Intravascular devices and methods of treating aneurysms of intracranial vessels

Abstract

The invention relates to an intravascular device and a method of treating an aneurysm of an intracranial vessel. An intravascular device for positioning in a lumen of an intracranial vessel to transfer blood flow from an aneurysm of the intracranial vessel includes an elastically deformable tubular body including a braid having (1) at least 38 interlaced bioabsorbable polymeric fibers and (2) 2 to 12 elastically deformable interlaced metal wires, where when in an expanded configuration, the fibers are interlaced with one another, and when in an expanded configuration, the fibers are interlaced with one another. The porosity of the braid ranges from 60% to 80%, and the expanded configuration is selected to allow a small amount of blood to enter the aneurysm at a low speed, which results in thrombosis and occlusion of the aneurysm and heals the aneurysm. And wherein the elastically deformable metal wires (1) are each configured to promote and / or maintain radial and / or axial expansion of the polymeric fibers in the tubular body in the lumen, and (2) comprise a radiopaque material configured to promote imaging.

Description

[0001] This application is a divisional application of patent application No. 201980018150.6 with the title "Bioabsorbable flow diversion stent" and with the filing date of 12 March 2019.

[0002] BACKGROUND OF THE INVENTION TECHNICAL FIELD

[0003] The present disclosure relates to stents made of braids of bioabsorbable polymeric fibers for implantation in the lumen of a mammal. Particular aspects of the present disclosure relate to stents made of such braids for use in directing blood flow from a pathology associated with a blood vessel. BACKGROUND

[0004] There are a large number of known medical devices in the prior art which are implanted in the blood vessels of the human body to treat various diseases. For example, an aneurysm is a bulging, balloon-like structure caused by a local weakness in the wall of a blood vessel. The aneurysm wall is thin and fragile and therefore at risk of rupture. A "flow diversion" stent has been proposed to treat aneurysms, by means of which an endoprosthesis is inserted to span the neck of the aneurysm to direct blood flow through the aneurysm so that it heals. Thus, the flow diversion eliminates the need to enter the aneurysm. Such flow diversion stents are described in, for example, US 871531 and US 8267986. US 871531 and US 8267986 describe stents made of braided metal wires. TM The Pipeline Flex embolization device (Medtronic) is used for endovascular treatment of large or giant wide-necked intracranial aneurysms. TM The Pipeline Flex device consists of 75% cobalt-chrome / 25% platinum tungsten wire.

[0005] The metal composition of the flow diversion stents known in the art has disadvantages. Since flow diversion stents are permanent and cannot be removed, they have various disadvantages, including the risk of thrombosis (which requires the patient to take antiplatelet drugs for a long time), the risk of hyperplasia, the prevention of blood vessel lumen remodeling or dilation, and the risk of blood vessel occlusion. They also have disadvantages in the CT and MRI situation after implantation since the signals reflected by the metal stents tend to be too bright.

[0006] There is therefore a need for an implantable device which eliminates or reduces the negative reactions of the body at the implantation site while being able to prevent or treat a disease. Bioabsorbable stents have advantages compared to metal stents, including non-permanence. However, clinical studies have shown that bioabsorbable coronary stents have a higher risk of thrombosis (Masayuki et al., Circulation 136, A15796-A15796; et al., ACC (Journal Am. Coll. Cardiol. 66, 1901–1914; Kang et al., ACC Cardiovasc. Interv. 9, 1203–1212). Furthermore, Waksmen et al. (Circ. Cardiovasc. Interv. 10, e004762) have demonstrated that stents with the bioabsorbable polymeric properties of PLLA exhibit higher thrombotic activity. Summary of the Invention

[0007] Other aspects and features of the invention will become apparent to those skilled in the art from the following description of specific embodiments of the invention in conjunction with the accompanying drawings.

[0008] This disclosure relates to a device comprising an elastically deformable tubular body for positioning within a body cavity defined by a body wall, the tubular body comprising a woven fabric of interlaced bioabsorbable polymer fibers, wherein the tubular body comprises at least 38 polymer fibers. In various embodiments, when the device is in an inflated state, the porosity of the woven fabric is in the range of about 5% to about 80%. In various embodiments, when the device is in an inflated state, the porosity of the woven fabric is in the range of about 60% to about 80%.

[0009] This disclosure relates to an apparatus comprising an elastically deformable tubular body for positioning within a body cavity defined by a body wall, the tubular body comprising a weave of interwoven bioabsorbable polymer fibers, wherein, when the apparatus is in an inflated state, the porosity of the weave is in the range of about 60% to about 80%. In various embodiments, the tubular body comprises at least 38 polymer fibers.

[0010] In various embodiments of the above-described apparatus, the fabric comprises 38 to 96 bioabsorbable polymer fibers. In various embodiments, the fabric comprises at least 44 bioabsorbable polymer fibers. In various embodiments, the fabric comprises at least 46 bioabsorbable polymer fibers. In various embodiments, the fabric comprises at least 48 bioabsorbable polymer fibers. In various embodiments, the fabric comprises at least 72 bioabsorbable polymer fibers. In various embodiments, the fabric comprises 44 bioabsorbable polymer fibers. In various embodiments, the fabric comprises 46 bioabsorbable polymer fibers. In various embodiments, the fabric comprises 48 bioabsorbable polymer fibers. In various embodiments, the fabric comprises 72 bioabsorbable polymer fibers. In various embodiments, the fabric comprises at least 96 bioabsorbable polymer fibers.

[0011] In various embodiments of the above-described device, the bioabsorbable polymer fibers have a diameter of at least about 30 μm. In various embodiments, the diameter of the bioabsorbable polymer fibers ranges from about 30 μm to about 80 μm. In various embodiments, the diameter of the bioabsorbable polymer fibers is about 40 μm. In various embodiments, the diameter of the bioabsorbable polymer fibers is about 50 μm. In various embodiments, the diameter of the bioabsorbable polymer fibers is about 60 μm. In various embodiments, the diameter of the bioabsorbable polymer fibers is about 70 μm. In various embodiments, the diameter of the bioabsorbable polymer fibers is about 80 μm.

[0012] In various embodiments of the above-described device, the bioabsorbable polymer fibers are interwoven in a 2-down-2-up-2 pattern. In various embodiments, the bioabsorbable polymer fibers are interwoven in a 1-up-2-down-2 pattern. In various embodiments, the bioabsorbable polymer fibers are interwoven in a 1-up-1-down-1 pattern.

[0013] In various embodiments of the above-described device, the diameter of the tubular body is approximately 4 mm. In various embodiments, the bioabsorbable polymer fibers are interwoven with a pitch angle of approximately 16° or less. In various embodiments, the bioabsorbable polymer fibers are interwoven with a pitch angle of approximately 14° or less.

[0014] In various embodiments of the above-described device, the diameter of the tubular body is approximately 5 mm. In various embodiments, the bioabsorbable polymer fibers are interwoven with a pitch angle of approximately 12° or less. In various embodiments, the bioabsorbable polymer fibers are interwoven with a pitch angle of approximately 10° or less.

[0015] In various embodiments of the above-described device, the diameter of the tubular body is approximately 3 mm. In various embodiments, the bioabsorbable polymer fibers are interwoven with a pitch angle of approximately 18° or less. In various embodiments, the bioabsorbable polymer fibers are interwoven with a pitch angle of approximately 16° or less.

[0016] In various embodiments of the above-described device, the diameter of the tubular body is approximately 7 mm. In various embodiments, the bioabsorbable polymer fibers are interwoven with a pitch angle of approximately 9° or less.

[0017] In various embodiments of the above-described device, when the device is in an expanded state, the pore density of the woven fabric is approximately 10 pores / mm. 2 Approximately 32 holes / mm 2 Within the range.

[0018] In various embodiments of the above-described device, the tubular body further includes a visualization aid. In various embodiments, the visualization aid comprises a radiopaque material. In various embodiments, the radiopaque material includes iodine or barium. In various embodiments, the visualization aid comprises at least one filament comprising the radiopaque material, wherein each filament is interwoven with a plurality of bioabsorbable polymer fibers to form part of a braid.

[0019] In various embodiments of the above-described device, the tubular body includes means for promoting and / or maintaining radial and / or axial expansion of the tubular body within a body cavity. In various embodiments, the means for promoting and maintaining expansion of the tubular body within a body cavity is at least one filament, wherein each filament is interwoven with a plurality of bioabsorbable polymer fibers to form part of a braid. In various embodiments, the at least one filament comprises a radiopaque material.

[0020] In various embodiments of the above-described apparatus, the at least one wire is an elastically deformable wire. In various embodiments, the elastically deformable wire comprises a nickel-titanium alloy or a cobalt-chromium-nickel alloy. In various embodiments, each wire independently comprises: a nickel-titanium alloy coated with a radiopaque material; a drawn filled tube (DFT) comprising a nickel-titanium alloy outer layer and a core containing a radiopaque material; a DFT having an outer layer containing a radiopaque material and a core containing a nickel-titanium alloy; a cobalt-chromium-nickel alloy coated with a radiopaque material; a DFT comprising a cobalt-chromium-nickel alloy outer layer and a core containing a radiopaque material; or a DFT having an outer layer containing a radiopaque material and a core containing a cobalt-chromium-nickel alloy.

[0021] In various embodiments of the above-described device, the non-transmissive material includes iodine or barium.

[0022] In various embodiments of the above-described device, the non-transparent material includes a non-transparent metal. In various embodiments, the non-transparent metal is tantalum, gold, platinum, or a combination thereof.

[0023] In various embodiments of the above-described apparatus, at least one wire comprises a tantalum-coated nickel-titanium wire.

[0024] In various embodiments of the above-described apparatus, at least one wire comprises a DFT consisting of a nitinol outer layer and a platinum core.

[0025] In various embodiments of the above-described device, at least one thread includes 2 threads, 3 threads, 4 threads, 5 threads, 6 threads, 7 threads, 8 threads, 9 threads, or 10 threads.

[0026] In various embodiments of the above-described apparatus, the plurality of polymer fibers include polylactide (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylactide-co-glycolic acid (PLGA), polyanhydride, polyorthoester, poly(N-(2-hydroxypropyl)methacrylamide), poly(l-asparagine), DLPLA-poly(dl-lactide), poly(L-lactic acid), LPLA-poly(l-lactide), PDO-poly(dioxane), PGA-TMC-poly(polyglycolic acid-co-trimethylene carbonate), PGA-LPLA-poly(l-lactide-co-glycolic acid), PGA-DLPLA-poly(dl-lactide-co-glycolic acid), LPLA-DLPLA-poly(l-lactide-co-dl-lactide), PDO-PGA-TMC-poly(glycolic acid-co-trimethylene carbonate-co-dioxane), or any combination thereof. In various embodiments, the plurality of polymer fibers include polylactide (PLA), polylactide-co-glycolic acid (PLGA), DLPLA-poly(dl-lactide), poly-L-lactic acid (PLLA), LPLA-poly(l-lactide), PGA-LPLA-poly(l-lactide-co-glycolic acid), PGA-DLPLA-poly(dl-lactide-co-glycolic acid), LPLA-DLPLA-poly(l-lactide-co-dl-lactide), or any combination thereof. In various embodiments, the plurality of polymer fibers include poly-L-lactic acid (PLLA).

[0027] In various embodiments of the above-described device, the tubular body comprises a therapeutic agent bound to a bioabsorbable polymer fiber. In various embodiments, the bioabsorbable polymer fiber is coated with the therapeutic agent. In various embodiments, the therapeutic agent is an antibiotic, antiviral agent, an analgesic, muscle relaxant, chemotherapeutic agent, intra-arterial vasodilator, calcium channel inhibitor, calcium channel antagonist, calcium channel blocker, transient receptor potential protein blocker, endothelin antagonist, blood thinner, antiplatelet agent, or any combination thereof. In various embodiments, the therapeutic agent is aspirin, heparin, ticagrelor, 5-fluorouracil, melphalan, or clopidogrel. In various embodiments, the therapeutic agent is paclitaxel, sirolimus, everolimus, temozolomide, cyclophosphamide, doxorubicin, irinotecan, azathioprine, methotrexate, cisplatin, or vincristine.

[0028] In various embodiments of the above-described device, the lumen is the lumen of a blood vessel. In various embodiments, the blood vessel is an intracranial blood vessel. In various embodiments, the device is used to locate near a pathology of the blood vessel to divert blood flow from that pathology. In various embodiments, the pathology is an aneurysm, cancer, infection, coronary artery disease, carotid atherosclerosis, or intracranial atherosclerosis.

[0029] In various embodiments of the above-described device, the device is positioned in the lumen at a site adjacent to or near the body wall to supply lactic acid to that site.

[0030] This disclosure relates to the use of a device as defined above for deployment within a body cavity to treat a pathology defining or adjacent to the body wall of that cavity. This disclosure relates to the use of a device as defined above, deployed within a body cavity to deliver a therapeutic agent to or adjacent to the body wall of that cavity. This disclosure relates to the use of a device as defined above, deployed within a body cavity to deliver lactate to a site adjacent to or adjacent to the body wall of that cavity. In various embodiments, the body wall is a blood vessel wall. In various embodiments, the blood vessel is an intracranial blood vessel. In various embodiments, the pathology is an aneurysm, cancer, infection, coronary artery disease, carotid atherosclerosis, or intracranial atherosclerosis.

[0031] This disclosure relates to a method of treating a pathology of or near the body wall, the method comprising deploying a device as defined above at a location near the pathology within a lumen defined by the body wall. This disclosure also relates to a method of delivering lactate to a site near or near a pathology of the body wall, the method comprising deploying a device as described above within a lumen defined by the body wall near the pathology. In various embodiments, the body wall is a vascular wall. In various embodiments, the vascular vessel is an intracranial vascular vessel. In various embodiments, the pathology is an aneurysm, cancer, infection, coronary artery disease, carotid atherosclerosis, or intracranial atherosclerosis. Attached Figure Description

[0032] In the accompanying drawings illustrating embodiments of the present invention

[0033] Figure 1 This is a perspective view of an implantable device according to the first embodiment, comprising a woven fabric of bioabsorbable polymer fibers.

[0034] Figure 2 This is a photograph of an embodiment of an implantable intravascular device comprising 48 interwoven poly-L-lactic acid (PLLA) polymer fibers;

[0035] Figure 3 The photograph shows an embodiment of an implantable intravascular device comprising 48 interwoven poly-L-lactic acid (PLLA) polymer fibers, demonstrating the device's elastic deformability.

[0036] Figure 4 This is a schematic diagram of an implantable device comprising a woven fabric of interlaced fibers, showing the pitch angle.

[0037] Figure 5This is a schematic diagram of a weaving machine that can be used to manufacture the apparatus disclosed herein;

[0038] Figure 6A This is an isometric view of an implantable device according to a second embodiment of the present invention, comprising a woven fabric of interwoven bioabsorbable polymer fibers and a translucent material.

[0039] Figure 6B yes Figure 6A Side view of the device shown;

[0040] Figure 7A This is a photograph of an embodiment of an implantable intravascular device comprising 44 interwoven poly-L-lactic acid (PLLA) polymer fibers and 4 radiopaque filaments;

[0041] Figure 7B yes Figure 7A A close-up photo of the device;

[0042] Figure 8A This is a photograph of an embodiment of an implantable intravascular device comprising 46 interwoven poly-L-lactic acid (PLLA) polymer fibers and 2 radiopaque filaments;

[0043] Figure 8B yes Figure 8A A close-up photo of the device;

[0044] Figure 9A This is a schematic diagram of a diversion application used to treat aneurysms;

[0045] Figure 9B This is a schematic diagram of a diversion application used to treat aneurysms;

[0046] Figure 10 This is a schematic diagram of a diversion application combined with aneurysm bridging;

[0047] Figure 11A These are early angiographic images of the arteries taken before device implantation, showing an aneurysm generated in the rabbit carotid artery with a daughter sac at the apex of the aneurysm.

[0048] Figure 11B Before device implantation Figure 11A The early venous angiography of the same aneurysm shown (same as the angiography above) shows rapid contrast flushing outside the cyst.

[0049] Figure 11C It is after the device is placed. Figure 11A and 11B The early venous angiography of the same aneurysm shown illustrates contrast agent stagnation within the aneurysm, indicating a diversion effect.

[0050] Figure 12A This is an angiographic image of the rabbit aorta after implantation of a device consisting of 44 bioabsorbable PLA fibers and radiopaque tantalum-coated nickel-titanium fibers.

[0051] Figure 12B It was one month after the device was implanted. Figure 12A The image shown is an angiographic photograph of the rabbit aorta.

[0052] Figure 13 This is a scanning electron micrograph (SEM) showing the persistent patency of the aortic collateral branch in rabbits one month after device implantation.

[0053] Figure 14 This is an overall histological image of a device implanted in the rabbit aorta, comprising 44 bioresorbable PLA fibers and 4 radiopaque tantalum-coated nickelinol fibers.

[0054] Figure 15 This is a scanning electron micrograph (SEM) showing a smooth new intima layer formed on the stent strut one month after the device was implanted in the rabbit aorta;

[0055] Figure 16A This is a histological cross-section of a rabbit aorta showing the persistence of the polymer fibers and the formation of a new intima on the fibers one month after implantation.

[0056] Figure 16B This is a histological cross-section of the rabbit aorta showing the persistence of the polymer fibers, the new intima formed on the fibers, and the lack of vigorous inflammatory response 2 months after the implantation of the device.

[0057] Figure 17 The photograph shows a device according to an embodiment disclosed herein, consisting solely of bioabsorbable PLLA polymer fibers, illustrating the device's self-expanding capability after being inserted into a catheter with an inner diameter of 0.027 inches and then ejected. Detailed Implementation

[0058] definition

[0059] As used in this article, "pathology" refers to the deviation from the normal structure and function that constitutes or characterizes a disease, symptom, or condition.

[0060] As used in this article, “including” means “including but not limited to”.

[0061] As used in this article, “composed of” means “including and limited to”.

[0062] As used herein, "drug" or "therapeutic agent" can refer to any of the various drugs, pharmaceutical compounds, or other bioactive agents that can be used as active agents for the prevention or treatment of disease.

[0063] As used in this article, “bioabsorbable,” “biodegradable,” and “bioresorbable” are synonymous with materials or structures that degrade or dissolve over time in living tissues or human systems.

[0064] As used herein, “body cavity” refers to a cavity defined by tubular structures in the body of a mammal, including but not limited to blood vessels, ureters, urethra, and bile ducts.

[0065] As used herein, “wall” refers to the tubular structures that form the body of a mammal, including but not limited to the walls of blood vessels, ureters, urethras, and bile ducts.

[0066] As used herein, a "stent" refers to a tubular structure that can be inserted into a body cavity. Stents include those capable of being inserted into obstructed channels to keep them open and restore the flow of blood or other fluids. Stents also include devices that are not primarily used to keep obstructed channels open but rather to guide fluid flow. Stents can also be used as supports for tissue growth (e.g., neointimal growth). Stents can also be used as platforms for delivering therapeutic agents. Stents can be made of metal or plastic.

[0067] As used in this article, “visual aid” refers to any structure that facilitates examination via X-ray fluoroscopy.

[0068] As used in this article, “elastic deformability” refers to an object that can autonomously return to its original shape after being released from a shape that has been bent, stretched, compressed or otherwise deformed.

[0069] As used in this article, "endovascular device" refers to a prosthesis that can be implanted into a body cavity or endovascular catheter.

[0070] As used in this article, “fiber” refers to the filaments, threads, tendrils or strands that form textiles.

[0071] As used herein, "polymer fiber" refers to a fiber comprising a series of repeating monomer units that have been cross-linked or polymerized. In some embodiments disclosed herein, only one polymer is used. In another embodiment, a combination of two or more polymers may be used. In yet another embodiment, the polymer may be used with a radiopaque material. Polymers and combinations of polymers can be used in different proportions to provide different properties. Polymers that may be used in this invention include, for example, stable polymers, biostable polymers, durable polymers, inert polymers, organic polymers, organic-inorganic copolymers, or inorganic polymers. Suitable polymers are bioabsorbable, biocompatible, absorbable, absorbable, degradable, and biodegradable polymers.

[0072] As used in this article, "drainage" refers to guiding bodily fluids away from pathology.

[0073] As used in this article, "porosity" for a device in its fully expanded state is the ratio of free area to total area, where free area equals total area minus material surface area. In other words, it is the percentage of the entire open and fiber-free surface area of ​​the device walls.

[0074] Detailed description

[0075] This disclosure generally relates to implantable devices, methods of manufacture, and uses for the prevention or treatment of pathologies. Any term or expression not expressly defined herein should have its generally accepted definition as understood by those skilled in the art. The following description is for specific embodiments or particular uses of the invention and is for illustrative purposes only, not for limiting the invention, and should therefore be given the broadest interpretation consistent with the entire specification and claims.

[0076] Reference Figure 1 and Figure 2 The apparatus for guiding the flow of bodily fluids by utilizing body cavity positioning according to a first embodiment of the present invention is shown in approximately 10 locations. (Refer to...) Figure 2 The device 10 includes an elastically deformable tubular body 12 formed of a woven fabric 14 of interlaced bioabsorbable polymer fibers 16. (See reference...) Figure 1 The tubular body 12 defines an inner lumen 18 through which body fluids can continue to flow when the device 10 is deployed within a body cavity. Overlapping bioabsorbable polymer fibers 16 define pores 22.

[0077] In the currently described embodiment, the braid 14 consists of 48 bioabsorbable polymer fibers. However, flow guidance can be achieved using braids consisting of as few as 38 or as many as 96 bioabsorbable polymer fibers. In various embodiments of the currently disclosed apparatus for flow guidance purposes, the braid may include 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, or 94 bioabsorbable polymer fibers. In a particular embodiment of the currently disclosed device for flow guidance purposes, the woven fabric may consist of 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, or 94 bioabsorbable polymer fibers.

[0078] For applications where flow diversion is not required or desired, the woven fabrics of the currently disclosed invention may include as few as 20 bioabsorbable polymer fibers, as few as 18 bioabsorbable polymer fibers, as few as 16 bioabsorbable polymer fibers, as few as 14 bioabsorbable polymer fibers, or as few as 12 bioabsorbable polymer fibers.

[0079] In the currently described embodiment, the braid 14 is composed of bioabsorbable polymer fibers 16 with a diameter of 50 μm. As disclosed herein, bioabsorbable polymer fibers used to manufacture devices for diversion will have a diameter of at least about 30 μm, and will typically have a diameter in the range of about 30 μm to about 80 μm. In various embodiments of the currently disclosed devices having diversion uses, the diameter of the bioabsorbable polymer fibers will be about 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, or 80 μm. Those skilled in the art will understand that bioabsorbable polymer fibers having any diameter within this range can be used to produce diversion devices.

[0080] For the drainage device, the tubular body is desired to have high flexibility, enabling it to be delivered through microcatheters and, in various applications, through tortuous blood vessels and into the intracranial circulation. Therefore, the upper limit of the diameter of the bioabsorbable polymer fiber will be determined by the desired flexibility of the tubular body and the diameter of the lumen in which the device is deployed.

[0081] Figure 3 The image shows the flexibility and elastic deformation capabilities of a device composed of 48 poly-L-lactic acid (PLLA) bioabsorbable fibers.

[0082] Porosity

[0083] The braided nature of the device is crucial for flow guidance applications. The braided fabric allows for the creation of tubular structures with a sufficiently high material surface area and sufficiently low porosity to prevent excessive lateral flow of fluid across the sides of the tubular structure, thus enabling the guidance of liquid flow away from any point of interest across which the device traverses. The braided fabric also allows for the foldability of the device within the microcatheter for delivery. Furthermore, the bioabsorbable polymer fibers slide against each other, facilitating the expansion and contraction of the tubular structure.

[0084] For drainage applications, porosity is one of the most important design factors. Lower porosity results in lower blood flow velocities at the inlet and outlet of the aneurysm sac, increasing the chance of thrombosis and faster occlusion. Reducing the porosity of the BW stent also reduces wall shear stress (WSS) in the aneurysm and the parent arterial wall. On the other hand, as porosity decreases, the pressure within the aneurysm sac dome increases, thereby increasing the risk of aneurysm rupture associated with drainage stents in current clinical trials.

[0085] For flow guiding applications, a porosity of about 60% to about 80% is desirable for the tubular material. In a preferred embodiment, the porosity is in the range of about 60% to about 70%. In various embodiments of the device disclosed herein, the porosity will be about 60%, about 65%, about 70%, about 75%, or about 80%. In various embodiments, a pore density of 10 pores / mm is desired. 2 Approximately 32 holes / mm 2 Within a certain range. In a specific embodiment, the pore density is approximately 18 pores / mm². 2 Those skilled in the art will understand that as the porosity of a tubular structure decreases, its flexibility / deformability may also decrease. Therefore, the required flexibility of a tubular structure also indicates the limit to which porosity can be reduced.

[0086] Pitch angle

[0087] The pitch angle during the weaving process is a crucial factor affecting the surface area and porosity of the material in the expanded tubular state, thus influencing the flow conductivity of the device. The pitch angle also affects the device's elasticity to deformation, and therefore its self-expansion properties. (Refer to...) Figure 4 A generally illustrated, at 212, is an elastically deformable tubular portion of the device according to an embodiment of the present disclosure. The tubular portion 212 comprises a plurality of bioabsorbable polymer fibers 216. Interlocking bioabsorbable polymer fibers 216 define apertures 218. During fabrication, the tubular portion 212 is drawn on a mandrel 230. The pitch angle 250 of the fabric is an angle formed between the bioabsorbable polymer fibers 216 and the transverse axis 260 of the tubular portion 212.

[0088] Reference Figure 5 The pitch angle 260 of the weave is effectively determined by the angle formed between the bioabsorbable fibers 280 (which extend from the carrier 240 to the mandrel 250) and the transverse axis 270 of the mandrel 250.

[0089] The pitch angle, tubular diameter factor, and bioabsorbable polymer fiber diameter factor together affect the porosity of the tubular material, thus influencing the flow-guiding capability of the device. Therefore, to achieve a porosity within the typical range of flow-guiding devices, these variables must be adjusted according to the diameter of the bioabsorbable polymer fibers or tubular material to be used. For example, for bioabsorbable polymer fibers with a diameter of 50 μm and a desired tubular diameter of 4 mm, the pitch angle should be approximately 16° or less, or 15° or less. For a desired tubular diameter of 5 mm, the pitch angle should be approximately 12° or less, or 11° or less. For a desired tubular diameter of 3 mm, the pitch angle should be approximately 18° or less, or 17° or less. For a desired tubular diameter of 7 mm, the pitch angle should be approximately 9° or less. Table 1 below provides general guidance for appropriate combinations of tubular diameter, fiber diameter, and pitch angle. However, those skilled in the art will understand that the indicated combination is not intended to be limiting, and that adjusting each factor accordingly to achieve a suitable porosity is entirely within the capabilities of a person skilled in the art.

[0090] Table 1. Recommended parameters for the flow guiding device used in this disclosure

[0091]

[0092] Because the pitch angle exerts tension on the fibers that can cause them to break, the achievable pitch angle also depends on the quality of the polymer fibers. Generally, a smaller pitch angle can reduce porosity and increase the material's surface area. By adding more fibers with smaller diameters, the device can achieve a smaller pitch angle, thereby obtaining lower porosity.

[0093] Bioabsorbable polymer fibers

[0094] The polymer fibers used to produce the disclosed device include bioabsorbable polymer materials. The polymer materials degrade in vivo at a controlled / predictable rate and over a known time period. The degradation rate can depend on the polymer material, the diameter of the bioabsorbable polymer fibers, physiological conditions, the porosity of the tubular structures, etc.

[0095] Refer again Figure 2The bioabsorbable polymer fiber 16 of the illustrated embodiment comprises poly-L-lactic acid (PLLA). However, any one or more of a plurality of bioabsorbable polymer fibers can be used, including those containing polylactide (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylactide-co-glycolic acid (PLGA), polyanhydride, polyorthoester, poly(N-(2-hydroxypropyl)methacrylamide), poly(1-asparagine), DLPLA-poly(dl-lactide), poly(L-lactic acid), and LPLA-poly(1-lactide). Fibers of PDO-poly(dioxane), PGA-TMC-poly(polyglycolic acid-co-trimethylene carbonate), PGA-LPLA-poly(l-lactide-co-glycolic acid), PGA-DLPLA-poly(dl-lactide-co-glycolic acid), LPLA-DLPLA-poly(l-lactide-co-dl-lactide), PDO-PGA-TMC-poly(glycolic acid-co-trimethylene carbonate-co-dioxane), or any combination thereof.

[0096] In some applications, it may be desirable to induce an inflammatory response in the tissue near the deployed device, thereby promoting scar tissue formation. For example, in diversion applications for treating aneurysms, increased scar tissue in the vessel wall at the aneurysm neck can improve vascular strength at that site and reduce the risk of aneurysm recurrence as the aneurysm heals. For such applications, embodiments employing bioabsorbable polymer fibers that form lactic acid upon degradation may be useful. The accumulation of acidic degradation products can lower the pH of surrounding tissues, potentially triggering inflammatory and foreign body reactions at the pathological site. Implantation of PLLA stents in the coronary arteries of pigs leads to the expression of NF-κB, an inflammatory marker that regulates the expression of various inflammatory cytokines. Therefore, specific embodiments of the present invention may utilize bioabsorbable polymer fibers, including: polylactide (PLA), polylactide-co-glycolic acid (PLGA), DLPLA-poly(dl-lactide), poly(L-lactic acid), LPLA-poly(l-lactide), PGA-LPLA-poly(l-lactide-co-glycolic acid), PGA-DLPLA-poly(dl-lactide-co-glycolic acid), LPLA-DLPLA-poly(l-lactide-co-dl-lactide), or any combination thereof.

[0097] The device disclosed herein exhibits unique structural features during axial extension / expansion or compression. When the structure expands, it is able to substantially adapt to strain or stress because the initially tilted fibers can freely pivot to a position parallel to the stress direction. Furthermore, the individual polymer fibers can slide relative to each other, thus providing the device with elasticity and flexibility.

[0098] Visual aids

[0099] This woven assembly possesses unique structural features when stretched or compressed axially. When stretched, the structure can substantially adapt to strain or stress because the initially tilted fibers can freely pivot to a position parallel to the stress direction. Additionally, the individual polymer fibers can slide relative to each other, thus providing the device with elasticity and flexibility.

[0100] For physicians, deploying the device within a body cavity is crucial for determining its location. Therefore, it is anticipated that the devices disclosed herein will include visualization aids. Consequently, various embodiments of the implantable devices disclosed herein will include radiopaque materials to facilitate imaging of the device within a body cavity via X-ray fluoroscopy.

[0101] Such radiopaque materials can include tantalum, platinum, tungsten, gold, iodine, or combinations thereof. The selection of radiopaque materials can be based on factors such as the bioabsorbable polymer fiber, the imaging technique, and the pathology to be treated.

[0102] Non-transparent materials can be attached to or in contact with polymer fibers in various ways, such as by covalently bonding non-transparent materials to bioabsorbable polymer fibers, bonding non-transparent materials to bioabsorbable polymer fibers, or other forms of connecting, contacting, bonding, mixing, or merging non-transparent materials with polymer fibers.

[0103] Reference Figure 6A , 6B Images 7A, 7B, 8A, and 8B, generally shown at 310, illustrate a device according to a second embodiment of the invention, utilizing body cavity positioning to facilitate the drainage of body fluids, including a visualization aid. Device 310 includes an elastically deformable tubular body 312 formed of a weave 314 of interwoven bioabsorbable polymer fibers 316. (See also...) Figure 1 A tubular body 312 defines an inner cavity 318 through which body fluids can continue to flow when the device 310 is deployed within the body cavity. A visualization aid is provided by four translucent threads 317 interwoven with bioabsorbable polymer fibers 316 to form part of a braid 314. The interwoven bioabsorbable polymer fibers 316 and translucent threads 317 define an aperture 322.

[0104] The embodiment shown in Figure 7 utilizes 44 bioabsorbable polymer fibers and 4 non-transparent filaments. Figure 8AThe illustrated embodiment utilizes 46 bioabsorbable polymer fibers and 2 translucent filaments. However, any number of translucent filaments can be used as a visualization aid. The number used can depend on various factors, including the properties of the materials comprising the translucent fibers. Even one translucent filament is sufficient. However, the ability to visualize the device increases with the number of translucent filaments used. In various embodiments, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 12 translucent filaments can be used. Preferably, an even number of translucent filaments is used to maintain balance. In a preferred embodiment, 6 or 8 translucent filaments are used. Those skilled in the art will understand that the resolution of the device can decrease with increasing translucent filament numbers, and therefore the selected number will reflect a balance between the detectability and sharpness of the image.

[0105] As described above, the non-transparent wire 317 may comprise non-transparent materials such as tantalum, platinum, tungsten, gold, iodine, or combinations thereof. In certain embodiments, the non-transparent wire may be elastically deformable. In some embodiments, the elastically deformable wire is made of a nickel-titanium alloy (e.g., nitinol), a cobalt-chromium alloy (e.g., Phynox), or a cobalt-chromium-nickel alloy. Each elastically deformable wire may be independently made of: a nickel-titanium alloy coated with a non-transparent material; a drawn filled tube (DFT) comprising a nickel-titanium alloy outer layer and a core containing non-transparent material; a DFT comprising a non-transparent material outer layer and a core containing a nickel-titanium alloy; a cobalt-chromium-nickel alloy coated with a non-transparent material; a DFT comprising a cobalt-chromium-nickel alloy outer layer and a core containing non-transparent material; or a DFT comprising a non-transparent material outer layer and a core containing a cobalt-chromium-nickel alloy. In certain embodiments, the non-transparent wire is a tantalum-coated nitinol wire. In other embodiments, the non-transparent wire comprises a DFT having a nitinol outer layer and a platinum core.

[0106] Promote and maintain expansion

[0107] Importantly, when deployed within a lumen, the outer surface of the currently disclosed tubular structures remains tightly adhered to the vessel wall, particularly in devices used for diversion applications within blood vessels. If the outer surface of the tubular structure is not tightly adhered to the vessel wall, a thrombus can form in the space between the tubular structure and the vessel wall, leading to vascular occlusion. Although embodiments of the devices disclosed herein, which consist only of bioabsorbable polymer fibers, are elastically deformable, they may be prone to shrinking or partially collapsing within the vessel. Furthermore, when bioabsorbable polymer fibers are stored in a compressed state for extended periods, they may lose some of their self-expanding capacity.

[0108] Therefore, various embodiments of the devices disclosed herein include means for promoting and / or maintaining radial expansion of a tubular body within a body cavity to keep the outer surface of the tubular body in close contact with the body wall. Such means also contribute to promoting and / or maintaining axial expansion of the device. Thus, promoting and / or maintaining radial and / or axial expansion can facilitate self-expansion of the device when deployed within a cavity.

[0109] Devices for promoting and / or maintaining the radial and / or axial expansion of a tubular body within a body cavity may include threads interwoven with a plurality of bioabsorbable polymer fibers to form a portion of a braid. In operation, the threads apply radial forces to the tubular structure to promote radial expansion upon deployment and to push the tubular structure against the body wall to maintain the tubular structure in a fully expanded shape and to adhere it to the body wall. In certain embodiments, the threads are elastically deformable. Elastically deformable threads may include nickel-titanium alloys or cobalt-chromium-nickel alloys.

[0110] A single thread is sufficient to facilitate and maintain the radial and / or axial expansion of the tubular body. However, the radial force exerted during tubular expansion increases with the number of threads used. In various embodiments, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 12 transmissive threads can be used. Preferably, an even number of transmissive threads is used to maintain balance. In a preferred embodiment, 6 or 8 transmissive threads are used.

[0111] It will be apparent to those skilled in the art that the same filament can be used both as a visual aid and as a device for promoting and / or maintaining radial and / or axial expansion. Therefore, the filament may comprise radiopaque materials such as tantalum, platinum, tungsten, gold, iodine, or combinations thereof. In certain embodiments, the radiopaque filament may be elastically deformable. In some embodiments, the elastically deformable filament is made of a nickel-titanium alloy (e.g., nitinol), a cobalt-chromium alloy (e.g., Phynox), or a cobalt-chromium-nickel alloy. Each elastically deformable filament may be independently made of: a nickel-titanium alloy coated with a radiopaque material; a drawn filled tube (DFT) comprising a nickel-titanium alloy outer layer and a core containing radiopaque material; a DFT comprising a radiopaque material outer layer and a core containing a nickel-titanium alloy; a cobalt-chromium-nickel alloy coated with a radiopaque material; a DFT comprising a cobalt-chromium-nickel alloy outer layer and a core containing a radiopaque material; or a DFT comprising a radiopaque material outer layer and a core containing a cobalt-chromium-nickel alloy. In certain embodiments, the radiopaque filament is a tantalum-coated nitinol filament. In other embodiments, the non-transparent wire comprises a DFT having a nitinol outer layer and a platinum core.

[0112] Therefore, the wire component can provide at least three independent advantages: 1) it allows for radiopaqueness and thus can be visualized by means of X-ray fluoroscopy; 2) it improves self-expansion; and 3) it increases radial force to maintain radial expansion (extrusion force and long-term outward force) to keep the outer wall of the tubular body in close contact with the body wall.

[0113] manufacture

[0114] Refer again Figure 4 and Figure 5 In this context, the device, as disclosed herein, can be formed, for example, by individual interwoven bioabsorbable polymer fibers and, in various embodiments, by said polymer fibers and said filaments, which are used to manufacture a braid forming a tubular structure.

[0115] For example, weaving tubular structures on a "pentapole" machine avoids the need for known laser cutting techniques used to manufacture devices deployed in body cavities. Instead, bioresorbable polymer fibers of different diameters can be woven onto a mandrel at different pitch angles to produce woven, hollow tubular bodies with varying porosities. The weave can be a linear fiber assembly with groups of interwoven bioresorbable fibers offset relative to the longitudinal axis of the structure. The weave can be clockwise or counterclockwise interwoven or helical fibers.

[0116] Several patterns of woven or interwoven fibers can be used. The invention is not limited to any of the following examples: “1-up-1-down-1” or “half-load” pattern; “2-down-2-up-2” or “diamond” pattern; “1-down-2-up-2” (also known as “1-up-2-down-2”) or “full-load” pattern; or other variations.

[0117] For a 1-bottom-2-top-2 pattern, a 48-fiber design can be produced using a 48-carryer machine. For a 1-top-1-bottom-1 pattern, a 96-carryer machine containing 48 fibers is required for design. The desired pattern can depend on several factors, including the tubular width, the diameter of the bioabsorbable polymer fibers, and the specific bioabsorbable polymer. For example, 2-bottom-2-top-2 increases the thickness of the weave, thus affecting the choice of tubular structures that can be made using this pattern.

[0118] Reference Figure 5 As described above, the pitch angle of the braid is the angle formed between the bioabsorbable polymer fibers 280 (or threads 290) (which extend from the carrier 250 to the mandrel 270) and the transverse axis 275 of the mandrel 270 (i.e., the axis perpendicular to the length direction of the mandrel 270).

[0119] Still refer to Figure 5In embodiments that optionally include non-transparent threads, the threads 290 are preferably loaded in pairs on opposing carriers 240 to balance the force within the woven product.

[0120] Regarding the embodiments disclosed herein (which include elastically deformable, radiopaque filaments requiring heat treatment to establish their original shape), in some embodiments, establishing the shape of the filaments may not be necessary or desirable. However, where establishing the original shape of the filaments is necessary, care must be taken not to shape (or "anneal") them into straight lines, as this would adversely affect the lower radial force applied during tubular expansion, causing the tubular body to lose its ability to expand adequately after deformation or transport through a conduit. Therefore, it is preferable to shape the filaments on a mandrel. However, it is undesirable to shape the filaments on a mandrel using bioabsorbable polymer fibers, because to shape the filaments, they must be heated to above 500 degrees Celsius, at which point the bioabsorbable polymer fibers would melt if they were simultaneously on the mandrel with the filaments. One option is to shape the filaments on a mandrel without polymer fibers. The shaped filaments can then be rewound onto a spool and then woven together with the bioabsorbable polymer fibers. Another option is to set the final weave design at a lower temperature (e.g.) to reduce any residual stress on the polymer fibers. In the final design, this will essentially set the bioabsorbable polymer fibers, rather than the non-transparent yarns. As mentioned above, another option is to simply forgo setting either the yarns or the bioabsorbable polymer fibers.

[0121] During manufacturing, some of the wires may unravel at the ends of the stent, potentially causing puncture of the body wall (e.g., a blood vessel) during delivery. The degree of wire unraveling may also depend on where the stent is cut from the mandrel. For example, if the stent is cut precisely where two wires overlap, the degree of unraveling will be less. Therefore, in some embodiments, welding the wires together may be preferred.

[0122] Therapeutic agent delivery

[0123] The device disclosed herein can also be used to deliver therapeutic agents to a pathology defined within or near a body wall. The bioabsorbable polymer fibers of the tubular body may be coated with or bound to a therapeutic agent, or the therapeutic agent may be incorporated into the bioabsorbable polymer fibers. The therapeutic agent may be slowly released over time to treat the pathology. In the case of an endovascular device implanted in a blood vessel, the therapeutic agent may be an antibiotic, antiviral agent, an analgesic, muscle relaxant, chemotherapeutic agent, intra-arterial vasodilator, calcium channel inhibitor, calcium channel antagonist, calcium channel blocker, transient receptor potential protein blocker, endothelin antagonist, blood thinner, antiplatelet agent, or any combination thereof.

[0124] In various embodiments, the therapeutic agent may include paclitaxel, sirolimus, everolimus, temozolomide, cyclophosphamide, doxorubicin, irinotecan, azathioprine, methotrexate, cisplatin, or vincristine. In specific cases of the drainage device disclosed herein for the treatment of aneurysms, the therapeutic agent may include one or more blood thinners / antiplatelet agents such as aspirin, heparin, ticagrelor, 5-fluorouracil, melphalan, or clopidogrel.

[0125] Therapeutic agents may also be used in the form of pharmaceutically acceptable salts or derivatives, and in the case of chiral active ingredients. Mixtures of optical isomers and racemic or diastereomers may also be used simultaneously. Similarly, therapeutic agents may include prodrugs, hydrates, esters, derivatives or analogs of compounds or molecules.

[0126] As mentioned above, in some cases, the polymer material itself can provide lactic acid during degradation, which can help heal and strengthen the body wall of pathological sites such as aneurysms.

[0127] The therapeutic agent can be washed off within a controlled timeframe (which has proven effective) to minimize side effects. The device disclosed herein can be placed close to the pathological site. In this way, since the therapeutic agent may not be delivered to organs not involved in the disease, as in cases of oral or intravenous administration of therapeutic agents, the therapeutic agent can target the disease while minimizing side effects.

[0128] At least two mechanisms can modulate the release kinetics of therapeutic agents: 1) a diffusion-controlled mechanism in which the therapeutic agent diffuses outward through the bulk polymer due to a concentration gradient; and 2) a degradation-controlled mechanism in which the release of the therapeutic agent depends on the hydrolysis or other degradation of the polymer material and the erosion of the polymer fiber surface.

[0129] The device disclosed herein can be configured such that the initial release of the therapeutic agent can be delayed to correspond to a delayed clinical manifestation of the disease. The desired timing of the therapeutic agent release can vary; for example, it can be immediate for patients already suffering from the disease. Alternatively, the device can be used prophylactically in patients at high risk of disease or pathology, in which case the desired timing of drug release may be delayed.

[0130] The device disclosed herein can also be configured to trigger the release of a therapeutic agent by introducing another therapeutic agent, a physiological condition, or any change within the body cavity.

[0131] Operation method

[0132] The currently disclosed devices, including elastically deformable tubular structures, can self-expand when deployed within a body cavity. The degree of expansion depends on the polymer material, the crystallinity of the polymer, the diameter of the polymer fibers, the diameter of the tubular structure, the braiding pitch angle, physiological conditions, the polymer annealing temperature, or the structural contribution of any included materials (e.g., radiopaque materials or similar components). Various embodiments of the devices disclosed herein can exhibit memory self-expansion in vivo.

[0133] The elastically deformable and self-expanding tubular structures of the devices disclosed herein can be configured into a radially compressed state for endoluminal catheter implantation. Once properly positioned near a pathology site within a body cavity, the devices are capable of radial and axial expansion, causing the outer surface of the tubular structure to adhere to the body wall defining the lumen. Radial expansion of the devices can be assisted by the expansion of a balloon attached to the catheter.

[0134] The devices disclosed herein can be pre-loaded in kits, such as sheaths or microcatheters, for easy delivery or immediate deployment. The kits may include devices as disclosed herein pre-loaded within delivery systems adapted to insert the devices into a patient, deliver the devices through body cavities (e.g., the patient's vascular system), and deploy the devices to desired locations for implantation into the patient. The aforementioned delivery systems may include sheaths, catheters, and / or other elements for inserting, delivering, guiding, deploying, and implanting vascular devices, or combinations thereof.

[0135] According to one embodiment of this disclosure, the endovascular device can be configured to guide blood flow away from downstream intravascular regions or disease sites. In particular, guiding blood flow through a vascular network may be necessary for the prevention or treatment of unruptured or ruptured cerebral aneurysms. (See also...) Figure 9A and Figure 9B An endovascular device 910 is deployed within a lumen 912 defined by a vessel wall 918 near an aneurysm 916, and is capable of expanding such that when the tubular body 914 is fully expanded, its outer surface adheres tightly to the vessel wall 918 and crosses the neck 919 of the aneurysm. The low porosity of the braided fabric thereby diverts blood flow through the neck of the aneurysm 916. Simultaneously, the braided fabric possesses sufficient porosity to allow small amounts of blood to enter the aneurysm sac at a low velocity, thereby leading to thrombosis and aneurysm occlusion, and promoting aneurysm healing. (Refer to...) Figure 9B The fabric also has sufficient porosity to allow enough blood to flow through the pores to reach healthy blood vessel branches (e.g., branch 920) and thus keep them open. The device can also span or partially span the blood vessel branches.

[0136] In another embodiment, the endovascular device according to the embodiments disclosed herein can be used to support a coil placed in an aneurysm to prevent prolapse into the parent vessel, for example, via aneurysm bridging. The endovascular device can be configured to be combined with a metal coil or balloon and fitted into a body cavity. See also... Figure 10 The aneurysm neck 1019 can be wide. In this case, the endovascular device 1010 can be used to reshape the neck 1019 and support the metal coil 1030 placed in the aneurysm 1016. The endovascular device can prevent the metal coil from moving within the body cavity 1012 defined by the vessel wall 1018, thereby preventing, for example, the coil from entering the parent vessel. After this procedure, the endovascular device 1010 is typically left in place, but in some embodiments it can be removed. In another embodiment, the endovascular device can be configured to fit into the body cavity in any way and support the metal coil.

[0137] Example

[0138] Although specific embodiments of the invention have been described and illustrated, these embodiments should be considered merely as illustrative of the invention and not as limiting the invention as interpreted in accordance with the appended claims.

[0139] Example 1

[0140] Reference Figure 4 They manufactured a device consisting of 48 bioabsorbable polymer fibers of poly-L-lactic acid with a molecular weight of 30,000 g / mol and a diameter of 50 μm.

[0141] Example 2

[0142] Referring to Figure 7, a device was fabricated consisting of 44 bioabsorbable polymer fibers of poly-L-lactic acid with a molecular weight of 30,000 g / mol and a diameter of 50 μm, interwoven with four transmissive fibers coated with tantalum nickelinol. This device has been tested in animal blood vessels (i.e., the rabbit aorta) and has been able to keep important collateral vessels open without obstructing any blood vessels.

[0143] Figure 11A and Figure 11B These are time-lapse angiographic images of early arterial and early venous aneurysms prior to device implantation. From Figure 11B The rapid clearance signal shown in the aneurysm indicates fluid inflow into the aneurysm. In contrast, Figure 11C The image shows an early venous phase following device implantation, where the signal is retained within the aneurysm. This indicates that blood is no longer freely flowing into the aneurysm and that the device has successfully diverted blood away from the aneurysm.

[0144] Reference Figure 12A andFigure 12B The rabbit aorta with the device implanted showed continuous angiographic patency and "jailed" collateral branches after one month. Figure 12B ). Figure 13 This is a scanning electron micrograph showing the continued patency of the collateral branch of the rabbit aorta one month after the device was implanted.

[0145] Reference Figure 14 The device exhibits excellent juxtaposition of blood vessel walls.

[0146] Figure 15 This is a scanning electron micrograph showing a smooth new inner membrane layer formed on the inner surface of the tubular body one month after the device was implanted.

[0147] Figure 16A This is a histological cross-section of a rabbit aorta showing the persistence of the polymer fibers and the formation of a new intima on the fibers one month after implantation of the device.

[0148] Figure 16B This is a histological cross-section of the rabbit aorta showing the durability of the polymer fibers, the new intima formed on the fibers, and the lack of vigorous inflammatory response two months after implantation of the device.

[0149] The lack of vigorous inflammatory response histologically at 2 months was attributed to the relatively small diameter (approximately 50 micrometers) of the bioresorbable polymer fibers. This currently disclosed stent contrasts with the bulky struts of previously FDA-approved laser-cut bioresorbable stents (marketed and sold by Abbott Vascular as the Absorb BVS stent).

[0150] As histological findings at 2 months showed, the formation of a new intima on the inner surface of the endosome and the lack of a vigorous inflammatory response demonstrated the device's biocompatibility with the vascular wall. The reaction of blood to polymer materials is important as it can lead to unwanted thrombosis or hemolysis. Regarding thrombotic reactions, the thrombogenicity of this device is compared to that of leading metal guide devices (i.e., Pipelines). TM The thrombotic activity of the pipeline was compared. As shown in Tables 2 and 3, the thrombotic activity of the pipeline was compared with that of the pipeline. TM In comparison, the device disclosed herein exhibits a lower percentage of thrombus-forming surface coverage and a lower hemolysis index.

[0151] Table 2 shows the connection with Pipeline TM In comparison, the thrombus surface coverage of the device disclosed herein is lower (tested according to ISO standards).

[0152] Table 2

[0153]

[0154] Table 3 presents the results of the in vitro hemolysis studies (conducted according to ASTM standards), showing the results compared to Pipeline. TM In comparison, the currently disclosed device has a lower hemolysis index.

[0155] Table 3

[0156]

[0157]

[0158] Without being bound by theory, it is believed that the small diameter (approximately 50 μm) of bioabsorbable polymer fibers contributes to the observed biocompatibility. In contrast, the relatively coarser polymer fibers of previously FDA-approved laser-cut bioabsorbable devices with a diameter of approximately 150 μm (marketed and sold by Abbott Vascular as Absorb BVS) are prone to thrombosis (refer to Expert Opin Drug Deliv. 2016 Oct; 13(10):1489-99).

[0159] Example 3

[0160] Reference Figure 8A A device was fabricated using 46 transmissive poly-L-lactic acid (PLL) fibers with a molecular weight of 30,000 g / mol and a diameter of 50 μm, interwoven with two transmissive tantalum-coated nickel-titanium fibers. This device has been tested in animal blood vessels and has been able to keep important collateral vessels open without obstructing any blood vessels.

[0161] Although specific embodiments of the invention have been described and illustrated, these embodiments should be considered merely as illustrative of the invention and not as limiting the invention as interpreted in accordance with the appended claims.

[0162] Related applications

[0163] This application claims priority to U.S. Patent Application No. 62 / 641891, the contents of which are incorporated herein by reference in their entirety.

Claims

1. An endovascular device for positioning within the lumen of an intracranial blood vessel to divert blood flow from an aneurysm of said intracranial blood vessel, said endovascular device comprising: A resiliently deformable tubular body comprising a braid having (1) at least 38 interwoven bioabsorbable polymer fibers and (2) 2 to 12 resiliently deformable interwoven metal filaments, wherein, when in an expanded configuration, the porosity of the braid is in the range of 60% to 80%, the expanded configuration being selected to allow a small amount of blood to enter the aneurysm at a low velocity, leading to thrombosis and occlusion of the aneurysm and causing the aneurysm to heal. The elastically deformable metal wires therein are (1) configured to promote and / or maintain the radial and / or axial expansion of the polymer fibers in the tubular body within the lumen, and (2) include a material configured to promote imaging of nontransmissive lines.

2. The apparatus according to claim 1, wherein, The diameter of the bioabsorbable polymer fibers is in the range of about 30 μm to about 80 μm.

3. The apparatus according to claim 1, wherein, The elastically deformable metal wire includes nickel-titanium alloy or cobalt-chromium-nickel alloy.

4. The apparatus according to claim 1, wherein, The non-transparent material includes non-transparent metals.

5. The apparatus according to claim 4, wherein, The radiopaque metal is tantalum, gold, platinum, or a combination thereof.

6. The apparatus according to claim 1, wherein, The polymer fibers include: polylactide (PLA), polylactide-co-glycolide (PLGA), poly-DL-lactide (DLPLA), poly(L-lactic acid), poly-L-lactide (LPLA), poly-L-lactide-co-glycolide (PGA-LPLA), poly-DL-lactide-co-glycolide (PGA-DLPLA), or poly-L-lactide-co-DL-lactide (LPLA-DLPLA).

7. The intravascular device according to claim 1, wherein, The woven fabric comprises 38 to 96 bioabsorbable polymer fibers.

8. The intravascular device according to claim 1, wherein, The woven fabric comprises at least 44 bioabsorbable polymer fibers, at least 46 bioabsorbable polymer fibers, at least 48 bioabsorbable polymer fibers, at least 72 bioabsorbable polymer fibers, or at least 96 bioabsorbable polymer fibers.

9. The intravascular device according to claim 1, wherein, The woven fabric comprises 44 bioabsorbable polymer fibers, 46 bioabsorbable polymer fibers, 48 ​​bioabsorbable polymer fibers, 72 bioabsorbable polymer fibers, or 96 bioabsorbable polymer fibers.

10. The intravascular device according to claim 1, wherein, The bioabsorbable polymer fibers have a diameter of at least 30 μm.

11. The intravascular device according to claim 1, wherein, The bioabsorbable polymer fibers have a diameter of 40 μm, 50 μm, 60 μm, 70 μm or 80 μm.

12. The intravascular device according to claim 1, wherein, The diameter of the tubular body is: 7 mm, wherein the bioabsorbable polymer fibers are interwoven at a pitch angle of 9° or less; 5 mm, wherein the bioabsorbable polymer fibers are interwoven at a pitch angle of 12° or less; 4 mm, wherein the bioabsorbable polymer fibers are interwoven at a pitch angle of 16° or less; or 3 mm, wherein the bioabsorbable polymer fibers are interwoven at a pitch angle of 18° or less.

13. The intravascular device according to claim 1, wherein, When the device is in an expanded state, the pore density of the woven fabric is 10 pores / mm. 2 Up to 32 holes / mm 2 Within the range.

14. The intravascular device according to claim 1, wherein, The radiopaque materials include iodine or barium.

15. The intravascular device according to claim 1, wherein, The elastically deformable metal wire includes one or more of the following: A nickel-titanium alloy coated with the aforementioned non-transmissive material; A drawn filled tube (DFT) comprising a nickel-titanium alloy outer layer and a core containing the radiopaque material; The DFT includes an outer layer containing the non-transparent material and a core containing a nickel-titanium alloy. A cobalt-chromium-nickel alloy coated with the aforementioned non-transparent material; The DFT includes a cobalt-chromium-nickel alloy outer layer and a core containing the radiopaque material; or The DFT includes an outer layer containing the non-transparent material and a core containing a cobalt-chromium-nickel alloy.

16. The intravascular device according to claim 1, wherein, The woven fabric is shaped by heating the interwoven bioabsorbable polymer fibers and the elastically deformable metal wires to a temperature that releases residual stress in the polymer fibers, rather than in the metal wires.

17. The intravascular device according to claim 1, wherein, The polymer fibers have been shaped and set, while the metal wires have not been shaped and set.

18. A method for treating an aneurysm of an intracranial vessel, the method comprising deploying an endovascular device as claimed in claim 1 in the lumen of the intracranial vessel near the aneurysm.

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