Transcatheter valve systems and methods for venous insufficiency

Abstract

The present application generally relates to a transcatheter anti-regurgitation venous valve endoprosthetic system comprising a replacement valve, a valve support frame, a crimping system, and a delivery system in order to treat patients suffering from chronic venous insufficiency, and to methods for using such systems.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of Provisional Application No. 63 / 340,867, filed May 11, 2022, and Provisional Application No. 63 / 404,150, filed September 6, 2022, which are incorporated herein by reference in their entirety. Technical Field

[0003] The present invention generally relates to a transcatheter anti-reflux venous valve endoprosthesis system, methods of making the same, and uses thereof. Background Art

[0004] Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities with venous hypertension, which causes a variety of pathologies including pain, swelling, edema, skin changes and ulcers. It is characterised by the inability of the venous valves to allow blood from the lower extremities to return to the heart, resulting in venous hypertension. Insufficient venous valves produce reflux, which can cause pain, itching and severe and uncontrollable swelling that can reduce mobility and lead to severe long-term ulcers.

[0005] More serious consequences of CVI include venous ulcers, which have an estimated prevalence of approximately 0.3%, but active or healing ulcers are seen in approximately 1% of the adult population. See Eberhardt RT, Raffetto JD. Chronicvenous insufficiency. Circulation. (2005) May 10;111(18):2398-409. It is estimated that approximately 2.5 million people in the United States suffer from severe cases of CVI, of which approximately 20% develop venous ulcers. The overall prognosis of venous ulcers is poor, with delayed healing and recurrent ulcers common. More than 50% of venous ulcers require long-term treatment lasting more than one year. Individuals with CVI suffer not only from the physical effects of the disease, but also endure psychological distress caused by unwanted color changes and raised skin. In severe cases of CVI involving deep vein thrombosis and pulmonary embolism, death may occur.

[0006] The socioeconomic impact of venous ulcers can also be significant, resulting in impaired ability to engage in social and occupational activities, which reduces quality of life and causes economic limitations. Disability associated with venous ulcers often results in loss of productive work time, estimated at 2 million workdays / year, and can lead to early retirement, which has been found in up to 12.5% ​​of workers with venous ulcers. Dasilva A, Navarro MF, Batalheiro J. "The importance of chronic venous insufficiency: various preliminary data on its medicosocial consequences" Phlebologie. 1992; 45: 439-43. The economic burden of venous ulcer disease on health care systems is evident: in the United States, an estimated $1 billion is spent annually on the treatment of chronic wounds, or up to 2% of the total health care budget in all Western countries, and recent estimates put the cost of venous ulcer care at $3 billion per year. See Eberhardt above.

[0007] Currently, approved therapies for the treatment of CVI are primarily limited to compression garments, compression pumps, and wound dressings. See Raffetto JD. Dermal pathology, cellular biology, and inflammation in chronic venous disease. Thromb Res. (2009); 123 Suppl 4: S66-71.

[0008] To meet the need for improved treatment for patients with CVI, enVeno Medical, Inc. of Irvine, California, has developed the VenoValve® system, which provides a permanent, single-use implant for chronic venous insufficiency. The functional component of the VenoValve® is a porcine aortic leaflet. The VenoValve® is surgically implanted in the deep veins of the lower extremities by a licensed health care professional and sutured to the repaired vein. A description of the VenoValve® replacement valve is provided in U.S. Patent No. 11285243, which is incorporated herein by reference in its entirety.

[0009] Some other transcatheter valves have been disclosed that require the use of multiple leaflets or a stent or frame design in order to differentiate between the inflow and outflow of blood when placed in a vein.

[0010] For example, published U.S. Application No. 20170196692, which is incorporated herein by reference in its entirety, describes an implantable valve having a spherical central portion. A transcatheter delivery system can be used to implant the valve, but the system needs to be able to engage and release a valve having an enlarged spherical portion that is wider than a natural human vein.

[0011] Published U.S. Application No. 20190328511 discloses a prosthetic transcatheter valve device having different antegrade and retrograde ends, which is incorporated herein by reference in its entirety. The antegrade end of the device includes a pair of leaflets positioned relative to each other.

[0012] Published US application 20090254175 (which is hereby incorporated by reference in its entirety) discloses a mesh stent having a grid with helical struts at both ends. The stent can accommodate at least two leaflets to form a one-way flow valve.

[0013] U.S. Patent No. 7,744,642 (which is hereby incorporated by reference in its entirety) describes a prosthetic transcatheter valve having a hollow base arranged as an inflow end, a plurality of struts connected to the base and extending to a blood outflow end, and inwardly directed flanges arranged at the blood outflow ends of the struts. The valve has leaflets in the gaps between the struts and is supported by a frame.

[0014] Published U.S. Application No. 20180078372 (which is incorporated herein by reference in its entirety) discloses a radially expandable frame having a plurality of leaflet frames with distinct inflow and outflow ends. The frame specifically requires scalloped inflow and outflow edges as functional features.

[0015] Published US Application No. 20030055492A1, which is incorporated herein by reference in its entirety, also discloses a self-expandable prosthetic transcatheter valve including more than two leaflets and a wire frame having at least one zigzag wire portion.

[0016] It has been observed that the ability to accurately guide and position a transcatheter valve for deployment in a patient's deep venous system is affected by a variety of factors, such as valve shape, valve size, target location, such as where the device is to be moved or positioned through a vein wall and / or at tortuous anatomy, etc. There may also be problems with the coupling between the venous frame for the valve to be delivered, all of which may result in a less accurate, and therefore less safe, device delivery process.

[0017] Given the prevalence and socioeconomic impact of CVT, there is a need for additional, alternative, and effective treatments for CVI that are less surgically invasive than current approaches and utilize a single-cusp valve, particularly for patients who are candidates for the transcatheter system described herein. Summary of the invention

[0018] The present invention provides a novel system design and delivery for treating chronic venous insufficiency.

[0019] A transcatheter valve system for implantation in a major vein of a patient is also presented.The transcatheter valve system may include a valve assembly.

[0020] According to example embodiments, a valve component may include at least one leaflet formed using continuous biological tissue.

[0021] In one aspect of the embodiment, the at least one leaflet can be formed from a flat sheet of continuous biological tissue folded to form a monocusp shape. In an example embodiment, the exact geometry is not replicated, but the function of a natural valve is achieved by opening and closing under physiologically relevant pressure gradients that induce vortex operation relative to blood flow using a monocusp leaflet that allows the leaflet to open and close smoothly and quickly. The tip of the at least one leaflet can be folded from continuous biological tissue, so no suturing is required to form the apex of the leaflet tip. However, suturing can be used to form the edge of the leaflet tip.

[0022] In example aspects, the biological tissue can be from a xenogeneic source.

[0023] In one aspect, the xenogeneic source is selected from the group consisting of porcine, bovine, and equine. In a preferred aspect, the xenogeneic source is porcine. In another aspect, the xenogeneic source is xenogeneic pericardium. In another aspect, the xenogeneic source is porcine pericardium.

[0024] In one aspect, the valve assembly can include exactly one leaflet. In one aspect of the exemplary embodiment, the tip of the leaflet is also formed by cutting continuous biological tissue into a shape having a top portion and a bottom portion (wall), the top portion being similar to the tip shape and the bottom portion being a generally rectangular shape; folding the top portion over the bottom rectangular portion to form the apex of a single valve of the leaflet; and suturing the top portion to the bottom rectangular portion of the biological tissue to form the edge of the single valve. In one aspect, the inflow skirt (inflow conduit) is attached to the wall (e.g., the rectangular bottom portion), which provides a way to avoid flow interruption on the inflow side of the device.

[0025] In another aspect, the inflow skirt is attached to the wall and the leaflet. In some specific aspects, the inflow skirt material can be made using biological tissue from a xenogeneic source. The xenogeneic source can be selected from a group including porcine, bovine, and equine. In one aspect, the xenogeneic source is porcine. In another aspect, the xenogeneic source is pericardium. In another aspect, the xenogeneic source is porcine pericardium. In one aspect, the inflow skirt material has the same source as the single valve leaflet. In another aspect, the inflow skirt material has an approximately rectangular shape. In another aspect, the inflow skirt material has a roughly square shape.

[0026] In more specific aspects, the biological tissue is fixed / crosslinked in a fixative for a period of time. In another aspect, the fixative is a solution comprising glutaraldehyde, formaldehyde, osmium tetroxide, genipin, hexamethylene diisocyanate (HMDI), a chemical or naturally occurring fixative. In one aspect, the fixative is glutaraldehyde. In another aspect, the fixative is 0.2% buffered isotonic glutaraldehyde.

[0027] In some aspects, the biological tissue is treated with a solution to reduce the bioburden level after fixation. In more specific aspects, the bioburden reduction solution is a mixture of isopropyl alcohol (IPA) and buffered isotonic glutaraldehyde. In specific aspects, the bioburden reduction solution has about 1% to 80% IPA contained in the solution mixture. In one aspect, the bioburden reduction solution has about 20% IPA contained in the solution mixture.

[0028] In some other aspects, biological tissue and inflow skirt are attached on another skirt located on the periphery. In some specific aspects, skirt material can use fabric skirt to manufacture. This fabric can include PET, PTFE fabric, ePTFE, degradable support, collagen support, hyaluronic acid support, fibrin, degradable or non-degradable material or biomaterial based on polymer. In a specific embodiment, material has ultra-low profile, enough porosity and suture retention, surface roughness, support for cell attachment and can attract the natural cells of migration so as to promote the surface area of ​​tissue ingrowth, for improving the sealing property of the device after implantation and long-term device migration resistance.

[0029] In another aspect, the skirt material has an approximately rectangular shape. In another aspect, the skirt material has a generally rectangular shape with a slightly wider portion (flare) at the inflow and / or outflow. In some specific aspects, the skirt material has a shape that matches the shape of the wall and inflow skirt when attached together.

[0030] In one aspect, the at least one leaflet is attached to the frame. In another aspect, the at least one leaflet is attached to the frame using sutures. The at least one leaflet can be attached to the frame so that it partially covers the perimeter of the frame. In another aspect, the at least one leaflet is attached to the frame so that it completely covers the perimeter of the frame.

[0031] In one exemplary aspect, the at least one leaflet attached to the inflow skirt material is attached to a frame. In one aspect, the at least one leaflet attached to the inflow skirt material is attached to a frame using sutures.

[0032] In an exemplary embodiment, the suture is a polybutester monofilament suture used to attach the inflow skirt material, the wall, and the leaflets to the frame. In one aspect, at least one leaflet attached to the inflow skirt material is attached to the frame, wherein at least one leaflet attached to the inflow skirt material is attached to the frame partially covering the perimeter of the frame. In another aspect, at least one leaflet attached to the inflow skirt material is attached to the frame, wherein at least one leaflet attached to the inflow skirt material is attached to the frame completely covering the perimeter of the frame. In another aspect, at least one leaflet attached to the inflow skirt material is attached to the frame using sutures.

[0033] In any of these example aspects, the leaflets can be covered with a fabric skirt before being sewn into the frame. Also, in any of these example aspects, at least one leaflet attached to the inflow skirt material can be covered with a fabric skirt before sewing it to the frame.

[0034] In an example embodiment, at least one leaflet attached to the inflow skirt material has an outer diameter of about 6 to about 18 mm when folded into a cylinder and attached to a circumferential fabric skirt that is attached to a frame. In one aspect, at least one leaflet attached to the skirt material has an outer diameter of about 9 mm to about 12 mm when folded into a cylinder and attached to a circumferential fabric skirt that is attached to a frame. The circumferential fabric skirt material helps prevent migration and aids in sealing, preventing flow circulation around the valve.

[0035] According to another example embodiment, a method of manufacturing a replacement transcatheter valve for a patient is described. The method includes: providing a continuous biological tissue that is subjected to a fixation process; cutting the fixed biological tissue into a specific shape so that there is a top portion and a bottom portion; folding the top portion onto the bottom portion to produce the apex of a single leaflet of the leaflet; and suturing the top folded portion to the bottom folded portion along the edge to form the single leaflet shape of the leaflet. The method may also include attaching the single leaflet to the tissue (inflow) skirt with a suture. The method may also include attaching the single leaflet sutured to the tissue inflow skirt to the fabric skirt.

[0036] In one aspect of the embodiment, the top portion can be similar to the shape of a natural tip. In another aspect, the bottom portion is generally rectangular in shape.

[0037] In one aspect, cutting a specific shape of biological tissue such as in Figure 3A as shown in .

[0038] In one aspect, the continuous biological tissue can be from a xenogeneic source.

[0039] In another aspect, the xenogeneic source is selected from the group consisting of porcine, bovine, and equine. In one aspect, the xenogeneic source is porcine. In another aspect, the xenogeneic source is pericardium. In another aspect, the xenogeneic source is porcine pericardium.

[0040] In an exemplary embodiment, the exact geometry is not replicated, but rather the function of a native valve is achieved by opening and closing under physiologically relevant pressure gradients that induce vortex operation relative to the blood flow using a single leaflet that allows the leaflet to open and close smoothly and quickly. The tip of at least one leaflet can be folded from continuous biological tissue, so that suturing is not required to form the apex of the leaflet tip. However, suturing can be used to form the edge of the leaflet tip. In one aspect, the single leaflet shape replicates the spherical geometry of a native valve with an apex and an edge to provide a spatial buffer between the single leaflet and the valve wall when the valve is in an open position, thereby preventing or reducing adhesion of the single leaflet to the valve wall and facilitating closing of the single leaflet valve when a sufficient flow pressure gradient is generated.

[0041] In another aspect, the inflow skirt material can be attached to the wall and manufactured using biological tissue from a xenogeneic source. The xenogeneic source can be selected from the group consisting of porcine, bovine, and equine. In one aspect, the xenogeneic source is porcine. In another aspect, the xenogeneic source is pericardium. In another aspect, the xenogeneic source is porcine pericardium. In another aspect, the inflow skirt material has the same source as the single valve leaflet.

[0042] In one example embodiment, a method of manufacturing includes attaching a leaflet to a frame. In one aspect, the method includes attaching the leaflet to the frame using sutures. In another aspect, the method includes attaching the leaflet to the frame so that it partially covers the perimeter of the frame. In another aspect, the method includes attaching the leaflet to the frame so that the leaflet completely covers the perimeter of the frame.

[0043] In one example embodiment, a method of manufacturing includes attaching a leaflet attached to an inflow skirt material to a frame. In one aspect, the method includes attaching the leaflet attached to the inflow skirt material to the frame using sutures. In another aspect, the method includes attaching the leaflet attached to the inflow skirt material to the frame so that it partially covers the perimeter of the frame. In another aspect, the method includes attaching the leaflet attached to the inflow skirt material to the frame so that it completely covers the perimeter of the frame.

[0044] In any of these aspects, the method of manufacturing may include attaching the leaflets to the fabric skirt before suturing the leaflets to the frame. Also in any of these aspects, the method of manufacturing may include attaching the leaflets attached to the inflow skirt material to the fabric skirt before suturing the leaflets to the frame. In one aspect, the fabric skirt can be natural or synthetic. In another aspect, the fabric is polyethylene terephthalate (PET). In another aspect, the fabric provides a material with an ultra-low profile, sufficient porosity and suture retention, surface roughness, a scaffold for cell attachment, and a surface area that can attract migrating natural cells to promote tissue ingrowth, for improving device sealing after implantation and long-term device migration resistance.

[0045] According to example embodiments, the valve assembly may include an implantable venous frame. The design of the venous frame described herein partially solves the deployment problem because the frame is compressible and expandable, such as self-expansion with chamber geometry, structure and holes for holding sutures, and strut components, chambers and crowns (with or without anchors) employed on the surface of the frame.

[0046] In one exemplary embodiment, the implantable framework has an anchor or hook at the distal end of the flared cylinder to help prevent migration when implanted. In some aspects, the anchor or hook helps to assist in the attachment of the venous framework before the PET skirt promotes cell and tissue growth into the device. In some aspects, the anchor or hook prevents the framework from shifting shortly after insertion. On the other hand, the anchor or hook can be positioned along the cylinder and can grasp and / or anchor into the natural vein. The anchor or hook can also be located at certain portions along the cylinder, such as the middle portion. The anchor or hook along the cylinder can also take the form of a separate tine. The anchor or hook can be provided with different sizes based on the natural vein.

[0047] In an exemplary embodiment, the implantable framework may include a first portion, a second portion, a third portion, and a fourth portion, such that each portion is interconnected with at least one other portion. In some aspects, the first portion is interconnected with the second portion, the second portion is interconnected with the third portion and the first portion, the third portion is interconnected with the second portion and the fourth portion, and the fourth portion is interconnected with the third portion. In some aspects, the plurality of portions are interconnected with a strut member.

[0048] In some exemplary embodiments, each portion may include about 2 to 16 sawtooth segments having 2 to 16 proximal peaks and about 2 to 16 distal peaks. In preferred aspects, each portion may include about twelve sawtooth segments having about twelve proximal peaks and about twelve distal peaks. The design of the frame provides radial strength and is compressible. In some aspects, the multiple portions are interconnected by connecting each alternating proximal peak of one portion to an alternating distal peak of another portion. In such aspects, there may be about six strut components between the two portions. In some other aspects, the multiple portions may be interconnected by connecting every third alternating proximal peak of one portion to every third alternating distal peak of another portion. In such aspects, there may be about four strut components between the two portions. In yet another other aspect, the multiple portions may be interconnected by every fourth alternating proximal peak of one portion to every fourth alternating distal peak of another portion. In such aspects, there may be three strut components between the two portions. In one aspect, the multiple sections are rigidly interconnected using strut members, which increases stability during valve deployment while balancing sufficient flexibility when the valve is functioning and rigidity in the vein.

[0049] In some aspects, the implantable frame can have suture holes at one or both ends, which can help attach the implantable frame to the valve assembly. In some specific aspects, the implantable frame has suture holes at both ends of the frame. In another embodiment, the suture holes are located at the crown of the frame serration. In another specific aspect, the suture holes have a diameter of about 0.5 mm, which allows the frame to have durability and stress distribution optimization. In some aspects, the diameter of the suture holes can be about 0.3 mm to about 1.0 mm. The suture can be sutured about three times around each pillar of the frame. On the other hand, the suture is sutured about once to about five times around each pillar of the frame. In another embodiment, the suture holes are located at the crown of the frame serration, wherein the crown can also be provided with anchors to reduce the possibility of migration. On the other hand, anchors or hooks can be positioned along the column and can grasp and / or anchor into a natural vein. Anchors or hooks can also be located at certain portions along the column, such as the middle portion. Anchors or hooks along the column can also take the form of separate tines. The anchors or hooks may be provided in different sizes based on the native vein.

[0050] In some aspects, the implantable framework has flared ends. For example, one end of the implantable framework can have an outer diameter D1, and the other end can have an outer diameter D2. In some aspects, D1 and D2 are substantially different. In some other specific aspects, D1 and D2 are substantially similar. In some specific aspects, D1 and D2 can be in the range of about 6 mm to about 18 mm, about 10.8 mm to about 14.4 mm.

[0051] In some aspects, the diameter of the implantable framework between the first portion and the second portion can have a diameter D3. In some specific aspects, D3 can be in the range of about 6 mm to about 18 mm, about 9 mm to about 12 mm. In some other aspects, D1 can be about 1 mm to about 3 mm larger than D3. The advantage of varying the size of the framework is to meet the needs of veins of different sizes and patients, and to provide a suitable vein anchor and reduce the possibility of migration.

[0052] In some aspects, the diameter of the implantable framework between the second portion and the third portion can have a diameter D4. In some specific aspects, D4 can be in the range of about 6 mm to about 18 mm, about 9 mm to about 12 mm. In some other specific aspects, D1 can be about 1 to about 3 mm larger than D4.

[0053] In some aspects, the diameter of the implantable framework between the third and fourth portions can have a diameter D5. In some specific aspects, D5 can be in the range of about 6 mm to about 18 mm, about 9 mm to about 12 mm. In some other specific aspects, D1 can be about 1 to about 3 mm larger than D5. In some specific aspects, D3 and D5 are substantially different. In some other specific aspects, D3 and D5 are substantially similar.

[0054] In an exemplary embodiment, the implantable frame can be flared at one end of the frame. In some aspects, the outer diameter of the flared end can be less than about 18 mm. In preferred aspects, the outer diameter of the flared end can be about 10.8 mm to about 14.4 mm.

[0055] In another exemplary embodiment, the implantable frame can be flared at both ends of the frame. In some aspects, the outer diameter of the flared end can be less than about 18 mm. In preferred aspects, the outer diameter of the flared end can be about 10.8 mm to about 14.4 mm.

[0056] In some aspects, the zigzag sections in the implantable framework create cells. In some aspects, the number of cells in the implantable framework is less than or equal to about 32. In some aspects, the number of cells in the implantable framework is about 24. In some aspects, the number of cells present in the implantable framework provides sufficient radial strength of about 2-60N, and reaches a range of about 17-20N.

[0057] In some aspects, the size of the strut components between two particular sections can be different. For example, the size of the strut components between the first section and the second section can be different from the size of the strut components between the third section and the second section.

[0058] In some aspects, the size of the strut components between two particular sections can be significantly similar. For example, the size of the strut components between the first section and the second section can be the same as the size of the strut components between the third section and the second section.

[0059] In one example embodiment, the implantable frame self-expands once crimped. In one embodiment, the frame is crimpable and has a radial strength of approximately 17-20N. In some aspects, the implantable frame includes a material capable of having a significant recoverable strain so as to present a low profile for delivery or implantation. After releasing the compressed self-expanding frame, preferably, the implantable frame is capable of radially expanding back to its original diameter or close to its original diameter. In some aspects, the implantable frame is made of a material having a high elastic strain (e.g., superelasticity) so as to undergo a large deformation and immediately return to its undeformed shape, and is heat treated.

[0060] Particularly preferred materials for self-expanding implantable frames include shape memory alloys that exhibit superelastic behavior (e.g., capable of significant deformation without plastic deformation). A frame made from such a material can be significantly compressed without permanent plastic deformation, for example, such that it can be compressed so that the maximum strain level in the stent or frame is below the recoverable strain limit of the material. Discussion of nickel-titanium alloys and other alloys that exhibit properties suitable for a frame can be found, for example, in U.S. Patent No. 5,597,378 (Jervis) (which document is incorporated herein by reference in its entirety) and International Application WO 95 / 31945 (Burmeister et al.) (which document is incorporated herein by reference in its entirety). The preferred shape memory alloy is Ni-Ti, but any other known shape memory alloy may also be used. Such other alloys include: Au-Cd, Cu-Zn, In-Ti, Cu-Zn-Al, Ti-Nb, Au-Cu-Zn, Cu-Zn-Sn, CuZn-Si, Cu-Al-Ni, Ag-Cd, Cu-Sn, Cu-Zn-Ga, Ni-Al, Fe-Pt, U-Nb, Ti-Pd-Ni, Fe-Mn-Si, etc. One suitable material having the desired properties for self-expansion is Nitinol, a nickel-titanium alloy that can recover up to 10% of its elastic deformation. This exceptionally large elastic range is often referred to as superelasticity.

[0061] In one exemplary embodiment, the implantable frame can be expanded by using an air bag. Such a frame may not be self-expanding. In some aspects, the implantable frame can be made of an inert, biocompatible material with high corrosion resistance that can be plastically deformed at lower moderate stress levels, such as tantalum. The implantable frame can be expanded by auxiliary (mechanical) expansion (such as air bag expansion and self-expanding devices). In some aspects, the implantable frame can be made of a material that can be plastically deformed by the expansion of a mechanical auxiliary device. When the air bag is deflated, the implantable frame can remain substantially in the expanded shape. Other acceptable materials include stainless steel, cobalt chromium, titanium ASTM F63-83 grade 1, niobium or high karat gold K19-22. A widely used material for balloon expandable structures is stainless steel, particularly 316L stainless steel. Alternative materials for mechanically expandable structural frames that maintain similar properties to stainless steel include tantalum, platinum alloys, niobium alloys and cobalt alloys.

[0062] In an exemplary embodiment, the implantable framework may also be coated or formed from one or more degradable synthetic materials (e.g., polymers) and / or naturally derived materials (e.g., biomaterials) and copolymers of degradable polymers and / or biomaterials. The bioactive material may be mixed or copolymerized with a bioabsorbable polymer or biomaterial. Alternatively, the bioactive material or a mixture of the bioactive material and a biostable or bioabsorbable polymer or biomaterial may be coated with a second layer comprising a bioabsorbable polymer or biomaterial.

[0063] Bioabsorbable polymers or biomaterials can be formed by copolymerization of compatible monomers or by coupling or copolymerization of functionalized chains with other functionalized chains or with monomers. Examples include cross-linked phosphorylcholine-vinyl alkyl ether copolymers and PC-batimastat copolymers, collagen, chitosan, hyaluronic acid and fibrin. In one aspect, the implantable framework can be coated with a coating between about 1 μm and about 50 μm or between about 3 μm and about 30 μm, but any suitable thickness can be selected.

[0064] In some aspects, when implanted, the absorption of the bioabsorbable polymer or biomaterial can release the bioactive agent. The bioabsorbable polymer or biomaterial can be formed by copolymerization of compatible monomers or by coupling or copolymerization of functionalized chains with other functionalized chains or with monomers. Examples include cross-linked phosphorylcholine-vinyl alkyl ether copolymers and PC-batimastat copolymers, collagen, chitosan, hyaluronic acid and fibrin. In some aspects, the implantable framework can be coated with a coating between about 1 μm and about 50 μm or between about 3 μm and about 30 μm, but any suitable thickness can be selected. The coating can include a bioactive material layer that contacts a separate layer containing a carrier, a bioactive material mixed with one or more carriers, or any combination thereof. The carrier can be biologically or chemically passive or active, but is selected and configured to provide a desired bioactive material release rate. In some aspects, when implanted, the absorption of the bioabsorbable polymer or biomaterial does not release the bioactive agent. In some aspects, the implantable framework can be tissue engineered (bioengineered).

[0065] In another exemplary embodiment, the implantable framework is made of non-degradable materials. Some examples of non-degradable materials include polymers, metals, and biomaterials. These materials for the implantable framework include materials that can provide suitable functional properties for mechanical load bearing, biocompatibility, elastic modulus, radiopacity, or other desired properties. For some exemplary embodiments, the material used to form the implantable framework may include a material that exhibits excellent corrosion resistance.

[0066] In some aspects, the material can be selected to be sufficiently radiopaque and to produce minimal artifacts in magnetic resonance imaging techniques (MRI). In some aspects, the implantable frame can include a metal, a metal alloy, a synthetic material, a naturally derived material, or any suitable combination thereof, such as a frame having multiple layers. In some aspects, the implantable frame can include nitinol, titanium, cobalt chromium, or PEEK. In preferred aspects, the implantable frame is made of nitinol.

[0067] In an exemplary embodiment, the implantable framework may receive surface modifications such as, but not limited to, electropolishing, passivation, anti-thrombotic coatings, coatings with suitable cell receptor binding sites embedded on the surface or in biological or polymeric coatings, coatings that promote tissue ingrowth, or combinations thereof.

[0068] In an exemplary embodiment, the implantable frame can allow for radial compression (e.g., crimping) of the implantable frame, which results in a low profile to be used with a catheter delivery system. In some aspects, the crimpability of the implantable frame is about 6 Fr to about 20 Fr. In preferred aspects, the crimpability of the implantable frame is about 12 Fr to about 16 Fr.

[0069] In an exemplary embodiment, the implantable framework can be manufactured using any suitable method known in the art. In some aspects, the complete framework structure is cut from a solid tube or sheet material, so the implantable framework is considered to be an integral unit. Laser cutting, water jet cutting, and photochemical etching are all methods that can be used to form a structural framework from sheet and tube raw materials. Those skilled in the art will understand other methods for manufacturing and / or shaping the complete framework structure as described above. The technology for forming the implantable framework is introduced in, for example, Dougal et al. "Stent Design: Implications for Restenosis" Rev. CarDiovasc Med. 3 (Suppl.5), S16-S22 (2002), which is cited herein as a whole.

[0070] In some embodiments, the connection between the multiple parts and the zigzag segments can be made by welding or other suitable connection methods. Other connection methods include using adhesives, thermal or chemical bonding, and / or attachment by mechanical means (e.g., pressing, welding, or suturing). In some aspects, parts of the implantable frame can be attached by applying an adhesive coating. In a preferred aspect, the implantable frame is manufactured by laser cutting from raw tubing material of nitinol having the following dimensions: an outer diameter of less than about 18 mm, such as an outer diameter of about 4 mm, and a thickness of less than about 1 mm, such as a wall thickness of about 0.52 mm.

[0071] In an exemplary embodiment, the implantable frame may be optionally sterilized using any suitable technique known in the art or its equivalent. For example, the implantable frame may be sterilized using gamma radiation, ethylene oxide, solution or electron beam sterilization, preferably gamma radiation. In some embodiments, the sterilized implantable frame meets approximately 10 -6 Minimum sterility assurance level (SAL).

[0072] In an exemplary embodiment, the implantable framework or its portion may optionally include a material that allows identification of the position or orientation of the implantable framework in a body passage. In some aspects, portions of the implantable framework may include radiopaque materials that can be identified by X-rays. In some aspects, the implantable framework may also include a material used with a contrast dye to identify the implantable framework in a body passage. Non-limiting examples of radiopaque materials include but are not limited to high-density metals (e.g., platinum, iridium, gold, silver, tantalum, or alloys thereof) or radiopaque polymer compounds. Radiopaque materials are highly visible under fluorescent illumination and are visible even at minimum thickness. In some aspects, in the eyelet structure attached to one or more bridging components, the radiopaque material may be gold, platinum, tungsten, or iridium and mixtures and alloys thereof.

[0073] According to aspects of the example embodiments of the implantable frame, it can be seen that variations are possible. It is also contemplated that other configurations of the implantable frame are possible, including, for example, variations having a fifth portion.

[0074] A transcatheter system may include one or more aspects of the transcatheter valve and implantable frame described above.

[0075] In one example embodiment, a method is disclosed that includes providing a transcatheter valve system for implantation in a major vein of a patient suffering from chronic venous insufficiency.

[0076] In one aspect of the embodiment, the leaflet is formed from a continuous biological tissue sheet folded into a single-valve shape. The single-valve shape can replicate the spherical geometry of a natural valve with a vertex and an edge. In an exemplary embodiment, the exact geometry is not replicated, but the function of the natural valve is achieved by opening and closing under a physiologically relevant pressure gradient, which uses a single-valve leaflet that allows the leaflet to open and close smoothly and quickly to cause vortex operation relative to the blood flow. The tip of at least one leaflet can be folded from continuous biological tissue, so no suturing is required to form the vertex of the leaflet tip. However, suturing can be used to form the edge of the leaflet tip. In another specific aspect, the suture hole has a diameter of about 0.5 mm, which can be optimized for durability and stress distribution. In an exemplary aspect, the suture holes are spaced about 1.5 mm apart. In other aspects, the suture holes can be spaced about 0.5 mm to about 3 mm apart from each other.

[0077] In another aspect, the suture spacing reduces leakage by overlapping the sutures. In one aspect, the single-valve shape replicates the spherical geometry of a natural valve having an apex and an edge so as to provide a spatial buffer between the single valve and the valve wall when the valve is in an open position, thereby preventing or reducing adhesion of the single valve to the valve wall and promoting closure of the single-valve valve when a sufficient flow pressure gradient is generated. The tip of the leaflet does not require sutures to form the apex of the leaflet tip. However, sutures can be used to form the edge of the leaflet tip. In one aspect, the tip of the leaflet is also formed by cutting a continuous biological tissue into a shape having a top portion and a bottom rectangular portion, the top portion being similar to the shape of the tip; folding the top portion onto the bottom rectangular portion to produce the apex of the single valve of the leaflet; and suturing the top portion onto the bottom rectangular portion of the biological tissue to form the edge of the single valve.

[0078] According to another exemplary embodiment, a transcatheter delivery device is provided. The present invention effectively provides a delivery system in which the delivery device can be manipulated and guided to implant a transcatheter valve into a vein. The delivery device includes, for example, an inner tube assembly, a sheath assembly, a catheter assembly, and a handle.

[0079] The inner tube assembly may include a flush port and a hypotube.

[0080] The sheath assembly includes a nose cone and a nose cone braided shaft. In one aspect, the sheath assembly is connected to the inner tube assembly by partially or completely covering the nose cone braided shaft of the sheath assembly with the hypotube of the inner tube assembly. The catheter assembly is configured to accommodate the transcatheter valve in a compressed configuration. The catheter assembly is slidably arranged on the sheath assembly and includes a proximal region and a distal region. In one aspect, one end of the proximal region of the catheter assembly is connected to the handle, and the other end of the proximal region of the catheter assembly is connected to the distal region of the catheter assembly.

[0081] On the other hand, one end of the distal region of catheter assembly is arranged to compressively hold described transcatheter valve with compression configuration, and the other end of the distal region of catheter assembly is connected with the proximal region of catheter assembly.The distal region of catheter assembly can be arranged to compressively hold the transcatheter valve with two shapes.The first shape has the first diameter, and the second shape has the second diameter.These two shapes can be continuous or assemble in fact.

[0082] The handle is configured to selectively move the catheter assembly relative to the sheath assembly. The delivery device can be configured to provide a resting state in which the distal region of the catheter assembly is closer to the nose cone and a delivery state in which the distal region of the catheter assembly is pulled away from the nose cone. The distal portion of the catheter is pulled back by turning a knob on the handle to expose the valve; thus, the handle slides the distal portion of the catheter back through the nose cone sheath.

[0083] In one example embodiment, the delivery device includes an indicator for when the self-expanding valve can no longer be repositioned. The indicator helps with the placement and delivery timing of the valve because it is clear how far the valve is extruded from the delivery device. Another embodiment of the indicator can indicate that the valve can no longer be retracted into the delivery device when the valve is approximately 20% expanded.

[0084] In a preferred exemplary embodiment, the delivery system provides three functions in one, as the device functions as a dilator, an introducer sheath, and a delivery system. In this embodiment, the three-in-one system allows the device to not require a dilator or introducer sheath separately, as the tapered bullet-shaped nose cone provides atraumatic access for use as a dilator, and the distal region of the catheter assembly has a continuous and uniform diameter for use as an introducer sheath.

[0085] The present invention also provides an improved method for treating chronic venous insufficiency (CVI) that is superior to conventional methods of controlling CVI by inactivating incompetent veins through chemical or mechanical occlusion. The transcatheter valves described herein will prevent blood from flowing back without permanently inactivating damaged veins, thereby providing an improved method for treating CVI by replacing and restoring the function of incompetent valves so that proper blood flow is maintained.

[0086] The present invention also provides a system for treating CVI of a patient. The system includes a transcatheter device and a delivery device as described above. The transcatheter device includes an implantable frame and a transcatheter valve attached to the frame. When the system is assembled to a static state, the catheter assembly in the delivery device compressively accommodates the transcatheter device in a compressed configuration on the sheath assembly. The system can transition to a delivery state in which the distal region of the catheter assembly is pulled away from the nose cone so that it exposes the transcatheter device on the nose cone to be released from the delivery device.

[0087] The present invention also provides a method for treating chronic venous insufficiency of a patient. The method includes receiving a transcatheter device, which includes an implantable frame and a transcatheter valve attached to the frame. The delivery device includes an inner tube assembly, a sheath assembly, a catheter assembly and a handle. The inner tube assembly includes a flushing port and a hypotube. The sheath assembly includes a nose cone and a nose cone braided shaft. In one aspect, the sheath assembly is connected to the inner tube assembly by partially or completely covering the nose cone braided shaft of the sheath assembly with the hypotube of the inner tube assembly. The catheter assembly is configured to accommodate the transcatheter valve in a compressed configuration. The catheter assembly is slidably arranged on the sheath assembly and includes a proximal region and a distal region. In one aspect, one end of the proximal region of the catheter assembly is connected to the handle, and the other end of the proximal region of the catheter assembly is connected to the distal region of the catheter assembly.

[0088] One end of the distal region of catheter assembly can be arranged to compressively accommodate the transcatheter valve in a compressed configuration, and the other end of the distal region of catheter assembly is connected with the proximal region of catheter assembly. In one aspect, the distal region of the catheter assembly arranged to compressively accommodate the transcatheter valve can have two shapes. The first shape has a first diameter, and the second shape has a second diameter. These two shapes can be essentially continuous or assembled. The handle is arranged to make the catheter assembly selectively move relative to the sheath assembly. The conveyor is arranged to provide a static state and a conveying state, in which the distal region of catheter assembly is closer to the nose cone, and in this conveying state, the distal region of catheter assembly is pulled away from the nose cone. In some respects, the method comprises a conveyor so that the catheter assembly in the conveyor will be contained in the sheath assembly in a compressed configuration of the transcatheter device compression.

[0089] The transcatheter valve may include biological tissue from a xenogeneic source. The biological tissue may include at least one leaflet from a xenogeneic source such as a pig, a cow, and a horse. In some aspects, at least one leaflet of the transcatheter valve is attached to the inflow skirt material, as described above. The method also includes providing a frame to which the transcatheter valve is attached via a fabric skirt. The transcatheter valve may be attached to the frame so that it partially or completely covers the periphery of the frame. In specific aspects, at least one leaflet attached to the skirt material is attached to the frame using sutures.

[0090] In one aspect, the method further comprises creating an opening in the main vein, the opening having a shape roughly corresponding to the patch. In the aforementioned aspects, the opening can generally be created on the external iliac vein, iliac vein, femoral vein, common femoral vein, popliteal vein, superficial venous system, great saphenous vein, deep vein or external jugular vein. The method can also include attaching the transcatheter valve to the main vein at the opening. In another aspect, the transcatheter has been fixed. In any of these aspects, the subject can be a human. BRIEF DESCRIPTION OF THE DRAWINGS

[0091] Figure 1A is a longitudinal view of a venous valve having a fabric skirt covering a frame, an inflow skirt, and leaflets according to an example embodiment.

[0092] Figure 1B is a longitudinal view of a venous valve fabric skirt covering frame according to an example embodiment.

[0093] Figure 1C is a longitudinal view of a venous valve leaflet attached to an inflow tissue skirt according to an example embodiment.

[0094] Figure 1D is a side perspective view of a venous valve having a fabric covered frame, inflow skirt, and leaflets according to an example embodiment.

[0095] Figure 1E is a front cut-away perspective view of a venous valve having a fabric-covered frame, inflow skirt, and leaflets according to an example embodiment.

[0096] Figure 2 is a side perspective view of a venous valve frame according to an example embodiment.

[0097] Figure 3A is a 2-D plan view of a leaflet according to an example embodiment.

[0098] Figure 3B is a 2-D plan view of a wall with leaflets and an inflow skirt, wherein a single flap is folded over the wall and the inflow skirt is attached to the base of the leaflets, according to an example embodiment.

[0099] Figure 3C is a longitudinal side perspective view of a leaflet folded over a wall and attached to an inflow skirt to form a conduit in accordance with an example embodiment.

[0100] Figure 3D and 3E is an overview of the parameters considered for a 10 mm transcatheter venous valve and a representative single valve abdominal curve in an example embodiment.

[0101] Figure 4A is a folded leaflet in an example embodiment wherein the smooth side is primarily organized with elastin fibers and the rough side is primarily organized with collagen fibers, the tissue composition being approximately 80% collagen and approximately 20% elastin.

[0102] Figure 4B It is the alignment of the suture holes on the folded leaflet tips with the suture holes on the supporting wall in the example embodiment.

[0103] Figure 4C is the fixation of temporary sutures at the seams of the folded leaflets in the example embodiment.

[0104] Figure 4D is a complete tissue leaflet sutured to the support wall (without inflow skirt and support wall sutures) after the two temporary sutures at the corners are removed in the example embodiment.

[0105] Figure 4E is an intact tissue leaflet sutured to a supporting wall in an exemplary embodiment, having an inflow skirt and temporary sutures securing the inflow skirt to the leaflet supporting wall.

[0106] Figure 4F is an intact tissue leaflet in an example embodiment wherein the inflow skirt is in the process of being sutured from the tissue edge to the attachment edge.

[0107] Figure 4G is an intact tissue leaflet in the example embodiment where the inflow skirt is being sutured and a triple locking knot following the double blanket suture secures the inflow skirt to the attachment edge.

[0108] Figure 4H is an intact tissue leaflet in an example embodiment, wherein the intact inflow skirt is completely sutured to the leaflet.

[0109] Fig. 4I is a complete tissue leaflet in an example embodiment, wherein the complete inflow skirt is completely sutured to the leaflet, the leaflet and skirt are folded in the axial / longitudinal direction and sutured at the ends, intended for insertion and fixation in a frame.

[0110] Figure 5 is a side perspective view of a tissue skirt according to an example embodiment.

[0111] Fig. 6A is a cover for the frame that is wrapped around a mandrel in an example embodiment.

[0112] Figure 6B is a fabric skirt cover for a frame that is inserted into the frame using a mandrel in an example embodiment.

[0113] Figure 6C is a fabric covered frame subassembly assembled in an example embodiment.

[0114] Figure 7 is a longitudinal perspective view of a valve assembly in an example embodiment with the peripheral and intermediate portions identified to aid in final assembly.

[0115] Fig. 8A is a tissue leaflet assembly on a mandrel inserted into a cover frame subassembly in an example embodiment.

[0116] Figure 8Bis a tissue leaflet assembly on a mandrel inserted into a cover frame subassembly in an example embodiment wherein a first temporary suture at one coronal eyelet is a medial thread.

[0117] Fig.9A is an illustration of initial suture lines for a final assembly of a transcatheter valve in an example embodiment, wherein the suture lines are located adjacent to struts of a bridge located on the perimeter side.

[0118] Fig. 9B is a top view of the final assembly of a transcatheter valve in an example embodiment, wherein a single ring is formed around the struts proximal to the strut bridges.

[0119] Fig. 9C It is a transcatheter valve in which a curved needle is reentered with the suture near the middle of the struts from the inside to the outside of the tissue skirt.

[0120] Fig.9D is a view of the final assembly of the transcatheter valve in an example embodiment, wherein the curved needle along with the suture reenters from the interior to the exterior of the tissue skirt near the middle of the struts.

[0121] Fig.9E is a side view of a transcatheter valve assembly in an example embodiment with a curved needle passed through an eyelet of the crown along with a suture.

[0122] Fig.9F is a view of tying a knot in an eyelet of a crown in a transcatheter valve assembly in an example embodiment.

[0123] Figure 9G is a top view of a peripheral portion of a transcatheter valve assembly in an example embodiment, wherein a curved needle is inserted through the fabric along with a suture through the middle of a diamond-shaped strut.

[0124] Figure 9H is a top view of a peripheral portion of a transcatheter valve assembly in an example embodiment, wherein a curved needle exits through the exterior of the fabric along with sutures to form a ring around the struts.

[0125] Fig.9I is a top view of a peripheral portion of a transcatheter valve assembly in an example embodiment, wherein a curved needle along with suture exits from the interior of a tissue skirt to the exterior of a fabric skirt to form a ring around a bridge.

[0126] Figure 9J is an upper perspective view of the final assembly of a transcatheter valve in an example embodiment, wherein a ring is formed around the strut bridges and the needle and suture are re-entered from the exterior to the interior of the tissue skirt.

[0127] Fig.10is a side perspective view of a disassembled conveyor system according to an example embodiment.

[0128] Fig.11A is a side cross-sectional view of an assembled conveyor system according to an example embodiment.

[0129] Fig. 11B is a side cutaway perspective view of a nose cone assembly having an inner tube assembly and a sheath assembly in a delivery device in an example embodiment.

[0130] Fig. 12A is a longitudinal cross-sectional view of a crimping system (crimper) assembly according to an example embodiment.

[0131] Fig. 12B It is in an example embodiment that a transcatheter valve is loaded onto a delivery system using a crimper and crimper pins.

[0132] Fig. 12C is a side and slightly upper perspective view of a crimper compressing a transcatheter valve in an example embodiment, with crimper pins used to assist.

[0133] Fig.12D is a side view of a crimper compressing a transcatheter valve in an example embodiment, wherein crimper pins are used to assist.

[0134] Fig.12E is an upper view of a crimper compressing a transcatheter valve in an example embodiment, wherein crimper pins are used to assist.

[0135] Fig.12F is a longitudinal cross-sectional view of a crimping system (crimper) assembly according to an example embodiment.

[0136] Figure 12G is based on Fig.12F A side view of the crimping system (crimper) assembly of the example embodiment shown. DETAILED DESCRIPTION

[0137] Figure 1A , 1D 1E and 1E show a fabric covered frame assembly, wherein the frame 140, the leaflets 130 and ( Figure 1C 120) wall ( Figure 1C ) 120 and flow into the skirt ( Figure 1C )110 are fixed together. Figure 1A is a longitudinal view of an assembled transcatheter valve wherein the leaflets 130 have support walls ( Figure 1C ) 120 and the attached inflow skirt ( Figure 1C )110. Figure 1AIn the embodiment, the end 100 of the frame is flared. The flared end 100 may be between about 2 mm and about 10 mm from the beginning of flaring to the end of flaring. Figure 1B is a longitudinal view of the frame assembly covered with fabric 105.

[0138] Figure 1C is a longitudinal view of the assembled leaflet and inflow skirt prior to insertion into the cover frame in one embodiment. Figure 1C In the embodiment, the inflow skirt is indicated by 110, wherein the continuous bio-leaflet is indicated by 120. Figure 1C 120, which shows a leaflet formed from a flat sheet of continuous biological tissue that is folded to form a single-petal shape with supporting walls. Figure 1D is a side perspective view of an assembled transcatheter valve with leaflets having support walls and an attached inflow skirt in a cover frame assembly. Figure 1E is a front perspective view of an assembled transcatheter valve with leaflets having support walls and an attached inflow skirt in a cover frame assembly.

[0139] Figure 2 is a venous valve frame without a cover in the example embodiment. Figure 2 The flared end of the frame is shown and is designated 200. The holes in the crown of the frame are Figure 2 The bridging member of the frame is shown as 210. Figure 2 The support of the frame is shown as 220. Figure 2 230. In a preferred exemplary embodiment, each section may include about twelve sawtooth segments, with about twelve proximal peaks 240 and about twelve distal peaks 240. The design of the frame provides radial strength and is compressible. In some aspects, each section may include about four to sixteen proximal peaks and about four to sixteen distal peaks.

[0140] In some aspects, multiple parts are interconnected by connecting each alternating proximal peak of a part with the alternating distal peak of another part. In such aspects, there can be about six pillar 230 components between the two parts. In some other aspects, the multiple parts can be interconnected by connecting every third alternating proximal peak of a part with every third alternating distal peak of another part. In such aspects, there can be about four pillar components between the two parts. In one aspect, multiple parts are rigidly interconnected using pillar components, which increases the stability when the valve is arranged, while balancing the sufficient flexibility when the valve works and the rigidity in the vein. In one aspect, the interconnected geometry formed by connecting each alternating proximal peak of a part with the alternating distal peak of another part provides sufficient flexibility to adapt to and simulate the natural expansion and contraction of the vein, thereby ensuring optimal stress distribution and providing suitable fit on a wider range of vein sizes. In one aspect, the interconnected geometry is designed to be sufficiently flexible to accommodate and simulate the natural expansion and contraction caused by transient increases in pressure and / or blood flow, including increases caused by muscle (e.g., calf muscle) activity (e.g., when the calf muscle contracts) and / or Valsalva maneuver.

[0141] Figure 2 The implantable frame has suture holes 210 on one or both ends, which can help attach the implantable frame to the valve assembly. In some specific aspects, the implantable frame has suture holes on both ends of the frame. In another embodiment, the suture holes 210 are located at the crown 210 of the frame serration.

[0142] Figure 3A is a cross-sectional view of an example leaflet according to an example embodiment of the present invention, showing the leaflet without an attached inflow skirt.

[0143] In one aspect of the exemplary embodiment, the tip of the leaflet is further formed by: cutting a continuous biological tissue into a shape having a tip-like top portion 320 and a generally rectangular bottom portion 310; folding the top portion 330 over the bottom rectangular portion to produce the apex of a single petal of the leaflet; and suturing the top portion to the bottom rectangular portion of the biological tissue to form the edge of the single petal, which is Figure 3B The entire leaflet is Figure 3A , where top portion 320 is the tip portion, 310 is the bottom portion, where 3 is the belly curve before folding. The outline of the top portion 320 folded is indicated as 330.

[0144] Figure 3Bis a side perspective view of a cross-sectional leaflet having a supporting wall 1 and an inflow skirt 2, wherein, in an exemplary embodiment, the inflow skirt 2 is attached to the base of the leaflet. In one aspect, the inflow skirt is attached to the wall, which provides a way to avoid flow interruption on the inflow side of the device. In another aspect, the inflow skirt 2 is attached to the wall and the leaflet 1. In some specific aspects, the skirt 2 material can be manufactured using biological tissue from a xenogeneic source. The xenogeneic source can be selected from a group including porcine, bovine, and equine. In one aspect, the xenogeneic source is porcine. In another aspect, the xenogeneic source is xenogeneic pericardium. In another aspect, the xenogeneic source is porcine pericardium. In one aspect, the skirt 2 material has an approximately rectangular shape.

[0145] Figure 3C A side perspective view of a folded leaflet 310 with skirt 2 is shown, wherein suture holes 300 can be seen. Single flap 320 is folded, and leaflet 310 with skirt 2 is folded. In one embodiment, the leaflet has multiple cusps, which can be bicuspid or tricuspid. In one embodiment, the design of the leaflet includes a ventral curve, which will be combined with Figure 3D Further introduction.

[0146] Figure 3D Various design shapes and angles in leaflets for transcatheter valves according to example embodiments are shown, including preferred designs that provide beneficial operation of the valve and leaflets. For example, for a 10 mm transcatheter venous valve, it can have a coaptation angle 340 of about 20-80 degrees, a free edge angle 350 between seam points of about 90-270 degrees, a total leaflet height 360 of about 6 mm-11 mm, a ratio of A+B to coaptation height of about 0.5-1, a seam to seam (CC) / flat width 380 of about 12 mm-20 mm, a coaptation gap 390 of about 0-3 mm, and a free edge distance 370 of about 14 mm-27 mm, as shown in FIG. Figure 3E shown.

[0147] Figure 3E Another example embodiment is shown, wherein Figure 3A The leaflets are formed for a 10 mm transcatheter venous valve having a preferred design according to example embodiments that provides beneficial operation of the valve and leaflets. For example, the leaflet design includes various structural relationships, such as a ventral curve, with a coaptation angle of approximately 30-65 degrees, a free edge angle between seam points of approximately 110-130 degrees, a total leaflet height of approximately 7 mm-10 mm, an A+B coaptation height ratio of approximately 0.85-0.95, a seam to seam (CC) / flat width of 16-18 mm, a coaptation gap of 0-2 mm, and a free edge distance of 17-22 mm.

[0148] A method for assembling a leaflet according to an exemplary embodiment of the present invention is Figures 4A to 4I In the statement, Figures 4A to 4I The various stages of the formation of leaflets 405 are shown. Figure 4E , 4G , 4H and 4I, the inflow skirt 425 is fixed to the leaflet 405. The inflow skirt can be attached to the leaflet only on the inflow side of the leaflet to prevent wind pocketing problems. The inflow skirt material helps prevent migration and assist flow. In example embodiments, the leaflet and inflow skirt can cover the entire valve.

[0149] In an example embodiment, the at least one leaflet with the inflow skirt material attached has a diameter of about 6 to 12 mm when folded into a cylinder. In one aspect, the at least one leaflet with the inflow skirt material attached has a diameter of about 9 mm to about 12 mm when folded into a cylinder.

[0150] According to another exemplary embodiment, the method includes: providing a continuous biological tissue that has been fixed; cutting the fixed biological tissue into a specific shape so that there is a top portion and a bottom portion; folding the top portion onto the bottom portion to produce the apex of a single leaflet of the leaflet; and suturing the top folded portion to the bottom folded portion along the edge to form the single leaflet shape of the leaflet. The method may also include attaching the single leaflet to the tissue inflow skirt by suturing. The method may also include attaching the single leaflet suturing to the tissue inflow skirt to the fabric skirt.

[0151] In one exemplary aspect, the suture holes on the tissue are spaced about 1.5 mm apart. In other aspects, the suture holes can be spaced about 0.5 mm to about 3 mm apart from each other. In another aspect, the suture spacing reduces leakage by overlapping the sutures.

[0152] At the beginning of the leaflet manufacturing process, the at least one leaflet can be formed from a flat sheet of continuous biological tissue that is folded to form a single-leaf shape. In an example embodiment, the exact geometry is not replicated, but the function of a native valve is achieved by using a single-leaflet leaflet that allows the leaflet to open and close rapidly to induce vortex flow manipulation relative to the blood flow. The tip of the leaflet can be folded from continuous biological tissue, so suturing is not required to form the apex of the leaflet tip. However, suturing can be used to form the edge of the leaflet tip. Figure 4A The leaflets in are formed by laser cutting porcine pericardial tissue into rectangular shapes, wherein the apex 415 of the animal donor remains intact.

[0153] In the exemplary embodiment, the smooth side of a leaflet of porcine pericardial laser-cut tissue is formed, approximately 10 mm. Figure 4AAs shown, the smooth side may be elastin fibers and the rough side may be collagen, wherein the cross section is approximately 80% collagen and approximately 20% elastin. Figure 4A As shown, the leaflets are folded on the supporting walls, as Figure 4B As shown, it is derived from a xenogeneic source, porcine, and is in a laser cut rectangular shape with smooth sides facing each other. The single leaflet and the valve wall prevent or reduce adhesion of the single leaflet to the valve wall when the valve is in the open position, and promote closing of the single leaflet valve when flow pressure is reduced.

[0154] exist Figure 4B In the embodiment, the suture hole formed in the supporting wall is aligned with the suture hole on the leaflet at the tip of the folded leaflet. The needle can then be passed through the first matching hole on the upper left side with a temporary suture (e.g., PTFE) to secure it in place. The temporary suture placed can be Figure 4C The suture should be inserted into the suture hole, not into the tissue around the suture hole. Excess suture can be removed. These steps can be repeated to secure the wall and leaflet to each other while more permanent sutures are placed. The temporary suture 400 reduces migration of the wall and leaflet and ensures that the suture holes of the two components are aligned.

[0155] After the temporary suture is in place, a needle with a polybutylene, monofilament, non-absorbable surgical suture may be inserted into the first matching hole in the upper left side of the leaflet and the supporting wall. Figure 4D The complete tissue leaflet (without skirt and supporting wall sutures) is shown after the two temporary sutures at the corners and the suture at the tip are completed. A continuous suture 410 can secure the wall to the leaflet by inserting the suture and needle into the same matching hole with a temporary knot. The excess suture can be removed. The suturing can continue in the next matching hole on the same side of the leaflet to form a double locking stitch. Once the last matching suture hole is reached, the needle can be passed through to form a triple locking stitch. The process can be repeated to suture the other side 410 of the leaflet tip. Figure 4D Two temporary sutures at the corners of the leaflet seams that can be removed using a suture needle are shown.

[0156] The skirt 425 can then be aligned with the inflow side of the leaflet 405. The skirt and leaflet can be oriented so that the smooth side of the skirt 425 and Figure 4B The supporting wall is visible. The skirt 425 can be folded over the top of the leaflet 405 so that the rough side of the skirt is visible. The bottom edge of the skirt 420 can be aligned with the bottom edge of the leaflet and the supporting wall. The side edges of the skirt should also be aligned with the side edges of the supporting wall. To assemble the leaflet assembly, a suture needle with a temporary suture (e.g., PTFE) can be used. In an exemplary embodiment, the needle is inserted through the skirt 425 and out through the leaflet supporting wall and secures it, such as Figure 4D As shown at 410. The needle may be inserted approximately 1 mm from the lower edge of the tissue and 0.5 mm from the left edge of the tissue.

[0157] Figure 4E Temporary sutures 420 are shown on the right and left sides of the leaflets and walls. Using a suture needle, for example, with polybutylene, monofilament, non-absorbable surgical suture and using the same suture holes as the temporary sutures, the needle can be inserted through the tissue skirt 425 and leaflet 405 to secure the skirt to the leaflet. The temporary sutures can then be removed so that the supporting wall of the leaflet can be sutured to the skirt 425 along the bottom edge using, for example, a double lock suture. The sutures can continue to the left of the attachment edge of the folded tip 415 up to about 1 mm.

[0158] Figure 4F The sutures are shown to be spaced approximately 1 mm apart and approximately 1 mm from the lower edge of tissue 430. Figure 4G As shown, the sutures may be spaced approximately 1 mm apart and approximately 1 mm from the lower edge of the tissue.

[0159] Figure 4H The skirt 435 is shown unfolding from the leaflets, walls, and the tip 440 is folded in the axial direction so that the tip is inside the fold. The edges of the tissue skirt / wall (which will become the seams of the tissue subassemblies) can be aligned. The sutures can be spaced approximately 1 mm apart and approximately 1 mm from the lower edge of the tissue. Fig. 4I As shown, the suture may be positioned approximately 0.5 mm from the outflow end of the tissue subassembly 445 and approximately 1 mm from the aligned edge of the assembly.

[0160] Figure 5 An unattached skirt is shown. In one aspect, the skirt is attached to the wall and leaflet skirt material. In some specific aspects, the skirt material can be made using biological tissue from a xenogeneic source. The xenogeneic source can be selected from a group including pigs, cows, and horses. In one aspect, the xenogeneic source is pigs. In another aspect, the xenogeneic source is xenogeneic pericardium. In another aspect, the xenogeneic source is porcine pericardium. In one aspect, the skirt material has the same source as the single leaflet. In some other aspects, the skirt material can be made using fabric. Such fabrics can include PET, PTFE fabrics, ePTFE, degradable stents, collagen stents, hyaluronic acid stents, fibrin, polymer-based degradable or non-degradable materials, or biomaterials. In a specific embodiment, the material has ultra-low porosity, suture retention, surface roughness, attachment stents, and surface area that can attract mesenchymal cells. In one aspect, the skirt is arranged on the inflow side of the valve to help flow.

[0161] The process of the exemplary embodiment of the overlay frame component is Fig. 6A , 6B and 6C. The material for the cover of the frame assembly may include PET, PTFE fabric, ePTFE, a degradable scaffold, a collagen scaffold, a hyaluronic acid scaffold, fibrin, a polymer-based degradable or non-degradable material, or a biomaterial. The cover for the frame is fixed to the frame. In the exemplary embodiment, polybutylene suture is used because it is strong and ductile.

[0162] Fig. 6A , 6B 6C shows a frame cover assembly to be arranged in the frame. In an exemplary embodiment, to assemble the device, a suture needle is prepared together with a polybutylene, monofilament, non-absorbable surgical suture. The overlapping ends of the fabric skirt are then grasped together (e.g., between the two longer ends) so that the ends of the fabric skirt are gathered together and the fabric skirt can be wrapped around a mandrel (identified as 620). The seam of the fabric skirt can be parallel to the mandrel, and the edge of the fabric skirt extends slightly beyond the end of the mandrel. The needle is then inserted inwardly approximately 1 mm below the free edge at the top of the skirt. Fixing should not be too close to the edge because the fabric may tear, especially when using a suture needle.

[0163] As shown, a knot may be made using the loose end loops, wherein the excess thread from the knot is retained. The needle may then be reinserted into the same hole to bring the needle to the outside where a stitch is made along the overlapping length. Fig. 6A As shown, a running suture designated 600 may have approximately 1 mm gaps between each stitch. Once the suture is at the bottom free edge of the skirt, the thread is wrapped around the end and the needle is inserted behind the last stitch made. A running stitch with approximately 1 mm gaps may be made, with no more gaps between each stitch, making the suture appear continuous. Fig. 6A In the process, the suture reaches the top free edge and an end knot is created.

[0164] like Figure 6B As shown, the frame cover is loaded around a mandrel (designated 620) through the inner diameter of the frame. Then, to secure the frame cover to the frame, a suture needle is prepared with a temporary suture (e.g., PTFE). Figure 6C As shown, the overlapping stitching lines are aligned with any eyelets in the crown on the frame cover. Figure 2 The eyelet is designated 210 in the figure and corresponds to an intermediate bridge of the frame and is in line with it. The eyelet in the crown of the frame is Figure 2 The bridging member of the frame is shown as 210. Figure 2 It is represented as 220 in Chinese.

[0165] The outer diameter of the fabric skirt can be aligned with the eyelets of the frame. From here, the frame cover (fabric skirt) can be attached to the frame by inserting a needle into any eyelet corresponding to one of the frame middle bridges. To secure the frame cover, a knot with loose end loops can be used, in Figure 6C 630. For the next eyelet, the process can be repeated using the same thread, wherein a double lock stitch can be used by wrapping the loop of the previous suture around the needle twice. An end knot can be used at the end of each suture, and any excess thread can be trimmed to complete the covering frame.

[0166] Figure 7 The orientation and directionality for valve assembly purposes in an exemplary embodiment are shown. To assemble the tissue leaflets into the previously formed cover frame subassembly, the tissue leaflet assembly can be arranged and inserted onto a tissue insertion mandrel having a diameter of approximately 9 mm, 9.5 mm, 10 mm, 10.5 mm, 11 mm, 11.5 mm, or 12 mm, depending on the size of the valve being assembled. During assembly, it is important to ensure that the tissue leaflet assembly is centered on the mandrel and that the tissue is not damaged. Then, as shown in FIG. Fig. 8A As shown, the tissue leaflet assembly can be inserted into the fabric skirt covered frame subassembly on a tissue insertion mandrel 800.

[0167] Once the tissue leaflet assembly is inserted into the fabric skirt covered frame assembly, the assembly will have inflow and outflow directions by identifying the inflow end as the end where the tissue flows into the skirt and the outflow end as the opposite end. After insertion into the tissue, the mandrel 800 can be carefully removed, such as with forceps, to ensure that the edges of the tissue are flush with the inflow / outflow diameter of the frame and to minimize wrinkles.

[0168] Fig. 8A An example embodiment is shown where a needle and temporary suture (eg, PTFE) is used to suture into one of the coronal eyelets 810 of the framework and secure. Figure 8B The first temporary suture is at one crown eyelet 810, and this step can be repeated for making four other eyelets on each crown 805 of the valve assembly have temporary knots. The temporary knots should be equidistantly arranged on twelve eyelets on each crown (inflow / outflow) of the valve assembly. A different number of eyelets can be used, such as 6, 7, 8, 9, 10, 11 or 12.

[0169] exist Figure 7 In FIG. 1 , the peripheral portion is shown as a flared end of an exemplary embodiment. To attach the peripheral 915 portion, a polybutylene, monofilament, non-absorbable surgical suture with a suture needle is assembled. Fig.9AAs shown, begin suturing one peripheral 915 portion (inflow or outflow). As suturing continues, position the bridge 905 connection and insert the needle near the bottom of the diamond-shaped support 925 on the peripheral portion. Fig.9A As shown, the needle should be inserted outside of the diamond, as shown at 900. Fig. 9B It is shown that at 910 the needle is passed through the other side of the support at 925. Fig. 9C As shown, a prepared needle (designated 920) having a polybutylene, monofilament, non-absorbable surgical suture is inserted into the first hole formed. Then, a loop of the suture is passed over the excess thread, the loop is pulled, and the excess thread can be trimmed off.

[0170] like Fig.9D As shown, from the inside of the frame, the needle is inserted at the side of the strut about 1 mm from the previous needle, about in the middle of the strut in the exemplary embodiment. The suture can be sutured about three times around each strut 925 of the frame. On the other hand, the suture is sutured about once to about five times around each strut 925 of the frame. The needle should reach the opposite side of the strut 925 into which it is inserted. On the outside of the frame, the needle can be inserted outside the diamond-shaped strut 925.

[0171] Fig.9E It is shown that another stitch can be placed around the diamond-shaped pillar 925 about 1 mm (away) from the last crown eyelet 935. Then, the curved needle can be passed through the eyelet 935 of the crown 935 and the suture can be brought out, as shown in FIG. Fig.9E As shown at 930 in FIG. Fig.9F As shown, the temporary suture can be removed with a feather scalpel blade before tying the double locking stitch knot, as shown at 940. Figure 9G In the embodiment of the present invention, the needle can be reinserted at 945 through the middle of the diamond-shaped support 925. Figure 9H In the embodiment, the reinserted curved needle can be passed back through the inside of the tissue skirt along with the suture, and the needle passes through the suture from the other side of the diamond-shaped pillar 925 back to the outside of the diamond-shaped pillar 925. Continue in this way to match the suture pattern and configuration on both sides of the diamond-shaped pillar 925.

[0172] Fig.9I An example embodiment is shown in which the curved needle is reinserted with the suture back through the fabric skirt from the outside of the tissue skirt to the inside. The needle is then brought out near the strut bridge at 950. When the sutured strut 925 has a bridge 905 connector connected to an adjacent portion, an additional single loop of suture can be created on the bridge 905 connector. Figure 9J As shown, a curved needle with suture can be passed over bridge 905 and the suture passed from the outside of the fabric skirt to the inside of the tissue inflow skirt to form a loop around bridge 905.

[0173] After suturing all the framework 925 struts, an end knot can be created and the previous steps can be repeated with another peripheral frame portion using polybutylene, monofilament, non-absorbable surgical sutures and sewing needles. The needle can be inserted directly into the periphery of the strut bridge 905 on an intermediate strut portion and the knot is secured. Keeping the leaflet open when suturing the middle portion of the tissue leaflet will help avoid damaging the leaflet. Since there is no eyelet for the middle portion, a single loop suture should continue to pass through the middle strut. When the sutured strut 925 has a bridge 905 connector with an adjacent portion, an additional single loop suture can be created on the bridge 905 connector. These steps can be repeated for the remaining struts on the middle portion 955. After suturing all the framework struts 925, an end knot can be created and the previous steps can be repeated for the remaining middle frame portion 955.

[0174] Fig.10 An exploded delivery system of one embodiment is shown with capsule, catheter, pusher shaft, strain relief, lead screw, lead screw knob, handle housing (lower and upper), female connector, screw insert, BHCS, and loctite. Fig.10 There is a handle portion, an operating system and a catheter system, which has a receiving area for the valve. Fig.10 In the delivery device, the capsule or RO marker is identified by the number 1. This indicator represents the point through which the valve has passed and must be deployed and cannot be retracted into the delivery device.

[0175] The capsule is numbered 2. The catheter is numbered 3; in one variation, it is 0.159 in. The pusher shaft that helps deploy the valve is Fig.10 The pusher shaft passes through the catheter to assist in loading the valve. The tab holder is located in Fig.10 The strain relief device is marked with the number 5. Fig.10 The number is 6 in the figure, and the lead screw is 7. Fig.10 The lead screw knob, identified as number 8 in the figure, is where a person can turn the mechanism to retract the pusher shaft or extend the pusher shaft. These mechanisms are partially covered by a handle housing, which is divided into two parts - in Fig.10 The lower part is marked with 10 and the upper part is marked with 9. The female connector is Fig.10 The number is 11. Fig.10 Insert the spiral insert marked 12 into Fig.10 In the handle housing marked as 10, wherein Fig.10 The BHCS marked 13 in the figure is inserted into the spiral insert. Loctite Fig.10 It is marked with number 14.

[0176] Fig.11AThe assembled conveyor system is shown in cross-section. Fig. 11B is a side cutaway perspective view of a nose cone assembly with a sheath assembly in an example embodiment system, the sheath assembly including a nose cone identified as number 1 and a nose cone braided shaft identified as number 2 connected to a hypotube (identified as number 3) of an inner tube assembly in a delivery device. In this embodiment, the three-in-one system allows the device to not require a separate dilator or introducer sheath because the tapered bullet-shaped nose cone provides atraumatic access for use as a dilator, and the distal region of the catheter assembly has a continuous and uniform diameter for use as an introducer sheath.

[0177] Fig. 12A A crimper in an example embodiment is shown, wherein 1 is a crimper front plate, 2 is a crimper element, 3 is a crimper handle, 4 is a crimper base, 5 is a crimper back plate, 6 is a spacer for a screw, 7 is a crimper element spring, and 8 is a socket head screw. The crimper is used to prepare a venous valve for loading into a delivery system. Fig. 12B As shown, the venous valve is arranged in the crimper and centered with the help of the crimper pin 1205. The crimper pin 1205 is used to help arrange the valve 1215 in the crimper and guide it into the delivery device 1210, as shown in FIG. Fig. 12B As shown at 1200. Fig. 12C The crimper is shown closed, with the valve held in place, and pushed into a delivery device, shown as 1210, to be loaded. Fig.12D Another angle of the crimper is shown where the crimper pins 1205 hold the delivery device in place. Fig.12E An upper angle of the crimper used to load the conveyor 1210 is shown.

[0178] Example enumerated aspects of the invention are described below.

[0179] 1. A method of manufacturing a valve for transcatheter delivery and deployment, comprising:

[0180] Arranging the biological tissue sheet into a substantially flat orientation;

[0181] folding the sheet so as to form a single-petal shape having an apex and at least two edges; and

[0182] Leaflets are formed that can be deployed via a catheter and operated as a valve using a single leaflet shape.

[0183] 2. The method according to example 1, further comprising: suturing the biological tissue to form at least two edges of a single flap shape.

[0184] 3. The method of embodiment 1, wherein the biological tissue is from a heterologous source.

[0185] 4. The method of example 3, wherein the heterologous source is selected from the group consisting of porcine, bovine and equine.

[0186] 5. The method of example 4, wherein the heterologous source is porcine.

[0187] 6. The method of example 3, wherein the xenogeneic source is pericardium.

[0188] 7. The method according to example 1, wherein the sheet is formed by cutting a continuous biological tissue so as to have a shape having a top portion and a bottom rectangular portion.

[0189] 8. The method of example 7, further comprising: folding the top portion over the bottom rectangular portion to create a single-petal apex.

[0190] 9. The method of example 8, further comprising: sewing the top portion to the bottom rectangular portion to form a single-petal shaped edge.

[0191] 10. The method of example 10, wherein the leaflets are attached to the inflow skirt material.

[0192] 11. The method of example 10, wherein the inflow skirt material is manufactured using biological tissue from a xenogeneic source.

[0193] 12. The method of example 11, wherein the heterologous source is selected from the group consisting of porcine, bovine, and equine.

[0194] 13. The method of example 11, wherein the xenogeneic source is pericardium.

[0195] 14. The method of example 10, wherein the inflow skirt material is made of a non-biological material.

[0196] 15. The method of example 11, wherein the inflow skirt material has a rectangular shape.

[0197] 16. The method of example 11, wherein the inflow skirt material has a generally rectangular shape with slightly wider end portions.

[0198] 17. The method of example 1, wherein the valve is attached to the frame.

[0199] 18. The method of example 17, wherein the leaflet is covered by a fabric skirt before sewing the leaflet to the frame.

[0200] 19. The method of example 10, wherein the leaflets attached to the inflow skirt material are covered by the fabric skirt before sewing it to the frame.

[0201] 20. The method of example 1, wherein the valve is a cylinder having a diameter of about 6 mm to about 18 mm.

[0202] 21. The method of example 20, wherein the valve forms a generally cylindrical shape having a diameter of approximately 9 mm to 12 mm.

[0203] 22. A method of manufacturing a replacement valve for transcatheter delivery and deployment, comprising:

[0204] subjecting continuous biological tissue to a fixation process;

[0205] cutting the fixed biological tissue so that there is a top portion and a bottom portion;

[0206] folding the top portion over the bottom portion to form an apex of the single-petal shape of the leaflet; and

[0207] The top folded portion is attached to the bottom folded portion to form a single leaflet.

[0208] 23. The method of example 22, further comprising: attaching the single leaflet to the inflow tissue skirt using sutures.

[0209] 24. The method of example 22, further comprising: attaching the single leaflet to the fabric skirt.

[0210] 25. The method of embodiment 22, wherein the biological tissue is from a xenogeneic source.

[0211] 26. The method of example 25, wherein the heterologous source is selected from the group consisting of porcine, bovine, and equine.

[0212] 27. The method of example 26, wherein the xenogeneic source is porcine.

[0213] 28. The method of example 25, wherein the xenogeneic source is pericardium.

[0214] 29. A replacement valve comprising:

[0215] A biological tissue that has been subjected to a fixation process and cut into a top portion and a bottom portion;

[0216] an apex formed by folding the top portion over the base portion so as to form a single-petal shaped apex of the leaflet; and

[0217] a single leaflet formed by attaching a top folded portion to a bottom folded portion, the leaflet providing a spatial buffer between the single leaflet and the valve wall when the valve is in an open position and facilitating closure of the single leaflet valve when a sufficient flow pressure gradient is generated;

[0218] A frame is coupled to the single valve leaflet.

[0219] 30. The valve of example 29, wherein the single leaflet is disposed toward one end of the frame.

[0220] 31. The valve of example 29 wherein the inflow skirt is attached to the valve wall to reduce flow disruption and thrombus formation.

[0221] 32. The valve of example 29, wherein the single leaflet is folded from a continuous biological tissue without being sutured to form the apex of the single leaflet.

[0222] 33. The valve of example 32, wherein: the single leaflet has a ventral curve and at least one of: a coaptation angle of about 20 degrees to 80 degrees, a free edge angle between commissure points of about 90 degrees to 20 degrees, a leaflet total height of about 6 mm to 11 mm, a coaptation height ratio of about 0.5-1, a commissure to commissure (CC) / flat width of about 12 mm-20 mm, a coaptation gap of about 0 to 3 mm, and a free edge distance of about 14 mm-27 mm.

[0223] 34. The valve of example 29 wherein the wall is attached to the leaflets.

[0224] 35. An implantable compressible venous framework comprising:

[0225] a first portion formed from a first plurality of segments;

[0226] a second portion connected to the first portion, the second portion being formed from a second plurality of segments, wherein the connected first portion and second portion form a hollow cylinder; and

[0227] The first plurality of segments include a first plurality of proximal peaks and a first plurality of distal peaks, and the second plurality of segments include a second plurality of proximal peaks and a second plurality of distal peaks.

[0228] 36. The intravenous frame according to example 35, wherein each end of the cylinder has a flare, the flare is between about 0 mm and about 10 mm from the start of the flare to the end of the flare, and the hollow cylinder can be compressed to 12 Fr-16 Fr.

[0229] 37. The intravenous framework of example 35, wherein each end of the post has a flare that anchors or hooks the framework to natural tissue during insertion.

[0230] 38. The intravenous frame according to example 35 further comprises: a third body portion connected to the second portion, the third portion being formed by a third plurality of segments, wherein the connected second portion and third portion form a hollow cylinder; and

[0231] The second plurality of segments includes a third plurality of proximal peaks and a second plurality of distal peaks, and the third plurality of segments includes a third plurality of proximal peaks and a second plurality of distal peaks.

[0232] 39. The intravenous frame according to Example 38 further comprises: a fourth body portion connected to the third portion, the fourth portion being formed by a fourth plurality of segments, wherein the connected third portion and fourth portion form a hollow cylinder; and

[0233] The third plurality of segments includes a fourth plurality of proximal peaks and a third plurality of distal peaks, and the fourth plurality of segments includes the third plurality of proximal peaks and a second plurality of distal peaks.

[0234] 40. The venous framework of example 35, further comprising: two to sixteen crowns formed on each of the first portion and the second portion to facilitate compressibility.

[0235] 41. The venous framework of example 40, further comprising: anchors or hooks along the column at the crown.

[0236] 42. The venous framework of example 40, wherein the radial strength can be 17-20N, depending on the number of segments and crowns.

[0237] 43. The venous framework of example 35, wherein the first portion and the second portion are self-expanding or assisted by a balloon expansion system.

[0238] 44. The venous framework of example 35, wherein the first portion and the second portion are covered by a material comprising a fabric or a coating.

[0239] 45. A method of making an implantable compressible venous framework comprising:

[0240] forming a first portion from a first plurality of segments;

[0241] forming a second portion connected to the first portion, the second portion being formed from a second plurality of segments, wherein the connected first and second portions form a hollow cylinder having flared ends;

[0242] The first plurality of segments includes a first plurality of proximal peaks and a first plurality of distal peaks, and the second plurality of segments includes a second plurality of proximal peaks and a second plurality of distal peaks, thereby providing stability and compressing the structure.

[0243] 46. ​​The method of example 45, further comprising: forming a third body portion connected to the second portion, the third portion being formed from a third plurality of segments, wherein the connected second portion and third portion form a hollow cylinder; and

[0244] The second plurality of segments includes a third plurality of proximal peaks and a second plurality of distal peaks, and the third plurality of segments includes a third plurality of proximal peaks and a second plurality of distal peaks.

[0245] 47. The method of example 45, further comprising: forming a fourth body portion connected to the third portion, the fourth portion being formed by a fourth plurality of segments, the connected third portion and fourth portion forming a hollow cylinder; and

[0246] The third plurality of segments includes a fourth plurality of proximal peaks and a third plurality of distal peaks, and the fourth plurality of segments includes the third plurality of proximal peaks and the second plurality of distal peaks.

[0247] 48. The method of example 45 further comprising: disposing a replacement valve leaflet within the first portion and the second portion, the replacement valve leaflet comprising a leaflet, a wall, and an inflow skirt.

[0248] 49. A curling device comprising:

[0249] Curler front plate;

[0250] a crimper element coupled to the crimper front plate; and

[0251] A crimper handle is coupled to the crimper element, wherein the crimper element is adapted to receive the compressible intravenous frame for delivering the frame into a vein via a catheter.

[0252] 50. The device of example 49, wherein the device compresses the compressible venous framework into a cylindrical shape.

[0253] 51. The device of example 49 further comprising: a non-blood contacting device having a crimping pin operable with the crimper element, wherein the pin is pushed through the crimper element to guide the compressible venous framework while maintaining the crimped state.

[0254] 52. A delivery system comprising: at least an inner tube assembly; a sheath assembly coupled to the inner tube assembly; a movable catheter assembly operable with the sheath assembly; and a handle, wherein the catheter assembly is adapted to receive a compressible intravenous frame for delivering the frame into a vein via a catheter.

[0255] 53. The device of example 52, wherein the sheath assembly is connected to the inner tube assembly by partially or completely covering the nose cone braided shaft of the sheath assembly with the hypotube of the inner tube assembly, and the sheath assembly and the inner tube assembly can pass a standard guide wire.

[0256] 54. The device of example 53 wherein the catheter assembly is slidably disposed on the sheath assembly and comprises a proximal region and a distal region.

[0257] 55. The device of Example 54, wherein: one end of the proximal region of the catheter assembly is connected to the handle, a second end of the proximal region of the catheter assembly is connected to the distal region of the catheter assembly, the one end of the distal region of the catheter assembly can be configured to compressively accommodate the transcatheter valve in a compressed configuration, and the second end of the distal region of the catheter assembly is connected to the proximal region of the catheter assembly.

[0258] 56. The device of example 55 wherein the handle is configured to controllably move the catheter assembly relative to the sheath assembly.

[0259] 57. The device of example 55 wherein controllably moving the handle provides a resting state in which the distal region of the catheter assembly is closer to the nose cone or a delivery state in which the distal region of the catheter assembly is pulled away from the nose cone.

[0260] 58. A curling device comprising:

[0261] Curler front plate;

[0262] a crimper element coupled to the crimper front plate;

[0263] a crimper handle coupled to the crimper element, wherein the crimper element is adapted to receive the compressible intravenous frame for delivering the frame into a vein via a catheter; and

[0264] A guide pin is operable with the crimper element to assist in loading the transcatheter device into the crimper.

[0265] 59. The device of example 58 wherein the guide pin has a wider base to be gripped and narrows to fit more narrowly within the crimping element.

[0266] 60. The device of example 58 wherein the guide pin allows passage of a nose cone of the transcatheter device.

[0267] 61. The device of example 60, wherein the guide pin is pushed to guide the transcatheter device therethrough while maintaining the transcatheter device in a crimped state.

[0268] 62. A transmission system comprising:

[0269] a first assembly including a catheter, a capsule, handle top and bottom housings, an advancer shaft, a tab holder, an index marker, a main screw knob, and a leadscrew;

[0270] A second assembly is coupled to the first assembly, the second assembly comprising a delivery system irrigation attachment and a nose cone assembly, wherein the entire distal end of the first assembly and the distal end of the second assembly have a single diameter.

[0271] 63. The delivery system of example 62 wherein: the first component includes a tab retainer at the end of the pusher shaft to securely hold the base of the device within the first component and aid in releasing / deploying the device upon implantation while the pusher shaft maintains column strength.

[0272] 64. The conveyor system of example 63, wherein the pusher shaft has a reduced diameter in a mid-section to prevent kinking and avoid friction during operation.

[0273] 65. The delivery system of example 62 further comprising: a guide pin operable with the first assembly and the second assembly to push the transcatheter device through the crimper to guide the transcatheter device while maintaining the transcatheter device in a crimped state.

[0274] 66. The delivery system of example 62, wherein the nose cone assembly and / or the distal end of the catheter includes an indicator marker (a radiopaque (RO) marker) that can be visualized by fluoroscopy.

Claims

1. A method of manufacturing a valve for transcatheter delivery and deployment, comprising: Arranging the biological tissue sheet into a substantially flat orientation; folding the sheet so as to form a single-petal shape having an apex and at least two edges; as well as Leaflets are formed that can be deployed via a catheter and operated as a valve using a single leaflet shape.

2. The method according to claim 1, further comprising: The biological tissue is sutured so as to form the at least two edges of the single-flap shape.

3. The method according to claim 1, wherein: The biological tissue is from a heterologous source.

4. The method according to claim 3, wherein: The xenogeneic source was selected from the group consisting of porcine, bovine, and equine.

5. The method according to claim 4, wherein: The source of the xenobiotic is porcine.

6. The method according to claim 3, wherein: The xenobiotic source is the pericardium.

7. The method according to claim 1, wherein: The sheet is formed by cutting a continuous biological tissue so as to have a shape having a top portion and a bottom rectangular portion.

8. The method according to claim 7, further comprising: The top portion is folded over the bottom rectangular portion to create the apex of the single petal.

9. The method according to claim 8, further comprising: The top portion is sewn to the bottom rectangular portion to form the edges of the single-petal shape.

10. The method according to claim 10, wherein: The leaflets are attached to the inflow skirt material.

11. The method according to claim 10, wherein: The inflow skirt material is fabricated using biological tissue from a xenogeneic source.

12. The method according to claim 11, wherein: The xenogeneic source was selected from the group consisting of porcine, bovine, and equine.

13. The method according to claim 11, wherein: The xenobiotic source is the pericardium.

14. The method of claim 10, wherein: The inflow skirt material is made of non-biological material.

15. The method of claim 11, wherein: The inflow skirt material has a rectangular shape.

16. The method of claim 11, wherein: The inflow skirt material has a generally rectangular shape with slightly wider end portions.

17. The method of claim 1, wherein: The valve is attached to the frame.

18. The method of claim 17, wherein: Before the leaflet is sewn to the frame, it is covered by a fabric skirt.

19. The method of claim 10, wherein: The leaflets attached to the inflow skirt material are covered by the fabric skirt before sewing it to the frame.

20. The method of claim 1, wherein: The valve is a cylinder with a diameter of about 6 mm to about 18 mm.

21. The method of claim 20, wherein: The valve forms a generally cylindrical shape with a diameter of approximately 9 mm to 12 mm.

22. A method of manufacturing a replacement valve for transcatheter delivery and deployment, comprising: subjecting continuous biological tissue to a fixation process; Cutting the fixed biological tissue so that there is a top portion and a bottom portion; folding the top portion over the bottom portion so as to form an apex of the single-petal shape of the leaflet; as well as The top folded portion is attached to the bottom folded portion to form a single leaflet.

23. The method according to claim 22, further comprising: The single leaflet is attached to the inflow tissue skirt using sutures.

24. The method of claim 22, further comprising: The single leaflet is attached to the fabric skirt.

25. The method of claim 22, wherein: The biological tissue is from a heterologous source.

26. The method of claim 25, wherein: The xenogeneic source was selected from the group consisting of porcine, bovine, and equine.

27. The method of claim 26, wherein: The source of the xenobiotic is porcine.

28. The method of claim 25, wherein: The xenobiotic source is the pericardium.

29. A replacement valve, comprising: A biological tissue that has been subjected to a fixation process and cut into a top portion and a bottom portion; an apex formed by folding the top portion over the base portion so as to form a apex of a single-petal shape of the leaflet; as well as a single leaflet formed by attaching a top folded portion to a bottom folded portion, the leaflet providing a spatial buffer between the single leaflet and the valve wall when the valve is in an open position and facilitating closure of the single leaflet valve when a sufficient flow pressure gradient is generated; A frame is connected to the single-valve leaflet.

30. The valve of claim 29, wherein: The single leaflet is arranged towards one end of the frame.

31. The valve of claim 29, wherein: The inflow skirt is attached to the valve wall to reduce flow disruption and thrombus formation.

32. The valve of claim 29, wherein: The single leaflet is folded from a continuous biological tissue without being sutured to form the apex of the single leaflet.

33. The valve of claim 32, wherein: The single leaflet has a ventral curve and at least one of: a coaptation angle of approximately 20 degrees to 80 degrees, a free edge angle between seam points of approximately 90 degrees to 20 degrees, a leaflet total height of approximately 6 mm to 11 mm, a coaptation height ratio of approximately 0.5-1, a seam to seam (CC) / flat width of approximately 12 mm-20 mm, a coaptation gap of approximately 0 to 3 mm, and a free edge distance of approximately 14 mm-27 mm.

34. The valve of claim 29, wherein: The wall is attached to the leaflet.

35. An implantable compressible venous framework comprising: a first portion formed from a first plurality of segments; a second portion connected to the first portion, the second portion being formed from a second plurality of segments, wherein the connected first portion and second portion form a hollow cylinder; and The first plurality of segments include a first plurality of proximal peaks and a first plurality of distal peaks, and the second plurality of segments include a second plurality of proximal peaks and a second plurality of distal peaks.

36. The venous framework of claim 35, wherein: Each end of the cylinder has a flare, the flare is between about 0 mm and about 10 mm from the start of the flare to the end of the flare, and the hollow cylinder can be compressed to 12Fr-16Fr.

37. The venous framework of claim 35, wherein: Each end of the post has a flare that anchors or hooks the frame to native tissue when inserted.

38. The venous framework of claim 35, further comprising: a third body portion connected to the second portion, the third portion being formed from a third plurality of segments, wherein the connected second and third portions form a hollow cylinder; and wherein the second plurality of segments includes a third plurality of proximal peaks and a second plurality of distal peaks, and the third plurality of segments includes a third plurality of proximal peaks and a second plurality of distal peaks.

39. The venous framework of claim 38, further comprising: a fourth body portion connected to the third portion, the fourth portion being formed from a fourth plurality of segments, wherein the connected third and fourth portions form a hollow cylinder; and The third plurality of segments includes a fourth plurality of proximal peaks and a third plurality of distal peaks, and the fourth plurality of segments includes the third plurality of proximal peaks and a second plurality of distal peaks.

40. The venous framework of claim 35, further comprising: Two to sixteen crowns are formed on each of the first portion and the second portion to aid in compressibility.

41. The venous framework of claim 40, further comprising: Anchors or hooks along the post at the crown.

42. The venous framework of claim 40, wherein: The radial strength can be 17-20N, depending on the number of sections and crowns.

43. The venous framework of claim 35, wherein: The first and second sections are either self-expanding or assisted by a balloon dilation system.

44. The venous framework of claim 35, wherein: The first portion and the second portion are covered by a material including a fabric or a coating.

45. A method of making an implantable compressible venous framework, comprising: forming a first portion from a first plurality of segments; forming a second portion connected to the first portion, the second portion being formed from a second plurality of segments, wherein the connected first and second portions form a hollow cylinder having flared ends; Wherein, the first plurality of segments includes a first plurality of proximal peaks and a first plurality of distal peaks, and the second plurality of segments includes a second plurality of proximal peaks and a second plurality of distal peaks, thereby providing stability and enabling compression of the structure.

46. ​​The method of claim 45, further comprising: forming a third body portion connected to the second portion, the third portion being formed from a third plurality of segments, wherein the connected second and third portions form a hollow cylinder; and The second plurality of segments include a third plurality of proximal peaks and a second plurality of distal peaks, and the third plurality of segments include a third plurality of proximal peaks and a second plurality of distal peaks.

47. The method of claim 45, further comprising: forming a fourth body portion connected to the third portion, the fourth portion being formed by a fourth plurality of segments, the connected third portion and fourth portion forming a hollow cylinder; as well as The third plurality of segments include a fourth plurality of proximal peaks and a third plurality of distal peaks, and the fourth plurality of segments include a third plurality of proximal peaks and a second plurality of distal peaks.

48. The method of claim 45, further comprising: A replacement valve leaflet is disposed within the first portion and the second portion, the replacement valve leaflet comprising a leaflet, a wall, and an inflow skirt.

49. A curling device comprising: Curler front plate; a crimper element coupled to the crimper front plate; as well as A crimper handle is coupled to the crimper element, wherein the crimper element is adapted to receive a compressible intravenous frame for delivering the frame into a vein via a catheter.

50. The apparatus of claim 49, wherein: The device compresses the compressible venous framework into a cylindrical shape.

51. The apparatus of claim 49, further comprising: A non-blood contacting device having a crimping pin operable with a crimper element wherein the pin is pushed through the crimper element to guide the compressible venous frame while maintaining a crimped state.

52. A conveying system comprising: at least the inner tube assembly; a sheath assembly coupled to the inner tube assembly; a movable catheter assembly operable with the sheath assembly; and a handle, wherein the catheter assembly is adapted to receive a compressible intravenous frame for delivering the frame into a vein via a catheter.

53. The apparatus of claim 52, wherein: The sheath assembly is connected to the inner tube assembly by partially or completely covering the nose cone braided shaft of the sheath assembly with the hypotube of the inner tube assembly, and the sheath assembly and the inner tube assembly are capable of passing a standard guide wire.

54. The apparatus of claim 53, wherein: The catheter assembly is slidably disposed on the sheath assembly and includes a proximal region and a distal region.

55. The apparatus of claim 54, wherein: One end of the proximal region of the catheter assembly is connected to the handle, and the second end of the proximal region of the catheter assembly is connected to the distal region of the catheter assembly, wherein one end of the distal region of the catheter assembly can be configured to compressively accommodate the transcatheter valve in a compressed configuration, and the second end of the distal region of the catheter assembly is connected to the proximal region of the catheter assembly.

56. The apparatus of claim 55, wherein: The handle is configured to controllably move the catheter assembly relative to the sheath assembly.

57. The apparatus of claim 55, wherein: Controllably moving the handle provides a resting state, in which the distal region of the catheter assembly is closer to the nose cone, or a delivery state, in which the distal region of the catheter assembly is pulled away from the nose cone.

58. A curling device comprising: Curler front plate; a crimper element coupled to the crimper front plate; a crimper handle coupled to the crimper element, wherein the crimper element is adapted to receive the compressible intravenous frame for delivering the frame into a vein via a catheter; as well as A guide pin is operable with the crimper element to assist in loading the transcatheter device into the crimper.

59. The apparatus of claim 58, wherein: The guide pin has a wider base to grasp and narrows to fit more narrowly within the crimping element.

60. The apparatus of claim 58, wherein: The guide pin allows passage of the nose cone of the transcatheter device.

61. The apparatus of claim 60, wherein: The guide pin is pushed to guide the transcatheter device through while maintaining the transcatheter device in a crimped state.

62. A conveying system comprising: a first assembly including a catheter, a capsule, handle top and bottom housings, an advancer shaft, a tab holder, an indicator marker, a main screw knob, and a leadscrew; A second assembly is coupled to the first assembly, the second assembly comprising a delivery system irrigation attachment and a nose cone assembly, wherein the entire distal end of the first assembly and the distal end of the second assembly have a single diameter.

63. The delivery system of claim 62, wherein: The first component includes a tab retainer at the end of the pusher shaft to securely hold the base of the device within the first component and aid in releasing / deploying the device upon implantation while the pusher shaft maintains column strength.

64. The delivery system of claim 63, wherein: The propeller shaft has a reduced diameter in the middle section in order to prevent kinking and avoid friction during operation.

65. The delivery system of claim 62, further comprising: A guide pin is operable with the first component and the second component to push the transcatheter device through the crimper to guide the transcatheter device while maintaining the transcatheter device in a crimped state.

66. The delivery system of claim 62, wherein: The nose cone assembly and / or the distal end of the catheter includes an indicator marker (radio-opaque (RO) marker) that can be visualized by fluoroscopy.

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