WO2025176845A1

WO2025176845A1 - Graft

Info

Publication number: WO2025176845A1
Application number: PCT/EP2025/054725
Authority: WO
Inventors: Wei Cheng; Ferdinand Maria Cornelis SOETERS
Original assignee: DSM IP Assets BV
Current assignee: DSM IP Assets BV
Priority date: 2024-02-22
Filing date: 2025-02-21
Publication date: 2025-08-28
Anticipated expiration: 2026-08-22

Abstract

A graft includes a tube having an inner film layer, an outer film layer disposed radially outward of the inner film layer, and a radiopaque element disposed between the inner film layer and the outer film layer. The radiopaque element may include a polymer material having a radiopacifier material contained therein, and the radiopacifier material imparts radiopacity to the radiopaque element. The graft may further include a reinforcing element disposed between the inner film layer and the outer film layer and/or a middle film layer disposed between the outer film layer and the inner film layer. The reinforcing element and the radiopaque element may be positioned on opposite sides of the middle film layer.

Description

Graft

Field

The disclosure relates to grafts, methods of making grafts, and the use of such grafts to treat various medical conditions, such as aortic aneurysms or peripheral artery disease.

Background

Grafts are commonly used to treat diseased blood vessels and other tubular structures within the body. For example, a graft may be employed to reinforce or radially open blood vessels for the purpose of restoring or maintaining blood flow. Grafts may be implanted in the coronary, aortic and peripheral vasculature, neurovasculature, and in other bodily conduits such as the urinary tract, the bile duct, and the tracheo-bronchial tree.

Grafts typically comprise a metal stent covered by a fabric, film, and/or membrane, and grafts of this type may also be known as a stent-graft. Various designs are possible for the metal stent, but they typically comprise a series of metal rings connected by metal bridges. The covering is typically a PTFE, an ePTFE (expanded PTFE) membrane, or a woven or knitted PET fabric.

Endovascular grafts require compressibility and flexibility to allow for proper positioning in the vasculature. Such grafts are either self-expandable or balloon expandable. A self-expandable graft expands upon removal of the constraint that keeps the graft from expanding. Balloon expandable grafts use a balloon to expand the graft. In either case, the graft must be compressible during delivery and positioning and expand to exert pressure on the vessel wall upon delivery.

Certain graft placements benefit from the graft including radiopaque markers that can be visualized under imaging modalities such as fluoroscopy to aid in precise deployment, e.g., for intracranial aneurysms. Such markers may be configured to show the position of the graft in general and/or certain portions of the graft. Other medical devices such as catheters, guidewires, implanted medical devices, etc., can also benefit from the use of radiopaque markers. Grafts are most frequently made radiopaque by attaching radiopaque markers to the stent frame. Such radiopaque markers are typically noble metals. However, this technique creates problems with corrosion and may impact flexibility of the stent. Radiopaque coatings may be used, but these have the tendency to flake off, which can be catastrophic. Accordingly, radiopaque markers may often be connected to grafts by suturing onto the stent frame. For example, International Application Publication No. WO 2020/180613, which is incorporated by reference herein, discloses a thin polyurethane having radiopaque particles throughout, which provides improved resistance to suture pullout and tearing, enabling more secure suturing to a stent frame.

Polymeric markers may be preferred to metal markers for existing techniques, because pure metal markers are not compressible, making crimping difficult. Moreover, as disclosed in WO 2020/180613, other compounded radiopaque markers may also have poor performance during crimping, due to the hard, brittle nature of compounded, heat- processed radiopaque polymers, which results in poor compliance to native tissue and/or insufficient crimpability and elasticity. Accordingly, many radiopaque materials are placed at the ends of the stent where the degree of crimping is less.

Polymeric markers also have the benefit of being moldable into better visualized constructions, such as rings (full, half, or quarter) that are not possible for metal. The rings allow for better visualization during docking than simple “dots” of metal placed at various locations. Further, grafts using polymeric markers are more easily handled and manufactured, as they have singular or relatively few components as compared to the numerous small pieces that must be attached when metal markers are used. Polymeric markers also provide improved performance when crimped, as discussed above. Noble metal markers are frequently used, but present disadvantages such as expensive cost, expensive process of introducing the marker (e.g., hand introducing coiled gold or platinum wire), reduced bonding strength of welding, and the potential to cause severe galvanic corrosion of the stent alloys if no extra coating protection is utilized. Polymeric markers do not suffer from these disadvantages.

Accordingly, there is a need for a graft that provides a reliable radiopaque marker that does not require suturing, is simple and efficient to manufacture, and avoids difficulties with crimping and elasticity. The present disclosure is provided to address this need and other needs in existing grafts and manufacturing techniques for such grafts. A full discussion of the features and advantages of the present invention is deferred to the following detailed description, which proceeds with reference to the accompanying drawings. Summary

Aspects of the disclosure relate to a graft including a tube having at least an inner film layer and an outer film layer disposed radially outward of the inner film layer, and a radiopaque element disposed between the inner film layer and the outer film layer. In one embodiment, the radiopaque element comprises a polymer material having a radiopacifier material contained therein, and the radiopacifier material imparts radiopacity to the radiopaque element. The graft may further include a reinforcing element disposed between the inner film layer and the outer film layer and/or a middle film layer disposed between the outer film layer and the inner film layer.

According to one embodiment, the reinforcing element is laminated between the middle film layer and the inner film layer. According to another embodiment, the radiopaque element is laminated between the middle film layer and the outer film layer.

According to another embodiment, the radiopacifier material is a particulate material dispersed within the polymer material of the radiopaque element. For example, the radiopaque element may contain from 40 to 95 wt.%, preferably 50 to 95 wt.% of the radiopacifier material. The radiopacifier material may be or include tantalum, gold, platinum, tungsten, iridium, platinum-tungsten, platinum-iridium, palladium, rhodium, barium sulfate, barium sulfide, bismuth subcarbonate, bismuth oxychloride, bismuth trioxide, ionic or non-ionic contrasting agents, iodipamide, iohexyl, iopamidol, iothalamate, ioversol, ioxaglate, and metrizamide, or a combination thereof, in various embodiments. The polymer material of the radiopaque element may be a thermoplastic polyurethane (TPU), and/or the inner film layer and the outer film layer comprise ultra-high molecular weight polyethylene (UHMWPE), in other embodiments. According to another embodiment, the radiopaque element is formed as an annular or partially annular strip of material.

In another embodiment, the graft includes a second radiopaque element disposed between the inner film layer and the outer film layer and spaced from the radiopaque element, the second radiopaque element comprising a second polymer material having a second radiopacifier material contained therein, wherein the second radiopacifier material imparts radiopacity to the second radiopaque element. Optionally, the second polymer material and the second radiopacifier material of the second radiopaque element are the same as the polymer material and the radiopacifier material of the radiopaque element. According to one embodiment, the second radiopaque element has a different peripheral shape from the radiopaque element. Additional aspects of the disclosure relate to graft including a tube having an inner film layer comprising ultra-high molecular weight polyethylene, a middle film layer comprising ultra-high molecular weight polyethylene and disposed radially outward of the inner film layer, and an outer film layer comprising ultra-high molecular weight polyethylene and disposed radially outward of the middle film layer, and further including a reinforcing element laminated between the middle film layer and the inner film layer and a radiopaque element laminated between the middle film layer and the outer film layer. The radiopaque element comprises a thermoplastic polyurethane material having a particulate radiopacifier material dispersed within the thermoplastic polyurethane material of the radiopaque element, and the particulate radiopacifier material imparts radiopacity to the radiopaque element. Any of the embodiments described above may be used in connection with these aspects.

Further aspects of the disclosure relate to a method of manufacturing a graft that includes positioning an inner film layer on a cylindrical mandrel, positioning a radiopaque element radially outward of the inner film layer on the cylindrical mandrel, positioning an outer film layer radially outward of the inner film layer on the cylindrical mandrel, such that the outer film layer covers the radiopaque element, and thermally bonding the inner film layer and the outer film layer together to connect the inner film layer, the radiopaque element, and the outer film layer together to form a tube. In one embodiment, the radiopaque element comprises a polymer material having a radiopacifier material contained therein, and the radiopacifier material imparts radiopacity to the radiopaque element.

One disadvantage of a radiopaque element comprising a polymer material having a radiopacifier material contained therein is that such radiopaque element may be less biostable than the virgin polymer material on its own. Achieving sufficient radiopacity in a polymer material typically requires high loading of radiopacifier material, with degradability generally increasing with higher amounts of radiopacifier material. The numerous microscopic interfaces between the polymer and the radiopacifier material can facilitate oxidative, hydrolytic, or enzymatic degradation of the polymer matrix. Accordingly, the present disclosure may further address the need for grafts comprising more biostable radiopaque elements and for methods of improving the biostability of radiopaque elements comprising polymer materials. According to one embodiment, the method further includes positioning a second radiopaque element radially outward of the inner film layer on the cylindrical mandrel and spaced from the radiopaque element, where the outer film layer is positioned to cover the radiopaque element, and the thermal bonding further connects the second radiopaque element to the inner and outer film layers to form the tube. In one embodiment, the second radiopaque element comprises a second polymer material having a second radiopacifier material contained therein, and the second radiopacifier material imparts radiopacity to the second radiopaque element.

The use of an ultra-high molecular weight polyethylene (UHMWPE) membrane as a film may provide certain advantages to the graft. Principally, a UHMWPE membrane allows for the disclosed method of forming a graft to be performed at desirable process conditions, enabling use of certain materials for radiopaque elements that would thermally degrade if the method was performed at the temperatures needed to soften and laminate other graft materials, such as ePTFE. This is because ePTFE requires a higher processing temperature relative to UHMWPE. This higher processing temperature may degrade radiopaque elements containing polymer materials during the process of forming a graft from ePTFE.

The inventions described herein may offer numerous improvements over prior art grafts including durability and reliability, simplicity or cost of manufacturing, cost, improved crimping and elasticity, reliability, biostability or other advantages.

Brief Description of Figures

FIG. 1 is a schematic exploded view of one embodiment of a structure of a graft according to aspects of the disclosure;

FIG. 2 is a side view of one embodiment of a graft having a structure as shown in FIG. 1 ;

FIG. 3 is a side view of a portion of the graft of FIG. 2 during one embodiment of a manufacturing method according to aspects of the disclosure;

FIG. 4 is an image of the graft of FIG. 2 under fluoroscopy;

FIG. 5 is a schematic cross-section view schematically showing a portion of the method of manufacturing of FIG. 3;

FIG. 6 is a side view of a stent and radiopacifier elements for use with another embodiment of a graft according to aspects of the disclosure;

FIG. 7 is a schematic exploded view of a graft manufactured using the stent and the radiopacifier elements of FIG. 6; FIG. 8 is a schematic exploded view of another embodiment of a graft according to aspects of the disclosure; and

FIG. 9 is a side view of another embodiment of a graft according to aspects of the disclosure.

Detailed Description

While this invention is susceptible of embodiments in many different forms, there are shown in the drawings and will herein be described in detail example embodiments of the invention with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the broad aspect of the invention to the embodiments illustrated. In the following description of various example structures according to the invention, reference is made to the accompanying drawings, which form a part hereof, and in which are shown by way of illustration various example devices, systems, and environments in which aspects of the invention may be practiced. It is to be understood that other specific arrangements of parts, example devices, systems, and environments may be utilized and structural and functional modifications may be made without departing from the scope of the present invention.

Various embodiments of the invention relate to a graft 10 that includes a tube 12 formed of a plurality of layers that define a tubular structure that is elongated between opposed first and second ends 13, 14 and has a cylindrical inner surface 15 defining a central passage 16 and a cylindrical outer surface 17 opposite the inner surface 15. The plurality of layers include a radiopaque element 40 that is disposed between the layers and at least a portion of which possesses radiopacity, i.e., opacity to electromagnetic waves within the radio wave portion (A = 10 to 100,000,000 m) and/or X-ray portion (A = 0.1 to 10 nm) of the electromagnetic spectrum. In other words, radio waves and/or X-rays are substantially unable to pass through the radiopaque element 40, or at least a portion thereof. The plurality of layers may include at least one film layer 20, 22, 24 and/or a reinforcing element 30 that define the tubular structure of the tube 12. The radiopaque element 40 may be disposed to cover one or more inner layers disposed radially inward of the radiopaque element 40 and may be covered by one or more outer layers disposed radially outward of the radiopaque element 40. In general, both the reinforcing element 30 and the radiopaque element 40 are disposed between the innermost and outermost film layers 20, 22, 24 and are laminated within the film structure, such that the reinforcing element 30 and the radiopaque element 40 are covered with at least one film layer 20, 22, 24 on both the inner and outer radial sides thereof. FIGS. 1-5 illustrate one embodiment of a graft 10, where FIGS. 1 and 5 schematically illustrates the separate portions and layers of the graft 10, FIGS. 2-4 illustrate an example of the graft 10, and FIGS. 3 and 5 also illustrate one embodiment of a method of production of the graft 10. In this embodiment, the graft 10 comprises a tube 12 formed of three film layers, including an inner film layer 20, a middle film layer 22, and an outer film layer 24, as well as a reinforcing element 30 and a radiopaque element 40. The outer film layer 24 is disposed radially outward of the inner and middle film layers 20, 22, and the middle film layer 22 is disposed radially outward of the inner film layer 20 and between the inner and outer film layers 20, 24.

The reinforcing element 30 in this embodiment is in the form of a stent as described herein that extends the entire length of the tube 12, from the first end 13 to the second end 14. In various embodiments, the reinforcing element 30 may extend axially beyond the ends of the film layers 20, 22, 24 at one or both ends 13, 14 of the tube 12; one or more of the film layers 20, 22, 24 may extend axially beyond the end of the reinforcing element 30 at one or both ends 13, 14 of the tube 12; and/or one or more of the film layers 20, 22, 24 may be axially aligned with the end of the reinforcing element 30 at one or both ends 13, 14 of the tube 12. In the embodiment of FIGS. 1-5, the reinforcing element 30 is disposed between the inner film layer 20 and the middle film layer 22 and is connected to both the inner and middle film layers 20, 22. In some embodiments, the reinforcing element 30 may include multiple separate elements that are separately connected to the tube 12, and such separate elements may be separated by smooth and/or corrugated portions of the material of the tube 12.

In some embodiments, multiple tubes may be positioned at various locations along the reinforcing element, thereby allowing for a first region comprising a first tube having within a first radiopaque element and a second region comprising a second tube having within a second radiopaque element. The first region and the second region may be separated by reinforcing element that is not covered by any film layer.

For example, in an embodiment, a first tube is formed from a first inner film layer, a first middle film layer, and a first outer film layer at a first location along a reinforcing element. The reinforcing element is disposed between the first inner film layer and the first middle film layer. A first radiopaque element is disposed between the first middle film layer and the first outer film layer. A second tube is formed from a second inner film layer, a second middle film layer, and a second outer film layer at a second location along the reinforcing element. The first tube and the second tube are not in contact with one another. The reinforcing element is disposed between the second inner film layer and the second middle film layer. A second radiopaque element is disposed between the second middle film layer and the second outer film layer.

The graft 10 in general includes at least one radiopaque element 40 connected to the tube 12 and laminated within the film structure of the tube 12, such that the radiopaque element(s) 40 is/are positioned between the inner and outer film layers 20, 24 and covered with at least one film layer 20, 22, 24 on both the inner and outer radial sides thereof. In the embodiment of FIGS. 1-5, the radiopaque element(s) 40 are disposed between the middle film layer 22 and the outer film layer 24 and are connected to both the middle and outer film layers 22, 24. The graft 10 may include radiopaque elements 40 having different peripheral shapes, sizes, arrangements, and orientations in various embodiments. The graft 10 illustrated in FIGS. 2-4 has a first radiopaque element 40A in the shape of an annular band that extends circumferentially around some or all of the tube 12 and a plurality of second radiopaque elements 40B shaped as a plurality of circular members arranged in an annular shape and distributed periodically around the circumference of the tube 12. The first radiopaque element 40A is axially spaced from the second radiopaque elements 40B in this embodiment, and the second radiopaque elements 40B are spaced approximately equal distances from each other. Additional shapes, sizes, arrangements, and orientations of radiopaque elements 40 may be used in other embodiments, as well as a larger or smaller number of radiopaque elements 40. In a further embodiment, the positions of the reinforcing element 30 and the radiopaque element(s) 40 may be transposed, such that the reinforcing element 30 is disposed between the middle film layer 22 and the outer film layer 24, and the radiopaque element(s) 40 are disposed between the inner film layer 20 and the middle film layer 22.

In some embodiments, the film layers 20, 22, 24 and/or the radiopaque element 30 can be further anchored to extra-matrix material within the tube structure, such as gel, rubber, foam or combinations thereof. This configuration may avoid or minimize iron leak or particle leak, which can result in corrosion of biological concerns. The risk of these concerns can thereby be reduced.

FIG. 4 illustrates the graft 10 of FIGS. 2-4 shown under fluoroscopy, including radiopaque elements 40 in the form of a film formed by hot pressing TPU granules loaded with tantalum particulate, as disclosed herein. This image demonstrates that the radiopaque elements 40 are all clearly visible under clinically relevant X-ray imaging conditions.

FIGS. 6-7 illustrate another embodiment of a graft 10 comprising a tube 12 that has a structure of layers including an inner film layer 20, a reinforcing element 30, a radiopaque element 40, and an outer film layer 24 in layered order, with no middle film layer. In general, in the embodiment of FIGS. 6-7, the reinforcing element 30 and the radiopaque element 40 are in contact with each other. More specifically, in this embodiment, the graft 10 includes two annular radiopaque elements 40C, 40D that are intertwined with the reinforcing element by threading the radiopaque elements 40C, 40D through gaps in the reinforcing element 30 to engage the radiopaque elements 40C, 40D with the reinforcing element 30 prior to lamination of the inner and outer films 20, 24. The two radiopaque elements 40C, 40D are axially spaced from each other along the tube 12. In other embodiments, the radiopaque element(s) 40 may be engaged with the reinforcing element 30 in a different configuration, including wrapping the radiopaque element(s) 40 on the inner or outer surface of the reinforcing element 30. FIG. 7 schematically illustrates the positioning and structure of the various layers of the graft 10, and it is understood that the graft 10 may include a layered configuration according to any embodiment as described herein. The graft 10 of FIGS. 6-7 is otherwise similar to the embodiment in FIGS. 1-5.

FIG. 8 illustrates another embodiment of a graft 10 comprising a tube 12 that has a structure of layers including an inner film layer 20, a radiopaque element 40, and an outer film layer 24 in layered order, with no middle film layer or reinforcing element. The radiopaque element 40 may have any configuration disclosed herein. The embodiment of FIG. 8 may also be used in connection with a portion of a graft 10 that does not include a reinforcing element 30, in a position spaced from one or more reinforcing elements 30 positioned at other locations in the graft 10, e.g., an axial gap between two stents as shown in FIG. 9. In such an embodiment, any additional film layer(s) present around the reinforcing element 30 (e.g., a middle layer 22) may extend through the gap, or such additional film layer(s) may also have a gap where no reinforcing element 30 is present. The graft 10 of FIG. 8 is otherwise similar to the embodiment in FIGS. 1-5.

FIG. 9 illustrates an embodiment of a graft 10 where the radiopaque element 40 is configured as multiple radiopaque elements 40E, 40F, and where the tube 12 includes a plurality of separate reinforcing elements 30. The reinforcing elements 30 in this embodiment are in the form of cylindrical stents that are spaced from each other axially along the length of the tube 12. The film layers 20, 22, 24 extend axially between the reinforcing elements 30 and interconnect the reinforcing elements 30. In this embodiment, the tube 12 may be considered to have a plurality of first sections 60 where the graft 10 is reinforced by one of the reinforcing elements 30, and a plurality of second sections 62 extending between the first sections 60 and between the first sections 60 and the ends of the tube 12. The second sections 62 are formed only of the film layers 20, 22, 24 in this embodiment. Additionally, in one embodiment, the second sections 62 may include corrugations or other structures that function to reinforce the respective second section 62 and/or provide flexibility to the section 62. Further, in one embodiment, the tube 12 may include only a single first section 60, with one or more second sections 62 at one or both ends of the first section 60. The radiopaque element 40 in this embodiment includes three radiopaque elements 40E formed as annular bands and positioned within the first sections 60 and two radiopaque elements 40F formed as annular bands and positioned within the second sections 60. In another embodiment, the radiopaque elements 40 may have a variety of configurations, such as the radiopaque element(s) 40E in the first section(s) 60 having different shapes, orientations, and/or arrangements than the radiopaque element(s) 40F in the second section(s) 62. The graft 10 of FIG. 9 is otherwise similar to the embodiment in FIGS. 1-5. In further embodiments, the graft 10 may include multiple sections that are branched with respect to each other, which may include sections that are reinforced and sections that are not reinforced, or the graft 10 may have a fenestrated configuration.

As discussed herein, FIGS. 1-9 illustrate potential embodiments of grafts 10 having at least one radiopaque element 40, and such embodiments can be combined or modified in various manners. Certain embodiments disclosed herein illustrate a radiopaque element 40 that is configured as a single piece or portion or multiple pieces or portions, and it is understood that any of the embodiments disclosed herein may include any number of pieces or portions of the radiopaque element 40, including multiple similar or identical configurations of the radiopaque element 40 or a mixture of multiple configurations of the radiopaque element 40. It is also understood that multiple different types of radiopaque materials may be used in one embodiment.

As discussed herein, the graft comprises at least two film layers 20, 22, 24, which may be the same or different, and a radiopaque element 40. Other components may be present, such as a reinforcing element 30. Such materials will now be described. Films

The tube 12 comprises at least two film layers 20, 22, 24. The film typically forms at least the inner surface 15 of the tube 12. In an embodiment where the tube 12 has multiple sections 60, 62, the film typically extends through each of the one or more first sections 60 and one or more second sections 62 of the tube 12 in a single piece. Thus, in an embodiment, each of the one or more first sections 60 and each of the one or more second sections 62 comprise the film. The film may be formed from multiple pieces, such as by bonding together multiple separate layers of film or by bonding together different sections of film at various interfaces (e.g., by thermal lamination). One exemplary method of forming the film is to helically wrap the material around a mandrel 19 (see FIGS. 3 and 5) and bonding the overlapping sections together to form a layer 20, 22, 24 of the film. The film is typically formed from a polymer material, such as PTFE (e.g., ePTFE), or UHMWPE (ultra-high molecular weight polyethylene). In an embodiment, the film is porous. In an embodiment, the film is microporous or nanoporous. In an embodiment, the film is non- porous.

In one embodiment, the film comprises polyethylene, preferably, ultra-high molecular weight polyethylene (UHMWPE). In an embodiment, the film is a microporous polyethylene film, such as a microporous UHMWPE film, also known as a UHMWPE membrane. A suitable commercially available UHMWPE film is Ulteeva Purity™ Membrane from DSM. In an embodiment, each film layer 20, 22, 24 has a thickness of from 10 to 100 pm, or from 30 to 60 pm. In an embodiment, multiple pieces or sub-layers of microporous UHMWPE film are bonded together using heat (thermal lamination) to create a film layer 20, 22, 24. In such an embodiment, each piece or sub-layer may have a thickness of from 5 to 25 pm, such as about 15 pm. Both porous and non-porous materials may be used.

As described herein, during manufacturing, the film layers 20, 22, 24 and the radiopaque element 40 are heated to a lamination temperature sufficient to soften the film layers 20, 22, 24 to permit lamination, but below the degradation temperature of the material of the radiopaque element 40 or another temperature that significantly changes an important property of the radiopaque element 40 (e.g., structural changes). In an embodiment, the lamination temperature of the material(s) of the film layers 20, 22, 24 is in a range having a lower end of 100°C, 110°C, 120°C, 130°C, or 140°C, and an upper end of 140°C, 150°C, 160°C, 170°C, 180°C, 190°C, or 200°C. The material may also have a melting point within these ranges. Such a low lamination temperature allows for processing at a temperature that is less than the degradation temperature of the material of the radiopaque element 40. For example, the film may have a lamination temperature of 130-160°C, more preferably 135-150°C.

In other embodiments, the film comprises one or more per- and polyfluoroalkyl substances (PFAS), such as polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene (ePTFE). However, such substances may require higher lamination temperatures than UHMWPE and may therefore be compatible with a smaller variety of materials for the radiopaque element 40.

Reinforcing Element

In an embodiment, the graft 10 comprises a reinforcing element 30. In an embodiment, the reinforcing element 30 is a stent. Various designs of stents may be suitable. In an embodiment, the reinforcing element 30 is a mesh stent. In an embodiment, the reinforcing element 30 is a zigzag stent. A zigzag stent may comprise multiple cylindrical elements in the form of crowns. The cylindrical elements are connected by bridges. In an embodiment, the reinforcing element 30 is a helical wire. In an embodiment, the stent comprises a plurality of cylindrical elements, such as a plurality of bands or crowns of a zigzag stent. In an embodiment, the stent comprises a plurality of cylindrical elements connected by one or more bridges. Typical stent materials are generally suitable for the reinforcing element 30. For example, the reinforcing element 30 may be a stent formed of a metal material, e.g., Nitinol.

Radiopaque Element

The tube 12 includes a radiopaque element 40 that is formed from a radiopaque material, i.e., a material that possesses radiopacity as disclosed herein. It is understood that it is not necessary that the entirety of the radiopaque element 40 is made of a material that possesses radiopacity, and that a radiopaque material may be formed of a mixture of different materials, one or more of which possesses radiopacity.

In one embodiment, the radiopaque material may be in the form of a polymer material having a radiopacifier material contained therein, to impart radiopacity to the radiopaque element 40. The polymer material itself may or may not have radiopaque properties. A radiopaque material of this type may be formed, e.g., by embedding a polymer material with a particulate radiopacifier material 42 (see FIG. 5) such as powder, fibers, etc. The radiopacifier material may be dispersed within the polymer material uniformly or non-uniformly, or may be concentrated in specific areas of the polymer material, e.g., the surfaces. The radiopacifier material may not be in particulate form in another embodiment. In accordance with an embodiment, a radiopaque element 40 comprises from 5 to 50 wt% of a polymer and from 50 to 95 wt% of a radiopacifier material, based on the total weight of the radiopaque element 40, where the radiopaque element 40 has a thickness of from 10 to 250 pm. In accordance with an embodiment, a radiopaque element 40 comprises from 5 to 50 wt% of a polymer and from 50 to 95 wt% of a radiopacifier material, based on the total weight of the radiopaque element 40, where the radiopaque element 40 has a thickness of from 20 to 250 pm. In an embodiment, the radiopaque element has a thickness of from 10-200 pm, 20-200 pm, or 25-200 pm. In particular, the structure and manufacture of the graft 10 according to embodiments disclosed herein permits the use of a radiopaque element 40 having smaller thickness than other polymer-based radiopaque markers that may require separate structural attachment such as sutures.

Examples of the polymer material for the matrix include various elastomeric polymers, such as thermoplastic polyurethane (TPU), thermoset polyurethane, or other polyurethane. The radiopaque material may be formed using different methods, which may depend on the identities of the matrix material and the radiopacifier material. In one example, granules of a polymer material loaded with a radiopacifier material are hot pressed to form a thin film (for example, with thickness < 40 pm), which can then be cut to an appropriate size and shape for the radiopaque element 40. The radiopaque element 40 in the embodiment of FIGS. 2-4 was made from TPU granules loaded with particulate tantalum, hot pressed into a thin film. In another example, as discussed herein, the radiopaque element 40 may be formed by casting as a film a composition comprising the polyurethane, the radiopacifier, and the solvent, and evaporating the solvent. Other techniques may be used, such as embedding a particulate or non-particulate radiopacifier material within a molten or other fluid polymer (e.g., prior to curing) and solidifying the polymer matrix.

When more than one radiopaque element 40 is used in the graft 10, additional radiopaque elements 40 may have the same or different shapes, structures, and orientations as compared to the first radiopaque element 40, and each other. Further, such additional radiopaque elements 40 may be made from the same or different materials (including the polymer matrix and/or the radiopacifier material) as compared to the first radiopaque element 40, and each other. Polyurethane

In an embodiment, the polyurethane comprises a backbone that comprises the reaction product of a diisocyanate, a polymeric aliphatic diol, and, optionally, a chain extender. In an embodiment, the polyurethane consists of a backbone that comprises the reaction product of a diisocyanate, a polymeric aliphatic diol, and, optionally, a chain extender. In an embodiment, the polyurethane further comprises an endgroup. In an embodiment, the polyurethane is thermoplastic. In an embodiment, the polyurethane is thermoset. In an embodiment, the polyurethane is linear. In an embodiment, the polyurethane is branched.

By a reaction product it is meant that the diisocyanate and polymeric aliphatic diol, and optionally the chain extender, are engaged in a simultaneous or sequential chemical reaction. For example, a reaction product of a diisocyanate, a polymeric aliphatic diol, and a chain extender is formed i) when the diisocyanate, polymeric aliphatic diol, and chain extender are all reacted together simultaneously, or ii) when a pre-polymer is first formed by reacting the diisocyanate and the polymeric aliphatic diol, and then this prepolymer is subsequently reacted with the chain extender.

In an embodiment, the polyurethane is devoid of a hydrophilic polymer moiety. Examples of hydrophilic polymer moieties are polyethylene oxide or polyoxazoline moieties.

In an embodiment, the polyurethane has a number average molecular weight (Mn) of at least 10,000 g/mol, 50,000 g/mol, 100,000 g/mol, 150,000 g/mol, 200,000 g/mol, or 250,000 g/mol. In an embodiment, the polyurethane has a Mn of 1 ,000,000 g/mol or less, 800,000 g/mol or less, 700,000 g/mol or less, 600,000 g/mol or less, or 500,000 g/mol or less.

In an embodiment the polyurethane is present in the radiopaque element 40 in an amount of 5 wt% or more, 6 wt% or more, 8 wt% or more, 10 wt% or more, 12 wt% or more, 15 wt% or more, 20 wt% or more, or 25 wt% or more, based on the total weight of the radiopaque element 40. In an embodiment the polyurethane is present in the radiopaque element 40 in an amount of 50 wt% or less, 45 wt% or less, 40 wt% or less, 35 wt% or less, 30 wt% or less, 25 wt% or less, 20 wt% or less, 15 wt% or less, or 10 wt% or less, based on the total weight of the radiopaque element 40. In an embodiment the polyurethane is present in the composition in an amount of 1 wt% or more, 2 wt% or more, 3 wt% or more, 4 wt% or more, 5 wt% or more, 6 wt% or more, 7 wt% or more, or 8 wt% or more, based on the total dry weight of the composition. By dry weight it is meant the total weight of the composition excluding any solvents. In an embodiment the polyurethane is present in the composition in an amount of 20 wt% or less, 15 wt% or less, 12 wt% or less, 10 wt% or less, 8 wt% or less, 7 wt% or less, 6 wt% or less, or 5 wt% or less, based on the total dry weight of the composition.

Various required and optional components of the polyurethane are described in further detail in the following sections.

Diisocyanate

The backbone of the polyurethane comprises the residue of a diisocyanate. In an embodiment, the diisocyanate comprises an average of at least 1 .9 isocyanate groups per molecule and an average of less than 2.7 isocyanate groups per molecule.

In an embodiment, the diisocyanate comprises an aliphatic diisocyanate. In an embodiment, the diisocyanate comprises an aromatic diisocyanate. In an embodiment, the diisocyanate comprises 4,4'-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 1 ,4-phenylene diisocyanate, hexamethylene diisocyanate (HDI), tetramethylene-1 ,4-diisocyanate, cyclohexane-1 ,4-diisocyanate, dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), or a mixture thereof. In an embodiment, the diisocyanate comprises hexamethylene diisocyanate, dicyclohexylmethane 4,4'-diisocyanate, isophorone diisocyanate, or a mixture thereof. In an embodiment, the diisocyanate consists of hexamethylene diisocyanate, dicyclohexylmethane 4,4'-diisocyanate, isophorone diisocyanate, or a mixture thereof. In an embodiment, the diisocyanate comprises 4,4'-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, or 1 ,4-phenylene diisocyanate. In an embodiment, the diisocyanate consists of 4,4'-diphenylmethane diisocyanate (MDI), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 1 ,4-phenylene diisocyanate, or a mixture thereof.

In an embodiment, the molecular weight of the diisocyanate is from 100 to 500 g/mol. In an embodiment, the molecular weight of the diisocyanate is from 150 to 260 g/mol. In an embodiment, the formulation from which the polyurethane is formed comprises at least 10 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, or at least 40 wt% of a diisocyanate, based on the total weight of the formulation. In an embodiment, the formulation from which the polyurethane is formed comprises at most 50 wt%, at most 40 wt%, at most 35 wt%, at most 30 wt%, at most 25 wt%, or at most 20 wt% of a diisocyanate, based on the total weight of the formulation. In an embodiment, the polyurethane comprises at least 10 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, or at least 40 wt% of the residue of a diisocyanate, based on the polyurethane. In an embodiment, the polyurethane comprises at most 50 wt%, at most 40 wt%, at most 35 wt%, at most 30 wt%, at most 25 wt%, or at most 20 wt% of the residue of a diisocyanate, based on the total weight of the polyurethane.

Polymeric Aliphatic Diol

The polyurethane comprises the residue of a polymeric aliphatic diol. A polymeric aliphatic diol comprises two OH groups and a backbone. The OH groups may be directly attached to the backbone or may be separated by a linker. For example, a hydroxyalkyl terminated polydimethylsiloxane (carbinol terminated) is a polymeric aliphatic diol.

In an embodiment, the polymeric aliphatic diol comprises a poly(alkylene oxide), a polycarbonate, a polysiloxane, a random or block copolymer thereof, or a mixture thereof. In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol, a polysiloxane diol, a random or block polycarbonate polysiloxane copolymer diol, or a mixture thereof. In an embodiment, the polymeric aliphatic diol comprises a mixture of a polycarbonate diol and a polysiloxane diol. In an embodiment, the polymeric aliphatic diol consists of a mixture of a polycarbonate diol and a polysiloxane diol. In an embodiment, the polymeric aliphatic diol comprises a poly(alkylene oxide) diol, a polycarbonate diol, or a mixture thereof.

In an embodiment, the polymeric aliphatic diol comprises a polyethylene oxide) diol, a polypropylene oxide) diol, a poly(tetramethylene oxide) diol, a poly(isobutylene) diol, a polyester diol, for example a polyester diol formed from adipic acid or isophtalic acid and a monomeric diol, an alkane diol, such as a hydrogenated polybutadiene diol or a polyethylene diol, a poly(hexamethylene carbonate) diol, a poly(polytetrahydrofuran carbonate) diol, a polysiloxane diol, a random or block copolymer diol of polyethylene oxide) and polypropylene oxide), a random or block copolymer diol of poly(ethylene oxide) and poly(tetramethylene oxide), a random or block copolymer diol of polyethylene oxide) and a polysiloxane, or a mixture thereof.

In an embodiment, the polymeric aliphatic diol comprises a polyethylene oxide) diol, a polypropylene oxide) diol, a poly(tetramethylene oxide) diol, a poly(isobutylene) diol, a polysiloxane diol, a random or block copolymer diol of polyethylene oxide) and polyeropylene oxide), a random or block copolymer diol of polyethylene oxide) and poly(tetramethylene oxide), a random or block copolymer diol of polyethylene oxide) and a polysiloxane, a random or block copolymer diol comprising a polysiloxane, or a mixture thereof.

In an embodiment, the polymeric aliphatic diol comprises a mixture of a polysiloxane diol and one or more of a polyethylene oxide) diol, a polyeropylene oxide) diol, a poly(tetramethylene oxide) diol, a random or block copolymer diol of polyethylene oxide) and polyeropylene oxide), and a random or block copolymer diol of polyethylene oxide) and poly(tetramethylene oxide). In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol that comprises a poly(hexamethylene carbonate) diol or a polyeolytetrahydrofuran carbonate) diol. In an embodiment, the polymeric aliphatic diol consists of polycarbonate diols. In an embodiment, the polymeric aliphatic diol consists of a poly(hexamethylene carbonate) diol, a poly olytetrahydrofuran carbonate) diol, or a mixture thereof. In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol having a Mn of at least 500 g/mol, at least 750 g/mol, at least 1000 g/mol, or at least 1500 g/mol. In an embodiment, the polymeric aliphatic diol comprises a polycarbonate diol having a Mn of at most 10,000 g/mol, at most 7500 g/mol, at most 5000 g/mol, at most 4000 g/mol, at most 3000 g/mol, or at most 2500 g/mol.

In an embodiment, the polymeric aliphatic diol comprises a polysiloxane diol, a polycarbonate diol, or a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol consists of a polysiloxane diol, a polycarbonate diol, a poly(tetramethylene oxide) diol, or a mixture thereof. In an embodiment, the polymeric aliphatic diol comprises a mixture of two or more of a polysiloxane diol, a polycarbonate diol, or a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol consists of a mixture of two or more of a polysiloxane diol, a polycarbonate diol, or a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol comprises a polysiloxane diol and one or more of a polycarbonate diol and a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol consists of a polysiloxane diol and one or more of a polycarbonate diol and a poly(tetramethylene oxide) diol. In an embodiment, the polymeric aliphatic diol comprises 15 wt% or less, 10 wt% or less, 5 wt% or less, 2 wt% or less, based on the total weight of polymeric aliphatic diol, or is devoid of hydrophobic poly(alkylene oxide). Hydrophobic poly(alkylene oxide)s are polypropylene oxide) and poly(tetramethylene oxide).

In an embodiment, the polymeric aliphatic diol comprises a C₂-Ci₆ fluoroalkyl diol or C2-C16 fluoroalkyl ether diol. In an embodiment, the polyurethane backbone comprises the residue of 1 H,1 H,4H,4H-Perfluoro-1 ,4-butanediol, 1 H,1 H,5H,5H-Perfluoro-1 ,5- pentanediol, 1 H,1 H,6H,6H-perfluoro-1 ,6-hexanediol, 1 H,1 H,8H,8H-Perfluoro-1 ,8- octanediol, 1 H,1 H,9H,9H-Perfluoro-1 ,9-nonanediol, 1 H,1 H,10H,10H-Perfluoro-1 ,10- decanediol, 1 H,1 H,12H,12H-Perfluoro-1 ,12-dodecanediol, 1 H,1 H,8H,8H-Perfluoro-3,6- dioxaoctan-1 ,8-diol, 1 H,1 H,11 H, 11 H-Perfluoro-3,6,9-trioxaundecan-1 ,11 -diol, fluorinated triethylene glycol, or fluorinated tetraethylene glycol.

In an embodiment, the C₂-Ci₆ fluoroalkyl diol or C₂-Ci₆ fluoroalkyl ether diol has an Mn of at least 150 g/mol, at least 250 g/mol, or at least 500 g/mol. In an embodiment, the fluoroalkyl diol or fluoroalkyl ether diol has a Mn of at most 1500 g/mol, at most 1000 g/mol, or at most 850 g/mol. In an embodiment, the C₂-Ci₆ fluoroalkyl diol or C₂-Ci₆ fluoroalkyl ether diol is present in an amount of at least 1 wt%, at least 2 wt%, or at least 5 wt%, based on the total weight of the polyurethane. In an embodiment, the C₂-Ci₆ fluoroalkyl diol or C₂-Ci6 fluoroalkyl ether diol is present in an amount of at most 15 wt%, at most 10 wt%, or at most 8 wt%, based on the total weight of the polyurethane.

In an embodiment, the polymeric aliphatic diol has a Mn of at least 200 g/mol, at least 250 g/mol, at least 300 g/mol, at least 400 g/mol, or at least 500 g/mol, at least 600 g/mol, at least 700 g/mol, at least 800 g/mol, at least 900 g/mol, or at least 1000 g/mol. In an embodiment, the polymeric aliphatic diol has a Mn of at most 10,000 g/mol, at most 8500 g/mol, at most 6000 g/mol, at most 5000 g/mol, at most 4000 g/mol, at most 3000 g/mol, at most 2000 g/mol, or at most 1500 g/mol.

In an embodiment, the polyurethane is formed from a formulation that comprises at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, or at least 60 wt% of a polymeric aliphatic diol, based on the total weight of the formulation. In an embodiment, the polyurethane is formed from a formulation that comprises at most 80 wt%, at most 70 wt%, at most 60 wt%, or at most 50 wt% of a polymeric aliphatic diol, based on the total weight of the formulation. In an embodiment, the polyurethane comprises at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, or at least 60 wt% of the residue of a polymeric aliphatic diol, based on the total weight of the polyurethane. In an embodiment, the polyurethane comprises at most 80 wt%, at most 70 wt%, at most 60 wt%, or at most 50 wt% of the residue of a polymeric aliphatic diol, based on the total weight of the polyurethane.

Chain Extender

The polyurethane may comprise the residue of a chain extender. A chain extender is an alkane diol having from 2 to 20 carbon atoms, wherein one or more carbon atoms may be substituted with oxygen. In an embodiment, the chain extender has a molecular weight of at least 60 g/mol, at least 70 g/mol, at least 80 g/mol, at least 90 g/mol, or at least 100 g/mol. In an embodiment, the chain extender has a molecular weight of at most 500 g/mol, at most from 400 g/mol, at most 300 g/mol, at most 200 g/mol, or at most 150 g/mol. In an embodiment, the chain extender comprises ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1 ,3-propanediol, 1 ,4-butanediol, 1 ,5- pentanediol, 1 ,6-hexanediol, or 1 ,8-octanediol.

In an embodiment, the polyurethane is formed from a formulation that comprises at least 1 wt%, at least 2 wt%, at least 5 wt%, at least 8 wt%, or at least 10 wt% of a chain extender, based on the total weight of the formulation. In an embodiment, the polyurethane is formed from a formulation that comprises at most 20 wt%, at most 15 wt%, at most 12 wt%, at most 10 wt%, at most 8 wt%, or at most 5 wt%, of a chain extender, based on the total weight of the formulation. In an embodiment, the polyurethane comprises at least 1 wt%, at least 2 wt%, at least 5 wt%, at least 8 wt%, or at least 10 wt% of the residue of a chain extender, based on the total weight of the polyurethane. In an embodiment, the polyurethane comprises at most 20 wt%, at most 15 wt%, at most 12 wt%, at most 10 wt%, at most 8 wt%, or at most 5 wt%, of the residue of a chain extender, based on the total weight of the polyurethane.

Endgroups

In an embodiment, the polyurethane comprises one or more endgroups. An endgroup is a moiety present at a terminal end of a molecule. In an embodiment, the polyurethane is linear and comprises an endgroup at each terminus of the backbone. In an embodiment, the endgroup is linear. In an embodiment, the endgroup is branched. In an embodiment, the polyurethane comprises an average of at least 0.1 endgroups, at least 0.25 endgroups, at least 0.5 endgroups, at least 1 endgroup, at least 1.5 endgroups, at least 1 .8 endgroups, about 2 endgroups, or at least 2 endgroups. In an embodiment, the polyurethane comprises an average of at most 4 endgroups an average of at most 2 endgroups, or an average of at most 2 endgroups.

An endgroup may be formed by reacting a terminal isocyanate group present after forming the polymer backbone with a coreactive group on a monofunctional moiety. For instance, a terminal isocyanate group may be reacted with 1 -octanol or octylamine to form a C₈ alkyl endgroup. Endgroups may also result from the inclusion of chain stoppers, such as monofunctional alcohols, in a formulation used in the formation of a polyurethane. For instance, a formulation for forming a polyurethane may comprise a diisocyanate, a polymeric aliphatic diol, a chain extender, and a monofunctional alcohol.

In an embodiment, the endgroup comprises a hydrophobic poly(alkylene oxide), a hydrophilic poly(alkylene oxide), a copolymer comprising a hydrophilic poly(alkylene oxide) and a hydrophobic poly(alkylene oxide), a polysiloxane, C₂-C₂o alkyl, C₂-Ci₆ fluoroalkyl, C₂-Ci₆ fluoroalkyl ether, or copolymers thereof. In an embodiment, the polysiloxane is a poly(dimethylsiloxane). In an embodiment, the hydrophilic poly(alkylene oxide) is polyethylene oxide). In an embodiment, the hydrophobic poly(alkylene oxide) is polypropylene oxide) or poly(tetramethylene oxide). In an embodiment, the endgroup comprises a hydrophobic poly(alkylene oxide), a hydrophilic poly(alkylene oxide), a copolymer comprising a hydrophilic poly(alkylene oxide) and a hydrophobic poly(alkylene oxide), C₂-C₂₀ alkyl, C₂-Ci₆ fluoroalkyl, C₂-Ci₆ fluoroalkyl ether, or copolymers thereof. Such endgroups may be formed with monofunctional alcohols, including carbinols, or amines of the foregoing.

In an embodiment, the endgroup comprises C₂-Ci₆ fluoroalkyl or C₂-Ci₆ fluoroalkyl ether. Such endgroups may be formed with monofunctional alcohols or amines comprising C₂-Ci₆ fluoroalkyl or C₂-Ci₆ fluoroalkyl ether.

In an embodiment, the endgroup is formed from a monofunctional alcohol or amine comprising C₂-Ci₆ fluoroalkyl or C₂-Ci₆ fluoroalkyl ether. In an embodiment, the endgroup is formed from 1 H,1 H-Perfluoro-3,6-dioxaheptan-1-ol, 1 H, 1 H-Nonafluoro-1 -pentanol, 1 H,1 H-Perfluoro-1-hexyl alcohol, 1 H,1 H-Perfluoro-3,6,9-trioxadecan-1-ol, 1H,1 H- Perfluoro-1 -heptyl alcohol, 1 H,1 H-Perfluoro-3,6-dioxadecan-1-ol, 1 H, 1 H-Perfluoro-1 -octyl alcohol, 1 H, 1 H-Perfluoro-1 -nonyl alcohol, 1 H,1 H-Perfluoro-3,6,9-trioxatridecan-1-ol, 1 H,1 H-Perfluoro-1 -decyl alcohol, 1 H, 1 H-Perfluoro-1 -undecyl alcohol, 1 H,1 H-Perfluoro-1 - lauryl alcohol, 1 H, 1 H-Perfluoro-1 -myristyl alcohol, or 1 H, 1 H-Perfluoro-1 -palmityl alcohol.

In an embodiment, the endgroup is monomeric and has a molecular weight of 200 g/mol or more, 300 g/mol or more, or 500 g/mol or more. In an embodiment, the endgroup is monomeric and has a molecular weight of 1 ,000 g/mol or less or 800 g/mol or less. In an embodiment, the endgroup is polymeric and has a Mn of 10,000 g/mol or less, 8,000 g/mol or less, 6,000 g/mol or less, or 4,000 g/mol or less. In an embodiment, the endgroup is polymeric and has a Mn of 500 g/mol or more, 1 ,000 g/mol or more, or 2,000 g/mol or more.

In an embodiment, the endgroup is present in an amount of at least 0.1 wt%, at least 0.2 wt%, at least 0.3 wt%, or at least 0.5 wt%, based on the total weight of the formulation from which the polyurethane is formed. In an embodiment, the endgroup is present in an amount of at most 3 wt%, at most 2 wt% or at most 1 wt%, based on the total weight of the formulation from which the polyurethane is formed. In an embodiment, the endgroup is present in an amount of at least 0.1 wt%, at least 0.2 wt%, at least 0.3 wt%, or at least 0.5 wt%, based on the total weight of the polyurethane. In an embodiment, the endgroup is present in an amount of at most 3 wt%, at most 2 wt% or at most 1 wt%, based on the total weight of the polyurethane.

Radiopacifier

The radiopaque element 40 comprises a radiopacifier. The radiopacifier imparts radiopacity to the radiopaque element 40. Examples of the radiopacifier material include tantalum, gold, platinum, tungsten, iridium, platinum-tungsten, platinum-iridium, palladium, rhodium, barium sulfate bismuth subcarbonate, bismuth oxychloride, bismuth trioxide, ionic or non-ionic contrasting agents, iodipamide, iohexyl, iopamidol, iothalamate, ioversol, ioxaglate, and metrizamide, or a combination thereof. A wide variety of other radiopacifier materials may be used, including various metals and metal oxides.

In an embodiment, the radiopacifier is present as particles. In an embodiment, the radiopacifier particles have an average particle diameter of 1 nm or more, 5 nm or more, 10 nm or more, 25 nm or more, 50 nm or more, 100 nm or more, or 200 nm or more. In an embodiment, the radiopacifier particles have an average particle diameter of 3 pm or less, 2 pm or less, 1000 nm or less, 800 nm or less, 700 nm or less, 600 nm or less, 500 nm or less, 400 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, 150 nm or less 100 nm or less, or 75 nm or less. Average particle diameter is measured using photon correlation spectroscopy (PCS) in accordance with ISO13321 :1996.

In an embodiment, the radiopacifier is subjected to a surface treatment with an adhesion promoter to promote adhesion to the polyurethane. In an embodiment, a composition used to form the radiopaque element 40 further comprises an adhesion promoter. In an embodiment, the adhesion promoter comprises a glycidyl methacrylate (GMA) modified random ethylene/acrylate copolymer, or a GMA and maleic anhydride (MA) modified random ethylene/acrylate copolymer. Commercial examples of these are Lotader® AX8840, AX8900 and AX8930, produced by Arkema.

In an embodiment, the radiopacifier is present in the radiopaque element 40 in an amount of 50 wt% or more, 55 wt% or more, 60 wt% or more, 65 wt% or more, 70 wt% or more, 75 wt% or more, 80 wt% or more, 85 wt% or more, 86 wt% or more, 87 wt% or more, 88 wt% or more, 89 wt% or more, or 90 wt% or more, based on the total weight of the radiopaque element 40. In an embodiment, the radiopacifier is present in the radiopaque element 40 in an amount of 95 wt% or less, 92 wt% or less, 90 wt% or less, 88 wt% or less, 86 wt% or less, 84 wt% or less, 82 wt% or less, 80 wt% or less, or 75 wt% or less, based on the total weight of the radiopaque element 40.

In an embodiment the radiopacifier is present in the composition in an amount of 15 wt% or more, 20 wt% or more, 25 wt% or more, 30 wt% or more, 35 wt% or more, 40 wt% or more, 45 wt% or more, or 50 wt% or more, based on the total dry weight of the composition. In an embodiment the radiopacifier is present in the composition in an amount of 55 wt% or less, 50 wt% or less, 45 wt% or less, 40 wt% or less, 35 wt% or less, 30 wt% or less, 25 wt% or less, or 20 wt% or less, based on the total dry weight of the composition.

Other Optional Components

In an embodiment, the formulation for forming the polyurethane comprises a catalyst. In an embodiment, the catalyst comprises stannous octoate, dibutyltin dilaurate, or an amine catalyst.

Additional components that may be present in the radiopaque element 40, the composition, or the formulation, include stabilizers, such as viscosity stabilizers, surfactants, antioxidants, or wetting agents. In an embodiment, the radiopaque element 40, the composition, or the formulation comprises a mold release agent. In an embodiment, the mold release agent is ethylene bis(stearamide).

Solvent

The compositions used to form a radiopaque element 40 typically comprise a solvent. The radiopaque element 40 may be formed in one embodiment by casting as a film a composition comprising the polyurethane, the radiopacifier, and the solvent, and evaporating the solvent. Typically, the polyurethane is first dissolved in the polyurethane, followed by dispersing the radiopacifier in the polyurethane.

In an embodiment, the solvent comprises tetrahydrofuran (THF), methyltetrahydrofuran (methyl-THF), dimethylacetamide (DMAc), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dichloromethane, chloroform, hexafluoroisopropanol, or a mixture thereof. In an embodiment, the solvent comprises tetrahydrofuran (THF), methyltetrahydrofuran (methyl-THF), dimethylacetamide (DMAc), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or a mixture thereof. In an embodiment, the solvent comprises tetrahydrofuran (THF) or methyl-tetrahydrofuran (methyl-THF).

A co-solvent may also be present. A co-solvent comprises less than 50 wt% of the total amount of solvent. In an embodiment, a co-solvent is present and is methanol, ethanol, isobutanol, propanol, methyl ethyl ketone, or a mixture thereof.

In an embodiment, the solvent comprises 40 wt% or more, 50 wt% or more, or 60 wt% or more of tetrahydrofuran (THF), methyl-tetrahydrofuran (methyl-THF), or a mixture thereof. In an embodiment, the solvent comprises 40 wt% or more, 50 wt% or more, or 60 wt% or more of tetrahydrofuran (THF), methyl-tetrahydrofuran (methyl-THF), or a mixture thereof, and methanol, ethanol, isobutanol, propanol, methyl ethyl ketone, or a mixture thereof at an amount of from 1 to 60 wt%, 1 to 50 wt%, or 1 to 40 wt%, based on the total amount of solvent in the composition.

In an embodiment, the solvent is present in the composition in an amount of at least 60 wt%, at least 65 wt%, at least 70 wt%, at least 75 wt%, at least 80 wt%, at least 85 wt%, at least 88 wt%, at least 89 wt%, at least 90 wt%, at least 91 wt%, at least 92 wt%, at least 93 wt%, at least 94 wt%, or at least 95 wt%, based on the total weight of the composition. In an embodiment, the solvent is present in the composition in an amount of at most 99.5 wt%, at most 99 wt%, at most 98 wt%, at most 97 wt%, at most 96 wt%, at most 95 wt%, or at most 94 wt%, based on the total weight of the composition.

Structure of Radiopaque Element

The radiopaque element 40 may be a stand-alone article, as opposed to a coating that is constrained to a substrate. A radiopaque element 40 may be formed by separating a coating from a substrate such that the coating is no longer constrained to the substrate. The radiopaque elements 40 disclosed herein can be provided in numerous forms, such as long ribbons, tapes, discs, or cylinders, such as a belt for a stent. In an embodiment, the radiopaque element 40 has a length of at least 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 times its thickness. In an embodiment, the radiopaque element 40 has a length of at most 5000, 2000, 1000, 500, 400, 300, 200, 100, 75, 50, 45, 40, 35, 30, 25, or 20 times its thickness. In an embodiment, the radiopaque element 40 has a length of at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 times its width. In an embodiment, the radiopaque element 40 has a length of at most 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, or 15 times its width.

In an embodiment, the radiopaque element 40 has a thickness of from 10 to 250 pm or 20 to 250 pm. In an embodiment, the radiopaque element 40 has a thickness of at least 20 pm, 25 pm, at least 30 pm, at least 40 pm, at least 50 pm, at least 60 pm, at least 70 pm, at least 80 pm, or at least 90 pm. In an embodiment, the radiopaque element 40 has a thickness of at most 200 pm, at most 190 pm, at most 180 pm, at most 170 pm, at most 160 pm, at most 150 pm, at most 140 pm, at most 130 pm, at most 120 pm, at most 110 pm, at most 100 pm, at most 90 pm, at most 80 pm, at most 70 pm, at most 60 pm, at most 50 pm, or at most 40 pm.

In an embodiment, the radiopaque element 40 has a length of at least 1 mm, at least 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, or at least 10 mm. In an embodiment, the radiopaque element 40 has a length of at most 100 mm, at most 75 mm, at most 50 mm, at most 30 mm, at most 20 mm, at most 15 mm, at most 10 mm, at most 9 mm, at most 8 mm, at most 7 mm, at most 6 mm, or at most 5 mm. In an embodiment, the radiopaque element 40 has a width of at least 1 mm, at least 2 mm, at least 3 mm, at least 4 mm, or at least 5 mm. In an embodiment, the radiopaque element 40 has a width of at most 10 mm, at most 8 mm, at most 7 mm, at most 6 mm, at most 5 mm, or at most 4 mm. In an embodiment, the radiopaque element 40 has a length of from 2 to 10 mm and a width of from 1 to 6 mm. In an embodiment, the radiopaque element 40 is a ribbon or strip. This form allows flexibility for the end user. The end user may trim the ribbon to an appropriate size and attach it to the medical device in a form that provides the desired radiopacity.

In an embodiment, the radiopaque element 40 is provided as a series of tabs separable from an underlying substrate. The individual tabs may be separated from the underlying substrate and attached to the radiopaque element 40 by the end user.

In an embodiment, the radiopaque element 40 is a fiber or yarn comprising a plurality of fibers. In such embodiment, the radiopaque element is typically arranged inside the polymer fiber and the radiopaque element has a particle size of typically 1 pm or less. Such materials may be formed by known processes, such as melt spinning, or gel spinning in the case of ultra-high molecular weight polyethylene yarns. The fibers or yarns may be formed into various constructions, such as braids, weaves, knits, or other textiles.

Forming Grafts

An exemplary method of forming a graft embodiment will now be explained, with reference to FIGS. 2-3 and 5. In an embodiment, the graft 10 is made by first obtaining a film layer 20 in the shape of a tube, which film will form the inner surface 15 of the graft. An example of such a procedure is disclosed in U.S. Patent Application Publication No. 2017/0360584, which is incorporated by reference herein in its entirety. To form the film into the shape of a tube, the film is cut to a selected size and wrapped around the outside diameter of a mandrel 19, as shown in FIGS. 3 and 5. Preferably, the mandrel 19 is first wrapped in a release layer (not shown), such as helically wrapped ePTFE tape, in order to facilitate removal of the tube 12 from the mandrel 19. A single layer or multiple layers of the film may be used to achieve the desired thickness of the inner film layer 20. The mandrel 19 may have a constant or variable outer diameter to create tubes of various geometries such a tapered tube. The film may be treated, such as wet with isopropyl alcohol, to enable the film to lay more smoothly.

Next, the desired size, spacing, and positioning of the radiopaque element(s) 40 are chosen, and the radiopaque element(s) 40 are positioned over the inner film layer 20 at the desired locations. Each radiopaque element 40 may be pre-cut to an appropriate size before using the radiopaque element 40 in the manufacturing process. An outer film layer 24 is placed over the radiopaque element(s) 40 to enclose the radiopaque element(s) 40 between the inner and outer film layers 20, 24. The radiopaque element(s) 40 and the outer film layer 24 may be secured to the mandrel 19, such as with wire, wrapping in ePTFE tape, or using heat-shrink tubing. The outer film layer 24 may be formed similarly to the inner film layer 20, such as by wrapping the outer film material around the radiopaque element(s) 40 and the inner layers (e.g., the film layers 20, 22 and reinforcing element 30) or placing layers of the film material over the radiopaque element(s) 40 and inner layers in a plurality of layers, and connecting the layers together. The outer film layer 24 in this embodiment will form the outer surface 17 of the graft 10 after lamination.

This process may be modified in various ways to result in various configurations. As described above, in some embodiments, the graft 10 includes a reinforcing element 30, such as a stent. In such an embodiment, the reinforcing element 30 may be placed on the mandrel 19 in an appropriate location, such as outside of the inner film layer 20, during the manufacturing process. As shown in FIGS. 3 and 5, the reinforcing element 30 is placed in contact with the outer surface of the inner film layer 20, and a middle film layer 22 is then placed in a position to partially or completely cover the reinforcing element 30. The middle film layer 22 may be formed similarly to the inner film layer 20, such as by wrapping the middle film material around the reinforcing element 30 and any other inner layers (e.g., the inner film layer 20) or placing layers of the film material over the reinforcing element 30 and other inner layers in a plurality of layers, and connecting the layers together. In this configuration, the radiopaque element(s) 40 are connected to the outer surface of the middle film layer 22, as shown in FIGS. 3 and 5. Multiple reinforcing elements 30 could be used to allow for the desired flexibility or in the event that corrugations will be added to the graft as described herein. The radiopaque element(s) 40 and any outer layers such as the outer film layer 24 are typically then laminated.

Next, the tube 12 is formed on the mandrel 19, for example, by bonding or otherwise connecting multiple layers of film together to form a single tube 12. This step will simultaneously laminate the radiopaque element 40 (and the reinforcing element 30 if present) between the film layers 20, 22, 24, and connect the film layers 20, 22, 24 together. Connection may be achieved by heating, such as in an air convection oven set at 150 °C for 10 minutes. Once cool, the tube 12 can be obtained by removing any inner and outer layers used in the process, such as an ePTFE tape release layer or any element used to secure the inner film layer 20 in place on the mandrel. In the case of a microporous UHMWPE film, the time and temperature should be chosen such that the porous nature of the film is not destroyed by thermal degradation. The time and temperature should also be chosen to avoid thermal degradation of the radiopaque element 40. A suitable temperature and time combination may be chosen based on the specific character of the material.

In the case that a corrugation is formed in the tube 12, this may be done as follows. The tube 12 formed above is positioned on a mandrel 19 of sufficient outer diameter such that the inner diameter of the tube fits snugly on the mandrel. In the case that an inner protective layer is used in the previous step, such as the helically wrapped ePTFE tape, the mandrel 19 in this step should have a greater diameter than the mandrel used in the previous step. For each corrugated section, two consecutive sections of the tube are pressed toward each other on the mandrel, such as by hand pressure, thereby buckling the film. The sections are pushed toward each other to create a plurality of corrugations and until strong resistance to further compression of the corrugated section is observed. The procedure is repeated at all other locations where a corrugated section is desired.

Finally, the graft 10 is heat-treated to set the corrugations in the film. In an embodiment, the graft 10 is merely covered with a shrink tube of appropriate size to protect the assembly and placed into a pre-heated oven, such as at 127 °C for 10 min. Another option would be to use a heat gun pre-treatment to partially “lock” the assembly in place. Afterwards, the assembly is removed from the oven, cooled, and then the graft 10 is obtained by removing it from the mandrel 19.

The reinforcing element 30 is connected to the film layers 20, 22, 24 such that the reinforcing element 30 is substantially immobile relative to the film layers 20, 22, 24. The step of connecting is typically carried out by thermal lamination (i.e. heat bonding). The step of connecting the reinforcing element 30 may be performed at the same time as the thermal lamination step used to form the film layers 20, 22, 24. Thus, multiple layers of film may be supplied and the one or more reinforcing elements positioned on the layers of film and then the thermal lamination step carried out in order to both form the film and connect the reinforcing element to the film. An outer film layer 24 covering both the reinforcing element(s) 30 and the inner or middle film layer 20, 22 may also be connected to the reinforcing element(s) 30 and the inner or middle film layer 20, 22. In an embodiment, the reinforcing element(s) 30 are positioned between two film layers (e.g., middle and outer film layers 22, 24) and the thermal lamination connects the three elements together. In an embodiment where the tube 12 includes one or more second sections 62 devoid of a reinforcing element 30, the second section 62 comprises a modification of the film configured to increase the radial strength and/or the flexibility of the tube 12 in the second section 62. In an embodiment, the second section 62 consists essentially of or consists of the film layers 20, 22, 24 and any radiopaque element present in the second section 62. In an embodiment, the second section 62 further comprises a helical wire that may extend across both the first and second sections 60, 62.

Various embodiments of grafts have been described herein, which include various components and features. In other embodiments, the grafts may be provided with any combination of such components and features. It is also understood that in other embodiments, the various devices, components, and features of the grafts described herein may be constructed with similar structural and functional elements having different configurations, including different ornamental appearances.

The graft 10 disclosed herein may have numerous applications in the body, such as in the cardiovascular and neurovascular spaces. The graft 10 may be used in, for example, the treatment of peripheral artery disease in a superficial femoral artery. In an embodiment, the graft has an outer diameter of from 1 or 2 to 10, 9 or 8 mm. In an embodiment, the tube has an outer diameter of from 1 or 2 to 10, 9 or 8 mm. The radiopaque element 40 provides numerous benefits as described herein, and the use of materials such as UHMWPE for the film layers 20, 22, 24 is particularly compatible with the radiopaque element 40 described herein. These materials provide a lamination temperature that is sufficiently low to permit lamination while not degrading the material of the radiopaque element 40 during manufacturing, permitting the radiopaque element 40 to be made from more fragile and/or thermally sensitive materials. For example, the lamination temperature for an UHMWPE membrane is typically below 150°C, while typical thermoplastic polyurethane (TPU) processing temperatures are >190°C. The temperature that would result in obvious plastic deformation/viscous flow for a radiopaque element formed of a TPU material as described herein would not be reached when heating at 150°C, but may be reached at higher lamination temperatures, e.g., greater than 190°C or 200°C. The use of the lamination process also avoids the need for suturing the radiopaque element 40 to the tube 12, providing a graft 10 that is simple and efficient to manufacture, and avoids difficulties with crimping and elasticity. The use of polymer- based markers provides advantages over metal markers, such as being moldable into more complex structures that are better visualized. Additionally, the structures and methods disclosed herein address the difficulties of introducing polymeric radiopaque markers into an endovascular device, such as a stent graft, including ensuring the radiopaque marker is firmly anchored to the graft, avoiding exposing such radiopaque markers directly to body fluid/blood, which is risky due to the fact the high loading of inorganic radiopaque compounds weakens biostability of the polymeric matrix, and providing low friction for endoluminal delivery because the marker is laminated within rather than on the surface of the graft. Polymeric radiopaque markers typically have high friction due to the elastomeric nature of the polymer matrix, and therefore, it is highly undesired to exposure the polymeric radiopaque marker as part of the outermost layer of the endoluminal device. Further, the attachment of the radiopaque element by lamination provides the ability to use larger markers or markers of specific geometry (e.g. rings, halfrings) without structural concerns. Still further benefits and advantages provided by the grafts described herein are apparent to those skilled in the art.

The radiopaque elements and forming techniques disclosed herein are disclosed for use in a stent-graft. However, these concepts can be incorporated into other devices and articles, possibly with some modifications. For example, these technologies can be used in connection with stent graft/covered-stents, grafts, occlusion devices, synthetic heart valve frames, and various delivery systems.

The following non-limiting and non-exhaustive description of exemplary embodiments is intended to further describe certain embodiments of the invention. . A graft comprising a tube comprising an inner film layer, an outer film layer disposed radially outward of the inner film layer, and a radiopaque element disposed between the inner film layer and the outer film layer, the radiopaque element comprising a polymer material having a radiopacifier material contained therein, wherein the radiopacifier material imparts radiopacity to the radiopaque element. . A graft comprising a tube having a plurality of layers defining a tubular structure, the plurality of layers comprising one or more inner layers defining an inner surface of the tube, an outer film layer disposed radially outward of the one or more inner layers, and a radiopaque element disposed between the outer film layer and the one or more inner layers. . The graft according to any one of the preceding embodiments, wherein the one or more inner layers includes an inner film layer and a reinforcing element disposed radially outward of the inner film layer. 4. The graft according to any one of the preceding embodiments, wherein the one or more inner layers further includes a middle film layer disposed between the reinforcing element and the radiopaque element.

5. The graft according to any one of the preceding embodiments, wherein the tube further comprises a reinforcing element disposed between the inner film layer and the outer film layer.

6. The graft according to any one of the preceding embodiments, wherein the radiopaque element is positioned radially outwardly of the reinforcing element.

7. The graft according to any one of the preceding embodiments, wherein the radiopaque element is engaged with the reinforcing element.

8. The graft according to any one of the preceding embodiments, wherein the tube further comprises a middle film layer disposed between the outer film layer and the inner film layer, wherein the reinforcing element is laminated between the middle film layer and the inner film layer.

9. The graft according to any one of the preceding embodiments, wherein the radiopaque element is laminated between the middle film layer and the outer film layer.

10. The graft according to any one of the preceding embodiments, wherein the tube further comprises a middle film layer disposed between the outer film layer and the inner film layer, such that the reinforcing element is positioned between the middle film layer and the outer film layer.

11 . The graft according to any one of the preceding embodiments, wherein the reinforcing element is a stent.

12. The graft according to any one of the preceding embodiments, wherein the tube further comprises a middle film layer disposed between the outer film layer and the inner film layer, such that the radiopacifier element is positioned between the middle film layer and the outer film layer.

13. The graft according to any one of the preceding embodiments, wherein the tube further comprises a middle film layer disposed between the outer film layer and the inner film layer to cover the reinforcing element, such that the reinforcing element is positioned between the middle film layer and the inner film layer.

14. The graft according to any one of the preceding embodiments, wherein the radiopacifier material is a particulate material dispersed within the polymer material of the radiopaque element.

15. The graft according to any one of the preceding embodiments, wherein the radiopaque element contains from 40 to 95 wt.%, preferably 50 to 95 wt.% of the radiopacifier material. 16. The graft according to any one of the preceding embodiments, wherein the radiopaque element has a thickness of from 10 to 250 pm.

17. The graft according to any one of the preceding embodiments, wherein the radiopaque element has a thickness of from 20 to 250 pm.

18. The graft according to any one of the preceding embodiments, wherein the radiopaque element has a thickness of at least 25 pm, at least 30 pm, at least 40 pm, at least 50 pm, at least 60 pm, at least 70 pm, at least 80 pm, or at least 90 pm.

19. The graft according to any one of the preceding embodiments, wherein the radiopaque element has a thickness of at most 200 pm, at most 190 pm, at most 180 pm, at most 170 pm, at most 160 pm, at most 150 pm, at most 140 pm, at most 130 pm, at most 120 pm, at most 110 pm, at most 100 pm, at most 90 pm, at most 80 pm, at most 70 pm, at most 60 pm, at most 50 pm, or at most 40 pm.

20. The graft according to any one of the preceding embodiments, wherein the radiopacifier material comprises tantalum, gold, platinum, tungsten, iridium, platinumtungsten, platinum-iridium, palladium, rhodium, barium sulfate bismuth subcarbonate, bismuth oxychloride, bismuth trioxide, ionic or non-ionic contrasting agents, iodipamide, iohexyl, iopamidol, iothalamate, ioversol, ioxaglate, and metrizamide, or a combination thereof.

21 . The graft according to any one of the preceding embodiments, wherein the polymer material of the radiopaque element is thermoplastic polyurethane (TPU).

22. The graft according to any one of the preceding embodiments, wherein at least one of the inner film layer, the outer film layer, and the middle film layer (if present) comprise ultra-high molecular weight polyethylene (UHMWPE).

23. The graft according to any one of the preceding embodiments, wherein the radiopaque element is formed as an annular or partially annular strip of material.

24. The graft according to any one of the preceding embodiments, further comprising a second radiopaque element disposed between the inner film layer and the outer film layer and spaced from the radiopaque element, the second radiopaque element comprising a second polymer material having a second radiopacifier material contained therein, wherein the second radiopacifier material imparts radiopacity to the second radiopaque element, and wherein, optionally, the second polymer material and the second radiopacifier material of the second radiopaque element are the same as the polymer material and the radiopacifier material of the radiopaque element.

25. The graft according to any one of the preceding embodiments, wherein the second radiopaque element has a different peripheral shape from the radiopaque element.

26. The graft according to any one of the preceding embodiments, wherein the graft comprises a plurality of radiopaque elements. 27. The graft according to any one of the preceding embodiments, wherein the graft comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 radiopaque elements.

28. The graft according to any one of the preceding embodiments, wherein the inner film layer comprises the inner surface of the tube.

29. The graft according to any one of the preceding embodiments, wherein the outer film layer comprises the outer surface of the tube.

30. The graft according to any one of the preceding embodiments, wherein the graft is fenestrated.

31 . The graft according to any one of the preceding embodiments, wherein the radiopaque element is configured as an annular band, and the second radiopaque element is part of a group of additional radiopaque elements arranged in an annular configuration spaced from the radiopaque element.

32. The graft according to any one of the preceding embodiments, wherein the radiopaque element is intertwined with the reinforcing element.

33. The graft according to any one of the preceding embodiments, wherein the radiopaque element is made from biostable materials.

34. The graft according to any one of the preceding embodiments, wherein the polymer material of the radiopaque element comprises a thermoset polyurethane.

35. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) is non-porous.

36. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises pores.

37. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises micropores.

38. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises nanopores.

39. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises a plurality of layers of ultra-high molecular weight polyethylene membrane.

40. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises from 2 to 8 layers of ultra-high molecular weight polyethylene membrane.

41 . The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a thickness of from 10 pm to 150, 100, 90, 80, 70, or 60 pm. 42. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a thickness of from 15, 20, 30 or 40 pm to 100, 90, 80, 70 or 60 pm.

43. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a thickness of from 15 pm to 60 pm.

44. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a lamination temperature in a range having a lower end of 100°C, 110°C, 120°C, 130°C, or 140°C, and an upper end of 140°C, 150°C, 160°C, 170°C, 180°C, 190°C, or 200°C.

45. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a lamination temperature of from 130°C to 160°C.

46. The graft of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a lamination temperature of from 135°C to 150°C.

47. The graft of any one of the preceding embodiments, wherein the stent comprises a zigzag stent.

48. The graft of any one of the preceding embodiments, wherein the reinforcing element comprises a helical wire.

49. The graft of any one of the preceding embodiments, wherein the stent comprises a plurality of cylindrical elements.

50. The graft of any one of the preceding embodiments, wherein the stent comprises a plurality of cylindrical elements connected by one or more bridges.

51 . The graft of any one of the preceding embodiments, wherein the stent is metal.

52. The graft of any one of the preceding embodiments, wherein the radiopaque element is formed of a film having a thickness of up to 40 pm.

53. The graft of any one of the preceding embodiments, wherein the graft has an outer diameter of from 1 or 2 to 10, 9 or 8 mm.

54. The graft of any one of the preceding embodiments, wherein the tube has an outer diameter of from 1 or 2 to 10, 9 or 8 mm.

55. The graft of any one of the preceding embodiments, wherein the tube comprises corrugations set in the inner film layer, the outer film layer, and the middle film layer (if present).

56. The graft of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations. 57. The graft of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations, wherein the corrugated section is devoid of reinforcing element.

58. The graft of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations, wherein the corrugated section is devoid of any radiopaque element.

59. The graft of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations, wherein the radiopaque element is positioned in the corrugated section.

60. The graft of any one of the preceding embodiments, wherein the corrugation is set, fixed, and/or locked in the inner film layer, the outer film layer, and the middle film layer (if present).

61 . The graft of any one of the preceding embodiments, wherein the modification is set, fixed, and/or locked in the inner film layer, the outer film layer, and the middle film layer (if present) as a result of thermal treatment.

62. The graft of any one of the preceding embodiments, wherein the film has been thermally treated to set, fix, and/or lock the modification in the film itself.

63. The graft of any one of the preceding embodiments, wherein modification is formed by buckling and thermally treating the inner film layer and/or the outer film layer.

64. The graft of any one of the preceding embodiments, wherein the corrugation comprises non-helical undulations of the film.

65. The graft of any one of the preceding embodiments, wherein the corrugation comprises a plurality of circular undulations.

66. The graft of any one of the preceding embodiments, wherein the corrugation is formed by compressing the inner film layer, the outer film layer, and the middle film layer (if present) axially along the axis of the tube and thermally treating the inner film layer, the outer film layer, and the middle film layer (if present).

67. A method of manufacturing a graft, comprising positioning an inner film layer on a cylindrical mandrel, positioning a radiopaque element radially outward of the inner film layer on the cylindrical mandrel, the radiopaque element comprising a polymer material having a radiopacifier material contained therein, wherein the radiopacifier material imparts radiopacity to the radiopaque element, positioning an outer film layer radially outward of the inner film layer on the cylindrical mandrel, such that the outer film layer covers the radiopaque element, and thermally bonding the inner film layer and the outer film layer together to connect the inner film layer, the radiopaque element, and the outer film layer together to form a tube.

68. The method according to any one of the preceding embodiments, further comprising positioning a reinforcing element between the inner film layer and the outer film layer.

69. The method according to any one of the preceding embodiments, wherein the radiopaque element is positioned radially outwardly of the reinforcing element.

70. The method according to any one of the preceding embodiments, wherein the radiopaque element is engaged with the reinforcing element.

71 . The method according to any one of the preceding embodiments, further comprising positioning a middle film layer between the outer film layer and the inner film layer to cover the reinforcing element, such that the reinforcing element is positioned between the middle film layer and the inner film layer.

72. The method according to any one of the preceding embodiments, further comprising positioning a middle film layer between the outer film layer and the inner film layer, such that the reinforcing element is positioned between the middle film layer and the outer film layer.

73. The method according to any one of the preceding embodiments, wherein the reinforcing element is a stent.

74. The method according to any one of the preceding embodiments, further comprising positioning a middle film layer between the outer film layer and the inner film layer, such that the radiopacifier element is positioned between the middle film layer and the outer film layer.

75. The method according to any one of the preceding embodiments, further comprising positioning a middle film layer between the outer film layer and the inner film layer to cover the reinforcing element, such that the reinforcing element is positioned between the middle film layer and the inner film layer.

76. The method according to any one of the preceding embodiments, wherein the radiopacifier material is a particulate material dispersed within the polymer material of the radiopaque element.

77. The method according to any one of the preceding embodiments, wherein the radiopaque element contains from 40 to 95 wt.%, preferably 50 to 95 wt.% of the radiopacifier material.

78. The method according to any one of the preceding embodiments, wherein the radiopacifier material comprises tantalum, gold, platinum, tungsten, iridium, platinumtungsten, platinum-iridium, palladium, rhodium, barium sulfate, bismuth subcarbonate, bismuth oxychloride, bismuth trioxide, ionic or non-ionic contrasting agents, iodipamide, iohexyl, iopamidol, iothalamate, ioversol, ioxaglate, and metrizamide, or a combination thereof.

79. The method according to any one of the preceding embodiments, wherein the polymer material of the radiopaque element is thermoplastic polyurethane (TPU).

80. The method according to any one of the preceding embodiments, wherein at least one of the inner film layer, the outer film layer, and the middle film layer (if present) comprise ultra-high molecular weight polyethylene (UHMWPE).

81 . The method according to any one of the preceding embodiments, wherein the radiopaque element is formed as an annular or partially annular strip of material.

82. The method according to any one of the preceding embodiments, further comprising positioning a second radiopaque element between the inner film layer and the outer film layer and spaced from the radiopaque element, such that the outer film layer covers the second radiopaque element, and the thermal bonding connects the inner film layer, the second radiopaque element, and the outer film layer together.

83. The method according to any one of the preceding embodiments, wherein the second radiopaque element comprises a second polymer material having a second radiopacifier material contained therein, and the second radiopacifier material imparts radiopacity to the second radiopaque element, and wherein, optionally, the second polymer material and the second radiopacifier material of the second radiopaque element are the same as the polymer material and the radiopacifier material of the radiopaque element.

84. The method according to any one of the preceding embodiments, wherein the second radiopaque element has a different peripheral shape from the radiopaque element.

85. The method according to any one of the preceding embodiments, further comprising positioning a plurality of radiopaque elements between the inner film layer and the outer film layer.

86. The method according to any one of the preceding embodiments, wherein the graft comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 radiopaque elements.

87. The graft of any one of the preceding embodiments, wherein the radiopaque element is formed of a film having a thickness of up to 40 pm.

88. The graft of any one of the preceding embodiments, further comprising forming the radiopaque element by hot pressing the polymer material loaded with the radiopacifier material into a film having a thickness of up to 40 pm.

89. The graft of any one of the preceding embodiments, wherein the radiopaque element is provided in the form of a ribbon, tape, disc, or cylinder, fiber, yarn, or textile.

90. The method according to any one of the preceding embodiments, wherein the inner film layer comprises the inner surface of the tube. 91 . The method according to any one of the preceding embodiments, wherein the outer film layer comprises the outer surface of the tube.

92. The method according to any one of the preceding embodiments, wherein the graft is fenestrated.

93. The method according to any one of the preceding embodiments, wherein the radiopaque element is configured as an annular band, and the second radiopaque element is part of a group of additional radiopaque elements arranged in an annular configuration spaced from the radiopaque element.

94. The method according to any one of the preceding embodiments, wherein the radiopaque element is intertwined with the reinforcing element.

95. The method according to any one of the preceding embodiments, wherein the radiopaque element is made from biostable materials.

96. The method according to any one of the preceding embodiments, wherein the polymer material of the radiopaque element comprises a thermoset polyurethane.

97. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) is non-porous.

98. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises pores.

99. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises micropores.

100. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises nanopores.

101. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises a plurality of layers of ultra-high molecular weight polyethylene membrane.

102. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) comprises from 2 to 8 layers of ultra-high molecular weight polyethylene membrane.

103. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a thickness of from 10 pm to 150, 100, 90, 80, 70, or 60 pm.

104. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a thickness of from 15, 20, 30 or 40 pm to 100, 90, 80, 70 or 60 pm.

105. The method of any one of the preceding embodiments, wherein the inner film layer, outer film layer, and/or the middle film layer (if present) has a thickness of from 15 pm to 60 pm. 106. The method of any one of the preceding embodiments, wherein the thermal bonding is carried out at a temperature in a range having a lower end of 100°C, 110°C, 120°C, 130°C, or 140°C, and an upper end of 140°C, 150°C, 160°C, 170°C, 180°C, 190°C, or 200°C.

107. The method of any one of the preceding embodiments, wherein the stent comprises a zigzag stent.

108. The method of any one of the preceding embodiments, wherein the reinforcing element comprises a helical wire.

109. The method of any one of the preceding embodiments, wherein the stent comprises a plurality of cylindrical elements.

110. The method of any one of the preceding embodiments, wherein the stent comprises a plurality of cylindrical elements connected by one or more bridges.

111. The method of any one of the preceding embodiments, wherein the stent is metal.

112. The method of any one of the preceding embodiments, wherein the graft has an outer diameter of from 1 or 2 to 10, 9 or 8 mm.

113. The method of any one of the preceding embodiments, wherein the tube has an outer diameter of from 1 or 2 to 10, 9 or 8 mm.

114. The method of any one of the preceding embodiments, wherein the tube comprises corrugations set in the inner film layer, the outer film layer, and the middle film layer (if present).

115. The method of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations.

116. The method of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations, wherein the corrugated section is devoid of reinforcing element.

117. The method of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations, wherein the corrugated section is devoid of any radiopaque element.

118. The method of any one of the preceding embodiments, wherein the tube comprises a corrugated section wherein the inner film layer, the outer film layer, and the middle film layer (if present) comprise one or more corrugations, wherein the radiopaque element is positioned in the corrugated section. 119. The method of any one of the preceding embodiments, wherein the corrugation is set, fixed, and/or locked in the inner film layer, the outer film layer, and the middle film layer (if present).

120. The graft of any one of the preceding embodiments, wherein the modification is set, fixed, and/or locked in the inner film layer, the outer film layer, and the middle film layer (if present) as a result of thermal treatment.

121. The graft of any one of the preceding embodiments, wherein the film has been thermally treated to set, fix, and/or lock the modification in the film itself.

122. The graft of any one of the preceding embodiments, wherein modification is formed by buckling and thermally treating the inner film layer and/or the outer film layer.

123. The graft of any one of the preceding embodiments, wherein the corrugation comprises non-helical undulations of the film.

124. The graft of any one of the preceding embodiments, wherein the corrugation comprises a plurality of circular undulations.

125. The graft of any one of the preceding embodiments, wherein the corrugation is formed by compressing the inner film layer, the outer film layer, and the middle film layer (if present) axially along the axis of the tube and thermally treating the inner film layer, the outer film layer, and the middle film layer (if present).

The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted. The term “plurality,” as used herein, indicates any number greater than one, either disjunctively or conjunctively, as necessary, up to an infinite number. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. While certain optional features are described as embodiments of the invention, the description is meant to encompass and specifically disclose all combinations of these embodiments unless specifically indicated otherwise or physically impossible.

Claims

Claims What is claimed is:

1. A graft comprising: a tube comprising: an inner film layer; and an outer film layer disposed radially outward of the inner film layer; and a radiopaque element disposed between the inner film layer and the outer film layer, the radiopaque element comprising a polymer material having a radiopacifier material contained therein, wherein the radiopacifier material imparts radiopacity to the radiopaque element.

2. The graft of claim 1 , further comprising a reinforcing element disposed between the inner film layer and the outer film layer.

3. The graft of claim 1 or 2, wherein the tube further comprises a middle film layer disposed between the outer film layer and the inner film layer, wherein the reinforcing element is laminated between the middle film layer and the inner film layer.

4. The graft of any one claims 1-3, wherein the radiopaque element is laminated between the middle film layer and the outer film layer.

5. The graft of any one of claims 2-4, wherein the reinforcing element is a stent.

6. The graft of any one of claims 1-5, wherein the radiopacifier material is a particulate material dispersed within the polymer material of the radiopaque element.

7. The graft of claim 6, wherein the radiopaque element contains from 40 to 95, preferably 50 to 95 wt.% of the radiopacifier material.

8. The graft of any one of claims 1-7, wherein the radiopacifier material comprises tantalum, gold, platinum, tungsten, iridium, platinum-tungsten, platinum-iridium, palladium, rhodium, barium sulfate bismuth subcarbonate, bismuth oxychloride, bismuth trioxide, ionic or non-ionic contrasting agents, iodipamide, iohexyl, iopamidol, iothalamate, ioversol, ioxaglate, and metrizamide, or a combination thereof.

9. The graft of any one of claims 1 -8, wherein the polymer material of the radiopaque element is thermoplastic polyurethane (TPU), and the inner film layer and the outer film layer comprise ultra-high molecular weight polyethylene (UHMWPE).

10. The graft of any one of claims 1-9, wherein the radiopaque element is formed as an annular or partially annular strip of material.

11 . The graft of any one of claims 1-10, further comprising a second radiopaque element disposed between the inner film layer and the outer film layer and spaced from the radiopaque element, the second radiopaque element comprising a second polymer material having a second radiopacifier material contained therein, wherein the second radiopacifier material imparts radiopacity to the second radiopaque element, and wherein, optionally, the second polymer material and the second radiopacifier material of the second radiopaque element are the same as the polymer material and the radiopacifier material of the radiopaque element.

12. The graft of claim 11 , wherein the second radiopaque element has a different peripheral shape from the radiopaque element.

13. The graft of any one of claims 1-12, wherein the radiopaque element has a thickness of from 10 to 250 pm.

14. The graft of any one of claims 1-12, wherein the radiopaque element has a thickness of from 20 to 200 pm.

15. The graft of any one of claims 1-14, wherein the radiopaque element is provided in the form of a ribbon, tape, disc, or cylinder.

16. The graft of any one of claims 1-14, wherein the radiopaque element is provided in the form of a fiber, yarn, or textile.

17. A graft comprising: a tube comprising: an inner film layer comprising ultra-high molecular weight polyethylene; a middle film layer comprising ultra-high molecular weight polyethylene and disposed radially outward of the inner film layer; and an outer film layer comprising ultra-high molecular weight polyethylene and disposed radially outward of the middle film layer; a reinforcing element laminated between the middle film layer and the inner film layer; and a radiopaque element laminated between the middle film layer and the outer film layer, the radiopaque element comprising a thermoplastic polyurethane material having a particulate radiopacifier material dispersed within the thermoplastic polyurethane material of the radiopaque element, wherein the particulate radiopacifier material imparts radiopacity to the radiopaque element.

18. A method of manufacturing a graft, comprising: positioning an inner film layer on a cylindrical mandrel; positioning a radiopaque element radially outward of the inner film layer on the cylindrical mandrel, the radiopaque element comprising a polymer material having a radiopacifier material contained therein, wherein the radiopacifier material imparts radiopacity to the radiopaque element; positioning an outer film layer radially outward of the inner film layer on the cylindrical mandrel, such that the outer film layer covers the radiopaque element; and thermally bonding the inner film layer and the outer film layer together to connect the inner film layer, the radiopaque element, and the outer film layer together to form a tube.

19. The method of claim 18, further comprising: positioning a second radiopaque element radially outward of the inner film layer on the cylindrical mandrel and spaced from the radiopaque element, the second radiopaque element comprising a second polymer material having a second radiopacifier material contained therein, wherein the second radiopacifier material imparts radiopacity to the second radiopaque element, wherein the outer film layer is positioned to cover the second radiopaque element, and the thermal bonding further connects the second radiopaque element to the inner and outer film layers to form the tube.