Mechanism for sealing and fixing irregular tissue within the body and method for sealing and fixing the same

Abstract

The present disclosure relates to a support structure for receiving an artificial valve intended to replace a valve, an artificial valve system, a method for sealing between natural tissue and an artificial implant, a kit for implanting an artificial valve, and a medium for use with the support structure. The technique provides the implant structure with high compatibility with various biological structures and allows optimal sealing and tissue fixation, thus realizing a personalized valve replacement procedure. The technique provides a precise fit for optimal sealing and fixation of various complex biological structures requiring prostheses.

Description

[Technical field]

[0001] FIELD OF THE DISCLOSURE The present disclosure relates to the field of sealing and fixation mechanisms for irregular tissue within the body and methods for sealing and fixation of irregular anatomical structures. [Background technology]

[0002] Although complex anatomical structures have many functional benefits, when disease processes create the need to repair or replace such structures, the complexity can make it extremely difficult to develop a suitable prosthesis. A good example of such a highly complex structure is the two atrioventricular heart valves, the mitral and tricuspid, both of which have variable contours and boundaries. In addition to being asymmetrical and saddle-like in shape, there is known to be a large degree of patient-to-patient variability regarding the valve structure and its three-dimensional configuration. Current approaches for mitral valve replacement include the surgical replacement of a universally shaped, pre-shaped, and pre-sized valve implant. Transcatheter devices are also based on a universal, prefixed structure and size. Summary of the Invention

[0003] To overcome the variability associated with the above, there is a need in the art to provide an implant structure that conforms to various anatomies to provide optimal sealing and tissue fixation while minimizing damage to tissue and adjacent anatomical structures. The techniques of the presently claimed subject matter provide precise placement with optimal sealing and fixation for complex anatomical sites requiring prosthetic devices, such as the mitral valve. More specifically, the techniques of the presently claimed subject matter provide a mechanism for real-time sealing and fixation of irregular anatomical structures.

[0004] According to a first aspect of the present disclosure, a support structure is provided for receiving a prosthetic valve intended to replace mitral and / or tricuspid valves, and / or semilunar valves such as aortic and pulmonary valves. The support structure may be configured as a mediator / spacer / adapter / docking station between the valve annulus anatomy and generic (i.e., round, symmetrical, commercially available) biological and / or synthetic valves, and may accommodate itself to the patient's valve anatomy by shaping the flexible material in real time (i.e., during valve replacement). The support structure may shape to the annulus anatomy, creating a flexible dynamic structure compatible with a variety of valve anatomy.

[0005] In some embodiments, the support structure can receive artificial valve leaflets, thus creating a fully functional valve. The support structure comprises a flexible retention element that defines an open cavity and can receive a plurality of shapeable elements, and a plurality of expandable reinforcing elements, whereby the plurality of shapeable elements and the plurality of expandable reinforcing elements are fully enclosed within the flexible retention element, thereby creating a highly compressible flexible dynamic support structure. The flexible retention element may be made of a material that is elastic to the extent that it can expand primarily radially when filled with the plurality of shapeable elements. In this context, it should be noted that the term "flexible material" refers to an elastic-plastic material that is specifically configured to have elastic physical properties and a deformation range with thermoplasticity, as well as a deformation range with plastic physical properties. The term "flexible structure" refers to the mechanical properties of the entire structure that are configured to be adaptable to any physical biological structure, as well as the ability to bend or flex easily without breaking. The flexibility may be variable across different parts of the flexible retention element, as well as across the entire flexible and dynamic structure. For example, the flexible retaining element may be divided into three parts, each with a different flexibility. The term "compressible structure" refers to the mechanical properties of the entire structure configured to be compressed (i.e., folded) to reduce size and / or volume. The multiple expandable reinforcing elements provide stability to the entire structure over time. The multiple shapeable elements may be configured as one independent whole unit with multiple sections connected one section to the other, or as several separate units.

[0006] As mentioned above, the subject matter disclosed herein relates to minimally invasive transcatheter replacement of valves such as mitral and / or tricuspid valves, and / or semilunar valves such as aortic and / or pulmonary valves. The support structure of the subject matter disclosed herein can be deployed onto the native mitral valve via a transapical or transseptal approach. However, the techniques disclosed herein are not limited to replacing the mitral and / or tricuspid valves, but may also be used to treat any other leaking or stenosed heart valves, such as semilunar valves, closure and sealing of congenital heart defects such as atrial or ventricular septal defects or patent ductus arteriosus, or any other arteriovenous fistula or shunt, as well as optimal left atrial appendage sealing and closure. Furthermore, the sealing and fixation techniques of the subject matter claimed herein may be applicable to optimal tissue attachment in ablation procedures of complex tortuous anatomical structures such as the atria, pulmonary veins, and renal arteries. In addition, this concept may be applicable to orthopedic implants, plastic surgery, neurosurgery, soft tissue surgery, and the like. Further applications for the concept of in situ patient-specific prosthetic attachment and sealing may also be applied.

[0007] The subject matter disclosed in this application includes a folded symmetric or asymmetric support structure. Once the support structure is unfolded and its proper position is confirmed via suitable imaging modalities such as fluoroscopy and / or echocardiography, the support structure is filled in situ with an optimal biocompatible material according to the patient's anatomy, including at least one of a suitable material in gas form (such as helium, carbon dioxide, or other), a suitable material in liquid form (such as saline, water for injection, liquid polymeric compound with possible hardening such as reverse thermal gel, hydrogel, medical grade silicone, or other fluid), or any other suitable material (such as any kind of biological matrix, hyperosmolar granules, etc.) that maintains flexibility and allows movement in harmony with the cardiac cycle. More specifically, the flexible retaining element can be shaped in situ.

[0008] In some embodiments, the flexible retaining element has an outer surface with a rough texture that allows the support structure to self-anchor to native tissue. The outer surface may define any possible pattern, such as a mesh-like pattern, a dot-like pattern, or a grid-like pattern. The outer surface may be made of a material that promotes rapid endothelial growth. The flexible retaining element may have an inner surface that interfaces with an open cavity, made of a material that allows smooth, linear blood flow and prevents thrombus formation and turbulence. The flexible retaining element may comprise at least one non-thrombogenic fabric mesh portion.

[0009] In some embodiments, each of the multiple shapeable elements is configured to be adjustable in size and shape in situ to self-fixate and seal the support structure to native tissue. Each of the at least one shapeable element can be filled separately or simultaneously in situ with at least one filling material that allows optimal sealing and tissue fixation to the mitral and / or tricuspid and / or semilunar valves while remaining flexible and allowing movement with the cardiac cycle. The filling material may have inherent flexibility properties that allow eccentric widening and expansion during in situ filling according to the patient's anatomy. The at least one filling material may include at least one fluid in the form of at least one gas, liquid, gel, powder, granules, or any combination thereof.

[0010] In some embodiments, the multiple expandable reinforcing elements are configured and operable to self-fixate and stabilize the support structure. Some of the expandable reinforcing elements may be positioned on or above the shapeable elements, which causes each shapeable element to expand radially. One of the reinforcing elements may define a fixed inner dimension of the open cavity and is configured and operable to maintain stability at the annulus level. In this regard, it should be noted that the reinforcing elements maintain the device at a fixed radius only at the waist (annulus level). The fabric and the shapeable elements allow mainly outward expansion at the atrial and ventricular levels, but also inward expansion. Thus, the inward expansion may contribute to the seal between the biological valve and the device at these levels that are more prevalent for leakage. Moreover, this inward expansion does not distort the biological valve (because the expansion is due to the shapeable elements, which are configured to conform to the structures that come into contact and are not aggressive in nature).

[0011] At least some of the plurality of expandable reinforcing elements may have the same or different physical properties, including at least one of shape or diameter.

[0012] In some embodiments, at least the shapeable element and the plurality of reinforcing elements each have a configuration that conforms to the patient's anatomy to provide at least a 270 degree seal between the support structure and the natural tissue.

[0013] In some embodiments, at least the shapeable element and the plurality of reinforcing elements each have a closed loop configuration that conforms to the patient's anatomy and provides a substantially 360 degree seal between the support structure and the natural tissue.

[0014] According to another broad aspect of the invention, there is provided a prosthetic valve system comprising a support structure as defined above and a plurality of prosthetic leaflets coupled to the support structure, the plurality of prosthetic leaflets being configured and operable as a one-way valve.

[0015] In some embodiments, the plurality of prosthetic leaflets are pre-fixed and pre-attached to the support structure, or alternatively, the plurality of prosthetic leaflets are integral to the support structure.

[0016] According to another broad aspect of the invention, there is provided a method of sealing between a native tissue and an artificial implant, the method comprising: advancing and deploying a flexible folded support structure having a plurality of shapeable elements onto a native mitral and / or tricuspid and / or semilunar valve via a transapical or transseptal procedure, filling at least one shapeable element of the flexible support structure with a filling material in situ, expanding an outer surface of the flexible support structure, and creating a seal between the native mitral and / or tricuspid and / or semilunar valve and the flexible support structure by forming a final contour of the flexible support structure according to a patient's anatomy.

[0017] In some embodiments, filling at least one shapeable element of a flexible support structure in situ with a filling material comprises filling a plurality of shapeable elements in situ, either separately or simultaneously.

[0018] In some embodiments, the method further comprises self-fixating the support structure to the native tissue.

[0019] According to another broad aspect of the invention, there is provided a kit for implanting a prosthetic valve comprising: a container capable of providing a sterile barrier; a sterile catheter received within the container, the sterile catheter having a distal end and a proximal end; and a sterile prosthetic valve received within the container removably coupled to the distal end of the sterile catheter, the sterile prosthetic valve including a plurality of prosthetic valve leaflets coupled with a flexible folded support structure as defined above, and a filling material capable of filling the flexible folded support structure and deploying the sterile prosthetic valve onto a native mitral and / or tricuspid and / or semilunar valve.

[0020] In some embodiments, the kit further comprises an injection device coupled to the flexible folded support structure, the injection device being used to inject the material used for filling and the flexible support structure according to the patient's anatomy.

[0021] In some embodiments, the injection device comprises a multi-lumen delivery structure having multiple lumens, one lumen of the multi-lumen structure configured to inject the filling material, the lumen comprising at least one injection port connected to at least one shapeable element of the flexible folded support structure.

[0022] In some embodiments, at least one injection port is configured as a one-way port that can be closed.

[0023] In some embodiments, the flexible folded support structure can be pre-filled with at least a portion of the filling material.

[0024] In some embodiments, the filling material comprises a hyperosmotic drug capable of expanding within the flexible, folded support structure upon exposure to liquid.

[0025] In some embodiments, the sterile prosthetic valve comprises a plurality of prefixed prosthetic leaflets configured as a combined permanent valve, the plurality of prefixed prosthetic leaflets being received within a flexible folded support structure.

[0026] In some embodiments, the plurality of prosthetic leaflets are pre-fixed and pre-attached to the flexible folded support structure, or alternatively, the plurality of prosthetic leaflets are integrated into the flexible folded support structure.

[0027] According to another broad aspect of the invention, there is provided a medium for use with a support structure to receive a prosthetic valve, the medium having an outer surface made with a rough texture that allows the support structure to self-anchor to native tissue, and an opposing inner surface made of a material that allows smooth, linear blood flow while preventing clot formation and turbulent flow through the valve.

[0028] In some embodiments, the opposing interior surface defines an open cavity.

[0029] In some embodiments, the exterior surface defines a mesh-like pattern, a dot-like pattern, or a grid-like pattern.

[0030] In some embodiments, the exterior surface is made of a material that promotes rapid endothelial growth.

[0031] In some embodiments, the medium is made of an elastic material that allows for primarily radial expansion of the support structure as it is shaped. The medium (i.e., fabric) can be configured to mostly allow expansion toward the native annulus.

[0032] In order to better understand the subject matter disclosed herein and to illustrate how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, and with reference to the accompanying screen images. [Brief description of the drawings]

[0033] [Figure 1] FIG. 1 is a schematic perspective view illustrating a possible configuration of a deployed support structure according to some embodiments of the presently disclosed subject matter. [Diagram 2] 2A-2C are top views illustrating different possible configurations of one shapeable element of an unfolded support structure according to some embodiments of the presently disclosed subject matter, and FIGs. 2D-2F are isometric views illustrating different possible configurations of an unfolded support structure according to some embodiments of the presently disclosed subject matter. [Diagram 3]3A-3D are schematic interior elevational views illustrating different possible configurations of the interior elements of a deployed support structure according to some embodiments of the presently disclosed subject matter. [Figure 4] 4A-4D are schematic cross-sectional views illustrating different possible configurations of a deployed support structure according to some embodiments of the presently disclosed subject matter. [Diagram 5] 5A-5D are side views showing possible configurations of media that may be used with a support structure to receive an artificial valve according to some embodiments of the subject matter disclosed herein, and FIGS. 5A1-5D1 are enlarged views of the media of FIGS. 5A-5D. [Figure 6] Figure 6A is an atrioventricular perspective view showing a possible configuration of a deployed support structure in a mitral valve according to some embodiments of the presently disclosed subject matter. Figures 6B-6D are atrial perspective views showing a mitral valve (Figure 6B), atrial perspective views showing a possible configuration of a deployed pre-shaped support structure in a mitral valve (Figure 6C), and atrial perspective views showing a possible configuration of a deployed pre-shaped support structure in a mitral valve (Figure 6D), according to some embodiments of the presently disclosed subject matter. Figures 6E-6F are atrial perspective views showing a possible configuration of a deployed pre-shaped support structure in a tricuspid valve (Figure 6E), and a possible configuration of a deployed pre-shaped support structure in a tricuspid valve (Figure 6F), according to some embodiments of the presently disclosed subject matter. [Figure 7] 7A-7D are various schematic diagrams illustrating possible configurations of a prosthetic valve system according to some embodiments of the presently disclosed subject matter. [Figure 8] FIG. 8 is a block diagram illustrating the main steps of a method for sealing between natural tissue and an artificial implant according to some embodiments of the presently disclosed subject matter. [Figure 9] FIG. 9 is a block diagram illustrating a kit for implanting a prosthetic valve, according to some embodiments of the presently disclosed subject matter. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] Reference is made to FIG. 1, which shows a schematic of a deployed anchoring and sealing support structure 100 for receiving a prosthetic valve according to broad embodiments disclosed herein. The support structure 100 comprises a flexible retention element 102 that defines an open cavity and can receive a plurality of shapeable elements 104 and a plurality of expandable reinforcing elements 106, whereby the plurality of shapeable elements 104 and the plurality of expandable reinforcing elements 106 are fully enclosed within the flexible retention element 102, thereby creating a highly compressible flexible dynamic support structure. In a specific non-limiting example, the support structure 100 may be configured as a folded symmetric or asymmetric hourglass structure. The flexible retention element 102 is configured and operable to connect and hold together the elements of the support structure, thereby creating a highly compressible flexible dynamic structure. The flexible dynamic structure can be adjusted to accommodate myocardial twisting and tissue repair as needed (e.g., the dynamic structure remains flexible and thus adapts to changes in anatomy after a procedure). The flexible retaining element 102 may be configured as an annular casing (i.e., a ring-shaped flexible casing) and may be made of a biocompatible and non-thrombogenic fabric with a mesh-like pattern. Each of the at least one shapeable element 104 is configured to be in situ adjustable in size and shape to self-fixate and seal the support structure to the native tissue. In particular, the plurality of shapeable elements 104 are configured for perivalvular leak prevention and real-time shaping of the support structure frame according to the patient's anatomy. More specifically, the plurality of shapeable elements 104 are configured as an expandable sleeve that can be filled and shaped in situ with any suitable filling material that is biologically safe, inert, durable, and non-thrombogenic, so that no harm occurs in the event of leakage. The filling material or a portion thereof may be present in the folded support structure prior to insertion. The filling process uses the patient's tissue as a mold for the final shaping of the support structure, shaping the support structure 100 according to the patient's specific anatomy and acting as a personalized, precise sealing mechanism to minimize paravalvular leakage.During filling of the shapeable elements 104, the outer diameter of each shapeable element 104 increases, forming its final outer shape in situ according to the native valve anatomy. The filling material defines an inherent flexibility that allows eccentric widening and expansion during in situ filling controlled by the operator. This allows the support structure outer wall to be precisely shaped according to the patient's valve anatomy, creating a maximum seal between the native valve and the support structure, minimizing paravalvular leakage while minimizing damage to adjacent anatomical structures. The multiple expandable reinforcing elements 106 are wrapped around / embedded with the flexible retaining element 102, and are intended to stabilize the support structure 100 over irregular tubular structures (e.g., mitral valve) and act as a scaffold. The multiple expandable reinforcing elements 106 maintain a fixed inner dimension of the support structure 100, thus avoiding the valve space from being compromised. The shapeable elements 104 can expand anteriorly (e.g., toward the septum) and posteriorly (e.g., toward the free wall) to engulf the native annulus on both its atrial and ventricular sides while avoiding expansion at the expense of the atrial and / or ventricular cavities or walls (particularly to avoid left ventricular outflow tract obstruction). The multiple expandable reinforcing elements 106 may be made of Nitinol (or any other compatible material). The multiple expandable reinforcing elements 106 generate annular waists 108 for stabilizing the flexible dynamic structure. The structural properties of the support structure 100 allow the waists 108 to be formed to fixate and engulf the native annulus on all sides.

[0035] In some embodiments, the inner diameter wall of the support structure is stiffer than the walls directly in contact with the anterior-lateral and posteromedial of the valve, allowing expansion only in the anterior-lateral-postomedial direction to promote waist formation and maximal sealing. The inner diameter wall of the support structure may be stiffer and more durable against filling pressures, allowing for a fixed inner diameter, thus avoiding concentric expansion and loss of lumen volume on either side of the annulus. Additional Nitinol (or any other suitable material) support may be added to the support structure inner wall for further reinforcement.

[0036] Please refer to Figures 2A-2C, which show top views of different possible configurations of one shapeable element of an unfolded support structure according to some embodiments of the presently disclosed subject matter. As mentioned above, the shapeable element is a closed loop element that is not limited to any particular geometric configuration. The shapeable element may have various shapes, sizes, or widths. Each shapeable element of the plurality of shapeable elements may be different or identical to each other. The shapeable element may have an asymmetric shape.

[0037] In some cases, irregular anatomical structures are located near critical anatomical structures (i.e., the left ventricular outflow tract posterior to the mitral valve), thus highlighting the importance of leaving these structures intact. For this reason, the shapeable element of the presently disclosed subject matter may only allow radial expansion in a specific vector while avoiding delicate structures. As shown in the non-limiting example of FIG. 2A, the shapeable element may have an asymmetric shape including a circular portion and an elliptical portion (D-shape). Alternatively, as shown in the non-limiting example of FIG. 2B, the shape of the shapeable element may define a bulge that bends the circular / elliptical portion outward. The configuration shown in FIG. 2C, in which the shapeable element has a symmetric shape including an elliptical portion and a bulge portion, may provide a 270-degree seal by allowing the posterior portion of the shapeable material to be semi-rigid, thus disabling the flexible material from expanding in this specific vector. This 270 degree sealing of the shapeable elements facilitates an optimal sealing effect between the structure and the natural tissue while avoiding contact with and / or damage to adjacent anatomical structures.

[0038] Reference is made to Figures 2D-2F, which show isometric views of possible configurations of the deployed support structure according to some embodiments of the presently disclosed subject matter. More specifically, an outline view of the entire deployed support structure is shown in Figure 2D. A cross-sectional view of the deployed support structure is shown in Figure 2E, showing a cross-sectional view of the inner element, the shapeable element, and the expandable stiffening element surrounded by the flexible retention element. Figure 2F shows an outline view of the entire deployed support structure including the shapeable element and the expandable stiffening element but not the flexible retention element.

[0039] Please refer to FIGS. 3A-3D, which show internal front views of possible configurations of different elements in deployed support structures 200A-200D according to some embodiments of the present disclosure. The plurality of expandable reinforcing elements 206A, 206A', 206B, 206B', 206C, and 206C' and the shapeable elements 204A and 204B are wrapped / embedded with the flexible retention element 202. In a specific non-limiting example, the plurality of expandable reinforcing elements 206A, 206B, and 206C may each have a semi-open or closed loop configuration that provides stability to the annulus. As shown in FIGS. 3A-3D, the plurality of expandable reinforcing elements 206A, 206A', 206B, 206B', 206C, and 206C' may have different or same shapes and / or diameters and / or widths. In this specific non-limiting example, the plurality of expandable reinforcing elements 206A, 206B, and 206C may be configured as three flexible closed loop or semi-open circular elements 206A, 206B, and 206C (i.e., atrium, annulus, and ventricle) made of any rigid and flexible material, such as Nitinol. In this specific non-limiting example, the closed loop or semi-open circular elements may have a stent-like pattern as shown in 206A, 206C, or a sinusoidal pattern as shown in 206A', 206B, 206C', allowing for flexibility and conformability. In this manner, the plurality of expandable reinforcing elements 206A, 206A', 206B, 206B', 206C, and 206C' may expand their diameter (e.g., with a stent-like or sinusoidal pattern) in response to radial forces exerted by the opening of the biological valve, allowing for stability on the one hand, and relative flexibility on the other.

[0040] In a specific, non-limiting example, the atrial ring 206A or 206A' is positioned above the shapeable element 204A, allowing it to compress toward the annulus during expansion, thus reducing the overall expansion and promoting radial expansion toward the peripheral border of the valve at the atrial level. The ventricular ring 206C or 206C' is positioned below the shapeable element 204B, allowing it to compress toward the annulus during expansion, thus reducing the overall expansion and promoting radial expansion toward the peripheral border of the valve at the ventricular level. Thus, in this example, the atrial ring 206A or 206A' and the ventricular ring 206C or 206C' are configured to radially expand each shapeable element 204A and 204B. The annular ring / waist 206B or 206B' is positioned between the two shapeable elements 204A and 204B and may comprise one or more elements. The plurality of shapeable elements 204A and 204B may be configured as two expandable fabric sleeves that are received on the distal ends of the support structures 200A-200D (e.g., at the atrial and ventricular levels), respectively. The two expandable fabric sleeves 204A and 204B may include any flexible material or flexible filling material, such as physiological liquids, gases, reverse thermal gels, hydrogels, highly permeable granules, medical grade silicone, liquid polymers, etc., that change physical state in response to different chemical reactions, such as UV light, reactions with additional liquid or non-liquid polymers, temperature, etc. However, the present disclosure is not limited to any use of a particular filling material.

[0041] 4A-4D, which show cross-sectional views of different possible configurations of support structures 400A-400D according to some embodiments of the presently disclosed subject matter, showing flexible retention elements 402 covering a plurality of expandable reinforcement elements 406A, 406A', 406B, 406B', 406C', and 406C and a plurality of shapeable elements 404A and 404B on one side, and covering an exposed plurality of expandable reinforcement elements 406A, 406A', 406B, 406B', 406C', and 406C and a plurality of shapeable elements 404A and 404B on the other side. The plurality of expandable reinforcing elements 406A, 406A', 406B, 406B', 406C', and 406C may be configured as scaffolds and / or may have exposed sharp edges designed to be anchored within the atrium, ventricle, or within the surrounding tissue on both sides of the valve for better tissue self-anchor and positional stability. The plurality of shapeable elements 404A and 404B and the flexible retaining element 402 may have the same characteristics as described above.

[0042] According to another broad aspect of the present disclosure, a medium is provided for use with a support structure that receives a prosthetic valve. The medium may be used with a support structure as described above or with any other commercially available support structure and / or prosthetic valve. The inventors have found that by using a medium having an outer surface made with a rough texture and an opposing inner surface made of a material that allows smooth and linear blood flow, the support structure can be self-fixed to the native tissue and thrombus formation and turbulent flow through the valve can be prevented. A flexible retaining element defines the outer wall of the support structure and may have an outer surface with a rough texture for significant friction that self-fixes the support structure to the native tissue and allows rapid epithelialization. This trait may be applied to generate microscopic damage to the annular semi-fibrous tissue, thereby further promoting rapid epithelialization. In particular, the outer surface / external surface of the medium that comes into contact with the native tissue may be made of and constructed in such a way that it is made of a mesh material composed of a material that promotes rapid endothelial growth and reduces or prevents residual leakage, such as a plurality of knitted interconnected loops, particularly interlocked knitted or woven fabrics, or any combination thereof. The knitted mesh may further comprise a tubular wall that substantially surrounds the outer surface of the flexible structure. The knitted or woven mesh may be made using any commercially available technique, such as braiding, interlacing, electrospinning, and / or dipping a porous mold into one or more reagents. The mesh may be single or multi-layered, with each layer having (or not having) a different texture and / or structure. For example, at least a portion of the knitted / woven / braided / electrospun mesh is based on a single fiber that may comprise multiple filaments. At least a portion of the mesh may be composed of an elastomeric material, such as polyurethane fibers, that may be mixed with additional materials for strength, durability, elasticity, antibacterial properties, and the like. Additionally, in a specific non-limiting example, the mesh material may be coated with a cell attachment promoting material by attaching it to a plasma polymer via amine and / or hydroxy group bonds. The inner surface opposite the medium may define an open cavity.

[0043] Reference is made to FIGS. 5A-5D, which show perspective views of possible configurations of media 500A-500D according to some embodiments of the subject matter disclosed herein. FIGS. 5A1-5D1 are enlarged portions of the outer surfaces of media 500A-500D, respectively. Media 500A-500D may be made of the same or different fabric portions, each portion may surround a different portion of the support structure. As shown in the figures, media 500A-500D may be configured as a mesh fabric lining as shown in FIG. 5D1. However, media 500A-500D are not limited to such configurations. Additionally or alternatively, the outer surfaces of media 500A-500D may define various fiber pattern arrangements (e.g., on different axes) configured to promote rapid endothelial growth and reduce or prevent residual leakage. For example, the fiber pattern arrangement may include a grid-like pattern 502A as shown in FIG. 5A1, a coarse-grained pattern 502B as shown in FIG. 5B1, a dot-like pattern 502C as shown in FIG. 5C1, or a mesh-like pattern 502D as shown in FIG. 5D1.

[0044] When the medium 502 is used with the support structure of the subject matter disclosed herein, the medium 502 may be made of at least one material with a certain elasticity, such as polyurethane, spider silk, etc., that allows for mainly radial expansion when modifying the shapeable element 500 within the flexible retention element 500 (e.g., a mesh material sleeve) in such a way that the filling material does not expand at the expense of the atrium or ventricle (proximal or distal to the annulus). As mentioned above, the filling material may include at least one fluid in the form of at least one gas, liquid, gel, powder, granules, or any combination thereof. The filling material may have inherent flexible properties, stability over a long period of time (at least 10 years), and should be biocompatible and non-thrombogenic, such as a hydrogel.

[0045] Please refer to FIG. 6A, which shows an atrioventricular perspective view of a possible configuration of the deployed support structure 1 according to some embodiments of the present disclosure. The expandable reinforcing elements and the shapeable elements are not shown in this view. This view shows the functional positioning of the deployed support structure 1 within the mitral valve. As mentioned above, the support structure of the presently disclosed subject matter may be used with any type of separate prosthetic or biological valve that is received in the open cavity defined by the support structure. The support structure thus acts as a custom annular waist that ultimately seals and self-anchores the prosthetic or bioprosthetic device to the native tissue.

[0046] Reference is made to Figures 6B-6D, which illustrate the step-by-step shaping process of the deployed support structure 1 within the mitral valve, as described in further detail below in connection with Figure 8. More specifically, Figure 6B illustrates an atrial view of the mitral valve, and Figure 6C illustrates the pre-shaped support structure 1 deployed within the mitral valve after deployment (before shaping). Figure 6D illustrates the deployed support structure 1 after shaping within the mitral valve, illustrating the sealing mechanism and fixation against the irregular anatomy of the mitral valve in real time. It is shown in the figures that it is possible to provide a sufficient and optimal seal between the deployed support structure 1 and the mitral valve.

[0047] Please refer to FIG. 6E-6F, which shows the step-by-step shaping process of the deployed support structure 1 in the tricuspid valve. More specifically, FIG. 6E shows the pre-shaped support structure 1 deployed in the tricuspid valve after deployment (before shaping). FIG. 6F shows the deployed support structure 1 after shaping in the tricuspid valve, showing the sealing mechanism and fixation to the irregular anatomy of the tricuspid valve in real time. The unique configuration of the deployed support structure 1 allows for sufficient and optimal sealing and tissue fixation to the mitral and tricuspid valves, as shown in the figures, with multiple shapeable elements each adjustable in situ in size and shape to self-fixate and seal the support structure to the native tissue. The support structure 1 of the presently disclosed subject matter is capable of fitting to any irregular anatomy as shown in these two non-limiting examples.

[0048] Please refer to FIGS. 7A-7D, which show different views of possible configurations of a prosthetic valve system 800 according to some embodiments of the present disclosure. FIG. 7A shows a perspective view of a prosthetic valve system 800 in which leaflets 802 are combined with a support structure 804 of the presently disclosed subject matter to provide an integrated prosthetic valve system 800. FIGS. 7B-7D show side, top, and cross-sectional views thereof, respectively. The leaflets 802 may be any commercially available leaflets, which upon deployment and shaping can immediately function as a permanent valve combined with the support structure 804. The leaflets 802 may be hidden within the support structure 804 prior to deployment. The leaflets 802 may be configured as implanted biological (or any other material, such as printed biomatrix, biologically inert polymer, etc.) leaflets. This configuration can provide a prosthetic valve system 800 that is an independent, stand-alone, fully functional prosthetic valve upon deployment and shaping within the valve space.

[0049] The leaflets may be configured as follows: (i) The leaflets may be pre-fixed / pre-attached to a support structure or may be ready to use when deployed. Permeable bovine / porcine pericardial (or other) tissue may be used for the leaflets as shown in Figures 7A-7D. (ii) The leaflets may be configured as integrated biological leaflets made from a biological (or other) matrix. (iii) Commercially available biological valve leaflets may be integrated into the system using the support structures as sealing and fixation lumen.

[0050] According to another broad aspect, the subject matter disclosed herein relates to a kit for implanting a prosthetic valve. The kit includes a container capable of providing a sterile barrier, a sterile catheter received in the container, the sterile catheter having a distal end and a proximal end, a sterile prosthetic valve received in the container removably coupled to the distal end of the sterile catheter, the sterile prosthetic valve including a plurality of prosthetic leaflets coupled to a flexible folded support structure, and a shaping / filling material capable of modifying and shaping the flexible folded support structure. When shaping the support structure onto the mitral and / or tricuspid and / or semilunar valve, the sterile prosthetic valve can be delivered and deployed into the inner rim of the support structure. Positioned and sealed between the mitral annulus, the support structure and the prosthetic valve can then be viewed by different imaging modalities. The kit may include an injection device removably coupled to the flexible folded support structure. The injection device may include a multi-lumen delivery structure having multiple lumens, one lumen of the multi-lumen structure configured to inject the filling material. The lumen comprises at least one injection port connected to at least one shapeable element of the flexible folded support structure. The shaping material may thus be advanced through the injection port of the injection device to reach directly into the support structure (including at least one injection port) and injected in a homogenous form. Once the unfolding and correct shaping is completed and maximal sealing is confirmed by transesophageal echocardiography (TEE) and fluoroscopy, the injection device may be separated and the port is sealed to prevent leakage. For example, the injection port may be configured as a one-way port influenced by an increase in hydraulic pressure in the support structure (or by any other closing and sealing mechanism that controls leakage of the shaping material). Alternatively, the support structure may be pre-filled with a hyperosmolar drug that expands in the support structure when exposed to any type of liquid. If a liquid polymer or gelatinous material is used as the filling material, the injection of the filling material may be in the form of a non-permeable closed capsule that is pierced and injected only in the vicinity of the support structure to reduce wear and clogging of the system.Alternatively, the support structure may be pre-loaded with a hyperosmotic drug that expands within the support structure upon exposure to any type of liquid.

[0051] The kit dimensions can be adapted according to the particular approach (transapical, transseptal, etc.) Other approaches may also be applied according to the location of the particular valve or anatomy.

[0052] According to another broad aspect of the present disclosure, a method is provided for in situ formation of custom (i.e., patient-specific) novel sealing and fixation mechanisms for implanting prosthetic devices into complex or irregular anatomical structures (such as heart valves), allowing precise shaping / fitting of the outer support structure wall according to the patient's own valvular (or other) anatomy, creating a seal between the native tissue and the support structure and minimizing paravalvular leakage, in real time under imaging.

[0053] Please refer to FIG. 8, which shows a flow chart illustrating the main steps of a method 600 for sealing between a native tissue and an artificial implant. The method 600 includes, at 602, advancing and deploying a flexible folded support structure having multiple shapeable elements (with or without leaflets) onto the native mitral and / or tricuspid and / or semilunar valves via a transapical or transseptal approach. The folded support structure of the presently disclosed subject matter is folded into a catheter in a compressed form under vacuum. The support structure may comprise multiple shapeable elements that are configured to be filled in situ separately or simultaneously to enable optimal sealing and tissue fixation onto the mitral and / or tricuspid and / or semilunar valves.

[0054] The following are non-limiting examples of specific procedures in which the deployment of the support structure is staged, where the shapeable elements are deployed in sequential steps rather than the entire support structure being deployed at once: A femoral vein puncture is performed and an introducer sheath is inserted into the vein. Under fluoroscopy and / or transesophageal echocardiography (TEE) guidance, a transseptal puncture is performed to allow access to the left atrium of the heart from the groin. A stiff wire may then be inserted through the native mitral valve (MV) into the left ventricular (LV) apex. The transseptal puncture (TSP) kit may then be withdrawn and the support structure delivery structure may be inserted over the wire into the LV apex. Once positioned at the LV apex, only the distal shapeable element may be exposed and then (partially crimped) withdrawn towards the MV. The distal shapeable element may then be deployed and the support structure may then be withdrawn further towards the annulus, with the annular waist also exposed at the MV annulus level. At this stage, stability may be tested. Once confirmed, the proximal shapeable element is deployed. At least one shapeable element is then shaped in situ at 604 with a filling material to increase the outer surface of the flexible support structure and form a final outer shape according to the patient's anatomy, also creating a seal between the native valve and the flexible support structure. More specifically, once the support structure is stabilized and properly positioned under imaging modalities (TEE and / or fluoroscopy), the shaping material increases in volume by injection / chemical reaction of a fluid medium. At this stage, the shapeable element reaches an optimal expansion point (controlled by the operator and may be reversible) where it interacts with the native anatomy of the MV annulus and achieves an adaptive seal.

[0055] In some embodiments, the method 600 may include releasing a plurality of pre-fixed prosthetic leaflets received within a flexible folded support structure in shaping 606A. The leaflets are configured as permanent valves. Alternatively, the method 600 may include deploying a replacement valve in 606B. In this way, transcatheter implantation of a commercially available prosthetic valve with a precise and patient-specific sealing mechanism is enabled. This is achieved by final shaping the support structure in situ with the support structure already in place, using the patient's unique anatomy as a mold. Retrieval of the support structure delivery structure and insertion of the prosthetic valve may be achieved using the same guidewire used to deliver and deploy the support structure. The prosthetic valve may be positioned with reference to the support structure waist to assess the exact location. Once the prosthetic valve position is confirmed under imaging modalities, the prosthetic valve is deployed and tested for stability, sealing, and functionality (i.e., paravalvular leakage between the support structure and the prosthetic valve, high gradients, left ventricular outflow tract obstruction (LVOTO), leaflet coaptation).

[0056] In some embodiments, the method 600 may include coupling the flexible folded support structure to a delivery system (i.e., injection device) at 608A prior to advancing and deploying the flexible folded support structure at 602, and decoupling the flexible folded support structure from the delivery system (i.e., injection device) at the end of the procedure at 608B. Final steps of the procedure include retrieval of the prosthetic valve delivery system, retrieval of the GW, and femoral vein closure.

[0057] Please refer to FIG. 9, which shows a block diagram illustrating the main functional elements of a kit 700 for implanting a prosthetic valve. The kit 700 includes a container 702 capable of providing a sterile barrier, a sterile catheter 704 received within the container 702, and a sterile prosthetic valve 706 received within the container 702 removably coupled to the distal end of the sterile catheter. The sterile prosthetic valve 706 includes a plurality of prosthetic leaflets coupled with a flexible folded support structure as described above. The plurality of prosthetic leaflets may be received within the flexible folded support structure or may be configured as pre-fixed prosthetic leaflets that function as a permanent valve. The plurality of prosthetic leaflets may be pre-fixed and attached to the flexible folded support structure. Alternatively, the plurality of prosthetic leaflets may be integrated into the flexible folded support structure. The shaping material 708 may have inherent flexibility properties, stability, and durability over long periods of time (at least 10 years), and should be biocompatible and non-thrombogenic. The shaping material 708 may include a hyperosmotic drug that can expand within the flexible folded support structure upon exposure to liquid. The flexible folded support structure may be pre-loaded with at least a portion of the shaping material 708. In some embodiments, the kit 700 further includes an injection device 710 that is removably coupled to the flexible folded support structure. The injection device 710 can fill and shape the flexible support structure according to the patient's anatomy. Optionally, the injection device 710 may also be capable of precisely deploying the flexible folded support structure at a specific location. The injection device 710 may include a multi-lumen delivery structure 712 having multiple lumens, one lumen of the multi-lumen structure configured to inject the filling material. The lumen includes at least one injection port that is connected to at least one shapeable element of the flexible folded support structure. The injection port may be configured as a one-way port that can be closed (e.g., when increased water pressure is applied). Once filling is complete and correct positioning has been achieved, the injection device 710 can be detached.

Claims

1. A support structure comprising: a flexible retention element defining an open cavity and capable of receiving (i) a plurality of shapeable elements configured to be adjustable in size and shape in situ to self-anchor and seal said support structure to native tissue; and (ii) a plurality of expandable reinforcing elements configured and operable to self-anchor and stabilize said support structure; A support structure, wherein the plurality of shapeable elements and the plurality of expandable reinforcing elements are arranged in planes generally parallel to each other, at least one of the plurality of expandable reinforcing elements is arranged above or below one of the plurality of shapeable elements, radially expanding the one shapeable element and fully encapsulating the plurality of shapeable elements and the plurality of expandable reinforcing elements within the flexible retaining element, thereby creating a highly compressible, flexible, dynamic support structure capable of accepting a prosthetic valve, the flexible retaining element being shapeable in situ to form a final outer shape according to a patient's anatomy.

2. 2. The support structure of claim 1, wherein the flexible retention element is made of at least one of: (i) an elastic material that can expand primarily radially when filled with the plurality of shapeable elements; or (ii) a material that promotes rapid endothelial growth.

3. The support structure of claim 1 , wherein the flexible retention element has an outer surface with a rough texture that enables the support structure to self-anchor to natural tissue.

4. The support structure of claim 3 , wherein the exterior surface defines a mesh-like pattern or a dot-like pattern or a grid-like pattern.

5. The support structure of claim 1 , wherein the flexible retention element has an inner surface connecting with the open cavity that is made of a material that allows smooth, linear blood flow while preventing clot formation and turbulence.

6. The support structure of claim 4 , wherein the flexible retention element comprises at least one non-thrombogenic fabric mesh portion.

7. 2. The support structure of claim 1, wherein each of the plurality of shapeable elements can be filled separately or simultaneously in situ with at least one filling material that provides sealing and tissue fixation to the mitral and / or tricuspid and / or semilunar valves while maintaining flexibility and allowing movement with the cardiac cycle.

8. 6. The support structure of claim 5, wherein the at least one filler material comprises at least one fluid in the form of at least one of a gas, liquid, gel, powder, granules, or any combination thereof.

9. The support structure of claim 1 , wherein one of the expandable reinforcing elements defines a fixed inner dimension of the open cavity and is configured and operable to maintain stability at the annulus level.

10. The support structure of claim 1 , wherein at least some of the plurality of expandable reinforcing elements have the same or different physical properties including at least one of shape or diameter.

11. 10. The support structure of claim 1, wherein the at least shapeable element and the plurality of reinforcing elements each have a closed loop configuration that conforms to a patient's anatomy to provide a substantially 360 degree seal between the support structure and natural tissue.

12. 13. A prosthetic valve system comprising: a support structure according to claim 1; and a plurality of prosthetic leaflets coupled to said support structure, said plurality of prosthetic leaflets being configured and operable as a one-way valve.

13. 1. A kit for implanting a prosthetic valve, comprising: a container capable of providing a sterile barrier; a sterile catheter received within the container, the sterile catheter having a distal end and a proximal end; a sterile prosthetic valve received within the container, the sterile prosthetic valve being removably coupled to the distal end of the sterile catheter and including a plurality of prosthetic valve leaflets coupled to a flexible folded support structure according to claim 1; a filling material that can be received within the container, filling the flexible folded support structure and deploying the sterile prosthetic valve onto the native mitral and / or tricuspid and / or semilunar valve; A kit comprising:

14. 14. The kit of claim 13, further comprising an injection device removably coupled to the container, the injection device capable of filling and shaping the flexible support structure according to a patient's anatomy.

15. The kit of claim 13 , wherein the flexible folded support structure is capable of being pre-loaded with at least a portion of the packing material.

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