Methods for implantation of regenerative / tissue engineering heart valve

Description

ATTORNEY DOCKET No. A0012763W001METHODS FOR IMPLANTATION OF REGENERATIVE / TISSUE ENGINEERING HEART VALVECROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 709,116, filed October 18, 2024, the entire content of which is incorporated herein by reference.FIELD

[0002] The present disclosure relates generally to an implantation of a heart valve assembly and, more particularly, to a method for implantation of a regenerative / tissue engineering heart valve.BACKGROUND

[0003] It is known to provide a prosthetic heart valve assembly for implanting a heart valve prosthesis within a target site of the vasculature of a patient. Tissued engineered heart valves (TEHVs) have the potential of improving durability over existing valve designs. However, implantation of the TEHV can be difficult.SUMMARY

[0004] The following presents a simplified summary of the disclosure to provide a basic understanding of some aspects described in the detailed description.

[0005] In an example, a method for replacing a valve of a heart with a tissue- engineered heart valve comprising leaflets made of regenerative tissue. The method comprising the steps of positioning a first valve comprising a frame and leaflets free of the regenerative tissue into the heart at a location spaced away from the valve of the heart; and positioning a second valve comprising a frame and leaflets comprising the regenerative tissue into the valve of the heart.

[0006] In an example, a method for replacing a valve of a heart with a tissue- engineered heart valve having leaflets made of regenerative tissue. The method comprisingthe steps of: positioning a transcatheter valve comprising a frame and leaflets comprising the regenerative tissue into the heart at a location spaced away from the valve of the heart; maintaining the transcatheter valve at the location spaced away from the valve of the heart for a predetermined period of time; after the predetermined period of time, re-capturing the transcatheter valve from the location spaced away from the valve of the heart; and repositioning the transcatheter valve into the valve of the heart.

[0007] Additional features and advantages of the aspects disclosed herein will be set forth in the detailed description that follows, and in part will be clear to those skilled in the art from that description or recognized by practicing the aspects described herein, including the detailed description which follows, the claims, as well as the appended drawings. It is to be understood that both the foregoing general description and the following detailed description present aspects intended to provide an overview or framework for understanding the nature and character of the aspects disclosed herein. The accompanying drawings are included to provide further understanding and are incorporated into and constitute a part of this specification. The drawings illustrate various aspects of the disclosure, and together with the description explain the principles and operations thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] These and other features, aspects and advantages are better understood when the following detailed description is read with reference to the accompanying drawings, in which:

[0009] FIG. 1 schematically illustrates example aspects of a first transcatheter heart valve prosthesis that includes a regenerative tissue, in accordance with aspects of the disclosure;

[0010] FIG. 2 illustrates a top-down view of the first transcatheter heart valve prosthesis of FIG. 1, in accordance with aspects of the disclosure;

[0011] FIG. 3 schematically illustrates example aspects of a second transcatheter heart valve prosthesis that is free of a regenerative tissue, in accordance with aspects of the disclosure;

[0012] FIG. 4 illustrates a top-down view of the second transcatheter heart valve prosthesis of FIG. 3, in accordance with aspects of the disclosure;

[0013] FIG. 5 illustrates a side view of a transcatheter delivery assembly for delivering the first transcatheter heart valve prosthesis and the second transcatheter heart valve prosthesis, in accordance with aspects of the disclosure;

[0014] FIG. 6 illustrates a side view the transcatheter delivery assembly for delivering the first transcatheter heart valve prosthesis and the second transcatheter heart valve prosthesis, in accordance with aspects of the disclosure;

[0015] FIG. 7 illustrates a cross-sectional view of the first transcatheter heart valve prosthesis of FIG. 1 positioned in an aortic valve of a heart, in accordance with aspects of the disclosure;

[0016] FIG. 8 illustrates a cross-sectional view of the second transcatheter heart valve prosthesis of FIG. 3 positioned in a descending portion an aorta, in accordance with aspects of the disclosure;

[0017] FIG. 9 schematically illustrates the first transcatheter heart valve prosthesis of FIG. 1 positioned in an aortic valve of a heart, in accordance with aspects of the disclosure;

[0018] FIG. 10 schematically illustrates the first transcatheter heart valve prosthesis of FIG. 1 positioned in an aortic valve of a heart and the second transcatheter heart valve prosthesis of FIG. 3 positioned in a descending portion an aorta, in accordance with aspects of the disclosure;

[0019] FIG. 11 illustrates example aspects of a third transcatheter heart valve prosthesis having a first prosthetic valve that includes a regenerative tissue and a second prosthetic valve that is free of a regenerative tissue, in accordance with aspects of the disclosure;

[0020] FIG. 12 illustrates a top-down view of the first prosthetic valve of the third transcatheter heart valve prosthesis taken along line 12-12 of FIG. 11, in accordance with aspects of the disclosure;

[0021] FIG. 13 illustrates a top-down view of the second prosthetic valve of the third transcatheter heart valve prosthesis taken along line 13-13 of FIG. 11, in accordance with aspects of the disclosure;

[0022] FIG. 14 schematically illustrates the third transcatheter heart valve prosthesis of FIG. 11 positioned in an aortic valve of a heart, in accordance with aspects of the disclosure;

[0023] FIG. 15 schematically illustrates the third transcatheter heart valve prosthesis of FIG. 11 positioned in an aortic valve and a stent with no leaflets placed in the second prosthetic valve, in accordance with aspects of the disclosure;

[0024] FIG. 16 schematically illustrates the first transcatheter heart valve prosthesis of FIG. 1 positioned in an aortic valve and the second transcatheter heart valve prosthesis of FIG. 3 positioned between the first transcatheter heart valve prosthesis and an aortic arch, in accordance with aspects of the disclosure;

[0025] FIG. 17 schematically illustrates the first transcatheter heart valve prosthesis of FIG. 1 positioned in an aortic valve, the second transcatheter heart valve prosthesis of FIG. 3 positioned between the first transcatheter heart valve prosthesis and an aortic arch, and a stent with no leaflets placed in the second transcatheter heart valve prosthesis, in accordance with aspects of the disclosure;

[0026] FIG. 18 schematically illustrates the first transcatheter heart valve prosthesis of FIG. 1 positioned in a descending portion of an aorta, in accordance with aspects of the disclosure; and

[0027] FIG. 19 schematically illustrates the first transcatheter heart valve prosthesis of FIG. 1 positioned in an aortic valve of a heart, in accordance with aspects of the disclosure.DETAILED DESCRIPTION

[0028] Aspects will now be described more fully hereinafter with reference to the accompanying drawings in which example aspects are shown. Whenever possible, the same reference numerals are used throughout the drawings to refer to the same or like parts. However, this disclosure may be embodied in many different forms and should not be construed as limited to the aspects set forth herein.

[0029] As used herein, the term “about” means that amounts, sizes, formulations, parameters, and other quantities and characteristics are not, and need not be, exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art.

[0030] Ranges can be expressed herein as from “about” one value, and / or to “about” another value. When such a range is expressed, aspects include from the one value to theother value. Similarly, when values are expressed as approximations by use of the antecedent “about,” it will be understood that the value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.

[0031] Directional terms as used herein - for example up, down, right, left, front, back, top, bottom, upper, lower, etc. - are made only with reference to the figures as drawn and are not intended to imply absolute orientation.

[0032] Unless otherwise expressly stated, it is in no way intended that any methods set forth herein be construed as requiring that its steps be performed in a specific order, nor that with any apparatus, specific orientations be required. Accordingly, where a method claim does not actually recite an order to be followed by its steps, or that any apparatus claim does not actually recite an order or orientation to individual components, or it is not otherwise specifically stated in the claims or description that the steps are to be limited to a specific order, or that a specific order or orientation to components of an apparatus is not recited, it is in no way intended that an order or orientation be inferred in any respect. This holds for any possible non-express basis for interpretation, including matters of logic relative to arrangement of steps, operational flow, order of components, or orientation of components; plain meaning derived from grammatical organization or punctuation, and; the number or type of aspects described in the specification.

[0033] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to “a” component includes aspects having two or more such components, unless the context clearly indicates otherwise.

[0034] The word “exemplary,” “example,” or various forms thereof are used herein to mean serving as an example, instance, or illustration. Any aspect or design described herein as “exemplary” or as an “example” should not be construed as preferred or advantageous over other aspects or designs. Furthermore, examples are provided solely for purposes of clarity and understanding and are not meant to limit or restrict the disclosed subject matter or relevant portions of this disclosure in any manner. It can be appreciated that a myriad of additional or alternate examples of varying scope could have been presented but have been omitted for purposes of brevity.

[0035] As used herein, the terms “comprising,” “including,” and variations thereof shall be construed as synonymous and open-ended, unless otherwise indicated. A list of elements following the transitional phrases comprising or including is a non-exclusive list, such that elements in addition to those specifically recited in the list may also be present.

[0036] The terms “substantial,” “substantially,” and variations thereof as used herein are intended to represent that a described feature is equal or approximately equal to a value or description. For example, a “substantially planar” surface is intended to denote a surface that is planar or approximately planar. Moreover, “substantially” is intended to denote that two values are equal or approximately equal. The term “substantially” may denote values within about 10% of each other, for example, within about 5% of each other, or within about 2% of each other.

[0037] Modifications may be made to the instant disclosure without departing from the scope or spirit of the claimed subject matter. Unless specified otherwise, “first,” “second,” or the like are not intended to imply a temporal aspect, a spatial aspect, an ordering, etc. Rather, such terms are merely used as identifiers, names, etc. for features, elements, items, etc. For example, a first end and a second end generally correspond to end A and end B or two different ends.

[0038] Unless otherwise indicated, the terms “distal” and “proximal” are used in the following description with respect to a position or direction relative to the treating clinician. “Distal” and “distally” are positions distant from or in a direction away from the clinician, and “proximal” and “proximally” are positions near or in a direction toward the clinician. In addition, the term “self-expanding” may be used in the following description with reference to one or more valve or stent structures of the prostheses hereof and is intended to convey that the structures are shaped or formed from a material that can be provided with a mechanical memory to return the structure from a compressed, collapsed, or constricted delivery configuration to an expanded deployed configuration or vice versa. Non- exhaustive exemplary self-expanding materials include stainless steel, a pseudo-elastic metal such as a nickel titanium alloy or nitinol, various polymers, or a so-called super alloy, which may have a base metal of nickel, cobalt, chromium, or other metal. Mechanical memory may be imparted to a wire or stent structure 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. Various polymers that can be made to have shape memorycharacteristics may also be suitable for use in aspects hereof to include polymers such as polynorborene, trans-polyisoprene, styrene-butadiene, and polyurethane. As well poly L-D lactic copolymer, oligo caprylactone copolymer and poly cyclo-octine can be used separately or in conjunction with other shape memory polymers.

[0039] Diseases associated with heart valves, such as those caused by damage or a defect, can include stenosis and valvular insufficiency or regurgitation. For example, valvular stenosis causes the valve to become narrowed and hardened which can prevent blood flow to a downstream heart chamber from occurring at the proper flow rate and may cause the heart to work harder to pump the blood through the diseased valve. Valvular insufficiency or regurgitation occurs when the valve does not close completely, allowing blood to flow backwards, thereby causing the heart to be less efficient. A diseased or damaged valve, which can be congenital, age-related, drug-induced, or in some instances, caused by infection, can result in an enlarged, thickened heart that loses elasticity and efficiency. Some symptoms of heart valve diseases can include weakness, shortness of breath, dizziness, fainting, palpitations, anemia and edema, and blood clots which can increase the likelihood of stroke or pulmonary embolism. Symptoms can often be severe enough to be debilitating and / or life threatening.

[0040] Heart valve prostheses have been developed for repair and replacement of diseased and / or damaged heart valves. Such heart valve prostheses can be percutaneously delivered and deployed at the site of the diseased heart valve through catheter-based delivery systems. Such heart valve prostheses generally include a frame or stent and a prosthetic valve mounted within the frame. Such heart valve prostheses are delivered in a radially collapsed or crimped configuration so that the heart valve prosthesis can be advanced through the patient’s vasculature. Once positioned at the treatment site, the heart valve prosthesis is expanded to engage tissue at the diseased heart valve region to, for instance, hold the heart valve prosthesis in position.

[0041] In some embodiments, the heart valve prosthesis may be delivered to and implanted at a treatment site within a patient to replace any of an aortic valve, a pulmonic valve, a mitral valve, and a tricuspid valve. The valve to be replaced may be a native valve or a previously-implanted prosthetic valve, such as a failed surgical replacement valve or a failed transcatheter valve. In the present disclosure, the invention will be described with reference to replacing the aortic valve, but as noted above, may similarly apply to replacingthe pulmonic valve, the mitral valve or the tricuspid valve. In the present disclosure, the invention will be described with reference to a transcatheter heart valve prosthesis; this should not be interpreted as limiting, as the heart valve prosthesis could be a surgical valve that is implanted following the methods described herein, including fixating via sutures and / or radial expansion.

[0042] With reference to FIGS. 1 and 2, in some aspects, a first transcatheter heart valve prosthesis 100 comprises an expandable stent frame 102. For example, as best shown in FIG. 2, the first transcatheter heart valve prosthesis 100 can comprise one or more leaflets 128 (e.g., two or more leaflets). In some examples, as shown, the one or more leaflets 128 can comprise three leaflets to emulate a tricuspid valve. For example, the one or more leaflets 128 can comprise a first leaflet 230, a second leaflet 232, and a third leaflet 234. In some aspects, the one or more leaflets 128 can comprise two leaflets, such as for example, to emulate a bicuspid valve. Any other suitable number of leaflets may be utilized.

[0043] The expandable stent frame 102 (for example) may be a self-expandable stent frame. In other non-limiting examples, the expandable stent frame 102 may include an expansion device (e.g., a balloon) configured to expand the expandable stent frame 102. In aspects, the expandable stent frame 102 can comprise an inner lumen 104 extending along an elongated axis 106. In some examples where the expandable stent frame 102 includes the expansion device, the expansion device can be positioned within the inner lumen 104. For example, the expansion device can comprise a balloon configured to receive saline, a contrast solution, or compressed air that may be delivered to the balloon to expand the expandable stent frame 102.

[0044] In aspects, the expandable stent frame 102 can comprise a proximal end 108 (outflow end) and a distal end 110 (inflow end). The expandable stent frame 102 can extend from the proximal end 108 to the distal end 110. In aspects, the proximal end 108 can be configured to be received within a capsule 535 of a transcatheter delivery assembly 530 (see, FIG. 5). In some non-limiting examples, the proximal end 108 can be slidably disposed within the capsule 535. In some embodiments, the expandable stent frame 102 can be configured to achieve a contracted orientation (shown in FIG. 6) and a fully expanded orientation (shown in FIG. 1).

[0045] The term “fully expanded orientation” should be construed to mean that the expandable stent frame 102 cannot expand any further with respect to the location at whichthe expandable stent frame 102 has been deployed (i.e., fully released from the transcatheter delivery assembly 530). In some cases, the term “fully expanded orientation” may refer to the expandable stent frame 102 not being capable of any further radial expansion regardless of the location at which the expandable stent frame 102 is deployed (e.g., the expandable stent frame 102 cannot radially expand any further, even when free from surrounding structure).

[0046] In some aspects, a proximal portion 112 of the expandable stent frame 102 adjacent the proximal end 108 can comprise a first plurality of cell structures 114. In further aspects, a distal portion 116 of the expandable stent frame 102 adjacent the distal end 110 can comprise a second plurality of cell structures 118. As show, the first plurality of cell structures 114 and the second plurality of cell structures 118 can comprise cell structures that can each be in a shape of a rhombus.

[0047] It should be understood that the expandable stent frame 102 is merely exemplary and any other suitable expandable stent frame may be utilized. Furthermore, the first plurality of cell structures 114 and the second plurality of cell structures 118 should not be limited to cell structures that are each in the shape of a rhombus and should not be limited to the number of cell structures and / or size of the cell structures shown in FIG. 1. Accordingly, more or less suitable cell structures with a variety of different shapes and sizes can be employed.

[0048] In some aspects, the first transcatheter heart valve prosthesis 100 can comprise a skirt 135 coupled to the expandable stent frame 102. As shown, in some examples, the skirt 135 can be coupled to the distal portion 116 of the expandable stent frame 102 and can be coupled to portions of an intermediate portion 122 of the expandable stent frame 102. For example, the skirt 135 can be coupled to the intermediate portion 122 of the expandable stent frame 102 and extend from the intermediate portion 122 towards the distal end 110 (e.g., the skirt can extend to any portion of the distal portion 116 or to the distal end 110). In other examples, the skirt 135 can extend along any length of the expandable stent frame 102. For example, the skirt 135 can extend along any length of the expandable stent frame 102 defined between the proximal end 108 and the distal end 110 of the expandable stent frame 102. The skirt 135 can be coupled to the expandable stent frame 102 by any suitable coupling means. For example, skirt 135 can be coupled to the expandable stent frame 102 by stitching, such as for example, coupling the skirt to theexpandable stent frame 102 by a stitching pattern that extends from the intermediate portion 122 of the expandable stent frame 102, and along the distal portion 116 of the expandable stent frame 102 (i.e., along one or more of the second plurality of cell structures 118).

[0049] In some aspects, the skirt 135 can comprise a radiopaque polymer. For example, a radiopaque polymer may be beneficial in facilitating a clinician in determining when the expandable stent frame 102 has been properly positioned within a patient. Any suitable polymer known in the art may be utilized. In other aspects, the skirt 135 can comprise a fabric. For example, the fabric may comprise any suitable material such as, but not limited to, woven polyester such as polyethylene terephthalate, polytetrafluoroethylene (PTFE), or other biocompatible materials. The skirt may be positioned at or near the distal end 110 to prevent paravalvular leakage of blood around the outside of the first transcatheter heart valve prosthesis 100 once implanted in the patient.

[0050] The first plurality of cell structures 114 can have an enlarged area relative to or compared to the second plurality of cell structures 118.. In particular, the first plurality of cell structures 114 may be larger than the second plurality of cell structures 118 and can provide access to one or more coronary arteries when the first transcatheter heart valve prosthesis 100 is implanted in the patient.

[0051] In some aspects, the expandable stent frame 102 can comprise one or more commissure points 136. The commissure points 136 can be utilized to couple die valve structure (e.g., the one or more leaflets 128 ) of the first transcatheter heart valve prosthesis 100 to the expandable stent frame 102. In some aspects, the valve structure can be coupled to the expandable stent frame 102 by a stitching pattern, such as tor example, by stitching the valve structure to the expandable stent frame 102 at the one or more commissure points 136, such as shown in FIG. 1. Any other suitable means of coupling the valve structure to the expandable stent frame 102 may be utilized.

[0052] In further aspects, the one or more commissure points 136 can comprise one or more radiopaque markers (e.g., one radiopaque marker, two radiopaque markers, three radiopaque markers, etc.). For example, one or more radiopaque markers can be located on any one of the one or more commissure points 136, such as for example, having one or more radiopaque markers on each of the one or more commissure points 136. In this way the expandable stent frame 102 and / or the valve structure can be located by a clinician (e.g., asurgeon) when maneuvering the expandable stent frame 102 through the vasculature and / or within a heart valve of a patient.

[0053] In aspects, as illustrated, the distal end 110 of the expandable stent frame 102 can comprise a plurality of crowns 138. In further aspects, at least one crown of the plurality of crowns 138 can comprise a paddle (not shown) configured to be received by the transcatheter delivery assembly 530 (see FIGS. 5 and 6).

[0054] In aspects, the proximal end 108 of the expandable stent frame 102 can comprise a plurality of crowns 140. For example, the proximal end 108 of the expandable stent frame 102 can comprise one crown, two crowns, three crowns, and so on. In some aspects, at least one crown of the plurality of crowns 140 of the proximal end 108 can comprise a paddle 142 configured to be received by the transcatheter delivery assembly 530 (see FIGS. 5 and 6). In one example, “received by” can mean “received within.” For example, the paddle can be received within the transcatheter delivery assembly 530.

[0055] In aspects, the one or more leaflets 128 are a tissue-engineered heart valve (TEHV). The tissue-engineered heart valve includes regenerative tissue that combines scaffolds, cells and biologically active molecules to make a functional tissue. Regenerative tissue has long-term regenerative and modeling capabilities and relies on the use of autologous, patient-specific cell sources, to create an immunologically safe product. The regenerative tissue relies on the ability of the recipient’s body to regenerate and remodel the TEHV once implanted in situ. After a predetermined period of time, the regenerative tissue will be both flexible and strong enough to function as the heart’s native valve replacement, as described in detail below.

[0056] Scaffold” refers to a structure of artificial or natural materials on which the regenerative tissue is grown to mimic a biological process. The scaffold may be one or more of the following: a decellularized extracellular matrix from connective tissue (e.g., xenogenic), a degradable matrix from bioresorbable polymer, synthetic, or porous scaffolds (e.g., polyhydroxyalkanoate, polylactic / polygly colic acid, polylactic acid-co-gly colic acid, poly caprolactone) or a matrix from biologic molecules (e.g., collagen, elastin, fibronectin, laminin, gelatine, hyaluronan). The matrix of biological cells may be cells from a donor organ that are stripped and a remaining collagen scaffold is used to grow the new regenerative tissue.

[0057] Tissue engineered heart valves have the potential for improving durability over existing valve designs. However, these TEHVs require a cell population / seeding step, which creates a challenge from scalability of this approach if the cell population / seeding step needs to be done outside the body (i.e., in a lab, etc.) for weeks / months. If the TEHV is placed in the heart, it is also critical that hemodynamics be maintained while the TEHV is populated / seeded. The present disclosure provides a method for delivering the TEHV in situ, while maintaining hemodynamics for the patient during cell population / seeding. As noted above, the present disclosure will be described in detail with respect to replacing an aortic valve 712 in an aorta 710 (FIG. 7) of a heart. However, the present disclosure applies similarly to placing other valves, including but not limited to, the pulmonic valve, the mitral valve or the tricuspid valve.

[0058] As shown in FIG. 1, the prosthetic leaflets 230, 232, 234 are attached to the expandable stent frame 102 such that when pressure at the distal end 110 exceeds pressure at the proximal end 108, the prosthetic leaflets 230, 232, 234 open to allow blood flow through the first transcatheter heart valve prosthesis 100 from the distal end 110 to the proximal end 108. When the pressure at the proximal end 108 exceeds pressure at the distal end 110, the prosthetic leaflets 230, 232, 234 close to prevent blood flow from the proximal end 108 to the distal end 110.

[0059] In aspects, similar to the first transcatheter heart valve prosthesis 100, the expandable stent frame 102 and, optionally, one or more of the skirt 135 and the commissure points 136, may also be made of the regenerative tissue. By making the expandable stent frame 102 and, optionally, one or more of the skirt 135 and the commissure points 136 from a regenerative tissue, the expandable stent frame 102 and one or more of the skirt 135 and the commissure points 136 can act as “bridges” between tissue of the heart and the leaflets 230, 232, 234 to promote the transfer and growth of the patient’s cells to the leaflets 230, 232, 234.

[0060] FIGS. 3-4 illustrate a second transcatheter heart valve prosthesis 300 that can be identical to the first transcatheter heart valve prosthesis 100 in all aspects, except a prosthetic valve of the second transcatheter heart valve prosthesis 300 does not include a regenerative tissue. The references numbers used for the second transcatheter heart valve prosthesis 300 are similar to those for the first transcatheter heart valve prosthesis 100 andare incremented by 200. The description of the second transcatheter heart valve prosthesis 300 is not repeated hereinbelow for brevity.

[0061] FIGS. 5 and 6 show schematically side views of a transcatheter delivery assembly 530 (e.g., “delivery assembly”) for delivering and deploying a transcatheter heart valve prosthesis (e.g., the first, second and third transcatheter heart valve prostheses 100, 300, 1100) according to embodiments hereof. One skilled in the art will realize that FIGS. 5 and 6 illustrate one example of a transcatheter delivery assembly 530 and that components illustrated in FIGS. 5 and 6 may be removed and / or additional components may be added. The transcatheter delivery assembly 530 includes a distal end 531, a proximal end 532, and a handle 533. The handle 533 enables a physician to manipulate a distal portion of the transcatheter delivery assembly 530 and includes actuators for moving parts of the transcatheter delivery assembly 530 relative to other parts. In the transcatheter delivery assembly 530, an outer shaft 534 is coupled to an actuator 539 of the handle 533 for moving the outer shaft 534 relative to an inner shaft 636.

[0062] A distal portion of the outer shaft 534, referred to as a capsule 535, is configured to surround a transcatheter heart valve prosthesis (e.g., the first, second and third transcatheter heart valve prostheses 100, 300, 1100) during delivery to the treatment site (e.g., a native heart valve) and is retracted from the transcatheter heart valve prosthesis to expose the transcatheter heart valve prosthesis such that it self-expands (in self-expanding embodiments). In this way, the capsule 535 is in frictional engagement with the first, second and third heart valve prostheses 100, 300, 1100. The inner shaft 636 can be coupled to the handle 533 (e.g., by being directly connected and in contact with the handle 533, or by being indirectly connected to the handle 533 with intermediate structures between the inner shaft 636 and the handle 533) and movement of the handle 533 can translate to movement of the inner shaft 636 and a distal tip or nose cone 537 coupled to a distal end of the inner shaft 636. The inner shaft 636 and distal tip or nose cone 537 may also be translated relative to the outer shaft 534 and the handle 533 via a tip retractor. In the embodiment shown, the inner shaft 636 includes a retainer 638 for receiving the paddles 142, 342 of the first and second transcatheter heart valve prostheses 100, 300.

[0063] When the actuator 539 is actuated, the actuator 539 moves the outer shaft 534 and the capsule 535 relative to the inner shaft 636, as shown in FIG. 6. As known to those skilled in the art, when the transcatheter delivery assembly 530 is in position such thatthe first, second or third transcatheter heart valve prostheses 100, 300, 1100 are at the desired position at the treatment site in the patient’s vasculature, the actuator 539 is actuated (e.g., rotated) to move the capsule 535 relative to the inner shaft 636 and the first, second or third transcatheter heart valve prostheses 100, 300, 1100 disposed between the inner shaft 636 and the capsule 535, thereby enabling the first, second or third transcatheter heart valve prostheses 100, 300, 1100 to deploy via self-expansion at the treatment site and release from the retainer 638, as shown in FIG. 6 (without showing the first, second or third transcatheter heart valve prostheses 100, 300, 1100).

[0064] In one embodiment, illustrated in FIGS. 7-10, the first transcatheter heart valve prosthesis 100 is positioned within the aortic valve 712 by attaching the first transcatheter heart valve prosthesis 100 to the transcatheter delivery assembly 530 (see, FIG. 6) and inserting it through an aorta 710 to the aortic valve 712. As illustrated in FIGS. 7 and 9, the first transcatheter heart valve prosthesis 100 is positioned such that the distal end 110 (inflow end) is oriented toward a left ventricle (not shown) of the heart and the proximal end 108 (outflow end) is oriented toward an aortic arch 916 (FIG. 9) of the heart. In aspects, once properly positioned, the first transcatheter heart valve prosthesis 100 can be sutured to the aortic valve 712. In aspects, the first transcatheter heart valve prosthesis 100 can expand and be held in the aortic valve 712 via an outwardly directed radial force (see, FIGS. 7 and 9). In aspects, the outwardly directed radial force may be achieved via the first transcatheter heart valve prosthesis 100 being self-expanding, ballon-expanded or mechanically- expanded.

[0065] The second transcatheter heart valve prosthesis 300 is attached to the transcatheter delivery assembly 530 (see, FIG. 6) and inserted through the aorta 710 until the second transcatheter heart valve prosthesis 300 is properly positioned in a descending aorta 814 (see, FIGS. 8 and 10). As illustrated in FIGS. 8 and 10, the second transcatheter heart valve prosthesis 300 is positioned so that the distal end 310 (inflow end) is oriented toward the aortic arch 916 (FIG. 9) of the heart and the proximal end 308 (outflow end) is oriented away from to the aortic arch 916 (FIG. 9). In aspects, once properly positioned, the second transcatheter heart valve prosthesis 300 can be sutured to the descending aorta 814. In aspects, the second transcatheter heart valve prosthesis 300 can expand and be held in the descending aorta 814 via an outwardly directed radial force (see FIGS. 8 and 10). In aspects, the outwardly directed radial force may be achieved via the second transcatheter heart valveprosthesis 300 being self-expanding, ballon-expanded or mechanically-expanded. The second transcatheter heart valve prosthesis 300 is configured to help maintain proper hemodynamics as the first transcatheter heart valve prosthesis 100 undergoes cell population / seeding. By positioning the second transcatheter heart valve prosthesis 300 in the descending aorta 814, the proper hemodynamics can be maintained in the aorta 710. The exposure of the first transcatheter heart valve prosthesis 100 (positioned in the aortic valve 712) to the proper hemodynamics assists the cells of the first transcatheter heart valve prosthesis 100 in developing in a way that makes them both flexible and strong enough for acting as a standalone valve.

[0066] In aspects, after a predetermined period of time, a stent (not shown) having no leaflets may be placed in the second transcatheter heart valve prosthesis 300 to force the leaflets 328 permanently to an open position. The open position allows for the free flow of blood through the second transcatheter heart valve prosthesis 300. The predetermined period of time is selected to be the time sufficient for the cells of the first transcatheter heart valve prosthesis 100 to develop to a condition that they are both flexible and strong enough to act as a standalone valve, i.e., to maintain hemodynamics in the patient without the assistance of the second transcatheter heart valve prosthesis 300. In aspects, the predetermine period of time can be between about 30 days and about 180 days.

[0067] In another embodiment, illustrated in FIGS. 11 - 15, an exemplary third transcatheter heart valve prosthesis 1100, according to another embodiment is illustrated. Aside from the materials used to construct a first prosthetic valve 1120A, a second prosthetic valve 1120B, an expandable stent frame 1102, and optionally, a skirt 1135 and commissure points 1136A of the third transcatheter heart valve prosthesis 1100, the description of the third transcatheter heart valve prosthesis 1100 is merely exemplary in nature and is not intended to limit the invention or application and uses of the invention.

[0068] The third transcatheter heart valve prosthesis 1100 includes an expandable stent frame 1102, the first prosthetic valve 1120A and the second prosthetic valve 1120B. The expandable stent frame 1102 of the third transcatheter heart valve prosthesis 1100 supports the first prosthetic valve 1120 A and the second prosthetic valve 1120B within an interior of the expandable stent frame 1102. In the example third transcatheter heart valve prosthesis 1100 shown in FIG. 11, the expandable stent frame 1102 is self-expandable. However, this is not meant to be limiting, and the expandable stent frame 1102 can beballoon-expandable or mechanically expandable in other embodiments. In some embodiments, the third transcatheter heart valve prosthesis 1100 may be delivered to and implanted at a treatment site within a patient to replace any of an aortic valve, a pulmonic valve, a mitral valve, and a tricuspid valve. The valve to be replaced may be a native valve or a previously-implanted prosthetic valve, such as a failed surgical replacement valve or a failed transcatheter valve. In the present disclosure, the invention will be described with reference to replacing the aortic valve, but as noted above, may similarly apply to replacing the pulmonic valve, the mitral valve or the tricuspid valve.

[0069] The expandable stent frame 1102 (for example) may be a self-expandable stent frame. In other non-limiting examples, the expandable stent frame 1102 may include an expansion device (e.g., a balloon) configured to expand the expandable stent frame 1102. In aspects, the expandable stent frame 1102 can comprise an inner lumen 1104 extending along a longitudinal axis 1106. In some examples where the expandable stent frame 1102 includes the expansion device, the expansion device can be positioned within the inner lumen 1104. For example, the expansion device can comprise a balloon configured to receive saline, a contrast solution, or compressed air that may be delivered to the balloon to expand the expandable stent frame 1102. In some embodiments, the expandable stent frame 1102 can be configured to achieve a contracted orientation (shown in FIG. 6) and a fully expanded orientation (shown in FIG. 11). It should be understood that the expandable stent frame 1102 is merely exemplary and any other suitable expandable stent frame may be utilized.

[0070] In aspects, the expandable stent frame 1102 can comprise a proximal end 1108 (outflow end) and a distal end 1110 (inflow end). The expandable stent frame 1102 can extend from the proximal end 1108 to the distal end 1110. In aspects, the proximal end 1108 can be configured to be received within the capsule 535 of the transcatheter delivery assembly 530 (see, FIG. 6). In some non-limiting examples, the proximal end 1108 can be slidably disposed within the capsule 535.

[0071] Referring to FIG. 12, the first prosthetic valve 1120A includes one or more leaflets 1128A (e.g., two or more leaflets). In some examples as shown, the one or more leaflets 1128A can comprise three leaflets to emulate a tricuspid valve. For example, the one or more leaflets 1128A can include a first leaflet 1230, a second leaflet 1232, and a third leaflet 1234. In some aspects, the one or more leaflets 1128A can comprise two leaflets,such as for example, to emulate a bicuspid valve. Any other suitable number of leaflets may be utilized. The leaflets 1128A open and close to regulate flow through the third transcatheter heart valve prosthesis 1100.

[0072] In aspects, the first prosthetic valve 1120A is a tissue-engineered heart valve (TEHV). As discussed above, the tissue-engineered heart valve includes regenerative tissue that combines scaffolds, cells and biologically active molecules to make a functional tissue. Regenerative tissue has long-term regenerative and modeling capabilities and relies on the use of autologous, patient-specific cell sources, to create an immunologically safe product. The regenerative tissue relies on the ability of the recipient’s body to regenerate and remodel the TEHV once implanted in situ. After a predetermined period of time, the regenerative tissue will be both flexible and strong enough to function as the heart’s native valve replacement, as described in detail below.

[0073] Scaffold” refers to a structure of artificial or natural materials on which tissue is grown to mimic a biological process. The scaffold may be one or more of the following: a decellularized extracellular matrix from connective tissue (e.g., xenogenic), a degradable matrix from bioresorbable polymer, synthetic, or porous scaffolds (e.g., polyhydroxyalkanoate, polylactic / polyglycolic acid, polylactic acid-co-glycolic acid, poly caprolactone) or a matrix from biologic molecules (e.g., collagen, elastin, fibronectin, laminin, gelatine, hyaluronan). The matrix of biological cells may be cells from a donor organ that are stripped and a remaining collagen scaffold is used to grow the new regenerative tissue.

[0074] Referring to FIG. 13, the second prosthetic valve 1120B includes one or more leaflets 1128B (e.g., two or more leaflets). In some examples as shown, the one or more leaflets 1128B can comprise three leaflets to emulate a tricuspid valve. For example, the one or more leaflets 1128B can include a first leaflet 1330, a second leaflet 1332, and a third leaflet 1334. In some aspects, the one or more leaflets 1128B can comprise two leaflets, such as for example, to emulate a bicuspid valve. Any other suitable number of leaflets may be utilized. The leaflets 1128B open and close to regulate flow through the third transcatheter heart valve prosthesis 1100. Furthermore, the leaflets 1128B can be designed to fully coapt and prevent regurgitation, or the leaflets 1128B can be designed to allow some transvalvular regurgitation (i.e. not fully coapt) so that the first prosthetic valve 1120A is exposed to more blood flow and / or pressure. Alternatively to transvalvular regurgitation, aportion 1103B of the expandable stent frame 1102 proximate the second prosthetic valve 1120B could have a skirt design (or lack thereof) to allow paravalvular leak.

[0075] As shown in FIG. 11, the leaflets 1128A, 1128B are attached to the expandable stent frame 1102 such that when pressure at the distal end 1110 exceeds pressure at the proximal end 1108, the leaflets 1128 A, 1128B open to allow blood flow through the third transcatheter heart valve prosthesis 1100 from the distal end 1110 to the proximal end 1108. When the pressure at the proximal end 1108 exceeds pressure at the distal end 1110, the leaflets 1128 A, 1128B close to prevent blood flow from the proximal end 1108 to the distal end 1110.

[0076] In some aspects, the third transcatheter heart valve prosthesis 1100 can comprise the skirt 1135 coupled to the expandable stent frame 1102. As shown, in some examples, the skirt 1135 can be coupled to a distal portion 1116 of the expandable stent frame 1102. The skirt 1135 can be coupled to the expandable stent frame 1102 by any suitable coupling means. For example, skirt 1135 can be coupled to the expandable stent frame 1102 by stitching, such as for example, coupling the skirt to the expandable stent frame 1102 by a stitching pattern.

[0077] In some aspects, the skirt 1135 can comprise a radiopaque polymer. For example, a radiopaque polymer may be beneficial in facilitating a clinician in determining when the expandable stent frame 1102 has been properly positioned within a patient. Any suitable polymer known in the art may be utilized. In other aspects, the skirt 1135 can comprise a fabric. For example, the fabric may comprise any suitable material such as, but not limited to, woven polyester such as polyethylene terephthalate, polytetrafluoroethylene (PTFE), or other biocompatible materials. The skirt may be positioned at or near the distal end 1110 to prevent paravalvular leakage of blood around the outside of the third transcatheter heart valve prosthesis 1100 once implanted in the patient.

[0078] In some aspects, a proximal portion 1112 of the expandable stent frame 1102 adjacent the proximal end 1108 can comprise a first plurality of cell structures 1114. In further aspects, the distal portion 1116 of the expandable stent frame 1102 adj acent the distal end 1110 can comprise a second plurality of cell structures 1118. As shown, the first plurality of cell structures 1114 and the second plurality of cell structures 1118 can each comprise a shape of a rhombus. The first plurality of cell structures 1114 can have an enlarged area relative to or compared to the second plurality of cell structures 1118. Inparticular, the first plurality of cell structures 1114 may be larger than the second plurality of cell structures 1118 and can provide access to one or more coronary arteries when the third transcatheter heart valve prosthesis 1100 is implanted in the patient.

[0079] In some aspects, the expandable stent frame 1102 can comprise one or more commissure points 1 136A to couple the valve structure (e.g., the one or more leaflets 1128A) of the first prosthetic valve 1120A to the expandable stent frame 1102 and one or more commissure points 1 136B to couple the valve structure (e.g., the one or more leaflets 1128B) of the second prosthetic valve 1120B to the expandable stent frame 1102. In some aspects, the valve structures can be coupled to the expandable stent frame 1102 by a stitching pattern, such as for example, by stitching the valve structures to the expandable stent frame 1102 at the one or more commissure points 1136A, 1136B, such as shown in FIG. 11. Any other suitable means of coupling the valve structures to the expandable stent frame 1 102 may be utilized.

[0080] In further aspects, the one or more commissure points 1136A, 1 136B can comprise one or more radiopaque markers (e.g., one radiopaque marker, two radiopaque markers, three radiopaque markers, etc.). For example, one or more radiopaque markers can be located on any one of the one or more commissure points 1136A, 1136B, such as for example, having one or more radiopaque markers on each of the one or more commissure points 1136A, 1136B. In this way the expandable stent frame 1102 and / or the valve structures can be located by a clinician (e.g., a surgeon) when maneuvering the expandable stent frame 1102 through the vasculature and / or within a heart valve of a patient.

[0081] In aspects, similar to the expandable stent frame 102, a portion 1103 A of the expandable stent frame 1102 proximate the first prosthetic valve 1120A can also be made of the regenerative tissue. In aspects, the skirt 1135A and the commissure points 1136A may also be made of the regenerative tissue. By making the portion 1103 A of the expandable stent frame 1102 and, optionally the skirt 1135A and the commissure points 1136A from the regenerative tissue, these components act as bridges between the heart and the leaflets 1128A to promote the transfer and growth of the patient’s cells to the leaflets 1128A. In aspects, a portion 1103B of the expandable stent frame 1102 proximate the second prosthetic valve 1120B may be free of the regenerative tissue. In aspects, an entirety of the expandable stent frame 1102 may be made of the regenerative tissue to aid in the transfer and growth of the patient’s cells to the leaflets 1128A.

[0082] Referring to FIGS. 14 and 15, the third transcatheter heart valve prosthesis 1100 is positioned within the aortic valve 712 by attaching the third transcatheter heart valve prosthesis 1100 to the transcatheter delivery assembly 530 (FIG. 6). The third transcatheter heart valve prosthesis 1100 is inserted through the aorta 710 to the aortic valve 712. As illustrated in FIG. 14, the third transcatheter heart valve prosthesis 1100 is positioned so the distal end 1110 (inflow end) is oriented toward the left ventricle (not shown) of the heart and the proximal end 1108 (outflow end) is oriented toward the aortic arch 916. In aspects, once properly positioned, the expandable stent frame 1102 of the third transcatheter heart valve prosthesis 1100 can be sutured to the aortic valve 712. In aspects, the third transcatheter heart valve prosthesis 1100 can expand and be held in the aortic valve 712 via an outwardly directed radial force (see, FIGS. 14 and 15). In aspects, the outwardly directed radial force may be achieved via the third transcatheter heart valve prosthesis 1100 being self-expanding, ballon-expanded or mechanically-expanded. In this orientation, the third transcatheter heart valve prosthesis 1100 is positioned such that the second prosthetic valve 1120B is closer to the aortic arch 916 than the first prosthetic valve 1120A. The second prosthetic valve 1120B is configured to help maintain proper hemodynamics as the first prosthetic valve 1120 A undergoes cell population / seeding. In aspects, the second prosthetic valve 1120B is designed to not be fully competent, but to allow some regurgitation (e.g. transvalvular and / or perivalvular regurgitation). By exposing the first prosthetic valve 1120Ato the proper hemodynamics, the cells of the first prosthetic valve 1120A are able to develop in a way that makes them both flexible and strong enough for acting as a standalone valve.

[0083] In aspects, after a predetermined period of time, a stent 1510 having no leaflets may be placed in the second prosthetic valve 1120B to permanently fix the leaflets 1128B in the open position and allow free flow of blood through the second prosthetic valve 1120B. The predetermined period of time is selected to be the time sufficient for the cells of the first prosthetic valve 1120 A to develop in a way that makes them both flexible and strong enough for acting as a standalone valve, i.e., without the assistance of the second prosthetic valve 1120B. The stent 1510 does not extend in the first prosthetic valve 1120 A such that the one or more leaflets 1 128 A may control the flow of blood through the third transcatheter heart valve prosthesis 1100. In aspects, when pressure at the distal end 1110 exceeds pressure at the proximal end 1108, the leaflets 1128 A open to allow blood flow through thethird transcatheter heart valve prosthesis 1100 from the distal end 1110 to the proximal end 1108. When the pressure at the proximal end 1108 exceeds pressure at the distal end 1110, the leaflets 1128A close to prevent blood flow from the proximal end 1108 to the distal end 1110.

[0084] In the embodiment illustrated, the first prosthetic valve 1120 A and the second prosthetic valve 1120B are both secured to the expandable stent frame 1102. In another embodiment, illustrated in FIGS. 16 and 17, the third transcatheter heart valve prosthesis 1100 is replaced by the first transcatheter heart valve prosthesis 100 and the second transcatheter heart valve prosthesis 300, described in detail above. The first transcatheter heart valve prosthesis 100 is positioned in the aortic valve 712, as described in detail above and the second transcatheter heart valve prosthesis 300 is attached to the transcatheter delivery assembly 530 (FIG. 6) and positioned between the first transcatheter heart valve prosthesis 100 and the aortic arch 916. The second transcatheter heart valve prosthesis 300 is positioned so the distal end 310 (inflow end) of the second transcatheter heart valve prosthesis 300 is oriented toward proximal end 108 (outflow end) of the first transcatheter heart valve prosthesis 100 and the proximal end 308 (outflow end) second transcatheter heart valve prosthesis 300 is oriented toward the aortic arch 916. The second transcatheter heart valve prosthesis 300 is configured to help maintain proper hemodynamics as the first transcatheter heart valve prosthesis 100 undergoes cell population / seeding. In aspects, the second prosthetic valve 1120B is designed to not be fully competent, but to allow some regurgitation (e.g. transvalvular and / or perivalvular regurgitation). By exposing the first transcatheter heart valve prosthesis 100 to the proper hemodynamics, the cells of the first transcatheter heart valve prosthesis 100 are able to develop in a way that makes them both flexible and strong enough for acting as a standalone valve. In this embodiment, a gap 1602 is formed between the first transcatheter heart valve prosthesis 100 and the second transcatheter heart valve prosthesis 300 may be optimized to allow for proper functioning of the first and second transcatheter heart valve prostheses 100, 300. In aspects, the gap 1602 may be between about 0 mm and about 60 mm., while in some cases there may be a negative gap 1602 (i.e. overlap of the frames inflow and outflow ends), depending on patient anatomy.

[0085] In aspects, after a predetermined period of time, the stent 1510 having no leaflets may be placed in the second transcatheter heart valve prosthesis 300 to permanentlyfix the one or more leaflets 328 of the second transcatheter heart valve prosthesis 300 in the open position and allow the free flow of blood through the second transcatheter heart valve prosthesis 300. The predetermined period of time is selected to be the time sufficient for the cells of the one or more leaflets 128 of the first transcatheter heart valve prosthesis 100 to develop in a way that makes them both flexible and strong enough for acting as a standalone valve, i.e., without the assistance of the second transcatheter heart valve prosthesis 300. The stent 1510 does not extend in the first transcatheter heart valve prosthesis 100 such that the one or more leaflets 128 of the first transcatheter heart valve prosthesis 100 may control the flow of blood through the first transcatheter heart valve prosthesis 100 and the second transcatheter heart valve prosthesis 300. In aspects, when pressure at the distal end 110 of the first transcatheter heart valve prosthesis 100 exceeds pressure at the proximal end 108 of the first transcatheter heart valve prosthesis 100, the one or more leaflets 128 of the first transcatheter heart valve prosthesis 100 open to allow blood flow through the first and second transcatheter heart valve prostheses 100, 300. When the pressure at the proximal end 108 of the first transcatheter heart valve prosthesis 100 exceeds pressure at the distal end 110 of the first transcatheter heart valve prosthesis 100, the one or more leaflets 128 close to prevent blood flow through the first transcatheter heart valve prosthesis 100.

[0086] In another embodiment, illustrated in FIGS. 18 and 19, the first transcatheter heart valve prosthesis 100 is first positioned within the aorta 710. As described in detail above, the first transcatheter heart valve prosthesis 100 is a tissue-engineered heart valve that includes one or more leaflets 128 (FIG. 1) made from a regenerative tissue.

[0087] In aspects, the transcatheter delivery assembly 530 positions the first transcatheter heart valve prosthesis 100 in the descending aorta 814. The surgeon then deploys partially (or fully) the first transcatheter heart valve prosthesis 100 to the aorta 710. In aspects, if the first transcatheter heart valve prosthesis 100 is fully deployed in the aorta, sutures 1822 (FIG. 18) may extend through the aorta 710 and out of a vasculature of the patient at the access site, so that the patient can leave an operating room / cath lab, but still allow the first transcatheter heart valve prosthesis 100 to be re-captured in the future by using the sutures 1822 (FIG. 18) as guides. The first transcatheter heart valve prosthesis 100 stays in the descending aorta 814 for a predetermined period of time that is selected to allow the regenerative tissue to be both flexible and strong enough to function as the heart’s native valve replacement. In aspects, the predetermined time may be at least 24 hours.

[0088] In aspects, native leaflets 1813 of the aortic valve 712 remain in place and continue to function while the first transcatheter heart valve prosthesis 100 is held in place in the descending aorta 814. The native leaflets 1813, if functioning properly, maintain proper hemodynamics as the first transcatheter heart valve prosthesis 100 undergoes cell population / seeding. The predetermined period of time is determined to be the time sufficient for the cells of the first transcatheter heart valve prosthesis 100 to develop in a way that makes them both flexible and strong enough for acting as a standalone valve.

[0089] In aspects, after the predetermined period of time, the first transcatheter heart valve prosthesis 100 may be recaptured by the transcatheter delivery assembly 530 and moved to the aortic valve 712 (see arrow A in FIG. 19). In aspects where the first transcatheter heart valve prosthesis 100 was fully deployed, the surgeon may use sutures 1822 (FIG. 18) left at an access site to guide the transcatheter delivery assembly 530 to the first transcatheter heart valve prosthesis 100 in the descending aorta 814 and use the features of the transcatheter delivery assembly 530 to recapture and at least partially collapse the first transcatheter heart valve prosthesis 100. The sutures 1822 may have a first end attached to the first transcatheter heart valve prosthesis 100 and a second end extending outside of the vasculature of the patient. Once the first transcatheter heart valve prosthesis 100 is captured and at least partially collapsed, the transcatheter delivery assembly 530 may move the first transcatheter heart valve prosthesis 100 to the aortic valve 712 (see arrow Ain FIG. 19) so that the one or more leaflets 128 may replace the native leaflets 1813. The first transcatheter heart valve prosthesis 100 may be deployed / expanded in the aortic valve 712 so the first transcatheter heart valve prosthesis 100 may maintain proper hemodynamics in the aorta 710.

[0090] In accordance with the disclosure, non-limiting aspects of the disclosure will now be described. Various combinations of the aspects can be provided in accordance with the disclosure.

[0091] Example 1: A method for replacing a valve of a heart with a tissue- engineered heart valve comprising leaflets made of a regenerative tissue. The method comprising the steps of positioning a first valve comprising a frame and leaflets free of the regenerative tissue into the heart at a location spaced away from the valve of the heart; and positioning a second valve comprising a frame and leaflets comprising the regenerative tissue into the valve of the heart.

[0092] Example 2: The method of Example 1, wherein the step of positioning a first valve comprises: placing the first valve in a descending portion of an aorta of the heart.

[0093] Example 3 : The method of Example 1, wherein the step of positioning a first valve comprises: placing the first valve between the second valve and an aortic arch of the heart.

[0094] Example 4: The method of any one of Examples 1-3, wherein, the first valve is configured to allow regurgitation via paravalvular and / or transvalvular leak.

[0095] Example 5: The method of any one of Examples 1-4, wherein, after the steps of positioning a first valve and positioning a second valve, a step of: inserting a stent free of leaflets into the first valve after a predetermined period of time.

[0096] Example 6: The method of any one of Examples 1-5, wherein the step of positioning a first valve comprises: placing the first valve on a transcatheter heart valve delivery assembly; and inserting the transcatheter heart valve delivery assembly and the first valve through an aorta of the heart to the location spaced away from the valve of the heart. The valve of the heart being an aortic valve.

[0097] Example 7: The method of any one of Examples 1-6, wherein the step of positioning a second valve comprises: placing the second valve on a transcatheter heart valve delivery assembly; and inserting the transcatheter heart valve delivery assembly and the second valve through an aorta of the heart to the valve of the heart. The valve of the heart being an aortic valve.

[0098] Example 8 : The method of Example 1 , wherein the first valve and the second valve are attached to a common frame.

[0099] Example 9: The method of Example 8, wherein the steps of positioning a first valve and positioning a second valve comprises: placing the common frame on a transcatheter heart valve delivery assembly; and inserting the transcatheter heart valve delivery assembly and the common frame through an aorta of the heart to the valve of the heart. The valve of the heart being an aortic valve.

[0100] Example 10: A method for replacing a valve of a heart with a tissue- engineered heart valve comprising leaflets made of a regenerative tissue. The method comprising the steps of: positioning a transcatheter valve comprising a frame and leaflets comprising the regenerative tissue into the heart at a location spaced away from the valve of the heart; maintaining the transcatheter valve at the location spaced away from the valveof the heart for a predetermined period of time; after the predetermined period of time, recapturing the transcatheter valve from the location spaced away from the valve of the heart; and re-positioning the transcatheter valve into the valve of the heart.

[0101] Example 11 : The method of Example 9, wherein the location spaced away from to the valve of the heart is spaced away from an aortic arch of an aorta of the heart.

[0102] Example 12: The method of any one of Examples 10-11, wherein the step of positioning a transcatheter valve comprises: placing the transcatheter valve on a transcatheter heart valve delivery assembly; and inserting the transcatheter heart valve delivery assembly and the transcatheter valve through an aorta of the heart to the location spaced away from the valve of the heart. The valve of the heart being an aortic valve.

[0103] Example 13: The method of any one of Examples 10-12, wherein the step of positioning a transcatheter valve comprises: positioning a first end of a suture outside a vasculature of a patient wherein a second end of the suture is secured to the transcatheter valve.

[0104] Example 14: The method of any one of Examples 10-13, wherein the step of positioning a transcatheter valve comprises: expanding at least a portion of the transcatheter valve at the location spaced away from the valve of the heart.

[0105] Example 15: The method of Example 14, wherein the step of re-positioning the transcatheter valve into the valve of the heart comprises: re-capturing the transcatheter valve from the location spaced away from the valve of the heart; and securing the transcatheter valve to the transcatheter heart valve delivery assembly.

[0106] Example 16: The method of any one of Examples 10-15, wherein the step of re-positioning the transcatheter valve into the valve of the heart comprises: securing the transcatheter valve to a transcatheter heart valve delivery assembly and positioning the transcatheter valve into the valve of the heart.

[0107] Example 17: The method of Example 16, wherein the step of securing the transcatheter valve to a transcatheter heart valve delivery assembly comprises: guiding the transcatheter heart valve delivery assembly by a suture. The suture comprising a first end outside a vasculature of a patient and a second end secured to the transcatheter valve.

[0108] Example 18: The method of any one of Examples 10-17, wherein the predetermined period of time is at least 24 hours.

[0109] It should be understood that while various aspects have been described in detail relative to certain illustrative and specific examples thereof, the present disclosure should not be considered limited to such, as numerous modifications and combinations of the disclosed features are possible without departing from the scope of the following claims.

Claims

What is claimed is:

1. A method for replacing a valve (712) of a heart with a tissue-engineered heart valve (100, 1120A) comprising leaflets (128, 1128A) made of regenerative tissue, the method comprising the steps of: positioning a first valve (300, 1120B) comprising a frame (302, 1102) and leaflets (328, 1128B) free of the regenerative tissue into the heart at a location spaced away from the valve (712) of the heart; and positioning a second valve (100, 1120A) comprising a frame (102, 1102) and leaflets (128, 1128A) comprising the regenerative tissue into the valve (712) of the heart.

2. The method of claim 1, wherein the step of positioning a first valve (300) comprises: placing the first valve (300) in a descending portion (814) of an aorta (710) of the heart.

3. The method of claim 1, wherein the step of positioning a first valve (300) comprises: placing the first valve (300, 1120B) between the second valve (100, 1120 A) and an aortic arch (916) of the heart.

4. The method of any one of claims 1 - 3, wherein the first valve (300) is configured to allow regurgitation via paravalvular and / or transvalvular leak.

5. The method of any one of claims 1 - 4, wherein, after the steps of positioning a first valve (300, 1120B) and positioning a second valve (100, 1120A), a step of: inserting a stent (1510) free of leaflets into the first valve (300, 1120B) after a predetermined period of time.

6. The method of any one of claims 1 - 5, wherein the step of positioning a first valve (300, 1120B) comprises: placing the first valve (300, 1120B) on a transcatheter heart valve delivery assembly (530); and inserting the transcatheter heart valve delivery assembly (530) and the first valve (300, 1120B) through an aorta (710) of the heart to the location spaced away from the valve (712) of the heart, wherein the valve (712) of the heart is an aortic valve.

7. The method of any one of claims 1 - 6, wherein the step of positioning a second valve (100, 1120A) comprises: placing the second valve (100, 1120 A) on a transcatheter heart valve delivery assembly (530); and inserting the transcatheter heart valve delivery assembly (530) and the second valve (100, 1120 A) through an aorta (710) of the heart to the valve (712) of the heart, wherein the valve (712) of the heart is an aortic valve.

8. The method of claim 1, wherein the first valve (1120B) and the second valve (1120 A) are attached to a common frame (1102).

9. The method of claim 8, wherein the steps of positioning a first valve (1120B) and positioning a second valve (1120A) comprises: placing the common frame (1102) on a transcatheter heart valve delivery assembly (530); and inserting the transcatheter heart valve delivery assembly (530) and the common frame (1102) through an aorta (710) of the heart to the valve (712) of the heart, wherein the valve (712) of the heart is an aortic valve.

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