows the sealing member 222 in a folded state separated from the heart valve.

[0224] It will be appreciated that a typical PVL skirt may be transformed from an unfolded state to a folded state by connecting, joining or attaching two opposing edges of the skirt.

[0225] The term "relaxed," as used herein, refers to a state of matter such that no physical force or pressure is being applied substantially.

[0226] The term "splayed relaxed state," as used herein, refers to a state of a material (e.g., seal member 222) that is both substantially relaxed and expanded, as disclosed herein above. According to some embodiments, in the relaxed state, a seal member (e.g., seal member 222) of the present invention has two opposing edges that are substantially spaced apart from one another, with substantially no applied physical force or pressure.

[0227] Reference is now made to Figures 4A-5C. Figure 4A illustrates a perspective view of a seal member 222, according to some embodiments. Figures 4B and 4C illustrate cross-sectional views of a seal member 222, according to some embodiments. Figures 4D-4F illustrate perspective views of various configurations of a seal member 222 in a cylindrically folded state, according to some embodiments. Figures 5A-5C illustrate various configurations of a seal member 222 mounted on a frame 106 of a prosthetic valve 100, according to some embodiments.

[0228] According to certain embodiments, a seal member 222 is provided that is configured to be mounted on (or coupled to) an outer surface of a frame 106 of a prosthetic valve 100 (see, e.g., FIGS. 5A-5C ), or of any other similar prosthetic valve known in the art. The seal member 222 can be connected / attached to the frame 106 using any suitable technique or mechanism. For example, the seal member 222 can be sutured to the frame 106 utilizing sutures that can extend around the struts 110. The seal member 222 can be provided in an unfolded state and can be connected / attached to the frame 106 by folding it onto the frame 106, thereby transforming the seal member 222 from the unfolded state to the folded state. Alternatively, the seal member 222 can be provided in an already folded state prior to attachment to the frame 106. For example, the frame 106 can be inserted into the seal member 222 that has already been folded into a cylindrical shape and sutured to such seal member. The seal member 222 can be configured to lie against the outer surface of the frame 106 when the prosthetic valve 100 is in a radially expanded state, as shown, and to fit snugly against the frame 106.

[0229] According to some embodiments, the seal member 222 has a 3D shape in its unfolded, relaxed state, as can be seen, for example, in Figures 4A-4C. According to some embodiments, the seal member 222 has an essentially 3D shape in its cylindrically folded state (Figures 4D-4F and Figures 5A-5C).

[0230] According to some embodiments, seal member 222 has a 3D elastic structure such that non-fibrous outer surface 280 of seal member 222 exhibits a plurality of raised portions 230 having peaks 205 and a plurality of non-ridged portions 250. In further embodiments, each of the plurality of non-ridged portions 250 is defined by an adjacent pair of the plurality of raised portions 230. In further embodiments, non-fibrous outer surface 280 is a smooth surface. In further embodiments, non-fibrous outer surface 280 is a single / continuous surface.

[0231] In some embodiments, raised portions 230 are ridges 230 and non-raised portions 250 are inter-ridge gaps 250. As used herein, the terms "raised portions 230" and "ridges 230" are interchangeable and refer to the same plurality of raised portions of seal member 222, as shown in Figures 4B-4C. As used herein, the terms "non-raised portions 250" and "inter-ridge gaps 250" are interchangeable and refer to the same plurality of non-raised portions of seal member 222, as shown in Figures 4B-4C.

[0232] 4A, for example, seal member 222 includes ridges 230 that give it a three-dimensional shape, as opposed to the substantially flat, two-dimensional (2D) shape it would assume in the absence of such ridges 230. Thus, it will be understood that the three-dimensional shape of three-dimensional (3D) seal member 222 includes (i) a spatial length dimension extending between outflow edge 207 and inflow edge 209 of seal member 222 (see FIGS. 4B and 4C), (ii) a spatial length dimension extending between first lateral edge 206 and second lateral edge 208 of seal member 222, and (iii) a spatial length dimension defined by ridge height (or thickness) 222RH of seal member ridges 230 (see FIG. 4C). It will further be appreciated that the 3D structure of the seal member 222 is due to the ridge height 222RH of the ridge 230, and that this ridge height 222RH is greater than the thickness of the flat 2D structure before the ridge 230 is formed on the upper surface by at least 1000%, preferably at least 2000%.

[0233] The terms "including" and / or "having", as used herein, are defined as comprising (i.e., open language).

[0234] According to some embodiments, seal member 222 includes a plurality of protrusions or ridges 230 extending spaced apart from first surface 202 of seal member 222. According to some embodiments, protrusions or ridges 230 are spaced apart from one another along first surface 202 of seal member 222. The plurality of ridges 230, according to some embodiments, define the 3D shape of seal member 222 when in an expanded, relaxed state (as can be seen in FIGS. 4A-4C).

[0235] According to some embodiments, the seal member 222 has four edges. According to some embodiments, the seal member 222 has four vertices. According to some embodiments, each of the four vertices of the seal member 222 is substantially at a right angle. The phrase "substantially at a right angle" refers to an angle in the range of 80° to 100°.

[0236] According to some embodiments, the seal member 222 has four substantially right-angled vertices and two sets of opposing edges (a first lateral edge 206 and a second lateral edge 208, and an outflow edge 207 and an inflow edge 209), where the opposing edges in each set are substantially parallel. According to some embodiments, the seal member 222 extends from the first lateral edge 206 to the second lateral edge 208 when the seal member 222 is in the unfolded state. According to some embodiments, the seal member 222 extends around the seal member centerline 211 when the seal member 222 is in the folded state. According to some embodiments, the seal member centerline 211 and the centerline 111 of the valve 100 are coaxial and may coincide when the seal member 222 is connected to the heart valve 100. According to some embodiments, the seal member 222 extends from the inflow edge 209 to the outflow edge 207. According to some embodiments, the seal member 222 extends from the inflow edge 209 toward the outflow edge 207 in both the folded and unfolded positions.

[0237] According to some embodiments, in the unfolded state, the seal member 222 is substantially rectangular. According to some embodiments, the distance between the first lateral edge 206 and the second lateral edge 208 is greater than the distance from the inflow edge 209 to the outflow edge 207.

[0238] According to some embodiments, the plurality of ridges 230 extend radially outwardly away from the centerline 211 of the seal member 222 in the collapsed state (see FIGS. 4D-4F). According to some embodiments, the plurality of ridges 230 extend radially outwardly (outwardly relative to the centerline 111) from the frame 106 of the valve 100 when the seal member 222 is mounted on the frame 106 (see FIGS. 5A-5C). According to some embodiments, the seal member 222 is collapsed by connecting the first lateral edge 206 and the second lateral edge 208 such that the plurality of ridges 230 are oriented radially away from the centerline 211 of the seal member (see, for example, FIG. 4D). According to some embodiments, the folded seal member 222 is bonded to the outer surface of the frame 106 of the prosthetic valve 100 such that the plurality of ridges 230 are oriented to extend radially away from the centerline 111.

[0239] In some embodiments, seal member 222 includes a plurality of interior channels 240, each channel 240 formed in second surface 204 of seal member 222. In further embodiments, the plurality of channels 240 correspond to a plurality of ridges 230, each ridge 230 including a corresponding channel 240 on the opposing surface of seal member 222. In further embodiments, the number of channels 240 is the same as the number of ridges 230, each of the plurality of channels 240 formed by a respective one of the plurality of ridges 230 on the opposing surface of seal member 222.

[0240] According to some embodiments, each of the plurality of channels 240 faces the centerline 211 of the seal member 222 in the collapsed state (see FIGS. 4A-4C). According to some embodiments, each of the plurality of channels 240 faces inward in the collapsed state of the seal member 222 (see FIGS. 4A-4C).

[0241] In the context of a sealing member of the present invention, such as sealing member 222, the term "inward" will be understood to refer to a radial direction from the face of the sealing member toward its centerline (e.g., sealing member centerline 211), while the term "outward" will refer to the opposite radial direction. According to some embodiments, the term "outward" refers to a direction toward the surrounding tissue of the native annulus to which prosthetic valve 100 is configured to attach.

[0242] According to some embodiments, each of the plurality of channels 240 faces toward the centerline 111 of the valve 100 when the seal member 222 is mounted on the frame 106 (see FIGS. 5A-5C). According to some embodiments, the seal member 222 is folded by connecting the first lateral edge 206 and the second lateral edge 208 with the plurality of channels 240 facing inward. According to some embodiments, the seal member 222 is folded by connecting the first lateral edge 206 and the second lateral edge 208 with the plurality of channels 240 facing toward the centerline 211 of the seal member.

[0243] According to some embodiments, a plurality of inter-ridge gaps 250 are formed on the surface of the first layer 210 between two adjacent ridges 230 of the seal member 222. According to further embodiments, one inter-ridge gap 250 is formed between the outflow edge 207 and one ridge 230, while another inter-ridge gap 250 is formed between the inflow edge 209 and another ridge 230. It will be appreciated that, according to some embodiments, the inter-ridge gaps 250 are spaces formed based on the three-dimensional shape of the seal member 222. Specifically, according to some embodiments, the plurality of inter-ridge gaps 250 face in the same direction as the ridges 230. According to some embodiments, each of the inter-ridge gaps 250 faces outward from the folded seal member 222.

[0244] According to some embodiments, the prosthetic heart valve 100 including the sealing member 222 is configured to be positioned (i.e., implanted) at a target implantation site (e.g., the aortic annulus in the case of an aortic valve replacement) so as to form contact between the arterial wall 105 and the plurality of ridges 230. Advantageously, the plurality of ridges 230 of the sealing member 222 are configured to contact the arterial wall 105 after expansion of the prosthetic heart valve 100 at the implantation site, thereby enabling a snug fit or engagement between the prosthetic heart valve 100 and the inner surface of the arterial wall 105, thereby improving the PVL seal around the implanted prosthetic heart valve.

[0245] According to some embodiments, the seal member 222 is configured to transition from an unfolded, relaxed state to a cylindrically folded state based on its elastic and / or flexible properties to form a cylindrically folded PVL skirt. The folded PVL skirt 222 may be adapted to be bonded to an outer surface of the frame 106 of the prosthetic valve 100, for example, during a valve assembly procedure. Alternatively, the unfolded seal member 222 may be folded around the outer surface of the frame 106 and bonded to such an outer surface to provide a similar product.

[0246] 4D-4F, the ridges 230 are shown following parallel path lines that extend in different directions. These may be perpendicular, horizontal, or diagonal relative to the centerline 211 of the cylindrically shaped seal member 222 in its collapsed state. It will be appreciated that the orientation of the ridges 230 in the collapsed state of the seal member 222 may be determined by the configuration of the ridges prior to folding, i.e., when the seal member 222 is in its unfolded state. For example, a seal member 222 (as shown in FIG. 4A) having ridges 230 following parallel path lines that extend from the first lateral edge 206 to the second lateral edge 208 may be folded by connecting the first lateral edge 206 to the second lateral edge 208 to form the cylindrical shape of the seal member 222. In this exemplary situation, when folded as described above, the seal member 222 in its folded configuration has a plurality of circumferentially extending ridges 230 that are substantially parallel to the inflow edge 209 and the outflow edge 207 (as shown in FIG. 4D ). In a second embodiment, the seal member 222 (unfolded, relaxed state not specifically shown) having a plurality of ridges 230 that follow parallel path lines extending from the inflow edge 209 to the outflow edge 207 may be folded by connecting the first lateral edge 206 to the second lateral edge 208 such that a cylindrical shape of the seal member 222 is formed. In this second exemplary configuration, when folded as described above, the seal member 222 in its folded configuration has a plurality of vertically oriented ridges 230 that are substantially perpendicular to the inflow edge 209 and the outflow edge 207 (as shown in FIG. 4E ). Similarly, angled or diagonal ridges in the unfolded state will result in diagonally oriented ridges 230 in the folded state of seal member 222, as shown in Figure 4F.

[0247] As described in detail herein, the shaping process for forming the ridges 230 on the seal member 222 is not limited to being performed before folding, and according to some embodiments, the ridges 230 may be formed on the first surface 202 of the seal member 222 after folding. In such cases, the orientation of the path lines of the ridges 230 is simple. Furthermore, the ridges of the seal member 222 according to the present invention need not form path lines that are parallel to one another.

[0248] According to some embodiments, each of the plurality of ridges 230 follows a path line that extends from the first lateral edge 206 to the second lateral edge 208 in the unfolded state of the seal member 222. According to some embodiments, each of the plurality of ridges 230 follows a path line that is perpendicular to either the first lateral edge 206 and / or the second lateral edge 208 in the unfolded state of the seal member 222. According to some embodiments, each of the plurality of ridges 230 follows a path line that is parallel to either the outflow edge 207 and / or the inflow edge 209 in the unfolded state of the seal member 222.

[0249] According to some embodiments, each of the plurality of ridges 230 follows a path line that extends circumferentially about the centerline 211 of the seal member 222 when the seal member is in the folded state. According to some embodiments, each of the plurality of ridges 230 follows a path line that extends circumferentially about the centerline 211 of the seal member when the seal member is in the folded state and mounted on the frame 106 of the prosthetic heart valve 100. According to some embodiments, each of the plurality of ridges 230 follows a path line that extends circumferentially about the centerline 211 of the seal member and that is parallel to either the outflow edge 207 and / or the inflow edge 209 when the seal member is in the folded state (see FIG. 4D ).

[0250] According to some embodiments, each of the plurality of ridges 230 follows a path line that extends from the inflow edge 209 to the outflow edge 207 in the unfolded state of the seal member 222. According to some embodiments, each of the plurality of ridges 230 follows a path line that is parallel to one of the first lateral edge 206 and / or the second lateral edge 208 in the unfolded state of the seal member 222. According to some embodiments, each of the plurality of ridges 230 follows a path line that is perpendicular to one of the outflow edge 207 and / or the inflow edge 209 in the unfolded state of the seal member 222.

[0251] According to some embodiments, each of the plurality of ridges 230 follows a path line that extends parallel to the centerline 211 of the seal member in the collapsed state of the seal member 222. According to some embodiments, each of the plurality of ridges 230 follows a path line that extends parallel to the centerline 111 when the seal member 222 is collapsed and mounted on the frame 106 of the prosthetic heart valve 100. According to some embodiments, each of the plurality of ridges 230 follows a path line that is perpendicular to either the outflow edge 207 and / or the inflow edge 209 in the collapsed state of the seal member 222 (see FIG. 4E ).

[0252] According to some embodiments, each of the plurality of ridges 230, in its unfolded state, follows a path line that extends diagonally along the surface of the seal member 222. According to some embodiments, each of the plurality of ridges 230, in its folded state, follows a path line that extends diagonally along the surface of the seal member 222. According to some embodiments, each of the plurality of ridges 230 follows a path line that extends diagonally relative to the centerline 111 when the seal member 222 is in its folded state and mounted on the frame 106 of the prosthetic heart valve 100 (see FIG. 4F ).

[0253] The various configurations and orientations described above may be advantageous with respect to different physiological and implantation-related requirements. For example, the configurations of Figures 4D and 5A may be advantageous due to the generally perpendicular orientation of the ridges 230 relative to the axial direction of flow when the valve 100 is attached to the annular or arterial wall 105, potentially improving the PVL seal therebetween.

[0254] According to some embodiments, the seal member 222 includes a first layer 210. According to some embodiments, the seal member 222 includes a first layer 210 and a second layer 220. According to further embodiments, the first layer 210 and the second layer 220 are each disposed outwardly relative to the outer surface of the frame 106 when the seal member 222 is coupled to the outer surface of the frame 106. According to further embodiments, the seal member 222 can include additional layers, as described in more detail herein.

[0255] According to some embodiments, the second layer 220 contacts the first surface 215 of the first layer 210. According to some embodiments, the second layer 220 contacts the first surface 215 of the first layer 210 when the sealing member 222 is in both the unfolded and folded states. According to some embodiments, the second layer 220 is attached to and / or covers the first surface 215 of the first layer 210. According to some embodiments, the first surface 215 of the first layer 210 faces outward when the sealing member 222 is in the folded state. According to some embodiments, the first surface 215 faces toward the implantation site (e.g., the annular wall or the arterial wall 105) when the sealing member 222 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site. According to further embodiments, the second layer 220 defines the first surface 202 of the sealing member 222, as shown in FIG. 4B . According to some embodiments, the first surface 202 of the seal member 222 faces outward when the seal member 222 is in a folded state. According to some embodiments, the first surface 202 of the seal member 222 faces toward the implantation site when the seal member 222 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site.

[0256] Without wishing to be bound by any theory or mechanism of action, the various seal members 222 disclosed herein form three-dimensional shapes that may be the result of a thermal shaping procedure. Such procedures are made possible or facilitated by the use of high-temperature moldable thermoplastic materials, as described in detail herein. To enable the thermoplastic material to be molded or shaped into a desired structure using a thin sheet of object, it is advantageous for the thermoplastic material to comprise or cover the object. This may be achieved, for example, by using a thermoplastic coating layer to coat the object or by using a thermoplastic layer to form the object. While a single thermoplastic layer may be sufficient to enable the shape-forming process, in some embodiments, it may be advantageous to include multiple thermoplastic layers, such as two layers. Specifically, it may be advantageous to configure the seal member 222 so that two outer layers comprise a thermoplastic material.

[0257] According to some embodiments, the seal member 222 includes a third layer 225 .

[0258] According to some embodiments, the third layer 225 contacts the second surface 216 of the first layer 210. According to some embodiments, the third layer 225 contacts the second surface 216 of the first layer 210 when the sealing member 222 is in both the unfolded and folded states. According to some embodiments, the third layer 225 is attached to and / or covers the second surface 216 of the first layer 210. According to some embodiments, the second surface 216 of the first layer 210 faces inward when the sealing member 222 is in the folded state. According to some embodiments, the second surface 216 faces away from the implantation site (e.g., the arterial wall 105) when the sealing member 222 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site. According to further embodiments, the third layer 225 defines the second surface 204 of the sealing member 222, as shown in FIG. 4C . According to some embodiments, the second surface 204 of the seal member 222 faces inward when the seal member 222 is in the folded state. According to some embodiments, the second surface 204 of the seal member 222 faces away from the anatomical wall at the implantation site when the seal member 222 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site.

[0259] According to some embodiments, seal member 222 includes both second layer 220 and third layer 225. According to some embodiments, second layer 220 is connected to third layer 225. According to some embodiments, second layer 220 and third layer 225 are integrated to cover first layer 210, as shown in FIG. 4C . According to some embodiments, second layer 220 and third layer 225 collectively form a coating that covers both first side 202 and second side 204 of seal member 222, respectively. According to some embodiments, second layer 220 and third layer 225 collectively form a coating that covers seal member 222.

[0260] Based on the above, it will be appreciated that, according to some embodiments, the unfolded sealing member 222 is folded into a folded state by connecting the first lateral edge 206 and the second lateral edge 208 over the second surface 204 so that the second surface 204 faces inward (toward the centerline 211 of the sealing member) and the first surface 202 faces outward when the sealing member 222 is in the folded state. Thus, when the folded sealing member 222 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at an implantation site, the second layer 220 contacts the anatomical wall (e.g., the inner surface of the annular wall or arterial wall 105) at the implantation site.

[0261] According to some embodiments, the seal member 222 extends between the first surface 202 and the second surface 204, and the seal member 222 has a total layer thickness 203 measured between the first surface 202 and the second surface 204 at one of the inter-ridge gaps 250, as shown in FIG. 4C. According to some embodiments, the total layer thickness 203 is measured from the first surface 202 of the seal member 222 to the second surface 216 of the first layer 210 (not shown). According to some embodiments, the total layer thickness 203 is measured from the first surface 202 of the seal member 222 (e.g., the second layer 220) to the second surface 204 (e.g., the third layer 225), as shown in FIG. 4C. According to some embodiments, the ridge height 222RH (e.g., the thickness as measured by the height of the ridges 230) of the seal member 222 is greater than the total layer thickness 203 by at least 1000%. In further embodiments, the ridge height 222RH is at least 2000%, at least 3000%, at least 4000%, at least 5000%, or at least 6000% greater than the total layer thickness 203 of the seal member 222. In still further embodiments, the ridge height 222RH is no greater than 6000%, no greater than 7000%, no greater than 8000%, no greater than 9000%, no greater than 10,000%, no greater than 20,000%, no greater than 30,000%, no greater than 40,000%, or no greater than 50,000% greater than the total layer thickness 203 of the seal member 222. Each possibility represents a different embodiment.

[0262] It should be understood that the present invention, including each identified component, is not limited to the embodiments shown in the drawings. Specifically, dimensions may be illustrated in the drawings for clarity and ease of understanding of the components, rather than reflecting actual dimensions and dimensional distribution. For example, although the thickness ratio between ridge height 222RH and total layer thickness 203 in FIGS. 4B-4C is moderate, as discussed above, the actual ratio is larger (e.g., ridge height 222RH is 10 to 60 times larger than total layer thickness 203). For example, in some non-constrained implementations, total layer thickness 203 may be in the range of 0.02 mm to 0.1 mm, while ridge height 222RH may be in the range of 0.5 mm to 3 mm.

[0263] According to some embodiments, the seal member 222 has a resilient 3D structure such that the non-fibrous outer surface 280 of the seal member 222 exhibits a plurality of raised portions 230 having peaks 205 and a plurality of non-raised portions 250, as disclosed hereinabove (see, e.g., FIGS. 4B-4C ). According to some embodiments, the non-fibrous outer surface 280 of the seal member 222 is defined as the outer surface of the first surface 202 combined with the outer surface of each of the plurality of raised portions 230 (i.e., the plurality of ridges 230). According to some embodiments, the peaks 205 are defined as the highest points along each of the outer surfaces of the plurality of raised portions 230 that extend away from the first surface 202 of the seal member 222. According to some embodiments, the height of each peak 205 is defined as the distance (e.g., ridge height 222RH) of the highest point along the outer surface of each of the plurality of raised portions 230 relative to the frame 106 when the sealing member 222 is coupled to the outer surface of the frame 106 of the prosthetic valve 100.

[0264] According to some embodiments, non-raised portions 250 are defined as inter-ridge gaps 250. In further such embodiments, the height of each non-raised portion 250 is defined as the distance of first surface 202 from frame 106 when seal member 222 is coupled to the outer surface of frame 106 of prosthetic valve 100 (e.g., total thickness 203 in the embodiment shown in FIGS. 4A-4C ). According to some embodiments, the distance of peak 205 from frame 106 is at least 1000% greater than the distance of non-raised portion 250 from frame 106 in the absence of an external force applied to press raised portion 230 against the frame (also conveniently referred to as the “relaxed state”). According to further embodiments, the distance of peak 205 from frame 106 is greater than the distance of non-raised portion 250 from the frame by at least 2000%, at least 3000%, at least 4000%, at least 5000%, or at least 6000%. Each possibility represents a different embodiment.

[0265] With respect to the force applied to deform the 3D shape of the sealing member, the term "external force" may relate to the force applied by the surrounding tissue (e.g., the annular wall or arterial wall 105) when the prosthetic valve 100 is deployed against the surrounding tissue, or may relate to the force applied by the inner wall of a sheath or capsule within which the valve 100 is held during storage or delivery to the implantation site.

[0266] The term "elastic," as used herein with respect to the 3D shape of the sealing member, refers to the sealing member, and more specifically the peaks or peak portions of the sealing member, being resistant to permanent deformation when such external forces are applied, yet tending to return to a relaxed state when the external forces are no longer applied.

[0267] The term "non-fibrous," as used herein with respect to the non-fibrous outer surface of a seal member of the present invention (e.g., non-fibrous outer surface 280 of seal member 222), refers to an outer surface of the seal member that is free of yarns and / or strands (including the absence of textured yarns and / or strands). Thus, the second layer defining the non-fibrous outer surface is necessarily a non-fibrous layer, which should be understood to be a nonwoven layer and a non-braided layer.

[0268] According to some embodiments, first layer 210 is formed from a flexible and / or elastic material configured to provide mechanical stability to seal member 222, and optionally configured to provide tear resistance (or tear strength) to seal member 222. In further embodiments, first layer 210 may be configured to allow for continued, durable attachment of seal member 222 to the outer surface of frame 106 of prosthetic valve 100, optionally by preventing irreversible deformation (e.g., resisting tearing), thereby providing mechanical stability to the structure, which may be advantageous.

[0269] As used herein, the terms "tear resistance" and "tear strength" are interchangeable and refer to a material's ability to resist the formation of tears when the material is subjected to an applied stress. A tear refers to the degree of notch or cut into the stressed material. A tear-resistant material can withstand large applied stresses and / or deformations without losing its integrity. According to some embodiments, the tear-resistant layer of the present invention (e.g., first layer 210) can be relatively thin and yet have sufficient strength to allow any covering or coating layers attached thereon to be sutured to the frame and to allow the prosthetic valve 100 to be crimped without tearing.

[0270] According to some embodiments, the tear-resistant layer (e.g., first layer 210) of the present invention may comprise a ripstop fabric. The term "ripstop," as used herein, refers to a reinforced woven fabric that is resistant to tearing and ripping. Ripstop fabrics typically refer to woven fabrics in which reinforcing yarns are woven in a crosshatch pattern at specified intervals, which can vary from fabric to fabric and, optionally, even within a single fabric. Depending on how the reinforcing yarns are incorporated, the woven fabric can exhibit various textures, such as a box pattern. According to some embodiments, the first layer (e.g., first layer 210) of the present seal member comprises a ripstop fabric, optionally including fibers formed from polyethylene terephthalate (PET). In further embodiments, the first layer (e.g., first layer 210) of the seal member comprises a tear-resistant ripstop fabric including PET.

[0271] According to some embodiments, first layer 210 includes at least one tear-resistant material. According to further embodiments, first layer 210 is formed from at least one tear-resistant material.

[0272] First layer 210 can be formed from a variety of suitable, and optionally biocompatible, materials, such as, but not limited to, various synthetic materials (e.g., polyethylene terephthalate (PET), polyester, polyamide (e.g., nylon), polypropylene, polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), etc.), natural tissue and / or fibers (e.g., bovine pericardium, silk, cotton, etc.), metals (e.g., metal mesh or braid including gold, stainless steel, titanium, nickel, nickel titanium (nitinol), etc.), and combinations thereof. Each possibility represents a different embodiment.

[0273] The first layer 210 can be a metal or polymer member, such as a shape memory metal or polymer member. The first layer 210 can be a woven fabric. It will be appreciated that the first layer 210 is not limited to a woven fabric. Other fabric constructions can be used, such as woven fabrics, knitted fabrics, woven webs, woven felts, filament-spun fabrics, and the like. The fabric of the first layer 210 can include at least one suitable material selected from various synthetic materials, natural tissues and / or fibers, metals, and combinations thereof, as described herein above.

[0274] According to some embodiments, first layer 210 comprises a tough, tear-resistant material, such as, but not limited to, polyethylene terephthalate (PET). According to further embodiments, first layer 210 comprises a tear-resistant PET fabric. According to further embodiments, first layer 210 comprises at least one tear-resistant knitted / woven PET fabric.

[0275] The tear-resistant materials (e.g., woven PET fabrics) of the present invention, according to some embodiments, may be woven from yarns using any known weave pattern, including simple plain weave, basket weave, twill weave, velour weave, and the like. The weave pattern includes warp yarns that run along the longitudinal length of the woven tear-resistant material (e.g., seal member 222) and weft yarns, also known as fill yarns, that run across the width or circumference of the woven tear-resistant material.

[0276] According to some embodiments, first layer 210 includes at least one flexible material. According to further embodiments, first layer 210 is formed from at least one flexible material. According to some embodiments, first layer 210 is flexible.

[0277] According to some embodiments, first layer 210 includes at least one elastic material. According to further embodiments, first layer 210 is formed from at least one elastic material. According to some embodiments, first layer 210 is elastic.

[0278] According to some embodiments, the tear-resistant layer (e.g., first layer 210) of a seal member (e.g., seal member 222) of the present invention comprises at least one tear-resistant, flexible material capable of withstanding a force load of greater than about 3 Newtons (N) before tearing. According to some embodiments, first layer 210 comprises at least one tear-resistant, flexible material capable of withstanding a force load of greater than about 5 Newtons (N) before tearing, thereby enabling seal member 222 to operate reliably without tearing during normal use. According to some embodiments, first layer 210 comprises at least one tear-resistant, flexible material capable of withstanding a force load of greater than about 7 Newtons (N) before tearing.

[0279] According to further embodiments, the at least one tear-resistant and flexible material in the first layer 210 can withstand a force load of greater than about 10 N before tearing. According to still further embodiments, the at least one tear-resistant and flexible material in the first layer 210 can withstand a force load of greater than about 15 N before tearing. According to still further embodiments, the at least one tear-resistant and flexible material in the first layer 210 can withstand a force load of greater than about 20 N before tearing. According to still further embodiments, the at least one tear-resistant and flexible material in the first layer 210 can withstand a force load of greater than about 25 N before tearing. According to still further embodiments, the at least one tear-resistant and flexible material in the first layer 210 can withstand a force load of greater than about 30 N before tearing. According to a preferred embodiment, the at least one tear-resistant and flexible material in the first layer 210 comprises a PET fabric and can withstand a load of up to about 20 N of force before tearing.

[0280] It will be understood that having a tear resistance of at least 5N means that the layer can be stretched at least axially (i.e., stretched so that the inflow edge 209 and outflow edge 207 are separated from each other) without tearing.

[0281] According to some embodiments, first layer 210 includes at least one biocompatible material. According to further embodiments, first layer 210 is formed from at least one biocompatible material. According to some embodiments, first layer 210 is biocompatible.

[0282] The term "biocompatible," as used herein, means that an implantable valve and its sealing members can contact living tissue or an organism without causing harm to the tissue or organism. Biocompatible materials and articles are substantially nontoxic in the in vivo environment of the implantation site and are not substantially rejected by the patient's physiological systems (i.e., are nonantigenic). This can be measured by the material's ability to pass biocompatibility tests set forth in International Organization for Standardization (ISO) Standard No. 10993, United States Pharmacopeia (USP) No. 23, and / or U.S. Food and Drug Administration (FDA) Blue Book Memorandum No. G95-1, "Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part-1: Evaluation and Testing." Typically, these tests measure a substance's toxicity, infectivity, inflammatory potential, irritancy, reactivity, hemolytic activity, carcinogenicity, and / or immunogenicity.

[0283] 4C , when first layer 210 is covered by second layer 220 and third layer 225, it will not contact tissue during implantation, and so it will be appreciated that in this case first layer 210 may be formed from a non-biocompatible material. Nevertheless, forming first layer 210 from a biocompatible material may be preferable in this case to avoid the risk of either second layer 220 or third layer 225 becoming worn or torn, thereby exposing a portion of first layer 210.

[0284] A sealing member of the present invention, such as sealing member 222, according to some embodiments, may further include silicone or other lubricious materials or polymers, which may aid in an extraction procedure to remove the prosthetic valve from its initial implantation site. Such lubricious materials are typically incorporated into and / or onto the outermost surface that will contact surrounding tissue (e.g., first surface 202 and / or second layer 220 of this exemplary sealing member 222). Additionally or alternatively, the outermost surface of a sealing member of the present invention (e.g., first surface 202 and / or second layer 220) may be smooth and / or include a low-friction or lubricious material. A lubricious material on the outermost surface may also reduce friction with the tissue of the native valve that contacts inflow end 104 (or other portions) of prosthetic valve 100, thereby preventing damage to the tissue.

[0285] According to some embodiments, first surface 202 and / or second layer 220 are continuous in a manner that is free of yarns and / or strands (including free of textured yarns and / or strands).

[0286] According to some embodiments, second layer 220 is configured to contact the implantation site tissue (i.e., the inner surface of the annular or arterial wall 105) and therefore is formed from at least one resilient biocompatible material. Additionally, according to some embodiments, second layer 220 is advantageously formed from a material that can prevent / resist and / or reduce the amount of tissue ingrowth around or onto sealing member 222, allowing for easy removal of valve 100 from the implantation site in the event an explantation procedure is required, as detailed above.

[0287] According to some embodiments, the second layer 220 can be formed from a variety of suitable biocompatible synthetic materials, such as, but not limited to, thermoplastic materials. Suitable thermoplastic biocompatible materials are selected from, but not limited to, polyamides, polyesters, polyethers, polyurethanes, polyolefins (such as polyethylene and / or polypropylene), polytetrafluoroethylene, and combinations and copolymers thereof. Each possibility represents a different embodiment. Thus, according to some embodiments, the second layer 220 is formed from a thermoplastic material. According to some embodiments, the second layer 220 includes a thermoplastic material. According to some embodiments, the second layer 220 is made of a thermoplastic material. According to some embodiments, the thermoplastic material is selected from the group consisting of polyamides, polyesters, polyethers, polyurethanes, polyolefins, polytetrafluoroethylene, and combinations and / or copolymers thereof.

[0288] According to some embodiments, the second layer 220 can be formed from a variety of suitable biocompatible synthetic materials, such as a thermoplastic material, including, but not limited to, a thermoplastic elastomer (TPE). According to some embodiments, the thermoplastic material is a thermoplastic elastomer. According to some embodiments, the thermoplastic material includes a thermoplastic elastomer (TPE).

[0289] As used herein, the terms "thermoplastic elastomer" or TPE are used interchangeably to refer to a copolymer or physical blend of polymers with thermoplastic and elastomeric properties, characterized by their elastic properties while being capable of being thermally shaped (i.e., under the application of heat, similar to thermoplastic polymers) to form 3D geometric shapes from their substantially 2D counterparts. Thermoplastic polyurethane (TPU) is an example of a TPE that comprises a linear, segmented block copolymer containing hard and soft segments. TPEs can be thermally processed to form various shapes using a variety of known methods, including injection molding, extrusion, 3D printing, thermoforming, and the like.

[0290] According to some embodiments, the thermoplastic elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations and variations thereof. Each possibility represents a different embodiment. According to some embodiments, the thermoplastic elastomer is TPU. According to some embodiments, the thermoplastic elastomer includes TPU.

[0291] According to some embodiments, second layer 220 comprises at least one anti-thrombogenic material configured to prevent the formation of blood clots (thrombi) around the implanted prosthetic heart valve in order to prevent and / or reduce tissue ingrowth therearound, thereby allowing for easy and safe removal of the valve from the surrounding tissue when needed, preferably without complex surgical procedures. According to some embodiments, second layer 220 comprises at least one thermoplastic elastomer anti-thrombogenic material. According to some embodiments, second layer 220 comprises at least one thermoplastic elastomer anti-thrombogenic material configured to prevent and / or reduce tissue ingrowth therearound. Such a material, according to some embodiments, comprises TPU.

[0292] The term "antithrombogenic," as used herein, refers to a material's resistance to platelet adhesion and subsequent thrombus formation and / or tissue ingrowth in vitro and / or in vivo.

[0293] According to some embodiments, second layer 220 comprises TPU.

[0294] When incorporated into seal member 222, third layer 225 may, according to some embodiments, be integral with second layer 220, as described further herein. When third layer 225 and second layer 220 are each formed as an integral coating over first layer 210, according to some embodiments, they are preferably formed from the same material. Even if third layer 225 and second layer 220 are each separate, according to some embodiments, they may have similar or identical compositions. According to some embodiments, third layer 225 and second layer 220 are each formed from the same material.

[0295] According to some embodiments, third layer 225 is formed from a thermoplastic material. According to some embodiments, third layer 225 includes a thermoplastic material. According to some embodiments, third layer 225 is made of a thermoplastic material. According to some embodiments, the thermoplastic material is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof.

[0296] Suitable thermoplastic materials for manufacturing the third layer 225 are those detailed herein with respect to the composition of the second layer 220 .

[0297] According to some embodiments, the third layer 225 comprises at least one thermoplastic elastomeric anti-thrombogenic material, which is configured to prevent and / or reduce surrounding tissue ingrowth.

[0298] According to some embodiments, the third layer 225 comprises TPU.

[0299] According to some embodiments, the seal member 222 includes a first layer 210 and a second layer 220, where the first layer 210 includes at least one tear-resistant material and the second layer 220 includes at least one thermoplastic and anti-thrombogenic material. According to some embodiments, the seal member 222 includes a first layer 210, a second layer 220, and a third layer 225, where the first layer 210 includes at least one tear-resistant material and the second layer 220 and the third layer 225 each include at least one thermoplastic and anti-thrombogenic material. According to further embodiments, the second layer 220 forms a 3D configuration in a relaxed, unfolded state. According to further embodiments, the third layer 225 forms a 3D configuration in a relaxed, unfolded state. According to some embodiments, the second layer 220 and the third layer 225 form a similar 3D configuration in a relaxed, unfolded state.

[0300] According to some embodiments, second layer 220 is configured to resiliently retain a 3D shape (i.e., has ridges 230), as described further herein. According to some embodiments, third layer 225 is configured to resiliently retain a similar 3D shape (i.e., has channels 240), as described further herein.

[0301] According to some embodiments, seal member 222 includes first layer 210 and second layer 220, where first layer 210 is configured to provide mechanical stability and tear resistance and is configured to support its structure, while second layer 220 is configured to form and maintain its 3D shape, and optionally configured to prevent and / or reduce tissue ingrowth onto its upper surface. According to some embodiments, seal member 222 includes first layer 210 and second layer 220, where first layer 210 is configured to provide mechanical stability and tear resistance and is configured to support its structure, while second layer 220 and third layer 225 are configured to form and maintain its 3D shape, and second layer 220 is optionally configured to prevent and / or reduce tissue ingrowth onto its upper surface.

[0302] It is envisioned that second layer 220, alone or in combination with optional third layer 225, may lack the ability to adequately maintain a durable attachment of seal member 222 to the exterior surface of frame 106. Specifically, second layer 220, and optional third layer 225, may have low tear resistance and may not be able to be durably sutured to frame 106. Advantageously, the combination of first layer 210 and second layer 220 can provide the necessary characteristics for seal member 222. While TPU can potentially reduce tissue ingrowth and maintain the 3D shape of seal member 222, it may be difficult to suture to the frame. According to some embodiments, second layer 220 including TPU is reinforced by first layer 210 including PET to provide the necessary strength to hold sutures.

[0303] Seal members comprising the thermoplastic elastomer (TPE) materials (e.g., TPU) of the present invention have excellent elasticity, outstanding recovery, minimal tissue ingrowth onto their upper surfaces, are capable of maintaining a 3D shape, and remain non-toxic and biocompatible. This unique combination of mechanical and biological properties provides a structure ideally suited for medical applications.

[0304] It is contemplated that utilizing a thermoplastic elastomer material, such as TPU, as one layer of the sealing member 222 allows for the sealing member 222 to be manufactured in a manner that allows for the formation of a desired 3D shape of the sealing member 222 having the resilient ridges 230. In some examples, the resilient ridges 230 of the sealing member 222 are advantageously configured to contact and press against the annular or arterial wall 105 at the implantation site after expansion of the prosthetic heart valve 100, thereby improving the PVL seal between the prosthetic heart valve 100 and the inner surface of the annular or arterial wall 105. Thus, according to some embodiments, each of the ridges 230 is resilient and compressible. The resilient and compressible properties of the ridges 230 can improve retention of the sealing member 222 against the tissue of the native heart valve at the implantation site.

[0305] According to some embodiments, the sealing member 222 has an elastic 3D shape that is configured to deform when an external force is applied to the sealing member (e.g., when pressed against the annular or arterial wall 105 or against the inner wall of the shaft or retention capsule), and is further configured to return to its original shape (i.e., relaxed shape) when the external force is no longer applied (e.g., when the valve is released from the shaft or capsule before being expanded).

[0306] According to some embodiments, a seal member of the present invention (e.g., seal member 222) has a resilient 3D structure / shape that is configured to deform when an external force exceeding a predefined threshold is applied, and that is configured to return to a relaxed state when the external pressure is removed. According to some embodiments, the predefined threshold external pressure is 300 mmHg.

[0307] It is understood that the compressibility of the ridges 230 is consistent with the elastic 3D structure of the second layer 220 in which the ridges 230 are formed, because the structure of the ridges 230 in the second layer 220 is restored when the compression on the ridges 230 ceases (e.g., when the sealing member 222 returns to a relaxed state).

[0308] According to some embodiments, the seal member 222 includes at least a first layer 210 including a tear-resistant material and a second layer 220 including a thermoplastic and anti-thrombogenic material. According to some embodiments, the seal member 222 further includes a third layer 225 including a thermoplastic and anti-thrombogenic material. According to further embodiments, the seal member 222 includes the first layer 210 including a tear-resistant material including a PET fabric and the second layer 220 including a thermoplastic and anti-thrombogenic material including a TPU, where the TPU has been heat-processed to form a 3D geometric shape along the first surface 202 of the seal member 222, thereby forming the plurality of ridges 230, as described above. According to further embodiments, the seal member 222 includes the third layer 225 including a thermoplastic and anti-thrombogenic material including a TPU, where the TPU has been heat-processed to form a 3D geometric shape along the second surface 204 of the seal member 222, thereby forming the plurality of channels 240, as described above.

[0309] Reference is now made to FIGS. 6A-6E and 7A-7C. FIGS. 6A-6B illustrate exemplary thermoforming steps for producing the unfolded seal member 222, according to some embodiments. Specifically, FIGS. 6A-6B illustrate heat treating steps for the flat flexible sheet 212, using placement on a mold 264 and heating, to produce the unfolded seal member 222, according to some embodiments. FIGS. 6C-6D illustrate heat treating steps for the flat flexible sheet 212, using placement on a mold 264, heating, and vacuum thermoforming, to produce the unfolded seal member 222, according to some embodiments. FIG. 6E illustrates heat treating steps for the flat flexible sheet 212, using thermoforming, including applying force to two opposing sides using a mold 264, to produce the unfolded seal member 222, according to some embodiments.

[0310] According to some embodiments, there is provided a PVL skirt 222 manufactured by the method of the present invention. According to some embodiments, there is provided a PVL skirt 222 in a folded state manufactured by the method of the present invention.

[0311] According to some embodiments, a method is provided for cost-effectively and simply manufacturing a seal member, such as seal member 222 as described hereinabove. According to some embodiments, the method includes (i) providing a tear-resistant flat sheet 212, (ii) subjecting the sheet to a thermal shaping process to form a 3D shape in an unfolded, relaxed state, and (iii) connecting two opposite edges of the sheet 212 in step (ii) to form a cylindrical seal member (or PVL skirt) in a cylindrically folded state.

[0312] According to some embodiments, the method includes: (i) preparing a flat flexible sheet 212 including a tear-resistant first layer 210 and a thermoplastic second layer 220; (ii) placing the flat flexible sheet 212 on a mold 264 at an elevated temperature to form a plurality of ridges 230 on the upper surface and reducing the temperature to maintain the elastic 3D structure of the thermoplastic second layer 220; and (iii) forming a cylindrical sealing member 222 by connecting two opposite edges of the sheet 212 in step (ii).

[0313] According to some embodiments, the method includes (i) providing a flat flexible sheet 212 including a tear-resistant first layer 210 disposed between a thermoplastic second layer 220 and a thermoplastic third layer 225 of the flat flexible sheet 212, (ii) placing the flat flexible sheet 212 on a mold 264 at an elevated temperature to form a plurality of ridges 230 on the second layer 220 and reducing the temperature to maintain the elastic 3D structure of the thermoplastic second layer 220, and (iii) connecting two opposite edges of the sheet 212 in step (ii) to form a cylindrical seal member 222 (i.e., folding the sheet 212). According to some embodiments, the heat treatment of the sheet 212 using the mold 264 in step (ii) comprises thermoforming.

[0314] It will be understood that any properties introduced above with respect to each of the layers (i.e., first layer 210, second layer 220, and third layer 225) apply equally to each layer when referring to the methods of the present invention. Specifically, according to some embodiments, first layer 210 comprises at least one biocompatible material. According to some embodiments, first layer 210 comprises at least one elastic material. According to some embodiments, first layer 210 comprises at least one flexible material. According to further embodiments, first layer 210 comprises a tear-resistant PET fabric. According to some embodiments, first layer 210 comprises at least one tear-resistant material. According to some embodiments, second layer 220 is formed from a thermoplastic material. According to some embodiments, third layer 225 is formed from a thermoplastic material. According to some embodiments, the thermoplastic material is selected from the group consisting of polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the thermoplastic material is a thermoplastic elastomer.

[0315] According to some embodiments, the thermoplastic elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations and variations thereof. Each possibility represents a different embodiment. According to some embodiments, the thermoplastic elastomer is TPU. According to some embodiments, the second layer 220 includes at least one anti-thrombogenic material. According to some embodiments, the second layer 220 includes TPU. According to some embodiments, the third layer 225 includes at least one anti-thrombogenic material. According to some embodiments, the third layer 225 includes TPU. According to some embodiments, the second layer 220 and the third layer 225 are formed from the same material. According to some embodiments, the third layer 225 is integral with the second layer 220, as described in more detail herein.

[0316] According to some embodiments, step (ii) involves placing flat flexible sheet 212 on mold 264, with second layer 220 positioned on the opposite side from mold 264. According to some embodiments, step (ii) involves placing flat flexible sheet 212 on mold 264, with third layer 225 positioned proximate to mold 264. According to some embodiments, step (ii) involves placing flat flexible sheet 212 on mold 264, with third layer 225 in contact with mold 264. According to some embodiments, step (ii) involves placing flat flexible sheet 212 on mold 264, with first layer 210 in contact with mold 264.

[0317] According to some embodiments, the ridges 230 formed in step (ii) are formed on the second layer 220, thereby forming corresponding channels 240 in the third layer 225. According to some embodiments, the ridges 230 formed in step (ii) are formed on the second layer 220, thereby forming corresponding channels 240 in the first layer 210.

[0318] It will be appreciated that the thermoplastic properties of second layer 220 (and, optionally, third layer 225) enable the thermal shaping process described above. Specifically, thermoplastic materials are transformed from an elastic, relatively hard state at low temperatures to a pliable, relatively soft state when heated. In step (ii), according to some embodiments, thermoplastic second layer 220 is heated to its pliable state, thereby enabling mold 264 to form a 3D shape including ridges 230 in thermoplastic second layer 220. While this thermal shaping process can be facilitated by the application of an external force, it has been found illustratively sufficient to enable thermal shaping by gravity alone, using a simple mandrel (as mold 264) placed under sheet 212 and heated in an oven.

[0319] This embodiment is shown in Figures 6A-6B, which separately show flat flexible sheet 212 as originally prepared and mold 264, which is shown as including a plurality of mandrels 268 spaced apart from one another, optionally evenly spaced apart from one another, according to some embodiments.

[0320] The term "mandrel," as used herein, refers to an elongated member, such as a rod or pipe, which may act as a core over which a thermoplastic material may be molded or otherwise shaped at elevated temperatures. Mandrel, as used herein, may relate to an elongated member, such as a rod or pipe, having a uniformly sized cross-sectional shape along its length.

[0321] According to some embodiments, step (i) further includes preparing a mold. FIG. 6A also shows mandrel 268 positioned on ground surface 267, which may be the floor of an oven according to some embodiments, since ground surface 267 is heated in step (ii) of the method. In some implementations, multiple mandrels may be integrally formed with a base plate (e.g., ground surface 267) and function as protrusions extending therefrom. In other implementations, mandrel 268 may be a separate component, attached to or removably positioned on a base plate (e.g., ground surface 267). FIG. 6B illustrates thermoforming sheet 212 into the three-dimensional shape of seal member 222.

[0322] Specifically, in the embodiment shown in FIGS. 6A-6B, flat flexible sheet 212 is placed on mandrel 268. As can be seen in this figure, thermoplastic second layer 210 and third layer 225 are each in an elastic state, according to some embodiments. Next, when sheet 212 is heated on mandrel 268, the portion of sheet 212 not positioned on mandrel 268 gravitationally collapses (e.g., until it contacts the oven floor), while the portion of sheet 212 positioned on mandrel 268 does not collapse due to interference from mandrel 268 ( FIG. 6B ). According to some embodiments, in step (ii), each ridge 230 is formed on a corresponding mandrel 268. After the 3D shape is formed, sheet 212 may be cooled, which causes thermoplastic second layer 220 to return to its elastic, non-flexible state. The mandrel is then removed, according to some embodiments, to provide the unfolded seal member 222 (FIG. 4A). Further, according to some embodiments, two opposing edges of the flexible sheet 212 are attached (e.g., stitched) to one another to provide the folded seal member 222.

[0323] As used herein, the term "gravitationally sinking" refers to a material that sinks in the direction of gravity.

[0324] As further seen in Figures 6A and 6B, the flat flexible sheet 212 may also include a third layer 225 that undergoes shaping similar to the second layer 220 as described further herein.

[0325] According to some embodiments, the sheet 212 in step (i) has a first side 202 and a second side 204, and the distance between the first side 202 and the second side 204 of the sheet 212 in step (i) constitutes an initial thickness 212T of the sheet 212 in step (i). Additionally, according to some embodiments, the sheet 212 in step (i) has a first lateral edge 206 and a second lateral edge 208, and the distance between the first lateral edge 206 and the second lateral edge 208 of the sheet 212 in step (i) constitutes an initial width 212W (not shown) of the sheet 212 in step (i). Furthermore, according to some embodiments, the sheet 212 in step (i) has an inflow edge 209 and an outflow edge 207, and the distance between the inflow edge 209 and the outflow edge 207 of the sheet 212 in step (i) constitutes an initial length 212L (not shown) of the sheet 212 in step (i). According to some embodiments, initial thickness 212T corresponds to or is the same as total layer thickness 203, as described above.

[0326] Specifically, according to some embodiments, the sheet 212 of step (i) is flat and substantially two-dimensional, meaning that the initial thickness 212T of the sheet 212 of step (i) is substantially smaller than the initial width 212W and the initial length 212L.

[0327] According to some embodiments, the sheet 212 produced in step (ii) is an unfolded, unfolded seal member 222. According to some embodiments, the first lateral edge 206 and the second lateral edge 208 of the sheet 212 in step (i) are the same as the first lateral edge 206 and the second lateral edge 208 of the seal member 222 produced in step (ii). According to some embodiments, the inflow edge 209 and the outflow edge 207 of the sheet 212 in step (i) are the same as the inflow edge 209 and the outflow edge 207 of the unfolded seal member 222 produced in step (ii).

[0328] According to some embodiments, practicing the methods of the present invention results in the formation of ridge 230, which has a ridge height 222RH, which is the thickness 222T of seal member 222 in its expanded, relaxed state. It will be understood that any reference to ridge height 222RH or thickness 222T is equivalent to the distance of peak 205 from the outer surface of frame 106 in the relaxed state of seal member 222 when bonded to frame 106. Similarly, any reference to initial thickness 212T is equivalent to the distance of non-raised portion 250 from the outer surface of frame 106 when seal member 222 is bonded to frame 106.

[0329] According to some embodiments, the thickness 222T of the seal member 222 in its unfolded, relaxed state after the thermal shaping step (ii) configured to form a 3D shape is at least 1000% greater than the initial thickness 212T of the sheet 212. According to some embodiments, the thickness 222T of the seal member 222 in its unfolded, relaxed state is at least 2000%, at least 3000%, at least 4000%, at least 5000%, or at least 6000% greater than the initial thickness 212T of the sheet 212.

[0330] It will be appreciated that the width 212W and length 212L of sheet 212 may also be altered somewhat by the practice of this process, but the significant dimensional change is the change in thickness (from 212T to 222T), which transforms the initial 2D structure of sheet 212 into the 3D structure of seal member 222. In some implementations, the resulting sheet 212 after step (ii) has a dimension greater than either the desired width 212W and / or the desired length 212L, and the method may include the additional step of cutting sheet 212 to the desired width 212W and / or the desired length 212L after step (ii) and before step (iii).

[0331] According to some embodiments, the tear-resistant flat sheet 212 of step (i) comprises a first layer 210 as described herein above. According to some embodiments, the sheet 212 of step (i) comprises a second layer 220 as described herein above. According to some embodiments, the sheet 212 of step (i) comprises a third layer 225 as described herein above. According to further embodiments, the tear-resistant flat sheet of step (i) comprises a PET fabric.

[0332] According to some embodiments, the method of the present invention comprises coating at least one side of a flat tear-resistant sheet with a thermoplastic polymer coating layer to obtain the sheet 212 of step (i).

[0333] According to some embodiments, treating the sheet to form the 3D shape in step (ii) comprises coating at least one side of the flat tear-resistant sheet while simultaneously thermoforming the sheet, as described herein above, to form the 3D coated shape in the extended, relaxed state. According to further embodiments, coating at least one side of the flat tear-resistant sheet comprises coating the tear-resistant first layer 210 with at least one of the thermoplastic second layer 220 and the thermoplastic third layer 225.

[0334] According to some embodiments, coating at least one surface of the flat tear-resistant sheet with a thermoplastic polymer coating layer is performed by a coating technique selected from brushing, spray coating, dip coating, immersion or impregnation, and combinations thereof. However, the present invention is not limited to these coating techniques, and other coating techniques, such as chemical vapor deposition, vapor deposition, chemical vapor deposition, physical vapor deposition, printing, and the like, may also be used appropriately. These techniques are generally suitable for medical fabrics. Furthermore, printing techniques, such as roller printing, stencil printing, screen printing, inkjet printing, lithography printing, 3D printing, and the like, may also be used with the present invention to apply the thermoplastic polymer coating.

[0335] According to some embodiments, step (ii) includes placing the flat flexible sheet 212 onto a mold 264 at an elevated temperature to form a plurality of ridges 230 on the second layer 220, and reducing the temperature to maintain the elastic 3D structure of the thermoplastic second layer 220.

[0336] It will be appreciated that the elevated temperature in step (ii) refers to a temperature at which the thermoplastic material comprising second layer 220 (and third layer 225) is pliable and soft, such that sheet 212 can be thermally formed into a 3D shape, according to some embodiments. Thus, the temperature will depend on the particular thermoplastic material used. It will also be appreciated that the reduced temperature in step (ii) refers to a temperature at which the thermoplastic material comprising second layer 220 (and third layer 225) is elastic, such that the thermoplastic material maintains its 3D structure. Because step (iii), in which sealing member 222 is folded into a cylindrical shape, is typically performed at ambient temperature, the reduced temperature in step (ii) may involve a reduction to ambient temperature (e.g., room temperature).

[0337] According to some embodiments, the elevated temperature in step (ii) is at least 50°C. According to some embodiments, the elevated temperature in step (ii) is at least 60°C. According to some embodiments, the elevated temperature in step (ii) is at least 70°C. According to some embodiments, the elevated temperature in step (ii) is at least 80°C. According to some embodiments, the elevated temperature in step (ii) is at least 90°C. According to some embodiments, the elevated temperature in step (ii) is at least 100°C. According to some embodiments, the elevated temperature in step (ii) is at least 120°C. According to some embodiments, heating the flat sheet to an elevated temperature comprises heating at least one side 212 of the sheet, or preferably at least two sides of the sheet, to a temperature selected from about 100°C to about 250°C, or preferably selected from about 120°C to about 200°C.

[0338] According to some embodiments, reducing the temperature in step (ii) comprises cooling the sheet 212 to a temperature below 40° C. According to some embodiments, reducing the temperature in step (ii) comprises cooling the sheet 212 to room temperature.

[0339] According to some embodiments, mold 264 is formed from a high temperature resilient material. According to some embodiments, mold 264 includes a high temperature resilient material. According to some embodiments, mold 264 is formed from a metal or metal alloy. Each possibility represents a separate embodiment. According to some embodiments, mold 264 includes a metal or metal alloy.

[0340] It will be appreciated that thermal shaping methods involving a mold may require a heat resistant mold 264 since the structure of the mold 264 should not change substantially during the method.

[0341] According to some embodiments, the mold 264 has an elongated structure. According to some embodiments, the mold 264 comprises an elongated mold. Specifically, as shown in FIG. 6B , the formed shape of the sheet 212 produced in step (ii) includes linear ridges 230 formed to follow a path line based on the elongated shape of the mold 264. However, according to some embodiments, the method of the present invention is not limited to the elongated mold 264, as other types of molds 264 will result in other types of ridges 230, as will be understood by those skilled in the art.

[0342] Specific types of elongated molds include, but are not limited to, a pipe, a shaft, a rod, and a mandrel. According to some embodiments, mold 264 includes at least one rod. According to some embodiments, mold 264 includes a plurality of rods. According to some embodiments, mold 264 includes a mandrel.

[0343] According to some embodiments, step (ii) includes placing the flat flexible sheet 212 on an elongated mold 264, which forms a plurality of ridges 230 on the second layer 220 at an elevated temperature, the ridges 230 extending from at least the first lateral edge 206 to the second lateral edge 208 of the sheet 212, and lowering the temperature to maintain the elastic 3D structure of the thermoplastic second layer 220. According to some embodiments, the ridges 230 are perpendicular to either the first lateral edge 206 and / or the second lateral edge 208 of the sheet 212 produced in step (ii). According to some embodiments, the ridges 230 are parallel to either the inflow edge 209 and / or the outflow edge 207 of the sheet 212 produced in step (ii). According to some embodiments, the plurality of ridges 230 are parallel to either the inflow edge 209 and / or the outflow edge 207 of the seal member fabricated in step (iii). Such a configuration is shown in Figures 4A and 4D.

[0344] According to some embodiments, step (ii) includes placing the flat flexible sheet 212 on an elongated mold 264, which extends from the inflow edge 209 to the outflow edge 207 to form a plurality of ridges 230 on the second layer 220 at an elevated temperature, the plurality of ridges 230 extending between the inflow edge 209 and the outflow edge 207 of the sheet 212, and maintaining the elastic 3D structure of the thermoplastic second layer 220 by lowering the temperature.

[0345] According to some embodiments, the ridges 230 are parallel to the first lateral edge 206 and the second lateral edge 207 of the sheet 212 produced in step (ii). According to some embodiments, the ridges 230 are perpendicular to the inflow edge 209 and the outflow edge 207 of the sheet 212 produced in step (ii). According to some embodiments, the ridges 230 are perpendicular to the inflow edge 209 and the outflow edge 207 of the seal member produced in step (iii). Such a configuration is shown in FIG. 4E.

[0346] According to some embodiments, step (ii) includes placing the flat flexible sheet 212 on an elongated mold 264, which extends obliquely along at least a portion of the second surface 204 of the sheet 212 to form, at an elevated temperature, a plurality of oblique ridges 230 on the second layer 220, the plurality of ridges 230 extending from the inflow edge 209 to the outflow edge 207 of the sheet 212, and reducing the temperature to maintain the elastic 3D structure of the thermoplastic second layer 220. Such a configuration is shown in FIG.

[0347] According to some embodiments, step (ii) further comprises removing the mold 264 from the sheet after the temperature has been reduced.

[0348] According to some embodiments, step (ii) further comprises cooling the processed sheet 212 to stabilize the desired 3D shape.

[0349] After the elastic 3D structure of the thermoplastic second layer 220 is obtained in step (ii), the resulting 3D sheet 212 can be folded into a cylindrical shape and sewn together to form a cylindrical sealing member 222.

[0350] According to some embodiments, step (iii) includes connecting two opposing edges (i.e., first lateral edge 206 and second lateral edge 208) of the sheet of step (ii) to form a cylindrically folded seal member 222 (or PVL skirt). The connection between the opposing edges can be achieved using at least one of adhesive, clipping, stitching, or heat, and optionally melting the edges. Alternatively, step (iii) includes bonding the seal member 222 to the outer surface of the frame 106 using at least one of adhesive, stitching, or heat, and optionally melting the edges of the seal member 222 around its periphery. Such bonding forces the seal member 222 into a cylindrically folded configuration due to the cylindrical shape of the frame 106 (see FIGS. 5A-5C).

[0351] Reference is now made to Figures 6C-6D, which illustrate the heat treating step of flat flexible sheet 212 using placement on mold 264, heating, and vacuum thermoforming to produce unfolded seal member 222, according to some embodiments.

[0352] According to some embodiments, there is provided a method for manufacturing a seal member 222 as described above in this specification, the method including: (i) providing a flat sheet 212 including (a) a tear-resistant first layer 210 and a thermoplastic second layer 220 as described above in this specification; (b) a mold 264 including a base 266, a plurality of protrusions, each of which is formed as a mandrel 268, and a vacuum source including openings 270; (ii) thermoforming the flat sheet 212 in a relaxed, unfolded state at an elevated temperature into a 3D shape by placing the flat sheet 212 on a plurality of elongated rods or on the mandrels 268 and applying a vacuum using the vacuum source utilizing the openings 270; and (iii) connecting two opposite edges of the sheet 212 in step (ii) to form a cylindrically folded cylindrical seal member (or PVL skirt).

[0353] According to some embodiments, the mandrel 268 is provided in the form of an elongated rod or protrusions. According to some embodiments, a method for manufacturing a seal member 222 as described herein above is provided, the method including: (i) providing (a) a flat sheet 212 including the tear-resistant first layer 210, the thermoplastic second layer 220, and the third layer 225 as described herein above; (b) a mold 264 including a base 266, a plurality of protrusions 268, and a vacuum source including openings 270; (ii) thermoforming the flat sheet 212 in a relaxed, unfolded state at an elevated temperature into a 3D shape by positioning the flat sheet 212 over the plurality of protrusions 268 and applying a vacuum using the vacuum source utilizing the openings 270; and (iii) connecting two opposite edges of the sheet 212 in step (ii) to form a cylindrically folded cylindrical seal member (or PVL skirt).

[0354] The properties of each of the first layer 210, second layer 220 and third layer 225 are as described herein above.

[0355] According to some embodiments, step (i) further includes providing a mold 264 including a base 266 and a plurality of protrusions 268 extending away from the base 266 parallel to the axis 214 (see FIG. 6C ) and spaced apart along the base 266. According to further embodiments, the base 266, the plurality of protrusions 268, or both, include a plurality of openings 270. According to some embodiments, the plurality of openings 270 are formed in the base 266. According to some embodiments, the plurality of openings 270 are part of a vacuum source. According to some embodiments, the plurality of openings 270 are connected (e.g., fluidly connected) to a vacuum pump.

[0356] According to a further embodiment, step (ii) further comprises supporting the sheet 212 with at least one holder. According to a further embodiment, step (ii) further comprises supporting the sheet 212 with at least two holders, a first holder 260 configured to secure / support the outflow edge 207 of the sheet and a second holder 262 configured to secure / support the inflow edge 209 of the sheet. According to some embodiments, the flat sheet is secured / supported by multiple holders (not shown). It will be understood that the holders may similarly secure / support oppositely located side edges.

[0357] According to some embodiments, step (ii) of the method includes thermally shaping the sheet using thermoforming to form a 3D shape in an unfolded, relaxed state using a mold 264 (see FIG. 6D).

[0358] According to some embodiments, step (ii) includes supporting the flat sheet 212 using at least a first holder 260 and a second holder 262, positioning the flat sheet 212 on a mold 264, heating the flat sheet to a thermoformable temperature, and driving the first holder 260 and the second holder 262 in respective directions to move the sheet 212 toward the mold 264, thereby effectively engaging the flat sheet with the protrusions 268 of the mold 264, thereby allowing the sheet 212 to conform to the protrusions 268.

[0359] According to some embodiments, step (ii) includes supporting the flat sheet 212 using at least a first holder 260 and a second holder 262, positioning the flat sheet 212 on a mold 264, heating the flat sheet to a thermoformable temperature, driving the first holder 260 and the second holder 262 in each direction to move the sheet 212 toward the mold 264, thereby effectively engaging the flat sheet 212 with the protrusions 268 of the mold 264, and applying a vacuum through the openings 270 to easily conform the sheet 212 to the protrusions 268.

[0360] According to some embodiments, step (ii) includes supporting a flat sheet using at least a first holder 260 and a second holder 262, positioning the flat sheet on a mold 264, heating the flat sheet to a thermoformable temperature, and lifting the mold 264 toward the flat sheet while the first holder 260 and the second holder 262 remain stationary relative to the movement of the mold or simultaneously move toward the mold 264, thereby effectively engaging the protrusions 268 of the mold 264 with the sheet 212 to easily fit the sheet into said mold 264.

[0361] According to some embodiments, step (ii) includes supporting a flat sheet using at least a first holder 260 and a second holder 262, positioning the flat sheet on a mold 264, heating the flat sheet to a thermoformable temperature, lifting the mold 264 toward the flat sheet while the first holder 260 and the second holder 262 remain stationary relative to the movement of the mold or simultaneously moving toward the mold 264, thereby effectively engaging the protrusions 268 of the mold 264 with the sheet 212, and applying a vacuum through openings 270 to easily conform the sheet to said mold 264.

[0362] According to some embodiments, heating the flat sheet to a thermoformable temperature can occur after forming an engagement between the mold 264 and the flat sheet.

[0363] As used herein, the term "thermoformable temperature" refers to the temperature at which second layer 220 (and, optionally, third layer 225), comprising a thermoplastic material, preferably TPU as described above, is heated to conform to the 3D shape of a mold without ignition or degradation, allowing for comfortable handling and thermal processing. According to some embodiments, the thermoformable temperature is at or above the glass transition temperature of the thermoplastic material. According to some embodiments, the thermoformable temperature is a temperature above the glass transition temperature of the thermoplastic material.

[0364] According to some embodiments, heating the flat sheet to a thermoformable temperature comprises heating at least one surface of the sheet, or preferably at least two surfaces of the sheet, to a temperature selected from about 100°C to about 250°C, or preferably from about 120°C to about 200°C. According to some embodiments, the elevated temperature in step (iii) is at least 50°C. According to some embodiments, the elevated temperature in step (iii) is at least 60°C. According to some embodiments, the elevated temperature in step (iii) is at least 70°C. According to some embodiments, the elevated temperature in step (iii) is at least 80°C. According to some embodiments, the elevated temperature in step (iii) is at least 90°C. According to some embodiments, the elevated temperature in step (iii) is at least 100°C. According to some embodiments, the elevated temperature in step (iii) is at least 120°C.

[0365] According to some embodiments, engagement of the seat 212 with the plurality of protrusions 268 forms the plurality of ridges 230, while engagement of the seat with the base 266 forms the plurality of inter-ridge gaps 250 in the seal member 222.

[0366] According to some embodiments, step (ii) further includes applying a reduced pressure between sheet 212 and mold 264 through opening 270 (e.g., by drawing a vacuum through opening 270) to stretch and pull the sheet toward mold 264 and to form a strengthened bond therebetween, thereby allowing sheet 212 to conform better to the shape of mold 264.

[0367] It will be appreciated that, according to some embodiments, part of the system for forming the 3D structure of the seal member includes a means for applying suction, such as a vacuum pump. According to some embodiments, the vacuum pump may be connected via a tube to an opening 270 in the base 266 (and / or the protrusions 268) from a side of the base 266 opposite the side of the plurality of protrusions 268. In this configuration, when the vacuum pump is activated, air is sucked through the opening 270 from the side of the protrusions 268 where the sheet 212 is held. As the sheet is heated in step (ii), the thermoplastic properties of the thermoplastic layers (second layer 220 and, optionally, third layer 225) make the thermoplastic layers flexible or thermoformable, thereby stretching and pulling the sheet 212 toward the mold 264 upon application of suction (i.e., negative pressure), according to some embodiments. When the heating is stopped and the thermoplastic layer is allowed to reach a temperature where it is harder and more elastic, external forces can no longer set the shape of the formed seal member 222, and the formed seal member 222 is elastically maintained in its newly formed 3D shape.

[0368] Reference is now made to Figure 6E, which illustrates the heat treatment of flat flexible sheet 212 using thermoforming, which, according to some embodiments, involves applying force using dies (264a, 264b) on two opposing sides of flexible sheet 212 to produce seal member 222 in an expanded state.

[0369] According to some embodiments, a method for manufacturing a seal member 222 is provided, the method including: (i) preparing (a) a flat sheet 212 including a tear-resistant first layer 210 and a thermoplastic second layer 220 as described hereinabove; and (b) a mold 264 including a first mold 264a and a second mold 264b, where first mold 264a includes a first base 266a and a plurality of first mold projections 268a, and second mold 264b includes a second base 266b and a plurality of second mold projections 268b. (ii) thermoforming the flat sheet 212 into a 3D shape at an elevated temperature by placing the flat sheet 212 between a plurality of first mold projections 268a and a plurality of second mold projections 268b and pressing the second mold 264b against the first mold 264a; and (iii) connecting two opposite edges of the sheet 212 in step (ii) to form a cylindrically folded cylindrical sealing member (or PVL skirt).

[0370] According to some embodiments, a method for manufacturing a seal member 222 is provided, the method including: (i) (a) a flat sheet 212 including a tear-resistant first layer 210, a thermoplastic second layer 220, and a third layer 225 as described herein; and (b) a mold 264 including a first mold 264a and a second mold 264b, where first mold 264a includes a first base 266a and a plurality of first mold projections 268a, and second mold 264b includes a second base 266b and a plurality of second mold projections 268b. (ii) thermoforming the flat sheet 212 into a 3D shape at an elevated temperature by placing the flat sheet 212 between a plurality of first mold projections 268a and a plurality of second mold projections 268b and pressing the second mold 264b against the first mold 264a; and (iii) connecting two opposite edges of the sheet 212 in step (ii) to form a cylindrically folded cylindrical sealing member (or PVL skirt).

[0371] The properties of each of the first layer 210, second layer 220, and third layer 225 are as described hereinabove. The temperature at which step (ii) is performed is also as described hereinabove.

[0372] According to some embodiments, the second mold 264b includes a second base 266b and a plurality of protrusions 268b extending away from the second base 266b and spaced apart from one another along the second base 266b.

[0373] According to some embodiments, step (ii) includes disposing the flat sheet 212 between the first mold projections 268a and the second mold projections 268b such that each of the first mold projections 268a (optionally, except for the outermost projections) is laterally positioned between the second mold projections 268b, the flat sheet 212 spacing the first mold projections 268a and the second mold projections 268b apart. According to some embodiments, step (ii) further includes pressing the second mold 264b against the first mold 264a to effectively engage the flat sheet 212 therebetween at an elevated temperature, thereby allowing the sheet 212 to conform to the aforementioned shape of the mold (see FIG. 6E). The second mold 264b and the first mold 264a may be identical to or different from each other.

[0374] According to some embodiments, step (ii) includes placing the flat sheet 212 between a plurality of first mold projections 268a and a plurality of second mold projections 268b, such that the plurality of first mold projections 268a and the plurality of second mold projections 268b are arranged alternately along both opposite sides of the sheet 212, each first mold projection 268a being arranged laterally between two second mold projections 268b (optionally excluding the outermost projections), the flat sheet 212 separating the first mold 264a and the second mold 264b, and step (ii) includes pressing the second mold 264b against the first mold 264a to effectively engage the flat sheet 212 therebetween at an elevated temperature, thereby allowing the flat sheet to conform to the shape of said molds.

[0375] According to some embodiments, step (ii) includes disposing the flat sheet 212 between a plurality of first mold projections 268a and a plurality of second mold projections 268b, such that the plurality of first mold projections 268a and the plurality of second mold projections 268b are arranged in a zipper-like configuration, and step (ii) includes pressing the second mold 264b against the first mold 264a, thereby effectively engaging the flat sheet 212 therebetween at an elevated temperature, thereby allowing the flat sheet to conform to the shape of the molds. According to some embodiments, step (ii) includes disposing the flat sheet 212 between a plurality of first mold projections 268a and a plurality of second mold projections 268b, such that the plurality of first mold projections 268a and the plurality of second mold projections 268b are arranged in a staggered configuration.

[0376] The terms "zipper configuration" and "staggered configuration," as used herein, can be understood from FIG. 6E. Specifically, as shown, a first mold inter-projection gap 269a is formed between each pair of adjacent first mold projections 268a. Similarly, according to some embodiments, a second mold inter-projection gap 269b is formed between each pair of adjacent second mold projections 268b. The zipper-like staggered configuration between the components of first mold 264a and second mold 264b is characterized by first mold projections 268a being located below and aligned with second mold inter-projection gaps 269b, and second mold projections 268b being located above and aligned with first mold inter-projection gaps 269a. Additionally, similar to conventional zipper-like configurations, the external (outermost) protrusion (which can refer to either the first mold protrusion 268a or the second mold protrusion 268b) does not necessarily have to be positioned above the inter-protrusion gap.

[0377] As disclosed hereinabove, a vacuum may be formed between the sheet 212 and each mold 264a and 264b to strengthen the attachment therebetween.

[0378] According to some embodiments, step (ii) further comprises cooling sheet 212 below a thermoformable temperature to stabilize the 3D shape in the unfolded, relaxed state of seal member 222. According to some embodiments, step (ii) further comprises removing said 3D shaped sheet 212 from molds 264a and 264b after the desired three-dimensional shape has been formed.

[0379] According to some embodiments, the method further includes (iii) connecting two opposing edges (i.e., first lateral edge 206 and second lateral edge 208) of the sheet of step (ii) to form a cylindrically folded cylindrical seal member (or PVL skirt). The connection between the opposing edges can be achieved using at least one of adhesive, stitching, or heat, and optionally melting the edges. Alternatively, step (iii) can include bonding the seal member 222 to the outer surface of the frame 106 using at least one of adhesive, stitching, or heat, and optionally melting the edges of the seal member 222 around its periphery (see FIGS. 5A-5C).

[0380] Reference is now made to Figures 7A-7C. Figure 7A illustrates flexible pre-coated sheet 212 in an unfolded, relaxed state, according to some embodiments. Figure 7B illustrates flexible pre-coated sheet 212 of Figure 7A being placed over mold 264, where flexible sheet 212 flexibly changes shape to form the shape of mold 264, according to some embodiments. Figure 7C illustrates a coating process for the reshaped flexible sheet 212 of Figure 7B, according to some embodiments.

[0381] According to some embodiments, a method for manufacturing a sealing member 222 is provided, the method including: (i) preparing a flat sheet 212 including a tear-resistant first layer 210 (see FIG. 7A ) and preparing a mold 264 including a base 266 and a plurality of protrusions 268; (ii) placing the flat sheet 212 on the mold 264, thereby engaging the flat sheet 212 with the mold 264, thereby allowing the sheet to conform to the mold 264 in a 3D shape (see FIG. 7B ), and covering the shaped sheet 212 with a second layer 220 (see FIG. 7C ); and (iii) connecting two opposite edges of the sheet in step (ii) to form a cylindrically folded cylindrical sealing member (or PVL skirt).

[0382] It will be appreciated that the phrase "fitted against said mold 264" is intended to mean that the flat sheet 212 is shaped similarly to the shape of the mold 264. More specifically, although the initial sheet 212 is flat, once placed and fitted against the mold 264, the sheet 212 roughly forms the shape of the protrusions 268 of the mold 264. This confirmation may be facilitated by gravity and / or assisted by an external force, according to some embodiments.

[0383] According to some embodiments, placing the flat sheet 212 onto the mold 264 involves allowing the sheet 212 to conform to the shape of said mold 264 by gravity.

[0384] As used herein, the term "gravity fitted" refers to material that is fitted onto the mold 264 in the orientation of gravity.

[0385] The properties of each of the first layer 210 and the second layer 220 are as described herein above.

[0386] According to some embodiments, the second layer 220 is formed from a thermoplastic material, and coating the 3D shaped sheet 212 with the second layer 220 in step (ii) comprises heat coating the shaped sheet 212 with the second layer 220 at an elevated thermoformable temperature. Heat coating can be performed using various coating techniques disclosed herein.

[0387] According to some embodiments, the pre-coated sheet 212 is engaged with the plurality of protrusions 268 of the mold 264 to form the plurality of ridges 230 corresponding to the desired 3D shape of the seal member 222, while the sheet is engaged with the base 266 to form the plurality of inter-ridge gaps 250. According to some embodiments, step (ii) further comprises stabilizing the 3D shape of the sheet 212 by cooling the sheet and / or the mold, optionally below a thermoformable temperature. According to some embodiments, step (ii) further comprises removing the formed 3D shaped sheet 212 from the mold 264. According to some embodiments, step (ii) further comprises removing the formed 3D shaped sheet 212 from the mold 264 when the 3D shape is elastically formed.

[0388] According to some embodiments, step (iii) involves connecting two opposing edges (i.e., first lateral edge 206 and second lateral edge 208) of the sheet from step (ii) to form a cylindrically folded cylindrical seal member (or PVL skirt). The connection between the opposing edges can be achieved using at least one of adhesive, stitching, or heat, and optionally melting the edges. Alternatively, step (iii) includes bonding the seal member 222 to the exterior surface of the frame 106 using at least one of adhesive, stitching, or heat, and optionally melting the edges of the seal member 222 around its periphery.

[0389] Reference is now made to Figures 8A-9C. Figure 8A illustrates a perspective view of a seal member 322 in an unfolded, relaxed state, according to some embodiments. Figures 8B and 8C illustrate cross-sectional views of a seal member 322, according to some embodiments. Figures 8D-8F illustrate perspective views of various configurations of a seal member 322 in a cylindrically folded state, according to some embodiments. Figures 9A-9C illustrate various configurations of a seal member 322 mounted on a frame 106 of a prosthetic valve 100, according to some embodiments.

[0390] According to another aspect, a seal member 322 is provided that is configured to be mounted on (or coupled to) an outer surface of a frame 106 of a prosthetic valve 100 (see, e.g., FIGS. 9A-9C ), or to any other similar prosthetic valve known in the art. According to certain examples, the present invention provides a prosthetic heart valve 100, comprising a frame 106 and a leaflet assembly 130 mounted therein, the frame including a plurality of intersecting struts 110, the frame being movable between a radially compressed state and a radially expanded state as disclosed hereinabove, the valve 100 further comprising a seal member 322 coupled to the outer surface of the frame 106, the seal member 322 having a three-dimensional (3D) shape in an unfolded, relaxed state.

[0391] The seal member 322 can be connected / attached to the frame 106 using any suitable technique or mechanism. For example, the seal member 322 can be sutured to the frame 106 utilizing sutures that can extend around the struts 110. The seal member 322 can be provided in an unfolded state and connected / attached to the frame 106 by folding it onto the frame 106, thereby transforming it from the unfolded state to the folded state. Alternatively, the seal member 222 can be provided in an already folded state prior to attachment to the frame 106. For example, the frame 106 can be inserted into the already cylindrically folded seal member 322 and sutured to such seal member 322. The seal member 222 can be configured to lie against the outer surface of the frame 106 when the prosthetic valve 100 is in the radially expanded state, as shown, for a snug fit against the frame 106.

[0392] According to some embodiments, the seal member 322 has a 3D shape in the unfolded, relaxed state, as can be seen, for example, in Figures 8A-8C. According to some embodiments, the seal member 322 has an essentially 3D shape in the cylindrically folded state (Figures 8D-8F and 9A-9C).

[0393] According to some embodiments, the seal member 322 has a 3D elastic structure such that the non-fibrous outer surface 380 of the seal member 322 exhibits a plurality of raised portions 330 having peaks 305 and a plurality of non-raised portions 350. In further embodiments, each of the plurality of non-raised portions 350 is defined by an adjacent pair of the plurality of raised portions 330. In further embodiments, the non-fibrous outer surface 380 is a smooth surface. In further embodiments, the non-fibrous outer surface 380 is a single / continuous surface.

[0394] In some embodiments, raised portions 330 are protrusions 330 and non-raised portions 350 are inter-protrusion gaps 350. As used herein, the terms "raised portions 330" and "protrusions 330" are interchangeable and refer to the same plurality of raised portions of seal member 322, as can be seen in Figures 8B-8C. As used herein, the terms "non-raised portions 350" and "inter-protrusion gaps 350" are interchangeable and refer to the same plurality of non-raised portions of seal member 322, as can be seen in Figures 8B-8C.

[0395] 8A , for example, seal member 322 includes a plurality of protrusions 330 that give seal member 322 a three-dimensional (3D) shape, as opposed to the substantially flat, two-dimensional shape that seal member 322 would assume if protrusions 330 were not present (see FIG. 10A ). Thus, it will be understood that the three-dimensional shape of three-dimensional seal member 322 includes (i) a spatial length dimension extending between outflow edge 307 and inflow edge 309 of seal member 322 (see FIGS. 8A , 8B, and 8C ), (ii) a spatial length dimension extending between first lateral edge 306 and second lateral edge 308 of seal member 322 (see FIG. 8A ), and (iii) a spatial length (thickness) dimension 322T, defined as the distance between protrusions 330 of the seal member and the height of its second surface 304 (see FIG. 8C ). It will further be appreciated that the 3D structure of the seal member 322 results in a thickness 322T that is at least 1000%, alternatively at least 2000%, greater than the thickness of the flat 2D structure before the protrusions 330 are formed on the upper surface.

[0396] According to some embodiments, the seal member 322 includes a plurality of protrusions 330 extending away from and spaced apart from one another along the first surface 302 of the seal member 322. The plurality of protrusions 330, according to some embodiments, define the 3D shape of the seal member 322 when in the expanded, relaxed state (as can be seen in FIGS. 8A-8C). According to some embodiments, the seal member 322 includes a flat surface (e.g., surface 316 or surface 304) opposite the first surface 302 when in the expanded, relaxed state. According to some embodiments, an inner layer (e.g., first layer 310) of the seal member 322 is flat when the seal member 322 is in the expanded, relaxed state.

[0397] According to some embodiments, the seal member 322 has four edges. According to some embodiments, the seal member 322 has four vertices. According to some embodiments, each of the four vertices of the seal member 322 is substantially at a right angle.

[0398] According to some embodiments, the seal member 322 has four substantially right-angled vertices and two sets of opposing edges (a first lateral edge 306 and a second lateral edge 308, and an outflow edge 307 and an inflow edge 309), where the opposing edges in each set are substantially parallel. According to some embodiments, the seal member 322 extends from the first lateral edge 306 to the second lateral edge 308 when the seal member 322 is in the unfolded state. According to some embodiments, the seal member 322 extends around the seal member centerline 311 when the seal member 322 is in the folded state. According to some embodiments, the seal member centerline 311 and the centerline 111 of the valve 100 are coaxial and may coincide when the seal member 322 is connected to the heart valve 100. According to some embodiments, the seal member 322 extends from the inflow edge 309 to the outflow edge 307. According to some embodiments, the seal member 322 extends from the leading edge 309 toward the leading edge 307 in both the folded and unfolded positions.

[0399] According to some embodiments, in the unfolded state, the seal member 322 is substantially rectangular. According to some embodiments, the distance between the first lateral edge 306 and the second lateral edge 308 is greater than the distance from the inflow edge 309 to the outflow edge 307.

[0400] According to some embodiments, each of the plurality of protrusions 330 extends radially outwardly away from the centerline 311 of the seal member when the seal member 322 is in a collapsed state (see FIGS. 8D-8F). According to some embodiments, each of the plurality of protrusions 330 extends radially outwardly away from the centerline 111 of the valve 100 when the seal member 322 is installed onto an upper surface (see FIGS. 9A-9C). According to some embodiments, the seal member 322 is collapsed by connecting the first lateral edge 306 and the second lateral edge 308 such that the plurality of protrusions 330 are oriented radially away from the centerline 311 of the seal member (see, for example, FIG. 8D). According to some embodiments, the seal member 322 in its folded state is coupled to the outer surface of the frame 106 of the prosthetic valve 100 such that the plurality of protrusions 330 are oriented to extend radially away from the centerline 111 (see, for example, FIG. 9A).

[0401] According to some embodiments, the seal member 322 further includes a plurality of inter-protrusion gaps 350, each gap 350 being located (or spaced) between two adjacent protrusions 330. According to further embodiments, one inter-protrusion gap 350 is formed between the outflow edge 307 and one protrusion 330, and another inter-protrusion gap 350 is formed between the inflow edge 309 and the other protrusion 330. The plurality of protrusions 330 and the plurality of inter-protrusion gaps 350 separating two adjacent protrusions 330, according to some embodiments, define the 3D shape of the seal member 322 when in the expanded, relaxed state. According to some embodiments, the plurality of inter-protrusion gaps 350 and the protrusions 330 face in the same direction.

[0402] Although the 3D shape of seal member 322 is not identical to the 3D shape of seal member 222, it will be understood that seal member 322 may comprise similar materials and / or have similar functionality and uses as those described herein above in connection with seal member 222. According to some embodiments, unlike the 3D shape of seal member 222, seal member 322 includes a flat surface (e.g., surface 316 or surface 304) located opposite first surface 302 when in an expanded, relaxed state.

[0403] According to some embodiments, the prosthetic valve 100 including the sealing member 322 is configured to be positioned (i.e., implanted) at a target implantation site (e.g., the aortic annulus in the case of an aortic valve replacement) to form contact between the arterial wall 105 and the plurality of protrusions 330, similar to the contact formed between the arterial wall 105 and the plurality of ridges 230 of the sealing member 222, as disclosed hereinabove. Advantageously, the plurality of protrusions 330 of the sealing member 322 are configured to contact the arterial wall 105 after expansion of the prosthetic heart valve 100 at the implantation site, thereby enabling a snug fit or engagement between the prosthetic heart valve 100 and the inner surface of the annular or arterial wall 105, thereby improving the PVL seal around the implanted prosthetic heart valve.

[0404] According to some embodiments, the seal member 322 is configured to be able to transition from an unfolded, relaxed state to a cylindrical, folded state based on elastic and / or flexible properties to form a cylindrical PVL skirt. The folded PVL skirt 322 may be bonded to the outer surface of the frame 106 of the prosthetic valve 100, for example, during a valve assembly procedure. Alternatively, the unfolded seal member 322 may be folded around the outer surface of the frame 106 and bonded to the outer surface of the frame to achieve a similar product.

[0405] According to some embodiments, the plurality of protrusions 330 may extend in different directions from the surface 302 to form a 3D shape on the top surface, which may be selected from an inverted U-shape, a hemisphere, a dome, a cylinder, a pyramid, a triangular prism, a pentagonal prism, a hexagonal prism, a flap, any other polygonal shape, and combinations thereof. Each possibility represents a different embodiment. According to further embodiments, the plurality of protrusions 330 may extend in different directions from the surface 302 to form parallel elongated 3D shapes on the top surface, which may be selected from an elongated U-shape, an elongated rectangular prism, an elongated rectangular prism, any other elongated polyhedron, and combinations thereof. Each possibility represents a different embodiment.

[0406] As used herein, the term "elongated 3D shape" refers to the elongated 3D shape of a protrusion (e.g., protrusion 330) of a seal member of the present invention, which can be characterized by having a variety of cross-sectional shapes selected from an inverted U-shape, a square, a rectangle, any other polygonal shape, and combinations thereof, each possibility representing a different embodiment.

[0407] 8D-8F, the plurality of protrusions 330 can extend in different directions from the surface 302, forming parallel elongated 3D shapes on the upper surface. The different directions can be perpendicular, horizontal, or diagonal relative to the centerline 311 of the cylindrical seal member 322 in its folded state. It will be appreciated that the orientation of the protrusions 330 in the folded state of the seal member 322 can be determined by the pre-folded configuration, i.e., the configuration of the seal member 322 when in its unfolded state. According to some embodiments, the seal member 322 has a resilient 3D shape, which includes the plurality of protrusions 330 forming a generally wavy configuration on the surface 302.

[0408] For example, seal member 322 may have a plurality of protrusions 330 that form a parallel elongated 3D shape and extend from first lateral edge 306 to second lateral edge 308 (as shown in FIG. 8A ), and seal member 322 may be folded by connecting first lateral edge 306 to second lateral edge 308 to form a cylindrical shape for seal member 322. In such an exemplary situation, upon such folding, seal member 322 in its folded shape will have a plurality of circumferentially extending protrusions 330 that are substantially parallel to inflow edge 309 and outflow edge 307 (as shown in FIG. 8D ).

[0409] In a second embodiment, the seal member 322 has a plurality of protrusions 330 that form a parallel elongated 3D shape and extend from the inflow edge 309 to the outflow edge 307 (not specifically shown in an unfolded, relaxed state). The seal member 322 may be folded by connecting the first lateral edge 306 to the second lateral edge 308 to form the cylindrical shape of the seal member 322. In such a second exemplary configuration, upon such folding, the seal member 322 in its folded shape has a plurality of vertically oriented protrusions 330 that are substantially perpendicular to the inflow edge 309 and the outflow edge 307 (as shown in FIG. 8E ).

[0410] Similarly, angled or diagonal projections in the unfolded state will result in diagonal projections in the collapsed state of seal member 322, as shown in Figure 8F.

[0411] As described in detail herein, the shape-forming process for forming the protrusions 330 on the seal member 322 is not limited to being performed before folding, and according to some embodiments, the protrusions 330 may be formed on the first surface 302 of the seal member 322 after folding. Furthermore, the protrusions 330 of the seal member 322 of the present invention need not form elongated 3D shapes that are parallel to one another.

[0412] According to some embodiments, each of the plurality of protrusions 330 follows a path line extending from the first lateral edge 306 to the second lateral edge 308 when the seal member 322 is in the unfolded state. According to some embodiments, each of the plurality of protrusions 330 follows a path line parallel to either the first lateral edge 306 and / or the second lateral edge 308 when the seal member 322 is in the unfolded state. According to some embodiments, each of the plurality of protrusions 330 follows a path line parallel to either the outflow edge 307 and / or the inflow edge 309 when the seal member 322 is in the unfolded state.

[0413] According to some embodiments, each of the plurality of protrusions 330 follows a path line extending circumferentially around the centerline 311 of the seal member when the seal member 322 is in its collapsed state (see FIG. 8D ). According to further embodiments, the plurality of protrusions 330 extends substantially perpendicular to the centerline 311 of the seal member when the seal member 322 is in its collapsed state, or substantially perpendicular to an axis parallel to the centerline 311. According to some embodiments, each of the plurality of protrusions 330 follows a path line extending circumferentially around the centerline 111, or a path line substantially perpendicular to the centerline 111, or an axis parallel to the centerline 111 when the seal member 322 is in its collapsed state and mounted on the frame 106 of the prosthetic heart valve 100 (see FIG. 9A ). According to some embodiments, each of the plurality of protrusions 330 follows a path line that is circumferentially about the centerline 311 of the seal member 322 and parallel to either the outflow edge 307 and / or the inflow edge 309 when the seal member 322 is in a folded state.

[0414] According to some embodiments, each of the plurality of protrusions 330 follows a path line that extends from the inflow edge 309 to the outflow edge 307 in the unfolded state of the seal member 322. According to some embodiments, each of the plurality of protrusions 330 follows a path line that is parallel to either the first lateral edge 306 and / or the second lateral edge 308 in the unfolded state of the seal member 322. According to some embodiments, each of the plurality of protrusions 330 follows a path line that is perpendicular to either the outflow edge 307 and / or the inflow edge 309 in the unfolded state of the seal member 322.

[0415] According to some embodiments, each of the plurality of protrusions 330 follows a path line that extends parallel to the centerline 311 of the seal member when the seal member 322 is in the folded state (see FIG. 8E ). According to some embodiments, each of the plurality of protrusions 330 follows a path line that extends parallel to the centerline 111 when the seal member 322 is in the folded state and mounted on the frame 106 of the prosthetic heart valve 100 (see FIG. 9B ). According to some embodiments, each of the plurality of protrusions 330 follows a path line that is perpendicular to either the outflow edge 307 and / or the inflow edge 309 of the seal member 322 when the seal member 322 is in the folded state.

[0416] According to some embodiments, each of the plurality of protrusions 330 follows a path line that extends obliquely along the surface of the seal member 322 in the unfolded state. According to some embodiments, each of the plurality of protrusions 330 follows a path line that extends obliquely along the surface of the seal member 322 relative to the centerline 111 in the folded state (see FIG. 8F). According to some embodiments, each of the plurality of protrusions 330 follows a path line that extends obliquely relative to the centerline 111 when the seal member 322 is in the folded state and mounted on the frame 106 of the prosthetic heart valve 100 (see FIG. 9C).

[0417] According to some embodiments, the seal member 322 includes a plurality of protrusions 330 extending around and / or away from the first surface 302, each protrusion being an elongated 3D shape selected from a hemisphere, a line (e.g., a ridge or band), a dome, a cube, a cylinder, a pyramid, and any other suitable polyhedron. Each possibility represents a different embodiment. According to further embodiments, each of the plurality of protrusions 330 forms an elongated 3D shape along the surface of the seal member 322 in a folded state (not shown). According to further embodiments, each of the plurality of protrusions 330 forms an elongated 3D shape along the surface of the seal member 322 in a folded state (not shown), extending radially around and / or away from the centerline 111 (see FIGS. 9A-9C ) when the seal member 322 is in a folded state and mounted on the frame 106 of the prosthetic heart valve 100. It will be understood that the term "elongated" refers to a raised portion (e.g., ridge 230 or protrusion 330, 430) having a length that is significantly greater than its width so that each raised portion surrounds the entire periphery of frame 106 or extends between the inflow and outflow edges of the seal member when the seal member is mounted thereon.

[0418] The various configurations and orientations described above may be advantageous with respect to different physiological and implantation-related requirements. For example, the configurations of Figures 8D and 9A may be advantageous due to the generally perpendicular orientation of the projections 330 relative to the axial direction of flow when the valve 100 is attached to the annular or arterial wall 105, potentially improving the PVL seal therebetween.

[0419] According to some embodiments, seal member 322 includes a first layer 310. According to some embodiments, first layer 310 is in the flat, unfolded, relaxed state of seal member 322.

[0420] According to some embodiments, the seal member 322 includes a first layer 310 and a second layer 320. According to further embodiments, the first layer 310 and the second layer 320 are each disposed outwardly relative to the outer surface of the frame 106 when the seal member 322 is coupled to the frame 106. According to further embodiments, the seal member 322 may include additional layers.

[0421] According to some embodiments, the second layer 320 contacts the first surface 315 of the first layer 310 (see FIG. 8B ). According to some embodiments, the second layer 320 contacts the first surface 315 of the first layer 310 in both the unfolded and folded states of the seal member 322. According to some embodiments, the second layer 320 is attached to and / or covers the first surface 315 of the first layer 310. According to some embodiments, the first surface 315 of the first layer 310 faces outward in the folded state of the seal member 322. According to some embodiments, the first surface 315 faces the implantation site (e.g., the annular wall or the arterial wall 105) when the seal member 322 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site. According to further examples, the second layer 320 defines the first surface 302 of the seal member 322, as shown in FIG. 8B . According to some embodiments, the first surface 302 of the seal member 322 faces outward in the folded state of the seal member 322. According to some embodiments, when the seal member 322 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site, the first surface 302 of the seal member 322 faces toward the implantation site.

[0422] According to some embodiments, the plurality of protrusions 330 extend away from the second layer 320 of the seal member 322 and are spaced apart from one another along the second layer 320, and the second layer 320 is attached to and / or covers the first surface 315 of the first layer 310.

[0423] Without wishing to be bound by any theory or mechanism of action, the various seal members 322 disclosed herein form three-dimensional shapes that may be the result of a thermal shaping procedure. Such procedures are made possible or facilitated by the use of high-temperature moldable thermoplastic materials, as described in detail herein. To enable the thermoplastic material to be molded or shaped into a desired structure using a thin sheet of object, it is advantageous for the thermoplastic material to comprise or cover the object. This may be achieved, for example, by using a thermoplastic coating layer to coat the object or by using a thermoplastic layer to form the object. While a single thermoplastic layer may be sufficient to enable the shape-forming process, in some embodiments, it may be advantageous to include multiple thermoplastic layers, such as two layers. Specifically, it may be advantageous to configure the seal member 322 so that two outer layers comprise a thermoplastic material.

[0424] According to some embodiments, the seal member 322 includes a third layer 325. According to some embodiments, the third layer 325 contacts the second surface 316 of the first layer 310 (see FIG. 8C ). According to some embodiments, the third layer 325 contacts the second surface 316 of the first layer 310 in both the unfolded and folded states of the seal member 322. According to some embodiments, the third layer 325 is attached to and / or covers the second surface 316 of the first layer 310. According to some embodiments, the second surface 316 of the first layer 310 faces inward when the seal member 322 is folded.

[0425] According to some embodiments, the second surface 316 faces away from the implantation site (e.g., arterial wall 105) when the sealing member 322 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site. According to further embodiments, the third layer 325 defines the second surface 304 of the sealing member 322, as shown in FIG. 8C . According to some embodiments, the second surface 304 of the sealing member 322 faces inward when the sealing member 322 is in a folded state. According to some embodiments, the second surface 304 of the sealing member 322 faces away from the anatomical wall at the implantation site when the sealing member 322 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at the implantation site.

[0426] According to some embodiments, the second surface 304 of the seal member 322 is flat (see FIG. 8C). According to other embodiments, the second surface 304 of the seal member 322 includes a plurality of additional protrusions 330 (not shown).

[0427] According to some embodiments, seal member 322 includes both second layer 320 and third layer 325. According to some embodiments, second layer 320 is connected to third layer 325. According to some embodiments, second layer 320 and third layer 325 are integrated to cover first layer 310, as shown in FIG. 8C . According to some embodiments, second layer 320 and third layer 325 collectively form a coating that covers both first side 302 and second side 304 of seal member 322, respectively. According to some embodiments, second layer 320 and third layer 325 collectively form a coating that covers seal member 322.

[0428] Based on the above, it will be appreciated that, according to some embodiments, the unfolded sealing member 322 may be folded into a folded state by connecting the first lateral edge 306 and the second lateral edge 308 over the second surface 304 such that the second surface 304 faces inward toward the centerline 311 of the sealing member and the first surface 302 faces outward in the folded state. Thus, when the folded sealing member 322 is mounted on the frame 106 of the prosthetic heart valve 100 and implanted at an implantation site, the second layer 320 and the plurality of protrusions 330 extending away from the second layer 320 contact an anatomical wall (e.g., the inner surface of the annular wall or arterial wall 105) at the implantation site.

[0429] According to some embodiments, seal member 322 extends between first surface 302 and second surface 304, and seal member 322 has a total layer thickness 303 measured between first surface 302 and second surface 304 at one of inter-projection gaps 350, as shown in FIG. 8C. According to some embodiments, said total layer thickness 303 is measured from first surface 302 of seal member 322 to second surface 316 of first layer 310 (not shown). According to some embodiments, total layer thickness 303 is measured from first surface 302 of seal member 322 (e.g., second layer 320) to second surface 304 (e.g., third layer 325), as shown in FIG. 8C.

[0430] According to some embodiments, the thickness 322T of the seal member 322 (defined as the distance between the seal member protrusion 330 and the second surface 304) is at least 1000% greater than the total layer thickness 303. In further embodiments, the thickness 322T is at least 2000%, at least 3000%, at least 4000%, at least 5000%, or at least 6000% greater than the total layer thickness 303 of the seal member 322. Each possibility represents a different embodiment. In still further embodiments, the thickness 322T is 6000% or less, 7000% or less, 8000% or less, 9000% or less, 10,000% or less, 20,000% or less, 30,000% or less, 40,000% or less, or 50,000% or less than the total layer thickness 303 of the seal member 322. Each possibility represents a different implementation.

[0431] 8B-8C are shown as moderate thickness ratios between thickness 322T and total layer thickness 303, it will be understood that, as discussed above, the actual ratio may be greater (e.g., thickness 322T may be 10 to 60 times greater than total layer thickness 303). For example, in some unconstrained implementations, total layer thickness 303 may be in the range of 0.02 mm to 0.1 mm, while thickness 322T may be in the range of 0.5 mm to 3 mm.

[0432] According to some embodiments, the 3D shape of the seal member 322 in its unfolded, relaxed state includes protrusions 330, each having a protrusion height 322PH that is a fraction of the thickness 322T. In further embodiments, each protrusion height 322PH and the total layer thickness 303 together define the thickness 322T of the seal member 322.

[0433] According to some embodiments, the seal member 322 has a resilient 3D structure such that the non-fibrous outer surface 380 of the seal member 322 exhibits a plurality of raised portions 330 having peaks 305 and a plurality of non-ridged portions 350, as disclosed hereinabove (see, e.g., FIGS. 8B-8C ). According to some embodiments, the non-fibrous outer surface 380 of the seal member 322 is defined as the outer surface of the first surface 302 combined with the outer surface of each of the plurality of raised portions 330 (i.e., protrusions 330). According to some embodiments, the peaks 305 are defined as the highest points along each of the outer surfaces of the plurality of raised portions 330 that extend away from the first surface 302 of the seal member 322. According to some embodiments, the height of each peak 305 is defined as the distance (e.g., thickness 322T) of the highest point along the outer surface of each of the plurality of raised portions 330 relative to the frame 106 when the sealing member 322 is bonded to the outer surface of the frame 106 of the prosthetic valve 100.

[0434] According to some embodiments, the non-raised portion 350 is defined as an inter-projection gap 350. In further such embodiments, the height of each non-raised portion 350 is defined as the distance of the first surface 302 from the frame 106 when the seal member 322 is coupled to the outer surface of the frame 106 of the prosthetic valve 100 (e.g., total thickness 303). According to some embodiments, the distance of the peak 305 from the frame 106 is at least 1000% greater than the distance of the non-raised portion 350 from the frame 106 in the absence of an external force applied to press the raised portion 330 against the frame. According to further embodiments, the distance of the peak 305 from the frame 106 is at least 1500%, at least 2000%, at least 3000%, at least 4000%, at least 5000%, or at least 6000% greater than the distance of the non-raised portion 350 from the frame. Each possibility represents a different implementation.

[0435] It will be understood that any reference to thickness 322T of seal member 322 is equivalent to the distance of peak 305 of raised portion 330 from the outer surface of frame 106 in the relaxed state of seal member 322 when bonded to frame 106. Similarly, any reference to total layer thickness 303 is equivalent to the distance of non-raised portion 350 from the outer surface of frame 106 when seal member 322 is bonded to frame 106.

[0436] According to some embodiments, first layer 310 comprises the same material as first layer 210, as described herein above. According to some embodiments, first layer 310 is formed from a flexible and / or elastic material configured to provide mechanical stability, and optionally tear resistance (or tear strength), to seal member 322. In further embodiments, first layer 310 is configured to allow for continued, durable attachment of seal member 322 to the outer surface of frame 106 of prosthetic valve 100, optionally by preventing irreversible deformation (e.g., resisting tearing), thereby providing mechanical stability to the structure during its use.

[0437] The first layer 310 can comprise various biocompatible woven fabrics, including, for example, materials such as various synthetic materials (e.g., polyethylene terephthalate (PET), polyester, polyamide (e.g., nylon), polypropylene, polyether ether ketone (PEEK), polytetrafluoroethylene (PTFE), etc.), natural tissue and / or fibers (e.g., bovine pericardium, silk, cotton, etc.), metals (e.g., metal mesh or braid including gold, stainless steel, titanium, nickel, nickel titanium (nitinol), etc.), and combinations thereof. Each possibility represents a different embodiment. The first layer 310 can be a metallic or polymeric member, such as a shape-memory metallic or polymeric member. The first layer 310 can be a woven fabric. It will be understood that the first layer 310 is not limited to a woven fabric. Other fabric structures can be used, such as woven fabrics, knitted fabrics, woven webs, woven felts, filament-spun fabrics, and the like. The fabric of the first layer 310 may comprise at least one suitable material selected from various synthetic materials, natural tissues and / or fibers, metals, and combinations thereof, as described herein above.

[0438] According to some embodiments, first layer 310 comprises at least one tear-resistant material, optionally comprising a PET fabric, configured to provide mechanical stability and tear resistance as well as structural support, similar to the properties and characteristics of first layer 210 as described herein above. According to further embodiments, first layer 310 comprises a tear-resistant PET fabric. According to further embodiments, first layer 310 comprises at least one tear-resistant knitted / woven PET fabric.

[0439] According to some embodiments, the first layer 310 includes at least one tear-resistant, flexible material that can withstand a force load of greater than about 3 N before tearing, thereby allowing the seal member 322 to operate reliably without tearing during normal use. According to further embodiments, the at least one tear-resistant, flexible material in the first layer 310 can withstand a force load of approximately 5 N, 7 N, 10 N, 15 N, 20 N, 25 N, 30 N, or more before tearing. Each possibility represents a different embodiment. According to still further embodiments, the at least one tear-resistant, flexible material in the first layer 310 can withstand a force load of greater than about 20 N before tearing. According to still further embodiments, the at least one tear-resistant, flexible material in the first layer 310 can withstand a force load of greater than about 30 N before tearing. According to a preferred embodiment, the at least one tear-resistant, flexible material in the first layer 310 comprises a PET fabric and can withstand a load of at least about 20 N of force before tearing. According to some embodiments, the flexible, tear-resistant material can withstand a load ranging from 15 N to 500 N. According to some embodiments, the flexible, tear-resistant material can withstand a load ranging from 20 N to 500 N.

[0440] According to some embodiments, the first layer 310 is formed from at least one biocompatible material, as disclosed hereinabove.

[0441] 8C , when first layer 310 is covered by second layer 320 and third layer 325, it will not contact tissue during implantation, and it will be appreciated that in this case first layer 310 may be formed from a non-biocompatible material. Nevertheless, forming first layer 310 from a biocompatible material may be preferable in this case to avoid the risk of either second layer 320 or third layer 325 becoming worn or torn, thereby exposing a portion of first layer 310.

[0442] According to some embodiments, at least one of second layer 320, third layer 325, and plurality of protrusions 330 comprises the same material as second layer 220, as described herein above. According to some embodiments, second layer 320 and plurality of protrusions 330 are configured to contact implantation site tissue (i.e., the inner surface of the annular or arterial wall 105) and therefore are formed from at least one resilient, biocompatible material. Furthermore, according to some embodiments, second layer 320 and plurality of protrusions 330 are advantageously formed from a material that can prevent / resist and / or reduce the extent of tissue ingrowth around or onto seal member 322, allowing for easier removal of valve 100 from the implantation site in the event an explantation procedure is required, as described in detail above.

[0443] According to some embodiments, the first surface 302 (i.e., second layer 320) of the seal member 322 is characterized by having a smooth and / or low-friction surface configured to reduce friction against tissue at the implantation site, thereby reducing tissue ingrowth thereon and allowing for easier removal of a previously implanted valve from the implantation site. According to some embodiments, each of the plurality of protrusions 330 is characterized by having a smooth and / or low-friction outer surface configured to reduce friction against tissue at the implantation site for reasons discussed herein above. According to some embodiments, the second layer 320 and / or each of the plurality of protrusions 330 may include silicone or other lubricious materials or polymers, which may aid in an extraction procedure for removing the prosthetic valve from the implantation site.

[0444] According to some embodiments, the second layer 320 and / or the plurality of projections 330 are continuous in a manner that does not include yarns and / or strands (including not including textured yarns or strands). According to further embodiments, the plurality of projections 330 do not have discontinuities that may extend along their entire width.

[0445] According to some embodiments, the second layer 320 and the plurality of protrusions 330 (and optionally the third layer 325) can be formed from a variety of suitable biocompatible synthetic materials, such as, but not limited to, thermoplastic materials. According to some embodiments, the thermoplastic materials are selected from the group consisting of polyamides, polyesters, polyethers, polyurethanes, polyolefins, polytetrafluoroethylene, and combinations and copolymers thereof. According to some embodiments, the second layer 320 and the plurality of protrusions 330 (and optionally the third layer 325) can be formed from a variety of suitable biocompatible synthetic materials, such as, but not limited to, thermoplastic materials, including thermoplastic elastomers (TPEs). According to some embodiments, the thermoplastic elastomers are selected from the group consisting of thermoplastic polyurethanes (TPUs), styrene block copolymers (TPSs), thermoplastic polyolefin elastomers (TPOs), thermoplastic vulcanizates (TPVs), thermoplastic copolyesters (TPCs), thermoplastic polyamides (TPAs), and combinations and variations thereof. Each possibility represents a different embodiment.

[0446] According to some embodiments, at least one of the second layer 320, the third layer 325, and the plurality of protrusions 330 comprises at least one thermoplastic and thrombogenic material, which comprises at least one thermoplastic elastomer, optionally including TPU. According to further embodiments, the second layer 320 and the plurality of protrusions 330 are configured to form a 3D shape of the sealing member 322 in a folded cylindrical state, which shape is configured to enhance PVL sealing between the prosthetic heart valve 100 and the inner surface of the annular or arterial wall 105, and optionally to prevent and / or reduce tissue ingrowth onto the upper surface. According to some embodiments, the second layer 320, the third layer 325, and the plurality of protrusions 330 comprise TPU.

[0447] When incorporated into the seal member 322, the third layer 325 may, according to some embodiments, be integral with the second layer 320, as described further herein. When the third layer 325 and the second layer 320 are each formed as an integral coating over the first layer 310, according to some embodiments, they may preferably be formed from the same material. Even if the third layer 325 and the second layer 320 are each separate, according to some embodiments, they may have similar or identical compositions. According to some embodiments, the third layer 325 and the second layer 320 are each formed from the same material.

[0448] According to some embodiments, each of the plurality of protrusions 330 is formed from a solid (i.e., non-hollow) material / object comprising at least one thermoplastic and thrombogenic material as described herein above, which optionally comprises TPU. According to further embodiments, each of the plurality of protrusions 330 is not hollow but is formed entirely from at least one thermoplastic and thrombogenic material as described herein above, which optionally comprises TPU. According to some embodiments, each of the plurality of protrusions 330 defines a solid structure.

[0449] According to some embodiments, the plurality of protrusions 330 and the plurality of inter-protrusion gaps 350 separating adjacent protrusions 330 along the second layer 320 are configured to contact the implantation site (i.e., the inner surface of the annular or arterial wall 105). According to some embodiments, the plurality of protrusions 330 are formed from the same material as the second layer 320, and therefore are formed from the same resilient, biocompatible material, and are configured to prevent / resist and / or reduce tissue ingrowth around the sealing member 322, thereby allowing for easy removal of the valve 100 from the implantation site should an explantation procedure be required.

[0450] According to some embodiments, the seal member 322 includes a first layer 310, a second layer 320, a plurality of protrusions 330 extending away from the second layer 320 and covering at least the first surface 302, and optionally a third layer 325, wherein the first layer 310 is configured to provide mechanical stability and tear resistance and to support the structure, while the second layer 320 and the plurality of protrusions 330 (and optionally the third layer 325) are configured to form and maintain an elastic 3D shape, and the second layer 320 and the plurality of protrusions 330 are optionally configured to prevent and / or reduce tissue ingrowth onto the upper surface.

[0451] It is envisioned that second layer 320 alone lacks the ability to support the structure of seal member 322, is unable to maintain good attachment to the exterior surface of frame 106, and optionally has low tear resistance. Advantageously, the combination of first layer 310, second layer 320 alone or second layer 320 with optional third layer 325, and plurality of protrusions 330 provides the desired characteristics for seal member 322. According to some embodiments, second layer 320 comprising TPU, alone or together with optional third layer 325, and plurality of protrusions 330 are reinforced by first layer 310 comprising PET to provide the necessary strength to retain sutures.

[0452] It is contemplated that a thermoplastic elastomer material, such as TPU, may be utilized as a layer of the seal member 322 and / or as a component within the plurality of protrusions 330 to form a desired 3D shape of the seal member 322 having the plurality of resilient protrusions 330. In some embodiments, the plurality of resilient protrusions 330 of the seal member 322 are advantageously configured to contact and compress against the annular or arterial wall 105 at the implantation site after expansion of the prosthetic heart valve 100, thereby improving the PVL seal between the prosthetic heart valve 100 and the inner surface of the annular or arterial wall 105. Thus, according to some embodiments, each of the plurality of protrusions 330 is resilient and resiliently compressible. The resilient and resiliently compressible properties of the plurality of protrusions 330 can potentially improve retention of the seal member 322 against the surrounding tissue of the native heart valve at the implantation site.

[0453] According to some embodiments, the sealing member 322 has an elastic 3D shape that is configured to deform when an external force is applied to the sealing member (e.g., when pressed against the annular or arterial wall 105 or against the inner wall of a sheath or capsule), and is further configured to return to its original shape (i.e., relaxed shape) when the external force is no longer applied (e.g., when the valve is released from the shaft or capsule before being expanded).

[0454] It is understood that the compressibility of the protrusions 330 is consistent with the elastic 3D structure of the second layer 320 to which the protrusions 330 are connected, because the structure of the protrusions 330 in the second layer 320 is restored when compression on the protrusions 330 ceases (e.g., when the sealing member 322 returns to a relaxed state).

[0455] According to some embodiments, the seal member 322 includes at least a first layer 310 including a tear-resistant material, a second layer 320 covering at least the first surface 302 and including a thermoplastic and anti-thrombogenic material, and a plurality of protrusions 330 extending away from the second layer 320. According to some embodiments, the seal member 322 further includes a third layer 325 including a thermoplastic and anti-thrombogenic material. According to further embodiments, the seal member 322 includes a first layer 310 including a tear-resistant material including a PET fabric, and a second layer 320 including a plurality of protrusions 330 extending therefrom and including a thermoplastic and anti-thrombogenic material including TPU. According to further embodiments, the seal member 322 includes a third layer 325 including a thermoplastic and anti-thrombogenic material including TPU.

[0456] 10A-10C, extrusion-based processing steps for manufacturing seal member 322, according to some embodiments, will now be described.

[0457] According to some embodiments, there is provided a PVL skirt 322 manufactured by the method of the present invention. According to some embodiments, there is provided a PVL skirt 322 in a folded state manufactured by the method of the present invention.

[0458] According to some embodiments, a method is provided for manufacturing a seal member, such as seal member 322 described hereinabove, in a cost-effective and simple manner. According to some embodiments, the method includes (i) providing a tear-resistant flat sheet 312, (ii) subjecting the sheet to a thermal shaping process to form a 3D shape in an unfolded, relaxed state, and (iii) connecting two opposite edges of the sheet 312 in step (ii) to form a cylindrical seal member (or PVL skirt) in a cylindrically folded state.

[0459] According to some embodiments, step (i) includes providing a tear-resistant flat sheet 312 including a first layer 310 comprising at least one tear-resistant material as described herein above, the tear-resistant material optionally comprising a PET fabric.

[0460] According to some embodiments, step (i) includes providing a flat flexible sheet 312 including a tear-resistant first layer 310 and a thermoplastic second layer 320. According to some embodiments, step (i) includes providing a flat flexible sheet 312 including the tear-resistant first layer 310 disposed between the thermoplastic second layer 320 and the thermoplastic third layer 325 of the flat flexible sheet 312 (see FIG. 10A ).

[0461] According to some embodiments, step (i) includes providing a flat flexible sheet 312 including a tear-resistant first layer 310 and coating at least a first side 315 of the first layer 310 with a thermoplastic coating to form a thermoplastic second layer 320. According to some embodiments, step (i) includes providing a flat flexible sheet 312 including a tear-resistant first layer 310 and coating a first side 315 and a second side 316 of the first layer 310 with a thermoplastic coating to form a thermoplastic second layer 320 and a thermoplastic third layer 325, respectively.

[0462] The coating of the tear-resistant first layer 310 can be performed by a coating technique selected from the group consisting of brushing, spray coating, dip coating, immersion or impregnation, and combinations thereof. However, the method according to the present invention is not limited to these coating techniques, and according to some embodiments, other coating techniques, such as chemical vapor deposition, vapor deposition, chemical vapor deposition, physical vapor deposition, printing, and the like, may be suitably used. Such techniques are generally suitable for medical fabrics. Furthermore, printing techniques, such as roller printing, stencil printing, screen printing, inkjet printing, lithographic printing, 3D printing, and the like, may also be used with the present invention to apply the thermoplastic polymer coating.

[0463] The thermoplastic coating can include the same material as the material forming the second layer 320. The thermoplastic coating can include thermoplastic materials such as polyamide, polyester, polyether, polyurethane, polyolefin, polytetrafluoroethylene, and combinations and copolymers thereof. The thermoplastic coating including a thermoplastic material can include thermoplastic elastomeric materials such as thermoplastic polyurethane (TPU), styrene block copolymer (TPS), thermoplastic polyolefin elastomer (TPO), thermoplastic vulcanizate (TPV), thermoplastic copolyester (TPC), thermoplastic polyamide (TPA), and combinations and variations thereof. Each possibility represents a different embodiment. The thermoplastic coating can include TPU. The thermoplastic coating can include a biocompatible and thrombogenic material as disclosed herein.

[0464] It will be understood that the properties introduced above for each of the layers (i.e., first layer 310, second layer 320, and third layer 325) apply equally to each layer when referring to the method of manufacturing the seal member. According to some embodiments, first layer 310 comprises a tear-resistant PET fabric. According to some embodiments, second layer 320, third layer 325, or both, comprise at least one thermoplastic material. According to some embodiments, second layer 320, third layer 325, or both, comprise at least one anti-thrombogenic thermoplastic elastomer material, including TPU. According to some embodiments, second layer 320 and third layer 325 are formed from the same material. According to some embodiments, third layer 325 is integral with second layer 320, as described in more detail herein.

[0465] According to some embodiments, step (ii) of forming a 3D shape in the unfolded, relaxed state by subjecting the sheet to a thermal shaping process involves an extrusion-based shaping process, which includes extruding a plurality of members 331 onto the surface 302 of the second layer 320 of the sheet 312. According to some embodiments, each member 331 comprises a molten composition including a thermoplastic material (optionally non-thrombogenic). In further embodiments, each member 331 is extruded using an extruder including an extruder die 332 (see FIG. 10B ). In further embodiments, each member 331 is an elongated member 331 and can extend from at least one of the outflow edge 307 toward the inflow edge 309 or from the first lateral edge 306 toward the second lateral edge 308.

[0466] The terms "extrusion" or "extrusion," as used herein, refer to the process of forcing a molten composition through a die orifice having a desired cross-sectional shape corresponding to the desired shape of the extrusion member 331. The process of forcing the molten composition through the die orifice is carried out under pressure and heat. The extrusion of the thermoplastic and thrombogenic material can be carried out by 3D printing, where the die orifice is a movable printer extrusion head.

[0467] The melt composition can include thermoplastic materials such as polyamides, polyesters, polyethers, polyurethanes, polyolefins, polytetrafluoroethylene, and combinations and copolymers thereof. The melt composition including thermoplastic materials can include thermoplastic elastomeric materials such as thermoplastic polyurethanes (TPUs), styrene block copolymers (TPSs), thermoplastic polyolefin elastomers (TPOs), thermoplastic vulcanizates (TPVs), thermoplastic copolyesters (TPCs), thermoplastic polyamides (TPAs), and combinations and variations thereof. Each possibility represents a different embodiment. The melt composition can include TPUs. The melt composition can include biocompatible and antithrombogenic materials as disclosed herein above.

[0468] The molten composition may further include various adhesives or additives configured to enhance adhesion between the extruded composition and the surface 302 of the second layer 320 of the sheet.

[0469] The molten composition can be extruded at an elevated temperature sufficient to transition the molten composition to a flowable molten state and extrude it under pressure through an extruder die 332 for forming and depositing on the surface 302 of the second layer 320 of the sheet 312. According to some embodiments, the elevated temperature in step (ii) is approximately greater than 100°C, greater than 125°C, greater than 150°C, greater than 175°C, greater than 200°C, greater than 225°C, greater than 250°C, greater than 275°C, greater than 300°C, or greater. Each possibility represents a different embodiment.

[0470] According to some embodiments, step (ii) includes extruding a plurality of members 331 onto the thermoplastic second layer 320 of the flat flexible sheet 312, where each extruded member 331 extends from at least a first lateral edge 306 to a second lateral edge 308 of the sheet 312, thereby forming a plurality of 3D shapes on the sheet configured to transition to the configuration of protrusions 330 of the seal member 322 depicted in Figure 8D. According to some embodiments, step (ii) includes extruding a plurality of members 331 onto the thermoplastic second layer 320 of the flat flexible sheet 312, where each extruded member 331 extends from an inflow edge 309 to an outflow edge 307 of the sheet 312, thereby forming a plurality of 3D shapes on the sheet configured to transition to the configuration of protrusions 330 of the seal member 322 depicted in Figure 8E.

[0471] According to some embodiments, step (ii) includes extruding a plurality of members 331 onto the thermoplastic second layer 320 of the flat flexible sheet 312, where each extruded member 331 extends diagonally along at least a portion of the second layer 320 of the flat flexible sheet 312, thereby forming a plurality of 3D shapes on the sheet configured to transition into the configuration of protrusions 330 of the sealing member 322 illustrated in FIG. 8F.

[0472] After extruding the elongated members 331, each containing the molten composition, onto the surface 302 of the second layer 320 of the sheet to form a 3D shape on the sheet, the 3D-shaped sheet can be cooled, thereby stabilizing the 3D shape in the expanded, relaxed state of the sealing member. During cooling of the 3D-shaped sheet, the molten composition transitions to a semi-rigid or elastic, relatively rigid state, and the shape of the extruded elongated members 331 can transition to form the shape of a plurality of protrusions 330 (see FIG. 10C ). This formation, according to some embodiments, may be facilitated by gravity and / or assisted by an external force. According to some embodiments, step (ii) further includes cooling (i.e., reducing the temperature of) the sheet 312 to a temperature below 40° C. According to further embodiments, the temperature reduction in step (ii) is cooling the sheet 312 to room temperature.

[0473] According to some embodiments, after cooling, each extruded elongate member 331 transitions to a semi-rigid or resilient, relatively rigid state, resulting in the formation of multiple protrusions 330 in the seal member 322, as shown in Figures 9A-9C.

[0474] It will be appreciated that the thermoplastic properties of each of the plurality of protrusions 330 enable the extrusion-based shape-forming process described above. Specifically, the thermoplastic material transforms from an elastic, relatively rigid state at low temperatures to a pliable, relatively soft state when heated and / or rendered fluid and molten under extrusion conditions. In step (ii), the thermoplastic molten composition, according to some embodiments, is heated under pressure within an extruder to form a molten state, thereby enabling the extruded plurality of elongated members 331 to form a 3D shape including the protrusions 330 after cooling and transforming to an elastic, relatively rigid state.

[0475] 10B-10C, a plurality of elongated members 331 comprising a thermoplastic melt composition are extruded onto surface 302 of second layer 320 of sheet 312, where the thermoplastic melt composition is in a flowable molten state at an elevated temperature, as disclosed above. According to some embodiments, in step (ii), each elongated member 331 is extruded onto surface 302 of second layer 320 to form a 3D shape on the sheet. After forming the desired 3D shape, sheet 312 can be cooled, which causes the thermoplastic melt composition to return to an elastic, non-compliant state, thereby transitioning to the shape of a plurality of protrusions 330, according to some embodiments, and stabilizing seal member 322 in an expanded state (FIG. 10C).

[0476] According to some alternative embodiments, step (ii) of forming a 3D shape in the unfolded, relaxed state by subjecting the sheet to a thermal shaping process involves an injection shaping process, which includes inserting the flat flexible sheet 312 into a mold (not shown) and adding / injecting a molten composition comprising a thermoplastic and anti-thrombogenic material as described herein into said mold, wherein the molten composition conforms to the shape of the mold on at least one side of the flat flexible sheet 312. The molten composition can be molded at an elevated temperature as described herein above. The molding process of forming the thermoplastic and anti-thrombogenic material into the desired 3D shape on at least one side of the coated sheet including the plurality of protrusions 330 on its upper surface can be performed, for example, by injection molding. After the thermoplastic and anti-thrombogenic material has formed the desired 3D shape on at least one surface of the sheet 312 inside the mold, the formed 3D molded coated sheet can be cooled and removed from the mold, thereby stabilizing the 3D shape in the expanded, relaxed state of the sealing member 322.

[0477] According to some embodiments, the step (i) sheet 312 has a first side 302 and a second side 304, and the distance between the first side 302 and the second side 304 of the step (i) sheet 312 constitutes the initial thickness 312T of the step (i) sheet 312 (see FIG. 10A ). According to some embodiments, the step (i) sheet 312 is flat and substantially two-dimensional. This means that the initial thickness 312T of the step (i) sheet 312 is significantly shorter compared to the initial width and / or length of the sheet 312. According to some embodiments, the initial thickness 312T corresponds to or is the same as the total layer thickness 303, as described above.

[0478] According to some embodiments, by performing the method of the present invention, a protrusion 330 is formed, which has a protrusion height 322PH that is a portion of the thickness 322T of the seal member 322 in its expanded, relaxed state (see FIG. 10C).

[0479] According to some embodiments, after forming the plurality of protrusions 330 in step (ii), the thickness 322T of the seal member 322 in its unfolded, relaxed state, configured to form a 3D shape, is at least 1000% greater than the initial thickness 312T of the sheet 312. According to further embodiments, the thickness 322T of the seal member 322 in its unfolded, relaxed state is at least 2000%, at least 3000%, at least 4000%, at least 5000%, or at least 6000% greater than the initial thickness 312T of the sheet 312. Each possibility represents a different embodiment.

[0480] It will be understood that any reference to thickness 312T of seal member 322 is equivalent to the distance of peak 305 from the outer surface of frame 106 in the relaxed state of seal member 322 when bonded to frame 106. Similarly, any reference to initial thickness 312T of sheet 312 is equivalent to the distance of non-raised portion 350 from the outer surface of frame 106 when seal member 322 is bonded to frame 106.

[0481] According to some embodiments, the thickness change of sheet 312 (from 312T to 322T) after the methods described herein is configured to transform the initial 2D structure of sheet 312 into the 3D structure of seal member 322. In some implementations, sheet 312 obtained after step (ii) has dimensions greater than either the desired final width and / or the desired final length, and the method can include the additional step of cutting sheet 312 to the desired final width and / or the desired final length after step (ii) and before step (iii).

[0482] Reference is now made to Figures 11A-11E, which illustrate processing steps utilizing multiple mask members 333 to fabricate a seal member 322, according to some embodiments.

[0483] According to some embodiments, there is provided a cost-effective and simple method for manufacturing a seal member 322 as described herein above, the method comprising: (i) providing a tear-resistant flat sheet 312 including a first layer 310 comprising at least one tear-resistant material, which optionally comprises a PET fabric (FIG. 11A); and coating at least one surface of the flat tear-resistant sheet with a thermoplastic polymer coating layer to form a second layer 320 on the upper surface; (ii) treating the sheet through a thermal shaping process using a mold 334 to form a 3D shape in an unfolded, relaxed state and to deposit a thermoplastic material non-uniformly on the second layer 320; and (iii) connecting two opposite edges of the sheet in step (ii) to form a cylindrical seal member (or PVL skirt) when folded into a cylinder.

[0484] According to some embodiments, step (i) includes coating the first side 315 and the second side 316 of the first layer 310 with a thermoplastic coating as defined herein above, thereby forming a thermoplastic second layer 320 and a thermoplastic third layer 325, respectively, on opposite sides of the flat sheet 312 (FIG. 11B).

[0485] According to some embodiments, step (i) of coating at least one side of the flat tear-resistant sheet with a thermoplastic polymer coating layer can be performed using at least one coating technique, as described herein above.

[0486] It will be understood that any properties introduced above with respect to each of the layers (i.e., first layer 310, second layer 320, and third layer 325) apply equally to each layer when referring to the method of manufacturing the seal member 322 of the present invention.

[0487] According to some alternative embodiments, step (i) involves providing a prefabricated tear-resistant flat sheet 312 comprising a tear-resistant first layer 310, a thermoplastic second layer 320, and optionally a thermoplastic third layer 325. According to further such embodiments, the first layer 310 comprises a PET fabric, and the second layer 320 and / or the third layer 325 each comprise TPU.

[0488] According to some embodiments, step (ii) involves placing a mold 334 including a plurality of spaced-apart mask members 333 on the sheet 312 and depositing a thermoplastic material into spaces formed between adjacent mask members 333. According to some embodiments, step (ii) involves placing a mold 334 including a plurality of spaced-apart mask members 333 on the surface 302 of the second layer 320 of the sheet 312 and depositing a thermoplastic material into spaces formed between adjacent mask members 333.

[0489] According to some embodiments, step (ii) involves preparing a mold 334 including a plurality of mask members 333 spaced apart from one another and disposing the plurality of mask members 333 on the surface 302 of the second layer 320 of the sheet 312 (see FIG. 11C). According to some embodiments, step (ii) of processing the sheet to form a 3D shape in an unfolded, relaxed state involves first preparing a mold 334 including a plurality of mask members 333, disposing the plurality of mask members 333 on the surface 302 of the second layer 320 of the sheet 312, and disposing the mask members 333 apart from one another on the surface 302, wherein each of the plurality of mask members 333 is positioned above a corresponding inter-protrusion gap 350 (see FIG. 11C). The mask members 333 may be equally spaced apart from one another, according to some embodiments.

[0490] According to some embodiments, step (ii) includes disposing a plurality of mask members 333 on the surface 302 of the second layer 320 of the sheet 312, where each mask member 333 extends from the first lateral edge 306 to the second lateral edge 308 of the sheet 312. According to some embodiments, step (ii) includes disposing a plurality of mask members 333 on the surface 302 of the second layer 320 of the sheet 312, where each mask member 333 extends from the inflow edge 309 to the outflow edge 307 of the sheet 312. According to some embodiments, step (ii) includes disposing a plurality of mask members 333 on the surface 302 of the second layer 320 of the sheet 312, where each mask member 333 extends diagonally along at least a portion of the second layer 320 of the flat flexible sheet 312.

[0491] According to some embodiments, step (ii) further comprises depositing a thermoplastic material into the spaces formed between adjacent mask members 333, wherein the deposition of the thermoplastic material is carried out by a technique selected from the group consisting of extrusion, brush coating, spray coating, chemical deposition, liquid deposition, vapor deposition, chemical vapor deposition, physical vapor deposition, roller printing, stencil printing, screen printing, inkjet printing, lithographic printing, 3D printing, and combinations thereof. Each possibility represents a different embodiment.

[0492] According to some embodiments, step (ii) further comprises depositing a thermoplastic material at an elevated temperature on the surface 302 of the second layer 320 of the sheet 312 into the spaces formed between adjacent mask members 333. The thermoplastic material may comprise a thermoplastic elastomer material, such as TPU, which is optionally also anti-thrombogenic, as disclosed herein above.

[0493] According to some embodiments, depositing a thermoplastic material involves depositing multiple thermoplastic coating layers, each of which may comprise a thermoplastic coating as defined herein above. The multiple thermoplastic coating layers may be configured to transition to a semi-solid or solid state after deposition, thereby forming the multiple protrusions 330. Deposition of the multiple thermoplastic coating layers may be performed by a coating technique selected from brush coating, spray coating, chemical deposition, liquid deposition, vapor deposition, chemical vapor deposition, physical vapor deposition, roller printing, stencil printing, screen printing, inkjet printing, lithographic printing, 3D printing, and combinations thereof. Each possibility represents a different embodiment. Deposition of the multiple thermoplastic coating layers may be performed by liquid deposition.

[0494] According to some embodiments, step (ii) comprises depositing a molten composition comprising a thermoplastic and anti-thrombogenic material (e.g., TPU) at an elevated temperature (liquid deposition), as described herein above. According to some embodiments, the deposition occurs within spaces formed between adjacent mask members 333 (see FIG. 11C). According to some embodiments, step (ii) further comprises cooling the mask members 333 and / or the deposited molten composition after deposition.

[0495] It will be appreciated that upon cooling, the molten composition transitions to a semi-solid or solid state, thereby forming a plurality of protrusions 330, each of which is disposed between adjacent mask members 333 (see FIG. 11D). According to a further embodiment, the molten composition is extruded in the direction of arrow 317 using an extruder equipped with an extruder die 332 (see FIG. 11C), thereby forming a plurality of protrusions 330, each of which is disposed between adjacent mask members 333.

[0496] According to some alternative embodiments, step (ii) comprises depositing a monomer composition into spaces formed between adjacent mask members 333 and polymerizing the monomer composition to transition the composition to a solid or semi-solid state, thereby forming a plurality of protrusions 330. According to some embodiments, each of the plurality of protrusions 330 is disposed between adjacent mask members 333. According to some embodiments, polymerization is initiated using a chemical initiator, a thermal initiator, irradiation, etc. Each possibility represents a separate embodiment.

[0497] According to some embodiments, the protrusions 330 are formed from a thermoplastic elastomer. According to some embodiments, the thermoplastic elastomer is polyurethane. It will be appreciated that polyurethanes can be prepared from the reaction of a polyol (e.g., diols, triols, and higher polyalcohols) with a polyisocyanate (e.g., diisocyanates, triisocyanates, and higher polyisocyanates). Thus, according to some embodiments, the monomer composition includes at least one of a polyol and a polyisocyanate, and according to some embodiments, polymerizing the composition involves contacting the monomer composition with a second monomer composition including another monomer (e.g., a polyol or a polyisocyanate).

[0498] According to some alternative embodiments, step (iii) further includes removing the plurality of mask members 333 from the surface 302 of the sheet to form a 3D shape in the unfolded, relaxed state of the sealing member after solidification of the plurality of protrusions 330, as disclosed above (see FIG. 11E).

[0499] According to some alternative embodiments, each of the plurality of mask members 333 has an elongated structure, and each of the plurality of protrusions 330 is formed between adjacent elongated mask members 333 .

[0500] According to some embodiments, step (iii) includes connecting two opposing edges (i.e., first lateral edge 306 and second lateral edge 308) of the sheet from step (ii) to form a cylindrically folded cylindrical seal member (or PVL skirt) (see, e.g., FIG. 20). The connection between the opposing edges can be achieved using at least one of adhesive, stitching, or heat, and optionally edge melting. Alternatively, step (iii) includes bonding the seal member 322 to the outer surface of the frame 106 using at least one of adhesive, stitching, or heat, and optionally edge melting of the seal member 322 around its periphery.

[0501] Reference is now made to Figures 12A-15. Figure 12A illustrates a perspective view of a seal member 422 in an expanded, relaxed state, according to some embodiments. Figures 12B-12H illustrate various cross-sectional views of a seal member 422, according to some embodiments. Figure 12F illustrates a perspective view of a seal member 422 including a plurality of apertures 435, according to some embodiments. Figure 12G illustrates a cross-sectional view of the seal member 422 of Figure 12F, according to some embodiments. Figures 13A-13C illustrate perspective views of various configurations of a seal member 422 in a cylindrically folded state, according to some embodiments. Figure 13D illustrates a perspective view of a folded seal member 422a, according to some embodiments. Figures 14A-14C illustrate various configurations of a seal member 422 mounted on a frame 106 of a prosthetic valve 100, according to some embodiments. Figure 14D illustrates a folded seal member 422a mounted on the frame 106 of the prosthetic valve 100, according to some embodiments. Figure 15 illustrates a configuration of a seal member 422 including multiple openings 435 mounted on the frame 106 of the prosthetic valve 100, according to some embodiments.

[0502] According to another embodiment, a seal member 422 is provided that is configured to be mounted on (or coupled to) an outer surface of the frame 106 of the prosthetic valve 100 (see, e.g., FIGS. 14A-14C ), or to any other similar prosthetic valve known in the art. The seal member 422 can be connected / attached to the frame 106 using any suitable technique or mechanism. For example, the seal member 422 can be sutured to the frame 106 using sutures that can extend around the struts 110. The seal member 422 can be configured to lie against the outer surface of the frame 106 when the prosthetic valve 100 is in a radially expanded state, as shown, for a snug fit against the frame 106.

[0503] According to certain embodiments, the present invention provides a prosthetic heart valve 100 including a frame 106 and a leaflet assembly 130 mounted within the frame, the frame including a plurality of intersecting struts 110, the frame being movable between a radially compressed state and a radially expanded state as disclosed hereinabove, the valve 100 further including a sealing member 422 coupled to an outer surface of the frame 106, the sealing member 422 having a three-dimensional (3D) shape in its expanded, relaxed state.

[0504] The seal member 422 can be provided in an unfolded state and can be connected / attached to the frame 106 by folding it onto the frame 106, thereby transforming the seal member 422 from the unfolded state to the folded state. Alternatively, the seal member 422 can be provided in an already folded state before attachment to the frame 106. For example, the frame 106 can be inserted into the seal member 422 that has already been folded into a cylindrical shape and sewn to such seal member.

[0505] According to some embodiments, seal member 422 has a 3D elastic structure such that non-fibrous outer surface 480 of seal member 422 exhibits a plurality of raised portions 430 having peaks 405 and a plurality of non-ridged portions 450. In further embodiments, each of the plurality of non-ridged portions 450 is defined by an adjacent pair of the plurality of raised portions 430. In further embodiments, non-fibrous outer surface 480 is a smooth surface. In further embodiments, non-fibrous outer surface 480 is a single / continuous surface.

[0506] Surface roughness is a component of surface texture. Surface roughness is quantified by the deviation of the normal vector of an actual surface from its ideal shape. If these deviations are large, the surface is considered rough; if they are small, the surface is considered smooth. Thus, as used herein, the term "smooth" refers to a surface in which the normal vector of the actual surface deviates only slightly from the ideal shape. A smooth surface is a substantially single / continuous surface that is free of fibers or irregular voids. The term "smooth" is not intended to be limited to the narrow meaning of a substantially flat surface without surface irregularities. Thus, raised portions, non-raised portions, and apertures in the sealing members of the present invention are considered not to affect the smoothness of the respective outer surfaces (280, 380, 480). Specifically, as will be understood by those skilled in the art, the outer surfaces (280, 380, 480) of the sealing members (222, 322, 422) of the present invention are intended to contact natural tissue when implanted. Without wishing to be bound by any theory or mechanism of action, it is believed that a smooth surface that is intended to contact such tissue resists or inhibits new tissue ingrowth onto the upper surface. Therefore, it is preferred that the outer surfaces (280, 380, 480) of the sealing members (222, 322, 422) of the present invention be smooth for various implementations of the present invention.

[0507] In some embodiments, raised portions 430 are protrusions 430 and non-raised portions 450 are inter-protrusion gaps 450. As used herein, the terms "raised portions 430" and "protrusions 430" are interchangeable and refer to the same plurality of raised portions of seal member 422, as can be seen in Figures 12B-12C. As used herein, the terms "non-raised portions 450" and "inter-protrusion gaps 450" are interchangeable and refer to the same plurality of non-raised portions of seal member 422, as can be seen in Figures 12B-12C.

[0508] According to some embodiments, seal member 422 has a 3D shape in its unfolded, relaxed state, as can be seen, for example, in Figures 12A-12G. According to some embodiments, seal member 322 has an essentially 3D shape in its cylindrically folded state (Figures 13A-13D and 14A-15).

[0509] Specifically, as can be seen, for example, in FIG. 12A, seal member 422 includes a plurality of protrusions 430 that define a three-dimensional (3D) shape as opposed to the substantially flat, two-dimensional shape that would be formed in the absence of such protrusions 430.

[0510] It will therefore be understood that the three-dimensional shape of the three-dimensional seal member 422 includes (i) a spatial length dimension extending between the outflow edge 407 and the inflow edge 409 of the seal member 422 (see, for example, Figures 12B and 12C), (ii) a spatial length dimension extending between the first lateral edge 406 and the second lateral edge 408 of the seal member 422 (see Figure 12A), and (iii) a spatial length dimension defined by the protrusion height (or thickness) 422T of the protrusion 430 of the seal member (see Figure 12C).

[0511] According to some embodiments, the seal member 422 includes at least one protrusion 430 extending away from the first surface 402 of the seal member 422 (see, eg, FIGS. 23A-B).

[0512] According to some embodiments, the seal member 422 includes a plurality of protrusions 430 extending away from and spaced apart from one another along the first surface 402 of the seal member 422. The plurality of protrusions 430, according to some embodiments, define the 3D shape of the seal member 422 in its unfolded, relaxed state (as can be seen in FIGS. 12A-12G). According to some embodiments, the seal member 422 includes a flat surface opposite the first surface 402 in its unfolded, relaxed state.

[0513] According to some embodiments, the seal member 422 has four edges. According to some embodiments, the seal member 422 has four vertices. According to some embodiments, each of the four vertices of the seal member 422 is a substantially right angle.

[0514] According to some embodiments, the seal member 422 has four substantially right-angled vertices and two sets of opposing edges (a first lateral edge 406 and a second lateral edge 408, and an outflow edge 407 and an inflow edge 409), where the opposing edges in each set are substantially parallel. According to some embodiments, the seal member 422 extends from the first lateral edge 406 to the second lateral edge 408 when the seal member 422 is in the unfolded state. According to some embodiments, the seal member 422 extends around a seal member centerline 411 when in the folded state. According to some embodiments, the seal member centerline 411 and the centerline 111 of the valve 100 are coaxial and may coincide when the seal member 422 is connected to the heart valve 100. According to some embodiments, the seal member 422 extends from the inflow edge 409 to the outflow edge 407. According to some embodiments, the seal member 422 extends from the inflow edge 409 toward the outflow edge 407 in both the folded and unfolded positions.

[0515] According to some embodiments, in the unfolded state, the seal member 422 is substantially rectangular. According to some embodiments, the distance from the first lateral edge 406 to the second lateral edge 408 is greater than the distance from the inflow edge 409 to the outflow edge 407.

[0516] According to some embodiments, each of the plurality of protrusions 430 extends radially outwardly away from the centerline 411 of the seal member 422 when the seal member 422 is in the collapsed state (see Figures 13A-13D).

[0517] According to some embodiments, the plurality of protrusions 430 may extend in different directions from the surface 402 to form a 3D shape on the top surface, which may be selected from an inverted U-shape, a hemisphere, a dome, a cylinder, a pyramid, a triangular prism, a pentagonal prism, a hexagonal prism, a flap, any other polygonal shape, and combinations thereof. Each possibility represents a different embodiment. According to further embodiments, the plurality of protrusions 430 may extend in different directions from the surface 402 to form parallel elongated 3D shapes on the top surface, which may be selected from an elongated U-shape, an elongated rectangular prism, an elongated rectangular prism, any other elongated polyhedron, and combinations thereof. Each possibility represents a different embodiment.

[0518] According to some embodiments, each of the plurality of protrusions 430 defines an elongated 3D shape and extends outwardly, radially away from the centerline 111 of the valve 100, when the seal member 422 is mounted on the frame 106 (see FIGS. 14A-15 ). According to some embodiments, the seal member 422 is folded by connecting the first lateral edge 406 and the second lateral edge 408 such that the plurality of protrusions 430 are oriented radially away from the centerline 411 of the seal member. According to some embodiments, the folded seal member 422 is coupled to the outer surface of the frame 106 of the prosthetic valve 100 such that the plurality of protrusions 430 are oriented radially away from the centerline 111 (see, for example, FIG. 14A ).

[0519] According to some embodiments, the seal member 422 is configured to be able to transition from an unfolded, relaxed state to a cylindrical, folded state based on elastic and / or flexible properties to form a cylindrical PVL skirt. The folded PVL skirt 422 may be bonded to the outer surface of the frame 106 of the prosthetic valve 100, for example, during a valve assembly procedure. Alternatively, the unfolded seal member 422 may be folded around the outer surface of the frame 106 and bonded to the outer surface of the frame to achieve a similar product.

[0520] According to some examples, each of the plurality of protrusions 430 defines a hollow lumen 431 therein (see FIGS. 12A-12C ), with each lumen 431 extending from the first lateral edge 406 toward the second lateral edge 408 of the seal member 422. According to some embodiments, each lumen 431 has an elongated cylindrical shape (including an elliptical cylindrical shape). However, it will be appreciated that the cross-section of each lumen 431 may have a different cross-sectional shape while providing the same function, such as a rectangular, elliptical, triangular, or any other suitable cross-sectional shape. Each possibility represents a different embodiment. Furthermore, according to some embodiments, it is contemplated that the cross-sectional shape of the hollow lumen 431 may not necessarily be uniform along its length.

[0521] According to some embodiments, each hollow lumen 431 includes two lumen edges. According to some embodiments, each hollow lumen 431 is open-ended at one or both of its lumen edges. According to further embodiments, each hollow lumen 431 is open-ended at both lumen edges. According to some embodiments, one open edge is located at the first lateral edge 406 and the other open edge is located at the second lateral edge 408 (see FIG. 12A ). According to some embodiments, one open edge is located at the inflow edge 409 and the other open edge is located at the outflow edge 407 (not shown).

[0522] According to some embodiments, both lateral ends of the seal member 422 are coupled to one another in a manner that, in the folded state, forms a continuous, closed hollow lumen 431 (i.e., both open edges are fluidly connected and form a continuous lumen). In such a situation, the folded seal member 422 may be coupled to the outer surface of the frame 106 of the prosthetic valve 100, with air trapped within the completely closed hollow lumen 431. In such a case, although the trapped air is completely contained within the hollow lumen 431 and is not exposed to the surrounding anatomical structures when the prosthetic valve 100 is implanted, the trapped air may still pose a risk to the patient if the protrusions 430 deteriorate or accidentally break in a manner that could release the trapped air or result in undesirable cavitation.

[0523] According to some embodiments, at least one edge of hollow lumen 431 (or any other portion) remains open-ended or exposed to the external environment when seal member 422 is coupled to frame 106. Alternatively or additionally, protrusions 430 can include openings (similar to openings 435 described later herein) exposing hollow lumen 431 to the surrounding environment. In such embodiments, prosthetic valve 100 can be crimped into a radially compressed state by a crimper in a manner that flattens protrusions 430 to prevent air from being trapped therein, and can be constrained in the crimped state (e.g., by being placed within a constraining sheath or capsule) as described above herein until and during the implantation process, thereby reducing the risk of introducing trapped air into the patient's body.

[0524] According to some embodiments, each of the plurality of protrusions 430 includes an elastic material 433 disposed therein (see FIGS. 12B-12C ), where the elastic material 433 is different from the material forming the protrusions 430. According to some embodiments, each of the plurality of protrusions 430 includes a compressible material 433 disposed therein. According to some embodiments, each of the hollow lumens 431 includes an elastic material 433 disposed therein. According to some embodiments, each elastic material 433 is configured to be compressed without permanent deformation (e.g., without experiencing plastic deformation) when an external force as described above is applied. According to some embodiments, the elastic material 433 includes an elastic foam, such as an elastic sponge. According to some embodiments, the elastic material 433 includes an elastic metal cylinder forming a hollow lumen therein. According to some embodiments, the elastic material 433 includes a porous elastic element / member, which is optionally elongated.

[0525] According to some embodiments, each of the plurality of protrusions 430 is a segmented protrusion 434 that includes at least two opposing flaps / members that together form the segmented protrusion 434. According to some embodiments, the seal member 422 includes a plurality of segmented protrusions 434 that are spaced apart and extend away from the first surface 402 of the seal member 422, each of the plurality of segmented protrusions 434 defining an interior space 431 a therebetween. According to further embodiments, each interior space 431 a extends from the opening 432 toward the first surface 402 (see, e.g., FIG. 12D ). According to some examples, the seal member 422 includes a flat surface located opposite the first surface 402 in the expanded, relaxed state.

[0526] According to some embodiments, the plurality of segmented projections 434 define a three-dimensional shape for the seal member 422 in both the unfolded, relaxed state (as shown in FIGS. 12D-12E) and the cylindric...

Claims

1. A prosthetic heart valve (100), comprising: a frame (106) having a plurality of intersecting struts (110), the frame (106) being movable between a radially compressed state and a radially expanded state; a leaflet assembly (130) mounted within said frame (106); a seal member (222; 322; 422) coupled to an outer surface of said frame (106), said seal member (222; 322; 422) extending from an inflow edge (209; 309; 409) toward an opposite outflow edge (207; 307; 407) and comprising a first layer (210; 310; 410) and a second layer (220; 320; 420) covering said first layer (210; 310; 410), wherein a non-fibrous outer surface (280; 380; 480) of said seal member (222; 322; 422) is formed from a material that is essentially molded to define a plurality of raised portions (230; 330; 430) having peaks (205; 305; 405) and a plurality of non-raised portions (250; 350; 450); A prosthetic heart valve, wherein the first layer (210; 310; 410) and the second layer (220; 320; 420) are disposed outwardly against the outer surface of the frame (106).

2. 2. The prosthetic heart valve of claim 1, wherein the raised portions (230; 330; 430) are configured to deform when an external pressure exceeding a predefined threshold is applied to the raised portions in a direction configured to press the raised portions against the frame (106) and to return to a relaxed state when the external pressure is no longer applied to the raised portions, a distance of the peaks from the frame (106) being greater compared to a distance of the non-raised portions (250; 350; 450) from the frame (106) in the relaxed state.

3. 3. The prosthetic heart valve of claim 1 or 2, wherein the non-fibrous outer surface (280; 380; 480) is a smooth surface.

4. The prosthetic heart valve of any one of claims 1 to 3, wherein the sealing member (222; 322; 422) includes a third layer (225; 325; 425), the second layer (220; 320; 420) and the third layer (225; 325; 425) collectively forming a coating over the first layer (210; 310; 410).

5. 5. The prosthetic heart valve of claim 1, wherein the first layer (210; 310; 410) comprises at least one tear-resistant polyethylene terephthalate (PET) fabric and / or the second layer (220; 320; 420) is formed from a biocompatible thermoplastic polyurethane (TPU).

6. The raised portion (230; 330; 430) of the seal member (222; 322; 422) includes a plurality of ridges spaced apart from one another along a first surface of the seal member (222; 322; 422), the second layer (220; 320; 420) forms the first surface of the seal member (222; 322; 422), each of the plurality of ridges extending outwardly from the outer surface of the frame (106), and the seal member (222; 322; 422) includes a plurality of ridges spaced apart from one another along a first surface of the seal member (222; 322; 422), the second layer (220; 320; 420) forms the first surface of the seal member (222; 322; 422), each of the plurality of ridges extending outwardly from the outer surface of the frame (106), 6. The prosthetic heart valve according to claim 1, wherein the sealing member (222; 322; 422) comprises a plurality of internal channels (240), each channel being formed in a second face of the sealing member (222; 322; 422), each of the plurality of channels being inwardly directed, preferably the number of the channels being the same as the number of the ridges (230), each of the plurality of channels being formed by a respective one of the plurality of ridges on an opposite face of the sealing member (222; 322; 422).

7. 7. The prosthetic heart valve of claim 6, wherein the non-raised portion (250; 350; 450) of the sealing member (222; 322; 422) includes a plurality of inter-ridge gaps formed on a surface of the first layer (210; 310; 410) between every two adjacent ridges of the sealing member (222; 322; 422).

8. 8. The prosthetic heart valve of claim 6 or 7, wherein the ridges follow parallel path lines extending along the first surface of the sealing member (222; 322; 422), the ridges being compressible, preferably the ridges follow parallel path lines extending substantially parallel to at least one of the inflow edge (209; 309; 409) or the outflow edge (207; 307; 407), or preferably the ridges follow parallel path lines extending substantially obliquely to at least one of the inflow edge (209; 309; 409) or the outflow edge (207; 307; 407).

9. 9. The prosthetic heart valve of claim 7 or 8, wherein the sealing member (222; 322; 422) has a total layer thickness measured between the first and second sides of the sealing member (222; 322; 422) at one of the inter-ridge gaps and a thickness of the sealing member (222; 322; 422) measured by the height of the ridges of the sealing member (222; 322; 422), the thickness of the sealing member (222; 322; 422) being at least 1000% greater than the total layer thickness.

10. 6. The prosthetic heart valve of claim 1, wherein the raised portion (230; 330; 430) of the seal member (222; 322; 422) includes a plurality of projections extending outwardly from a periphery of the first surface of the seal member (222; 322; 422), the plurality of projections being spaced apart from one another along the first surface, each of the plurality of projections being compressible, and preferably the seal member (222; 322; 422) includes a flat second surface opposite the first surface when in an expanded, relaxed state.

11. 11. The prosthetic heart valve of claim 10, wherein the non-raised portion (250; 350; 450) of the seal member (222; 322; 422) includes a plurality of inter-projection gaps, each gap being located between two adjacent projections, and the plurality of inter-projection gaps facing in the same direction as the projections.

12. 12. The prosthetic heart valve of claim 10 or 11, wherein each of the plurality of protrusions extends around the first surface and away from the first surface to form a 3D shape thereon, the 3D shape being selectable from the group consisting of an inverted U-shape, a hemisphere, a dome, a cylinder, a pyramid, a triangular prism, a pentagonal prism, a hexagonal prism, a flap (438), a polygon, and combinations thereof, and preferably the plurality of protrusions form an elongated 3D shape and extend substantially parallel to at least one of the inflow edge (209; 309; 409) or the outflow edge (207; 307; 407), or preferably the plurality of protrusions form an elongated 3D shape and extend substantially obliquely to at least one of the inflow edge (209; 309; 409) or the outflow edge (207; 307; 407).

13. 13. The prosthetic heart valve of claim 11 or 12, wherein the sealing member (222; 322; 422) has a total layer thickness measured between the first surface and the second surface at one of the inter-projection gaps and a thickness of the sealing member (222; 322; 422) defined as the distance between the projection and the second surface, the thickness of the sealing member (222; 322; 422) being greater than the total layer thickness by at least 1000%.

14. 14. The prosthetic heart valve of claim 10, wherein each of the plurality of protrusions defines a solid structure, or each of the plurality of protrusions defines a hollow lumen therein, and preferably each of the plurality of protrusions includes a plurality of openings (435) spaced apart along the protrusion, each opening configured to provide fluid communication between the hollow lumen and an external environment outside the opening, and each of the hollow lumens contains a medicinal composition (436) disposed therein, or preferably each of the hollow lumens includes an elastic porous member disposed therein, the elastic porous member including a medicinal composition disposed therein, and each of the plurality of protrusions includes a plurality of openings spaced apart along the protrusion.

15. 12. The prosthetic heart valve according to claim 10 or 11, wherein each of the plurality of protrusions is a split protrusion (434), and each of the plurality of split protrusions forms an internal space (431a) between the split protrusions, and the internal space extends between an opening (432) of each split protrusion and the first surface of the sealing member (222; 322; 422), or between an opening of each split protrusion and the first surface of the first layer (210; 310; 410), and preferably the opening in each of the plurality of split protrusions is symmetrical with respect to an axis (414) extending through the center of each split protrusion, thereby forming a symmetrical internal space, or the opening in each of the plurality of split protrusions is obliquely offset with respect to an axis extending through the center of each split protrusion, thereby forming an asymmetrical internal space (431a).

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