Single-channel heart valve with integral leaflets and skirt - Patents.com

Abstract

[0003] Embodiments of the present application relate to prosthetic heart valves constructed of animal tissue, in which the leaflets are integral with an inner skirt. One embodiment includes an implantable heart valve assembly having a plurality of leaflets, an inner skirt, and a metal frame, wherein the plurality of leaflets and the inner skirt are formed from a continuous piece of animal tissue. Another embodiment includes a method of making an implantable heart valve assembly, the method including placing a piece of pericardial tissue on a mold, bridging the pericardial tissue in place on the mold, removing the pericardial tissue from the mold, and attaching the pericardial tissue to the frame, wherein the pericardial tissue forms a seamless joint between the plurality of leaflets and the inner skirt. Other embodiments are also included.

Description

[Technical field]

[0001] SUMMARY OF THE DISCLOSURE The present embodiments relate to prosthetic heart valves constructed from animal tissue, in which the leaflets are integral with an inner skirt. [Background technology]

[0002] Heart valve surgery can be performed to repair or replace diseased heart valves.For example, heart valve replacement can be applied when there is narrowing of native heart valves, commonly called stenosis, or when there is leakage or regurgitation of native valves.Repair or replacement of diseased heart valves can include, for example, the introduction of prosthetic heart valves that contain biological tissues that are foreign to the patient (e.g., heterografts or xenografts). Summary of the Invention

[0003]

[0005] Embodiments of the present application relate to a prosthetic heart valve constructed of animal tissue, in which the leaflets are integral with an inner skirt. In a first aspect, an implantable heart valve assembly is included having a plurality of leaflets, an inner skirt, and a metal frame, in which the plurality of leaflets can comprise animal tissue, and in which the inner skirt can comprise animal tissue, and in which the plurality of leaflets and the inner skirt are formed from a continuous piece of animal tissue.

[0004] In a second aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the animal tissue has a thickness of between 100 and 500 microns. In a third embodiment, in addition to one or more of the preceding or following embodiments, or as an alternative to some embodiments, the animal tissue exhibits different degrees of cross-linking in different regions of the implantable heart valve assembly.

[0005] In a fourth embodiment, in addition to one or more of the preceding or following embodiments, or as an alternative to some embodiments, the device can further include an outer skirt, which can include animal tissue.

[0006] In a fifth embodiment, in addition to one or more of the preceding or following embodiments, or as an alternative to some embodiments, the plurality of leaflets, the inner skirt, and the outer skirt are formed from a continuous piece of animal tissue.

[0007] In a sixth embodiment, in addition to one or more of the preceding or following embodiments, or as an alternative to some embodiments, the plurality of leaflets, the inner skirt, and the outer skirt are formed from a single piece of pericardium.

[0008] In a seventh aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the outer skirt wraps around the end of the metal frame and is positioned to rest against an outer surface of the metal frame.

[0009] In an eighth embodiment, in addition to one or more of the preceding or following embodiments, or as an alternative to some embodiments, the plurality of leaflets and the inner skirt are sutured to a metal frame. In a ninth embodiment, in addition to one or more of the preceding or following embodiments, or as an alternative to some embodiments, the inner skirt can include a longitudinal suture.

[0010] In a tenth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the inner skirt is seamless. In an eleventh aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the plurality of leaflets can include a commissure, a nadir, and a reinforcing structure, the reinforcing structure being positioned in the region of at least one of the commissure and the nadir.

[0011] In a twelfth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the plurality of leaflets exhibit a curved bias from in situ bridging.

[0012] In a thirteenth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the plurality of leaflets exhibits a symmetric pericardial fiber orientation. In a fourteenth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the plurality of leaflets exhibits an asymmetric pericardial fiber orientation.

[0013] In a fifteenth aspect, a method of making an implantable heart valve assembly is included, the method including the steps of placing a piece of pericardial tissue over a mold, bridging the pericardial tissue in place over the mold, removing the pericardial tissue from the mold, and attaching the pericardial tissue to a frame, wherein the pericardial tissue forms a seamless joint between a plurality of valve leaflets and an inner skirt.

[0014] In a sixteenth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the method may further include a step of cutting pericardial tissue to form a valve leaflet edge.

[0015] In a seventeenth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the method may further include suturing the pericardial tissue in place over the form.

[0016] In an eighteenth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the method may further include wrapping the ends of the pericardial tissue over and above the ends of the frame to form an outer skirt.

[0017] In a nineteenth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the step of placing the piece of pericardial tissue onto the mold further includes wrapping the sheet of pericardial tissue around the mold and forming sutures longitudinally along the mold to hold the pericardial tissue in place.

[0018] In a twentieth aspect, in addition to one or more of the preceding or following aspects, or as an alternative to some aspects, the step of placing the piece of pericardial tissue onto the mold further includes the step of placing a non-planar piece of new pericardial tissue onto the mold.

[0019] This Summary is an overview of some of the teachings of the present application and is not intended to be an exclusive or exhaustive treatment of the present subject matter. Further details are found in the detailed description and the appended claims. Other aspects will become apparent to one of ordinary skill in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof, each of which should not be construed in a limiting sense. The scope of the present application is defined by the appended claims and their legal equivalents.

[0020] The aspects may be more fully understood in connection with the following figures. [Brief description of the drawings]

[0021] [Figure 1] FIG. 2 is a schematic perspective view of a valve in a closed state in a portion of an environment in which it can be used, according to various embodiments of the present application; [Diagram 2] 1 is a schematic end view of a valve in a closed state in a portion of an environment in which it can be used, according to various embodiments of the present application. FIG. [Diagram 3] 1 is a perspective view of an implantable valve according to various embodiments of the present application. [Figure 4] FIG. 2 is a perspective view of a mold according to various embodiments of the present application. [Diagram 5] FIG. 2 is a perspective view of tissue draped over a form in accordance with various embodiments of the present application. [Figure 6] 1 is a cross-sectional view of tissue draped over a form in accordance with various embodiments of the present application. [Figure 7] FIG. 1 illustrates a perspective view of tissue being wrapped around a form in accordance with various embodiments of the present application. [Figure 8] FIG. 1 illustrates a perspective view of tissue being wrapped around a form in accordance with various embodiments of the present application. [Figure 9]FIG. 1 illustrates a perspective view of tissue wrapped around a form in accordance with various embodiments of the present application. [Figure 10] 1 is a cross-sectional view of tissue being cross-linked on a mold in accordance with various embodiments of the present application. [Figure 11] 1 is a cross-sectional view of tissue being cross-linked on a mold in accordance with various embodiments of the present application. [Figure 12] 1 is a cross-sectional view of a mold being removed from tissue according to various embodiments of the present application. [Figure 13] 1 is a cross-sectional view of a portion of a heart valve according to various embodiments of the present application. [Figure 14] 1 is a schematic end view of a closed valve according to various embodiments of the present application. [Figure 15] 1 is a schematic end view of a closed valve according to various embodiments of the present application. [Figure 16] 1 is a schematic end view of a closed valve according to various embodiments of the present application. [Figure 17] 1 is a schematic diagram illustrating a method of making a heart valve, according to various embodiments of the present application. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] Various modifications and alternative forms of the embodiments are possible, the details of which are shown by way of example and drawings and will be described in detail below. However, it should be understood that the scope of the present application is not limited to the specific aspects described. Rather, the present invention encompasses modifications, equivalents, and alternative forms that fall within the spirit and scope of the present application.

[0023] The human body has four heart valves: the pulmonary, tricuspid, aortic, and mitral valves. The purpose of the heart valves is to allow blood to flow in a specific direction through the heart and out of the heart into the major blood vessels that lead to it, such as the aorta and pulmonary artery. As the heart muscle contracts and relaxes, the valves open and close, allowing blood to alternately flow into the ventricles and atria.

[0024] Prosthetic valves designed to replace valves in the human body often include two or more leaflets (usually three) attached to a frame. The prosthetic valve can be configured to allow unidirectional flow through the valve by separating the leaflets from each other to open the valve, thereby allowing flow, coapting the leaflets together to close the valve (coaptation), thereby blocking flow, etc. In some cases, the prosthetic valve can further include an inner skirt and / or an outer skirt to restrict the path of flow through the valve.

[0025] The various embodiments described herein provide valves with a reduced number of seams between separate pieces of tissue material, increasing durability and strength while improving simplicity. The various embodiments described herein also address manufacturing challenges of multi-component assemblies.

[0026] In various embodiments of the present application, a single continuous piece of natural tissue is used for several valve components, such as the leaflets, inner skirt, and outer skirt (if the outer skirt is included with the valve). In some embodiments, the tissue material can be attached or joined to the frame through a series of sutures. In various embodiments, the inner skirt 106 can be seamless. In various embodiments, the outer skirt can be seamless. In various embodiments, the leaflets, inner skirt, and / or outer skirt can be seamless such that they are all formed from a single, integral piece of tissue, without suturing or otherwise attaching two or more pieces of tissue together.

[0027] FIG. 1 shows a schematic diagram of a closed valve 100 in a tube 114, according to various embodiments. FIG. 2 shows an end view of the closed valve 100. It should be understood that the valve 100 can be any type of heart valve (e.g., mitral valve, aortic valve, etc.). In use, the valve 100 can be implanted (e.g., surgically or through transcatheter delivery) in a mammalian heart. The heart valve 100 can include an inlet 116. The heart valve 100 can also include an outlet 118. The valve 100 can be configured to allow unidirectional flow through the valve 100, as depicted by arrow 112, which can represent blood flow during systole.

[0028] The valve 100 can include a frame 102 that defines a central lumen 220 (see FIG. 2), which in some embodiments can be substantially cylindrical. The side of the frame 102 and other components that faces the central lumen 220 can be referred to as the luminal surface 222 or luminal side. The opposite side of the frame 102 and other components (e.g., the side that faces away from the central lumen 220) can be referred to as the abluminal surface 224 or abluminal side. In various embodiments, the frame 102 can have a substantially circular cross-section. However, in other embodiments, the frame 102 can have a non-circular cross-section, such as an oval or D-shape. In some embodiments, the non-circular frame 102 can be advantageously used to repair a mitral valve or another non-circular valve in the body.

[0029] The valve 100 can include multiple leaflets 104 disposed within a central lumen 220. Each leaflet 104 includes a free or coaptation edge 108 that is movable relative to an inner skirt 106 and can coapt with the coaptation edge 108 of another polymeric leaflet 104 along a coaptation region 110. In various embodiments, the multiple leaflets 104 are formed together such that the multiple leaflets 104 are formed as a single unit. In some embodiments, the "root edge" can be the edge of the leaflet opposite the coaptation edge 108, such as where the leaflet 104 coapts to the inner skirt 106. In various embodiments herein, the leaflets 104 can be integral with other structures (e.g., not present as two separate pieces that are joined together along a seam), such as an integral skirt (inner and / or outer), base structure, reinforcement, liner, leaflet, etc. In such a situation, the "root edge" is not a cut or otherwise divided edge, but rather the location opposite the coaptation edge where the leaflet integrally meets those other structures.

[0030] The coaptation edges 108 of the leaflets 104 move to be coapted to one another in the closed position (FIGS. 1 and 2) to substantially restrict fluid from flowing through the valve 100 in a direction opposite to the direction of arrow 112. Specifically, the leaflets 104 may be coapted to fill or close a central lumen 220 of the valve 100, thereby preventing fluid flow opposite to the direction of arrow 112.

[0031] 3 shows a perspective view of an implantable valve 100, according to various embodiments. The valve 100 can include a frame 102, leaflets 104, and an inner skirt 106. In some embodiments, the valve 100 can include an outer skirt (not shown in FIG. 3). In some cases, the frame 102 can include multiple frame struts 326. However, frames that do not include separate struts are also contemplated herein.

[0032] The leaflets 104 may include a commissure edge. The leaflets 104 may further include two connectors. One connector may be located at either end of the commissure edge such that the connector contacts or is adjacent to the frame 102. In some cases, the connector may be referred to as a commissure or a commissure mounting tab. The connector may be integral with other portions of the leaflets 104 and other portions of the valve such that the leaflets 104, inner skirt 106, and potentially other portions are a single piece.

[0033] In various embodiments, the implantable valve 100 can include an inner skirt 106. The inner skirt 106 can define a substantially tubular shape. The inner skirt 106 can be disposed on or supported by a luminal surface of the frame 102. The luminal surface of the frame 102 can be a surface of the frame 102 that defines a central lumen 220. The inner skirt 106 can direct fluid, such as blood, flowing through the valve 100. The inner skirt 106 can ensure that fluid flows through the central lumen 220 of the valve 100 and does not flow around the leaflets 104 when the leaflets 104 are in a closed configuration.

[0034] In some embodiments, the implantable valve 100 can include an outer skirt (not shown). The outer skirt can define a substantially tubular shape. The outer skirt can be disposed on an abluminal surface of the frame 102. The abluminal surface of the frame 102 can be the surface of the frame 102 that is outside of the central lumen 220. The outer skirt can be disposed between the frame 102 and a wall of the tube 114 to prevent fluids, such as blood, from flowing around the valve 100. The outer skirt can ensure that fluids flow through the valve 100 and not around the valve 100 to ensure that fluid flow can be stopped when the leaflets 104 are in a closed position.

[0035] In various embodiments, the leaflets 104 and inner skirt 106 are formed from a continuous piece of animal-derived tissue. In various embodiments, the leaflets 104, inner skirt 106, and outer skirt are formed from a continuous piece of animal-derived tissue. In various embodiments, the leaflets 104, inner skirt 106, and outer skirt are formed from a single piece of pericardium.

[0036] 4-11, various steps in making the valve 100 are shown. Referring now to FIG. 4, a perspective view of a mold 428 (or form or mandrel) is shown, according to various embodiments of the present application. The mold 428 includes a recess 430. In some embodiments, the recess 430 can have a concave shape. The mold 428 also includes a body 432. In some embodiments, the body 432 can have a circular cross-section to result in a valve 100 having a circular central lumen 220. However, it should be understood that other mold shapes are contemplated herein and different mold 428 shapes can result in different valves 100, such as a D-shaped mold 428 resulting in a D-shaped heart valve 100. In some embodiments, the mold body 432 can have an elliptical cross-section.

[0037] The mold 428 can be used to form and / or shape portions of the heart valve 100, such as the leaflets 104, the inner skirt 106, and in some embodiments, the outer skirt. The mold 428 can be used to form and / or shape a sheet of tissue into a desired configuration having the leaflets 104 and the inner skirt 106. The mold 428 can be made from many different materials, including substantially rigid materials such as metals, polymers, ceramics, glasses, composites, etc. However, in some embodiments, the mold 428 may not be substantially rigid and may be capable of some deformation.

[0038] A single continuous piece of tissue can be placed onto or around the form as part of the process of transitioning the tissue from its original shape (e.g., a flat sheet) to a valve shape (where the leaflets and inner skirt are defined).

[0039] In some embodiments, the mold 428 can include a depression 430. The depression 430 can be aligned with the portion of the tissue that defines the leaflets. Additionally, the mold body 432 can be aligned with the portion of the tissue that defines the inner skirt.

[0040] 5, a perspective view of tissue 534 being draped over a form 428 is shown, according to various embodiments of the present application. The form 428 includes a plurality of depressions 430, such as a number of depressions 430 equal to the desired number of leaflets in the valve 100. In many embodiments, the form 428 defines three depressions 430 to result in a valve 100 having three leaflets 104. The form 428 also includes a body 432, which can be sized and shaped to result in the desired size and shape of the inner skirt 106, and in some embodiments, the outer skirt.

[0041] 5 specifically shows a single continuous sheet of tissue 534 being draped over form 428, such as the portion of tissue 534 moving in the direction of arrows 536 and arrow 538. The tissue 534 may be soft, flexible, and / or malleable such that the tissue 534 can assume the shape defined by the outer portion of form 428 (including that defined by the depressions and body). A single continuous piece of tissue 534 may be used to form multiple leaflets 104, inner skirt 106, and outer skirt.

[0042] 6, a cross-sectional view of tissue 534 is shown after it has been draped over the form 428, according to various embodiments of the present application. It can be seen that the indentations 430 are aligned with the leaflets 104. The inner skirt 106 can be the portion of tissue that surrounds the body 432 of the form 428.

[0043] In some embodiments, the tissue 534 can be held onto the mold 428 using vacuum pressure. In some embodiments, the tissue 534 can be held onto the mold 428 using positive fluid pressure. In some embodiments, the tissue 534 can be held onto the mold 428 using mechanical tension. In some embodiments, the tissue 534 can be held onto the mold 428 using sutures.

[0044] In some embodiments, depending on how the tissue 534 is positioned on the mold 428, the tissue 534 can be cut along cut lines 642, etc. to define a joint edge and provide an opening through the tissue 534 that allows blood to pass through the valve 100 and out the outlet 118.

[0045] In various embodiments, the valve 100 can include an outer skirt. The outer skirt 668 can extend beyond the inner skirt 106 on the form 428, for example beyond a line 670. Once the tissue 534 is positioned on and / or coupled to the frame 102, the outer skirt 668 can be flipped or folded (e.g., wrapped around a bottom edge of the frame) over the line 670 to form the outer skirt 668 over the frame 102. In various embodiments, the outer skirt is wrapped around an end of the metal frame 102 and positioned to rest against an outer surface of the metal frame 102.

[0046] In contrast to Figure 5, in some embodiments, tissue 534 can be wrapped laterally around form 428. Referring to Figure 7, a perspective view of tissue 534 being wrapped around form 428 is shown, according to various embodiments of the present application. Instead of draping tissue 534 over form 428, tissue 534 can be wrapped around form 428, as indicated by arrow 744.

[0047] Referring to FIG. 8, a perspective view of tissue 534 being wrapped around a form 428 is shown according to various embodiments of the present application. The two ends of tissue 534 can be joined with a suture 848, such as a single longitudinal suture. Thus, a seam 802 is formed where the two ends meet. However, the seam 802 extends along the longitudinal axis and does not divide the inner skirt region from the leaflets and / or does not divide the inner skirt region from the outer skirt region. The suture 848 can include multiple sutures for attaching the two ends of the same tissue piece 534 together. The suture 848 can have sutures of various densities. The sutures can also be used to tightly draw the tissue 534 to the form 428 so that the tissue 534 takes the same shape as the outer surface of the form 428. A portion of the tissue 534 can then be pushed inward in the direction of arrows 844 and 846 to cause the tissue 534 to conform to the shape of the depression 430.

[0048] Referring to FIG. 9, a perspective view of tissue 534 wrapped around a mold 428 is shown according to various embodiments of the present application. FIG. 9 includes the features shown in FIG. 8, but further illustrates a second suture 946 that may be included in some embodiments. The second suture 946 may be used to hold the tissue 534 in place against the mold surface, similar to the suture 848. In some embodiments, the second suture 946 may be removed from the remainder of the tissue 534, such as by cutting along a line 950. In this manner, the second suture 946 does not become part of the completed valve. Rather, the second suture 946 is only used in the process of forming the valve. Cutting along the line 950 may also create an opening through the tissue 534 to form the outlet 118 of the central lumen 220.

[0049] 10 and 11, cross-sectional views of tissue 534 being cross-linked on form 428 are shown, according to various embodiments of the present application. FIG. 10 shows fixative solution 1052 being applied to tissue 534. In some embodiments, fixative solution 1052 can be sprayed onto tissue 534 while tissue 534 is on form 428. In other embodiments, tissue 534 can be immersed in a tank or container 1154 of fixative solution 1052, as shown in FIG.

[0050] Cross-linking of the tissue 534 allows the tissue 534 to maintain its shape after the mold 428 is removed or separated from the tissue 534. In some embodiments, the degree of cross-linking is substantially uniform across all portions of the tissue 534. However, in some embodiments, the animal tissue 534 exhibits different degrees of cross-linking in different regions of the assembly of the implantable heart valve 100. For example, in some embodiments, the portions of the tissue 534 that form the valve leaflets are more highly cross-linked than other regions, such as the regions that form the inner skirt and / or the outer skirt. This can be done according to a variety of methods. In some embodiments, the tissue, while still on the mold, can be immersed upside down in the fixation solution with the leaflet ends facing down, such that the regions of the leaflets are immersed in the fixation solution, but the portions that form the inner skirt are not. In other embodiments, the tissue can be immersed in the fixation solution such that the ends of the inner skirt are immersed in the fixation solution. Thus, in some embodiments, the regions of the valve leaflets are more highly cross-linked than the regions of the inner skirt to provide toughness to the leaflets. However, in some embodiments, the inner skirt region is more highly cross-linked than the leaflet regions. In this manner, the degree of cross-linking in different regions of the valve can be independently optimized.

[0051] After the tissue 534 is cross-linked on the mold 428, the mold 428 can be removed from the tissue 534 as shown in Figure 12. Figure 12 illustrates a cross-sectional view of the mold 428 being removed from the tissue 534, according to various embodiments of the present application. The mold 428 can be separated from the tissue 534, such as by moving the mold in the direction of arrow 1256 while holding the tissue 534 stationary.

[0052] 13, a cross-sectional view of a portion of a heart valve 100 is shown, according to various embodiments of the present application. The heart valve can include leaflets 104 and an inner skirt 106. In various embodiments, the leaflets 104 can exhibit a curved bias from in situ bridging, as shown in FIG.

[0053] In some embodiments, the heart valve can include one or more reinforcing structures, such as reinforcing portions of tissue 534. The reinforcing structures can be placed in areas of high stress caused by movement of the leaflets 104 or by sutures attaching the bridged tissue 534 to the frame 102. The reinforcing structures can include additional animal tissue or polymeric materials so that the heart valve can be effectively thicker at the location of the reinforcing structures. In some embodiments, the reinforcing structures can include a polymer mesh, such as a polyethylene terephthalate (PET) mesh. In some embodiments, the reinforcing structures can include one or more outer reinforcing portions 1358 and / or one or more inner reinforcing portions 1360.

[0054] In various embodiments, each of the multiple leaflets 104 can include a commissure and a nadir 1357. The commissure can refer to the area of ​​the leaflet 104 where it meets an adjacent leaflet 104 around the circumference of the valve. The nadir 1357 can refer to the area of ​​the leaflet 104 where it joins with the inner skirt 106. In various embodiments, a reinforcing portion 1359 can be disposed at the nadir 1357 of the leaflet. In some embodiments, the reinforcing portion 1359 can be positioned in the area of ​​at least one of the commissure and the nadir 1357.

[0055] It is understood that animal-derived tissues may have fibers (including, but not limited to, collagen fibers) and / or other structures therein that exhibit a degree of directionality such that the tissue is more elastic in one direction than another. In various embodiments of the present application, the directional properties of the tissue can be purposefully aligned in a particular direction relative to the structure of the valve being fabricated.

[0056] 14-16 illustrate various ways in which native fibers in tissue, such as pericardial tissue, can be arranged in a valve 100. Referring to FIG. 14, a schematic end view of a closed valve 100 is shown, according to various embodiments of the present application. The tissue of the leaflets 104 can include fibers 1462. The fibers 1462 can be aligned such that the fibers exhibit a symmetric radial arrangement about the valve 100. The symmetric radial arrangement can provide desirable symmetric properties (such as symmetric bending properties) for each leaflet. However, in other embodiments, the fibers 1462 of the leaflets 104 can exhibit an asymmetric arrangement, as shown in FIGS. 15-16.

[0057] Frame The frame 102, or at least some components thereof, can be formed from a variety of materials, including, but not limited to, polymers, metals, metal alloys, ceramics, and composites. Exemplary materials can include, among others, biocompatible materials. Exemplary materials can include, among others, corrosion-resistant metals and metal alloys. In some embodiments, the frame 102 can be formed at least in part from Nitinol or NiTiCo. In some embodiments, the frame 102 can be formed at least in part from a cobalt-chromium alloy. In some embodiments, the frame 102 can be formed at least in part from platinum. In some embodiments, the frame 102 can be formed at least in part from a tantalum alloy. In some embodiments, the frame 102 can be formed at least in part from stainless steel.

[0058] organization The tissues used in the heart valves described herein can include naturally occurring tissues, such as animal tissues. In various embodiments, bovine, porcine, ovine or caprine tissues can be used as the naturally occurring tissues. In some embodiments, the naturally occurring tissues can specifically include pericardial tissue. However, other types of tissues can also be used, such as renal capsule tissue, small intestinal submucosa, cultured animal tissue, etc.

[0059] In various embodiments, the animal tissue 534 has a thickness between 100 and 500 microns. In some embodiments, the thickness can be greater than 100 microns, 130 microns, 160 microns, 190 microns, 220 microns, or 250 microns. In some embodiments, the thickness can be less than 1000 microns, 850 microns, 700 microns, 550 microns, 400 microns, or 250 microns. In some embodiments, the thickness can be in the range of 100 microns to 1000 microns, or 130 microns to 850 microns, or 160 microns to 700 microns, or 190 microns to 550 microns, or 220 microns to 400 microns.

[0060] In some embodiments, the thickness can be measured when the tissue is fresh (unfixed), hi some embodiments, the thickness can be measured when the tissue is fixed (crosslinked).

[0061] Crosslinking of tissues can be performed according to various methods. In some embodiments, homobifunctional crosslinkers can be used. In some embodiments, heterobifunctional crosslinkers can be used. In some embodiments, the compound for crosslinking comprises one or more of amine reactive groups, carboxyl-amine reactive groups, sulfhydryl reactive groups, aldehyde reactive groups, photoreactive groups, hydroxyl reactive groups, or azide reactive groups. In some embodiments, crosslinking is performed by exposing the tissue to a glutaraldehyde solution. However, many other compounds can be used to perform crosslinking.

[0062] method Many different methods are contemplated herein, including but not limited to methods of making, methods of using, etc. Aspects of the operation of the systems / devices described elsewhere in this application may be implemented as operations of one or more methods according to various embodiments of this application.

[0063] 17 shows a flow chart illustrating a method of making an implantable heart valve assembly. The method may include a step 1790 of placing a piece of pericardial tissue on a mold. The method may include a step 1792 of bridging the pericardial tissue in place on the mold. The method may include a step 1794 of removing the pericardial tissue from the mold. The method may further include a step 1796 of attaching the pericardial tissue to a frame. In some embodiments, the pericardial tissue forms a seamless joint between the leaflets and the inner skirt.

[0064] In some embodiments, the method may further include cutting the pericardial tissue to form the leaflet margin. In some embodiments, the method may further include placing pericardial tissue in place over the form.

[0065] In some embodiments, the method may further include wrapping the ends of the pericardial tissue over and above the ends of the frame to form an outer skirt. In some embodiments, crosslinking is performed by exposing the tissue to a glutaraldehyde solution. In some embodiments, the method may further include using vacuum pressure to hold the pericardial tissue on the mold. In some embodiments, the method may further include using fluid pressure to hold the pericardial tissue on the mold. In some embodiments, the method may further include using mechanical tension to hold the pericardial tissue on the mold. In some embodiments, the method may further include wrapping a sheet of pericardial tissue around the mold and forming a suture longitudinally along the mold to hold the pericardial tissue in place. In some embodiments, the method may further include placing a piece of pericardial tissue on the mold.

[0066] It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates to the contrary. Also, it should be noted that the term "or" is generally used in its sense including "and / or" unless the content clearly dictates to the contrary.

[0067] It should also be noted that, as used herein and in the appended claims, the phrase "configured" describes a system, apparatus, or other structure that is constructed or configured to perform a particular task or adopt a particular configuration. The phrase "configured" may be used interchangeably with other similar phrases, such as arranged and constructed, constructed and arranged, constructed, manufactured and arranged, etc.

[0068] All publications and patent applications in this specification are indicative of the level of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated by reference.

[0069] As used herein, the recitation of numerical ranges by endpoints is intended to include all numbers subsumed within that range (eg, 2 to 8 includes 2.1, 2.8, 5.3, 7, etc.). The headings used in this application are provided for consistency with suggestions under 37 CFR 1.77 or to otherwise provide organizational guidance. These headings should not be considered to limit or characterize the invention(s) recited in any claims that may arise from this disclosure. As an example, a heading may refer to a "Field," but the claims should not be limited by the language selected under this heading to describe the so-called field of technology. Furthermore, the description of a technology in the "Background" is not an admission that the technology is prior art to any invention in this disclosure. The "Summary" should also not be considered a feature of the invention(s) recited in the claims.

[0070] The embodiments described herein are not intended to be exhaustive or to limit the invention to the precise form disclosed in the following detailed description. Rather, the embodiments are chosen and described so that those skilled in the art can appreciate and understand the principles and implementations thereof. Thus, aspects have been described with reference to various specific preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the present application.

Claims

1. 1. An implantable heart valve assembly, comprising: a plurality of valve leaflets comprising animal tissue; an inner skirt comprising animal tissue; a metal frame having a luminal surface and an abluminal surface; the plurality of leaflets and the inner skirt are formed from a continuous piece of animal tissue; an implantable heart valve assembly, wherein the plurality of leaflets and the inner skirt are coupled to the metal frame with the inner skirt positioned on the luminal surface of the metal frame, the inner skirt being positioned upstream of the plurality of leaflets.

2. The implantable heart valve assembly of claim 1 , wherein the animal tissue exhibits different degrees of cross-linking in different regions of the implantable heart valve assembly.

3. 3. The implantable heart valve assembly of claim 1 or 2, further comprising an outer skirt comprising animal tissue.

4. The implantable heart valve assembly of claim 3 , wherein the plurality of leaflets, the inner skirt, and the outer skirt are formed from a single continuous piece of animal tissue.

5. The implantable heart valve assembly of any one of claims 1 to 4, wherein the inner skirt comprises a longitudinal suture.

6. The implantable heart valve assembly of any one of claims 1 to 5, wherein the inner skirt is seamless.

7. The implantable heart valve assembly of any one of claims 1 to 6, wherein the leaflets exhibit a curved bias from bridging at their locations.

8. The implantable heart valve assembly of any one of claims 1 to 7, wherein the leaflets exhibit a symmetric pericardial fiber orientation.

9. The implantable heart valve assembly of any one of claims 1 to 8, wherein the leaflets exhibit an asymmetric pericardial fiber orientation.

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