Bioalloy braided self-expanding biodegradable stent

Abstract

To provide an implantable device including a tube including a plurality of biodegradable, biocompatible metal wires braided together.SOLUTION: In the expanded state, the tube is coated with a flexible, conformal biodegradable polymer, and when compressed and the compression is released, the flexible, conformal biodegradable polymer-coated tube self-expands to the expanded state.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Patent Application No. 63 / 006,565, filed April 7, 2020, the entire disclosure of which is incorporated herein by reference. [Background technology]

[0002] Current bioabsorbable stents are typically made from varying amounts of bioplastics and biocompatible metals, but are subject to significant performance limitations based on the inherent properties of the biocompatible materials used to construct the stent.

[0003] Both bioplastics and biocompatible metals are not radiopaque, making device delivery and tracking difficult, especially in clinical situations involving precise vessel sizing and implant placement. Additionally, bioplastic scaffolds lack inherent strength and flexibility, especially compared to non-absorbable materials.

[0004] To compensate for certain properties such as lack of strength, stents made from bioplastics generally require more material (i.e., greater mass, thicker struts) and, as a result, have a longer absorption time after insertion (i.e., years instead of months).

[0005] Biocompatible metals have mechanical properties that are quite similar to those of non-absorbable metals, but the combination of design and manufacturing techniques available to maintain these properties in implantable devices is limited, often resulting in suboptimal performance (e.g., high failure rates due to fracture and / or premature degradation) for a limited set of use conditions (e.g., vessel diameter) or delivery systems for deployment (e.g., balloon expandability). Summary of the Invention

[0006] The present disclosure is therefore directed to improvements in bioabsorbable devices, such as stents, that address one or more of the above-mentioned problems, such as suboptimal performance and limited applications due to either poor visibility, the design of the stent, or the biomaterials from which such bioabsorbable stents are made, and / or a combination thereof, and particularly addresses the challenges associated with accurate vessel sizing and implantation of bioabsorbable stents. Magnesium stents, and more particularly magnesium stents based on self-expanding braided wire, are engineered to have faster absorption times (e.g., months instead of years) and improved visibility, and address one or more limitations associated with current bioabsorbable stents as described above and prior art bioabsorbable stents.

[0007] Disclosed herein are various embodiments of hybrid self-expanding biodegradable stents (HSEBS). For purposes of this disclosure, the term "hybrid" generally refers to the incorporation of radiopaque (RO) metal wires (e.g., single, composite, and / or multiple wire strands) that enhance the visibility of the device upon implantation (e.g., using radiological techniques or other imaging modalities). The term "self-expanding" generally refers to the ability to recover a majority of the as-manufactured diameter upon delivery into a lumen. The term "biodegradable stent" generally refers to the device's ability to be safely absorbed after implantation, based on the predominance of biocompatible metal wire components (e.g., single, composite, or multiple wire strands) used to construct the device. The terms "biocompatible metal" and "of a biocompatible metal" refer to metals that are biocompatible and biodegradable when implanted in a living organism, such as a human. The HSEBS may be fabricated from a braided tube containing wires of a biodegradable, biocompatible metal intertwined clockwise and counterclockwise around a mandrel, with or without a permanently coated RO wire. The addition of radiopaque wires to the HSEBS allows for end-to-end visualization of the entire length of the stent and tracking of the stent during implantation and other procedures.

[0008] In various embodiments, the biodegradable, biocompatible metal wire may be made from a magnesium alloy (MA), where a majority (e.g., at least 80%) of the wire may be magnesium. In certain embodiments, the RO wire may be made from a non-degradable metal. In certain embodiments, the MA may be made from a medical-grade material and may be free of rare earth elements.

[0009] In certain embodiments, the MA may be alloyed magnesium (e.g., greater than 90% w / w Mg), which may contain zinc, calcium, and manganese to form a strong, ductile alloy, and is free of rare earth elements, making the alloy suitable for implantation in various structures, including blood vessels such as arteries and veins.

[0010] In particular embodiments, the MA may be chemically composed of at least 80% w / w magnesium, zinc, zirconium, and rare earth elements, where the MA may be biocompatible and may have high tensile strength, yield strength, and elongation. In some embodiments, the biodegradable metal may also include iron and zinc.

[0011] In some embodiments, the RO wire may be made from a metal with a low modulus of elasticity and a high yield stress for large elastic strains, which serves both radiopacity and mechanical roles in the braided structure. The modulus of elasticity is a key factor in the resilience of a metal and its ability to recover from compression, and is essentially a defined material property inherent to the alloy / material system. In some alloys, the modulus of elasticity can be slightly altered and increased by further processing the metal / alloy. For example, in terms of modulus (lowest to highest), magnesium has a low modulus of elasticity of 5 megapounds per square inch (Mpsi) compared to other braidable metals / alloys, compared to the significantly higher moduli of Nitinol or nickel-titanium alloys (~8-12 Mpsi), titanium (10-14 Mpsi), stainless steel, platinum, and tantalum (20-25 Mpsi), and cobalt-chromium alloys (25-30 Mpsi).

[0012] RO wire may be made from biocompatible metals such as gold, platinum, and tantalum, because these metals have a higher density than the material of the stent, allowing the stent to be easily seen on an X-ray. In certain embodiments, the diameter of the RO wire may be reduced by between 25% and 40% compared to the diameter of the magnesium alloy wire, which helps to compensate for the mechanical properties of the RO wire and prevents deformation of the HSEBS incorporating the RO wire.

[0013] In particular embodiments, the RO wire may be a composite material, which may be made from MA tubing or a shape memory alloy such as nickel titanium (or nitinol), and may include a core material to enhance visibility. In some embodiments, particularly the latter shape memory alloy, the composite wire may provide both visibility and mechanical support to the braided structure. In some embodiments, the biodegradable tubular MA composite may include a core of radiopaque powder material, which typically provides radiodensity to the radiolucent material.

[0014] In other embodiments, the radiopaque element may comprise a wire strand wrapped around the RO core wire, which may serve both radiopacity and mechanical roles in the braided structure.

[0015] In some embodiments, the multiple wires making up the braided tube may be wrapped and woven around a single mandrel in a clockwise and counterclockwise manner in a one-over-one-under (1x1) pattern. In other embodiments, the wires may be wrapped and woven in a 2x2 (two over, two under) braid pattern. In general, braiding wires refers to wrapping wires in clockwise and counterclockwise directions, e.g., over and under each other as they cross, into a tubular shape (e.g., around a mandrel), and weaving them together.

[0016] In certain embodiments, the braided tube may be initially formed in an expanded configuration so that it can regain or re-expand its expanded state after compression, and in one particular embodiment, the preferred number of wires is 24. In various embodiments, the angle of the braided wires is 30° or greater relative to the longitudinal axis of the mandrel at the intersection of the wires.

[0017] In particular embodiments, the ratio and / or configuration of permanently coated non-degradable metal wires to biodegradable biocompatible metal wires may be 1:1 or less of the total number of wires required to make the braided tube. In embodiments for a 24-wire braided configuration, this ratio may be 1:11 or less, since most (>90%) of the braided configuration is absorbable unless composite wires are used.

[0018] In some embodiments, to prevent dissimilar metals from contacting each other, the RO wire may be coated with a permanent (i.e., non-biodegradable) polymer coating, thereby inhibiting or preventing galvanic corrosion. In various embodiments, the polymer may be made from a dielectric, insulating material that can withstand very high temperatures.

[0019] In particular embodiments, the tube may be cut into smaller segments (or "braided stents") of various lengths. In certain embodiments, the braided tube may be cut into braided stents at the point where the wire has made at least one full revolution (360°) along its longitudinal axis (e.g., on a mandrel), reducing the likelihood of fraying the wire ends. In some embodiments, the initial cut of the hybrid tube may separate shorter braided segments from the hybrid tube, and the final cut provides a uniform end length for the stent, reducing the risk of wire deformation and improving symmetry and uniformity of the stent.

[0020] In some embodiments, the distal wires may be bonded to one another and the ends of the device may be closed using bonded cuffs that include both absorbable and non-absorbable elements. In other embodiments, the ends of the stent may be closed during the braiding process by looping the wires back into the pattern of the braided tube.

[0021] In certain embodiments, the braided stent may be self-expanding, where a self-expanding stent may recover from a compressed state to a diameter that is at least 50% of its as-created diameter (i.e., the diameter of the pre-compressed configuration) after being compressed, constrained, and released from a delivery system such as a catheter.

[0022] In various embodiments, the stent may be coated with a biodegradable polymer. In some embodiments, the coating may be applied by spraying and / or dip-coating a layer onto the braided stent to produce a conformal, flexible coating, where the biodegradable polymer coating may be used to adjust the bioabsorption profile of the Mg-based substrate when implanted in tissue.

[0023] The conformal, flexible coating uniformly bonds the wires at their intersections, adhering to the surface of the stent while preventing the wires from sliding past one another. The applied coating may, in certain embodiments, reduce or prevent deformation of the wires and allow the braided stent to achieve uniform expansion when released from restraints.

[0024] Conformal, flexible coatings of the type described herein also improve the mechanical properties of the stent, particularly its ability to recover or re-expand to a desired diameter and shape, and more importantly, reduce or prevent distortion of the stent ends. This may be achieved through a combination of the elastic properties of the stent and the conformal, flexible coating, the latter being used to control the bioabsorption profile and improve the recovery or re-expansion performance of the stent. In certain embodiments, the conformal, biodegradable polymer may contain a plasticizer. In some embodiments, the conformal properties of the polymer may be optionally adjusted by using various biocompatible plasticizers. In some embodiments, the plasticizer-containing polymer aids in the elastic recovery of the stent while deployed.

[0025] In various embodiments, a conformal, flexible, biodegradable polymer coating (with or without added plasticizers) may be applied evenly to the entire stent, resulting in a uniform coating of approximately 10 micrometers thickness covering the entire stent. In some embodiments, the coating thickness may be less than 10 micrometers and / or greater than 10 micrometers to accelerate the degradation of the biodegradable metal or extend the longevity of mechanical properties.

[0026] In particular embodiments, the coating may be applied to the stent in layers to achieve a coating that is about 10 micrometers thick in the middle portion of the stent and up to 30 micrometers, but preferably about 20 micrometers thicker, at each end of the stent, covering about 5% to 50% of the length of the stent starting at each edge, and preferably embedding about 10% to 20% of the length of the stent. In some embodiments, individual bands and / or rings may be applied to embed and / or suspend the open ends of the wire ends of a braided stent.

[0027] Thus, one embodiment provides an implantable device comprising a tube comprising a plurality of wires of a biodegradable, biocompatible metal braided together; the tube is coated with a flexible, conformal, biodegradable polymer in an expanded state such that when compressed and released, the flexible, conformal, biodegradable polymer-coated tube self-expands back to the expanded state. [Brief explanation of the drawings]

[0028] Various objects, features, and advantages of the presently disclosed subject matter can be more fully understood when considered in conjunction with and with reference to the following detailed description of the disclosed subject matter, in which like reference numerals identify like elements and in which:

[0029] FIG. 1 shows a HSEBS made from a braided tube containing biodegradable, biocompatible metal wires 10 and RO wires 11 intertwined in a clockwise and counterclockwise manner.

[0030] Figure 2 illustrates different configurations in which RO wires can be positioned. For example, in stent 101 (left panel), there are two RO wires, positioned opposite each other (i.e., 180° apart) when viewed in cross section. In this particular two-wire configuration, the RO wires provide radiopacity to the braided structure. In stent 102 (center panel), there are four RO wires, two of which are wound clockwise and two of which are wound counterclockwise, such that the wire intersections are positioned opposite each other (i.e., 180° apart) when viewed in cross section, as in the two-wire configuration. In this case, the RO wires may provide both radiopacity and mechanical functions. On the other hand, stent 103 (right panel) has a four-wire configuration, but all wires are wound in the same direction and positioned 90° apart (when viewed in cross section) for optimal visibility and additional design stability, especially for braided stents with small wire diameters.

[0031] Figure 3 shows several images to illustrate the lack of visibility offered by magnesium and magnesium alloys. Image A shows a stenotic lesion (white arrow). Image B presents an intravascular image of the struts of an implanted magnesium stent (green arrow). The magnesium and magnesium alloy stent is visible with intravascular imaging, such as intravascular ultrasound, but remains undetectable with fluoroscopic imaging (Image C).

[0032] Figure 4 provides a pictorial example of a braided hybrid self-expanding biodegradable stent (HSEBS) implanted in the artery of a domestic pig. Image A shows a stent 103 with 20 magnesium alloy (MA) wires and 4 RO wires. The RO wire to MA wire ratio is 1:5. Image B shows a stent 101 with an RO wire to MA wire ratio of 1:11, where the wires are positioned opposite each other (i.e., 180° apart) when viewed in cross section.

[0033] Figure 5 shows a laser-cut, non-degradable metal stent with individual markers added to the ends of the stent, particularly its tip (see arrows in the main image and inset, where the inset corresponds to the dotted box in the main image), to improve the visibility of the stent. These markers may be made of gold, platinum, or tantalum. These markers generally have a higher density than the stent material, allowing the ends (or other distal portions) of the stent to be easily visualized by angiography.

[0034] Figure 6 is an image of a 24-wire HSEBS with RO wire to MA wire arrangement in a 1:11 configuration, where RO wires 11 are arranged opposite each other (i.e., 180° apart) when viewed in cross section in two RO wire configurations. RO wires 11' represent the RO wires spanning the length of the stent. Also shown is the angle α at which the RO and MA wires are wrapped relative to the longitudinal axis of the braided tube.

[0035] Figure 7 shows how the hybrid tube in panel A undergoes an initial cut (a) to produce shorter braided segments from the longer hybrid tube, followed by a finish cut (b) to create a more uniform end length for the stent, reducing the risk of wire deformation and improving stent symmetry and uniformity, i.e., producing wire ends that are substantially the same length as each other. Panel A of Figure 7 also shows how the hybrid braided tube may undergo the same cutting process, with an initial rough cut followed by a second cut to trim the wire ends, in which the wires make an additional quarter-turn along the longitudinal axis of the mandrel (a). The paired wire ends may then be separated and aligned parallel to each other and secured with a polymer cuff 20. Once each pair of wire ends (panel A) is connected (e.g., using a cuff), the wire ends protruding from the cuffed ends are trimmed to form a closed-ended stent. Alternatively, pairs of wire ends may be bent to form loops (Figure 7, panel B) and aligned parallel to each other and secured in a polymer cuff 20 by pushing the wires into the cuff.

[0036] Figure 8 shows a closed-end stent A, in which paired wire ends are separated and aligned parallel to each other and may be secured with a polymer cuff. This stent is produced using a 2x2 braid pattern.

[0037] Figure 9 shows a closed-end stent B (left image), in which paired wire ends are bent to form loops, aligned parallel to each other and approximately perpendicular to the longitudinal axis of the stent, and secured with a polymer cuff by forcing the wires into the cuff. The stent, in this case, is made from zinc, calcium, and manganese-containing MA wire (ZXM) and includes a 1 x 1 braid pattern with a 65° braid angle along the x-axis / relative to the longitudinal axis. The image on the right in Figure 9 shows the closed-end stent of ZXM braid after it has been compressed to its loading diameter and loaded into a 7 mm glass tube to simulate stent placement in a blood vessel.

[0038] FIG. 10 shows braided stents, both of which have a conformal, biodegradable polymer (CBP) coating. The image on the left is of a stent coated with a CBP coating without a plasticizer, and the image on the right is of a stent coated with a CBP coating with a plasticizer. CBP coatings, with or without plasticizers, are used to bind wires together at their intersections and prevent them from slipping relative to one another. However, only CBP coatings with plasticizers help prevent wire end deformation and wire disengagement from intersections, especially in stents with open-ended configurations, which are at high risk of wire end deformation and polymer delamination during stent cycling (e.g., compression, loading, and expansion). The image on the left in FIG. 10 includes dotted lines, which indicate the original position of wires that have disengaged at some intersections and consequently slipped relative to other wires (indicated by arrows). On the other hand, the wires of the stent in the image on the right in FIG. 10 are not disengaged at their intersections.

[0039] 11 shows that the CBP coating can be applied in a thicker layer at the edges or ends of each stent segment to form a polymer ring to completely embed the open-ended wire ends, with some examples indicated using solid lines and asterisks (*). Creating the polymer ring at the ends of the stent segments can be achieved by a number of procedures, such as dipping, spraying, and / or applying a ring onto the edges of the stent in one or more applications of the polymer solution, and / or applying the polymer to the edges of the stent using a more concentrated polymer solution (e.g., 2x). DETAILED DESCRIPTION OF THE INVENTION

[0040] In accordance with some embodiments of the disclosed subject matter, mechanisms (which may include apparatus, systems, methods, and media) for improved stent-like bioabsorbable devices are provided, along with procedures for making and using such devices.

[0041] The present disclosure presents embodiments for a novel hybrid self-expanding and bioabsorbable wire-based braided stent that, among other challenges, addresses the durability issues associated with permanent stents and stent-like devices and the lack of mechanical strength associated with known biodegradable bioplastic (polymer) stents by presenting an alternative option to self-expanding braided stents made largely of metallic biometals.

[0042] This novel hybrid braided stent provides temporary structural support to biological lumens, including but not limited to arteries, cavities, ducts, tracts, tracts, and veins.

[0043] Magnesium (Mg) is known to be useful for creating medical implant devices due to its biocompatibility and degradability, making it an ideal material for clinical applications. Mg is also an essential element for the human body, as it promotes protein synthesis, contributes to nerve and muscle function and bone growth, and regulates blood sugar. Like calcium, potassium, and sodium, Mg is essential for the proper functioning of the human body.

[0044] Although Mg and Mg alloys have been used in the past for stents and other types of bioabsorbable stents, conventional methods for manufacturing stents made from Mg and Mg alloys have several drawbacks, including lack of radiodensity, unfavorable mechanical properties, and rapid biocorrosion and degradation.

[0045] Although implants can be visualized using alternative imaging modalities, such as intravascular imaging (Figure 3B), visibility (i.e., lack of radiodensity) is one of the major drawbacks of many bioabsorbable / degradable implants (Figure 3C). The inability to visualize a bioabsorbable device using fluoroscopic imaging guidance can lead to serious adverse events, such as thrombosis, scar tissue formation, and more. This, in turn, can lead to reduced blood flow or embolization, e.g., in cardiac arteries, potentially resulting in a myocardial infarction (i.e., heart attack).

[0046] While the goal of using bioabsorbable / degradable stents is to achieve complete degradation of the biomaterial(s) and eventual absorption by the body, this disclosure describes the functionality and utility of a hybrid device, in which a combination of an absorbable Mg alloy and a non-absorbable, non-degradable metal is used to create a self-expanding Mg-based stent that provides radiopacity / radiodensity.

[0047] As mentioned above, stent visibility remains a major obstacle for known bioabsorbable / degradable stents / scaffolds. Failure to properly visualize the stent can increase the likelihood of misconfiguration when implanted within the body, for example, due to suboptimal or improper placement. The inability to visualize the entire stent structure, for example, when using fluoroscopic imaging guidance, puts both the implant and the patient at risk.

[0048] In the former situation (i.e., risk of product failure), the user cannot see the implant and so the implant is essentially operating blind. In the latter situation (i.e., risk to the patient due to product failure), the patient is potentially susceptible to the severe adverse events described above. The ability to visualize a bioabsorbable / degradable implant is paramount to the functionality and performance of the device not only upon implantation but also during the period following implantation.

[0049] Although the difficulties associated with visualizing Mg-based stents using radiation-emitting imaging modalities can lead to potential failure of the stent construct, the material from which the stent construct is made is important. It has been recognized in the scientific literature that current bioabsorbable stent platforms lack sufficient visibility under medical imaging for optimal implantation.

[0050] For any functional stent, the manufacturing process used to fabricate the device must be compatible with the material so that the inherent properties of the material are preserved to avoid performance failure of the implanted device.

[0051] For bioabsorbable stents made from biocompatible metallic materials, manufacturing processes involving localized thermal energy, such as welding or laser cutting, or extreme mechanical stress, such as wire bending, can alter the inherent properties of the biocompatible metallic material, making the stent more susceptible to fracture or uneven biodegradation. A braided manufacturing process for biocompatible metallic materials avoids many of these drawbacks.

[0052] Thus, disclosed herein are bioabsorbable stents that are improved over existing bioabsorbable braided wire stents based on a combination of novel structural features that provide radial strength, greater expandability with greater resistance to fracture, and / or improved fluoroscopic imaging visibility.

[0053] For example, wire-based stents such as those disclosed herein are not subject to laser heat-affected zones, which can alter the microstructure and properties of Mg or Mg alloys. Also, there is greater control over wire processing and strength than with extruded tubing, which is typically fully annealed to reduce yield strength / rebound and maximize elongation, but is more prone to failure. Hybrid self-expanding bioabsorbable stents (HSEBS) such as those disclosed herein contain biodegradable metallic wires and either radiopaque composites of degradable magnesium alloys or non-degradable radiopaque metallic wires made from radiopaque materials.

[0054] The self-expanding feature of the disclosed embodiments results from the combination of the bioabsorbable (e.g., Mg or Mg alloy) wires that together make up half or more of the wires of the HSEBS, and in some cases, the non-degradable nature of the RO wire, especially when the wires are braided together and coated with a conformal flexible polymer.

[0055] This combination can be compressed prior to delivery to a subject (e.g., a patient) and, when uncompressed, results in a stent that is self-expandable to an expanded position that can be 50% or more of the as-created (pre-compressed) diameter of the HSEBS, with this self-expansion occurring as a result of the combination of the elastic and flexible polymer coating on the wires and the interaction between these components, such as the braiding of the wires and the attachment of the coating, and the fact that the coating maintains interconnections between the wires and the intersections.

[0056] Preferably, the wires of the disclosed embodiments of the HSEBS are fabricated in an expanded configuration and then compressed and constrained within a delivery system. Upon release from the delivery system, the wires "spring back," i.e., self-expand to a predetermined diameter. This ability of the wires to recover some or all of their fabricated diameter (e.g., recover at least 50% of their fabricated diameter) is based, at least in part, on the elastic properties of the metal(s). In various embodiments, the wires may have a relatively low modulus of elasticity (e.g., as low as 5 Mpsi / 35 GPa) and a high yield stress, resulting in large elastic strains.

[0057] In other embodiments, applying a conformal flexible polymer to the braided tube while the tube is in an expanded state provides resilience (resilience) to the tube so that when the compressive force on the tube is released, the tube re-expands to some or all of its original, pre-compression diameter.

[0058] In various embodiments, the HSEBS may be fabricated from Mg-based wire, which contains rare earth alloying minerals, or in other embodiments, is substantially free of rare earth alloying minerals.

[0059] The former (i.e., containing rare earth elements) provides alloys with additional strength, resistance to permanent deformation over time with constant load or stress (i.e., metal creep), and increased corrosion resistance, while the latter (i.e., not containing rare earth elements) eliminates the possibility of clinically and histologically induced side effects.

[0060] In general, alloys (including Mg alloys) that are free of rare earth minerals and corrosion products are expected to produce little or no systemic or localized cytotoxic effects. Thus, the selection of a biocompatible metal depends on the application and / or intended use of the HSEBS.

[0061] In other embodiments, HSEBS may also be made from other biodegradable metals alloyed with various proportions of alloying metals, including alkali metals and selected transition metals and rare earth elements, such as aluminum, calcium, copper, dysprosium, iron, lithium, magnesium, manganese, yttrium, zirconium, and zinc.

[0062] Combinations of different biocompatible metals and biocompatible metal alloys can be used to influence the degradation and mechanical behavior of the resulting HSEBS, which, depending on its formulation, may be used for a variety of applications.

[0063] In one particular embodiment, Mg is alloyed with zinc, calcium, and manganese ( 3 90% Mg) to produce a strong, ductile, rare earth-free wire that is suitable for implantation inside blood vessels such as arteries and veins. In one example, the rare earth-free MA contains 1% zinc, 0.3% calcium, and 0.15% manganese, with a magnesium content of over 98%.

[0064] In another embodiment, a magnesium alloy (MA) wire may be provided that includes zinc, zirconium, and rare earth elements and has at least 80% magnesium. This particular MA wire is biocompatible, has high tensile strength, yield strength, and elongation, and is composed of 10% dysprosium, 1% neodymium, 1% zinc, and 0.2% zirconium, with the balance being 87% magnesium.

[0065] As mentioned above, the radiopacity of a stent is important because it allows the device to be visualized during radiographically guided procedures. Two main factors that contribute to the radiopacity of a metal are the density and atomic number of the metal. Mg allows radiation to pass more freely, making itself and its alloys radiolucent, which is the case with 316L stainless steel (@7.99 g / cm). 3 ) has a lower density (@1.74g / cm 3 ) because

[0066] 316L stainless steel is made primarily from iron (Fe), with a density of 7.8g / cm 3 and has atomic number 26, which is 2 g / cm for Mg. 3 Contrast this with iron, which has a density less than 12 and an atomic number of 12. Materials such as Fe that are better at blocking the passage of electromagnetic radiation are called x-ray opaque or radiopaque materials.

[0067] To improve the visibility of non-degradable metallic vascular stents, such as those made from 316L stainless steel, in some cases, discrete markers (FIG. 5) may be added to the stent (e.g., at the ends) to improve the visibility of the stent, especially at its distal end. These markers may be made from gold, platinum, or tantalum. These markers generally have a higher density than the stent material, allowing the ends (or other distal portions) of the stent to be more easily seen by angiography.

[0068] However, the significantly lower density of Mg compared to 316L stainless steel makes Mg-based HSEBS essentially invisible under fluoroscopy, and thus individual markers alone are likely not sufficient to visualize an otherwise nearly radiolucent stent by radiography.

[0069] Therefore, instead of using individual markers, embodiments of the HSEBS devices disclosed herein may include a magnesium alloy radiopaque composite or a non-degradable radiopaque metal wire (FIGS. 1, 4, and 6), such as a tantalum wire, that runs the entire length of the HSEBS rather than just the distal portion (FIG. 5), thereby providing continuous end-to-end visibility for the stent. In various embodiments, the non-degradable radiopaque wire may include other biocompatible materials, such as gold, platinum, iridium, iron, or tungsten, either alone or as part of an alloy. The addition of a radiopaque wire thus allows the stent to be visualized on an x-ray, allowing an otherwise transparent biocompatible metal wire stent to be viewed under fluoroscopic imaging guidance (FIG. 4).

[0070] Various numbers of radiopaque wires may be used. Certain embodiments of the disclosed HSEBS devices may include at least two radiopaque (RO) wires, while in other embodiments, no more than four RO wires may be braided within the structure of the HSEBS (FIGS. 2 and 4). In certain embodiments, the RO wires extend along the entire length of the braided structure (FIG. 6). In two- and four-wire configurations (101 and 102), the RO wires may be positioned opposite each other (or 180° apart) when viewed in cross section, whereas for four-wire configurations, the wires may be positioned 90° apart (103) for optimal visibility and additional design stability. More generally, in various embodiments, the RO wires may be positioned approximately equally spaced from each other when viewed in cross section, although other distributions are also possible.

[0071] In some embodiments, the RO wire may be absorbable and may include a radiopaque material, for example as a core. In particular embodiments, a magnesium composite wire with a radiopaque core may be used. For example, a drawn fill tube (DFT) 登録商標 ) wire (Fort Wayne Metals, Indiana) has an extruded shell material of one element or alloy (e.g., Mg or Nitinol) and a core containing another metallic / non-metallic material, and is an established material used in the manufacture of medical devices and may be used as RO wire.

[0072] In certain embodiments, MA tubing (e.g., pultruded filled Mg tubing) may be used, which is filled with a powdered radiopaque material to produce an RO composite wire with a biodegradable shell, providing the wire with mechanical properties more similar to those of non-absorbable metals and allowing stents or other devices containing the MA tubing to be degradable and radiopaque. The radiopaque powder may include one or more known radiopaque agents, such as barium, bismuth, tantalum, and tungsten, and may comprise up to 40% of the area of ​​the core material in the magnesium alloy composite wire.

[0073] In particular embodiments, the powdered radiopaque material filling the MA tube may preferably be a non-metallic radiopaque material often used in medical applications, such as bismuth trioxide (Bi2O3). Other fillers (or radiopaque agents) typically consist of high-density powders such as barium compounds (e.g., barium sulfate (BaSO4), tantalum oxide (Ta2O5), or tungsten carbide (WC)), and may be effective in attenuating the energy of the x-ray beam as it passes through the material, reducing its intensity by absorbing or deflecting all or part of the beam.

[0074] Hollow MA alloy tubes may be manufactured using modern work-hardening (cold working) methods. For use in making stents, the outer diameter of the hollow MA tube may range from 0.1 mm to 1 mm, while the RO material may comprise between 10% and 40% of the area of ​​the inner core material.

[0075] In certain applications, such as vascular stenting where leaving nothing behind in the body is an advantage, particularly in cerebral and coronary artery stenting where the vessels are small and prone to reocclusion, as well as in some non-vascular / venous applications such as ureteral and biliary stenting where fluoroscopic imaging guidance may be required to visualize the stent and where the stent may degrade or disappear over time, composite RO wire is an alternative to non-degradable RO wire, which is particularly useful when removal of the stent is indicated (e.g., ureteral stenting).

[0076] In other embodiments, the non-degradable RO wire may be made from a metal with elastic properties, with a low modulus and a high yield stress for large elastic strains, and thus may act as a resorbable scaffold for the stent, such as cobalt alloys and nitinol (FIG. 2; 102). Thus, in various disclosed embodiments, the non-degradable RO wire may provide predetermined mechanical properties as well as provide radiopacity in the braided structure, for example, when the non-degradable RO wire is arranged in a "crisscross" configuration.

[0077] In various embodiments, non-degradable RO wire may also be made from a shape memory alloy such as nickel-titanium (NiTi or Nitinol), which may allow for greater deformation and strain due to the alloy's greater elasticity and / or by leveraging the material's thermal memory. Nitinol wire may be used to provide additional mechanical support to the braided structure.

[0078] In certain embodiments, the nitinol wire may also include a core wire to enhance visibility by creating a nitinol composite. In one particular embodiment, NiTiDFT 登録商標 Wire (Fort Wayne Metals, Indiana) may be used that incorporates radiopaque materials such as, but not limited to, the most commonly used RO marker materials, such as gold, platinum, and tantalum, as well as the radiopaque powders / opacifiers mentioned above, so that other RO materials may comprise 10% to 40% of the core material. In this case, the nitinol composite may provide both visibility and mechanical support for the braided structure, thus aiding in the self-expansion of the HSEBS.

[0079] The non-degradable metallic materials that may comprise the structure of various embodiments of HSEBS are chemically dissimilar to one another, which can lead to corrosion, or galvanic corrosion, of the biocompatible metal. Galvanic corrosion occurs when two dissimilar metals come into contact in the presence of an electrolyte. Electrolytes are found in all bodily fluids, including blood, and may include sodium, calcium, potassium, and magnesium salts. When galvanic corrosion occurs, corrosion occurs at and near the point where the two metals come into contact. HSEBS have multiple such contact points.

[0080] Therefore, to reduce or eliminate the galvanic effects of dissimilar metals that may comprise the HSEBS structure, an insulating, dielectric, permanent (i.e., non-biodegradable) polymer coating, such as polyimide (PI), may be applied to the RO wire. PI, an imide monomer, may be applied to insulate non-degradable metallic wires.

[0081] In various embodiments, the polymer may be made from dielectric insulating materials that can withstand very high temperatures, including polyimides and fluoropolymers (e.g., Moldflon's PTFE and PFA). These polymers can be selected based on the metal being used, the application and location where the device will be used, and how the material will ultimately be processed, such as braided, annealed, and / or heat treated.

[0082] Biodegradable polymers may be used to prevent premature degradation of biocompatible metallic Mg-based substrates. The use of certain biodegradable polymer coatings to control and slow the degradation of Mg-based stents is known to those skilled in the art and has been reported in the scientific literature.

[0083] In various embodiments, a conformal biodegradable polymer (CBP) may be applied to the HSEBS to bind the wires at their intersections and prevent wire slippage. The CBP coating adheres to the surface of the stent. The CBP coating may also prevent wire ends from deforming and allow uniform expansion to be achieved when the braided stent is released from its restraints (FIG. 10). The image on the left side of FIG. 10, showing a stent coated with CBP without plasticizer, includes dotted lines indicating the original position of wires that have disengaged at some intersections and consequently slipped relative to other wires (displacement indicated by arrows). On the other hand, the wires of the stent in the image on the right side of FIG. 10 are coated with CBP containing plasticizer and have not disengaged at their intersections. Thus, particularly in stents with an open-ended configuration such as that shown in FIG. 10, the plasticizer helps prevent wire deformation and also helps prevent wires from disengaging at their intersections.

[0084] In some embodiments, conformal biodegradable polymers suitable for such applications include, but are not limited to, poly(L-lactide) or PLLA; poly(DL-lactide) or PLA; poly(L-lactide-co-D,L-lactide); or polyglycolide or PGA; poly(caprolactone) and copolymers thereof, such as poly(lactide-co-glycolide). In various embodiments, the biodegradable polymer may also contain a drug-eluting component, such as those disclosed in U.S. Pat. No. 9,849,008, which is incorporated herein by reference in its entirety. In some embodiments, the biodegradable polymer may contain or be coated with an antiproliferative drug-containing coating, which may include a limus drug (i.e., rapamycin or a derivative thereof) or a taxane drug.

[0085] In certain embodiments, the conformal properties of the polymer may optionally be modified by the use of a biocompatible plasticizer. Suitable plasticizers include, but are not limited to, alkyl citrate esters such as triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, or tri(2-ethylhexyl) citrate.

[0086] In particular embodiments, the conformal biodegradable polymer may include poly(D,L-lactide-co-glycolide) and acetyl tri-n-butyl citrate (ATBC) plasticizer. In some embodiments, the polymer with the plasticizer may aid in the elastic recovery of the stent during deployment. Adding a plasticizer to the biodegradable polymer provides more elasticity to the conformal coating, reducing the risk of coating delamination and rupture during stent / PPS use cycles. Furthermore, the biodegradable polymer plasticizer aids in the elastic recovery of the stent from a constrained state to a recovered state.

[0087] The present disclosure provides sufficient detail to enable one skilled in the art of implantable medical devices to create one or more embodiments of the disclosed device (HSEBS) with the desired number of wires, braiding pattern, and angle, using, for example, a commercially available programmable braider.

[0088] In one embodiment, the HSEBS may comprise a biodegradable metallic wire, such as a magnesium alloy radiopaque composite wire, or a non-degradable RO wire made from a transition metal such as Ta, which is dielectrically coated with a durable coating, such as with PI, to provide a device with enhanced visibility, and which is coated with a conformal biodegradable polymer coating, such as PLGA.

[0089] In a preferred embodiment, an automated braiding system with programmable pick count, braid length, and braiding speed may be used, allowing for the production of braided structures with, for example, greater flexibility, stiffness, kink resistance, good torque response, and radial / hoop strength.

[0090] The preferred braided structure utilizes a carrier configured to unwind wire from a horizontally oriented bobbin, allowing even the most tension-sensitive materials to be braided without rotation or twisting, however, other braiding / weaving methods can be used to achieve the desired braided tube structure.

[0091] Preferably, the HSEBS is intertwined in a one-over-one-under (1x1) pattern, and the braided tube is produced by winding multiple biodegradable and non-degradable wires in a clockwise and counterclockwise manner around a single mandrel, although other patterns for the braided tube may be used in various embodiments.

[0092] The size of the mandrel, the number of wires per braided tube structure, the wire diameter and properties, and the braid angle are also factors that affect braid behavior such as elastic recovery, hoop strength, and / or radial strength, and the preferred braided tube structure is produced in a continuous length in a 1x1 pattern on a single mandrel.

[0093] In a preferred embodiment, the braided tube structure may be made with 24 wires. A 24-wire tubular structure maintains structural stability for the preferred wire and braid mandrel sizes and targeted braid angles. A 24-wire braided tube structure minimizes deformation at the intersections of the Mg wires for the preferred HSEBS embodiment.

[0094] In a preferred embodiment, the bioabsorbable magnesium (Mg) wire is alloyed with materials with or without rare earth elements and has an outer diameter in the range of 0.1 mm to 0.2 mm.

[0095] For example, Mg wire containing rare earth elements may contain 80 to 90% magnesium by weight concentration (%w / w) and may be alloyed with more than 10% w / w of rare earth materials such as dysprosium, which gives the Mg wire higher strength, and may contain other alloying elements such as neodymium, zinc, and zirconium in a %w / w composition ranging from 0.1-5%. Another example is Mg wire containing more than 95% magnesium without rare earth materials and other alloying elements such as zinc, manganese, and zirconium in a weight concentration range of 0.1% to 5%.

[0096] The braided tube structure has a braid angle along the longitudinal axis of the mandrel / stent at the point where the wires cross, that is, the braid angle is the angle between the crossing wires and a line parallel to the long axis of the tube (see angle α in Figure 6). In certain preferred embodiments, the braid angle is between 60 and 65 degrees.

[0097] The biodegradable wire of the braided structure may comprise a biodegradable magnesium alloy radiopaque composite wire having an outer diameter similar to that of the non-composite magnesium wire (e.g., in the range of 0.1 mm to 0.2 mm), where the RO core of the magnesium alloy radiopaque composite wire comprises 10 to 40% of the wire diameter.

[0098] In contrast, the diameter of non-degradable RO wire, when contained in a braided tubing, is generally smaller than the diameter of biodegradable wire.

[0099] In various embodiments, the diameter of the non-degradable RO wire may be 25% to 40% smaller than the diameter of the magnesium alloy wire, in part to compensate for the mechanical properties of the non-degradable RO wire and in part to avoid kinking of the braided tubing.

[0100] In some embodiments, tantalum (Ta) wire may be used as a non-degradable RO wire to increase the visibility or radiopacity of the HSEBS, typically a radiolucent biocompatible metal braided stent that is visible under fluoroscopic imaging guidance. However, other materials that are considered biocompatible and radiopaque can also be used, such as gold, iridium, iron alloys, platinum, platinum group elements, silver, titanium, tantalum, tungsten, etc.

[0101] Ta wire is generally stronger than the biodegradable Mg wire used to fabricate the braided tube structures of preferred embodiments of HSEBS (UTS of ∼60 ksi for Mg alloy biodegradable wire vs. ∼250 ksi for Ta wire), the modulus of elasticity is higher for Ta (∼21 Mpsi vs. ∼5 Mpsi), and at a given diameter (e.g., 100 μm for Ta vs. 150 μm for Mg), the bending stiffness is approximately equal.

[0102] For preferred embodiments, the ratio of RO wire to biodegradable wire should not exceed 1:11 in a 24-wire configuration, as this would mean that most (>90%) of the braided tube is bioabsorbable unless composite non-degradable wire is used, in which case a wire ratio of 1:5 may be used for a 24-wire braided structure.

[0103] In a preferred embodiment, the non-degradable RO wire component of the HSEBS is coated with a dielectric, insulating, permanent polymer coating, such as polyimide (PI), to insulate the non-degradable metallic wire and thereby prevent galvanic corrosion between the dissimilar metals that make up the braided stent.

[0104] In a preferred embodiment, PI is used because PI monomers offer excellent dielectric and mechanical properties, as well as chemical inertness. Compared to other fluoropolymers, PI can be applied in multiple thin layers to improve substrate adhesion. PI also can withstand very high temperatures, up to 240°C (464°F) for continuous use and up to 400°C (752°F) for short-term exposure, while minimizing the generation of volatile materials.

[0105] The hybrid braided tube structure may be cut into short segments to produce the HSEBS. For stability, the braided tube is generally cut into stents once the wire has completed at least one full turn (360°) along its longitudinal axis on the mandrel, reducing the likelihood of fraying the wire ends.

[0106] Preferably, the hybrid tube undergoes an initial cut to produce shorter braided segments from the longer hybrid tube, followed by a finish cut to create a more uniform end length for the stent, reducing the risk of wire deformation and improving symmetry and uniformity of the stent.

[0107] In a preferred embodiment, the biodegradable polymer comprises poly(D,L-lactide-co-glycolide) and acetyl tri-n-butyl citrate (ATBC) plasticizer. As previously mentioned, the CBP coating prevents wire deformation and migration and also provides a restoring force that allows the braided stent to achieve uniform expansion when unconstrained. It also aids in the elastic recovery of the stent during deployment.

[0108] A preferred polymer is poly(D,L-lactide-co-glycolide) Resomer. 登録商標 RG858S (Merck, Darmstadt, Germany), which is a soft amorphous material with a relatively fast degradation rate (e.g., <9 months). ATBC plasticizer is a low-volatility compound with good plasticizing effect. It is a safe plasticizer and is used in many industries, including the manufacture of medical products.

[0109] In various embodiments, the CBP coating, with or without a plasticizer, may be applied evenly to some or all of the stent, resulting in a coating having a generally uniform thickness of at least 5 micrometers covering the stent. However, in various embodiments, the CBP coating may be applied at a thickness less than and / or greater than 10 micrometers to promote degradation of the biodegradable metal or conversely to extend the longevity of mechanical properties. The CBP coating may be applied by spraying a layer and / or by dip-coating the braided stent to produce a conformal coating.

[0110] Additionally, the CBP coating can be applied in a thicker layer, with or without plasticizer, at the edges or ends of each stent segment to form a discrete polymer ring (FIG. 11) completely embedding the open ends of the wire ends. Forming the polymer rings at the ends of the stent segments can be accomplished by a number of procedures, such as dipping, spraying, and / or applying one or more rings onto the edges of the stent with the polymer solution, and / or applying the polymer to the edges of the stent using a more concentrated polymer solution (e.g., 2x).

[0111] The polymer rings protect the stent, and by embedding the wire ends, particularly in braided stents, they protect the ends of the stent from deformation during stent loading and deployment. At both ends (or both edges) of the HSEBS of the stent, a thicker layer may be applied, which in various embodiments may cover 5% to 40% of the total length of the stent at each edge, and preferably 10 to 20% of the total length of the stent at each edge. In other embodiments, individual polymer rings—up to 50% of the stent—may be applied to secure / suspend the wire ends of a braided hybrid stent and prevent bending and distortion of the wire ends (FIG. 11).

[0112] In yet other embodiments, the disclosed biodegradable stents may be made using only biodegradable wires (i.e., without braiding RO wire into the stent), in which case non-degradable metallic bands (FIGS. 8 and 9) may be used to join paired wire ends to create closed ends, which provide structural stability and radiopacity to the stent. Methods for joining paired wire ends are known to those skilled in the art. In one embodiment, the wire pairs may be joined by, for example, a radiopaque cuff, as described in WO 2018 / 145029 A1, which is incorporated herein by reference in its entirety.

[0113] In another embodiment, the HSEBS may be entirely coated / coated with a thick CBP coating to create a graft-like coating that surrounds the entire stent. The term "thick" coating in this case refers to a coating with elastic properties having a relatively low Young's modulus that covers the entire braided tube and the areas / chambers between the wires at the intersections to create a sleeve-like or graft-like coating (FIG. 11).

[0114] These sleeve-like coatings consist of at least one biodegradable polymer or biodegradable copolymer or mixtures thereof. In a preferred embodiment, the biodegradable polymer is polylactic-co-glycolic acid (PLGA) with a relatively high intrinsic viscosity between 0.5 and 2.5 dL / g, and preferably between 1 and 2 dL / g.

[0115] The coating may optionally contain at least one additive used to improve the elastic properties of the coating, this additive having a mass ratio of 1% to 50% of the weight of the coating, and preferably 5% to 15% of the weight of the coating.

[0116] In some embodiments, the additive may be a bio-based plasticizer, which means a plasticizer that is biodegradable and / or can be metabolized by cells of the human body. In yet other embodiments, the additive is selected from alkyl citrate esters, including but not limited to, triethyl acetyl citrate, tributyl citrate, tributyl acetyl citrate, tri(2-ethylhexyl) citrate, trioctyl acetyl citrate, and trihexyl citrate.

[0117] This type of coating can be applied by a variety of methods, including dipping, spraying, and brushing. Preferably, the sleeve coating is applied to the stent by an automated dip method using a concentrated solution of the coating material in a suitable solvent, such as chloroform, dichloromethane, or dimethyl sulfoxide. Sleeve coating can be achieved by the dip method using a solution containing between 2 and 12% by weight (i.e., high viscosity), preferably between 4 and 6% by weight, of polymer, with the balance by weight being solvent.

[0118] In various embodiments, the braid pattern may be 2x2 (2 above, 2 below) (FIG. 8), and in various other embodiments, other suitable braid patterns may be used. Furthermore, in certain embodiments, the braided tube may be made on any standard braiding machine using either a horizontal or vertical braiding machine.

[0119] Braided structures can also generally be manufactured using any multiple of four wires, with the most common configurations being 8, 12, 16, 24, 32, 48, 64, 72, 96, 144, and up to 288 wires using a variety of commercially available braiding machines. Typically, half of the total number of wires are wound in one direction and the other half in the opposite direction to create a crossover braid pattern. In one particular embodiment, the preferred number of wires is 24, where a 24-wire tubular configuration maintains the stability of the HSEBS for the preferred wire and braid mandrel size and targeted braid angle, and minimizes wire deformation at the crossover points.

[0120] For other applications and / or embodiments, the outer diameter of the wire may range from 0.1 mm to 0.2 mm; however, in various embodiments, the outer diameter may range from 0.01 mm to 1.0 mm, depending on the type of biodegradable metal, the desired braid angle, and the number of wires required to create the braided tube. Furthermore, other factors such as the size of the stent or other implantable device and its intended target (e.g., large blood vessels or smaller arteries) will also help determine the diameter of the wire used, with larger implantable structures using larger diameter wires and smaller structures using smaller diameter wires.

[0121] In various embodiments, the size / diameter of the wires and mandrel, as well as the number of wires per braided tube, may affect the braid angle, but generally, the angle should be 30° or greater. In some embodiments, the braid angle may be between 60° and 65° for braided structures having 24 wires. In particular embodiments, the braid angle may be at least 50° for braided structures having 32 or more wires.

[0122] In various embodiments, RO wire may be used to improve the visibility of the HSEBS, allowing a mostly transparent biocompatible metal braided stent to become visible under fluoroscopic imaging guidance. As has been described, other biocompatible materials and radiopaque powders may be used to produce either magnesium alloy radiopaque composites or non-degradable radiopaque wires.

[0123] In specific embodiments, the ratio and / or arrangement of permanently coated non-degradable metallic wires to biodegradable, biocompatible metallic wires may not exceed 1:1 of the total number of wires required to produce the braided tube. In certain embodiments, the ratio of non-degradable to degradable wires may be as low as 1:1, or as high as 1:5, 1:11, 1:71, or other intermediate ratios. In one specific embodiment for a 24-wire braided structure, this ratio may not exceed 1:11 because most (>90%) of the braided structure is resorbable unless composite wires are used. In other embodiments, the ratio of composite to biodegradable metallic wires may be 1:5 in a 24-wire braided structure and 1:71 or greater for a 288-wire braid.

[0124] In other embodiments, the hybrid braided tube may undergo a cutting process similar to the preferred embodiment as described (ie, an initial rough cut followed by a second cut to trim the wire ends).

[0125] The hybrid tube may also undergo an initial cut to separate a shorter segment of the hybrid tube, and a second cut once the wire has completed an additional quarter turn along the longitudinal axis of the mandrel (element (a) in FIGS. 7A and 7B). The paired wire ends may then be separated, aligned parallel to each other, and secured with polymer cuffs (FIGS. 7A and 8). Once each pair of end wires is connected with a cuff 20, the wire ends protruding from the cuffed ends may be trimmed (FIG. 7A) to form a closed-ended stent.

[0126] Alternatively, the hybrid tube may also undergo an initial cut to separate a shorter segment of the hybrid tube, and a second cut once the wire has completed an additional quarter turn along the long axis of the mandrel (element (a) in Figures 7A and 7B). The paired wire ends are then aligned parallel to each other and approximately perpendicular to the longitudinal axis of the stent to form a loop, which is secured with a polymer cuff 20 (Figures 7B and 9).

[0127] Thus, while the present invention has been described above in connection with particularly preferred embodiments and examples, the invention is not necessarily so limited, and numerous other embodiments, examples, uses, modifications, and derivatives of such embodiments, examples, and uses are intended to be encompassed by the appended claims.

[0128] In the following, exemplary embodiments of the present invention are presented, each of which is made up of a combination of various elements. 1. An implantable device comprising: a tube comprising a plurality of biodegradable, biocompatible metal wires braided together; the tube is coated with a flexible, conformal, biodegradable polymer in an expanded state, and upon compression and decompression, the flexible, conformal, biodegradable polymer-coated tube self-expands to the expanded state; the flexible, conformal, biodegradable polymer bonds the braided wires of the tube together at a plurality of wire intersections to prevent sliding movement between the wires; the flexible, conformal, biodegradable polymer comprises a plasticizer; An implantable device wherein the tube further comprises one or more radiopaque wires to provide radiopacity to the tube. 2. The implantable device of claim 1, wherein at least one of said one or more radiopaque wires comprises a composite wire. 3. The implantable device of claim 2, wherein at least one of said one or more radiopaque wires comprises a magnesium alloy radiopaque composite wire. 4. The implantable device of claim 1, wherein said one or more radiopaque wires comprise one or more non-degradable radiopaque wires. 5. The implantable device of claim 4, wherein said one or more non-degradable radiopaque wires comprise a biocompatible radiopaque metal. 6. The implantable device of claim 5, wherein the diameter of said one or more non-degradable radiopaque wires is 25% to 40% smaller than the diameter of each of said plurality of biodegradable biocompatible metal wires. 7. The implantable device of claim 6, wherein said biocompatible radiopaque metal comprises at least one of gold, platinum, tantalum, iridium, iron, or tungsten. 8. The implantable device of claim 7, wherein said one or more non-degradable radiopaque wires are coated with a permanent polymer coating to inhibit galvanic corrosion. 9. The implantable device of claim 8, wherein said permanent polymeric coating comprises a dielectric insulating material. 10. The implantable device of claim 9, wherein said permanent polymer coating comprises at least one of a polyimide or a fluoropolymer. 11. The implantable device of any one of 1 to 10 above, wherein said plurality of biodegradable, biocompatible metal wires contain at least 80% w / w magnesium. 12. The implantable device of any one of 1 to 10 above, wherein said plurality of biodegradable, biocompatible metal wires comprises a magnesium alloy containing at least 90% w / w magnesium and at least one of zinc, calcium, or manganese. 13. The implantable device of any one of 1 to 10 above, wherein said plurality of biodegradable, biocompatible metal wires further comprise at least one of an alkali metal, a transition metal, or a rare earth metal. 14. The implantable device of any one of 1 to 10 above, wherein the tube is cut into at least two segments, and in each of the at least two segments of the tube, each of the wires completes at least one full rotation around the longitudinal axis of the tube. 15. The implantable device of any one of 1 to 10 above, wherein the flexible, biodegradable polymer comprises a conformal coating. 16. The implantable device of claim 15, wherein the flexible, biodegradable polymer further comprises at least one of: poly(L-lactide) (PLLA); poly(DL-lactide) (PLA); poly(L-lactide-co-D,L-lactide); polyglycolide (PGA); poly(D,L-lactide-co-glycolide); or poly(caprolactone). 17. The implantable device of claim 15, wherein the plasticizer comprises at least one citrate alkyl ester biocompatible plasticizer comprising triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, or tri(2-ethylhexyl) citrate. 18. The implantable device of claim 15, wherein the flexible, biodegradable polymer comprises a conformal polymer comprising poly(D,L-lactide-co-glycolide) and acetyl tri-n-butyl citrate (ATBC) plasticizer. 19. The implantable device of claim 15, wherein said flexible, biodegradable polymer further comprises an antiproliferative agent or an antiproliferative agent-containing coating.

Claims

1. 1. An implantable device comprising: a tube comprising a plurality of biodegradable, biocompatible metal wires braided together; the tube is coated with a flexible, conformal, biodegradable polymer in an expanded state, and upon compression and decompression, the flexible, conformal, biodegradable polymer-coated tube self-expands to the expanded state; the flexible, conformal, biodegradable polymer bonds the braided wires of the tube together at a plurality of wire intersections to prevent sliding movement between the wires; An implantable device wherein the flexible, conformal, biodegradable polymer comprises a plasticizer.

2. 10. The implantable device of claim 1, wherein said plurality of biodegradable, biocompatible metal wires contain at least 80% w / w magnesium.

3. 10. The implantable device of claim 1, wherein the plurality of biodegradable, biocompatible metallic wires comprise a magnesium alloy containing at least 90% w / w magnesium and at least one of zinc, calcium, or manganese.

4. 10. The implantable device of claim 1, wherein the plurality of biodegradable, biocompatible metallic wires further comprise at least one of an alkali metal, a transition metal, or a rare earth metal.

5. the tube is cut into at least two segments; 2. The implantable device of claim 1, wherein in each of the at least two segments of the tube, each of the wires completes at least one full turn around the longitudinal axis of the tube.

6. The implantable device of claim 1 , wherein the flexible, biodegradable polymer comprises a conformal coating.

7. 7. The implantable device of claim 6, wherein the flexible, biodegradable polymer further comprises at least one of: poly(L-lactide) (PLLA); poly(DL-lactide) (PLA); poly(L-lactide-co-D,L-lactide); polyglycolide (PGA); poly(D,L-lactide-co-glycolide); or poly(caprolactone).

8. 7. The implantable device of claim 6, wherein the plasticizer comprises at least one citrate alkyl ester biocompatible plasticizer comprising triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, or tri(2-ethylhexyl) citrate.

9. 7. The implantable device of claim 6, wherein the flexible, biodegradable polymer comprises a conformal polymer comprising poly(D,L-lactide-co-glycolide) and acetyl tri-n-butyl citrate (ATBC) plasticizer.

10. 7. The implantable device of claim 6, wherein the flexible, biodegradable polymer further comprises an antiproliferative agent or an antiproliferative agent-containing coating.

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