Polymer materials with medical applications and methods for manufacturing

Abstract

Valves constructed from low porosity leaflets are disclosed. The valves disclosed herein may be integrated into a variety of structures, such as valved conduits and transcatheter stents, and may be constructed of one or more layers. Embodiments herein are also directed to methods of using the same and methods of making the same.

Description

POLYMER MATERIALS WITH MEDICAL APPLICATIONS AND METHODS FOR MANUFACTURINGCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of and priority to U.S. provisional patent application No. 63 / 813,526, filed May 28, 2025, and to provisional U.S. patent application No. 63 / 654,676, filed May 31, 2024, the disclosures of which are hereby incorporated by reference in their entirety.BACKGROUND

[0002] The porosity of materials used for medical applications can significantly affect both the biological interactions of the material such as tissue ingrow th, as well as the physical properties of the material such as suture retention strength. For example, it is well evidenced that implanted expanded polytetrafluoroethylene (ePTFE) configurations with an average pore diameter of sixty microns or more promote greater tissue in-growth and lower suture retention strength compared to configurations with pore diameters less than five microns. However, while this broad understanding has been applied, there is limited public exploration or understanding of the effect of precision manipulation of pores in medical materials.SUMMARY

[0003] Various embodiments are directed to a multi-layered material for use in a medical device.

[0004] In one embodiment, a multi-layered material for use in a medical device includes at least two outer layers, wherein each outer layer includes a surface porosity of 1% to 10%; and one or more inner layers, wherein each inner layer includes a surface porosity of about 25% to about 50%.

[0005] In some embodiments, each outer layer has a thickness of 0.1pm to 10pm.

[0006] In some embodiments, each inner layer has a thickness greater than 10 pm.

[0007] In some embodiments, each inner layer has a thickness of 0.1 pm to 10pm.

[0008] In some embodiments, each outer layer has a thickness of greater than 10pm.

[0009] In some embodiments, each outer layer is constructed from expanded polytetrafluoroethylene (ePTFE).

[0010] In some embodiments, each inner layer is constructed from at least one of polyurethane, silicone, and polytetrafluoroethylene (PTFE).

[0011] In some embodiments, at least one outer layer includes a coating or infusion of heparin, paclitaxel, coumadin, warfarin, PTFE, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents.anti-inflammatory agents, anti-proliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

[0012] In some embodiments, the multi-layered material is configured to form a part of a cardiovascular graft.

[0013] In some embodiments, the multi-layered material is configured to form a part of a heart valve leaflet.

[0014] In some embodiments, each outer layer includes pores with an average pore area of 0. 1 pm2to 5 pm2.

[0015] In some embodiments, each inner layer includes pores with an average pore area of 5 pm2to 15 pm2.

[0016] In some embodiments, each of the outer layers and each of the inner layers further includes at least one bump or at least one wrinkle.

[0017] In one embodiment, a multi-layered material for use in a medical device includes a first layer including a surface porosity’ of 1% to 10%; and a second layer including a surface porosity of greater than 10%.

[0018] In some embodiments, each of the first layer and the second layer has a thickness of 0.1 pm to 10pm.

[0019] In some embodiments, one of the first layer and the second layer has a thickness of 0.1pm to 10pm and one of the first layer and the second layer has a thickness greater than 10 pm.

[0020] In some embodiments, each of the first layer and the second layer is constructed from expanded polytetrafluoroethylene (ePTFE).

[0021] In some embodiments, at least one of the first layer and the second layer includes a coating or infusion of heparin, paclitaxel, coumadin, warfarin, PTFE, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, antibacterial agents, anti-inflammatory agents, anti-proliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

[0022] In some embodiments, the multi-layered material is configured to form a part of a cardiovascular graft.

[0023] In some embodiments, the multi-layered material is configured to form a part of a heart valve leaflet.

[0024] In some embodiments, each of the first layer and the second layer includes pores with an average pore area of 0. 1 pm2to 5 pm2.

[0025] In some embodiments, each of the first layer and the second layer further include at least one bump or at least one wrinkle.

[0026] In one embodiment, a multi-layered material for use in a medical device includes a first layer comprising a surface porosity of about 1% to about 10%, a second layer comprising a surface porosity of greater than 10%. and a third layer compnsing a surface porosity of about 1% to about 10%.

[0027] In some embodiments, each of the first layer, second layer, and third layer has a thickness of about 0.1pm to about 10pm.

[0028] In some embodiments, at least one of the first layer, second layer, and third layer has a thickness of about 0. 1 pm to about 10pm and at least one of the first layer and the second layer has a thickness greater than 10pm.

[0029] In some embodiments, each of the first layer, second layer, and third layer is constructed from expanded polytetrafluoroethylene (ePTFE).

[0030] In some embodiments, at least one of the first layer, second layer and third layer comprises a coating of heparin, paclitaxel, coumadin, warfarin, PTFE, polyurethanecopolymer, biological growth factors, collagen, carbon, proteins, anti-platelet agents, antithrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, antiproliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

[0031] In some embodiments, at least one of first layer, second layer, and third layer has been infused with heparin, paclitaxel, coumadin, warfarin, PTFE, a polyurethane-copolymer, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, anti-proliferative agents, endothelial cell grow th promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

[0032] In some embodiments, the multi-layered material is configured to form a part of a cardiovascular graft.

[0033] In some embodiments, the multi-layered material is configured to form a part of a heart valve leaflet.

[0034] In some embodiments, each of the first layer and the second layer comprises pores with an average pore area of about 0. 1 pm2to about 5 pm2.

[0035] In some embodiments, each of the first layer and the second layer further comprise at least one bump or at least one wrinkle.

[0036] In one embodiments, a method for making a multi-layered material for use in a medical device includes providing a first layer having a surface porosity of about 1% to about 10% and a second layer having a surface porosity of greater than about 10 %, superimposing an inner surface of the second layer to an outer surface of the first layer; and heating the first layer and the second layer to attach the first layer and the second layer; wherein the first layer and the second layer are heated beyond a sintering temperature of at least one of the first layer and the second layer.BRIEF DESCRIPTION OF THE DRAWINGS

[0037] FIGS. 1A and IB depict side views of an illustrative valved conduit in a closed position and an open position, respectively, in accordance with an embodiment.

[0038] FIGS. 2A and 2B depict end views of an illustrative valved conduit in an open position and a closed position, respectively, in accordance with an embodiment.

[0039] FIG. 3A depicts a schematic of the position of a valve in relation to a conduit in accordance with an embodiment.

[0040] FIG. 3B depicts a schematic of a valved conduit in a closed position with the lengths illustrated in FIG. 3A superimposed over the valve components.

[0041] FIG. 4 depicts an illustrative leaflet in accordance with an embodiment.

[0042] FIGS. 5A and 5B depict a valved conduit that has been inverted such that the valve is on an outward facing side of the conduit and a valved conduit with the valve on an inner surface of the conduit, respectively, in accordance with embodiments.

[0043] FIGS. 6A and 6B depict an illustrative tapered dimple created between the leaflet and an inner surface of the conduit in a longitudinal view and a cross-sectional view, respectively.

[0044] FIGS. 7A-D depict various views of an illustrative tapered dimple in accordance with an embodiment.

[0045] FIGS. 8A and 8B depict various views of an illustrative fixing stencil in accordance with an embodiment.

[0046] FIG. 9A depicts an illustrative stent in accordance with an embodiment. FIG. 9B depicts a pair of opposing chevron-shaped structures within the stent. FIG. 9C depicts a single chevron-shaped structure with median and lateral vertices. FIGS. 9D and 9E depict the stentwith a plurality of attachment points in an expanded configuration and a collapsed configuration, respectively.

[0047] FIG. 10 illustrates a schematic design of a leaflet made from a non-stretchable material in accordance with an embodiment.

[0048] FIGS. 11 A and 1 IB depict an illustrative stent with a valve in an open position and a closed position, respectively.

[0049] FIG. 12A shows a stent with a valved conduit in a deployed configuration and a crimped configuration, where the conduit and the valve are non-stretchable. FIG. 12B shows images of a stent with a valve in an open configuration and a closed configuration, respectively, from the aortic side and the ventricular side, respectively.

[0050] FIG. 13 is a SEM image of a leaflet illustrating a material having an average pore area, an average pore diameter, and a surface porosity, according to an embodiment.

[0051] FIGS. 14A and 14C are SEM images of a Gore Preclude Membrane. FIGS. 14B and 14D are SEM images of a leaflet illustrating an illustrative material having a surface porosity according to an embodiment. FIG. 14E depicts the quantification of the SEM images of FIGS. 14B, 14D, 14A, and 14C, respectively.

[0052] FIGS. 15A-D are graphs of an ultimate tensile stress, a burst pressure, a suture retention strength, and a suture retention 45-degree orientation, respectively, for a leaflet according to an embodiment as compared to a Gore Preclude Membrane.

[0053] FIGS. 16A and 16B are graphs of a bending modulus in MPa and a bending modulus in N / mm2, respectively, for a leaflet according to an embodiment as compared to a Gore Preclude Membrane.

[0054] FIGS. 17A and 17B are graphs of a membrane tension and a stress, respectively, for a leaflet according to an embodiment as compared to a Gore Preclude Membrane.

[0055] FIGS. 18A-D depict SEM images of a leaflet having reduced thrombogenicity according to an embodiment as compared to a Gore Preclude Membrane depicted in FIGS. 18E-H.

[0056] FIGS. 19A-B depict SEM images of a multi-layer conduit having a luminal surface with a reduced thrombogenicity according to an embodiment as compared to a Gore Preclude Membrane (depicted in FIG. 19C) and a BARD Impra Conduit (depicted in FIG. 19D).

[0057] FIGS. 20A-B illustrate diagrams of materials with pores and pore attributes according to an embodiment.

[0058] FIGS. 21-22 depict diagrams of pore shapes, orientations and arrangements in accordance with various embodiments.

[0059] FIG. 23 illustrates an exploded view of a multi-layer material in accordance with an embodiment.

[0060] FIGS. 24A-B illustrate a porous material before and after 3D shaping in accordance with an embodiment.

[0061] FIG. 25 depicts poly mer membranes after deformation for shaping in accordance with an embodiment.

[0062] FIGS. 26A-J depict various valves and grafts in accordance with embodiments.

[0063] FIGS. 27A-B depict fluoroscopic views of a conduit with radiopaque markings before and after expansion with a balloon angioplasty catheter, respectively, in accordance with an embodiment.

[0064] FIG. 28 depicts a conduit with radiopaque marking with an end plastically deformed into a flared conical shape in accordance with an embodiment.

[0065] FIGS. 29A-C depict an in vitro thrombogenicity comparison of materials with vary ing microstructures in accordance with an embodiment.

[0066] FIG. 30 depicts nine examples of porous microstructures that vary in isotropicity and compactness in accordance with embodiments.

[0067] FIG. 31 depicts nine examples of porous microstructures that vary7in isotropicity and intemodal distance in accordance with embodiments.

[0068] FIG. 32 depicts nine examples of porous microstructures that vary in isotropicity and surface porosity in accordance with embodiments.

[0069] FIGS. 33A-H and 34A-I depict a comparison of a commercial monolayer fluoropolymer material and various multi-layer fluoropolymer materials, along with relative comparisons of rigidity, suture retention strength, surface porosity7, intemodal distance, and volumetric porosity in accordance with an embodiment.

[0070] FIGS. 35A-B are graphs that depict a comparison of a multi-layer material, Gore Preclude Membrane (a single-layer commercial low-porosity7ePTFE membrane) and porcine aortic valve tissue, with respect to plate structural rigidity7and suture retention strength, respectively, in accordance with an embodiment.

[0071] FIGS. 36A-C are graphs that illustrate mechanical properties of a plastically deformable polymer material at multiple expansion multiples in accordance with an embodiment.DETAILED DESCRIPTION

[0072] Before the invention is described, it is to be understood that this invention is not limited to the particular systems, methodologies or protocols described, as these may vary. It is also to be understood that the terminology7used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present disclosure.

[0073] For the purpose of this disclosure, the term “pore” means a volume of empty space in a material. A pore may be defined either by a three-dimensional volume of empty7space or by a two-dimensional area of empty space with the implied third dimension then being equal to thickness of the layer of the material it exists in (such that it forms a hole through the layer where at each depth the two-dimensional shape of the hole is the same).

[0074] For the purposes of this disclosure, the term “pore area” means the two-dimensional area of a pore independent of the third dimension (i.e. depth) of the pore through the material in which it exists.

[0075] For the purposes of this disclosure, the term “pore volume” means the three- dimensional volume of a pore.

[0076] As used herein, the term “pore diameter” means the longest diameter of a pore (major axis).

[0077] For the purposes of this disclosure, “pore orientation” means the angle between the major axis of a non-circular pore and an axial direction of the material in which the pore exists. If the axis is not specified, the axial direction is the non-depth directional axis for which the angle between that axis and the major axis of the non-circular pore is the smallest.

[0078] For the purposes of this disclosure, “porosity” is the ratio of the sum of each pore volume of a material to the total volume of the material if it were perfectly solid. For example, a cube of 1 mm side length (thus 1 mm3total volume if perfectly solid) that contains two 0. 1 mm3pores (thus 0.2mm3total pore volume) has a porosity7of 20%.

[0079] For the purposes of this disclosure, “surface porosity” is the ratio of the sum of each pore area to the total area of the material if it had no pores. For example, a square surface of 1mm side length (thus 1mm2total area if perfectly solid) that contains two pores each having a 0.1mm2pore area (thus 0.2mm2total pore area) has a surface porosity7of 20%.

[0080] For the purposes of this disclosure, “inter-nodal distance” defines the minimum linear distance between the perimeter of two pores.

[0081] For the purposes of this disclosure, “layer” refers to a portion of a material that is separable into an independent object from the remainder of the construct or an independentobject that is combined with others into a construct and that retains identifiable properties different from its surroundings.

[0082] For the purpose of this disclosure, the term '‘plastically deformable material’’ means a material that may change its shape, size, or both shape and size in response to a deforming force placed thereon, and which does not fully recover its original shape, size, or both shape and size once the deforming force has been removed.

[0083] For the purpose of this disclosure, the term “elastic material” means a material that may change its shape, size, or both shape and size in response to a deforming force placed thereon, and which recovers its original shape, size, or both shape and size once the deforming force has been removed.

[0084] For the purpose of this disclosure, the term “yield strength” means the smallest deforming force that, when applied to a material, will result in anon-recoverable change in the shape, size, or both shape and size of the material.

[0085] For the purpose of this disclosure, the term “ultimate tensile strength” means the smallest deforming force that, when applied to a material, will result in a break or failure of the material.

[0086] For the purpose of this disclosure, a material’s “bounding” is the volume (if three- dimensional) or area (if two dimensional) of a given shape or material if that shape or material were perfectly solid.

[0087] For the purpose of this disclosure, a shape’s “bounding box” is the smallest possible theoretical cube (if three-dimensional) or square (if two-dimensional) that fully encloses the shape.

[0088] As used herein, the term “about” means plus or minus 10% of the numerical value of the number with which it is being used. Therefore, about 50% means in the range of 45% to 55%.

[0089] As used herein, with respect to circularity the term “generally” means plus or minus 10% of the numerical value of the number with which it is being used. Therefore, generally circular means the smallest diameter is no less than 90% of the largest diameter.

[0090] As used herein, with respect to orientation and isotropicity the term “generally” means plus or minus 5 degrees from the orientation referenced. Therefore, a line that is generally parallel to a direction has an angle of 5 degrees or less from that orientation.

[0091] As used herein, the term “average pore area” means the average area of the pores in a layer of material having a plurality’ of pores. The average pore area is calculated by addingthe pore area of the plurality of pores of a layer of material and dividing by the total number of pores in that layer of material.

[0092] As used herein, the term “average pore diameter’’ means the average diameter of the pores in a one-layered or multi-layered material having a plurality of pores. The average pore diameter is calculated by adding the pore diameter of the plurality of pores of the onelayered or multi-layered material and dividing by the total number of pores therein.

[0093] As used herein, the term “total thickness” means the sum of the thicknesses of each layer of a conduit, a valve, a leaflet or other object or construct having more than one layer of material.

[0094] As used herein, the term “rotate” means the movement of an object around an axis. This can involve turning or spinning the object such that different parts of the object move through different arcs or angles and can be a partial or complete rotation.

[0095] As used herein, the term “translation” means the linear movement of an object from one location to another. This linear motion can occur along any axis in a straight line.

[0096] As used herein, the term “non-stretching” refers to materials that do not exhibit any appreciable elongation or expansion under amounts of tension they may experience within expected use conditions.

[0097] Various embodiments are directed towards the use of porous materials that serve one or more medical purposes, or as a component of a construct that serves one or more medical purposes.

[0098] Various embodiments are directed towards assemblies constructed of one or more porous layers to serve as membranes. Such embodiments include, but are not limited to, membranes which may impart strength, serv e to guide a structure along or hold a structure to a particular shape or orientation, function as a barrier to fluids or cells, function as a foundation to allow or regulate fluid movement or cellular growth, or a combination of any of these functions. Membrane assemblies may also serve any number of other or additional roles, including aesthetic purposes or as a connection for other constructs. Potential applications of membranes include, but are not limited to, pericardial membranes, dura membranes, hernia patches, urethral membranes, vaginal membranes, vascular patches, heart valve leaflets, venous valves, cardiovascular conduits, dermatological membranes, membranes for plastic surgery, dental floss, dental separators, luminal surface or tubing for catheters, or as part of a ventricular assist device.

[0099] V arious embodiments are directed towards porous materials used for cardiovascular valves. Such embodiments may include, but are not limited to, cardiac valve leaflets (includingthe aortic, mitral, pulmonary, or tricuspid positions), venous valve leaflets, a portion or all of the conduit of a stentless valved conduit, a portion or all of the inner or outer wrap of a stented valved conduit, and a portion or all of the delivery system of a transcatheter valve or other valve type.

[0100] Various embodiments are directed towards porous materials used for cardiovascular conduits. Such embodiments may include, but are not limited to, cardiac shunts, cardiac grafts, dialysis access grafts, peripheral vascular grafts, venous grafts, coronary artery bypass grafts, branched aortic grafts, endovascular grafts, a portion or all of the inner or outer wrap of stent grafts, and conduit support structures such as integrated rings, removable rings, integrated spirals, and removable spirals.

[0101] Various embodiments are directed towards porous materials used for minimally invasive devices. Such embodiments include, but are not limited to, vascular catheters, cardiac catheters, urethral catheters, patent foramen ovale closure devices, atrial septal defect devices, ventricular septal defect closure devices, vascular plugs, vascular stents, cardiac stents, branched aortic stents, neural stents, urethral stents, bronchial stents, biliary stents, esophageal stents, or ureteral stents. It should be appreciated that any form of stent could also be a stentgraft.

[0102] Various embodiments are directed towards plastically deformable materials for expandable or shape-changing medical devices. Such embodiments include, but are not limited to, expandable and / or shape-changeable vascular grafts, expandable and / or shape-changeable cardiac valves, expandable and / or shape-changeable venous valves, expandable and / or shape- changeable stentless valved conduits, expandable and / or shape-changeable stented valves, expandable and / or shape-changeable stented valved conduits, expandable and / or shape- changeable vascular stents, expandable and / or shape-changeable cardiac stents, expandable and / or shape-changeable dialysis access grafts, expandable and / or shape-changeable vascular wraps, expandable and / or shape-changeable vascular bands, expandable and / or shape- changeable implantable membranes.

[0103] Various embodiments are directed to polymer materials with medical applications and the methods for creating such materials.

[0104] In some embodiments, a polymer material may contain only polymers. In some embodiments, a polymer material may contain both polymer materials and other materials.

[0105] In some embodiments, a polymer material may have multiple layers. In some embodiments, the polymer is a single layer. In some embodiments the polymer material is multi-layered. In other embodiments, a multi-layered polymer may have as few as 2 layers oras many as 100 layers. In some embodiments, a multi-layered polymer may have more than 100 layers, including as many at 10,000 layers or greater.

[0106] In some embodiments, the microstructure of the polymer material may be defined. In some embodiments, the microstructure of each layer of a multi-layered polymer material may be defined. In some embodiments, the microstructure of only one or more layers of a multi-layered polymer material may be defined, while others may be allowed to vary or remain undefined.

[0107] In some embodiments, the bulk structure of the polymer may be defined. In some embodiments, the bulk microstructure and the microstructure of one or more layers may be defined. In some embodiments, the bulk structure and microstructure of one or more layers may differ. In some embodiments, the bulk structure may be substantially the same as the microstructure of one or more layers.

[0108] In some embodiments, the arrangement of multiple layers may be defined. In some embodiments, between one layer and all other layers, the arrangement may vary between outer and inner layers, between each of the layers, between a subset of the layers or any combination thereof. In some embodiments, the arrangement of multiple layers may vary with respect to porosity, pore orientation, pore size, pore shape, pore arrangement, layer material, layer material processing, layer geometry, layer thickness, layer dimensions, layer physical properties, layer coatings, infused agents or any combination thereof. In some embodiments, the properties of one or more layers may be defined or known but undefined and one or more layers may be unknown or undefined. In some embodiments, the properties of one or more layers may be defined only with respect to an acceptable range of one or more properties.

[0109] FIGS. 20A-B illustrate diagrams of materials with pores 2001 and pore attributes. In some embodiments, the material comprises a first length 2002 and a second length 2003. In some embodiments, each of the pores 2001 has a first length 2004 and a second length 2005. For a given porous material, the geometry of individual pores 2001 may be varied in a number of ways. In three dimensions, pores 2001 may have non-directionally oriented structures such as a sphere or cube, directionally oriented structures such as a cylinder or triangular prism, or amorphous structures that do not match a simple geometric shape. Amorphous pores 2001 may or may not be directionally oriented (with the average location of the shape being along a directional axis from the center point as defined by the shape’s bounding box). With respect to surface porosity, pores 2001 may have non-directionally oriented shapes such as a circle or square, directionally oriented shapes such as an ellipse or rectangle, or amorphous structures that do not match a simple geometric shape. Amorphous pores 2001 may be non-directionally-l ioriented or may be directionally oriented (with the average location of the shape being along a directional axis from the center point as defined by the shape's bounding box). For directionally oriented pores, both with respect to three-dimensional or two-dimensional orientation, the orientation may be parallel to a given axis of the material or oriented at any angle 2006 away from that axis. Examples of potential orientations of a directionally oriented pore with respect to a material axis include 1°, 2°, 3°, 4°, 5°. 6°, 7°, 8°, 9°, 10°, 11°, 12°, 13°. 14°, 15°, 16°, 17°, 18°, 19°. 20°, 21°, 22°, 23°, 24°. 25°, 26°. 27°, 28°. 29°, 30°, 31°, 32°, 33°. 34°, 35°. 36°, 37°.38°, 39°, 40°, 41°, 42°, 43°, 44°, 45°, 46°, 47°, 48°, 49°, 50°, 51°, 52°, 53°, 54°, 55°, 56°, 57°,58°, 59°, 60°, 61°, 62°, 63°, 64°, 65°, 66°, 67°, 68°, 69°, 70°, 71°, 72°, 73°, 74°, 75°, 76°, 77°,78°, 79°, 80°, 81°, 82°, 83°, 84°, 85°, 86°, 87°, 88°, 89°, 90°, 91°, 92°, 93°, 94°, 95°, 96°, 97°,98°, 99°, 100°. 101°. 102°, 103°, 104°, 105°, 106°, 107°. 108°. 109°, 110°, 111°, 112°, 113°, 114°, 1 15°, 1 16°, 1 17°, 118°, 119°, 120°, 121°, 122°, 123°, 124°, 125°, 126°, 127°, 128°, 129°,130°, 131°, 132°, 133°, 134°, 135°, 136°, 137°, 138°, 139°, 140°, 141°, 142°, 143°, 144°, 145°,146°, 147°, 148°, 149°, 150°, 151°, 152°, 153°, 154°, 155°, 156°, 157°, 158°, 159°, 160°, 161°,162°. 163°. 164°. 165°, 166°, 167°, 168°, 169°, 170°, 171°, 172°, 173°, 174°, 175°, 176°, 177°,178°, 179°, or 180°.

[0110] FIGS. 21 and 22 depict diagrams of materials 2101 / 2201 comprising pores 2102 / 2202 with various pore shapes, orientations and arrangements. Individual pores 2102 / 2202 may also have a variety of sizes. For example, an individual pore volume may be in the range of Inm3to IxlO10km3. Examples of pore volumes that may be targeted for an individual pore used in a material for medical applications include very small pores within the range of 0.1pm3- 1.0pm3, small pores in the range of 1.0pm3- 5.0pm3, medium pores in the range of 5pm3- 40pm3, and large pores in the range of 40pm3- 200pm3. More specifically, pores may be generally 0.01pm3, 0.05pm3, 0.1pm3, 0.2pm3, 0.3pm3, 0.4pm3. 0.5pm3, 0.6pm3, 0.7pm3, 0.8pm3, 0.9pm3, 1pm3, 1.25pm3, 1.5pm3, 1.75pm3, 2pm3, 2.5pm3, 3pm3, 3.5pm3, 4pm3, 4.5pm3, 5pmJ, 5.5pm3, 6pm3, 6.5pm3, 7pm3, 7.5pm3, 8pm3, 8.5pm3, 9pm3, 9.5pm3, 10pm3, l lpm3, 12pm3, 13pm3, 14pm3, 15pm3, 16pm3, 17pm3, 18pm3, 19pm3, 20pm3, 21pm3, 22pm3, 23pm3, 24pm3, 25pm3, 26pm3. 27pm3, 28pm3. 29pm3, 30pm3, 31pm3, 32pm3,33pm3, 34pm3, 35pm3, 36pm3, 37pm3, 38pm3, 39pm3, 40pm3, 41pm3, 42pm3, 43pm3,44pm3, 45pm3, 46pm3, 47pm3, 48pm3, 49pm3, 50pm3, 51pm3, 52pm3, 53pm3, 54pm3,55pm3, 56pm3, 57pm3, 58pm3, 59pm3, 60pm3, 61pm3, 62pm3, 63pm3, 64pm3, 65pm3,66pm3, 67pm3, 68pm3, 69pm3, 70pm3. 71pm3, 72pm3, 73pm’. 74pm3, 75pm , 76pm3,77pm3, 78pm3, 79pm3, 80pm3, 81pm3. 82pm3, 83pm3. 84pm3, 85pm3. 86pm3, 87pm3.88pm3, 89pm3, 90pm3, 91pm3, 92pm3, 93pm3, 94pm3, 95pm3, 96pm3, 97pm3, 98pm3, 99pm3,100pm3, 101pm3, 102pm3, 103pm3, 104pm3, 105pm3, 106pm3. 107pm3, 108pm3, 109pm3,110pm3, 111pm3, 112pm3, 113pm3, 114pm3, 115pm3, 116pm3. 117pm3. 118pm3. 119pm3,120pm3, 121pm3, 122pm3, 123pm3, 124pm3, 125pm3, 126pm3, 127pm3, 128pm3, 129pm3,130pm3, 131pm3, 132pm3, 133pm3, 134pm3, 135pm3, 136pm3, 137pm3, 138pm3, 139pm3,140pm3, 141pm3, 142pm’, 143pm3, 144pm3, 145pm3, 146pm3, 147pm3, 148pm3, 149pm3,150pm3, 151pm3, 152pm3, 153pm3, 154pm3, 155pm3, 156pm3. 157pm3. 158pm3, 159pm3,160pm3, 161pm3, 162pm3, 163pm3, 164pm3, 165pm3, 166pm3. 167pm3. 168pm3. 169pm3.170pm3, 171pm3, 172pm3, 173pm3, 174pm3, 175pm3, 176pm3, 177pm3, 178pm3, 179pm3,180pm3, 181pm3, 182pm3, 183pm3, 184pm3, 185pm3, 186pm3, 187pm3, 188pm3, 189pm3,190pm3, 191pm3, 192pm3, 193pm3, 194pm3, 195pm3, 196pm3, 197pm3, 198pm3, 199pm3, or 200pm3. Examples of pore areas that may be targeted for an individual pore used in a material for medical applications include very small pores with areas in the range of 0.1pm2- 1.0pm2, small pores with areas in the range of 1.0pm2- 5.0pm2, medium pores with areas in the range of 5pm2- 40pm2, and large pores with areas in the range of 40pm2- 200pm2. More specifically, pores may be generally 0.01pm2, 0.05pm2, 0.1pm2, 0.2pm2, 0.3pm2, 0.4pm2. 0.5pm2, 0.6pm2, 0.7pm2, 0.8pm2, 0.9pm2, 1pm2, 1.25pm2, 1.5pm2, 1.75pm2, 2pm2, 2.5pm2, 3pm2, 3.5pm2, 4pm2, 4.5pm2, 5pm2, 5.5pm2, 6pm2, 6.5pm2, 7pm2, 7.5pm2, 8pm2, 8.5pm2, 9pm2, 9.5pm2, 10pm2, 11pm2, 12pm2, 13pm2, 14pm2, 15pm2, 16pm2, 17pm2, 18pm2, 19pm2, 20pm2, 21pm2, 22pm2. 23pm2. 24pm2, 25pm2, 26pm2, 27pm2, 28pm2, 29pm2, 30pm2, 31pm2, 32pm2, 33pm2, 34pm2. 35pm2. 36pm2, 37pm2, 38pm2, 39pm2, 40pm2, 41pm2, 42pm2, 43pm2, 44pm2, 45pm2. 46pm2, 47pm2, 48pm2, 49pm2, 50pm2, 51pm2, 52pm2, 53pm2, 54pm2, 55pm2, 56pm2, 57pm2, 58pm2, 59pm2, 60pm2, 61pm2, 62pm2, 63pm2, 64pm2, 65pm2, 66pm2, 67pm2, 68pm2, 69pm2, 70pm2, 71pm2. 72pm2, 73pm2, 74pm2, 75pm2, 76pm2, 77pm2, 78pm2, 79pm2, 80pm2, 81pm2, 82pm2. 83pm2. 84pm2, 85pm2, 86pm2, 87pm2, 88pm2, 89pm2, 90pm2, 91pm2, 92pm2, 93pm2, 94pm2, 95pm2, 96pm2, 97pm2, 98pm2, 99pm2, 100pm2, 101pm2, 102pm2, 103pm2, 104pm2, 105pm2, 106pm2, 107pm2, 108pm2, 109pm2, 110pm2, 111pm2, 112pm2, 113pm2, 114pm2,115pm2, 116pm2, 117pm2, 118pm2, 119pm2, 120pm2, 121pm2, 122pm2, 123pm2, 124pm2,125pm2, 126pm2, 127pm2, 128pm2, 129pm2, 130pm2, 131pm2. 132pm2. 133pm2, 134pm2,135pm2, 136pm2, 137pm2, 138pm2, 139pm2, 140pm2, 141pm2, 142pm2, 143pm2, 144pm2,145pm2, 146pm2, 147pm2, 148pm2, 149pm2, 150pm2, 151pm2, 152pm2, 153pm2, 154pm2,155pm2, 156pm2, 157pm2, 158pm2, 159pm2, 160pm2, 161pm2, 162pm2, 163pm2, 164pm2,165pm2, 166pm2, 167pm2, 168pm2, 169pm2, 170pm2, 171pm2. 172pm2, 173pm2, 174pm2,175pm2, 176pm2, 177pm2, 178pm2, 179pm2, 180pm2, 181pm2. 182pm2. 183pm2. 184pm2.185pm2, 186pm2, 187pm2, 188pm2, 189pm2, 190pm2, 191pm2. 192pm2, 193pm2, 194pm2, 195pm2, 196pm2, 197pm2, 198pm2. 199pm2, or 200pm2.

[0111] In addition to the geometry of each individual pore 2102 / 2202, a material’s porosity is influenced by the amount and arrangement of multiple pores 2102 / 2202. A single material may have no pores, a single pore, or any number of pores such that the sum of the total volume of the pores is less than the material's total bounded volume (porosity less than 100%). Such a material may contain a single type, size and orientation of pores, such as spherical pores of 2pm diameter, multiple sizes of the same type and orientation of pore, such as elliptical pores ranging from 0.5pm - 4pm major diameter, each oriented 35° from the axis defining the materials width and 25° from the axis defining the materials depth, multiple types of the same size and orientation of pore, such as spherical pores of 3pm3volume and elliptical pores of 3pm3volume with each major axis oriented parallel to the material length and perpendicular to the material’s width and depth, and multiple orientations of the same type and size of pore, such as all rectangular prism pores with a length of 1mm, width of 0.1mm, and height of 0.2mm, oriented randomly. A material may also have a combination of pores of varying types, sizes and orientations.

[0112] The motif described above for three dimensions applies for two dimensions as well with respect to surface porosity. A material’s surface porosity may have no pores, a single pore, or any number of pores such that the sum of the total area of the pores is less than the total bounded area of the material (so that the porosity is less than 100%). Surface pores may be comprised of a single type, shape and orientation of pore, multiple types, shapes and orientations of pores, or any combination thereof.

[0113] Volumetric pores and / or surface pores may be arranged in an evenly distributed manner such that the intemodal distance 2007 between each pore is about equal. Volumetric pores and / or surface pores may be arranged in a periodic manner such that the arrangement of each pore for a first region is generally the same as a second region separated from the first in a way that does not match the intra-regional pattern but repeats for additional regions. Volumetric pores and / or surface pores may be arranged in a grouped manner such that the arrangement of pores in a region is similar to other regions, which may be dispersed from each other in a manner unrelated to the intra-regional arrangement. Volumetric pores and / or surface pores may be arranged in a random manner such that there is no clear pattern of arrangement of each pore. Furthermore, each category of arrangement may be directionally oriented or may not be directionally oriented. A single material may have a single, multiple, or all categories ofpore arrangements present. Arrangements of pores may be comprised of any combination of pore types, sizes, and orientations as disclosed above.

[0114] Porous materials may be single-layered or multi-layered. Multi-layered porous materials may have any number of layers. A multi-layer material may have 2-10 layers, 11-30 layers, 30-100 layers, or 100-100000 layers. A multi-layer material may have layers that total 1, 2, 3, 4. 5, 6, 7. 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21. 22. 23. 24, 25, 26, 27, 28,29. 30. 31. 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46. 47. 48. 49. 50. 51. 52. 53.54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102,103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118. 119, 120, 121,122, 123. 124, 125, 126, 127, 128. 129, 130. 131, 132, 133, 134, 135. 136, 137. 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159,160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178,179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197,198, 199, 200. or more. Each layer may have the same pore types, sizes, orientations and arrangements, or different layers may have different pore Apes, sizes, orientation and / or arrangements. Each layer of a multi-layer material may have the same material chemical structure (i.e. each layer is ePTFE) or may have different structures (i.e. one or more layers of ePTFE. one or more layers of Polyurethane, one or more layers of Silicone, one or more layers of porcine pericardium). A multi-layer material may have a mixture of porous or non-porous layers. For a multi-layer material which has layers of differing material chemistries, has one or more non-porous layers, or both, the pores of each porous layer may vary by pore type, size, orientation, and / or arrangement.

[0115] Each layer of a multi-layer material may comprise a surface porosity. In some embodiments, each layer of the multi-layer material comprises the same surface porosity. In some embodiments, each layer of the multi-layer material comprises a different surface porosity. In some embodiments, a layer of the multi-layer material comprises a surface porosity of about 1%, about 2%, about 3%, about 4%, about 5%. about 6%, about 7%. about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%. about 36%, about 37%, about 38%, about 39%, about 40%, about 41%. about 42%. about 43%. about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about57%, about 58%, about 59%. about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%. about 67%, about 68%, about 69%, about 70%, 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, or any value between any two of these values. In some embodiments, each layer of a multi-layer material comprises a surface porosity of about 1% to about 10 %, about 1% to about 15%, about 1% to about 20%, about 1% to about 25%. about 15% to about 20%, or about 25% to about 50%. In some embodiments, each layer of a multi-layer material comprises a surface porosity of greater than about 10%, greater than about 15%, greater than about 20%, greater than about 25%, greater than about 30%, greater than about 35%, greater than about 40%, greater than about 45%, or greater than about 50%.

[0116] FIG. 23 illustrates an exploded view of a multi-layer material in accordance with an embodiment. The multi-layered materials may include multiple layers of the same thickness or may include layers of different thicknesses. Individual layer thickness of a multi-layer material may be extremely thin (in the range of 0.1pm - 1 m), ven' thin (in the range of 1pm - 10pm), moderately thin (in the range of 10pm - 100pm), mildly thick (in the range of 0. 1mm -1mm), moderately thick (in the range of 1mm -2cm), thick (in the range of 2cm -10cm), or very thick (in the range of 10cm -100cm). Layer thicknesses may also be thinner than 0.1pm or thicker than Im. In some embodiments, each of the multiple layers may have a thickness of about 0.01pm, 0.05pm, 0.1pm, 0.2pm, 0.3pm, 0.4pm, 0.5pm, 0.6pm, 0.7pm, 0.8pm, 0.9pm, 1pm. 1.25pm, 1.5pm, 1.75pm, 2pm, 2.5pm, 3pm, 4pm, 5pm, 7pm, 8pm, 9pm, 10pm, 15pm. 25pm, 30pm, 40pm, 50pm, 60pm, 70pm, 80pm, 90pm, 100pm, 0.2mm, 0.3mm, 0.33mm, 0.35mm 0.4mm, 0.42mm, 0.45mm, 0.5mm, 0.53mm, 0.55mm, 0.6mm, 0.63mm, 0.65mm, 0.7mm, 0.75mm. 0.8mm, 0.85mm, 0.9mm, 0.95mm, 1mm, 1.05mm, 1.1mm, 1.15mm, 1.2mm, 1.25mm, 1.3mm. 1.4mm, 1.5mm, 1.6mm. 1.7mm, 1.8mm, 1.9mm, 2mm. 3mm, 3.5mm, 4mm, 4.2mm, 4.5mm, 5mm, 5.3mm, 5.5mm, 6mm, 6.3mm, 6.5mm, 7mm, 7.5mm 8mm, 8.5mm 9mm, 9.5mm 10mm, 10.5mm, 11mm, 11.5mm, 12mm, 13mm, 14mm, 15mm, 16mm, 7mm, 18mm, 19mm, 2cm, 2.5cm, 3cm, 3.5cm, 4cm, 4.5cm, 5cm, 5.5cm, 6cm, 6.5cm, 7cm, 7.5cm, 8cm, 8.5cm, 9cm, 9.5cm, 10cm, 15cm, 20cm. 25cm, 30cm. 35cm, 40cm, 45cm, 50cm, 55cm, 60cm, 65cm, 70cm, 75cm, 80cm, 85cm, 90cm, 95cm, or 100cm. In some embodiments, each of the multiple layers may have a thickness greater than about 10 pm.

[0117] A multi-layered material that includes porous material layers which have oriented pores and / or oriented pore arrangements may include such layers so that the orientation of one layer relative to another layer may be parallel, perpendicular, or at any other angle. For example, one layer of a multi-layered material may be oriented relative to another layer in amulti-layer material at an angle of 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°. 10°, 11°, 12°, 13°, 14°, 15°, 16°, 17°, 18°, 19°, 20°, 21°, 22°. 23°, 24°. 25°, 26°, 27°, 28°, 29°, 30°, 31°. 32°, 33°. 34°, 35°,36°, 37°, 38°, 39°, 40°, 41°, 42°, 43°, 44°, 45°, 46°, 47°, 48°, 49°, 50°, 51°, 52°, 53°, 54°, 55°,56°, 57°, 58°, 59°, 60°, 61°, 62°, 63°, 64°, 65°, 66°, 67°, 68°, 69°, 70°, 71°, 72°, 73°, 74°, 75°,76°, 77°, 78°, 79°, 80°, 81°, 82°, 83°, 84°, 85°, 86°, 87°, 88°, 89°, 90°, 91°, 92°, 93°, 94°, 95°,96°, 97°, 98°, 99°. 100°, 101°, 102°, 103°, 104°, 105°, 106°, 107°, 108°. 109°, 110°, 111°, 112°. 113°. 1 14°. 1 15°, 1 16°, 117°, 118°, 119°, 120°, 121°, 122°, 123°, 124°, 125°. 126°, 127°.128°, 129°, 130°, 131°, 132°, 133°, 134°, 135°, 136°, 137°, 138°, 139°, 140°, 141°, 142°, 143°,144°, 145°, 146°, 147°, 148°, 149°, 150°, 151°, 152°, 153°, 154°, 155°, 156°, 157°, 158°, 159°,160°, 161°, 162°. 163°, 164°, 165°, 166°, 167°, 168°, 169°, 170°, 171°, 172°, 173°, 174°, 175°,176°. 177°, 178°, 179°, or 180°. Multiple oriented layers in a multi-layered material may be oriented in the same way relatively to any other layer, or in multiple different ways. For example, if a single layer of a multi-layer material has a pore arrangement oriented parallel to direction X, another layer in the material may oriented also parallel, a third layer may be oriented at an angle of 30°, a fourth layer may be oriented at an angle of 60°, a fifth angle may be oriented perpendicular, a sixth layer may have no orientation, a seventh layer may be oriented at an angle of 45°, and a eighth layer may be oriented parallel.

[0118] Single-layer porous materials may have any shape or size. Illustrative geometries of a single-layer porous material include a flat sheet, a cylinder, tube, a sphere, a tube, a box, or any number of other shapes including more complex shapes. Multi-layer materials may also have any total shape or size. Illustrative geometries of a multi-layer porous material include a flat sheet, a cylinder, tube, a sphere, a tube, a box, or any number of other shapes including more complex shapes. Individual layers of a multi-layer material may have any shape or size. Illustrative geometries of individual layers of a multi-layer material include a flat sheet, a cylinder, tube, a sphere, a tube, a box, or any number of other shapes including more complex shapes.

[0119] Single-layer porous materials, multi-layer materials, and each layer of a multi-layer of material may be virtually any material or combination of materials including: polytetrafluoroethylene, expanded polytetrafluorethylene, fluorinated ethylene propylene, polypropylene, acrylonitrile butadine styrene, polyethylene, low molecular weight polyethylene, high molecular weight polyethylene, ultra-high molecular weight polyethylene, polyurethane, silicone, siloxane, polyurethane-siloxane copolymers, polyvinyl chloride, polyester, polylactic acid (PLA). polyglycolic acid (PGA), polycaprolactone (PCL). polyhydroxyalkanoates (PHAs), polydioxanone (PDO), poly orthoesters (POEs),polyanhydrides, polyphosph azenes, and biopolymers such as chitosan, alginate, hyaluronic acid, acetyl, polyvinyl alcohol, polyesters, polycarbonates, a methacrylate polymer, a vinyl benzene polymer, a 2 -hydroxy ethyl acrylate polymer, a butyl acrylate polymer, a 2-ethylhexyl acrylate polymer, a vinyltrimethoxysilane polymer, a vinyltriethoxysilane polymer, a vinyltoluene polymer, an a-methyl styrene polymer, a chlorostyrene polymer, a styrenesulfonic acid polymer, rubbers, hydrogels, other polymers, polymer blends or copolymers, nitinol, other shape-memory alloys, nickel, titanium, cobalt, chromium, cobaltchromium alloy, gold, silver, aluminum, copper, magnesium, tungsten, steel, stainless steel, steel carbide, tantalum, platinum, iridium, palladium, rhodium, beryllium, zirconium, other metals and alloys, porcine tissue, porcine pericardium, porcine vascular tissue, bovine tissue, bovine pericardium, bovine vascular tissue, human tissue, human pericardium, human vascular tissue, caprine tissue, murine tissue, avian tissue, marine organism tissue, other biologic tissues, collagen, pyrolytic carbon, graphite, graphene, bioactive glass, calcium phosphate ceramics, hydroxyapatite, tricalcium phosphate, alumina, zirconia, silicon nitride, other ceramics, scaffolds design for degradation, scaffolds designed for tissue ingrowth and decellularized extracellular matrices.

[0120] Single-layer porous materials, multi-layer materials, and / or each layer of a multilayer material may also include coatings or combinations of coatings including heparin, paclitaxel, coumadin, warfarin, PTFE, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents, antiinflammatory agents, anti-proliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, and combinations thereof.

[0121] Single-layer porous materials, multi-layer materials, and / or each layer of a multilayer material may also include infused agents and / or materials, or combinations of infused agents and / or materials including heparin, paclitaxel, coumadin, warfarin, PTFE, polyurethanecopolymers, biological growth factors, collagen, carbon, proteins, anti-platelet agents, antithrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, antiproliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, and combinations thereof.

[0122] Single-layer porous materials, multi-layer materials, and / or each layer of a multilayer of material may be created or modified by processes or combinations of processes including, extrusion, sintering, wrapping, molding, die cutting, melting, welding, laser welding,additive manufacturing, laser sintering, laser cutting, milling, lathing, chemical welding, adhesives, mechanical fixturing, injection molding, freezing, clamping, friction, compounding, layering, baking, static electrical binding, mixing, vacuum forming, pressurization, electrospinning, or electrolytic deposition.

[0123] Multiple layers may be created by a variety of means including by one or more of the following methods: stacking, folding, sliding, or wrapping layers around a mandrel or other form, laying multiple flat layers on top of one another, sliding cylindrical layers over one another, folding layers, helically wrapping layers around a structure, and twisting two or more layers together.

[0124] Each layer of a multi-layer material, or a material as a whole, may be generally flat and smooth. For example, a flat and smooth sheet would not meaningfully and / or variably extend beyond the generally two-dimensional space defined by the sheet or conduit itself (apart from its own thickness). Each layer of a multi-layer material, or a material as a whole, may also be non-flat or non-smooth. For example, a material may contain a single wrinkle, multiple wrinkles, a periodic arrangement of wrinkles, or a random arrangement of wrinkles. FIGS. 24A and 24B illustrate a porous material before and after 3D shaping, respectively. The porous material is shaped to include a bump 2401. A material may contain a single bump, multiple bumps, a periodic arrangement of bumps, or a random arrangement of bumps. Such wrinkles or bumps may be created by applying shaping to one or more layers, by inducing tensile or compressive stress in one or more layers, by applying different heats to one or more layers, by applying a different material between layers, including one that may induce a chemical reaction, or any number of other methods. FIG. 25 depicts polymer membranes after deformation for shaping. The polymer membranes comprise deformations 2501 to shape the polymer membranes to match anatomical leaflet shapes.

[0125] FIGS. 26A-C depicts an illustrative transcatheter aortic valve replacement (TAVR) from a top view (26A), a bottom view7(26B), and a side view7(26C), respectively. The TAVR comprises a plurality of leaflets 2601 which have been 3D shaped to more closely match anatomical leaflet shapes. FIGS. 26D-E depict illustrative surgical valves. The surgical valves comprise a plurality of leaflets 2602 which have been 3D shaped to match anatomical leaflet shapes. In some embodiments, the surgical valves may be one of an aortic valve or a mitral valve. FIGS. 26F-G depict an illustrative valved conduit. The valved conduit comprises a plurality of leaflets 2603 w hich have been 3D shaped to match anatomical leaflet shapes.

[0126] Radiopaque indicators may be added to or integrated with layers or multi-layered assemblies. Examples of radiopaque materials which may be used are indicators tungsten, gold,tantalum, bismuth, tungsten, iodine. Methods of integrating radiopaque materials include directly embedding, melting, or adhering, or mixing with another substance that may be added such as an ink that may be pad-printed. One example is using an ink that includes tungsten and pad printing the ink directly onto the layers. FIGS. 26H-26J depict illustrative vascular grafts comprising radiopaque markings 2604. FIGS. 26H and 261 depict the radiopaque markings photographed under visible light, and FIG. 26J depicts the radiopaque markings photographed under x-ray light. FIG. 27 A depicts a conduit with radiopaque markings before plastic deformation imaged under x-ray light, and FIG. 27B depicts a conduit with radiopaque markings after plastic deformation imaged under x-ray light. FIG. 28 depicts a conduit with radiopaque markings and an end plastically deformed into a flared and conical shape.

[0127] Support structures may be added to or integrated with layers or multi-layered assemblies. Support structures may be constructed from one or more biocompatible polymers (including multi-layer polymer constructs), metals, or other materials. Support structures may have cross-sectional geometries that are circular, oval, rectangular, D-shaped or other geometries. Support structures may be included via embedding, melting, sintering, adhering, or other methods. Support structure inclusion may be aided by additional materials such as by using fluorinated ethylene propylene (FEP) to improve integration of a PTFE support structure to a PTFE membrane or conduit. Examples of support structures included integrated rings, removable rings, integrated spirals, and removable spirals.

[0128] Various embodiments are directed towards multi-layer materials that have different inner and outer layers. Inner and outer layers may differ by any pore attribute or pore structure attribute (size, shape, orientation, arrangement, type, surface porosity, volumetric porosity, anisotropicity). differ by material type or chemistry, differ by thickness, differ by layer orientation, differ by coating, differ by infused agent, differ by method of construction, differ by method of layering or attachment, or differ in any other way. FIG. 30 depicts images of layers which vary by anisotropicity' and surface porosity, FIG. 31 depicts images of layers which vary by anisotropicity and intemodal distance (IND), and FIG. 32 depicts images of layers which vary by anisotropicity and total surface pore area.

[0129] One non-limiting example of layer thicknesses of a multi-layered material with 10 layers may be 10 layers of ePTFE each of about 2.5pm thickness. An example of a multilayered material with 16 layers may be 4 layers of ePTFE of about 2.5pm thickness, 4 layers of ePTFE of about 5pm thickness, 4 layers of polyurethane of about 1pm thickness, and 4 layers of Silicone of about 10pm thickness. An example of a material with 30 layers may be28 layers of ePTFE each about 4pm, 1 layer of a urethane-siloxane copolymer with 1mm thickness, and 1 layer of ePTFE with a 0.75mm thickness.

[0130] One non-limiting example is a material which has outer layers having a lower surface porosity (less than 15%) and inner layers having a higher surface porosity (greater than 15%). The lower surface porosity of the inner layers may serve to prevent fluid infiltration through the material and / or reduce cellular infiltration through the material, while the higher inner layer surface porosity contributes to a high overall porosity %, which may serve to increase the flexibility of the material.

[0131] Another non-limiting example is a multi-layer material having a total of between 10-30 layers, of which two layers are outer layers and between 8-28 layers are inner layers. Each of the outer layers has a thickness of between 2pm - 5pm, an average pore area of between 0.5pm2- 2.5pm2and a surface porosity between 1% - 10%. The inner layers each have a thickness of between 0.1pm - 0.2pm, an average pore area between 5pm2- 15 pm2, and total volumetric porosity of the inner layers between 25% - 50%. Such a material would be expected to be more flexible than a material of similar total thickness that is constructed from one or more layers that match the pore area and surface porosity of the outer layer described above in this paragraph due to the relatively high overall porosity of the described material. The multi-layer material would also be expected to be more resistant to fluid infiltration and cellular ingrowth than a material of similar total thickness that is constructed from one or more layers that match the pore area and surface porosity of the inner layers described above in this paragraph due to its low surface porosity. Such an example could be produced as a flat sheet to allow for cutting (for example by blade, die, or laser) into a shape, or could be produced in tubular form for example to ease attachment to a stent, or could be produced in conical form for example to allow for attachment to a surgical valve frame which features a taper to improve valve dynamics. Such an example could also be modified using heat and pressure (for example via a shaped metal mold with the material sandwiched between mold plates and heated to between 350°C - 400°C in a furnace for 30-180min) to provide 3-dimensional shaping, such as to enhance hydrodynamic performance when used as heart valve leaflets.

[0132] Another non-limiting example is a multi-layer conduit constructed from 2 tubular layers, of which one layer is an abluminal layer and one layer is a luminal layer. In this example, the abluminal layer has a higher thickness and porosity as compared to the luminal layer. In some embodiments, the abluminal layer has a thickness between 0.3mm - 1 ,2mm, an intemodal distance of 10pm - 40pm, and a total volumetric porosity of greater than 20% while the luminal layer has a thickness of less than 0.1mm and a total volumetric porosity’ of less than 10%. Theluminal layer would be expected to prevent fluid entry through the multi-layer conduit up to higher pressures than the abluminal layer would alone even if the total thickness of such a conduit is the same as the multi-layer conduit described due to its lower porosity. The multilayer conduit would be expected to be more flexible than a conduit which is constructed from a similar total thickness of a material which matches the luminal layer as the multi-layer conduit has a higher total porosity. Additionally, the abluminal layer may provide the multi-layer conduit with improved kink resistance compared to a conduit constructed from the luminal layer alone. In other non-limiting examples, additional layers outside of the abluminal layer or between the luminal and abluminal layers to further modify the multi-layer constructs properties, such as by adding a layer of elastomer between the luminal and abluminal layers to enhance sealing following puncture with a dialysis needle, and / or by adding spiralized or ringed PTFE on the abluminal surface to further enhance kink and crush resistance. One or more of the luminal, abluminal, and optional intermediary layers described above could themselves be formed from multiple layers. For example, the luminal layer may itself be constructed from multiple layers to provide the desired properties on the luminal side, while featuring properties on the opposite side that enhance fusion to the abluminal layer to prevent delamination.

[0133] Another non-limiting example includes using a higher-porosity surface to improve the attachment between multiple separately manufactured materials. For example, a luminal material constructed of 2-10 ePTFE layers that have generally radially oriented pores of between 0.1pm2- 1.5pm2may not have strong attachment to an ePTFE conduit such as a single-layer conduit of between 10pm - 40pm inter-nodal distance and a 0.3mm - 1.2mm thickness when sintered together. However, by having the surface of the luminal material that contacts the ePTFE conduit have a higher porosity, such as 4pm2- 10pm2, the attachment may be improved. This would prevent separation of the luminal material from the conduit, such as due to cyclic blood pressure when used as a vascular conduit, without compromising the properties of the surfaces that can be contacted directly by biologic forces, as the layer added to improve attachment would be in the assembled material’s interior. To further improve the features of such an assembled material, radiopaque markings, support structures, and / or additional polymer layers may be added to the assembled material.

[0134] Another non-limiting example involves utilizing multi-layer materials for the luminal, abluminal or both covers of a covered stent construct such as a stent-graft or the covered portion of a transcatheter valve. A cover material constructed of between 3-25 ePTFE layers may be created which includes an inner surface layer closer to the lumen, an outer surface layer further from the lumen, and 1-23 interior layers. Each of the inner surface layerand the outer surface layer may be single- or multi-layered, and each is defined by similar microstructures compared to the interior layers. In order to allow for stent deployment, all layers or the average of all layers may have oriented porosity to provide lower radial strength. The outer surface layer may have higher porosity than the interior layers in order to allow for ingrow th and integration with the body to prevent stent migration. The inner surface layer may- have lower porosity than the outer surface layer to provide increased strength and tearresistance. The inner surface layer may have lower porosity to reduce thrombosis and / or ingrowth on the luminal surface including when the cover material is the only cover used (i.e. there is not both a luminal and abluminal cover). The inner surface layer may alternatively have higher porosity to encourage endothelialization. or to improve adhesion between another contract (i.e. between a luminal and abluminal cover around the stent, or two the stent itself). Cover materials may be directly adhered, sintered, or melted to the stent constmct, or adhered, sintered or melted to another layer (i.e. the luminal to abluminal layer) including by utilizing the gaps between the stent struts. Another material may also be used to improve adherence, such as FEP. The cover material may also be wrapped around the stent constmct. including by helically wrapping.

[0135] A valved conduit is a conduit having a valve disposed within it. A valved conduit is typically mounted on a stent before deployment. There are tw o types of stents on which the valved conduits are ordinarily mounted: a self-expanding stent and a balloon-expandable stent. To place such valved conduits and stents into a delivery apparatus and ultimately into a patient, the valved conduit and the stent must first be collapsed or crimped to reduce its circumferential size.

[0136] To date, the design and construction of these valved conduits have necessitated the use of a stretchable material in order to accommodate the change in shape that a conduit goes through between a collapsed state (for introduction through a small vessel) and an expanded state (for function in the final deployed position). Disclosed herein are transcatheter stents that have substantially the same length between the collapsed state and the expanded state and aid in use of non-stretchable conduits and valve structures.

[0137] Various embodiments are directed to valved conduits having leaflets that do not contact the w all of the conduit in an open position (FIG. IB). As illustrated in FIGS. 1A and IB, an exemplary7valved conduit encompassed by such embodiments may include a conduit 10 having an inner surface 11 and an outer surface 12. A valve 100 composed of one or more leaflets may be disposed within the conduit 10 and attached to the inner surface 11 of theconduit 10. In the open position (FIG. IB), a sinus gap G separates the inner surface of the conduit 11 from the valve 100.

[0138] FIGS. 2A and 2B illustrate an interior downstream, cross-sectional view of an exemplary valve encompassed by FIGS. 1 A and IB in an open, FIG. 2A, and closed, FIG. 2B, configuration. In the open configuration (FIG. 2A), fluid flows through the valve, forcing the fan portion of a leaflet 201 towards the inner surface of the conduit. In the closed configuration (FIG. 2B), the fan portion of the leaflet 201 may form a closure against fluid backflow. FIGS. 2A and 2B show a conduit 20 having an inner surface 21 and an outer surface 22, and a valve composed of one or more leaflets 201 that are attached to the inner surface 21 of the conduit 20. In the open configuration (FIG. 2A), a sinus gap 202 is created between the leaflets 201 and the inner surface 21 of the conduit 20 that allows the leaflets 201 to fully extend without contacting the inner surface 21 of the conduit 20. In embodiments such as those depicted in FIGS. 2A and 2B in which the valve includes two leaflets, at least a portion of the leaflets 201 may overlap along a diameter of the conduit 20 when in the closed configuration (FIG. 2B), thereby substantially blocking flow of fluid through the conduit 20. In embodiments in which the valve includes one leaflet, the leaflet may contact the inner surface of the conduit opposite the attachment site of the valve, and in embodiments in which the valve includes three or more leaflets, the leaflets may overlap at a longitudinal axis of the tube.

[0139] In some embodiments, a conduit has an attachment point on an inner surface of the conduit. In some embodiments, a valve is attached to the conduit at the attachment point. In some embodiments, the valve is attached to the conduit at one or more attachment points. In some embodiments, the valve is attached to the conduit at a plurality of attachment points. In some embodiments, the vale is attached to the conduit at least one attachment point.

[0140] In some embodiments, the valve may be attached to the conduit by suturing, welding, fusion, applying an adhesive, clamping, sintering, heating, chemical welding, static electric, frictional forces, lasering, and combinations thereof. Where the valve is attached to the conduit by welding, fusion, adhesive, sintering, or the like which form a line of attachment rather than a single point, the valve is considered to be attached to the conduit at a plurality of attachment points.

[0141] The sinus gap 202 between the inner surface 21 of the conduit 20 and the leaflets 201 can be created by any means. For example, in some embodiments, the width W of the leaflets 201 may be shorter than the length of conduit between attachment points. Dr This arrangement is illustrated in FIGS. 3A and 3B. FIG. 3A shows a simple diagram of the valve configuration in which the leaflet 301 of a valve encompassed by the embodiments describedabove is disposed within a conduit 30 such that the width, W (dashed line), of the leaflet 301 is shorter than the portion of the conduit, Df, between a first attachment point, fi, connecting the leaflet 301 to the inner surface 31 of the conduit 30 and a second attachment point, fz, connecting the leaflet 301 to the inner surface 31 of the conduit 30. This valve configuration is further illustrated in FIG. 3B using the example valve depicted in FIG. 2B. The portion of the conduit, Df, between the first attachment point, fi, and the second attachment point, fz, is longer than the width. W (dashed line), of the leaflet 301.

[0142] In some embodiments, a valve gap may be formed by the valve in a closed configuration. Specifically, as shown in FIG. 2B, a multi-leaflet valve and at least a portion of a conduit inner surface may be disposed to form a valve gap 203 formed at the intersection of at least a portion of the inner surface of the conduit and a portion of the fan edge.

[0143] FIG. 4 is an illustration of a valve 44 unfolded on single plane with the width, W, of the leaflet illustrated in FIG. 2B identified (dashed line). In some embodiments, the leaflet may have additional features than those illustrated in FIG. 4. For example, although FIG. 4 shows a valve 44 configured to create two leaflets, 401a and 401b, a leaflet for a single leaflet valve or a leaflet for a three or four leaflet valve may include the same elements in a similar configuration.

[0144] Each leaflet 401a, 401b may include an outer sinus edge 402a, 402b, an inner sinus edge 403a, 403b, and an open sinus edge 404a, 404b. In embodiments in which the leaflet includes two or more leaflets, the open sinus edge 404a, 404b of each leaflet 401a, 401b may by coextensive as illustrated in FIG. 4. In some embodiments, the valve 44 may have a commissure 420 connecting the first leaflet 401a and the second leaflet 401b. In particular embodiments, the commissure 420 may be a perpendicular intersection connecting each inner sinus edge 403a. 403b with the meeting point of the open sinus edges 404a. 404b, creating a linear connection perpendicular to the open sinus edges 404a, 404b and at an angle to the inner sinus edges 403a, 403b.

[0145] In some embodiments, each leaflet 401a, 401b may further include a fan 410a, 410b having a fan edge 411a, 411b extending beyond the open sinus edge 404a, 404b away from the outer sinus edge 401a, 401b and inner sinus edge 402a, 402b. The fan 410a, 410b may allow the leaflets of the valve to contact one another or overlap w hen the valve is in the closed position (see FIG. 3B) stopping flow' of fluid through the valve. The fan 410a, 410b may have any shape, and in certain embodiments, the fan 410a, 410b may have a curved shape with a wide section on one side of the leaflet and a narrow section on the opposite side of the leaflet. In some embodiments, the narrow' section of the fan 410a of a first leaflet 401a may connectto a narrow section of the fan 410b of the second leaflet 401b at the commissure 420, and in particular embodiments, the narrow section of the fan 410a of a first leaflet 401a may connect to a narrow section of the second leaflet 401b at the commissure 420 at the connection point of the open sinus edges 404a, 404b.

[0146] FIGS. 5A and 5B show a leaflet 54 such as that described in FIG. 4 attached to a conduit 50. In FIG. 5 A, the conduit 50 is inverted such that the leaflet 54 is disposed on the outside of the conduit 50, and the conduit 50 is reverted such that the leaflet 54 is inside the conduit 50. Thus, an inner surface 51 is on the outside of the conduit 50 in FIG. 5 A, and the inner surface 51 is inside the conduit 50 in FIG. 5B. An outer surface 52 is on the inside of the conduit 50 in FIG. 5A, and the outer surface 52 is outside the conduit 50 in FIG. 5B. The leaflet 54 may be attached to the inner surface 51 of the conduit 50 at the respective outer sinus edge 502a and 502b and the respective inner sinus edge 503a and 503b (503a is on the opposite side of the conduit 54). Each of the outer sinus edges 502a, 502b and inner sinus edge 503a, 503b may be attached to the conduit by a substantially fluid impervious connection such as, for example, suturing (as shown), fusion, applying an adhesive, or welding. The commissure 520 may also be attached to the inner surface 51 of the conduit 50 by, for example, suturing (as shown), applying an adhesive, or welding. The open sinus edges 504a, 504b are not attached to the conduit 50, and remain open to fluids flowing through the conduit 50. The opening creates a sinus 530a, 530b between the inner surface 51 of the conduit 50 and each leaflet 501a, 501b, and each open sinus edge 504a. 504b.

[0147] FIGS. 6A and 6B are three-dimensional representations of a leaflet 601 (dark shading) on an inverted conduit 60 to show the sinus 630 created by the leaflet 601. FIG. 6A is a longitudinal view-, and FIG. 6B is a cross-sectional view. As shown in FIG. 6A, the leaflet 601 is attached to the conduit at the outer sinus edge 602 and inner sinus edge 603 by a substantially fluid impervious connection such as, for example, suturing, applying an adhesive, or welding. A tapered dimple 65 in the conduit 60 may be underlying the leaflet 601 and may provide a conduit side of the sinus 630 and allow the valve to achieve the configuration illustrated in FIG. 6B when the conduit 60 is returned to its original shape (i.e. reverted such that the outer surface 62 of the conduit 60 is on an outer surface of the structure). Because the width of the leaflet 601 changes along its length, the degree to which the conduit must bend also changes along the length of the conduit 60.

[0148] This arrangement is further illustrated in FIGS. 7A-7D. In FIG. 7A, a valve is in an inverted configuration and shows a leaflet 701 of the valve disposed within a conduit 70 such that the width, W (dashed line), of the leaflet 701 is shorter than the portion of the conduit, Df,between a first attachment point, fi and a second attachment point, fz. connecting the leaflet 701 to the inner surface of the conduit 70. FIG. 7B is a perpendicular cross section of the valve of FIG. 7 A illustrating the tapered dimple 75. D is the length of the leaflet 701. Wd depth of the dimple 75, i.e. the depth of the gap between the leaflet 701 and the conduit 70, which, as illustrated, varies with D from the open edge 704 of the leaflet 701 to a point where the outer sinus edge 702 and the inner sinus edge 703 meet (see FIG. 7D). FIG. 7C and FIG. 7D show the valve in operable configuration where the conduit has been reverted such that the valve is on the inner surface of the conduit 70 and the conduit 70 has retained its cylindrical shape. The leaflet 701, which has an open edge 704 width, W, that is less than the circumference of the conduit 70 between attachment points may be suspended below the inner surface of the conduit 70 by a depth, Wd, which varies with the length, B, of the leaflet 701 creating a sinus 730. With reference to FIG. 7D, in some embodiments, the leaflet 701 may have a substantially triangular shape. Therefore, the leaflet width, W, may also vary with the length, B, of the leaflet 701.

[0149] A valve having leaflets as described and discussed above may reduce the contact of the leaflets and, in some embodiments, fans attached to the open sinus edge, with the inner surface of the conduit when the valve is in open configuration. Reduced contact with the inner surface of the conduit decreases the likelihood that the valve will stick in open configuration and may also reduce wear on the leaflet over many cycles. Thus, the valves of various embodiments may provide improved long term use when implanted as part of a medical device. For example, in some embodiments, the valves described above may be used as a shunt for connecting of the right ventricle to the pulmonary artery following a Norwood operation, as frequently performed for the treatment of single-functional-ventricle-disorders such as Hypoplastic Left Heart Syndrome. In other embodiments, the valves described above may be used for the correction or reconstruction of the right ventricle outflow tract (RVOT) for congenital heart disorders such as tetralogy of Fallot, Truncus Arterious, DextroTransposition of the Great Arteries, Pulmonary Atresia of Intact Ventricular Septum, or Aortic Valvular Disease. In still other embodiments, the valves described above may be incorporated into a stent and deployed as artificial valves in adult and pediatric patients.

[0150] The conduits 10, 20, 30, 50, 60, 70, and 1101, the valves 100, 44, 1102 and the leaflets 201, 301, 54, 601, 701, 801 of various embodiments may be constructed from a material. In some embodiments, the material comprises any biocompatible and hemocompatible polymer. In some embodiments, the material can be a fluoropolymer. In some embodiments, the material can be a polymer. In some embodiments, the matenal can be polytetrafluoroethylene, expanded polytetrafluoroethylene, polyester, polyethyleneterephthalate, polydimethylsiloxane, polyurethane, and combinations thereof. In some embodiments, the material may be extruded. In some embodiments, the material may be an extruded fluoropolymer. In some embodiments, the material may be an extruded polymer. In some embodiments, the fluoropolymer can be polytetrafluoroethylene, expanded polytetrafluoroethylene, and combinations thereof. In some embodiments, the polymer can be polyester, polyethylene terephthalate, polydimethylsiloxane, polyurethane, and combinations thereof. In some embodiments, the material may be a fluoropolymer coated with a bioactive coating. In some embodiments, the material may be surface-modified to include a surface coating or a bioactive material. In some embodiments, the material may be a polymer coated with a bioactive coating. In some embodiments, the material may be surface-modified to include a surface coating or a bioactive material. The surface coating or bioactive material may be an anti-coagulant coating or an anti-coagulant material that promotes biocompatibility such as, for example, coumadin, heparin, a heparin derivative, a Factor Xa inhibitor, a direct thrombin inhibitor, hementin, sintered porous titanium microspheres, a carbon coating, or combinations thereof. The surface coating may be another hemocompatible polymer such as a polyurethane, polysiloxane, polycarbonate, polyurethane copolymer (for example poly- carbonate-urethane, poly-carbonate-urethane-siloxane, poly-urethane-urea, poly-urethane- urea-siloxane), or silicone. In some embodiments the material may be infused with another material or a bio-active agent. The infused agent or material may be an anti-coagulant coating or an anti-coagulant material that promotes biocompatibility such as. for example, coumadin. heparin, a heparin derivative, a Factor Xa inhibitor, a direct thrombin inhibitor, hementin, sintered porous titanium microspheres, a carbon coating, or combinations thereof. The infused agent or material may be an anti-microbial agent such as rifampin, chlorhexidine, minocycline, 5-FU, or other anti-microbial, anti-bacterial, or anti-infective agents.

[0151] In some embodiments, the material is non-stretchable. In some embodiments, the material is non-stretchable, biocompatible, and hemocompatible. Non-limiting examples of non-stretchable, biocompatible and hemocompatible materials that can be used to make the conduits or valves are polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyethylene terephthalate (PET), polydimethyl siloxane (PDMS), polyethylene (PE), polypropylene (PP), polyesters, polycarbonates, polyvinyl chloride (PVC), hydrogels, for example polyurethane, polysiloxane, polycarbonate, polyurethane-copolymers (for example poly-carbonate-urethane, poly-carbonate-urethane-siloxane, poly-urethane-urea, poly- urethane-urea-siloxane). or silicone and the like. In some embodiments, the biocompatible and hemocompatible material may be polymer-coated with a bioactive coating. In someembodiments, the biocompatible and hemocompatible polymer may be surface-modified or infused to include a bioactive material.

[0152] In some embodiments, the conduit, the valve, or the leaflet are made from a layer of the material. In some embodiments, the conduit, the valve, or the leaflet are made from multiple layers of the material. In some embodiments, the conduit, the valve, or the leaflet are made from more than one material. In some embodiments, the conduit, the valve, or the leaflet are made from one or more layers of the material. In some embodiments, the conduit, the valve, or the leaflet are made from at least two layers of the material. In some embodiments, the conduit, the valve, or the leaflet are made from a first layer of a first material and a second layer of a second material.

[0153] The conduit 10, 20, 30, 50, 60, 70, and 1101 described herein may generally be flexible, and the size of the conduits of various embodiments may vary depending on the intended use of the valve. In some embodiments, the conduit may have a diameter in a range of about 40 mm to about 15 mm, about 25 mm to about 2 mm, about 20 mm to about 2 mm, about 15 mm to about 2 mm, about 10 mm to about 2 mm, about 8 mm to about 3 mm, about 5 mm to about 3 mm, or any range or individual diameter encompassed by these example ranges. In other embodiments, the conduit may have a diameter in a range of about 25 mm to about 5 mm, about 20 mm to about 8 mm, about 15 mm to about 10 mm, or any range or individual diameter encompassed by these example ranges. In some embodiments, the conduit may have a diameter in a range of about 2 mm to about 40 mm, about 2 mm to about 30 mm. about 2 mm to about 20 mm, about 2 mm to about 10 mm, about 2 mm to about 5 mm. In some embodiments, the conduit may have a diameter in a range of about 5 mm to about 40 mm, about 10 mm to about 40 mm, about 20 mm to about 40 mm. In some embodiments, the conduit diameter is about 2 mm. In some embodiments, the conduit diameter is about 3 mm. In some embodiments, the conduit diameter is about 4 mm. In some embodiments, the conduit diameter is about 5 mm. In some embodiments, the conduit diameter is about 6 mm. In some embodiments, the conduit diameter is about 7 mm. In some embodiments, the conduit diameter is about 8 mm.

[0154] In some embodiments, the conduit may have a thickness in a range of about 0.05 mm to about 0.5 mm, about 0.5 mm to about 2.0 mm, about 0.5 mm to about 1.5 mm, or any range or individual thickness encompassed by these illustrative ranges. In some embodiments, the conduit thickness is about 0.05 mm. In some embodiments, the conduit thickness is about 0.5 mm. In some embodiments, the conduit thickness is about 1.5 mm. In some embodiments.the conduit thickness is about 2 mm. In some embodiments, the conduit thickness is about 1 mm.

[0155] In some embodiments, the conduit comprises more than one layer of the material. In some embodiments, the conduit comprises multiple materials. For example, the conduit may comprise a material having a first yield strength and first ultimate tensile strength and may be impregnated with a second material having a second yield strength and / or second ultimate tensile strength. In some embodiments, the conduit may be fabricated from two or more elastic or plastically deformable materials woven together.

[0156] In embodiments in which the conduit includes more than one layer of the material, each layer of a multi-layer conduit may be composed of the same material. In other embodiments, each layer of a multi-layer conduit may be composed of a different material. In further embodiments, each layer of a multi-layer conduit may be composed of a material characterized by different mechanical properties. For example, an inner layer of a multi-layer conduit may include a material having a first yield strength and a first ultimate tensile strength and an outer layer that may include a second material having a second yield strength and / or a second ultimate tensile strength. The first yield strength may be greater than, about equal to, or less than the second yield strength. The first ultimate tensile strength may be greater than, about equal to, or less than the second ultimate tensile strength. Alternatively, an inner layer may include an elastic or plastically deformable material, and an outer layer may include an inelastic or frangible material.

[0157] In some embodiments, the conduit may be composed of one or more layers of a low porosity material (pore area percentage less than 20%) and one or more layers of a high porosity material (pore area percentage greater than 20%). In some embodiments, one or more layers of the low porosity material may have a pore area percentage of less than or equal to 20%, less than or equal to 15%, less than or equal to 10%, less than or equal to 5%, less than or equal to 4%, less than or equal to 3%, less than or equal to 2% or less than or equal to 1%. In some embodiments, the high porosity material may have a pore area percentage of greater than or equal to 20%, greater than or equal to 30%, greater than or equal to 40%, greater than or equal to 50%, greater than or equal to 60%, greater than or equal to 70%, greater than or equal to 80%, or greater than or equal to 90%.

[0158] Conduits composed of multiple layers may have expansion capabilities depending on the material properties of the multiple layers. In some embodiments, a conduit comprising a biodegradable outer layer and an elastic or plastically deformable inner layer may be expanded due to the force of a fluid flowing therein but only after the outer layer has degraded.In some embodiments, a conduit having an inelastic or frangible outer layer and an elastic or plastically deformable inner layer may remain in an unexpanded state until sufficient force, for example, supplied by an inserted expansion device, is applied internally to rupture the outer layer and thus permit the inner layer to expand.

[0159] In some embodiments, the conduit materials, formulations, and / or mechanical properties may be constant over the longitudinal dimension of the conduit. In some embodiments, the conduit materials, formulations, and / or mechanical properties of the conduit may vary along the length or any partial length of the conduit. Conduits having multiple branches may have mechanical properties that differ between the branches and / or a main cylindrical tube of the conduit.

[0160] In certain embodiments, the conduits described above may include additional components. In some embodiments, the conduit may include a stent that is attached to or encapsulated by the material of the conduit, or an inner layer may include a stent while an outer layer may include an elastic or plastically deformable material. In some embodiments, a conduit may be composed of a biodegradable outer layer and an elastic or plastically deformable inner layer. In some further examples, a multi-layer conduit may include a first inner layer comprising a woven material and a second outer layer comprising a woven material. It may be understood that the woven material composing the inner layer may be the same as the woven material composing the outer layer. Alternatively, the woven material composing the inner layer may differ from the woven material composing the outer layer.

[0161] In some embodiments, the conduit may comprise a valve. In some embodiments, the valved conduit may include a conduit having a first conduit layer having an inner surface in physical communication with an outer surface of a second conduit layer and the valve is disposed within the second conduit layer. As one example of such a multi-layer valved conduit, the first conduit layer may be composed of a first plastically deformable material having ayield strength of about 0.1 MPa to about 4 MPa, and the second conduit layer may be composed of the same plastically deformable material as the first layer. In an alternative example, the multilayer valved conduit may be composed of a first conduit layer having a first plastically deformable material having a yield strength of about 0.1 MPa to about 4 MPa, and a second conduit layer composed of a second material that may differ from the first material. In still another example, the valved conduit may have a first conduit layer composed of a woven material, a second conduit layer composed of a woven material, or both the first conduit layer and the second conduit layer may each be composed of a woven material. In some embodiments of the multi-layer valved conduit, the first conduit layer may be biodegradable. In somealtemative embodiments of a multi-layer valved conduit, the first conduit layer may include a non-plastically deformable material. In yet another embodiment, the multi-layer valved conduit may include a stent as part of the second conduit layer.

[0162] In some embodiments, the conduit has a yield strength. In some embodiments, the yield strength is about 0.1 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.2 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.3 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.4 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.5 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.6 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.7 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.8 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.9 MPa to about 4 MPa. In some embodiments, the yield strength is about 1 MPa to about 4 MPa. In some embodiments, the yield strength is about 0.1 MPa to about 0.2 MPa. In some embodiments, the yield strength is about 0. 1 MPa to about 0.3 MPa. In some embodiments, the yield strength is about 0. 1 MPa to about 0.4 MPa. In some embodiments, the yield strength is about 0.1 MPa to about 0.5 MPa. In some embodiments, the yield strength is about 0.1 MPa to about 0.6 MPa. In some embodiments, the yield strength is about 0. 1 MPa to about 0.7 MPa. In some embodiments, the yield strength is about 0.1 MPa to about 0.8 MPa. In some embodiments, the yield strength is about 0. 1 MPa to about 0.9 MPa. In some embodiments, the yield strength is about 0. 1 MPa to about 1 MPa. In some embodiments, the yield strength is about 0. 1 MPa. In some embodiments, the yield strength is about 0.2 MPa. In some embodiments, the yield strength is about 0.3 MPa. In some embodiments, the yield strength is about 0.4 MPa. In some embodiments, the yield strength is about 0.5 MPa. In some embodiments, the yield strength is about 0.6 MPa. In some embodiments, the yield strength is about 0.7 MPa. In some embodiments, the yield strength is about 0.8 MPa. In some embodiments, the yield strength is about 0.9 MPa. In some embodiments, the yield strength is about 1 MPa. In some embodiments, the yield strength is about 2 MPa. In some embodiments, the yield strength is about 3 MPa. In some embodiments, the yield strength is about 4 MPa.

[0163] The valve 100, 44, 1102 or leaflet 201, 301, 54, 601, 701, and 801 may have a thickness of about 0.05 mm to about 0.3 mm in various embodiments, and this thickness may vary within the valve. In some embodiments, the valve may comprise a material having a thickness or total thickness of about 0.05 mm to about 0.3 mm, about 0. 1 mm to about 0.3 mm, about 0.15 mm to about 0.3 mm, about 0.2 mm to about 0.3 mm. about 0.25 mm to about 0.3 mm, about 0.05 mm to about 0.25 mm, about 0. 1 mm to about 0.25 mm, about 0.2 mm to about0.25 mm, about 0.05 mm to about 0.2 mm, about 0.1 mm to about 0.2 mm, about 0. 15 mm to about 0.2 mm, or a value within any of these range. For example, in some embodiments, the sinus portion of the leaflet may have be thicker than the fan portion or the fan portion may be thicker than the sinus portion of the leaflet. The thickness of the valve may be selected to provide sufficient flexibility to allow the valve to obtain the open and closed configurations under the pressure of the flow of fluid through the conduit. The dimensions of each leaflet may vary depending on the diameter of the conduit and the number of leaflets making up the valve. For example with reference to FIG. 7D, in various embodiments, the ratio of the length, B, of a leaflet 701, to the width, W, of the leaflet may be about 0.2 to about 2, about 0.3 to about 2, about 0.4 to about 2, about 0.5 to about 2, about 0.6 to about 2, about 0.75 to about 2, about 1 to about 2, about 1 to about 1, or any ratio between any two of these ratios. In some embodiments, the ratio of the width of the leaflet to a portion of the conduit circumference between the attachment points may be about 0.63 to about 1, about 0.7 to about 1, about 0.5 to about 1, or any ratio between any two of these ratios. The ratio of the width, W, the leaflet 701 to the diameter of the conduit may be about 0.02 to about 3, about 0.05 to about 3. about 0.08 to about 3, about 0.1 to about 3, about 0.2 to about 3, about 0.5 to about 3, about 1 to about 3, about 0.9 to about 1.7, or any ratio therebetween or any ratio encompassed by these example ratios. In some embodiments, including a commissure 420 (FIG. 4) i.e. valves having more than one leaflet, the ratio between a length of the commissure 420 and the width, W, of the leaflet 401 may be about 0.05 to about 2, about 0.1 to about 2, about 0.2 to about 2, about 0.3 to about 2, about 0.5 to about 2, or any ratio between any two of these ratios. The ratio of the inner sinus edge 703 the leaflet 701 to the width, W, of the leaflet 701 may be about 0.2 to about 2.5, about 0.3 to about 2.5, about 0.4 to about 2.5, about 0.5 to about 2.5, about 0.6 to about 2.5, about 0.75 to about 2.5, about 1 to about 2.5, about 1 to about 1. or any ratio between any two of these ratios.

[0164] In various such embodiments, the width, W, of the leaflet 701 may be about 1 mm to about 10 mm, about 2 mm to about 7 mm, about 2 mm to about 5 mm, about 20mm to about 40 mm, about 10 mm to about 30 mm, or any individual width or range encompassed by any of these example width ranges. The length, B, of the leaflet 701 may be about 5 mm to about 40 mm, about 5 mm to about 30 mm, about 8 mm to about 25 mm, about 10 mm to about 20 mm, or any individual length, B, or range encompassed by any of these example length ranges. The length of the inner sinus edge 703 and the outer sinus edge 704 may each, individually, be about 5 mm to about 45 mm. about 5 mm to about 35 mm, about 8 mm to about 30 mm, about 10 mm to about 20 mm, or any individual length or range encompassed by any of these examplelength ranges. In some embodiments, multiple leaflet valves may have no commissure, and in other embodiments, multiple leaflet valves may have a commissure having a length of about 0.05 mm, about 0.1 mm, about 0.2 mm, about 0.3 mm, about 0.5 mm, about 0.8 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, about 4.0 mm, about 6.0 mm, about 8.0 mm, about 10.0 mm, about 12.0 mm, or any width within a range encompassed by any two of these example lengths.

[0165] Although FIGS. 2-7 illustrate valve structures composed of one or two leaflets, the valve of other embodiments may be composed of any number of leaflets. For example, embodiments include a valve having three and four leaflets in which each leaflet has an inner and outer sinus edge, a fan edge, a fan, and a commissure between each neighboring leaflet. For example, a three-leaflet valve may include two commissures: one commissure between a first leaflet and a second leaflet, and a second commissure between the second leaflet and a third leaflet. Equivalent metrics to those described above can be used to describe each leaflet of a multi -leaflet valve. The valve may incorporate a closure formed by the juxtaposition, proximity, and / or overlap of three or four fan structures. The mutual disposition of some portions of the three or four fan edges along with the inner surface of the conduit may result in a gap similar to the gap area described above. In some embodiments, the entire valve along with the leaflets are made from a single piece of biocompatible material as shown in FIG. 10.

[0166] The valve described herein is not limited to a particular utility. For example, in some embodiments, the valve described herein can be used as a heart valve for use in cardiac, coronary or vascular procedures, and may be composed of one or more leaflets. The valve may encompass, as non-limiting examples, a single-leaflet heart valve having a single heart valve leaflet, or a multi-leaflet heart valve having more than one heart valve leaflet. Each heart valve leaflet may include a sinus edge, a fan edge, a sinus structure, and a fan structure, and additional structural components such as, without limitation, a conduit (which may be tube-like, stentlike, or multi-layered such as a tube within a stent) and one or more conduit sinus structures. The valve may encompass a single-leaflet valve having a single-leaflet valve structure, or a multi-leaflet valve structure composed of either multiple single-leaflet valve structures or a multi-leaflet valve structure.

[0167] In some embodiments, leaflets are constructed from at least one layer of the material with each layer having a plurality of pores, with each individual pore being defined by a pore area. In some embodiments, the plurality of pores may be disconnected, such that there is limited communication between the pores, separated by a solid node of matenal. In some embodiments, the plurality of pores have the same pore area. In some embodiments, theplurality of pores have a different pore area. In some embodiments, the pore area is about 1 square micron. In some embodiments, the pore area is about 0.5 square micron. In some embodiments, the pore area is about 0.25 square micron. In some embodiments, the pore area is about 0. 1 square micron. In some embodiments, the pore area is less than 1 square micron. In some embodiments, the pore area is less than 0.5 square micron. In some embodiments, the pore area is less than 0.25 square micron. In some embodiments, the pore area is less than 0. 1 square micron. In some embodiments, the pore area is up to 1 square micron. In some embodiments, the pore area is up to 0.5 square micron. In some embodiments, the pore area is up to 0.25 square micron. In some embodiments, the pore area is up to 0.1 square micron. In some embodiments, the pore area is in a range of about 0.05 square micron to about 1 square micron. In some embodiments, the pore area is in a range of about 0. 1 square micron to about 1 square micron. In some embodiments, the pore area is in a range of about 0.25 square micron to about 1 square micron. In some embodiments, the pore area is in a range of about 0.5 square micron to about 1 square micron. In some embodiments, the pore area is in a range of about 0.05 square micron to about 0.5 square micron. In some embodiments, the pore area is in a range of about 0.05 square micron to about 0.25 square micron. In some embodiments, the pore area is in a range of about 0.05 square micron to about 0.1 square micron.

[0168] In some embodiments, leaflets are constructed from at least one layer of the material with a layer having a plurality of pores, with each individual pore being defined by a pore area. In some embodiments, the plurality of pores may be disconnected, such that there is limited communication between the pores, separated by a solid node of material. In some embodiments, the plurality7of pores have a different pore area. In some embodiments, the plurality of pores having a different pore area are defined by an average pore area for the material. The average pore area is calculated by adding the pore area of the plurality of pores and dividing by the total number of pores. In some embodiments, the average pore area is about 1 square micron. In some embodiments, the average pore area is about 0.5 square micron. In some embodiments, the average pore area is about 0.25 square micron. . In some embodiments, the average pore area is about 0. 1 square micron. In some embodiments, the average pore area is less than 1 square micron. In some embodiments, the average pore area is less than 0.5 square micron. In some embodiments, the average pore area is less than 0.25 square micron. In some embodiments, the average pore area is less than 0.1 square micron. In some embodiments, the average pore area is up to 1 square micron. In some embodiments, the average pore area is up to 0.5 square micron. In some embodiments, the average pore area is up to 0.25 square micron. In some embodiments, the average pore area is up to 0. 1 square micron. In some embodiments,the average pore area is in a range of about 0.05 square micron to about 1 square micron. In some embodiments, the average pore area is in a range of about 0. 1 square micron to about 1 square micron. In some embodiments, the average pore area is in a range of about 0.25 square micron to about 1 square micron. In some embodiments, the average pore area is in a range of about 0.5 square micron to about 1 square micron. In some embodiments, the average pore area is in a range of about 0.05 square micron to about 0.5 square micron. In some embodiments, the average pore area is in a range of about 0.05 square micron to about 0.25 square micron. In some embodiments, the average pore area is in a range of about 0.05 square micron to about 0. 1 square micron.

[0169] In some embodiments, leaflets are constructed from at least one layer of a material having a plurality of pores, with each individual pore being defined by a pore diameter. In some embodiments, the plurality of pores may be disconnected, such that there is limited communication between the pores, separated by a solid node of material. In some embodiments, the plurality' of pores have the same pore diameter. In some embodiments, the plurality of pores have a different pore diameter. In some embodiments, the pore diameter is about 1 micron. In some embodiments, the pore diameter is about 0.5 micron. In some embodiments, the pore diameter is about 0.25 micron. In some embodiments, the pore diameter is about 0.1 micron. In some embodiments, the pore diameter is less than 1 micron. In some embodiments, the pore diameter is less than 0.5 micron. In some embodiments, the pore diameter is less than 0.25 micron. In some embodiments, the pore diameter is less than 0. 1 micron. In some embodiments, the pore diameter is up to 1 micron. In some embodiments, the pore diameter is up to 0.5 micron. In some embodiments, the pore diameter is up to 0.25 micron. In some embodiments, the pore diameter is up to 0.1 micron. In some embodiments, the pore diameter is in a range of about 0.05 micron to about 1 micron. In some embodiments, the pore diameter is in a range of about 0.1 micron to about 1 micron. In some embodiments, the pore diameter is in a range of about 0.25 micron to about 1 micron. In some embodiments, the pore diameter is in a range of about 0.5 micron to about 1 micron. In some embodiments, the pore diameter is in a range of about 0.05 micron to about 0.5 micron. In some embodiments, the pore diameter is in a range of about 0.05 micron to about 0.25 micron. In some embodiments, the pore diameter is in a range of about 0.05 micron to about 0. 1 micron.

[0170] In some embodiments, leaflets are constructed from at least one layer of a material having a plurality of pores, with each individual pore being defined by a pore diameter. In some embodiments, the plurality of pores may be disconnected, such that there is limited communication between the pores, separated by a solid node of material. In someembodiments, the plurality of pores have a different pore diameter. In some embodiments, the plurality of pores having a different pore area defined by an average pore diameter for the material. The average pore diameter is calculated by adding the pore diameter of the plurality of pores and dividing by the total number of pores. In some embodiments, the average pore diameter is about 1 micron. In some embodiments, the average pore diameter is about 0.5 micron. In some embodiments, the average pore diameter is about 0.25 micron. In some embodiments, the average pore diameter is about 0.1 micron. In some embodiments, the average pore diameter is less than 1 micron. In some embodiments, the average pore diameter is less than 0.5 micron. In some embodiments, the average pore diameter is less than 0.25 micron. In some embodiments, the average pore diameter is less than 0.1 micron. In some embodiments, the average pore diameter is up to 1 micron. In some embodiments, the average pore diameter is up to 0.5 micron. In some embodiments, the average pore diameter is up to 0.25 micron. In some embodiments, the average pore diameter is up to 0.1 micron. In some embodiments, the average pore diameter is in a range of about 0.05 micron to about 1 micron. In some embodiments, the average pore diameter is in a range of about 0. 1 micron to about 1 micron. In some embodiments, the average pore diameter is in a range of about 0.25 micron to about 1 micron. In some embodiments, the average pore diameter is in a range of about 0.5 micron to about 1 micron. In some embodiments, the average pore diameter is in a range of about 0.05 micron to about 0.5 micron. In some embodiments, the average pore diameter is in a range of about 0.05 micron to about 0.25 micron. In some embodiments, the average pore diameter is in a range of about 0.05 micron to about 0. 1 micron.

[0171] In some embodiments, leaflets are constructed from a material having a thickness. In some embodiments, the thickness is about 0.3 mm. In some embodiments, the thickness is about 0. 1 mm. In some embodiments, the thickness is about 0.075 mm. In some embodiments, the thickness is about 0.05 mm. In some embodiments, the thickness is about 0.045 mm. In some embodiments, the thickness is about 0.04 mm. In some embodiments, the thickness is about 0.035 mm. In some embodiments, the thickness is about 0.03 mm. In some embodiments, the thickness is about 0.025 mm. In some embodiments, the thickness is about 0.02 mm. In some embodiments, the thickness is about 0.015 mm. In some embodiments, the thickness is about 0.01 mm. In some embodiments, the thickness is less than 0.3 mm. In some embodiments, the thickness is less than 0. 1 mm. In some embodiments, the thickness is less than 0.075 mm. In some embodiments, the thickness is less than 0.05 mm. In some embodiments, the thickness is less than 0.045 mm. In some embodiments, the thickness is less than 0.04 mm. In some embodiments, the thickness is less than 0.035 mm. In someembodiments, the thickness is less than O.O3 mm. In some embodiments, the thickness is less than 0.025 mm. In some embodiments, the thickness is less than 0.02 mm. In some embodiments, the thickness is less than 0.015 mm. In some embodiments, the thickness is less than 0.01 mm. In some embodiments, the thickness is up to 0.3 mm. In some embodiments, the thickness is up to 0.1 mm. In some embodiments, the thickness up to 0.075 mm. In some embodiments, the thickness is up to 0.05 mm. In some embodiments, the thickness is up to 0.045 mm. In some embodiments, the thickness is up to 0.04 mm. In some embodiments, the thickness is up to 0.035 mm. In some embodiments, the thickness is up to 0.03 mm. In some embodiments, the thickness is up to 0.025 mm. In some embodiments, the thickness is up to 0.02 mm. In some embodiments, the thickness is up to 0.015 mm. In some embodiments, the thickness is up to 0.01 mm. In some embodiments, the thickness is in a range of about 0.01 mm to about 0.3 mm. In some embodiments, the thickness is in a range of about 0.015 mm to about 0.3 mm. In some embodiments, the thickness is in a range of about 0.02 mm to about 0.3 mm. In some embodiments, the thickness is in a range of about 0.025 mm to about 0.3 mm. In some embodiments, the thickness is in a range of about 0.03 mm to about 0.3 mm. In some embodiments, the thickness is in a range of about 0.035 mm to about 0.3 mm. In some embodiments, the thickness is in a range of about 0.04 mm to about 0.3 mm. In some embodiments, the thickness is in a range of about 0.01 mm to about 0.1 mm. In some embodiments, the thickness is in a range of about 0.01 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.015 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.02 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.025 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.03 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.035 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.04 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.045 mm to about 0.075 mm. In some embodiments, the thickness is in a range of about 0.01 mm to about 0.05 mm. In some embodiments, the thickness is in a range of about 0.015 mm to about 0.05 mm. In some embodiments, the thickness is in a range of about 0.02 mm to about 0.05 mm. In some embodiments, the thickness is in a range of about 0.025 mm to about 0.05 mm. In some embodiments, the thickness is in a range of about 0.03 mm to about 0.05 mm. In some embodiments, the thickness is in a range of about 0.035 mm to about 0.05 mm. In some embodiments, the thickness is in a range of about 0.04 mm to about 0.05 mm. In some embodiments, the thickness is in a range of about 0.045 mm to about 0.05 mm.

[0172] In some embodiments, leaflets are constructed from multiple layers of a material, wherein the multiple layers of the material have a total thickness. In some embodiments, the total thickness is about 0.3 mm. In some embodiments, the total thickness is about 0. 1 mm. In some embodiments, the total thickness is about 0.075 mm. In some embodiments, the total thickness is about 0.05 mm. In some embodiments, the total thickness is about 0.045 mm. In some embodiments, the total thickness is about 0.04 mm. In some embodiments, the total thickness is about 0.035 mm. In some embodiments, the total thickness is about 0.03 mm. In some embodiments, the total thickness is about 0.025 mm. In some embodiments, the total thickness is about 0.02 mm. In some embodiments, the total thickness is about 0.015 mm. In some embodiments, the total thickness is about 0.01 mm. In some embodiments, the total thickness is less than 0.3 mm. In some embodiments, the total thickness is less than 0. 1 mm. In some embodiments, the total thickness is less than 0.075 mm. In some embodiments, the total thickness is less than 0.05 mm. In some embodiments, the total thickness is less than 0.045 mm. In some embodiments, the total thickness is less than 0.04 mm. In some embodiments, the total thickness is less than 0.035 mm. In some embodiments, the total thickness is less than 0.03 mm. In some embodiments, the total thickness is less than 0.025 mm. In some embodiments, the total thickness is less than 0.02 mm. In some embodiments, the total thickness is less than 0.015 mm. In some embodiments, the total thickness is less than 0.01 mm. In some embodiments, the total thickness is up to 0.3 mm. In some embodiments, the total thickness is up to 0.1 mm. In some embodiments, the total thickness up to 0.075 mm. In some embodiments, the total thickness is up to 0.05 mm. In some embodiments, the total thickness is up to 0.045 mm. In some embodiments, the total thickness is up to 0.04 mm. In some embodiments, the total thickness is up to 0.035 mm. In some embodiments, the total thickness is up to 0.03 mm. In some embodiments, the total thickness is up to 0.025 mm. In some embodiments, the total thickness is up to 0.02 mm. In some embodiments, the total thickness is up to 0.015 mm. In some embodiments, the total thickness is up to 0.01 mm. In some embodiments, the total thickness is in a range of about 0.01 mm to about 0.3 mm. In some embodiments, the total thickness is in a range of about 0.015 mm to about 0.3 mm. In some embodiments, the total thickness is in a range of about 0.02 mm to about 0.3 mm. In some embodiments, the total thickness is in a range of about 0.025 mm to about 0.3 mm. In some embodiments, the total thickness is in a range of about 0.03 mm to about 0.3 mm. In some embodiments, the total thickness is in a range of about 0.035 mm to about 0.3 mm. In some embodiments, the total thickness is in a range of about 0.04 mm to about 0.3 mm. In some embodiments, the total thickness is in a range of about 0.01 mm to about 0.1 mm. In someembodiments, the total thickness is in a range of about 0.01 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.015 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.02 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.025 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.03 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.035 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.04 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.045 mm to about 0.075 mm. In some embodiments, the total thickness is in a range of about 0.01 mm to about 0.05 mm. In some embodiments, the total thickness is in a range of about 0.015 mm to about 0.05 mm. In some embodiments, the total thickness is in a range of about 0.02 mm to about 0.05 mm. In some embodiments, the total thickness is in a range of about 0.025 mm to about 0.05 mm. In some embodiments, the total thickness is in a range of about 0.03 mm to about 0.05 mm. In some embodiments, the total thickness is in a range of about 0.035 mm to about 0.05 mm. In some embodiments, the total thickness is in a range of about 0.04 mm to about 0.05 mm. In some embodiments, the total thickness is in a range of about 0.045 mm to about 0.05 mm.

[0173] In some embodiments, leaflets are constructed from multiple layers of material, wherein the multiple layers of material have a total thickness. In some embodiments, leaflets are constructed from multiple layers of material, where the layers are substantially similar in thickness. In other embodiments, leaflets are constructed from multiple layers of material where the layers differ significantly in thickness. For example, a leaflet may be constructed from two layers, one of which is approximately 0.040 mm thick, and another is approximately 0.005 mm thick, resulting in a total thickness of 0.045 mm.

[0174] As illustrated in FIG. 13, in some embodiments, leaflets are constructed from a material having a surface porosity. In some embodiments, the surface porosity may be between 1% and 15% (inclusive). In some embodiments, the surface porosity is about 15%. In some embodiments, the surface porosity is about 14%. In some embodiments, the surface porosity is about 13%. In some embodiments, the surface porosity is about 12%. In some embodiments, the surface porosity is about 11%. In some embodiments, the surface porosity is about 10%. In some embodiments, the surface porosity is about 9%. In some embodiments, the surface porosity7is about 8%. In some embodiments, the surface porosity' is about 7%. In some embodiments, the surface porosity is about 6%. In some embodiments, the surface porosity is about 5%. In some embodiments, the surface porosity is about 4%. In some embodiments, the surface porosity is about 3%. In some embodiments, the surface porosity is about 2%. In someembodiments, the surface porosity is about 1%. In some embodiments, the surface porosity is less than 15%. In some embodiments, the surface porosity is less than 14%. In some embodiments, the surface porosity is less than 13%. In some embodiments, the surface porosity is less than 12%. In some embodiments, the surface porosity is less than 11%. In some embodiments, the surface porosity is less than 10%. In some embodiments, the surface porosity is less than 9%. In some embodiments, the surface porosity is less than 8%. In some embodiments, the surface porosity is less than 7%. In some embodiments, the surface porosity is less than 6%. In some embodiments, the surface porosity is less than 5%. In some embodiments, the surface porosity is less than 4%. In some embodiments, the surface porosity is less than 3%. In some embodiments, the surface porosity is less than 2%. In some embodiments, the surface porosity is in a range of about 1% to about 15%. In some embodiments, the surface porosity' is in a range of about 2% to about 15%. In some embodiments, the surface porosity is in a range of about 3% to about 15%. In some embodiments, the surface porosity is in a range of about 4% to about 15%. In some embodiments, the surface porosity is in a range of about 5% to about 15%. In some embodiments, the surface porosity is in a range of about 6% to about 15%. In some embodiments, the surface porosity' is in a range of about 7% to about 15%. In some embodiments, the surface porosity is in a range of about 8% to about 15%. In some embodiments, the surface porosity is in a range of about 1% to about 14%. In some embodiments, the surface porosity is in a range of about 1% to about 13%. In some embodiments, the surface porosity is in a range of about 1% to about 12%. In some embodiments, the surface porosity' is in a range of about 1% to about 11%. In some embodiments, the surface porosity is in a range of about 1% to about 10%. In some embodiments, the surface porosity is in a range of about 1% to about 9%. In some embodiments, the surface porosity' is in a range of about 1% to about 8%. In some embodiments, the surface porosity' is in a range of about 1% to about 7%. In some embodiments, the surface porosity is in a range of about 1% to about 6%. In some embodiments, the surface porosity is in a range of about 1% to about 5%. In some embodiments, the surface porosity' is in a range of about 1% to about 4%. In some embodiments, the surface porosity' is in a range of about 1% to about 3%. In some embodiments, the surface porosity is in a range of about 1% to about 2%. In some embodiments, the surface porosity is in a range of about 2% to about 8%. In some embodiments, the surface porosity’ is in a range of about 3% to about 8%. In some embodiments, the surface porosity' is in a range of about 4% to about 8%. In someembodiments, the surface porosity is in a range of about 2% to about 7%. In some embodiments, the surface porosity is in a range of about 2% to about 6%. In some embodiments, the surface porosity is in a range of about 2% to about 5%. In some embodiments, the surface porosity is in a range of about 2% to about 4%. In some embodiments, the surface porosity is in a range of about 2% to about 3%. In some embodiments, the surface porosity is in a range of about 2% to about 2%. In some embodiments, the surface porosity is in a range of about 3% to about 5%. In some embodiments, the surface porosity is in a range of about 1% to less than 15%.

[0175] In some embodiments, leaflets are constructed from multiple layers of material, at least two layers of which are anisotropic with differing orientations. For example, in some embodiments, two layers may be anisotropic with orientations that are perpendicular to one another. In other embodiments, two layers may be anisotropic with orientations that are offset by less than 90 degrees, but greater than 10 degrees, relative to each other. In some embodiments, two layers may be anisotropic with orientations that are not parallel relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 90 degrees to about 10 degrees, about 85 degrees to about 10 degrees, about 80 degrees to about 10 degrees, about 75 degrees to about 10 degrees, about 70 degrees to about 10 degrees, about 65 degrees to about 10 degrees, about 60 degrees to about 10 degrees, about 55 degrees to about 10 degrees, about 50 degrees to about 10 degrees, about 45 degrees to about 10 degrees, about 40 degrees to about 10 degrees, about 35 degrees to about 10 degrees, about 30 degrees to about 10 degrees, about 25 degrees to about 10 degrees, about 20 degrees to about 10 degrees, about 15 degrees to about 10 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 90 degrees to about 15 degrees, about 90 degrees to about 20 degrees, about 90 degrees to about 25 degrees, about 90 degrees to about 30 degrees, about 90 degrees to about 35 degrees, about 90 degrees to about 40 degrees, about 90 degrees to about 45 degrees, about 90 degrees to about 50 degrees, about 90 degrees to about 55 degrees, about 90 degrees to about 60 degrees, about 90 degrees to about 65 degrees, about 90 degrees to about 70 degrees, about 90 degrees to about 75 degrees, about 90 degrees to about 80 degrees, about 90 degrees to about 85 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 90 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 85 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 80 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that areoffset by about 75 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 70 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 65 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 60 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 55 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 50 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 45 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 40 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 35 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 30 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 25 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 20 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 15 degrees relative to each other. In some embodiments, two layers may be anisotropic with orientations that are offset by about 10 degrees relative to each other.

[0176] Disclosed herein are transcatheter stents with valved conduits. An exemplary stent is shown in FIG. 9A. The stent 900 has three contiguous portions or regions, a proximal portion 901, an intermediate portion 902, and a distal portion 903. The proximal portion 901 has a relatively larger cross-section in the expanded configuration, while the intermediate portion 902 and the distal portion 903 have relatively smaller cross-section in the expanded configuration. The intermediate portion 902 is in the form of a cylinder having a substantially constant diameter along its length. In some embodiments, the intermediate portion 902 may have a variable diameter along its length. A transition section 901a may taper inwardly from the proximal portion 901 to the intermediate portion 902. Further, the proximal portion 901 faces the aorta and the distal portion 903 faces the annulus when the stent is deployed.

[0177] In some embodiments, proximal portion 901 and the distal portion 903 is made of a series of cells arranged in one or more annular rows around the stent. The cells may be spindle-shaped structures 904, as shown in FIG. 9A, and may be defined as structures having a wider central section with tapering ends. For example, in FIG. 9A, the proximal portion 901 and the distal portion 903 are each made up of two annular row-s of spindle-shaped structures.In other embodiments, proximal portion 901 and the distal portion 903 may each have three, four, or five annular rows of spindle-shaped structures. It should be appreciated that as the number of annular rows increase, the area formed by each spindle-shaped structure may decrease correspondingly, to maintain the length of the proximal portion 901 and the distal portion 903. Further, the area of spindle-shaped structures in the proximal portion 901 may be larger than the area of spindle-shaped structures in the distal portion 903. It will be appreciated that the shape of the cells is not limited to spindle-shaped structures and can also encompass other shapes, such as diamond shapes, rhomboid shapes, and the like.

[0178] In some embodiments, the intermediate portion 902 is made of a series of chevronshaped structures 905 arranged in two or more annular rows opposed to each other. For clarity', an isolated pair of opposing chevron-shaped structures are depicted in FIG. 9B. For example, in FIG. 9A, the intermediate portion 902 has two annular rows 902a, 902b of chevron-shaped structures 905 opposing each other. Row 902a is towards the proximal portion 901, and row 902b is towards the distal portion 903. The number of chevron-shaped structures 905 in each annular row may vary. For example, in FIG. 9 A there are 12 chevron-shaped structures 905 in each annular row 902a, 902b. In other embodiments, the number of chevron-shaped structures 905 in each annular row may vary' from 4 to 24.

[0179] In some embodiments, the intermediate portion 902 of the stent 900 further has one or more attachment points 906 to facilitate attachment of the conduit and / or the valve structure, as shown in FIG. 9A. The attachment points 906 are present on the median vertices of one or more chevron-shaped structures 905. For example, FIG. 9C shows a single chevron-shaped structure 905 with a pair of median vertices 906a, 906b, and a pair of lateral vertices 907a, 907b. Proximal median vertex 906a faces towards the proximal portion 901 of the stent, and distal median vertex 906b faces towards the distal portion 903 of the stent. Preferably, the conduit and / or the valve structure may be attached to the proximal and distal median vertices (906a, 906b) of the chevron-shaped structures 905 present in the intermediate portion 902 of the stent. The number of attachment points may vary, ranging from 6 to 20, depending on the size of the stent and the conduit / valve structure. The conduit and / or the valve structure may be attached to the attachment points 906 by suturing, welding, fusion, applying an adhesive, or any combination thereof. The attachment points 906 are disposed at a selected distance between each other such that the distance between the attachment points does not substantially change when the stent is collapsed (crimped) from an expanded configuration.

[0180] In FIG. 9D, the stent 900 is shown in expanded configuration with a plurality' of attachment points 906a, 906b, 906c, and 906d in the intermediate portion 902. When the stent900b is collapsed (as shown in FIG. 9E), the distance between the attachment points 906a and 906b, between attachment points 906c and 906d, and between attachment points 906b and 906c essentially remain the same. Attachment points 906c and 906d rotate with respect to 906a and 906b and compensates for the longitudinal stretching of the stent. In addition, 906a and 906b translate together and 906c and 906d translate together in opposite directions. Therefore, although the intermediate portion 902 changes length when it undergoes the transition from expanded configuration to the collapsed configuration, the length of multiple regions (in this example 906a-906b, 906b-906c, and 906c-906d) remain substantially the same.

[0181] Due to the non-stretching nature of the portions of the stent, it can accommodate conduits and valve structures made of non-stretch material. Non-limiting examples of nonstretch material that can be used to make the conduits and valve structures are polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyethylene terephthalate (PET), poly dimethyl siloxane (PDMS), polyethylene (PE), polypropylene (PP), polysiloxane, polycarbonate, polyurethane copolymer (for example poly-carbonate-urethane, poly-carbonate-urethane-siloxane, poly-urethane-urea, poly-urethane-urea- siloxane), polyesters, polycarbonates, polyvinyl chloride (PVC), hydrogels, a methacrylate polymer, a vinyl benzene polymer, a 2-hydroxyethyl acrylate polymer, a butyl acrylate polymer, a 2-ethylhexyl acrylate polymer, a vinyltrimethoxysilane polymer, a vinyltriethoxysilane polymer, a vinyltoluene polymer, an a-methyl styrene polymer, a chlorostyrene polymer, a styrenesulfonic acid polymer, and a combination thereof.

[0182] The stent disclosed herein may be made from cobalt, titanium, nickel, chromium, stainless steel, a polymer, a pseudo-elastic metal, alloys thereof, or any combination thereof. In some embodiments, the stent may be made from a nickel titanium alloy, such as nitinol. In some embodiments, the stents disclosed herein are self-expandable stents. As used herein, a self-expandable stent refers to a structure / component has a mechanical memory to return to the expanded or deployed configuration. Mechanical memory may be imparted to the framework structure that forms the stent by thermal treatment to achieve a spring temper in stainless steel, for example, or to set a shape memory in a susceptible metal alloy, such as nitinol, or a polymer.

[0183] It will be understood by one of ordinary skill in the art that the length of each portion of the stent 900 may vary according to the application and is not limited to the proportions shown in FIG. 9 A. For example, in one embodiment, the length of the intermediate portion 902 is equal to the length of the leaflet of a valve structure described herein, for example length B of leaflet 701 as shown in FIG. 7D. In some embodiments, the length of the intermediateportion 902 is such that the distance between the two attachment points 906a and 906c is equal to the length B of the leaflet 701 shown in FIG. 7D. In some embodiments, the length of the intermediate portion 902 may be about 5 mm to about 40 mm, about 5 mm to about 30 mm, about 8 mm to about 25 mm, about 10 mm to about 20 mm, or any value or range of values between any two of these endpoints. In some embodiments, the length of the proximal portion 901 may be from about 5 mm to about 50 mm. about 5 mm to about 40 mm, about 5 mm to about 30 mm, about 5 mm to about 20 mm. about 25 mm to about 50 mm. or about 35 mm to about 50 mm. In some embodiments, the distal portion 903 may have a length of about 3 mm to about 20 mm, about 3 mm to about 15 mm, about 3 mm to about 10 mm, or about 3 mm to about 5 mm or a value within any of these ranges. It should be appreciated that the length described herein of various portions may not vary irrespective of whether the stent is in expanded configuration (deployed state) or collapsed configuration (crimped state).

[0184] In some embodiments, the diameter of the proximal portion 901 may be from about 5 mm to about 50 mm, about 5 mm to about 40 mm, about 5 mm to about 30 mm, about 5 mm to about 20 mm, about 5 mm to about 10 mm, or any individual width or range encompassed by these example ranges. In some embodiments, the proximal portion 901 of the stent may have a substantially constant diameter along its length. In some embodiments, the proximal portion 901 may taper inwardly towards the intermediate portion 902.

[0185] In some embodiments, the diameter of the intermediate portion 902 may be from about 5 mm to about 50 mm, about 5 mm to about 40 mm, about 5 mm to about 30 mm, about 5 mm to about 20 mm, about 5 mm to about 10 mm, or any individual width or range encompassed by these example ranges. In some embodiments, the intermediate portion 902 of the stent may have a substantially constant diameter along its length. In some embodiments, the intermediate portion 902 may have variable diameter along its length.

[0186] In some embodiments, the diameter of the distal portion 903 may be from about 5 mm to about 50 mm, about 5 mm to about 40 mm, about 5 mm to about 30 mm, about 5 mm to about 20mm, about 5 mm to about 10mm, or any individual width or range encompassed by these example ranges. In some embodiments, the distal portion 903 of the stent may have a substantially constant diameter along its length. In some embodiments, the free edge of the distal portion 903 may taper outward.

[0187] FIG. 10 illustrates an embodiment of a valve structure 1000 that may be attached to the stent 900. The valve 1000 is made of a single piece of biocompatible material, having 3 leaflets 1001. A commissure 1002 exists between each leaflet. The outer sinus edge and inner sinus edge of each leaflet can be attached to the intermediate portion 902 of the stent. In someembodiments, each leaflet of the valve is attached to the intermediate portion 902 at a pair of attachment points, and each attachment point present on opposing annular row of chevron shaped structures. For example, the regions lOOOa-c on the valve may be attached to the attachment points 906a-c present on the intermediate portion of the stent, as show n in FIG. 9D. For example, 1000a is attached to 906a, 1000b is attached to 906b, and 1000c is attached to 906c. Because the distance between the attachment points 906a-906b and 906b-906c do not change when the stent is expanded or collapsed, a valve made from anon-stretchable material may be used. In addition, other regions of the leaflet can also be used to attach the valve to the stent, such as the commissure region 1002. In some embodiments, the valve is directly attached to the stent. In other embodiments, the valve is attached to the inner surface of a conduit, and the conduit is attached to the stent. In further embodiments, the valve and the conduit are concurrently attached to the same regions of the stent.

[0188] In some embodiments, the stent includes a valved conduit (a conduit having a valve). In other embodiments, the stent includes a valve directly attached to the stent. FIGS. 11A and 1 IB show an exemplary embodiment of stent 1100 having a conduit 1101 disposed on an inner surface of the stent 1100, and a valve 1102. In some embodiments, the valve 1102 may be attached directly to the inner surface of the stent 1100, without conduit 1101 disposed between the valve and the stent. In another embodiment, a sheath may also be located on the outer surface of the stent. The conduit and / or the sheath may cover all or only a portion of the length and circumference of the stent. Further, the valve contained within the stents of such embodiments can have any number of leaflets. For example, the stent 1100 in FIGS. 11A and 1 IB has three leaflets; however, embodiments include stents with valves having two leaflets as illustrated in FIGS. 2A-B and 3A-B or one leaflet as illustrated in FIGS. 1A-B. Similarly, the valved conduits described above and exemplified in FIGS. 1-3 can include three leaflets. Each leaflet of the stent 1100 of various embodiments may include a gap when the valve is in an open position (FIG. 11 A) and, therefore, may have a width that is shorter than the portion of the conduit between attachment points.

[0189] Various embodiments are directed to a fixing stencil 840. In some embodiments as illustrated in FIGS. 8A-B, the fixing stencil 840 may include a stencil head 841 and a handle 842. The stencil head 841 may substantially triangular flat surface 843 having a base 844, a first outer edge 845, a second outer edge 846, and a tip 847, and a triangular curved surface 848. In various embodiments, the triangular curved surface 848 may be tapered laterally from a longitudinal axis extending from the handle 842 to the first outer edge 845 and from the longitudinal axis to the second outer edge 846. The triangular curved surface 848 may befurther curved from the base 844 to the tip 847 creating a complex of curved surfaces having a tetrahedral shape extending away from the base 844 to the tip 847. In some embodiments, the stencil head 841 may further include holes or slots 849 along the first outer edge 845 and second outer edge 846 to allow physical fixturing, for example, suturing, welding, adhesive application, or other means for attaching the leaflet 801 to the conduit 80 without contacting the stencil head 841. In other embodiments, the stencil head 841 may be pierceable or locally destructible along the first outer edge 845 and second outer edge 846 to allow removal of the stencil head 841 after fixturing.

[0190] The handle 842 of various embodiments may be any means for manipulating and holding the fixing stencil 840 in place while the valve is attached to the conduit. For example, in some embodiments, the handle 842 may be sized and shaped to be gripped by a human hand. In other embodiments, the handle 842 may include one or more tabs or wings sized and shaped for holding the fixing stencil 840 to the conduit and valve using surgical tools, claps, vice grips, or other tools.

[0191] The size of the stencil head 841 may vary depending on the size and shape of the valve that will be produced using the fixing stencil 840. In general, the length, Bs, from the base 844 to the tip 847 of the stencil head 841 may be substantially the same length, B, as the leaflet 801. The variable width, WSL, of the substantially triangular flat surface may substantially correspond to the variable width of the triangular leaflet and the variable depth, DSL, of the triangular curved surface 884 may substantially corresponding to the depth of the sinus 830. Thus, the stencil head may be configured to have substantially the same shape and volume as the sinus 830 created between the leaflet 801 and the portion of the conduit 80 making up the tapered dimple 85.

[0192] In various embodiments, the width, WSL, of the stencil head 841 may be about 1 mm to about 10 mm, about 2 mm to about 7 mm, about 2 mm to about 5 mm, about 20 mm to about 40 mm, about 10 mm to about 30 mm, or any individual width or range encompassed by any of these example ranges. The length, Bs, of the stencil head 841 may be about 5 mm to about 40 mm, about 5 mm to about 30 mm, about 8 mm to about 25 mm, about 10 mm to about 20 mm, or any individual length or range encompassed by any of these example ranges. The length of the first outer edge 845 and second outer edge 846 may each, individually, be about 5 mm to about 45 mm, about 5 mm to about 35 mm, about 8 mm to about 30 mm, about 10 mm to about 20 mm, or any individual length or range encompassed by any of these example ranges. The depth, DSL, of the stencil head 841 at the base 844 may be about 1 mm to about 10mm, about 1 mm to about 7 mm, about 1 mm to about 5 mm, or any individual depth or range encompassed by any of these example ranges.

[0193] In some embodiments, the fixing stencil 840 may further include stabilizing components for stabilizing the stencil head 841 during fixturing. For example, the stabilizing components may include a clamp positioned to hold the tapered dimple 85 or an apparatus that substantially fills the remainder of the conduit. In certain embodiments, the stencil head 841 may be capable of transmitting heat to the conduit to aid in fixturing by fusing the leaflet 801 to the conduit 80 or aiding in deformation of the conduit 80 by creating a sinus bulge at the sinus when the fixing stencil 840 is removed.

[0194] Further embodiments directed to methods for making the valved conduits described above are considered within the scope of this disclosure. Such embodiments may include the steps of inverting a conduit, bending a portion of the conduit to create a tapered dimple, attaching a leaflet to the conduit on a surface surrounding the tapered dimple, reverting the conduit, and / or placing the leaflet on an inner surface of the conduit. The step of attaching can be carried out by suturing, welding, fusing, using an adhesive, and the like or combinations thereof. In some embodiments, the method may further include the step of deforming the conduit to produce a sinus bulge. In some embodiments, bending can be carried out using a fixing stencil configured to hold the conduit in a bent form to create a tapered dimple. The fixing stencil may have substantially the same shape as the tapered dimple. In various embodiments, the fixing stencil may have one or more of the parts described above.

[0195] In some embodiments, a method of making a valve may include the step of cutting a valve structure from a biocompatible material. In certain embodiments, the step of cutting the valve structure may be preceded by a step of marking the biocompatible material, and in some embodiments, marking may be earned out by tracing a valve structure stencil having substantially the same shape as the valve structure onto the biocompatible material. In other embodiments, the marking can be carried out using a stamp having substantially the same shape as the valve structure. In still other embodiments, the step of cutting can be carried out using a die cutting machine. Where the leaflets of the valve comprise more than one layer of the material, in some embodiments, two or more layers of the material may be attached to each other. In some embodiments, the two or more layers may be attached through one or more of the following: physical connections, such as sutures or clamps, welding, sintering, heating, such as applied heat through one or more plates, single or concentric cylinders, or laser, chemical welding, adhesive, static electric or frictional forces. For purposes of this disclosure, in embodiments where the layers of the material are attached to make the leaflet but distinctionbetween the layers has been lost, such leaflet should still be considered to have more than one layer.

[0196] In some embodiment, the method of making a valved conduit may further include the step of marking an inner surface of the conduit with a location form attaching the leaflet to the conduit, thereby providing proper placement and alignment of the leaflets. Marking can be carried out by various means. For example, in some embodiments, marking can be carried out using a sinus stencil, and the marking on the inner surface of the conduit can be substantially the same as the sinus stencil. In such embodiments, the sinus stencil may have a shape and dimension for showing the location of the tapered dimple on the unbent inner surface of the conduit. Therefore, the sinus stencil may be wider than the valve structure, but the markings may have essentially the same shape as the leaflet after the conduit is bent.

[0197] EXAMPLE 1

[0198] The objective of the study was to compare the microstructure and material properties of a multi-layer leaflet (termed PECA or PECA Leaflet Material) according to some embodiments described above to a multi-layer leaflet currently marketed (termed Gore or Gore Preclude Membrane having a total average thickness of 0.1 mm). According to some embodiments described above, the PECA Leaflet Material comprises a multi-layer leaflet made of ePTFE having a total thickness of 0.045 mm, wherein the multi-layers of the leaflet are anisotropic with orientations that are offset by less than 90 degrees, but greater than 10 degrees, relative to each other. The PECA Leaflet Material, depicted in FIG. 14B (side A) and FIG. 14D (side B), has a reduction in surface percent porosity when compared to Gore, depicted in FIG. 14A (side A) and FIG. 14C (side B). The quantifications of these data are illustrated in FIG. 14E.

[0199] Under similar conditions described above, and when compared to Gore, the PECA Leaflet Material has improved ultimate tensile stress in both the X-direction (dark bars) and Y- direction (gray bars) as illustrated in FIG. 15 A, improved burst pressure as illustrated in FIG. 15B, improved suture retention strength in both the X-direction (dark bars) and Y-direction (gray bars) as illustrated in FIG. 15C, and improved suture retention in a 45 degree orientation as illustrated in FIG. 15D. Additionally, when compared to Gore, the PECA Leaflet Material displays augmented elastic modulus measured in MPa as illustrated in FIG. 16A, and no change in bending modulus measured inN / mm2as illustrated in FIG. 16B. The PECA Leaflet Material further displays reduced membrane tension compared to Gore as depicted in FIG. 17A, and reduced stress as depicted in FIG. 17B.

[0200] EXAMPLE 2

[0201] The objective of the study was to assess the luminal and abluminal surface thrombogenic properties of the PECA Leaflet Material as described in Example 1 and compare it to the Gore Preclude Membrane that is intended to resist thrombosis.

[0202] The PECA Leaflet Material comprises a multi-layer leaflet made of ePTFE having a surface porosity of about 4% (about 2% on Side A and about 6% on side B), a total thickness of 0.045 mm, wherein the multi-layers of the leaflet are anisotropic with orientations that are rotated by less than 90 degrees, but greater than 10 degrees, relative to each other. The PECA Leaflet Material was compared to the Gore Preclude Membrane having a total average thickness of 0.1 mm in a blood-contacting environment. In order to compare and assess the differential activated platelet and fibroblast growth on the material, multiple samples (n=3) of each material were cut into Ixlcm pieces and prepared for blood exposure in 2 ml Centrifuge tubes and weighed. Sheep blood was then treated with 0.5 units of heparin per mL of blood. The blood was then re-calcified using Calcium Chloride and an arterial blood gas analyzer was used to read calcium levels until a reading of 1-1.5 mmol / L was attained. This blood was added to the 2 mL centrifuge tubes with the different materials to be tested and filled to the top to avoid the presence of air. The tubes were placed on a rocker at 37°C. All samples were removed after 15 mins of incubation and were rinsed for 5 minutes five times. The first rinse was with 100 units / mL heparin solution in saline, and the other four rinsing procedures were performed with saline. These samples were then collected and prepared appropriately for visualization using Scanning Electron Microscopy (SEM) and a qualitative analysis was performed.

[0203] A significantly lower amount of activated platelet adhesion and fibroblastic activity7was observed in the PECA Leaflet Material (FIGS. 18C and 18D) when compared to Gore (FIGS. 18G and 18H). FIGS. 18B and 18D illustrate the PECA Leaflet Material on both the Side A and Side B, respectively, surfaces prior to the addition of blood. FIGS. 18A and 18B illustrate Gore on both the Side A and Side B, respectively, surfaces prior to the addition of blood.

[0204] The SEM images confirm the PECA Leaflet Material displays improved microstructure and material properties and is more resistant to thrombosis compared to the Gore Preclude Membrane. It was concluded qualitatively that the PECA Leaflet Material showed little or no signs of thrombosis or fibrotic growth as the material itself was visible throughout the image without signs of platelets, fibrin, or cells. The Gore materials showed significant amounts of activated platelet growth along with fibrous growth seen as a result of thrombosis of blood on the material.

[0205] EXAMPLE 3

[0206] A method of making a conduit, valve, or leaflet having multiple layers of material is exemplified below. The inner surface of a first layer of material is superposed to the outer surface of a second layer of material. The first layer and the second layer are attached by providing heat beyond the melting temperature of at least one of the first layer or the second layer. The melting temperature of at least one of the first layer or the second layer may be determined by routine experimentation of one skilled in the art.

[0207] Alternatively, a plate is provided to support the first layer of material when superposed to the second material. Heat is then provided, beyond the melting temperature of at least one of the first layer or the second layer, to attach the first layer and the second layer. Following removal of the plate and heat, the multiple layers of material may be formed into a conduit, a valve, or a leaflet by any cutting method known in the art. Non-limiting examples of cutting methods include the use of scissors, a blade, die cutting, laser cutting or combinations thereof.

[0208] For example, a valved conduit may be made by extruding and placing two tubular layers such that there are an outer and an inner concentric layer. An inner and an outer concentric cylindrical fixture are placed within the inner concentric layer and outside the outer concentric layer and heated to beyond the melting temperature of at least one layer.

[0209] Leaflets may be made by cutting the tubular layers and placing them to form sheets, one lying on top of the other. Plates are placed sandwiching the two layers and heat is applied beyond the melting temperature of at least one layer. When the plates or heating cylinders are removed, the layers are sintered and may be formed into leaflets by hand (with scissors, blade, etc.), by die cut, by laser cut, or the like.

[0210] EXAMPLE 4

[0211] The objective of the study was to assess the luminal and abluminal surface thrombogenic properties of a multi-layer conduit featuring one low porosity layer (the luminal layer) and one high porosity7layer (the abluminal layer) using the process described in Example 3 and compare it to the Gore Preclude Membrane that is intended to resist thrombosis, and a BARD commercially available graft that is intended to allow some thrombosis.

[0212] The PECA conduit comprises a multi-layer conduit made of ePTFE having a luminal surface porosity7of about 4%, and abluminal surface porosity7of greater than 20%, a total luminal-layer thickness of 0.045 mm. and a total abluminal layer thickness of about 1mm. The PECA conduit was compared to the Gore Preclude Membrane having a total average thickness of 0. 1 mm in a blood-contacting environment and the BARD Impra Conduit havinga surface porosity of greater than 20%. In order to compare and assess the differential activated platelet and fibroblast growth on the material, multiple samples (n=3) of each material were cut into 1x1 cm pieces and prepared for blood exposure in 2 ml Centrifuge tubes and weighed. Sheep blood was then treated with 0.5 units of heparin per mL of blood. The blood was then re-calcified using Calcium Chloride and an arterial blood gas analyzer was used to read calcium levels until a reading of 1-1.5 mmol / L was attained. This blood was added to the 2 mL centrifuge tubes with the different materials to be tested and filled to the top to avoid the presence of air. The tubes were placed on a rocker at 37°C. All samples w ere removed after 15 mins of incubation and were rinsed for 5 minutes five times. The first rinse was with 100 units / mL heparin solution in saline, and the other four rinsing procedures were performed with saline. These samples were then collected and prepared appropriately for visualization using Scanning Electron Microscopy (SEM) and a qualitative analysis was performed.

[0213] A significantly low er amount of activated platelet adhesion and fibroblastic activity was observed in the luminal surface the PECA Leaflet Material luminal surface (FIG. 19A) when compared to Gore (FIG. 19C). Higher amounts of growth were seen on both the abluminal surface of the PECA Leaflet Material (FIG. 19B) and BARD (FIG. 19D).

[0214] The SEM images confirm the PECA conduit displays a luminal surface that features improved microstructure and material properties and is more resistant to thrombosis compared to the Gore Preclude Membrane, while maintaining an abluminal surface which is less resistant to thrombosis than the Gore Preclude Membrane. It was concluded qualitatively that the conduit formed of the PECA Leaflet Material showed little or no signs of thrombosis or fibrotic growth as the material itself w as visible throughout the image w ithout signs of platelets, fibrin, or cells, while the abluminal surface did allow for some thrombosis and / or fibrotic grow th. The Gore materials showed a small amount of thrombosis, while the BARD Impra Conduit showed the most thrombosis.

[0215] EXAMPLE 5

[0216] The obj ective of the study was to assess the rigidity, suture retention strength (SRS), surface porosity, intemodal distance (IND), and volumetric porosity of Gore Preclude Membrane as compared to various multi-layered materials. The multi-layered materials were comprised of ePTFE with 21 layers (PECA 1), 11 layers (PECA 2), and 15 layers (PECA 3). The PECA materials were produced with the intention of featuring outer layers with surface porosities of less than 15%, less than 10% and less than 5% while using internal layers with porosities of greater than 30%, greater than 40%, and greater than 30%, respectively, in orderto showcase the ability to produce materials that vary' in strength, flexibility, and porosity in an independent (not directly correlated) manner within a small range of intemodal distances.

[0217] Rigidity' was determined by using a micrometer to measure the material ample dimensions, fixturing the sample such that a portion of the sample was unsupported in free space in a cantilever position, imaging the sample along with a reference to determine the amount of deflection from parallel, measuring the mass of the free portion from the edge of the fixture with an analytical balance, and calculating the bending modulus using the equation for a cantilever beam. This bending modulus calculation was then combined with the Poisson’s ratio of the material, measured by stretching the material using an ADMET eXpert 7601 XLT tensile tester at a rate of 50mm / min and measuring the sample thickness with a micrometer, to determine the flexural rigidity of the material. Suture Retention Strength was determined by placing a 5-0 Prolene suture 2mm from the edge of each material and using a ADMET eXpert 7601 XLT tensile tester to pull the suture at a rate of 50mm / min while measuring the maximum force. Intemodal distance was determined by acquiring an image using a scanning electron microscope at a magnification of 250x. ToupView Image Software was used to measure the distance between nodes of the material, with at least 10 measurements of representative size used to determine an average IND. Surface Porosity was determined using Adobe Photoshop to threshold the image such that the material and pores were white and black, respectively, and divide the total number of pixels remaining that represented the material by the total number of image pixels. Volumetric Porosity was determined by using an analytical balance to determine the weight of the material, using a micrometer to measure the material volume, and dividing the weight of the material by the weight of an equivalent volume of non-porous PTFE.

[0218] The Gore Preclude Membrane had a volumetric porosity of 32.3%, a rigidity' of 8.8 Pa*cm3, an SRS of 347 gF, a surface porosity of 15.9%. and an average IND of 1.4 pm. PECA 1 had a volumetric porosity of 38.7%, a rigidity' of 10.0 Pa*cm3, an SRS of 518 gF, a surface porosity of 13.1%, and an average IND of 2.0 pm. PECA 2 had a volumetric porosity of 50.0%, a rigidity of 7.2 Pa*cm3, an SRS of 625 gF, a surface porosity of 7.0%, and an average IND of 1.4 pm. PECA 3 had a volumetric porosity of 37.7%, a rigidity of 6.5 Pa*cm3. an SRS of 351 gF, a surface porosity of 3.3%, and an average IND of 1.8 pm. The comparison of each measurement is provided in FIGS. 34E-34I. SEM images of the Gore Preclude Membrane, PECA 1, PECA 2, and PECA 3 are provided in FIGS. 34A-D, respectively. FIGS. 33A-H provide direct comparisons of the measurements as compared to the measurements of the Gore Preclude Membrane.

[0219] EXAMPLE 6

[0220] The objective of the study was to assess plate flexural rigidity and the SRS of a multi-layered membrane, a pericardial Gore Preclude Membrane, and porcine aortic valve tissue. The multi-layered materials were comprised of ePTFE with outer layers with less than 15% porosity and inner layers of greater than 25% porosity.

[0221] Plate flexural rigidity was determined by using a micrometer to measure the material ample dimensions, fixturing the sample such that a portion of the sample is unsupported in free space in a cantilever position, imaging the sample along with a reference to determine the amount of deflection from parallel, measuring the mass of the free portion from the edge of the fixture with an analytical balance, and calculating the bending modulus using the equation for a cantilever beam. This bending modulus calculation is then combined with the Poisson’s ratio of the material, measured by stretching the material using an ADMET eXpert 7601 XLT tensile tester at a rate of 50mm / min and measuring the sample thickness with a micrometer, to determine the flexural rigidity of the material. Suture Retention Strength was determined by placing a 5-0 Prolene suture 2mm from the edge of each material and using a ADMET eXpert 7601 XLT tensile tester to pull the suture at a rate of 50mm / min while measuring the maximum force.

[0222] The plate flexural rigidity testing showed both the multi-layered membrane and the Gore Preclude Membrane had a rigidity of about 9.5 kN*mm while the porcine aortic valve had a rigidity of about 10.1 kN*mm. The SRS testing showed that the PECA multi-layered membrane had an SRS of about 500 gF, the Gore Preclude Membrane had an SRS of about 350 gF, and the porcine aortic valve had an SRS of about 625 gF. The results show the PECA multi-layered membrane exhibited a higher flexibility as compared to other material while maintaining a high SRS as well. Graphical depictions of the results are provided in FIGS. 35 A- B.

[0223] EXAMPLE 7

[0224] The objective of the study was to assess the SRS, strength after puncture, and the burst strength of plastically deformable polymer material at multiple expansion multiples. This test evaluated materials with a single layer with anisotropic pores comprised of ePTFE and testing was performed at expansion multiples of 1.0, 1.2 and 1.4.

[0225] Suture Retention Strength was determined by placing a 5-0 Prolene suture 2mm from the edge of each material and using a ADMET eXpert 7601 XLT tensile tester to pull the suture at a rate of 50mm / min while measuring the maximum force. Strength After Repeated Puncture was determined by puncturing one-third of the conduit circumference with a 16-gaugedialysis needle with a density of 24 punctures per cm2of the puncture surface area (one-third of the conduit circumference). The punctured conduit is then fixtured using two pins held in an ADMET eXpert 7601 XLT tensile tester and stretched at a rate of 50mm / min until breaking to determine the maximum circumferential tensile strength after puncturing (maximum load divided by 2X the sample length). Burst strength is determined by clamping a 1” x T’ material sample in a fixture that has a central hole sufficient for the tight traverse of a 3" hemispheric radius probe. The probe is traversed through at a rate of 50mm / min while attached to an ADMET eXpert 7601 XLT tensile tester and the maximum force to break the material is measured to calculate the bursting load of the material.

[0226] The SRS testing showed that the polymer material had an SRS of about 700 gF at 1.0 expansion, about 875 gF at 1.2 expansion, and about 900 gF at 1.4 expansion. The strength after puncture testing showed that the polymer material had a strength of about 1.9 N / mm at 1.0 expansion, about 3.0 N / mm at 1.2 expansion, and about 3.1 N / mm at 1.4 expansion. The burst strength testing showed that the polymer material had a burst strength of about 11 ,000 mmHg at 1.0 expansion, about 12,000 mmHg at 1.2 expansion, and about 12,250 mmHg at 1.4 expansion. Each test showed an improvement in the mechanical properties of the polymer material as the expansion multiple was increased. Graphical depictions of the results are provided in FIGS. 36A-C.

[0227] EXAMPLE 8

[0228] The objective of the study was to assess the in vitro thrombogenicity of materials with varying microstructures. The microstructures tested included multi-layered materials comprised of ePTFE targeted for vary ing layers of ingrowth and / or thrombosis. The low- thrombosis material had outer layers with a surface porosity of less than 5% and IND of less than 3pm. the medium-thrombosis material had outer layers with greater than 5% but less than 15% surface porosity' and less than 5pm IND, and the high-thrombosis material had outer layers with greater than 15% surface porosity’ and greater than 5 m IND.

[0229] In order to compare and assess the differential activated platelet and fibroblast growth on the material, samples of the material were cut into Ixlcm pieces and prepared for blood exposure in 2 ml Centrifuge tubes and weighed. Sheep blood was then treated with 0.5 units of heparin per mL of blood. The blood w as then re-calcified using Calcium Chloride and an arterial blood gas analyzer was used to read calcium levels until a reading of 1-1.5 mmol / L was attained. This blood was added to the 2 mL centrifuge tubes with the different materials to be tested and filled to the top to avoid the presence of air. The tubes placed on a rocker at 37°C.All samples were removed after 15 mins of incubation and were rinsed for 5 minutes five times. The first rinse was with 100 units / mL heparin solution in saline, and the other four rinsing procedures were performed with saline. These samples were then collected and prepared appropriately for visualization using Scanning Electron Microscopy (SEM) and a qualitative analysis was performed.

[0230] The material comprising outer layers with a surface porosity of less than 5% and IND of less than 3pm provided the lowest thrombogenicity with the SEM image provided in FIG. 29A. The platelets and thrombus are seen in the SEM image in the orange boxes 2901. The material comprising outer layers with greater than 5% but less than 15% surface porosity and less than 5pm IND provided the second lowest thrombogenicity with the SEM image provided in FIG. 29B. The platelets and thrombus are seen in the SEM image in the orange box 2902. The material comprising outer layers with greater than 15% surface porosity and greater than 5pm IND provided the highest thrombogenicity with the SEM image provided in FIG. 29C. The platelets and thrombus are seen in the SEM image in the orange boxes 2903.

Claims

CLAIMSWhat is Claimed is:

1. A multi-layered material for use in a medical device, the multi-layered material comprising: at least two outer layers, wherein each outer layer comprises a surface porosity of about 1 % to about 10%; and one or more inner layers, wherein each inner layer comprises a surface porosity of about 25% to about 50%.

2. The multi-layered material of claim 1 , wherein each outer layer has a thickness of about 0. 1pm to about 10pm.

3. The multi-layered material of claim 2, wherein the inner layer has a thickness greater than 10 pm.

4. The multi-layered material of claim 1 , wherein each inner layer has a thickness of about 0. 1 pm to about 10pm.

5. The multi-layered material of claim 4, wherein each outer layer has a thickness of greater than 10pm.

6. The multi-layered material of claim 1, wherein each outer layer is constructed from expanded polytetrafluoroethylene (ePTFE).

7. The multi-layered material of claim 1, wherein each inner layer is constructed from at least one of polyurethane, a polyurethane copolymer, silicone, and polytetrafluoroethylene (PTFE).

8. The multi-layered material of claim 1, wherein at least one outer layer comprises a coating of heparin, paclitaxel, coumadin, warfarin, PTFE, a polyurethane copolymer, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, anti-proliferative agents, endothelial cell grow th promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

9. The multi-layered material of claim 1, wherein the multi-layered material is configured to form a part of a cardiovascular graft.

10. The multi-layered material of claim 1, wherein the multi-layered material is configured to form a part of a heart valve leaflet.

11. The multi-layered material of claim 1, wherein each outer layer comprises pores with an average pore area of about 0.1 pm2to about 5 pm2.

12. The multi-layered material of claim 1. wherein each inner layer comprises pores with an average pore area of about 5 pm2to about 15 pm2.

13. The multi-layered material of claim 1, wherein each of the outer layers and each of the inner layers further comprises at least one bump or at least one wrinkle.

14. A multi-layered material for use in a medical device, the multi-layered material comprising: a first layer comprising a surface porosity of about 1% to about 10%; and a second layer comprising a surface porosity of greater than 10%.

15. The multi-layered material of claim 14, wherein each of the first layer and the second layer has a thickness of about 0. 1 pm to about 10pm.

16. The multi-layered material of claim 14, wherein one of the first layer and the second layer has a thickness of about 0.1pm to about 10pm and one of the first layer and the second layer has a thickness greater than 10pm.

17. The multi-layered material of claim 14, wherein each of the first layer and the second layer is constructed from expanded poly tetrafluoroethylene (ePTFE).

18. The multi-layered material of claim 14, wherein at least one of the first layer and the second layer comprises a coating of heparin, paclitaxel, coumadin, warfarin, PTFE, polyurethane copolymer, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, anti-proliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

19. The multi-layered material of claim 14, wherein at least one of the first layer and the second layer has been infused with heparin, paclitaxel, coumadin, warfarin, PTFE, a polyurethane-copolymer, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, anti-proliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

20. The multi-layered material of claim 14, wherein the multi-layered material is configured to form a part of a cardiovascular graft.

21. The multi-layered material of claim 14, wherein the multi-layered material is configured to form a part of a heart valve leaflet.

22. The multi-layered material of claim 14, wherein each of the first layer and the second layer comprises pores with an average pore area of about 0. 1 pm2to about 5 pm2.

23. The multi-layered material of claim 14, wherein each of the first layer and the second layer further comprise at least one bump or at least one wrinkle.

24. A multi-layered material for use in a medical device, the multi-layered material comprising: a first layer comprising a surface porosity of about 1% to about 10%; a second layer comprising a surface porosity of greater than 10%; and a third layer comprising a surface porosity of about 1% to about 10%.

25. The multi-layered material of claim 24. wherein each of the first layer, second layer, and third layer has a thickness of about 0. 1 pm to about 10pm.

26. The multi-layered material of claim 24, wherein at least one of the first layer, second layer, and third layer has a thickness of about 0. 1pm to about 10pm and at least one of the first layer and the second layer has a thickness greater than 10pm.

27. The multi-layered material of claim 24, wherein each of the first layer, second layer, and third layer is constructed from expanded polytetrafluoroethylene (ePTFE).

28. The multi-layered material of claim 24, wherein at least one of the first layer, second layer, and third layer comprises a coating of heparin, paclitaxel, coumadin. warfarin. PTFE, polyurethane-copolymer, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, anti-proliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

29. The multi-layered material of claim 24, wherein at least one of first layer, second layer, and third layer has been infused with heparin, paclitaxel, coumadin, warfarin, PTFE, a polyurethane-copolymer, biological growth factors, collagen, carbon, proteins, anti-platelet agents, anti-thrombotic agents, anti-coagulants, anti-bacterial agents, anti-inflammatory agents, anti-proliferative agents, endothelial cell growth promoters, extracellular matrix components, bioactive agents, therapeutic agents, radiopaque agents, or any combination thereof.

30. The multi-layered material of claim 24, wherein the multi-layered material is configured to form a part of a cardiovascular graft.

31. The multi-layered material of claim 14, wherein the multi-layered material is configured to form a part of a heart valve leaflet.

32. The multi-layered material of claim 24, wherein each of the first layer and the second layer comprises pores with an average pore area of about 0. 1 pm2to about 5 pm2.

33. The multi-layered material of claim 24, wherein each of the first layer and the second layer further comprise at least one bump or at least one wrinkle.

34. A method for making a multi-layered material for use in a medical device, the method comprising: providing a first layer having a surface porosity of about 1% to about 10% and a second layer having a surface porosity of greater than about 10 %, superimposing an inner surface of the second layer to an outer surface of the first layer; and heating the first layer and the second layer to attach the first layer and the second layer;wherein the first layer and the second layer are heated beyond a sintering temperature of at least one of the first layer and the second layer.

Images