Neurovascular implants and delivery systems

Abstract

Implants, devices and systems are disclosed that are deployable within the neurovasculature of a subject. The implants are configured to enhance conformability to the vessel wall and have features and coatings designed to be thrombophilic. Devices for implant deployment are configured to accurately deploy the implant, resheath a partially deployed implant, and reliably detach the implant without distorting the position of the implant.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This specification claims priority to U.S. patent application Ser. No. 63 / 281,923, entitled "NEUROVASCULAR DEVICES HAVING THREE DIMENSIONAL CONFIGURATIONS AND SURFACE CHEMISTRIES FOR ENHANCED THROMBORESISTANCE AND / OR ENDOTHELIALIZATION," filed on November 22, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to devices, systems, and methods for treating vascular disease, including devices, systems, and methods for controlled and selective delivery of a stent implant into a patient's vasculature. [Background technology]

[0003] The mammalian circulatory system comprises the heart, which acts as a pump, and a vascular system that transports blood to various locations in the body. Due to the forces exerted on the blood vessels by the flowing blood, the blood vessels can develop various vascular defects. One common vascular defect, known as an aneurysm, forms as a result of the weakening of the blood vessel wall followed by the swelling and dilation of the blood vessel wall. If an aneurysm is left untreated, the blood vessel wall gradually thins and becomes damaged, and at some point, it may rupture due to the continued pressure of the blood flow. Neurovascular aneurysms, or cerebral aneurysms, affect approximately 5% of the population. They have more serious, life-threatening consequences than other aneurysms, especially since the rupture of a cerebral aneurysm can cause cerebral hemorrhage, which can be fatal.

[0004] Cerebral aneurysms are sometimes treated by highly invasive techniques that involve a surgeon accessing the aneurysm through the skull and sometimes the brain to place a ligation clip around the neck of the aneurysm to prevent blood from flowing into the aneurysm.

[0005] A minimally invasive treatment procedure involves the delivery of an embolization material or device to the aneurysm. The delivery of such an embolization material or device can be used to promote hemostasis or to completely fill the aneurysm cavity. The embolization material or device is typically placed into the vasculature of the body via a microcatheter to block blood flow through the aneurysmal vessel by forming an embolism or to form such an embolism within the aneurysm resulting from the vessel. Various coil embolization devices are known. Coils generally consist of a wire, usually made of a metal (e.g., platinum) or metal alloy, wound into a helical configuration. The coils of such devices may themselves be formed into a secondary coil shape or may be formed into any of a variety of more complex secondary shapes. Coils are commonly used to treat cerebral aneurysms, but suffer from several limitations, including low packing density, compression due to hydrodynamic pressures from blood flow, poor stability in wide-necked aneurysms, and complex and difficult placement as most aneurysm treatments using this approach require the placement of multiple coils.

[0006] Various implants, such as stents, can be delivered to a patient's vascular site, such as an aneurysm, via a microcatheter to retain embolic material or coils within the aneurysm, divert blood flow, and / or maintain patency of the vascular lumen. Typically, the implant is releasably held on the distal end of either a delivery microcatheter or a guidewire contained within the microcatheter, from which it is controllably released to the vascular site to be treated. The clinician delivering the implant must navigate the microcatheter or guide catheter through the vasculature, and in the case of intracranial treatment sites, manipulation of the microcatheter is through a tortuous microvasculature. This delivery can be visualized with fluoroscopy or other suitable means. Ablation can occur by a variety of means, including electrolytic ablation, chemical ablation, mechanical ablation, hydrostatic ablation, and thermal ablation. Once the microcatheter-loaded implant is positioned at the desired vascular placement site, the clinician attempts to detach the implant from the catheter or guidewire without distorting the positioning of the implant.

[0007] Various existing implant removal / delivery techniques each have their own advantages and disadvantages. For example, one mechanical deployment system retracts an outer sleeve proximally to expose a self-expanding stent implant constrained by the sleeve. Unfortunately, the stent may be prematurely deployed as the outer tube is partially retracted, expanding the exposed portion of the stent and propelling the stent distally beyond the desired deployment site. Also, once the stent is partially unsheathed, it may be determined that the stent needs to be adjusted for deployment. With existing systems, the stent has a tendency to dislodge from the sheath and contact the vessel wall, making adjustment or retraction of the stent difficult or impossible. Additionally, existing stents typically have one or more free apices or free structural portions that may embed in tissue even when partially deployed, making adjustment or retraction of the stent even more difficult or impossible.

[0008] Although stents are useful in retaining embolic material or coils within the aneurysm, the stent implant itself can cause its own complications. Perhaps the main complication of stent implants is the promotion of thrombus formation by the presence of the stent itself, resulting in the risk of embolism and stroke. Incomplete apposition of the stent, or lack of contact between the stent structure and the underlying vessel wall that is not over the side branch, is another factor that promotes thrombosis with the stent implant. In the tortuous microvasculature of the intracranial treatment site, it is difficult to achieve complete apposition of the stent. Another complication of using covered stents or stent grafts that include a sleeve of polymeric material around the stent lumen is the possibility of inadvertently occluding small perforating or branch vessels proximal to the aneurysm.

[0009] In addition, neurovascular devices are also indicated for the treatment of intracranial artery stenosis (ICAS). ICAS accounts for approximately 10% of stroke cases. However, its incidence varies by ethnicity, with 5%-10% of strokes in whites, 15%-29% of strokes in blacks, and 30%-50% of strokes in Asians. Strokes from ICAS are due to three mechanisms: a) artery-to-artery embolism, b) hypoperfusion, and c) plaque progression and occlusion of the perforator. Approximately 67% of ICAS cases occur in non-basilar arteries (e.g., intracranial and extracranial ICA), and the remaining approximately 33% of ICAS cases occur in the basilar artery. Intraoperative risks in ICAS stenting are significant and are mainly due to perforator occlusion. Plaque rupture is also a possibility, but remains unconfirmed, as ICAS pathobiology is less understood (or studied) than coronary artery lesions. Angioplasty (including stenting) in basilar ICAS is associated with high intraoperative risk due to the significant number of perforations. Restenosis occurs over a longer time frame in angioplasty (including stenting) cases. Although the SAAMPRIS, WASID, and WARSS trials provide hypothesis-generating insights into the mechanisms of clinical events, effective treatments have yet to be realized. Thus, the treatment of ICAS also presents a significant clinical need for improved neurovascular implants.

[0010] Despite efforts to date, there remains a need for improved intraluminal stent implants and improved removal / delivery devices. Summary of the Invention

[0011] Provided herein is a thrombophilic stent-implant having a hemodynamically enhanced shape, enhanced conformability to maximize adhesion of the implant to the vessel wall, and / or a thrombophilic coating. Also provided herein is a delivery device that allows for precise placement of the stent-implant, re-sheathing of a partially exposed stent-implant, and reliable peeling of the stent-implant without distorting the positioning of the stent-implant.

[0012] The implants described herein may be permanently implantable, deployed and retrieved, or part of an interventional catheter or other temporary intravascular device. In neurovascular applications, the implant may be an aneurysm bridge or other implant related to stroke prevention or treatment. For example, the implants described herein may be used for stent-assisted coil embolization of wide-necked aneurysms, treatment of intracranial atherosclerotic stenosis, or to maintain flow in acute ischemic stroke in conjunction with thrombectomy therapy. The implants described herein may also be used in other blood vessels and / or vasculature of the body, such as for the treatment and / or prevention of aneurysms, vascular stenosis, heart disease, arterial disease, deep vein thrombosis, or other diseases.

[0013] The combination of hemodynamic geometry and surface modifications disclosed herein produces thromboembolism-resistant implants over a range of flow rates from about 5 ml / min to about 400 ml / min. This combination should minimize or prevent all types of thrombi (red, white, mixed) and leukocyte-thrombi combinations by targeting multiple mechanisms of thrombus formation. Furthermore, the implants described herein with the combination of geometry and surface modifications can be both thrombogenic at the implant site and resistant to emboli flowing distal to the implant site. In some embodiments, the implants accelerate the rate of functional endothelialization.

[0014] The implant shape may be optimized for load-bearing function, anatomical compliance, hydrodynamic interactions for low platelet activation, and / or ease of procedural placement. The implant surface may be designed to modulate and prevent deleterious interactions between the implant surface and platelets and / or causative proteins, and to prevent platelet activation beyond the surface and near the implant by interacting with both the surface-contacting platelet population and the wall-proximal excess platelet population.

[0015] Disclosed herein is a self-expanding, thrombophilic intraluminal implant comprising a generally tubular frame. The generally tubular frame can comprise a proximal portion, a distal portion, and a central portion. The proximal portion can comprise a ring extending around the circumference of the tubular frame, the ring comprising a plurality of ring struts, adjacent pairs of the ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern. The distal portion can comprise a ring extending around the circumference of the tubular frame, the ring comprising a plurality of ring struts, adjacent pairs of the ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern. A central portion may be disposed between the proximal and distal portions, the central portion including a plurality of longitudinally spaced rings extending along a circumference of the tubular frame and a plurality of connecting struts extending at least partially along the circumference of the tubular frame, each ring of the plurality of rings having a plurality of ring struts, adjacent pairs of ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern, each connecting strut of the plurality of connecting struts connecting a distal apices of one ring of the plurality of rings to a proximal apices of an adjacent ring of the plurality of rings.

[0016] In the above intraluminal implants, or other implementations as described herein, one or more of the following features may also be provided: In some implementations, each linking strut of the plurality of linking struts connects each one of the plurality of distal apexes of one of the plurality of rings of the central portion to each one of the plurality of proximal apexes of an adjacent ring of the plurality of rings of the central portion, except for each one of the plurality of distal apexes of the most distal ring of the central portion and each one of the plurality of proximal apexes of the most proximal ring of the central portion, such that the central portion does not include a free apex. In some implementations, each distal apex of the plurality of distal apexes of the most distal ring of the central portion connects to each proximal apex of the plurality of proximal apexes of the ring of the distal portion, and each proximal apex of the plurality of proximal apexes of the most proximal ring of the central portion connects to each distal apex of the plurality of distal apexes of the ring of the proximal portion. In some implementations, a distal apex of each of the plurality of distal apexes of one ring of the plurality of rings in the central portion is rotationally offset from a proximal apex of each of the plurality of proximal apexes of an adjacent ring of the plurality of rings in the central portion such that at least a portion of each connecting strut of the plurality of connecting struts extends along at least a partially helical path around the circumference of the tubular frame. In some implementations, at least a portion of each of the multiple connecting struts connecting a distal apex of the multiple distal apexes of one ring of the multiple rings of the central portion to a proximal apex of the multiple proximal apexes of an adjacent ring of the multiple rings of the central portion extends along a helical path in a first helical direction at least partially around the circumference of the tubular frame, and at least a portion of each of the multiple connecting struts connecting a distal apex of the multiple distal apexes of an adjacent ring of the multiple rings of the central portion to a proximal apex of the multiple proximal apexes of another adjacent ring of the multiple rings of the central portion extends along a helical path in a second helical direction generally opposite to the first helical direction at least partially around the circumference of the tubular frame. In some implementations, the intraluminal implant further comprises one or more struts extending generally proximally from each one or more proximal apexes of the multiple proximal apexes of the ring of the proximal portion. In some implementations, each of the one or more generally proximally extending struts includes a neck portion and a connecting portion, the connecting portion configured to connect to a radiopaque marker.In some implementations, the intraluminal implant further comprises one or more struts extending generally distally from one or more respective distal apexes of the plurality of distal apexes of the ring of the distal portion. In some implementations, each of the one or more generally distally extending struts comprises a neck portion and a connecting portion, the connecting portion configured to connect to a radiopaque marker. In some implementations, the intraluminal implant further comprises one or more radiopaque markers configured to connect to the one or more generally proximally extending struts and / or the one or more generally distally extending struts at the connecting portion. In some implementations, the proximal portion flares radially outward in a proximal direction. In some implementations, the distal portion flares radially outward in a distal direction. In some implementations, the plurality of connecting struts do not overlap one another. In some implementations, the intraluminal implant is configured such that there is less incomplete apposition between the intraluminal implant and an inner wall of a blood vessel when the intraluminal implant is disposed on the inside of a bend in a blood vessel than when the intraluminal implant is disposed on the outside of a bend in the blood vessel. In some implementations, the central portion of the tubular frame has a diameter of about 3 mm. In some implementations, the intraluminal implant, when centrally placed within a flexible silicone U-shaped bend tube with an inner diameter of 3 mm and a bend radius of 4.9 mm, has 16 or fewer malappositions with the inner wall of the U-shaped bend tube. In some implementations, the maximum malapposition distance for the 16 or fewer malappositions is 0.400 mm or less. In some implementations, the average malapposition distance for the 16 or fewer malappositions is 0.120 mm or less. In some implementations, the central portion of the tubular frame has a diameter of about 4 mm. In some implementations, the implant has a length between about 10 mm and about 50 mm. In some implementations, the tubular frame is cut from a tube of approximately the same diameter as the diameter of the central portion of the tubular frame. In some implementations, the implant does not include a graft, covering, or liner. In some implementations, the intraluminal implant further comprises a heparin coating.

[0017] Disclosed herein is a self-expanding, thrombophilic intraluminal implant comprising a generally tubular frame including a plurality of longitudinally spaced rings extending around a circumference of the tubular frame, each ring having a plurality of ring struts, adjacent pairs of ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern, and a plurality of linking struts extending at least partially around a circumference of the tubular frame, each linking strut of the plurality of linking struts connecting a distal apice of one of the plurality of rings to a proximal apice of an adjacent ring of the plurality of rings, the tubular frame having a wall thickness of about 45 μm or less, and the implant including a heparin coating.

[0018] In the above intraluminal implants, or other implementations as described herein, one or more of the following features may also be provided: In some implementations, the heparin coating has a thickness of about 30 nm or less. In some implementations, the heparin coating has a mass of about 1.0 ug or less. In some implementations, the ratio of the mass of the heparin coating to the total surface area of ​​the implant is about 0.007 ug / mm 2 In some implementations, the ratio of the mass of the heparin coating to the wall thickness of the tubular frame is about 0.007 μg / mm or more. In some implementations, the ratio of the mass of the heparin coating to the abluminal surface area of ​​the implant is about 0.03 μg / mm or more. 2 In some implementations, the ratio of the thickness of the heparin coating to the wall thickness of the tubular frame is about 0.00016 or more. In some implementations, the overall equivalent particle size of the heparin coating is about 101 μm in diameter or less. In some implementations, the ratio of the heparin activity of the heparin coating to the wall thickness of the tubular frame is about 0.80 pmol AT / cm 2 / μm or more. In some implementations, the tubular frame has a diameter of about 3 mm. In some implementations, the tubular frame has a diameter of about 4 mm. In some implementations, the implant has a length between about 10 mm and about 50 mm. In some implementations, the implant does not include a graft, covering, or liner.

[0019] Disclosed herein are methods of stenting a vessel in a patient, the methods including using the intraluminal implants, delivery devices and / or systems described above.

[0020] Disclosed herein is a system having one or more of the features of the preceding description.

[0021] Disclosed herein is an implant having one or more of the features of the foregoing description.

[0022] Disclosed herein is an intraluminal delivery device having one or more of the features of the foregoing description.

[0023] Disclosed herein is a method of treating the vasculature of a patient including one or more of the features described above.

[0024] For purposes of summarizing the disclosure, certain aspects, advantages, and novel features of certain implementations have been described herein. It should be understood that not necessarily all such advantages may be achieved in accordance with any particular implementation of the technology disclosed herein. Thus, implementations disclosed herein may be implemented or performed in a manner that achieves or optimizes one advantage or advantages taught herein without necessarily achieving other advantages that may be taught or suggested herein.

[0025] Certain features of the present disclosure are described below with reference to the drawings. The illustrated implementations are intended to be illustrative and not limiting of the implementations. Various features of different disclosed implementations can be combined to form additional implementations that are part of the present disclosure. [Brief description of the drawings]

[0026] [Figure 1A] FIG. 1A illustrates the insertion of a microcatheter through the groin into the neurovascular region of a patient, according to some embodiments of the present disclosure. [Figure 1B] FIG. 1B is a diagram illustrating potential treatment sites in the basilar and non-basilar arteries of a patient, according to some embodiments of the present disclosure. [Figure 2A] 2A-2E are diagrams illustrating a self-expanding, thrombophilic intraluminal implant according to some embodiments of the present disclosure. [Figure 2B] 2A-2E are diagrams illustrating a self-expanding, thrombophilic intraluminal implant according to some embodiments of the present disclosure. [Figure 2C] 2A-2E are diagrams illustrating a self-expanding, thrombophilic intraluminal implant according to some embodiments of the present disclosure. [Figure 2D] 2A-2E are diagrams illustrating a self-expanding, thrombophilic intraluminal implant according to some embodiments of the present disclosure. [Figure 2E] 2A-2E are diagrams illustrating a self-expanding, thrombophilic intraluminal implant according to some embodiments of the present disclosure. [Diagram 3] FIG. 3 illustrates the intraluminal implant of FIGS. 2A-2E in a non-fitting bend test, according to some embodiments of the present disclosure. [Figure 4] FIG. 4 illustrates a variation of the intraluminal implant of FIGS. 2A-2E, according to some embodiments of the present disclosure. [Diagram 5] FIG. 5 illustrates a variation of the intraluminal implant of FIGS. 2A-2E, according to some embodiments of the present disclosure. [Figure 6] FIG. 6 illustrates a delivery wire according to some embodiments of the present disclosure. [Figure 7A] 7A-7B are diagrams illustrating a core wire of the delivery wire of FIG. 6, according to some embodiments of the present disclosure. [Figure 7B]7A-7B are diagrams illustrating a core wire of the delivery wire of FIG. 6, according to some embodiments of the present disclosure. [Figure 8A] 8A-8D show a bumper for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 8B] 8A-8D show a bumper for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 8C] 8A-8D show a bumper for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 8D] 8A-8D show a bumper for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 9A] 9A-9E show couplers for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 9B] 9A-9E show couplers for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 9C] 9A-9E show couplers for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 9D] 9A-9E show couplers for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 9E] 9A-9E show couplers for the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 10A] 10A-10B show details of the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 10B] 10A-10B show details of the delivery wire of FIG. 6 according to some embodiments of the present disclosure. [Figure 11A] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11B] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11C]11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11D] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11E] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11F] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11G] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11H] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 11I] 11A-11I illustrate an intraluminal implant delivery system according to some embodiments of the present disclosure. [Figure 12A] 12A-12C are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 12B] 12A-12C are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 12C] 12A-12C are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 13Aa] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Ab] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Ba] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Bb]13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Ca] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Cb] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Da] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Db] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Ea] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Eb] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Fa] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Fb] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Ga] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 13Gb] 13Aa-Gb illustrate delivery of an intraluminal implant adjacent to an aneurysm according to some embodiments of the present disclosure. [Figure 14A] 14A-14F illustrate other implementations of an endoluminal implant delivery system according to some embodiments of the present disclosure. [Figure 14B]14A-14F illustrate other implementations of an endoluminal implant delivery system according to some embodiments of the present disclosure. [Figure 14C] 14A-14F illustrate other implementations of an endoluminal implant delivery system according to some embodiments of the present disclosure. [Figure 14D] 14A-14F illustrate other implementations of an endoluminal implant delivery system according to some embodiments of the present disclosure. [Figure 14E] 14A-14F illustrate other implementations of an endoluminal implant delivery system according to some embodiments of the present disclosure. [Figure 14F] 14A-14F illustrate other implementations of an endoluminal implant delivery system according to some embodiments of the present disclosure. [Figure 15A] 15A-15E are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 15B] 15A-15E are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 15C] 15A-15E are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 15D] 15A-15E are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 15E] 15A-15E are diagrams illustrating delivery of an intraluminal implant according to some embodiments of the present disclosure. [Figure 16A] 16A-16D are diagrams illustrating implementations of radiopaque markers according to some embodiments of the present disclosure. [Figure 16B] 16A-16D are diagrams illustrating implementations of radiopaque markers according to some embodiments of the present disclosure. [Figure 16C] 16A-16D are diagrams illustrating implementations of radiopaque markers according to some embodiments of the present disclosure. [Figure 16D]16A-16D are diagrams illustrating implementations of radiopaque markers according to some embodiments of the present disclosure. [Figure 17A] 17A-17G illustrate a method of treating an aneurysm according to some embodiments of the present disclosure. [Figure 17B] 17A-17G illustrate a method of treating an aneurysm according to some embodiments of the present disclosure. [Figure 17C] 17A-17G illustrate a method of treating an aneurysm according to some embodiments of the present disclosure. [Figure 17D] 17A-17G illustrate a method of treating an aneurysm according to some embodiments of the present disclosure. [Figure 17E] 17A-17G illustrate a method of treating an aneurysm according to some embodiments of the present disclosure. [Figure 17F] 17A-17G illustrate a method of treating an aneurysm according to some embodiments of the present disclosure. [Figure 17G] 17A-17G illustrate a method of treating an aneurysm according to some embodiments of the present disclosure. [Figure 17H] FIG. 17H illustrates a variation of the method of treating the aneurysm of FIGS. 17A-17G, according to some embodiments of the present disclosure. [Figure 18A] 18A-18B show an introducer sheath according to some embodiments of the present disclosure. [Figure 18B] 18A-18B show an introducer sheath according to some embodiments of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] Various features and advantages of the present disclosure will now be described with reference to the accompanying drawings. The following description is merely exemplary in nature and is in no way intended to limit the present disclosure, its application, or uses. The present disclosure extends beyond the specifically disclosed implementations and / or uses, and their obvious modifications and equivalents. Thus, it is intended that the scope of the present disclosure should not be limited by the specific implementations described below. Features of the illustrated implementations can be modified, combined, removed, and / or substituted as would be apparent to one skilled in the art upon consideration of the principles disclosed herein. Furthermore, the implementations disclosed herein may include several novel features, none of which are solely responsible for their desirable attributes or are essential to the implementation of the systems, devices, and / or methods disclosed herein.

[0028] overview The present disclosure describes various implementations of intraluminal implants (e.g., stent implants), intraluminal implant delivery devices, intraluminal implant systems, and methods of implanting intraluminal implants. Such implants, devices, systems, and methods can be used to stent a patient's blood vessels, such as blood vessels of the patient's neurovasculature. Furthermore, such implants, devices, systems, and methods can be used to treat aneurysms in the patient, such as neurovascular aneurysms, and / or to treat intracranial and / or extracranial arterial stenosis. The implants, devices, systems, and methods disclosed herein can advantageously enable accurate placement of an implant within a patient's blood vessels, retraction of a partially exposed or deployed implant, and / or reliable release of the implant without distorting the positioning of the implant. Furthermore, the implants, devices, systems, and methods disclosed herein can advantageously provide a thrombophilic intraluminal implant. For example, the intraluminal implants disclosed herein can be configured to maximize adhesion between the implant and the vessel wall and minimize malapposition between the implant and the vessel wall, which can advantageously prevent and / or reduce areas of stagnant or low flow of bodily fluids (e.g., blood) through the vessel in which the implant is placed. Such configurations can be particularly advantageous in the tortuous microvasculature of intracranial treatment sites, which can have small diameter vessels with tight bends. As another example, the intraluminal implants disclosed herein can be configured to have a thrombophilic coating, such as a heparin coating. As another example, the intraluminal implants disclosed herein can be configured to have little effect on bodily fluids, such as blood, flowing therethrough after implantation. Additionally, the implants disclosed herein can be advantageously configured to prevent and / or limit occlusion of small perforating or branching vessels proximate to the site of the implant. For example, the intraluminal implants disclosed herein can have a frame without a graft / sleeve to prevent and / or limit the flow of bodily fluids through the frame of the implant.

[0029] The intraluminal implants, devices, systems, and methods described herein can be adapted for percutaneous delivery. Thus, the intraluminal implants described herein can be configured to be delivered via a delivery device (e.g., a catheter-based delivery device) described herein, have a collapsed configuration for delivery into a patient, and can expand from the collapsed configuration to an expanded configuration for implantation into the patient. For example, the intraluminal implants described herein can be self-expanding with an expansion ratio of at least about 2:1, at least about 3:1, at least about 4:1, at least about 5:1, at least about 6:1, at least about 7:1, or at least about 8:1. In some implementations, the implants, devices, and systems described herein can be configured for implantation within a patient's vasculature. For example, an intraluminal implant as described herein can be percutaneously implanted through a patient's artery via a delivery device as described herein to an intracranial delivery site within the patient. Such an intraluminal implant can stent a patient's blood vessel at the intracranial delivery site to allow blood flow through the vessel. Delivery can be through a guidewire lumen of a catheter / microcatheter or a PTCA balloon. Target treatment arteries can include anterior-distal-M1, M2, M3, Acom, ACA, posterior, basilar, Pcom, among others, as described herein. Delivery can be remote or robotically controlled. Delivery can also be with two catheters (microcatheter, .088 guide) rather than three catheters.

[0030] The intraluminal implants, devices, and systems described herein can be sized and configured for implantation of the implant within a target vessel of interest in a patient. For example, the intraluminal implants, devices, and systems described herein can be sized and configured for implantation of the implant within any intracranial vessel, such as the anterior cerebral artery, the internal carotid artery, the basilar artery, the anterior inferior cerebellar artery, the middle cerebral artery, the posterior inferior cerebellar artery, the vertebral artery, the anterior communicating artery, the posterior cerebral artery, the posterior communicating artery, the lenticular cerebral artery, the internal carotid artery, or any one or more of the branches of these vessels. As another example, the intraluminal implants, devices, and systems described herein can be sized and configured for implantation of the implant in any cardiac vessel, such as the intimal vein, anterior cardiac vein, right marginal vein, small cardiac vein, great cardiac vein, anterior interventricular vein, septal vein, Marshall's oblique vein, left marginal vein, left posterior vein, left atrial vein, posterior interventricular vein, acute marginal artery, left circumflex artery, left anterior descending artery, septal artery, conus branch, SA nodal branch, left circumflex artery, obtuse marginal artery, posterolateral branch, right coronary artery, posterior descending artery, or any one or more of these branches.

[0031] Intraluminal implants, which may also be referred to herein as implants, stents, and / or stent-implants, can have an expanded (e.g., implanted) diameter in the range of about 1 mm to about 6 mm, about 2 mm to about 5 mm, about 3 mm to about 4 mm, or can have a diameter greater than about 1 mm or less than about 6 mm depending on the application. In some implementations, the implants described herein can have an unconstrained expanded diameter in the range of about 1 mm to about 6.5 mm, about 2 mm to about 5.5 mm, about 3 mm to about 4.5 mm, or can have a diameter greater than about 1 mm or less than about 6.5 mm depending on the application. Implants as described herein can be oversized relative to the intended vessel and thus can impart an outward force to the vessel in which it is implanted (e.g., to improve fixation within the vessel). The implant can have an expanded (e.g., implanted) length in the range of about 5 mm to about 50 mm, about 5 mm to about 45 mm, about 5 mm to about 40 mm, about 5 mm to about 35 mm, about 5 mm to about 30 mm, about 10 mm to about 30 mm, about 10 mm to about 25 mm, about 15 mm to about 23 mm, or can have a length greater than about 5 mm or less than about 50 mm, depending on the application.

[0032] The intraluminal implants described herein configured for implantation within a patient's blood vessel can include a generally tubular, expandable frame (configured for percutaneous delivery as described herein) having a thrombophilic coating. The tubular frame can have a proximal end, a distal end, and a lumen extending from the proximal end to the distal end. The tubular frame can generally comprise a plurality of rings extending around the circumference of the tubular frame, with adjacent rings generally being connected to one another by a plurality of connecting struts. The ring struts and connecting struts of the frame can be configured to provide the intraluminal implant with enhanced flexibility and conformability. Additionally, the tubular frame can generally be free of free apices along a central portion of the tubular frame to facilitate the ability of the implant to be retracted and / or repositioned after partial placement of the implant.

[0033] The tubular body can be made of a material configured to expand upon delivery, and such a material can comprise a shape memory material, such as Nitinol. In some implementations, the expandable body can be configured to fold / crimp radially. In some variations, the expandable body can comprise a material with no or little shape memory, and a balloon can be used to expand the expandable body for implantation. Such a balloon can be an occlusive balloon, or a non-occlusive balloon, such as a hollow balloon. The intraluminal implant can include one or more coatings, such as one or more anti-thrombogenic coatings and / or one or more drug-eluting coatings. In some implementations, the implant can comprise a drug-eluting implant for the treatment of ICAD / ICAS, for example, having anti-restenotic properties and / or in an acute stroke setting. In some implementations, it is desirable to utilize a material and / or coating that prevents ingrowth within the implant to facilitate later retrieval and / or removal of the implant. Conversely, in some cases it may be desirable to utilize materials and / or coatings that permit and / or promote ingrowth within the implant and / or around the frame and either the implant's struts or radiopaque markers.

[0034] Vascular access for delivery of endoluminal implants as described herein may include the internal jugular vein, subclavian vein, femoral vein, and / or others. From such access points, the implant may be advanced within the patient's vasculature by a delivery device (e.g., a delivery catheter) as described herein until the desired location of implantation is reached, whereupon the implant may be delivered and expanded for implantation. An introducer sheath, guidewire, guide catheter, access catheter, and / or other devices or components may be utilized for delivery, as well as standard imaging methods. Additionally, the implants and associated delivery devices described herein may include radiopaque features to facilitate delivery and implantation.

[0035] One or more intraluminal implants as described herein can be implanted in a patient. In some cases, it may be beneficial to have only one intraluminal implant implanted in a patient, or it may be beneficial to have multiple intraluminal implants implanted in a patient. When multiple intraluminal implants are implanted in a patient, such implants can work together as necessary to achieve a desired therapeutic outcome. Additionally, intraluminal implants of the same size or different sizes can be implanted in the same patient.

[0036] In any of the implementations described herein, the implantable device may be configured and / or coated for use in treating aneurysms and / or ICAS.

[0037] The coating of the implant can inhibit or substantially inhibit thrombus formation (e.g., the coating can be thrombophilic). In some implementations, the implant shape and / or coating can promote or substantially prevent endothelialization. Thrombophilicity can be achieved, for example, by reducing protein adsorption, cell adhesion, and / or platelet and coagulation factor activation (e.g., low platelet stress accumulation (δdt)). Endothelialization can be achieved by promoting endothelial cell migration and adhesion from the intimal surface of the native vessel wall or from circulating endothelial progenitor cells onto the implant, and / or by seeding endothelial cells onto the implant prior to implantation. In preferred embodiments, the coating is thin, robust (e.g., does not flake off with mechanical friction), and / or can be deposited on a metallic surface, such as nitinol, cobalt chrome, stainless steel, etc. The coating properties can be achieved by selection of the coating material, processing of the coating on the implant, and / or design of the coating surface. In some implementations, the implant shape can be optimized to achieve low platelet stress accumulation while maintaining other load-bearing properties of the implant.

[0038] In some implementations, a coating for an implant can include a passive thromboembolism-resistant coating, such that the coating interacts with proteins and blood components or factors (e.g., platelets, cells, etc.) at the implant surface. As described elsewhere herein, preferred non-limiting implementations of passive thromboembolism-resistant coatings include poly(vinylidene fluoride co-hexafluoropropylene) (PVDF-HFP), fluorophosphazene, heparin-polyvinylpyrrolidone-poly(ethylene glycol) (HEP-PVP-PEG), and phosphorylcholine polyvinylpyrrolidone (PC-PVP).

[0039] In some embodiments, a coating for an implant can include an active thromboembolism-resistant coating, such that the coating interacts with proteins and blood components or factors (e.g., platelets, cells, etc.) at the implant surface and / or near-surface regions. The active thromboembolism-resistant coating can include a local elution system and / or a coating configured to capture (e.g., interact with or bind to surface receptors) proteins and / or blood components, such as endothelial progenitor cells (EPCs).

[0040] In some implementations, the implant coating can reduce the risk of procedural and / or immediate post-procedural risk during treatment of ICAS. In some implementations, the implant for treating ICAS is configured for insertion into a non-basilar artery, as shown in FIG. 1B. In some implementations, the implant for treating ICAS is configured for insertion into the basilar artery, as shown in FIG. 1B. In some implementations, the implant for treating ICAS is configured to stabilize plaque, reduce the likelihood of rupture or rupture, and / or prevent restenosis. In some implementations, the implant for treating ICAS is configured for use with dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT).

[0041] Coating materials include fluorinated or perfluoropolymers (e.g., polyvinylidene fluoride (PVDF) or its copolymers, fluorophosphazenes, etc.); plasma-deposited fluorine materials; zwitterionic materials; polyvinylpyrrolidone (PVP); phosphorylcholine (PC); poly(butyl methacrylate) (PBMA); polydimethyl siloxane (PDMS); albumin, glycosaminoglycans (GAGs); sulfonic acid materials, glyme materials; polyethylene glycols (PEGs); glycol, PEG-based materials; carboxybetaine, sulfobetaine, or methacrylate versions thereof; self-assembled monolayers (e.g., fluorosilane); heparin or heparin-like molecules or other anticoagulants; direct thrombin inhibitors (e.g., hirudin, bivalirudin, lepirudin, desirudin, argatroban, inogatran, melagatran, ximelagatran, dabigatran, etc.); curcumin; thrombomodulin; prostacyclin; DMP728 (platelet GPIIb / IIIa antagonist); chitosan or sulfated chitosan; hyaluronic acid; tantalum-doped titanium oxide; oxynitrides; oxide layers, inorganic materials such as diamond-like carbon (DLC) or fluorinated DLC, silicon carbide, and the like.

[0042] In some implementations, the coating comprises primarily heparin. The heparin coating can be made according to the methods described in U.S. Pat. No. 5,529,986, which is incorporated herein by reference in its entirety. Additionally or alternatively, the heparin coating can be made using a photochemical crosslinker such as benzophenone, according to the methods described in U.S. Pat. No. 7,550,444, which is incorporated herein by reference in its entirety. For example, the heparin coating can be applied to a polyvinylidene fluoride-co-hexafluoropropylene (PVDF-HFP) surface. The PVDF-HFP surface can be on, for example, a drug-eluting stent, such that the heparin is applied on or under the PVDF-HFP surface. For example, polyethyleneimine (PEI) is adsorbed onto the PVDF coating from a solution (pure PEI or PEI diluted in water, methanol, ethanol, or chloroform). A polymeric complex of heparin and polylysine is prepared and applied to the PEI layer as described in U.S. Patent No. 5,529,986, the entirety of which is incorporated herein by reference. Chemisorption occurs, binding the heparin to the surface via one or more ionic interactions.

[0043] In some implementations, the heparin coating may be thin, for example, in the range of about 1 nm to about 1 μm, preferably less than 1 μm, or less than 100 nm, or less than 50 nm, or less than 15 nm, or less than 10 nm, as measured by a transmission electron microscope focused ion beam (TEM-FIB). In some implementations, the heparin coating may be thin, for example, in the range of about 5 nm to about 15 nm, about 5 nm to about 12 nm, about 4 nm to about 13 nm, preferably about 5.4 nm to about 12 nm, and more preferably about 8 nm to about 9 nm, as measured by a TEM-FIB.

[0044] In some implementations, it is desirable to reduce or eliminate light exposure when applying these coatings to implants containing Nitinol. The surface of electropolished Nitinol contains titanium oxide, which acts as a photocatalyst and can degrade many organic molecules. Electropolished Nitinol devices are substantially depleted of nickel ions and contain amorphous TiO. X (See, e.g., Nagaraja, S. and Pelton, A. “Corrosion resistance of a Nitinol ocular microstent: Implications on biocompatibility”, J. Biomed Mater Res. 2020;108B:2681-2690). Photocatalysis with TiO2 is most efficient when ultraviolet (UV) light (e.g., wavelengths less than about 413 nm, less than about 420 nm, less than about 415 nm, or between about 315 nm and about 415 nm) is used. Irradiation of titanium dioxide in the presence of oxygen and water produces hydroxyl radical species that can degrade heparin and other organic species (See, e.g., Blazkova, A. et al., “Photocatalytic degradation of heparin over titanium dioxide” J. Materials Science 30(1995)729-733, which is incorporated herein by reference in its entirety). Hydroxyl radicals generated during this process can cause the decomposition of organic species, including heparin. Additionally, this process can also render the implant surface more hydrophilic or relatively hydrophilic, which can potentially interfere with the interaction between the implant surface and various primers or coatings, such as those described herein. Thus, in some implementations, it is advantageous to modify the hydrophobicity of the implant surface after treatment, e.g., to increase the hydrophobicity of the implant surface (e.g., to make it more hydrophobic) to improve bonding with primers and / or coatings.

[0045] To prevent photodegradation of heparin and similar materials, light exposure should be minimized during manufacture, storage, shipping, and end use. This can be done by storing the coated device in polyimide tubing or other opaque storage containers that block UV light.

[0046] In some implementations, the coating contains primarily plasma-deposited fluorine to form a hydrophobic surface. The fluorine may come from a fluorocarbon gas (plasma fluorination) such as perfluoropropylene (C3F6), and can crosslink precursor molecules on the device surface to form a more robust coating.

[0047] In some implementations, the coating consists primarily of plasma-deposited glymes. Glymes are glycol ether solvents that share the same repeating units as poly(ethylene oxide) (PEO) and poly(ethylene glycol) (PEG), and therefore exhibit some of the same biological properties as materials derived from these polymers. Glymes can be derived, for example, from tetraglyme (CH3O(CH2CH2O)4CH3), and precursor molecules can be crosslinked on the device surface to form a more robust coating.

[0048] In some implementations, the coating consists primarily of phosphorylcholine biomaterials. Phosphorylcholine is the hydrophilic polar head group of several phospholipids, including many that form the bilayer cell membrane on red blood cells. Phosphorylcholine is zwitterionic, containing a negatively charged phosphate covalently bonded to a positively charged choline group. The high polarity of the molecule is thought to endow phosphorylcholine biomaterials with a strong hydration shell that resists protein absorption and cell adhesion. Phosphorylcholine is commonly used in coatings for coronary drug-eluting stents to prevent restenosis and resist thrombosis. Polymeric phosphorylcholine biomaterials can have both hydrophobic domains and phosphorylcholine groups attached to the polymer chains, with the hydrophobic domains anchoring the polymer chains to the surface being coated and the phosphorylcholine groups orienting toward the aqueous biological environment. Phosphorylcholine biomaterials can be used to coat metals such as stainless steel, nitinol, titanium, gold, and platinum; plastics such as polyolefins, polyvinyl chloride (PVC), poly(methyl methacrylate) (PMMA), polyethylene terephthalate (PET), polyurethane (PU), polycarbonate, polyamide, polyimide, polystyrene, and polytetrafluoroetylene (PTFE); rubbers such as silicone, latex, and polyisobutylene (PIB); glass; ceramics; and biological tissues such as tooth enamel. Phosphorylcholine conjugated polymers can also be used to form bulk biomaterials in which the polymer backbone is crosslinked.

[0049] In some implementations, the polymer backbone can be a methacrylate polymer incorporating phosphorylcholine. In many implementations, phosphorylcholine groups will comprise at least 1%, 5%, 10%, 15%, 20%, 25%, or more than 25% of the functional groups attached to the polymer backbone. These polymers may be synthetically generated to allow precise control over the molecular structure, but may also closely mimic naturally occurring biomolecules. A variety of monomers are included in phosphorylcholine polymers, useful for tailoring phosphorylcholine biomaterials for drug delivery by varying their exact chemistry and influencing their interactions with drug payloads. Phosphorylcholine biomaterials can be easily tuned for water content, hardness, and / or elasticity. Coatings of phosphorylcholine biomaterials are applied to surfaces by reliable and reproducible solution-based techniques and are relatively simple to sterilize. Suitable compositions of phosphorylcholine include Vertellus PC1036 and / or PC1059.

[0050] In some implementations, the coating primarily comprises a fluorinated or perfluorinated polymer applied by a solution-based process. Similar to plasma-deposited fluorinated surfaces, the fluorinated or perfluorinated polymer results in a hydrophobic surface. To promote adhesion, a primer such as poly n-butyl methacrylate (PBMA), preferably about 264 kDa to 376 kDa, is first applied to the implant. A suitable polymer precursor may be poly(vinylidene fluoride co-hexafluoropropylene) (PVDF-HFP), preferably having a molecular weight of about 254 kDa to 293 kDa. The PVDF-HFP may be applied via a solvent with low surface tension, preferably a fast-evaporating solvent, to facilitate spreading. The polymer solution may be applied by dip coating, or by spin or dry techniques. Heat drying or forced air may be applied to the freshly coated device to reduce webbing. Fluorinated and perfluoropolymers can be crosslinked on the implant surface to produce a more robust coating. Other suitable fluoropolymers include polyvinylidene fluoride (PVDF), fluorophosphazene, fluorinated ethylene propylene, tetrafluoroethylene, hexafluoropropylene, and fluorinated silanes (e.g., perfluoroundecanoylsilane).

[0051] Preferred non-limiting examples of coating combinations include PC, PEG, heparin and PVP; PC and PEG; heparin, PEG and PVP; PC and PVP; PEG-co-PBMA-co-PEG; PC and PBMA; PEG and PBMA, either random or block structure. For example, one or more polymers can be added to enhance the adhesion of the implant (e.g., PBMA) to the metal surface, enhance the biomimetic properties of the implant (e.g., phosphorylcholine), enhance the protein repellency of the implant (e.g., PEG), etc. The ratio and / or branching (e.g., linear, branched, hyperbranched, interdigitated, multi-armed star, etc.) of two or more polymers can be optimized depending on the type of disease (e.g., aneurysm, intracranial atherosclerosis, etc.), location, time after the inciting injury or accident, etc.

[0052] In some implementations, the polymer for coating the device can include a terpolymer containing PC-co-X-co-PEG in a random or block configuration, where X comprises a metal attachment group such as PBMA. For example, the polymer configuration can include PC-X-PEG; X-PC-PEG (block); X-PEG-PC (block); or X-(PEG-PC-PEG-PC-PEG-PC-PEG-PC-PEG-PC) (random). The branching architecture of the polymer (e.g., linear, branched, hyperbranched, comb-like, multi-arm star, etc.) can also be optimized.

[0053] In some implementations, the coating can include surface modifying additives (SMA) that are block copolymers with one block miscible with the bulk polymer and the other block immiscible with the bulk polymer and functional blocks added during thermal processing. In some implementations, the SMA processing can be modified to further promote surface blooming by secondary processing such as optimizing to a temperature slightly below the glass transition (Tg) of the bulk polymer but above the SMA-Tg, allowing migration of the SMA while minimizing changes to the thermal properties of the bulk polymer. In some implementations, the extrusion or molding section that forms the tube or wire can be exposed to a solvent environment that plasticizes the bulk polymer, which may promote migration of the SMA. In some implementations, a good solvent (e.g., up to 80% solubility in the solvent) may be used for migration of the SMA, while a marginal solvent (e.g., 0.5% solubility in the solvent or less) can be used for the bulk polymer to plasticize the bulk polymer to form the tube, wire, and / or film. Table 1 summarizes solvents that can be used for SMA migration, where X is insoluble, O is soluble, # is partially soluble, and * is unknown. Exposure to the solvent can be direct contact or a solvent-wet environment with constant or cyclic on-off solvent exposure durations. In some implementations, the SMA and bulk polymer can be electrosprayed, electrospun, or solution spun to form tubes, wires, and / or films.

[0054] Table 1 Solvents for SMA migration [Table 1]

[0055] In some implementations, SMAs can be used as coatings for catheter systems due to their outside diameter / inside diameter (OD / ID) lubricity due to hydrophilic blocks of SMAs, including polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), poly(acrylamide) (PAAm), poly(n-isopropylacrylamide) (NIPAAM), carboxymethyl cellulose (CMC), and other polymers.

[0056] In some implementations, SMAs can be used as coatings for catheter systems as OD / ID low friction surfaces. For example, in such applications, SMAs can be in fluorinated blocks including, but not limited to, hexafluoropolypropylene (HFP), vinylidene fluoride (VDF), and other fluoropolymers.

[0057] In some implementations, the SMA can be used as a coating for polymeric implants or catheter systems for OD / ID thrombophilicity. For example, in such applications, the SMA can be in a functional block including, but not limited to, PEG, polycarbonate (PC), polyvinylidene difluoride (PDVF), terpolymers of tetrafluoroethylene, hexafluoropropylene, and vinylidene fluoride (THV), and other polymers. In some implementations, the OD and ID can be asymmetrically coated with two different SMAs as above. For example, PEG can be used for the OD and PVDF for the ID.

[0058] In some implementations, the SMA structure can be modified with unsaturated allyl, acrylate, and -SH groups on the SMA. After blooming to the surface, these groups can be used to crosslink with surface coatings, including hydrophilic coatings for catheters. In some implementations, using a triblock architecture (where the flanking blocks are immiscible with the bulk polymer) instead of a diblock architecture increases the thermodynamic driving force to the surface due to the different block size ratios and molecular weights of the flanking and bulk polymer blocks. In some implementations, using a triblock architecture (where the flanking blocks are miscible with the bulk polymer) instead of a diblock architecture increases the stability of the polymer surface due to the different block size ratios and molecular weights of the flanking and bulk polymers.

[0059] In some implementations, the SMA structure may be modified to include a thrombophilic head group, such as fluorine or PEG, which confers thromboembolic resistance to the surface of the implant that comes into contact with blood after blooming onto the surface.

[0060] The coating material can be applied to the implant surface according to a number of processes, depending on the composition selected. These processes include, but are not limited to, plasma deposition, glow discharge deposition, chemical vapor deposition, low pressure chemical vapor deposition, physical vapor deposition (liquid or solid source), plasma enhanced chemical vapor deposition, plasma assisted chemical vapor deposition, pyrolysis (e.g., with fluoropolymers such as parylene), spray coating, dip coating, spin coating, magnetron sputtering, sputter deposition, ion plating, powder coating, thermal spray coating, silanization, and / or layer-by-layer polymerization. Some processes (e.g., silanization or layer-by-layer polymerization) may be particularly useful for forming thin coatings. Application processes can be broadly classified as deposition processes or solution-based processes. In some implementations, deposition processes proceed according to equilibrium or non-equilibrium reactions and can use stable precursors or easily vaporized active precursors. Deposition processes may be particularly suitable for creating conformal coatings that apply certain compositions only selectively to different regions of the device, especially when complex patterns or shapes are involved. Deposition can be performed in a relatively short time and can easily produce thin, high purity coatings (e.g., thicknesses of less than 20 nm, 20 nm to 50 nm, 50 nm to 75 nm, 75 nm to 100 nm, 100 nm to 150 nm, 150 nm to 300 nm, 300 nm to 500 nm, greater than 500 nm, or any range in between). Solution-based processes result in reliable molecular structures and can be easily adapted to sterilization without altering molecular structure and / or biological activity. Many of the materials can be cured after application by thermal melting and / or crosslinking.

[0061] In some implementations, the implant can be primed prior to applying the coating. Primed implants can facilitate adhesion of the coating to the implant (e.g., to the implant's struts or wires). Surface priming can be done by mechanical means such as media blasting, sanding, scribing, etc. Mechanical priming can increase the surface area of ​​the implant. The increased surface area can promote adhesion of coating molecules and / or coating cells (e.g., endothelial cells). In some implementations, electropolishing of the implant can be deoptimized to achieve at least some surface roughness of the implant. Surface priming can be done by chemical means such as etching (e.g., plasma etching) or other surface functionalization methods such as irradiation with hydrogen or nitrogen ions to activate molecular binding sites. Surface priming can be done by pre-coating with a substrate that aids in the deposition of the final polymer coating, such as deposition (e.g., parylene, silane, etc.), sputter coating, and / or electroplating coating (e.g., platinum, gold, aluminum oxide) of the substrate. In some implementations, multiple coating layers or multiple coatings can be applied to the implant. The priming of the implant can include growing excess material (e.g., Nitinol) on the surface. The priming can be done by a sacrificial particle method, where particles are attached to the surface, excess material of the implant is grown on such particles, and the implant is then heat cycled to remove the particles, the excess material grown thereon, and at least some of the material attached to such excess material from the implant surface to form a microporous surface. The priming can be done on the underlying implant and / or on one or more coatings of the implant. In some implementations, the priming layer can be reactively removed from a portion of the implant using, for example, heat treatment, photochemical treatment, sonication, and / or treatment with electromagnetic fields.

[0062] In some implementations, the hydrophobicity of the implant surface can be increased to improve adhesion of primers and / or coatings, especially when such primers and / or coatings are applied directly to the surface of a Nitinol implant. Nitinol implants, for example, can be electropolished to reduce the risk of corrosion thereof, resulting in a thin surface layer of titanium oxide. This titanium oxide layer changes the wettability of the surface in response to UV light. For example, the air-water contact angle of electropolished Nitinol is reported to be typically in the range of 45 degrees to 95 degrees (e.g., from very hydrophilic to very hydrophobic). Primers such as PEI and PAV can bind to surfaces using the hydrophobic effect, so changes in the surface free energy of Nitinol can affect the adhesion of primers and coatings.

[0063] The method of cleaning the implant can increase the hydrophobicity of the surface of the implant. For example, bleach can be used to clean the implant. A hydrocarbon can be applied to the implant to increase the hydrophobicity of its surface. For example, a high boiling solvent that is poorly miscible with water, such as an alkane (hexane, heptane, octane, or higher alkane) or cyclohexanone, can be applied to the implant to increase its hydrophobicity. A fluorocarbon can be applied to the implant to increase the hydrophobicity of its surface. For example, perfluorooctane (CF3(CF2)6CF3), Fluorinert FC-40 or FC-70, or 1,1,2,2,9,9,10,10-octafluoro[2,2]paracyclophane can be applied to the implant to increase its hydrophobicity. The implant surface can be modified with an aminosilane, such as (3-aminopropyl)triethoxysilane, or a silane, such as carboxysilanetriol, to increase its hydrophobicity. For example, the implant surface can be modified with carboxyethylsilanetriol, disodium salt; or N-(trimethoxysilylpropyl)ethylenediamine, triacetic acid, trisodium salt (available from Gelest, Mitsubishi Chemical) to increase the hydrophobicity of the surface. These silanes provide carboxy functional groups that can be covalently bonded to poly(allylamine) hydrochloride. The implant surface can be modified with fluorosilanes such as (tridecafluoro-1,1,2,2-tetrahydrooctyl)silane (available from Gelest, Mitsubishi Chemical), 1H,1H,2H,2H-perfluorooctyltriethoxysilane (available from Millipore-Sigma), or trifluoropropyltrimethoxysilane (available from Shin-Etsu Chemical) to increase the hydrophobicity. In some implementations, the silane and primer can be combined in a single step, for example, with dimethoxysilylmethylpropyl modified (polyethyleneimine) or trimethoxysilylpropyl modified (polyethyleneimine) (available from Gelest).

[0064] Alternatively or in addition to increasing the hydrophobicity of the surface of a nitinol implant, there are various other ways to improve the bond and / or durability of the bond between a coating as described herein (e.g., a heparin coating) and the surface of a nitinol implant. The surface of a nitinol implant can be modified by physical vapor deposition of a tantalum layer, such as provided by Denton Vacuum, Moorestown, NJ, USA, to increase the hydrophobicity and / or improve its bond. The surface of a nitinol implant can be coated with aluminum oxide (Al2O3) by vapor deposition to increase the hydrophobicity and / or improve its bond. The surface of a nitinol implant can be sputter coated with carbon or platinum to increase the hydrophobicity and / or improve its bond. The surface of a nitinol implant can be roughened to increase the hydrophobicity and / or improve its bond. The surface of a nitinol implant can be roughened by mechanical abrasion, such as microblasting, to increase the hydrophobicity and / or improve its bond. The surface of the Nitinol implant can be roughened to increase hydrophobicity and / or improve its bonding properties, for example, by wet chemical etching using chemical etchants H2SO4 / H2O2, HCl / H2SO4, and NH4OH / H2O2. The surface of the Nitinol implant can be coated with polydimethylsiloxane (PDMS), for example, with molecular weights as low as about 100 and as high as about 100,000, to increase hydrophobicity and / or improve its bonding properties. In some implementations, the surface of the Nitinol implant can be roughened by laser irradiation, then coated with a solution of PDMS, and then cured to increase hydrophobicity and / or improve its bonding properties. The surface of the Nitinol implant can be roughened by magnetic field assisted discharge machining or mangane electropolishing to increase hydrophobicity and / or improve its bonding properties. The surface of the Nitinol implant can be made hydrophobic or more hydrophobic by adding doping elements to the Nitinol, such as NiTiTa or NiTiCr.The surface of a nitinol implant can be made hydrophobic or more hydrophobic by plasma treatment, for example with fluorocarbon or HF gas. The surface of a nitinol implant can be made hydrophobic or more hydrophobic by deposition of a coating from P2i. In some implementations, a titanium oxide layer on the surface of a nitinol implant can be made hydrophobic or more hydrophobic by exposure to infrared light. The surface of a nitinol implant can be coated with a parylene, including parylene-C, parylene-N, parylene-F, parylene-D, parylene-HT, and parylene-AF4, to increase hydrophobicity and / or improve its binding properties.

[0065] Additionally or alternatively, the implant may contain a complete or partial luminal layer of endothelial cells or may be seeded with endothelial cells prior to implantation.

[0066] In some implementations, the coating can be treated to improve adhesion between the coating and the implant. For example, all or substantially all of the solvent can be removed from the coating to rearrange and / or compact the polymer chains. Preferred implementations for improving the adhesion of the coating include, but are not limited to, chemical etching, particulate etching, saturating the environment with evaporated solvent, heat treatment, and / or post-coating solvent immersion or spraying, as described in turn below.

[0067] Chemical etching (e.g., HF, HF+HNO3, etc.) can provide a textured surface that can allow the coating to have more surface area for deposition. This method can produce a wide range of surface roughness. Particulate etching (e.g., with plastic parts or baking soda) can also roughen the surface of the device. It works the same as chemical etching, but the etching particles are larger, leaving larger defects.

[0068] Additionally, by saturating the environment with an evaporated version of the same solvent used in the solution coating the implant, the coating can be allowed to spread evenly over the implant surface without drying out before a uniform or substantially uniform coating is produced.

[0069] After coating is complete, the coated implant can be heat treated to facilitate removal of the solvent from the coating and to smooth the surface of the coating. Heat treatment can be carried out at a temperature between 30°C and 80°C. Alternatively or additionally, heat treatment at elevated temperatures not only removes the solvent but also aligns the polymer chains into a dense structure, resulting in a thinner, smoother coating. For example, heat treatment can be carried out at a temperature between 81°C and 250°C.

[0070] A post-coating solvent dip or spray can also, or alternatively, smooth the surface of the coating and / or reduce the thickness of the coating. In such implementations, suitable solvents are those used in the original coating solution and / or solvents that dissolve the polymer. The dip or spray step may be performed for a short period of time or may reach equilibrium before the original coating is completely removed.

[0071] In some implementations, a plasma clean prior to coating leaves a slight charge on the surface of the stent implant, allowing for a smoother coating.

[0072] The coating is preferably thin to reduce the risk of tissue debris creating dangerous embolism, especially in neurovascular applications. For the same reason, the coating is preferably durable and resistant to the generation of tissue debris during friction that occurs when the implant is expanded (e.g., when the struts rub against each other or may rub against parts of its delivery device). In some implementations, the coating thickness is about 300 nm or less. Coating materials that are mechanically robust and do not peel or crack after coating are particularly suitable for thicker coatings (e.g., 300 nm thick coatings). In some implementations, the coating thickness is about 3 nm or less, 5 nm or less, 8 nm or less, 10 nm or less, 15 nm or less, 20 nm or less, 25 nm or less, 30 nm or less, 40 nm or less, 50 nm or less, 60 nm or less, 75 nm or less, 100 nm or less, 150 nm or less, 200 nm or less, or 300 nm or less. In some implementations, the coating thickness may be greater than 300 nm or less than 3 nm (e.g., Angstrom levels). Thinner coatings (e.g., 75 nm thick or less) may provide robust performance in endothelialization and / or anti-thrombogenicity while minimizing the mechanical contribution of the coating to flow characteristics through the central lumen of the implant. Thinner coatings may be less likely to generate larger sized tissue debris that may result in the risk of embolization such as stroke. In preferred implementations, the coating thickness may be about 4 nm to 15 nm, 5 nm to 20 nm, 5 nm to 30 nm, 25 nm to 50 nm, 30 nm to 50 nm, 30 nm to 40 nm, 40 nm to 50 nm, 35 nm to 40 nm, 40 nm to 60 nm, 50 nm to 60 nm, less than 25 nm thick, less than 15 nm thick, greater than 4 nm thick, or greater than 60 nm thick. Coatings within the optimal range may provide sufficient surface coverage and reduced thrombogenicity while minimizing potential toxicity concerns. For example, in some implementations, the amount of coating material in a thin coating is below the toxicity threshold, even if all of the coating were stripped from the device.The coverage and thickness of the coating can be determined by scanning electron microscopy (SEM). In some implementations, 100% surface coverage is achieved. In some implementations, less than 100% surface coverage is achieved (e.g., 25%, 50%, 75%, 80%, 90%, less than 25%, between 90-100%, or any range therebetween). In some implementations, the device may not require 100% surface coverage to achieve sufficient antithrombogenic properties. Durability can be evaluated by performing SEM before and after simulated fatigue. Also, in a preferred implementation, the coated implant meets the USP788 standard. That is, the coated implant produces no more than 600 particles of 25 μm or greater, or no more than 6000 particles between 10 μm and 25 μm. Additionally, the implant preferably does not produce particulates less than about 2 μm.

[0073] The coatings can be applied separately to different regions of the implant. In some implementations, the inner diameter of the implant lumen is coated to optimize thrombophilia and the outer diameter of the implant is coated to optimize endothelialization, or vice versa. Alternatively, the outer diameter of the implant can be left uncoated (e.g., only the inner diameter of the implant is coated) to reduce the risk of embolic debris as the implant passes through a delivery device and is positioned within a vessel. In some implementations, the coating is optimized to promote endothelialization toward the center of the implant (e.g., along the portion configured to be positioned proximate to the aneurysm neck) and reduce thrombosis toward the proximal and distal ends of the implant. Promoting endothelialization near the aneurysm neck can promote the growth of an intimal layer that occludes the aneurysm from the vessel. Various combinations of the aforementioned spatial distributions can also be applied. One specific implementation can include applying an anti-CD34 endothelial progenitor cell (EPC) capture coating to the central portion of the implant facing the opening of the aneurysmal sac, while coating the proximal and distal ends with PVDF-HFP. Another implementation can include a mixed spatial distribution pattern of PVDF-HFP and EPC capture coatings on the inner diameter of the implant. Indicators of the distribution pattern can be quantified by the spatial periodicity of the EPC domains and the size of the EPC domains, and the combination of these two indices determines the overall area percentage of EPC and PVDF-HFP domains. A special case can be 100% coverage with the EPC capture coating. The spatial distribution of the multifunctional coating pattern provides thromboembolic protection at different timescales: acute (t=0-1d), subacute (t=1-30d), and long-term (>30d). Mechanistically, EPC / PVDF-HFP patterned coatings are thromboembolic resistant by modulating blood proteins and platelets at the surface and near-surface regions, with an additional biological outcome being faster isolation and sealing of the aneurysmal sac from the parent vessel.Furthermore, such changes in properties along the length of the implant can be achieved as a gradient of properties, rather than as distinct regions with distinct properties. The difference in properties can be achieved by varying the composition of the coating and / or by a coating differentiation process when applying the coating. The composition of the coating at any point can include one or more of the materials described above. In some implementations, such conformal coating methods can be used to promote endothelialization of the implant along the aneurysm neck so that the aneurysm is eventually sealed off from the natural lumen of the blood vessel.

[0074] At least some of the surface modifications described herein can be classified as actual coatings (25 nm to 1000 nm, or even up to 5000 nm). Coatings can be deposited macroscopically, e.g., PVDF-HFP, THV, PC-PBMA, PEG-PBMA, or can be coated using surface graft techniques (2 nm to 25 nm or even up to 100 nm thick; molecular level surface reactions; e.g., fluorination, PC graft, PEG graft, or heparin graft).

[0075] Thromboresistance may be achieved by different mechanisms of action in different regions of a coated implant. For example, a coating may act to prevent platelet adhesion, which is effective in areas of relatively high shear and high flow rates, but is less effective in areas of stagnant, low flow rates where thrombin-fibrin is more likely to initiate and grow clots. Thus, minimizing potential stasis points may be important. This can be accomplished by minimizing the total area of ​​the leading edges, rounding the leading edges of each strut or strut portion that impedes blood flow, and optionally rounding the trailing edges of the downstream-facing struts as well. Also, if the concave surface of the apex faces upstream, the apex may provide a potential stasis point. Preconditioning the "downstream" facing apex to be biased radially outward may allow the apex to be embedded a little deeper into the adjacent vessel wall, lowering the apex profile and reducing interference with blood flow. Upstream pointing apexes may be biased radially outward as well.

[0076] The physical design of an implant can affect its biocompatibility, particularly by the way it alters the natural blood flow. Platelet activation can be reduced by reducing the stresses experienced by platelets as blood flows across the implant. Both the amount of device material encountered by the flowing blood (i.e., the percentage of the vessel cross-section that the device occupies) and the angle at which the device meets the blood flow (take-off angle) can affect the stresses experienced by platelets and the resulting activation.

[0077] The implant may be a permanent or temporary intravascular scaffold, such as a deployable vascular stent or a temporary scaffold. In some implementations, the implant may be an aneurysm treatment device. In such implementations, the implant provides mechanical support to the coils or other embolic implants, preventing them from falling into the bloodstream and allowing for high packing density of the coils. In some implementations, the implant may temporarily retain the coil or implant within the aneurysm. When the packing density of the coils is high enough, the coils may exert sufficient pressure on each other to retain the coils within the aneurysm and prevent them from falling through the aneurysm neck into the bloodstream. In some implementations, the implant may remain implanted within the vessel and facilitate retention of the coil within the aneurysm. The implant may extend at least about 3 mm or 4 mm or more beyond the edge of the aneurysm neck in both proximal and distal directions to mechanically support the border.

[0078] Prior to expansion, the implants described herein can be sized to be received within a tubular delivery sheath / catheter having an inner diameter of about 0.41 mm to about 0.54 mm (e.g., the outer diameter of the implant may be collapsed to about 0.40 mm to about 0.48 mm). In various implementations, the central portion (or the portion of the implant in contact with the aneurysm) has a gap between the struts (e.g., the largest dimension of the gap) of less than about 0.125 mm, less than about 0.150 mm inches, less than about 0.175 mm, less than about 0.225 mm, less than about 0.250 mm, less than about 0.275 mm, less than about 0.300 mm, less than about 0.325 mm, less than about 0.350 mm, less than about 0.375 mm, less than about 0.400 mm, or greater than about 0.400 mm. In some implementations, the gap is preferably about 0.200 mm or less to prevent coil dislodgment and promote high coil packing density. In some implementations, the gaps between the struts of the implants described herein can be as small as practical, but also large (0.500 mm to 1.1 mm) to allow a microcatheter to pass therethrough. In some implementations, the gaps between the struts near the proximal and / or distal ends of the implants described herein can be larger than the gaps between the struts located adjacent the aneurysm neck (e.g., near the center of the implant). Regions with larger gap dimensions can form localized regions of lower density compared to regions with smaller gap dimensions. In some implementations, the gaps between the low density regions can have a larger area or dimension (e.g., diameter) than the gaps between the high density regions by about 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 150%, 175%, 200%, 250%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, 1000%, 2000%, 5000%, between 100% and 105%, greater than 5000%, or any percentage within these ranges.

[0079] The intraluminal implants, devices, systems and methods disclosed herein have been described in particular embodiments that may provide certain advantages, but such descriptions are not intended to be limiting. The intraluminal implants described herein may be implanted in various blood vessels and / or passageways of a patient, including blood vessels (e.g., veins, arteries) of a patient's vascular system, a patient's lymphatic system, a patient's reproductive system, and the like.

[0080] Any and / or all of the implementations and / or features of the intraluminal implants, devices, systems, and methods described and / or illustrated herein may be applied to and / or utilized with the various devices, systems, and methods described and / or illustrated in U.S. Provisional Patent Application No. 63 / 281,923, entitled "ENHANCED THROMBORESISTANCE AND / OR ENDOTHELIALIZATION FOR THREE Dimensional Configurations and Surface Chemistry," filed November 22, 2021, the entire contents of which are incorporated herein by reference. Any and / or all of the implementations and / or features of the intraluminal implants, devices, systems, and methods described and / or illustrated herein, such as the thrombophilic intraluminal implants and related delivery devices, may be applied to U.S. Provisional Patent Application No. 63 / 281,923.

[0081] Intraluminal implants FIG 1A is a simplified diagram of the anatomy of a subject 1 with an implant delivery catheter 1100 used to establish a percutaneous pathway through the subject's vasculature to a neurovascular site of the subject for delivery of an implant 100 via a delivery wire 600. FIG 1B is a simplified diagram of the basilar and non-basilar arterial anatomy of subject 1. The implants, devices, and systems described herein can be configured to access and be positioned within the anatomy shown in FIG 1B or elsewhere within the subject's body as described herein.

[0082] 2A-2E show implementations of an intraluminal implant 100. FIG. 2A is a perspective view, FIG. 2B is an end view, FIG. 2C-2D are side views, and FIG. 2E is a flattened pattern view of the implant 100. The implant 100 can be cut (e.g., laser cut) from a tube to form the generally tubular frame 110 shown. The tube used to form the implant 100 can be a shape memory material such as Nitinol and / or a superelastic material. Additionally, the tube cut to form the tubular frame 110 can be an expansion tube of approximately the same diameter as the final implant diameter (e.g., unconstrained / expanded diameter), which can be an advantageous manufacturing method over shape setting to the final diameter. In some implementations, the implant can be cut from a tube that is later shape set to the final diameter, or the implant can be manufactured from a wire that is shape set to the configuration shown and described herein. The tubular frame 110 of the implant 100 can generally be cut, shape set, media blasted (e.g., to remove the carbon layer resulting from shape setting), and electropolished. Electropolishing can advantageously provide rounded edges to the tubular frame 110. The implant 100 is self-expanding and can have a collapsed or crimped configuration upon delivery and an expanded configuration upon implantation.

[0083] As shown in at least FIG. 2A , the implant 100 can generally have a proximal end 101 and a distal end 102 in which a tubular frame 110 defines a lumen 104 having a longitudinal axis 103. As further shown, the implant 100 can include one or more radiopaque markers. Such radiopaque markers can be disposed at or adjacent to the proximal end 101 and / or the distal end 102. For example, and as shown in FIG. 2A , the implant 100 can include one or more proximal radiopaque markers 181 at the proximal end 101 and one or more distal radiopaque markers 182 at the distal end 102. In some implementations, the implant 100 can include at least one proximal radiopaque marker 181, such as one, two, three, four, five, or more proximal radiopaque markers 181. In some implementations, the implant 100 can include at least one distal radiopaque marker 182, such as one, two, three, four, five, or more distal radiopaque markers 182. Such radiopaque markers can be connected (e.g., crimped) to the implant 100 (e.g., connected to the tubular frame 110 of the implant 100) or can be an integral part of the implant 100. The radiopaque markers 181, 182 can facilitate visualization of the implant 100 during delivery and implantation. In some implementations, the radiopaque markers 181, 182 are sized and configured to be at or just above a threshold of visibility when photographed during delivery of the implant 100. Such a size and configuration of the radiopaque markers 181, 182 helps provide a thrombophilic implant 100 by preventing the radiopaque markers themselves from causing thrombosis after implantation.

[0084] 2A, a portion or end of the implant 100 can be flared radially outward. For example, a portion of the implant 100 adjacent the proximal end 101 can be flared radially outward in the proximal direction and / or a portion of the implant 100 adjacent the distal end 102 can be flared radially outward in the distal direction. Such flared portions can advantageously ensure alignment between the proximal and distal ends of implant 100 (and any radiopaque markers of implant 100, e.g., radiopaque markers 181, 182) and the wall of the vessel into which implant 100 is implanted, particularly near or near curves in the vessel, ensure the lowest possible profile at the proximal and distal ends of implant 100 when implanted in the vessel, thereby, for example, minimizing or eliminating the effect of implant 100 on the flow of bodily fluids (e.g., blood) through the vessel at the implantation site, facilitate fixation of implant 100 in a desired position during delivery and when implanted in the vessel, and / or facilitate prevention of migration of implant 100 from a desired position when implanted in the vessel. In some implementations, implant 100 does not have flared proximal and / or distal portions or ends.

[0085] The implant 100 (e.g., the tubular frame 110 of the implant 100) can have a thickness (e.g., wall thickness) of about 10 microns (μm) to about 100 μm, about 20 μm to about 90 μm, about 25 μm to about 80 μm, about 30 μm to about 70 μm, about 35 μm to about 60 μm, about 40 μm to about 55 μm, about 40 μm to about 50 μm, about 40 μm, about 41 μm, about 42 μm, about 43 μm, about 44 μm, about 45 μm, about 46 μm, about 47 μm, about 48 μm, about 49 μm, less than about 60 μm, less than about 50 μm, or greater than about 25 μm. Such thin wall thicknesses can advantageously minimize or eliminate the effect of the implant 100 on the flow of bodily fluids (e.g., blood) through the blood vessels at the implantation site. The widths of the struts of the implant 100, such as the plurality of ring struts 122, 142, 162, the plurality of connecting struts 145, the one or more proximally extending struts 125, and / or the one or more distally extending struts 165, can be approximately the same as their wall thickness (e.g., the wall thickness of the tubular frame 110). In some implementations, the width of the plurality of connecting struts 145 is less than the width of the plurality of ring struts 122, 142, 162. Such a configuration can make the implant 100 more flexible, kink resistant, and / or compatible with the adjacent vessel wall. In some implementations, the widths of the struts of the implant 100 are approximately the same as one another. In some implementations, at least some of the widths of the struts of the implant 100 are different from one another.

[0086] The implant 100 (e.g., the tubular frame 110 of the implant 100) can have a diameter 111 of about 1 mm to about 6 mm, about 1.5 mm to about 5.5 mm, about 2 mm to about 5 mm, about 2.5 mm to about 4.5 mm, about 3 mm to about 4 mm, about 3 mm, about 4 mm, less than about 5 mm, or greater than about 2 mm. Such diameter can be measured along a central portion (e.g., not including the expanded distal and proximal ends / proximal and distal portions, if any) of the implant 100 when in an expanded / unconstrained state.

[0087] The implant 100 (e.g., the tubular frame 110 of the implant 100) can have a length 112 of about 5 mm to about 70 mm, about 8 mm to about 65 mm, about 10 mm to about 60 mm, about 12 mm to about 55 mm, about 15 mm to about 50 mm, about 15 mm, about 16 mm, about 20 mm, about 23 mm, about 30 mm, about 40 mm, about 50 mm, less than about 50 mm, less than about 25 mm, or greater than about 12 mm. Such lengths can be measured when the implant 100 is in an expanded / unconstrained state.

[0088] 2C is a side view of the implant 100 without radiopaque markers (e.g., showing only the tubular frame 110), and FIG. 2D is a side view of the implant 100 with radiopaque markers 181, 182. Generally, the implant 100 may include a tubular frame 110 and radiopaque markers 181, 182. As shown in these side views, the implant 100 (e.g., the tubular frame 110) may generally include a plurality of longitudinally spaced rings extending around the circumference of the tubular frame 110. The plurality of rings may generally be connected to one another by a plurality of connecting struts that extend at least partially around the circumference of the tubular frame 110.

[0089] 2C-2D , the implant 100 (e.g., tubular frame 110) can include a proximal portion 120, a distal portion 160, and a central portion 140 between the proximal portion 120 and the distal portion 160. The proximal portion 120 can be disposed adjacent the proximal end 101, and the distal portion 160 can be disposed adjacent the distal end 102. The proximal portion 120 can include a ring 121 extending along the circumference of the tubular frame 110. The ring 121 can include a plurality of ring struts 122, with adjacent pairs of the ring struts joining at a plurality of proximal apices 123 and a plurality of distal apices 124 to form a chevron pattern as shown. Similarly, the distal portion 160 can include a ring 161 extending along the circumference of the tubular frame 110. The ring 161 can include a plurality of ring struts 162, with adjacent pairs of the ring struts joining at a plurality of proximal apices 163 and a plurality of distal apices 164 to form a chevron pattern as shown. In implementations of the implant 100 including proximal and / or distal ends, proximal and / or distal portions of a flare, such flare can originate at the proximal and / or distal portions 120 and / or distal portions 160, respectively (e.g., where the proximal and / or distal portions 120 and / or distal portions 160 connect to the central portion 140). The central portion 140 can include a plurality of longitudinally spaced rings 141 extending around the circumference of the tubular frame 110. Each ring of the plurality of rings 141 can include a plurality of ring struts 142, with adjacent pairs of the ring struts joining at a plurality of proximal and / or distal apices 143 and a plurality of distal apices 144 to form a chevron pattern as shown. Although FIGS. 2C-2D show the implant 100 having a central portion 140 with five rings 141, the implant 100 can include less than five rings 141, five rings 141, or more than five rings 141.

[0090] The central portion 140 may also include a number of connecting struts 145 that extend at least partially around the circumference of the tubular frame 110. Each connecting strut of the number of connecting struts 145 may connect a distal apex of one of the plurality of rings 141 to a proximal apex of an adjacent ring of the plurality of rings 141, as shown. Also, as shown, each connecting strut of the number of connecting struts 145 connects each one of a plurality of distal apexes 144 of one of the plurality of rings 141 of the central portion 140 to each one of a plurality of proximal apexes 143 of an adjacent ring of the plurality of rings 141 of the central portion 140, except for each one of a plurality of distal apexes of the distal-most ring of the central portion 140 and each one of a plurality of proximal apexes of the proximal-most ring of the central portion 140, such that the central portion 140 does not include a free apex (e.g., no apexes are unconnected). In other words, implant 100 can be configured to have no unconnected apices between its proximal end 101 and its distal end 102, but may have free apices at its proximal end 101 and its distal end 102, as shown. Such a configuration can advantageously facilitate repositioning of implant 100, if necessary during delivery, since there are no apices to catch on the distal edge / end of the delivery catheter and / or tissue. Additionally, such a configuration can advantageously facilitate repositioning or removal of implant 100 after implantation of implant 100.

[0091] 2C-2D , each distal apex of the plurality of distal apexes of the distal-most ring of the central portion 140 can be connected to each proximal apex of the plurality of proximal apexes 163 of the ring 161 of the distal portion 160. Similarly, each proximal apex of the plurality of proximal apexes of the proximal-most ring of the central portion 140 can be connected to each distal apex of the plurality of distal apexes 124 of the ring 121 of the proximal portion 120. Additionally, as shown, each distal apex of the plurality of distal apexes 144 of a ring of the plurality of rings 141 of the central portion 140 can be rotationally offset from each proximal apex of the plurality of proximal apexes 143 of an adjacent ring of the plurality of rings 141 of the central portion 140. In such a configuration, at least a portion of each linking strut of the plurality of linking struts 145 connecting such rotationally offset distal apices 144 and proximal apices 143 can extend along a helical path at least partially around the circumference of the tubular frame 110. Such helical path can extend in a first helical direction between an adjacent set of rings 141 of the central portion 140 and in a second helical direction generally opposite to the first helical direction between a next adjacent set of rings 141 of the central portion 140, as shown. In other words, a row of linking struts 145 (e.g., connecting an adjacent set of rings 141) can extend at least partially in one helical direction around the circumference of the tubular frame 110, and a next row of linking struts 145 (e.g., connecting an adjacent set of rings 141) can extend at least partially in the opposite helical direction around the circumference of the tubular frame 110. As shown, multiple connecting posts 145 can be configured so that they do not overlap one another.

[0092] Thus, the implant 100 (e.g., the tubular frame 110 of the implant 100) may generally include rings, such as the ring 141, which may have a chevron-shaped configuration, longitudinally alternating with the connecting struts 145, as described above. Combining such configurations of the tubular frame 110 may provide a highly conformable implant 100 to minimize malapposition between the implant and the vessel. Also, such configurations of the tubular frame 110 may allow the implant 100 to self-expand to a variety of different diameters and configurations of the adjacent vessel wall, rather than expanding to a substantially constant diameter throughout the length of the implant 100. For example, such configurations of the rings (e.g., the rings 141, 121, and 161) may advantageously provide radial conformance of the implant 100 (e.g., the tubular frame 110 of the implant 100) to allow the implant 100 to expand and contract to conform to the vessel wall (e.g., the inner vessel wall). Moreover, such helical winding of the plurality of linking struts 145 can advantageously provide longitudinal conformance of the implant 100 (e.g., the tubular frame 110 of the implant 100), such as allowing the implant 100 to expand and conform along the outside of a bend or curve in a blood vessel and contract and conform along the inside of a bend or curve in a blood vessel. Furthermore, such alternating helical paths of adjacent rows of linking struts 145, when present, can help relieve torque or twisting of the implant 100.

[0093] In some implementations, the diameter of the implant 100 can be adjusted by increasing or decreasing the number of ring struts 122, 142, and 162 that make up the proximal, central, and distal rings 121, 141, and 161, respectively. With an increase or decrease in the number of ring struts 142, the number of linking struts 145 can be increased or decreased depending on the type to ensure that there are no unlinked distal apices 144 and / or unlinked proximal apices 143. In some implementations, the length of the implant 100 can be adjusted by increasing or decreasing the number of rings 141. With an increase or decrease in the number of rings 141, the number of linking struts 145 can also be increased or decreased.

[0094] 2C and 2E , the implant 100 (e.g., the tubular frame 110 of the implant 100) can include one or more generally proximally extending struts 125 and / or one or more generally distally extending struts 165. Such one or more generally proximally extending struts 125 can extend from one or more proximal apexes of each of a plurality of proximal apices 123 of the ring 121 of the proximal portion 120. Similarly, such one or more generally distally extending struts 165 can extend from one or more distal apexes of each of a plurality of distal apices 164 of the ring 161 of the distal portion 160. Each of the one or more generally proximally extending struts 125 and each of the one or more generally distally extending struts 165 can be configured to connect to a radiopaque marker, such as a proximal radiopaque marker 181 and a distal radiopaque marker 182, respectively. Each of the one or more generally proximally extending struts 125 can include a neck portion 126 and a connecting portion 127, where the connecting portion 127 is disposed proximal to the neck portion 126 and configured to connect to the proximal radiopaque marker 181. Similarly, each of the one or more generally distally extending struts 165 can include a neck portion 166 and a connecting portion 167, where the connecting portion 167 is disposed distal to the neck portion 166 and configured to connect to the distal radiopaque marker 182. For example, the connecting portions 127, 167 can have an oval shape with a through hole configured to receive a crimped radiopaque marker. In some implementations, the implant 100 (e.g., the tubular frame 110 of the implant 100) can include at least one proximally extending strut 125, such as one, two, three, four, five, or more proximally extending struts 125. The number of proximally extending struts 125 can correspond to the number of proximal radiopaque markers 181. Similarly, in some implementations, the implant 100 (e.g., the tubular frame 110 of the implant 100) can include at least one distally extending strut 165, such as one, two, three, four, five, or more distally extending struts 165. The number of distally extending struts 165 can correspond to the number of proximal radiopaque markers 182.If included, proximally extending struts 125 and / or distally extending struts 165 can extend proximally and distally at an angle to longitudinal axis 103 so as to continue as an extension of the radially outward expansion of proximal portion 120 and / or distal portion 160, respectively. Proximally extending struts 125 and / or distally extending struts 165, in combination with proximal radiopaque marker 181 and / or distal radiopaque marker 182, respectively, can be configured to releasably couple with a delivery wire for delivery of implant 100, as described further below.

[0095] Implant 100 (e.g., tubular frame 110 of implant 100) can be configured to have a minimum abluminal surface area (e.g., the exterior surface area that is the surface area in contact with the wall of the vessel into which implant 100 is implanted). For example, implant 100 (e.g., tubular frame 110 of implant 100) can have an abluminal surface area of ​​about 3% to about 11%, about 4% to about 10%, about 5% to about 9%, about 4%, about 5%, about 5.5%, about 5.8%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.1%, about 8.5%, greater than about 3%, or less than about 10%.

[0096] The implant 100 (e.g., the tubular frame 110 of the implant 100) can be configured to have a minimal end view surface area. In other words, the implant 100 can be configured to occupy a minimal portion of the vessel cross-section in which it is implanted. For example, the implant 100 (e.g., the tubular frame 110 of the implant 100) can occupy less than about 20%, less than about 15%, less than about 14%, less than about 13%, less than about 12%, less than about 11%, less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, between about 3% and about 7%, between about 4% and about 6%, about 4.5%, or about 5.9% of the cross-sectional area defined by the outer diameter of the implant 100 when viewed down its longitudinal axis 103 at its unconstrained / expanded end. In some implementations, the central portion 140 of the implant 100 (e.g., the tubular frame 110), at its unconstrained / expanded end surface, when viewed below its longitudinal axis 103, can occupy less than about 20%, less than about 15%, less than about 14%, less than about 13%, less than about 12%, less than about 11%, less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, between about 3% and about 7%, between about 4% and about 6%, about 4.5%, or about 5.9% of the cross-sectional area defined by the outer diameter of the central portion 140 of the implant 100.

[0097] In some implementations, the implant 100 (e.g., the tubular frame 110 of the implant 100) is configured to provide less malapposition between the inner wall of the vessel in which it is placed and the implant 100 when placed inside a vessel bend than when placed outside the vessel bend. Such a configuration can advantageously limit or eliminate potential areas of low or stagnant flow inside a vessel bend, providing a thrombophilic implant 100.

[0098] The implant 100 can have a mass of about 0.50 mg to about 6.00 mg, about 1.00 mg to about 4.00 mg, about 2.00 mg, about 2.10 mg, about 2.20 mg, about 2.30 mg, about 2.40 mg, about 2.50 mg, about 2.60 mg, about 2.70 mg, about 2.80 mg, about 2.90 mg, about 3.00 mg, at least about 0.50 mg, or about 4.00 mg or less. For example, an implant 100 described herein having a diameter of about 3.0 mm and a length of about 15 mm can have a mass of about 2.04 mg. As another example, an implant 100 described herein having a diameter of about 3.0 mm and a length of about 20 mm can have a mass of about 2.09 mg. As another example, an implant 100 described herein having a diameter of about 3.0 mm and a length of about 23 mm can have a mass of about 2.36 mg. As another example, an implant 100 described herein having a diameter of about 4.0 mm and a length of about 20 mm can have a mass of about 2.50 mg. As another example, an implant 100 described herein having a diameter of about 4.0 mm and a length of about 23 mm can have a mass of about 2.69 mg.

[0099] coating The implant 100 can have a coating as described herein, such as a thrombophilic coating. For example, the implant 100 including the tubular frame 110 and radiopaque markers, such as the radiopaque markers 181, 182, can have a heparin coating. The heparin coating can include a single layer or multiple layers. In some implementations, the coating of the implant 100 can include a polyamine layer (e.g., a cationic polyamine layer) attached to the surface of the implant 100 and a heparin complex layer attached to the polyamine layer (e.g., attached via ionic interactions or covalent bonds). Furthermore, in some implementations, such a polyamine layer followed by a heparin complex layer can be repeatedly deposited to form multiple layers on the implant 100. For example, the implant 100 can have a polyamine layer, a heparin complex layer, a polyamine layer, a heparin complex layer, and so on. Such repeated lamination can produce implants 100 having two alternating layers of polyamine and heparin, three alternating layers of polyamine and heparin, four alternating layers of polyamine and heparin, or more. The heparin coating of implant 100, if included, can completely cover implant 100 such that there are no exposed or uncoated portions of implant 100. In some implementations, the heparin coating of implant 100 is configured to be a permanent coating (e.g., a non-eluting coating). In some implementations, the heparin coating can be applied to a polymer layer (e.g., a fluoropolymer) that is applied to a surface of implant 100. In some implementations, the heparin coating is applied directly to the surface of implant 100, which can be a nitinol surface as described herein.

[0100] The heparin coating of the implant 100 can have a thickness of less than about 60 nm, less than about 50 nm, less than about 40 nm, less than about 30 nm, less than about 25 nm, less than about 20 nm, less than about 15 nm, less than about 14 nm, less than about 13 nm, less than about 12 nm, less than about 11 nm, less than about 10 nm, less than about 9 nm, less than about 8 nm, less than about 7 nm, less than about 6 nm, less than about 5 nm, about 20 nm, about 19 nm, about 18 nm, about 17 nm, about 16 nm, about 15 nm, about 14 nm, about 13 nm, about 12 nm, about 11 nm, about 10 nm, about 9 nm, about 8 nm, about 7 nm, about 6 nm, about 5 nm, about 4 nm, from about 3 nm to about 60 nm, from about 4 nm to about 30 nm, or from about 5 nm to about 20 nm. Such thickness of the heparin coating can be measured in a dry state (e.g., in a vacuum) using transmission electron microscope focused ion beam (TEM-FIB) imaging. Moreover, such thickness of the heparin coating can be an average thickness of thicknesses measured at various locations on the implant 100. The heparin coating of the implant 100 can have a uniform or substantially uniform thickness. For example, the thickness of the heparin coating of the implant 100 can be within three standard deviations, two standard deviations, or one standard deviation of the average thickness measured. A thin heparin coating provides certain advantages. For example, if the entire coating is flaked to form a single embolic particle, its diameter will be less than about 101 μm. If the entire coating is flaked to form a particle with a diameter of 10 μm, there will be about 1000 particles, which is at least about six times lower than the limit according to USP788.

[0101] The heparin coating of the implant 100 may be less than about 1.50 μg, less than about 1.25 μg, less than about 1.00 μg, less than about 0.90 μg, less than about 0.80 μg, less than about 0.70 μg, less than about 0.60 μg, less than about 0.55 μg, less than about 0.50 μg, less than about 0.45 μg, less than about 0.40 μg, less than about 0.35 μg, less than about 0.3 The antibody can have a mass of less than 0 μg, less than about 0.25 μg, about 0.75 μg, about 0.70 μg, about 0.65 μg, about 0.60 μg, about 0.55 μg, about 0.50 μg, about 0.45 μg, about 0.40 μg, about 0.35 μg, about 0.30 μg, about 0.25 μg to about 0.75 μg, or about 0.30 μg to about 0.60 μg.

[0102] The heparin coating of the implant 100 has a heparin content of approximately 10 pmol AT / cm as measured by an antithrombin (AT) binding assay. 2 Ultra, about 15 pmol AT / cm 2 Ultra, about 20 pmol AT / cm 2 Ultra, about 25 pmol AT / cm 2 Ultra, about 30 pmol AT / cm 2 Ultra, about 35 pmol AT / cm 2 Ultra, about 40 pmol AT / cm 2 Ultra, about 45 pmol AT / cm 2 Ultra, about 50 pmol AT / cm 2 Ultra, about 55 pmol AT / cm 2 Super, about 60 pmol AT / cm 2 Ultra, about 65 pmol AT / cm 2 Ultra, about 70 pmol AT / cm 2 Ultra, about 20 pmol AT / cm 2 , about 25 pmol AT / cm 2 , about 30 pmol AT / cm 2 , about 35 pmol AT / cm 2 , about 40 pmol AT / cm 2 , about 45 pmol AT / cm 2 , about 50 pmol AT / cm 2 , about 55 pmol AT / cm 2 , about 60 pmol AT / cm 2 , about 65 pmol AT / cm 2, or about 70 pmol AT / cm 2 The surfactant may have an activity (eg, surface activity).

[0103] When provided with a heparin coating as described herein, the implant 100 has a ratio of the mass of the heparin coating to the total surface area of ​​the implant 100 of about 0.005 μg / mm 2 ~Approx. 0.011μg / mm 2 , about 0.007μg / mm 2 ~ approx. 0.009μg / mm 2 , about 0.005μg / mm 2 Ultra, approximately 0.007μg / mm 2 Ultra, approximately 0.008μg / mm 2 Ultra, approximately 0.015μg / mm 2 Less than 0.009 μg / mm 2 Less than 0.008 μg / mm 2 , or about 0.009 μg / mm 2 It can be said that:

[0104] When provided with a heparin coating as described herein, the implant 100 has a ratio of the mass of the heparin coating to the abluminal surface area of ​​the implant 100 of about 0.01 μg / mm 2 ~ approx. 0.06μg / mm 2 , about 0.02 μg / mm 2 ~about 0.05μg / mm 2 , about 0.03 μg / mm 2 ~ approx. 0.04μg / mm 2 , about 0.01 μg / mm 2 Ultra, about 0.02μg / mm 2 Ultra, approximately 0.03μg / mm 2 Over 0.06μg / mm 2 Less than about 0.05 μg / mm 2 Less than 0.03μg / mm 2 , about 0.035μg / mm 2 , or about 0.04 μg / mm 2 It can be said that:

[0105] When having a heparin coating as described herein, the implant 100 can have a ratio of the mass of the heparin coating to the wall thickness of the implant 100 of about 0.005 μg / mm to about 0.015 μg / mm, about 0.007 μg / mm to about 0.014 μg / mm, about 0.008 μg / mm to about 0.013 μg / mm, greater than about 0.005 μg / mm, greater than about 0.007 μg / mm, greater than about 0.008 μg / mm, less than about 0.015 μg / mm, less than about 0.013 μg / mm, about 0.008 μg / mm, about 0.009 μg / mm, about 0.010 μg / mm, about 0.011 μg / mm, about 0.012 μg / mm, or about 0.013 μg / mm.

[0106] When the implant 100 has a heparin coating as described herein, the ratio of the thickness of the heparin coating to the wall thickness of the implant 100 (eg, the tubular frame 120) can be about 0.00005 or greater, such as about 0.00016 or greater.

[0107] When the implant 100 has a heparin coating as described herein, the ratio of activity of the heparin coating to the wall thickness of the implant 100 is about 0.30 pmol AT / cm 2 / μm or more, approximately 0.35pmolAT / cm 2 / μm, approximately 0.40pmolAT / cm 2 / μm or more, approximately 0.45pmolAT / cm 2 / μm or more, approximately 0.50pmolAT / cm 2 / μm or more, approximately 0.55pmolAT / cm 2 / μm or more, approximately 0.60pmolAT / cm 2 / μm, approximately 0.65pmolAT / cm 2 / μm, approximately 0.70pmolAT / cm 2 / μm or more, approximately 0.75pmolAT / cm 2 / μm, approximately 0.80pmolAT / cm 2 / μm or more, approximately 0.85pmolAT / cm 2 / μm or more, approximately 0.90pmolAT / cm 2 / μm, approximately 0.95pmolAT / cm 2more than / μm, approximately 1.00 pmol AT / cm 2 more than / μm, approximately 1.10 pmol AT / cm 2 more than / μm, approximately 1.15 pmol AT / cm 2 more than / μm, approximately 1.20 pmol AT / cm 2 more than / μm, approximately 1.25 pmol AT / cm 2 more than / μm, approximately 1.30 pmol AT / cm 2 more than / μm, approximately 1.35 pmol AT / cm 2 more than / μm, approximately 1.40 pmol AT / cm 2 more than / μm, approximately 1.45 pmol AT / cm 2 more than / μm, approximately 1.50 pmol AT / cm 2 more than / μm, approximately 0.45 pmol AT / cm 2 / μm, approximately 0.50 pmol AT / cm 2 / μm, approximately 0.55 pmol AT / cm 2 / μm, approximately 0.60 pmol AT / cm 2 / μm, approximately 0.65 pmol AT / cm 2 / μm, approximately 0.70 pmol AT / cm 2 / μm, approximately 0.75 pmol AT / cm 2 / μm, approximately 0.80 pmol AT / cm 2 / μm, approximately 0.85 pmol AT / cm 2 / μm, approximately 0.90 pmol AT / cm 2 / μm, approximately 0.95 pmol AT / cm 2 / μm, approximately 1.00 pmol AT / cm 2 / μm, approximately 1.10 pmol AT / cm 2 / μm, approximately 1.15 pmol AT / cm 2 / μm, approximately 1.20 pmol AT / cm 2 / μm, approximately 1.25 pmol AT / cm 2 / μm, approximately 1.30 pmol AT / cm 2 / μm, or approximately 1.35 pmol AT / cm 2 It can be / μm.

[0108] In some implementations, the implant 100 does not include a graft, covering, or liner. For example, in some implementations, the implant 100 includes only a coating as described herein.

[0109] Table 2 below summarizes preferred configurations and characteristics of the implant 100 according to some embodiments of the present disclosure.

[0110] Table 2. Preferred implant configurations and characteristics [Table 2]

[0111] Close Contact FIG. 3 illustrates a bend test of the intraluminal implant 100 according to FIGS. 2A-2E. In this case, the 3 mm diameter implant 100 is shown centrally deployed in a flexible silicone U-shaped bent tube 30 with a bend radius of 4.9 mm and an inner diameter of 3 mm. The left image shows one half of the implant 100 in the U-shaped bent tube, and the right image shows the other half of the implant 100 in the U-shaped bent tube. Circled are the locations of the malapposition between the implant 100 and the inner wall of the U-shaped bent silicone tube 30 in this test, with the circled location 31 having a malapposition of less than 0.10 mm, the circled location 32 having a malapposition of 0.10 mm or more and less than 0.20 mm, and the circled location 33 having a malapposition of 0.20 mm or more. In this example, the implant 100 had 15 locations that were measured to have at least some malapposition between the implant 100 (e.g., the implant's posts) and the inner wall of the U-shaped bent silicone tube. The maximum malapposition measured between the implant 100 (e.g., the implant's post) and the inner wall of the U-shaped bent silicone tube was 0.375 mm. Additionally, the average malapposition measured between the implant 100 (e.g., the implant's post) and the inner wall of the U-shaped bent silicone tube was 0.116 mm.

[0112] An implant as described herein (e.g., implant 100) can be configured to have at least some misfits between the implant and the flexible silicone U-bend tube 30, as described in the Misfit Bend Test above, such as about 50 or less, about 30 or less, about 25 or less, about 20 or less, about 15 or less, about 10 or less, or about 5 or less. The implants described herein (e.g., implant 100) can be configured such that the maximum incomplete contact between the implant and the flexible silicone U-shaped bend tube 30 described in the Incomplete Contact Bend Test above is about 1.00 mm or less, about 0.75 mm or less, about 0.50 mm or less, about 0.40 mm or less, about 0.375 mm or less, about 0.35 mm or less, about 0.325 mm or less, about 0.30 mm or less, about 0.275 mm or less, about 0.25 mm or less, about 0.225 mm or less, about 0.20 mm or less, about 0.175 mm or less, about 0.15 mm or less, about 0.125 mm or less, about 0.10 mm or less, about 0.075 mm or less, or about 0.05 mm or less. Additionally, the implants described herein (e.g., implant 100) can be configured such that the average incomplete contact between the implant and the flexible silicone U-bend tube 30 described in the Incomplete Contact Bend Test above is about 0.35 mm or less, about 0.325 mm or less, about 0.30 mm or less, about 0.275 mm or less, about 0.25 mm or less, about 0.225 mm or less, about 0.20 mm or less, about 0.175 mm or less, about 0.15 mm or less, about 0.125 mm or less, about 0.120 mm or less, about 0.115 mm or less, about 0.10 mm or less, about 0.075 mm or less, about 0.05 mm or less, or about 0.025 mm or less.

[0113] Implant Modifications FIG. 4 illustrates an implant 400 that is a variation of the implant 100 described with respect to FIGS. 2A-2E. The implant 400 may be similar to the implant 100 in some or many respects. For example, the implant 400 may have a generally tubular frame 410 having a proximal end 401, a distal end 402, and a plurality of longitudinally spaced rings 441 extending around the circumference of the tubular frame 410 that are the same as or similar to the tubular frame 110 and the plurality of rings 141 of the implant 100. Each ring of the plurality of rings 441 of the implant 400 may include a plurality of ring struts 442, with adjacent pairs of the ring struts joining at the plurality of proximal apices 443 and the plurality of distal apices 444 to form a chevron pattern as illustrated that is the same as or similar to the plurality of rings 141, the plurality of ring struts 142, the plurality of proximal apices 143, and the plurality of distal apices 144 of the implant 100. Additionally, implant 400 can include a plurality of linking struts 445 extending at least partially around the circumference of tubular frame 410, with each linking strut of plurality of linking struts 445 connecting a distal apex of one ring of plurality of rings 441 to a proximal apex of an adjacent ring of plurality of rings 441, as shown the same as or similar to linking struts 145 of implant 100. Implant 400 can include a thrombophilic coating, such as a heparin coating, the same as or similar to a coating that may be included on implant 100.

[0114] Implant 400 may differ from implant 100 in that it may exclude a proximal portion having a ring and / or a distal portion having a ring (e.g., proximal portion 120 having ring 121 and / or distal portion 160 having ring 161) as may be included in implant 100, although in some implementations implant 400 may include such proximal and / or distal portions. Implant 400 may also differ from implant 100 in that it may exclude a flared end / portion as may be included in implant 100, although in some implementations implant 400 may include such a flared end / portion. Implant 400 may differ from implant 100 in that it may exclude one or more proximally extending struts and / or one or more distally extending struts along with radiopaque markers that may be included in implant 100 (e.g., one or more proximally extending struts 125, one or more distally extending struts 165, and radiopaque markers 181, 182), although in some implementations implant 400 may include such one or more proximally extending struts, such one or more distally extending struts, and / or such radiopaque markers.

[0115] FIG. 5 illustrates an implant 500 that is a variation of the implant 100 described with respect to FIGS. 2A-2E. The implant 500 may be similar to the implant 100 in some or many respects. For example, the implant 500 may have a generally tubular frame 510 having a proximal end 501 and a distal end 502 that are the same as or similar to the generally tubular frame 110 of the implant 100. The implant 500 may differ from the implant 100 in that instead of having longitudinally spaced rings 141 (e.g., discrete rings longitudinally spaced along the length of the implant), the implant 500 may include a continuous ring 541 that spirals around the circumference of the tubular frame 510. The ring 541 may include a plurality of ring struts 542, with adjacent pairs of the ring struts joining at a plurality of proximal apices 543 and a plurality of distal apices 544 to form a chevron pattern as shown. Additionally, implant 500 can include a plurality of linking struts 545 extending at least partially around the circumference of tubular frame 510, with each linking strut of plurality of linking struts 545 connecting a distal apice of plurality of distal apices 544 to a proximal apice of plurality of proximal apices 543, similar to linking struts 145 of implant 100. Implant 500 can include a thrombophilic coating, such as a heparin coating, the same or similar to the coating that may be included on implant 100.

[0116] Implant 500 may further differ from implant 100 in that it may exclude a proximal portion having a ring and / or a distal portion having a ring (e.g., proximal portion 120 having ring 121 and / or distal portion 160 having ring 161) as may be included in implant 100, although in some implementations implant 500 may include such proximal and / or distal portions. Implant 500 may also differ from implant 100 in that it may exclude a flared end / portion as may be included in implant 100, although in some implementations implant 500 may include such a flared end / portion. Implant 500 may differ from implant 100 in that it may exclude one or more proximally extending struts and / or one or more distally extending struts along with radiopaque markers that may be included in implant 100 (e.g., one or more proximally extending struts 125, one or more distally extending struts 165, and radiopaque markers 181, 182), although in some implementations implant 500 may include such one or more proximally extending struts, such one or more distally extending struts, and / or such radiopaque markers.

[0117] Delivery System 6 is a diagram illustrating a delivery wire 600, according to some embodiments of the present disclosure. The delivery wire 600 can extend generally longitudinally between its proximal end 601 and distal end 602. The delivery wire 600 can include a core wire 700, a proximal coil 620, a bumper 800, a distal coil 640, a coupler 900, a spacer coil 660, and a radiopaque coil 680, as shown. As described herein, the delivery wire 600 can be configured to travel through an implant delivery catheter and deliver an implant as described herein, such as the implant 100.

[0118] 7A-7B are side views of core wire 700 of delivery wire 600 of FIG. 6 according to some embodiments of the present disclosure. Core wire 700 can extend approximately a length 704 between its proximal end 701 and its distal end 702. Core wire 700 can include one or more substantially constant diameter sections and one or more tapered sections to produce core wire 700 having a larger diameter at its proximal end 701 than at its distal end 702. For example, and as shown in Figures 7A-7B, core wire 700 can include a first constant diameter portion 710 having a diameter 711 and a length 712, a first tapered portion 720 having a length 722, a second constant diameter portion 730 having a diameter 731 and a length 732, a second tapered portion 740 having a length 742, a third constant diameter portion 750 having a diameter 751 and a length 752, a third tapered portion 760 having a length 762, and a fourth constant diameter portion 770 having a diameter 771 and a length 772. As shown, a first constant diameter section 710 can extend distally from a proximal end 701 of the core wire 700, a first tapered section 720 can extend distally from the first constant diameter section 710, a second constant diameter section 730 can extend distally from the first tapered section 720, a second tapered section 740 can extend distally from the second constant diameter section 730, a third constant diameter section 750 can extend distally from the second tapered section 740, a third tapered section 760 can extend distally from the third constant diameter section 750, and a fourth constant diameter section 770 can extend distally from the third tapered section 760 and terminate at the distal end 702 of the core wire. In some implementations, core wire 700 is a stainless steel spring wire (eg, type 304 stainless steel) that has been ground to form one or more constant diameter sections and one or more tapered sections.

[0119] The core wire 700 may have a length 704 of at least about 1000 mm. In some implementations, the core wire 700 has a length 704 of about 1900 mm. In such implementations, the length 712 of the first constant diameter section 710 may be about 1500 mm, the length 722 of the first tapered section may be about 60 mm, the length 732 of the second constant diameter section 730 may be about 200 mm, the length 742 of the second tapered section 740 may be about 40 mm, the length 752 of the third constant diameter section 750 may be about 88 mm, the length 762 of the third tapered section 760 may be about 4 mm, and the length 772 of the fourth constant diameter section 770 may be about 8 mm. The core wire 700 may have a maximum diameter of about 0.75 mm or less. In some implementations, the core wire 700 has a maximum diameter of about 0.3810 mm. In such implementations, the diameter 711 of the first constant diameter section 710 may be approximately 0.3810 mm, the diameter 731 of the second constant diameter section 730 may be approximately 0.1778 mm, the diameter 751 of the third constant diameter section 750 may be approximately 0.0762 mm, and the diameter 771 of the fourth constant diameter section 770 may be approximately 0.0559 mm. Further, in such implementations, the first tapered section 720 may taper over its length 722 from the first constant diameter section diameter 711 to the second constant diameter section diameter 731, the second tapered section 740 may taper over its length 742 from the second constant diameter section diameter 731 to the third constant diameter section diameter 751, and the third tapered section 760 may taper over its length 762 from the third constant diameter section diameter 751 to the fourth constant diameter section diameter 771. Although preferred lengths and diameters of core wire 700 and its constant diameter and tapered sections 710, 720, 730, 740, 750, 760, and 770 are provided, any of such lengths and / or diameters may be less than or greater than those given, and / or such lengths and / or diameters may scale as the core wire decreases or increases in length and / or diameter.Although not shown, in some implementations, the core wire 700 may include an inner lumen configured to receive a guidewire therethrough (thus, the delivery wire 600 may be configured to have a guidewire extend therethrough).

[0120] With reference to FIG. 7B, the core wire 700 can include one or more markers 780. The one or more markers 780 can be configured as one or more visual indicators useful for delivery of an implant as described herein. For example, the core wire 700 can be laser marked to create the one or more markers 780. As shown in FIG. 7B, the core wire 700 can include three markers 780, although the core wire can include one, two, three, four, five, or more markers 780. Also, as shown in FIG. 7B, the markers 780 can each have a length 782 and can be spaced apart from one another by a length 784. In some implementations, the length 782 of the markers 780 is between about 6 mm and about 14 mm (e.g., about 10 mm), and the spacing length 784 is between about 6 mm and about 14 mm (e.g., about 10 mm). The lengths 782 of the markers 780 can be the same or different, and the spacing lengths 784 therebetween can be the same or different. The marker 780 can be included in the first constant diameter section 710. For example, the distal-most end of the distal-most marker 780 can be located approximately 1350 mm distal from the proximal end 701 of the core wire 700.

[0121] 8A-8D are diagrams illustrating a bumper 800 of the delivery wire 600 of FIG. 6 according to some embodiments of the present disclosure. FIG. 8A illustrates a side view, FIG. 8B illustrates an end view, FIG. 8C illustrates another side view, and FIG. 8D illustrates a perspective view of the bumper 800. The bumper 800 can have a generally tubular body 820 having a proximal end 801, a distal end 802, a length 812, and a longitudinal axis 803 extending between the proximal end 801 and the distal end 802, an outer diameter 806, and an inner diameter 805 defining a lumen 804. As shown, the bumper 800 can have a helical cut surface 807 at its proximal end 801. Such helical cut surface 807 can be configured to mate with an end of a coil, such as the distal end of the proximal coil 620. Additionally, as shown, bumper 800 can have a substantially flat surface 808 at its distal end 802. Bumper 800 can be configured to be attached to core wire 700, for example, over core wire 700. For such attachment, bumper 800 can have through holes 809 extending along the sides of bumper 800 from inner diameter 805 through outer diameter 806 (e.g., through a thickness of tubular body 820 of bumper 800). Through holes 809 can be configured to weld and attach bumper 800 to core wire 700.

[0122] The length 812 of the bumper 800 can be between about 0.500 mm and about 0.9 mm, such as about 0.762 mm. The outer diameter 806 of the bumper 800 can be between about 0.200 mm and about 0.400 mm, such as about 0.330 mm. The inner diameter 805 of the bumper 800 can be between about 0.070 mm and about 0.130 mm, such as about 0.0965 mm. The bumper 800 can be made of stainless steel (e.g., 304 stainless steel).

[0123] 9A-9E are diagrams illustrating a coupler 900 of the delivery wire 600 of FIG. 6 according to some embodiments of the present disclosure. FIG. 9A illustrates a side view, FIG. 9B illustrates an end view, FIG. 9C illustrates a cross-sectional side view of FIG. 9A, and FIG. 9D-9E illustrate perspective views of the coupler 900. The coupler 900 can have a generally tubular body 920 having a proximal end 901, a distal end 902, a length 912, and a longitudinal axis 903 extending between the proximal end 901 and the distal end 902, an outer diameter 906, an inner diameter 905 defining a lumen 904, and a hub 930 adjacent the proximal end 901. The tubular body 920 of the coupler 900 can have a helical cut surface 907 at its distal end 902. Such helical cut surface 907 can be configured to mate with an end of a coil, such as the proximal end of the spacer coil 660. Additionally, as shown, the tubular body 920 of the coupler 900 can have a substantially flat surface 908 at its proximal end 901. The coupler 900 can be configured to be attached to the core wire 700, for example, over the core wire 700. For such attachment, the coupler 900 can have one or more through holes 909 extending along a side of the coupler 900 from the inner diameter 905 through the outer diameter 906 (e.g., through a thickness of the tubular body 920 of the coupler 900). The one or more through holes 909 can be configured to weld and attach the coupler 900 to the core wire 700.

[0124] Coupler 900 can be configured to releasably engage an implant described herein, such as implant 100, to deliver the implant. To this end, hub 930 can have one or more slots 931 extending radially outwardly of the outer diameter 906 of tubular body 920 and configured to releasably receive at least a portion of an implant as described herein. For example, one or more slots 931 can be configured to releasably receive neck portions 126 of one or more proximally extending struts 125 of implant 100 (e.g., each slot can receive a neck portion of a proximally extending strut).

[0125] 9A-9E , the one or more slots 931 of the hub 930 can have a width 937 at the outer diameter 906 of the tubular body 920 and can have a slot angle 938. The one or more slots 931 of the hub 930 can define a hub portion 932 having a hub portion angle 933. The hub 930 can have a hub diameter 935 and a hub length 936. Additionally, the hub 930 can have a proximal portion 940 having a proximal portion length 946 and a proximal face 941 that can be at an angle 944 with respect to the longitudinal axis 903, and a distal portion 950 having a distal portion length 956 and a distal face 951. The angle 944 of the proximal face 941 can advantageously facilitate retraction of the delivery wire 600 within the catheter after it has been extended distally therefrom, as described with respect to delivery of an implant (e.g., the angle can help prevent snagging of the delivery wire 600 at the catheter tip). The hub 930 can have three hub sections 932 and three slots 931 therebetween, as shown, although the hub 930 can be configured to have less than three of each or more than three of each.

[0126] The length 912 of the coupler 900 can be between about 0.300 mm and about 1.000 mm, for example, about 0.635 mm. The outer diameter 906 of the tubular body 920 of the coupler 900 can be between about 0.065 mm and about 0.265 mm, for example, about 0.165 mm. The inner diameter 905 of the tubular body 920 of the coupler 900 can be between about 0.05 mm and about 0.1965 mm, for example, about 0.0965 mm. The diameter 935 of the hub 930 can be between about 0.200 mm and about 0.500 mm, for example, about 0.381 mm. The length 936 of the hub 930 can be between about 0.050 mm and about 0.400 mm, for example, about 0.178 mm. A width 937 of the one or more slots 931 at the outer diameter 906 of the tubular body 920 can be between about 0.030 mm and about 0.130 mm, for example, about 0.086 mm. A slot angle 938 of the one or more slots 931 can be between about 20 degrees and about 80 degrees, for example, about 50 degrees. A hub portion angle 933 of the hub portion 932 can be between about 40 degrees and about 110 degrees, for example, about 70 degrees. A proximal portion length 946 of the proximal portion 940 can be between about 0.020 mm and about 0.080 mm, for example, about 0.051 mm. An angle 944 of the proximal face 941 can be between about 15 degrees and about 115 degrees, for example, about 60 degrees, relative to the longitudinal axis 903. The distal portion length 956 of the distal portion 950 can be between about 0.020 mm and about 0.230 mm, for example about 0.127 mm. The coupler 900 can be made of stainless steel (eg, 304 stainless steel).

[0127] 10A-10B are diagrams illustrating a side view of the delivery wire 600 of FIG. 6, according to some embodiments of the present disclosure. As previously described, the delivery wire 600 can include the core wire 700 described with respect to FIGS. 7A-7B, the proximal coil 620, the bumper 800 described with respect to FIGS. 8A-8D, the distal coil 640, the coupler 900 described with respect to FIGS. 9A-9E, the spacer coil 660, and the radiopaque coil 680, as shown. The core wire 700 can extend through each of the proximal coil 620, the bumper 800, the distal coil 640, the coupler 900, the spacer coil 660, and the radiopaque coil 680.

[0128] The proximal coil 620 can be made of stainless steel (e.g., type 304 stainless steel) spring wire having a wire diameter of about 0.0635 mm wound into a coil having an inner diameter of about 0.203 mm and an outer diameter of about 0.381 mm. The length of the proximal coil 620 can be between about 200 mm and about 400 mm, for example about 292 mm.

[0129] The distal coil 640 can be made of stainless steel (e.g., type 304 stainless steel) spring wire having a wire diameter of about 0.025 mm wound into a coil having an inner diameter of about 0.076 mm and an outer diameter of about 0.152 mm. The length of the distal coil 640 can be between about 0.500 mm and about 1.500 mm, such as about 1.02 mm. In some implementations, the length of the distal coil 640 can be on the order of or greater than the length of the proximal radiopaque marker 181 and / or the length of the connecting portion 127 of one or more proximally extending struts 125 of the implant 100.

[0130] The spacer coil 660 can be made of stainless steel (e.g., type 304 stainless steel) spring wire wound into a coil having a wire diameter of about 0.025 mm, with an inner diameter of about 0.076 mm and an outer diameter of about 0.152 mm. The length of the spacer coil 660 can be between about 2.000 mm and about 10.000 mm, such as about 3.277 mm, about 5.461 mm, or about 6.807 mm. In some implementations, the length of the spacer coil 660 can be adjusted based on the length of an implant, such as the implant 100.

[0131] The radiopaque coil 680 may be made of a radiopaque material (e.g., 92 / 8 platinum-tungsten) wire wound into a coil having a wire diameter of about 0.030 mm and an inner diameter of about 0.076 mm and an outer diameter of about 0.152 mm. The length of the radiopaque coil 680 may be between about 10.000 mm and about 35.000 mm, such as about 17.221 mm, about 21.387 mm, about 22.631 mm, or about 25.121 mm. In some implementations, the length of the radiopaque coil 680 may be adjusted based on the length of an implant, such as the implant 100. In some implementations, the length of the radiopaque coil 680 may be configured to be approximately the same length as the length of the implant 100 after the implant 100 is placed in the blood vessel 5, which may include the collapsed length of the implant 100. In such implementations, the length of the spacer coil 660 can be adjusted accordingly based on the length of the radiopaque coil 680 and the configuration of the implant 100 (eg, the length and diameter of the implant 100).

[0132] 10A-10B, the proximal end of the proximal coil 620 can be attached (e.g., welded) to the core wire 700, which extends through the proximal coil 620. In some implementations, the proximal end of the proximal coil 620 is attached to the core wire 700 along the second constant diameter section 730 of the core wire 700. The distal end of the proximal coil 620 can be attached to the proximal end 801 of the bumper 800, with the core wire 700 extending through the lumen 804 of the bumper 800. For example, the distal end of the proximal coil 620 can mate with and be attached (e.g., welded) to the helical cut surface 807 of the proximal end 801 of the bumper 800. The bumper 800 can be attached (e.g., welded) to the core wire 700 via a through hole 809. In some implementations, the bumper 800 is attached to the core wire 700 along the third constant diameter section 750 of the core wire 700. The distal end 802 of the bumper 800 can be disposed adjacent to the proximal end of the distal coil 640, through which the core wire 700 extends. For example, the proximal end of the distal coil 640 can rest against the flat surface 808 of the distal end 802 of the bumper 800. The proximal end 901 of the coupler 900 can be disposed adjacent to the distal end of the distal coil 640, through which the core wire 700 extends through the lumen 904 of the coupler 900. For example, the flat surface 908 of the proximal end 901 of the coupler 900 can rest against the distal end of the distal coil 640. The coupler 900 can be attached (e.g., welded) to the core wire 700 via one or more through holes 909. In some implementations, the coupler 900 is attached to the core wire 700 along the third constant diameter section 750 of the core wire 700. The proximal end of the spacer coil 660 can be attached (e.g., welded) to the distal end 902 of the coupler 900 with the core wire 700 extending through the spacer coil 660. For example, the proximal end of the spacer coil 660 can mate with and be attached (e.g., welded) to the helical cut surface 907 of the distal end 902 of the coupler 900.The proximal end of the radiopaque coil 680 can be attached (e.g., welded) to the distal end of the spacer coil 660, and the core wire 700 can extend through the radiopaque coil 680. The distal end of the radiopaque coil 680 can be attached (e.g., welded) to the distal end 702 of the core wire 700. For example, the distal end of the radiopaque coil 680 can form a bullet-shaped nosing end with the distal end 702 of the core wire 700 to form a rounded tapered distal end 602 of the delivery wire 600. In some implementations, the radiopaque coil 680 is attached to the core wire 700 at the distal end of the fourth constant diameter section 770 of the core wire 700.

[0133] 10A-10B, the proximal coil 620 can be attached to the core wire 700 at a length 615 from the distal end 602 of the delivery wire 600. The length 615 can be at least about 200 mm or at least about 300 mm, for example, about 312 mm. The proximal coil 620 and bumper 800, when mated as shown, can have a combined length 614 of between about 150 mm and about 315 mm, for example, about 292 mm. The distal end 802 of the bumper 800 and the proximal end 901 of the coupler 900 can be separated by a length 613 that is the same as the length of the distal coil 640. The length 613 can be between about 0.500 mm and about 1.500 mm, for example, about 1.02 mm. In some implementations, the length 613 can be on the order of or greater than the length of the proximal radiopaque marker 181 and / or the length of the connecting portion 127 of one or more proximally extending struts 125 of the implant 100. The portion of the delivery wire 600 between the proximal end 901 of the coupler 900 and the distal end 602 of the delivery wire 600 can have a length 612. The length 612 can be between about 15.00 mm and about 30.00 mm, for example, about 21.08 mm. The length 611 can be the same as the length of the radiopaque coil 680 and can be between about 10.000 mm and about 35.000 mm, for example, about 17.221 mm, about 21.387 mm, about 22.631 mm, or about 25.121 mm. Lengths 612 and 611 (and thus the lengths of coupler 900, spacer coil 660 and / or radiopaque coil 680) can be adjusted based on the length of the implant that delivery wire 600 is configured to deliver, such as implant 100 described herein. Length 616 can be the same as the length of core wire 700, and can be at least about 1000 mm, such as about 1900 mm. Although examples of configurations, connections, and relative positioning of components of delivery wire 600 have been described above, modifications of such configurations, connections, and relative positioning are intended to be within the scope of the present disclosure.

[0134] 11A-11I are diagrams illustrating an intraluminal implant delivery system 1100, according to some embodiments of the present disclosure. The intraluminal implant delivery system 1100, which may also be referred to herein as an implant delivery system or an implant placement system, can include a delivery wire 600 as described herein, an implant (e.g., implant 100) as described herein, and a catheter 1140. FIG. 11A is a perspective view of the implant delivery system 1100. FIG. 11B is a close-up perspective view of a distal end of the implant delivery system 1100 with a portion of the wall of the catheter 1140 removed from view. FIGS. 11C-11D are close-up perspective views of the proximal and distal ends 101 and 102, respectively, of the implant 100 in a folded configuration within the implant delivery system 1100 with a portion of the wall of the catheter 1140 removed from view. FIGS. 11E-11G are side views and associated cross-sectional views of the proximal end 101 of the implant 100 in a folded configuration within the implant delivery system 1100. 11H-11I show side views and associated cross-sectional views of the distal end 102 of the implant 100 in a folded configuration within the implant delivery system 1100. FIG.

[0135] 11A, the catheter 1140 can have a generally tubular body with a lumen 1144 extending between an access port 1111 at its proximal end 1101 and an exit port 1112 at its distal end 1102. As shown, the catheter 1140 can include a hub 1120 adjacent the access port 1111 at its proximal end 1101. The access port 1111 can be configured to attach to a hemostatic valve, such as a rotating hemostatic valve (not shown). The lumen 1144 of the catheter 1140 can have a larger diameter at its proximal end, such as through at least a portion of the access port 1111 and / or through at least a portion of the hub 1120, and narrow to a smaller diameter within or distal to the access port 1111 or the hub 1120. In some implementations, the lumen 1144 can have substantially the same diameter along the entire length of the catheter 1140, including through the access port 1111 and the hub 1120. For example, the lumen 1144 of the catheter 1140 can have an inner diameter of about 0.300 mm to about 0.600 mm, e.g., about 0.419 mm. The outer diameter of the catheter 1140 distal to the hub 1120 can vary along the length of the catheter or can be substantially the same along its length. For example, the outer diameter of the catheter 1140 distal to the hub 1120 can be about 0.400 mm to about 1.000 mm, such as about 0.787 mm near the proximal end distal to the hub 1120 and about 0.610 mm at the distal end 1102. The effective length of the catheter 1140 (e.g., the length of the catheter 1140 distal to the hub 1120) can be about 100 cm to about 200 cm, e.g., about 150 cm. Additionally, the catheter 1140 can be a hybrid structure having one or more braided sections and / or one or more coiled sections that make up the wall of the catheter 1140. Although exemplary configurations of the catheter 1140 have been described above, modifications to such configurations are intended to be within the scope of the present disclosure. For example, the catheter 1140 can be configured to maintain the implant 100 in a folded configuration on the delivery wire 600 while the implant 100 and delivery wire 600 are within the lumen 1144 of the catheter 1140.As another example, the catheter 1140 can be configured to access a neurovascular site of the subject 1 to deliver the implant 100 .

[0136] 11B shows a close-up of the distal end 1102 of the implant delivery system 1100 with the implant 100 in a folded configuration over the delivery wire 600 and within the lumen 1144 of the catheter 1140 with a portion of the wall of the catheter 1140 removed. As shown, the lumen 1144 of the catheter 1140 can be configured to cooperate with the delivery wire 600 to maintain the implant 100 in its folded configuration.

[0137] 11C-11I further illustrate the interaction between the implant 100, the delivery wire 600, and the catheter 1140 of the implant delivery system 1100. As shown in FIGURES 11C and 11E-11F, the hub 930 of the coupler 900 can be configured to receive at least a portion of the implant 100. For example, one or more slots 931 of the hub 930 can be configured to receive the neck portions 126 of one or more proximally extending struts 125 of the implant 100. With such a configuration, as the delivery wire 600 is moved (e.g., longitudinally) relative to the lumen 1144 of the catheter 1140, the implant 100 is moved with the delivery wire 600 due to interactions between the coupler 900 (e.g., the hub 930 of the coupler 900), the implant 100 (e.g., the neck portion 126 of one or more proximally extending struts 125 of the implant 100), and the catheter 1140 (e.g., the lumen 1144 of the catheter 1140). Further explaining, a hub diameter 935 of the hub 930 and the lumen 1144 can be configured to prevent the neck portion 126 of the one or more proximally extending struts 125 of the implant 100 from moving out of the one or more slots 931 of the hub 930 while the hub 930 is disposed within the lumen 1144. Additionally, one or more proximally extending struts 125 of implant 100 may be configured to flare distally and proximally of neck portion 126 such that distal and proximal faces 951, 941 of hub 930 press against such flared portions upon distal or proximal movement of delivery wire 600 relative to lumen 1144. Thus, distal and / or proximal movement of delivery wire 600 relative to catheter 1140 while hub 930 is located within lumen 1144 will correspondingly move implant 100 distally and / or proximally.

[0138] In some implementations, the distal surface 951 of the hub 930 can interact with other portions of the implant 100 to move the implant 100 distally when the delivery wire 600 is moved distally relative to the catheter 1140. Alternatively, or in combination, the bumper 800 (e.g., the flat surface 808 of the bumper 800) can interact with a portion of the implant 100 (e.g., the connector portion 127 of one or more proximally extending struts 125 and / or the proximal radiopaque marker 181) to move the implant 100 distally when the delivery wire 600 is moved distally relative to the catheter 1140. In some implementations, the proximal surface 941 of the hub 930 can interact with other portions of the implant 100 to move the implant 100 proximally when the delivery wire 600 is moved proximally relative to the catheter 1140. For example, the proximal surface 941 can interact with the connector portion 127 of one or more proximally extending struts 125 and / or the proximal radiopaque marker 181 to move the implant 100 proximally when the delivery wire 600 is moved proximally relative to the catheter 1140.

[0139] 11A-11H, a portion of the delivery wire 600 can be configured to pass through the implant 100 (e.g., the lumen 104 of the implant 100) when the implant 100 is folded thereover and the neck portion 126 of one or more proximally extending struts 125 is disposed within one or more slots 931 of the coupler 900. For example, FIGS. 11C, 11E, and 11G show the connector portion 127 of one or more proximally extending struts 125 of the implant 100 and the proximal radiopaque marker 181 connected thereto folded around the delivery wire (e.g., folded around the distal coil 640 and the core wire 700 extending therethrough) between the coupler 900 (e.g., the proximal surface 941 of the hub 930 of the coupler 900) and the bumper 800 (e.g., the distal flat surface 808 of the bumper 800). 11D, 11H, and 11I show a portion of implant 100 (e.g., some or all of implant 100 other than one or more proximally extending struts 125) folded around coupler 900, spacer coil 660, and radiopaque coil 680. As shown in these same figures, the distal end of 102 of implant 100 can be substantially aligned with distal end 602 of delivery wire 600 when implant 100 is folded around delivery wire 600 and within lumen 1144 of catheter 1140.

[0140] 12A-12C are diagrams illustrating the delivery of an intraluminal implant 100 via a delivery wire 600 and a catheter 1140. FIG. 12A illustrates the implant 100 folded relative to the delivery wire 600, with the distal ends 102 and 602 of the implant 100 and delivery wire 600, respectively, substantially aligned with one another (e.g., longitudinally) and adjacent to an exit port 1112 of the catheter 1140. This may be the relative positioning used during advancement of the implant delivery system 1100 within the subject 1 to a desired implantation site. FIG. 12B illustrates a partially enlarged view of the implant 100 with a portion of the implant 100 (e.g., beginning at its distal end 102) extending distally from the exit port 1112 of the distal end 1102 of the catheter 1140. Also illustrated is at least a portion of the delivery wire 600 (e.g., beginning at its distal end 602) extending distally from the exit port 1102 of the catheter 1140. To achieve such partial expansion of the implant 100, the delivery wire 600 can be moved distally relative to the catheter 1140 and / or the catheter 1140 can be moved proximally relative to the delivery wire 600. In some implementations, it is advantageous to simultaneously move the catheter 1140 proximally and the delivery wire 600 distally during deployment of the implant 100. In the partially expanded state shown in FIG. 12B (which may also be referred to herein as a partially deployed state), the relative movement between the delivery wire 600 and the catheter 1140 can either pull the implant 100 back into the catheter 1140 or continue thereafter, eventually completely releasing the implant 100 from the exit port 1112 of the catheter 1140 and the delivery wire 600, as shown in FIG. 12C.As described herein, the implant delivery system 1100 can be configured so that the implant 100 can be withdrawn within the lumen 1144 of the catheter 1140 (e.g., to adjust its position or to remove it from the subject 1) while the hub 930 of the coupler 900 of the delivery wire 600 remains within the lumen 1144 of the catheter 1140 and / or while at least a portion of one or more proximally extending struts 125 remain within the lumen 1144 of the catheter 1140.

[0141] In some implementations, it may be desirable to advance the implant delivery system 1100 within the subject 1 with the distal end 102 of the implant 100 and the distal end 602 of the delivery wire 600 spaced apart from the exit port 1112. For example, it may be desirable to advance the implant delivery system 1100 within the subject 1 with the distal end 102 of the implant 100 and the distal end 602 of the delivery wire 600 recessed within the lumen 1144 of the catheter 1140. Such relative positioning of the implant 100 and the delivery wire 600 relative to the catheter 1140 may advantageously allow the distal tip of the catheter 1140 to at least partially deflect while traversing within the subject. In some implementations, it may be desirable to advance the implant delivery system 1100 within the subject 1 with the distal end 102 of the implant 100 and the distal end 602 of the delivery wire 600 substantially aligned with the exit port 1112. In some implementations, the implant delivery system 1100 can be advanced within the subject 1 while the implant 100 and delivery wire 600 are moved proximally and / or distally relative to the exit port 1112 of the catheter 1140 to adjust the flexibility of the distal tip or portion of the catheter 1140 during advancement. Such adjustment of flexibility during advancement can improve the ability of the implant delivery system 1100 to navigate the blood vessels of the subject 1.

[0142] 13Aa-13Gb illustrate delivery of an intraluminal implant 100 adjacent an aneurysm 7 within a blood vessel 5 according to some embodiments of the present disclosure. Throughout Figures 13Aa-Gb, the upper panels (e.g., Figures 13Aa, 13Ba, 13Ca, 13Da, 13Ea, 13Fa, 13Ga) show an open cross-section of a blood vessel 5 into which the implant 100 is deployed and a schematic diagram of the implant delivery system 1100 (e.g., the catheter 1140, the delivery wire 600, and the implant 100), while the lower panels (e.g., Figures 13Ab, 13Bb, 13Cb, 13Db, 13Eb, 13Fb, 13Gb) show similar open cross-sections but instead show the radiopaque features of the implant delivery system 1100 (e.g., the catheter 1140, the delivery wire 600, and the implant 100) that a care provider would visualize during delivery of the implant under radiography and / or fluoroscopy.

[0143] 13Aa-13Ab illustrate an implant delivery system 1100 positioning an implant 100 (hidden from view) within a catheter 1140 adjacent an aneurysm 7 in a pre-deployment state of the implant 100. As shown, the catheter 1140 may include a distal radiopaque marker 1182 adjacent its distal end 1102 and a proximal radiopaque marker 1181 spaced proximally from the distal end 1102. Additionally, as shown, in the pre-deployment state, the distal end of the radiopaque coil 680 and the at least one distal radiopaque marker 182 of the implant 100 may be substantially longitudinally aligned with one another and located proximal to the distal radiopaque marker 1182 of the catheter 1140 (showing that the distal ends 102 and 602 of the implant 100 and delivery wire 600, respectively, are within the lumen 1144 of the catheter 1140).

[0144] 13Ba-13Bb illustrate the implant delivery system 1100 with the distal end of the radiopaque coil 680, at least one distal radiopaque marker 182 of the implant 100, and the distal radiopaque marker 1182 of the catheter 1140 substantially aligned with one another. Such alignment can be achieved by moving the catheter 1140 proximally relative to the delivery wire 600 (and thus the implant 100) and / or moving the delivery wire 600 distally relative to the catheter 1140. In such positioning, the distal ends 102 and 602 of the implant 100 and delivery wire 600, respectively, can be located within the lumen 1144 and adjacent to the exit port 1112 of the catheter 1140.

[0145] 13Ca-13Cb illustrate the implant delivery system 1100 with the implant 100 partially positioned (e.g., approximately 25% positioned) within the blood vessel 5 and adjacent but distal to the aneurysm 7. As shown, the distal end of the radiopaque coil 680 and the at least one distal radiopaque marker 182 of the implant 100 are both distal to the distal radiopaque marker 1182 of the catheter 1140. Also, the distal end of the radiopaque coil 680 is distal to the at least one distal radiopaque marker 182 of the implant 100. Such positioning can be achieved by moving the catheter 1140 proximally relative to the delivery wire 600 (and thus the implant 100) and / or moving the delivery wire 600 distally relative to the catheter 1140 than is shown in FIGS. 13Ba-13Bb. In such positioning, the distal end 602 of the delivery wire 600 can extend distally of the distal end 102 of the implant 100 and distally and outwardly of the exit port 1112 of the catheter 1140. Additionally, the distal end 102 and at least a portion of the implant 100 can extend distally and outwardly from the exit port 1112 of the catheter 1140 and extend radially outwardly against the inner wall of the blood vessel 5.

[0146] 13Da-13Db show the implant delivery system 1100 in another state in which the implant 100 is partially deployed (e.g., about 50% deployed) resulting in more of the implant 100 being deployed within the vessel 5 than in the partially deployed state shown in FIGS. 13Ca-13Cb. In this partially deployed state, the implant 100 extends at least partially across the aneurysm 7. As shown, both the distal end of the radiopaque coil 680 and the at least one distal radiopaque marker 182 of the implant 100 are distal to the distal radiopaque marker 1182 of the catheter 1140 than shown in FIGS. 13Ca-13Cb. Also, as shown, the distal end of the radiopaque coil 680 is distal to the at least one distal radiopaque marker 182 of the implant 100 than shown in FIGS. 13Ca-13Cb. Such positioning can be achieved by moving the catheter 1140 proximally relative to the delivery wire 600 (and thus the implant 100) and / or moving the delivery wire 600 distally relative to the catheter 1140 than is shown in Figures 13Ca-Cb. In such positioning, the distal end 602 of the delivery wire 600 can extend further distal to the distal end 102 of the implant 100 and further distal and outward from the exit port 1112 of the catheter 1140 than is shown in Figure 13C. Additionally, more of the implant 100 can extend distally and outward from the exit port 1112 of the catheter 1140, spreading radially outward against the inner wall of the blood vessel 5 that it surrounds.

[0147] 13Ea-13Eb show the implant delivery system 1100 in another state where the implant 100 is partially deployed (e.g., about 75% deployed) and at the resheathability limit. In other words, FIGS. 13Ea-13Eb show the implant delivery system 1100 in a position where further deployment of the implant 100 may result in the implant 100 being fully deployed within the vessel 5. As shown, more of the implant 100 is deployed within the vessel 5 than in the partially deployed state shown in FIGS. 13Da-13Db. The implant 100 in this partially deployed, resheathable limit state extends further across the aneurysm 7 than shown in FIGS. 13Da-13Db. As shown, the distal end of the radiopaque coil 680 and the at least one distal radiopaque marker 182 of the implant 100 are both distal to the distal radiopaque marker 1182 of the catheter 1140 than is shown in Figures 13Da-13Db. Also, as shown, the distal end of the radiopaque coil 680 can be distal to the at least one distal radiopaque marker 182 of the implant 100 than is shown in Figures 13Da-13Db. Further still, as shown, the proximal end of the radiopaque coil 680 can be substantially aligned with the distal radiopaque marker 1182 of the catheter 1140, which can advantageously indicate that the implant 100 is at its resheathability limit. Such positioning can be achieved by moving the catheter 1140 proximally relative to the delivery wire 600 (and thus the implant 100) and / or moving the delivery wire 600 distally relative to the catheter 1140 than is shown in Figures 13Da-13Db. In such positioning, the distal end 602 of the delivery wire 600 can extend further distal to the distal end 102 of the implant 100 and further distal and outward of the exit port 1112 of the catheter 1140 than is shown in Figures 13Da-13Db. Additionally, more of the implant 100 can extend distally and outward from the exit port 1112 of the catheter 1140, spreading radially outward against the inner wall of the blood vessel 5 that it surrounds.

[0148] 13Fa-13Fb illustrate the implant delivery system 1100 with the implant 100 nearly fully deployed (e.g., about 95% deployed), and in some implementations, past the resheathability limit. As shown, more of the implant 100 is deployed within the vessel 5 than the partially deployed state shown in FIGS. 13Ea-13Eb. In this nearly fully deployed state, the implant 100 extends across the aneurysm 7. As shown, both the distal end of the radiopaque coil 680 and the at least one distal radiopaque marker 182 of the implant 100 are distal to the distal radiopaque marker 1182 of the catheter 1140 than is shown in FIGS. 13Ea-13Eb. Also, as shown, the distal end of the radiopaque coil 680 can be distal to the at least one distal radiopaque marker 182 of the implant 100 than is shown in FIGS. 13Ea-13Eb. Further still, as shown, the proximal end of the radiopaque coil 680 can be distal to the distal radiopaque marker 1182 of the catheter 1140, and the at least one proximal radiopaque marker 181 of the implant can be substantially aligned with the distal radiopaque marker 1182 of the catheter 1140, which can advantageously indicate that the implant 100 has exceeded its resheathability limit. Such positioning can be achieved by moving the catheter 1140 proximally relative to the delivery wire 600 (and thus the implant 100) and / or moving the delivery wire 600 distally relative to the catheter 1140 than is shown in FIGS. 13Ea-13Eb. In such positioning, the distal end 602 of the delivery wire 600 can extend further distally of the distal end 102 of the implant 100 and further distal and outward of the exit port 1112 of the catheter 1140 than is shown in Figures 13Ea-13Eb. Additionally, more of the implant 100 can extend distally and outwardly from the exit port 1112 of the catheter 1140, spreading radially outward against the inner wall of the blood vessel 5 that it surrounds.

[0149] 13Ga-13Gb illustrate the implant delivery system 1100 with the implant 100 fully deployed within the blood vessel 5. As shown, more of the implant 100 is deployed within the blood vessel 5 than in the nearly fully deployed state shown in FIGS. 13Fa-13Fb. In this fully deployed state, the implant 100 extends across the aneurysm 7 (e.g., at least partially distal and at least partially proximal to the aneurysm 7) and is no longer connected to the delivery wire 600. As shown, both the distal end of the radiopaque coil 680 and the at least one distal radiopaque marker 182 of the implant 100 are distal to the distal radiopaque marker 1182 of the catheter 1140 than is shown in FIGS. 13Fa-13Fb. Also, as shown, the distal end of the radiopaque coil 680 can be distal of the at least one distal radiopaque marker 182 of the implant 100 than is shown in Figures 13Fa-13Fb. Still further, as shown, the at least one proximal radiopaque marker 181 of the implant 100 can be distal of the distal radiopaque marker 1182 of the catheter 1140, which can advantageously indicate that the implant 100 is fully deployed and is no longer connected to the delivery wire 600. Such positioning can be achieved by moving the catheter 1140 proximally relative to the delivery wire 600 (and thus the implant 100) and / or moving the delivery wire 600 distally relative to the catheter 1140 than is shown in Figures 13Fa-13Fb. In such positioning, the distal end 602 of the delivery wire 600 can extend further distal to the distal end 102 of the implant 100 and further distal and out of the exit port 1112 of the catheter 1140 than is shown in Figures 13Fa-Fb. Furthermore, none of the implant 100 can be contained by the catheter 1140 and all of the implant 100, including the proximal end 101, can extend radially outward against the inner wall of the blood vessel 5 surrounded thereby.

[0150] 14A-14F are diagrams illustrating another implementation of an endoluminal implant delivery system 1400, according to some embodiments of the present disclosure. FIG. 14A is a perspective view of the implant delivery system 1400. FIG. 14B is a close-up perspective view of the distal end of the implant delivery system 1400 with a portion of the wall of the catheter 1440 removed from view. FIGs. 14C-14D are side views and associated cross-sections of the proximal end 1501 of the implant 1500 in a folded configuration within the implant delivery system 1400. FIGs. 14E-14F are side views and associated cross-sections of the distal end 1502 of the implant 1500 in a folded configuration within the implant delivery system 1400.

[0151] The intraluminal implant delivery system 1400 may be similar or identical in some or many respects to the implant delivery system 1100 and / or may include any of the functionality of the implant delivery system 1100. For example, the implant delivery system 1400 may comprise a catheter 1440 having a generally tubular body having a lumen 1444 extending between an access port 1411 at the proximal end 1401 and an exit port 1412 at the distal end 1402, similar to or identical to the catheter 1140 having a proximal end 1101, an access port 1111, an exit port 1112, a distal end 1102, and a lumen 1144. Additionally, the catheter 1440 may include a hub 1420 adjacent the access port 1411 at the proximal end 1401, similar to or the same as the hub 1120 of the catheter 1140. Implant delivery system 1400 may also be configured to deliver a folded implant 1500 on a delivery wire 1600 similar to implant 100 and delivery wire 600 of implant delivery system 1100, although the implant 1500 and delivery wire 1600 may be configured differently. For example, as shown, delivery wire 1600 may extend generally longitudinally between its proximal end 1601 and distal end 1602, similar or identical to delivery wire 600. Delivery wire 1600 may also have a core wire 1700 having one or more markers 1780 similar or identical to core wire 700 having markers 780 of delivery wire 600. Delivery wire 1600 may have a proximal coil 1620, a proximal coupler 1900, and in some implementations a distal coupler 2000, which may differ from delivery wire 600 in that proximal coupler 1900 and distal coupler 2000 are configured to interact with implant 1500 for its delivery. Similar to delivery wire 600, delivery wire 700 may be configured to travel through catheter 1440 and deliver implant 1500.

[0152] The proximal coupler 1900 of the delivery wire 1600 can have a generally tubular body 1920 having a lumen 1904 extending between its proximal end 1901 and distal end 1902. As shown at least in FIGS. 14C-14D, the proximal coupler 1900 can have one or more windows configured to receive and releasably couple at least a portion of the implant 1500 for delivery thereof. For example, the proximal coupler 1900 can have a first window 1940, a second window 1950, and a third window 1960. The first window 1940 and the second window 1950 can be at least partially aligned with one another across a side of the proximal coupler 1900 and separated from one another by a strut 1930. The third window 1960 can provide a through hole through which the proximal coupler 1900 can be attached (e.g., welded) to the core wire 1700 of the delivery wire 1600.

[0153] The distal coupler 2000 of the delivery wire 1600, if included, can have a generally tubular body 2020 having a lumen 2004 extending at least partially from its proximal end 2001 to its distal end 2002, and a closed rounded distal end 2002. As shown at least in FIGS. 14E-14F, the distal coupler 2000 can have one or more windows configured to receive and releasably couple at least a portion of the implant 1500 for delivery thereof. For example, the distal coupler 2000 can have a first window 2040, a second window 2050, and a third window 2060. The first window 2040 and the second window 2050 can be at least partially aligned with one another across a side of the distal coupler 2000 and separated from one another by struts 2030. The third window 2060 can provide a through hole through which the distal coupler 2000 can be attached (eg, welded) to the core wire 1700 of the delivery wire 1600.

[0154] Implant 1500 may be the same or similar in some or many respects to implants 100, 400, and / or 500 and / or may include any of the functionality of implants 100, 400, and / or 500. For example, implant 1500 may include a ring 1541 consisting of a plurality of ring struts 1542 joining at a plurality of proximal apices 1543 and a plurality of distal apices 1544 joined by connecting struts 1545 similar or the same as ring 141, 121, 161, a plurality of ring struts 142, 122, 162, a plurality of proximal apices 143, 123, 163, a plurality of distal apices 144, 124, 164, and a plurality of connecting struts 145 of implant 100. Implant 1500 may differ from implants 100, 400, and / or 500 in the way in which it is configured to releasably connect with an associated delivery wire 1600. 14C-14D , the implant 1500 can have a proximally extending strut 1530 configured to releasably connect / interact with a proximal coupler 1900 of a delivery wire 1600 for delivery of the implant 1500. The proximally extending strut 1530 can have a neck portion 1532 and a proximal flag 1533, the proximal flag having a proximal surface 1535, a free end 1534, and a distal surface 1536. The neck portion 1532 can be configured to extend proximally over one or more proximal radiopaque markers 1581 that extend proximally from the implant 1500 when the implant 1500 is in a collapsed state within the catheter 1444, and to extend proximally about the delivery wire 1600. The proximal flag 1533 extends proximally from the neck portion 1532 and can be configured to releasably connect with the proximal coupler 1900 of the delivery wire 1600. To this end, the free end 1534 of the proximal flag 1533 can be inserted into the first window 1940 and the first window 1950 of the proximal coupler 1900 such that the proximal flag 1533 extends at least partially through the first window 1940 and the second window 1950. Also, the proximal surface 1535 and / or the distal surface 1536 can be angled relative to the longitudinal axis of the implant 1500 as shown to facilitate connection and interaction between the proximal flag 1533 and the proximal coupler 1900.The struts 1930 of the proximal coupler 1900 can prevent the proximal flag 1533 from sliding radially outwardly off the proximal coupler 1900, and the lumen 1444 of the catheter 1440 can prevent the proximal flag 1533 from sliding out of the first and second windows 1940, 1950 while the proximal coupler 1900 remains within the lumen 1444 of the catheter 1440. Additionally, the proximal and distal surfaces 1535, 1536 of the proximal flag 1533 can interact with corresponding proximal and distal surfaces of the first and second windows 1940, 1950 for advancement or retraction of the implant 1500 relative to the catheter 1440 when the delivery wire 1600 is advanced or retracted relative to the catheter 1440.

[0155] If the implant 1500 has sufficient pushability, the implant 1500 and delivery wire 1600 can be releasably connected only via the proximal flag 1533 and the proximal coupler 1900. If the implant 1500 does not have sufficient pushability, the implant 1500 and delivery wire 1600 can be releasably connected in a similar manner via the distal flag 1553 and the distal coupler 2000 of the distally extending strut 1550 of the implant 1500, in addition to releasably connecting via the proximal flag 1533 and the proximal coupler 1900. As shown in at least FIGS. 14E-14F, the implant 1500 can have a distally extending strut 1550 configured to releasably connect / interact with the distal coupler 2000 of the delivery wire 1600 for delivery of the implant 1500. The proximally extending strut 1550 can have a neck portion 1552 and a distal flag 1553, the distal flag having a proximal surface 1555, a free end 1554, and a distal surface 1556. The neck portion 1552 can be configured to extend distally beyond one or more proximal radiopaque markers 1582 extending distally from the implant 1500 and extend distally about the delivery wire 1600 when the implant 1500 is in a collapsed state within the catheter 1444. The distal flag 1553 extends distally from the neck portion 1552 and can be configured to releasably connect with a distal coupler 2000 of the delivery wire 1600. To this end, the free end 1554 of the distal flag 1553 can be inserted into the first window 2040 and the second window 2050 of the distal coupler 2000 such that the distal flag 1553 extends at least partially through the first window 2040 and the second window 2050. Also, the proximal surface 1555 and / or the distal surface 1556 can be angled relative to the longitudinal axis of the implant 1500 as shown to facilitate connection and interaction between the distal flag 1553 and the distal coupler 2000.The struts 2030 of the proximal-distal coupler 2000 can prevent the distal flag 1553 from sliding radially outwardly off the distal coupler 2000, and the lumen 1444 of the catheter 1440 can prevent the distal flag 1553 from sliding out of the first and second windows 2040, 2050 while the distal coupler 2000 remains within the lumen 1444 of the catheter 1440. Additionally, the proximal and distal surfaces 1555, 1556 of the distal flag 1553 can interact with corresponding proximal and distal surfaces of the first and second windows 2040, 2050 for advancement or retraction of the implant 1500 relative to the catheter 1440 when the delivery wire 1600 is advanced or retracted relative to the catheter 1440. If the implant 1500 has sufficient pushing force to advance and / or retract through the catheter 1440 via only the connection between the proximal flag 1533 and the proximal coupler 1900, the implant 1500 may not have a strut 1550 extending distally and the delivery wire 1600 may not have a distal coupler 2000.

[0156] 15A-15E are diagrams illustrating delivery of an implant 1500 over a delivery wire 1600 and a catheter 1440 according to some embodiments of the disclosure. FIG. 15A illustrates the implant 1500 folded about the delivery wire 1600 within the lumen 1444 of the catheter 1440, with the distal flag 1550 inserted into the first and second windows 2040 and 2050 of the distal coupler 2000 and adjacent the exit port 1412 of the catheter 1440. This can be the relative positioning used during advancement of the implant delivery system 1400 to a desired implantation site within the subject 1. FIG. 15B illustrates the implant 1500 still folded about the delivery wire 1600, with a portion of the implant 1500 extending distally from the exit port 1412 of the distal end 1402 of the catheter 1140. Also shown is at least a portion of the delivery wire 1600 extending distally from the exit port 1412 of the catheter 1440, and the distal flag 1550 beginning to disengage from the distal coupler 2000. To achieve such partial extension and subsequent partial severing of the implant 1500 and delivery wire 1600, the delivery wire 1600 can be moved distally relative to the catheter 1440 and / or the catheter 1440 can be moved proximally relative to the delivery wire 1600. In some implementations, it is advantageous to simultaneously move the catheter 1440 proximally and the delivery wire 1600 distally during placement of the implant 1500. 15B, relative movement between the delivery wire 1600 and the catheter 1440 can either pull the implant 1500 back into the catheter 1440, completely reconnecting the distal flag 1550 and the distal coupler 2000, or continue as is and eventually disengage the flag 1550 from the distal coupler 2000, as shown in FIG. 15C. In other words, once the distal flag 1550 is fully extended distally from the exit port 1412 from within the lumen 1444 of the catheter 1440, the distal flag 1553 can be decoupled from the distal coupler 2000.15D illustrates the implant 1500 partially expanded with a portion of the implant 1500 extending distally from the exit port 1412 of the distal end 1402 of the catheter 1440. Also shown is at least a portion of the delivery wire 1600 extending distally from the exit port 1412 of the catheter 1440. To achieve such partial expansion of the implant 1500, the delivery wire 1600 can be moved distally relative to the catheter 1440 and / or the catheter 1440 can be moved proximally relative to the delivery wire 1600 than is shown in FIG. In the partially expanded state shown in FIG. 15D (which may also be referred to herein as a partially deployed state), relative movement between the delivery wire 1600 and the catheter 1440 can either pull the implant 1500 back into the catheter 1440 or continue, eventually completely releasing the implant 1500 from the exit port 1412 of the catheter 1440 and the delivery wire 1600, as shown in FIG. 15E. Such relative movement can be accomplished by a releasable connection between the proximal flag 1533 and the proximal coupler 1900, as described above. The implant delivery system 1400 can be configured such that the implant 1500 can be withdrawn within the lumen 1444 of the catheter 1440 (e.g., for adjustment of position or removal from the subject 1) while the coupler 1900 of the delivery wire 1600 remains within the lumen 1444 of the catheter 1440. In embodiments in which the implant 1500 does not have a distally extending strut 1550 with a distal flag 1553 and the delivery wire 1600 does not have a distal coupler 2000, the implant 1500 can be deployed from the catheter 1440 via interaction between the proximal flag 1533 and the proximal coupler 1900, as described above.

[0157] 16A-16D illustrate various implementations of radiopaque markers of an implant 1500 according to some aspects of the present disclosure. Each of FIGS. 16A-16D illustrates a proximal and / or distal end of an implant 1500 with a plurality of ring struts 1542 connecting at either one of a plurality of proximal apices 1543 or one of a plurality of distal apices 1544, respectively. FIG. 16A illustrates an implementation in which a proximal flag 1533 and / or a distal flag 1553 includes radiopaque material 1580 (e.g., within a portion of the flag), such proximal flag 1533 extending from a corresponding proximally extending strut 1530, or such distal flag 1553 extending from a corresponding distally extending strut 1550. FIG 16B illustrates an implementation in which the proximal flag 1533 and / or the distal flag 1553 are comprised of radiopaque material 1580 and such proximal flag 1533 extends from a corresponding proximally extending strut 1530 or such distal flag 1553 extends from a corresponding distally extending strut 1550. FIG 16C illustrates an implementation in which the proximally extending strut 1530 and / or the distally extending strut 1550 include islets of tissue 1583 incorporating radiopaque material 1580. FIG 16D illustrates an implementation in which the proximal radiopaque marker 1581 and / or the distal radiopaque marker 1582 include radiopaque material 1580.

[0158] 17A-17G illustrate a method of treating an aneurysm 7 of a blood vessel 5 according to some embodiments of the present disclosure. The method described with respect to FIG. 17A-17G is intended to be a general, non-limiting method for treating an aneurysm using any of the implant delivery systems and / or components thereof described herein, such as implant delivery system 1100, implant delivery system 1400, or variations thereof. FIG. 17A-17G illustrate a general progression of a method of deploying a coil 4000 as well as an implant 3100. FIG. 17A illustrates the use of a catheter 3000 to establish a pathway to the aneurysm 7. FIG. 17B illustrates the use of guidewires 3200, 4200 to help guide catheters 3440, 4440 for both the implant 3100 and the coil 4000, respectively, to the aneurysm 7 (although in some embodiments, the use of such guidewires may not be or may not be necessary). FIG. 17C illustrates the placement of the coil catheter 4440 within the aneurysm 7 to deliver the coil 4000 and the implant catheter 3440 within the vessel 5 adjacent the aneurysm 7 to place the implant 3100. FIG. 17D illustrates the catheters 3440, 4440 upon removal of the guidewires 3200, 4200. FIG. 17E illustrates the placement of the implant 3100 and coil 4000 from their respective catheters 3440, 4440. FIG. 17F illustrates the aneurysm 7 filled with the expanded implant 3100 and coil 4000 upon placement. FIG. 17G illustrates the filled aneurysm 7 after the catheters 3440, 4440 have been retracted and the implant 3100 has been implanted within the vessel 5 adjacent the aneurysm 7. 17H illustrates an alternative method in which the implant 3100 is first deployed within the blood vessel 5 adjacent the aneurysm 7, and the coil catheter 4440 extends through the implant 3100 and into the aneurysm 7 for deployment of the coil 4000. Such an alternative may advantageously facilitate retention of the coil 4000 within the aneurysm during and after deployment.

[0159] Alternatively or in addition, the catheter 4440 can release a two-stage in situ gel with a secondary chemical trigger to fill the aneurysmal sac or arteriovenous malformation. For example, the first stage consists of injecting a shear-thinning gel (e.g., Bingham plastic-like liquid, graft or copolymer with phenylboron groups for glucose interaction, polyvinyl alcohol (PVA), polyethyleneimine (PEI), gelatin, polyethylene glycol (PEG), polyalginate, hyaluronic acid, and glycosaminoglycans (GAGs), etc.) into the aneurysmal sac with or without a coil. The second stage may include crosslinking by injecting benign metabolic products (e.g., glucose, fructose, etc.) into the viscous gel precursor liquid. In some implementations, salt concentration, calcium ion concentration, ethanol, riboflavin, and other metabolic properties can be used instead of or in addition to glucose and / or fructose.

[0160] In some implementations, the catheter 4440 can release a two-stage in situ gel using a physical trigger to fill the aneurysmal sac or arteriovenous malformation. For example, the first stage consists of injecting a shear-thinning gel (e.g., Bingham plastic-like liquid, Pluronics, PNIPPAM plus Pluronics, etc.) into the aneurysmal sac with or without a coil. The second stage can include a physical crosslinking stage, such as by injecting a benign hot / cold saline into a viscous gel precursor liquid. Alternatively, body temperature is sufficient to crosslink the gel.

[0161] In some implementations, a two-stage in situ gel may be coated onto or incorporated into the aneurysm coil prior to deployment. The pre-coated coil may be deployed with liquids such as shear-thinning plastics including Bingham, Pluronic, PNIPPAM plus Pluronic, and other similar polymers or viscous gel precursor liquids, including grafts or copolymers containing phenylboron groups for glucose interaction, polyvinyl alcohol (PVA), polyethyleneimine (PEI), gelatin, polyethylene glycol (PEG), polyalginate, hyaluronic acid, glycosaminoglycans (GAGs). Secondary chemical or physical crosslinks may be induced as described elsewhere herein.

[0162] In some implementations, the implants described herein can be designed only to aid in the placement of the coil 4000 and can be removed after the coil 4000 has been filled into the aneurysm 7. Such implants can then optionally be replaced with permanent implants, which may be of a substantially similar or different design. Alternatively, as described herein, the implants can function as permanent implants that remain in place after the aneurysm 7 has been deployed and filled with the coil 4000.

[0163] In some implementations, particularly for the treatment of ICAS, the implants described herein can be deployed within a blood vessel to cover plaque within the vessel.

[0164] 18A-18B are diagrams illustrating an introducer sheath 5000 according to some embodiments of the present disclosure. FIG. 18A is a side view of introducer sheath 5000, and FIG. 18B is an associated cross-sectional side view. The introducer sheath 5000 can be configured to facilitate insertion of an implant as described herein, such as implant 100, 400, 500, or 1500, in a collapsed state about a delivery wire as described herein, such as delivery wire 600 or 1600, through a proximal end of a catheter as described herein, such as catheter 1140 or 1440, and / or through a proximal end of a hemostatic valve attached to the proximal end of a catheter as described herein. 18A-18B, the introducer sheath 5000 can have a generally tubular body 5006 having a proximal end 5001, a distal end 5002, a length 5009, and a longitudinal axis 5003 extending between the proximal end 5001 and the distal end 5002, and an inner diameter 5005 defining a lumen 5004. The introducer sheath 5000 can include one or more substantially constant diameter sections and one or more tapered sections to produce an introducer sheath 5000 having a larger outer diameter at its proximal end 5001 than at its distal end 5002. For example, and as shown in Figures 18A-18B, the introducer sheath 5000 can include a first constant diameter portion 5010 having an outer diameter 5011 and a length 5012, a first tapered portion 5020 having a length 5022, a second constant diameter portion 5030 having an outer diameter 5031 and a length 5032, a second tapered portion 5040 having a length 5042, and a third constant diameter portion 5050 having an outer diameter 5051 and a length 5052. As shown, a first constant diameter section 5010 can extend distally from a proximal end 5001 of the introducer sheath 5000, a first tapered section 5020 can extend distally from the first constant diameter section 5010, a second constant diameter section 5030 can extend distally from the first tapered section 5020, a second tapered section 5040 can extend distally from the second constant diameter section 5030, and a third constant diameter section 5050 can extend distally from the second tapered section 5040 and terminate at the distal end 5002 of the introducer sheath 5000. In some implementations, the distal end 5002 of the introducer sheath 5000 is rounded to facilitate engagement with, for example, a hemostasis valve or a catheter.The introducer sheath 5000 can include a jacket 5007 and a liner 5008 disposed within the jacket along at least a portion of its length. For example, the liner 5008 can extend distally from the proximal end 5002 along at least a portion of the jacket 5007 (e.g., from the proximal end 5002 to at least a portion of the second constant diameter section 5030). The jacket 5007 can include Grilamid TR55LX. The liner 5008 can include, for example, extruded or dip coated PTFE. When assembled, the liner 5008 and jacket 5007 can produce an introducer sheath 5000 having a substantially constant inner diameter 5005 of the lumen 5004, as shown. The inner diameter 5005 of the lumen 5004 can be configured to receive an implant folded over a delivery wire therethrough and maintain the implant folded over the delivery wire while both are disposed within and / or moved through the introducer sheath 5000. In some implementations, the inner diameter 5005 can be between about 0.200 mm and about 0.600 mm, for example, about 0.427 mm.

[0165] The introducer sheath 5000 can have a length 5009 of at least about 250 mm. In some implementations, the introducer sheath 5000 has a length 5009 of about 500.126 mm. In such implementations, the length 5012 of the first constant diameter section 5010 can be about 492.100 mm, the length 5022 of the first tapered section 5020 can be about 1.727 mm, the length 5032 of the second constant diameter section 5030 can be about 2.921 mm, the length 5042 of the second tapered section 5040 can be about 2.057 mm, and the length 5052 of the third constant diameter section 5050 can be about 1.321 mm. The introducer sheath 5000 can have a maximum outer diameter of about 3 mm or less. In some implementations, the introducer sheath 5000 has a maximum outer diameter of about 1.346 mm. In such implementations, the outer diameter 5011 of the first constant diameter section 5010 can be approximately 1.346 mm, the outer diameter 5031 of the second constant diameter section 5030 can be approximately 0.787 mm, and the outer diameter 5051 of the third constant diameter section 5050 can be approximately 0.597 mm. Further, in such implementations, the first tapered section 5020 can taper over its length 5022 from the first constant diameter section outer diameter 5011 to the second constant diameter section outer diameter 5031, and the second tapered section 5040 can taper over its length 5042 from the second constant diameter section outer diameter 5031 to the third constant diameter section outer diameter 5051. Considering the substantially constant inner diameter 5005 of the introducer sheath 5000, further in such an implementation, the thickness 5013 (e.g., wall thickness) of the first constant diameter portion 5010 may be approximately 0.460 mm (which may include the jacket 5007 and the liner 5008), the thickness 5033 of the second constant diameter portion 5030 may be approximately 0.175 mm (which may include the jacket 5007 and the liner 5008), and the thickness 5053 of the third constant diameter portion 5050 may be approximately 0.838 mm.Although exemplary lengths and diameters of the introducer sheath 5000 and its constant diameter and tapered sections 5010, 5020, 5030, 5040, and 5050 are provided, any of such lengths and / or diameters may be less than or greater than those given and / or such lengths and / or diameters may expand as the length and / or diameter of the introducer sheath decreases or increases.

[0166] In a preferred method of use, the implant 100 can be folded over the delivery wire 600 (e.g., with one or more slots 931 of the hub 930 of the coupler 900 of the delivery wire 600 receiving the neck portions 126 of one or more proximally extending struts 125 of the implant 100) as described herein and positioned within the lumen 5004 of the introducer sheath 5000 such that the implant 100 remains in the folded state. This can be, for example, the shipping configuration of the delivery wire 600, implant 100, and introducer sheath 5000. To introduce the delivery wire 600 with the implant 100 folded therearound into the catheter 1140, the introducer sheath 5000 can be partially inserted into the proximal end of a hemostatic valve attached to the proximal end 1101 of the catheter 1140. The hemostatic valve can then be tightened and the system flushed through the hemostatic valve (e.g., until fluid exits the proximal end 5001 of the introducer sheath 5000). The hemostatic valve can then be loosened and the introducer sheath 5000 can be advanced further distally until the distal end 5002 seats on the hub 1120 of the catheter 1140. The hemostatic valve can then be tightened again to lock the introducer sheath 5000 in place relative to the catheter 1140. The delivery wire 600 with the implant 100 collapsed around it can then be advanced distally until the entire implant 100 is within the catheter 1140. The delivery wire 600 can be advanced distally until the distal-most marker 780 of the core wire 700 of the delivery wire 600 is adjacent the proximal end 5001 of the introducer sheath 5000. The introducer sheath 5000 can then be removed by loosening the hemostatic valve, pinning the delivery wire 600, and pulling the introducer sheath 5000 proximally over the delivery wire 600. The delivery wire 600 can be advanced until the same distal-most marker 780 is adjacent the proximal end of the hemostatic valve. The position of the implant 100 within the catheter 1140 can be adjusted under radiographic and / or fluoroscopic guidance by moving the delivery wire 600 and catheter 1140 relative to one another, preferably as described herein, deployed within subject 1.

[0167] Although the implants, devices, systems, and methods disclosed herein have been described with respect to treating aneurysms, such as neurovascular aneurysms, and / or treating intracranial arterial stenosis in a patient, such disclosure is non-limiting. The implants, devices, systems, and methods disclosed herein can be used to treat other conditions in a patient and / or to stent any blood vessel in a patient. For example, the implants, devices, systems, and methods disclosed herein can be utilized and / or adapted to any situation in which it is desirable to implant a stent implant having thrombophilic properties. As another example, the implants, devices, systems, and methods disclosed herein can be utilized and / or adapted to any situation in which it is desirable to precisely position the implant at the implantation site. As another example, the implants, devices, systems, and methods disclosed herein can be utilized and / or adapted to any situation in which it is desirable to adjust the position of the implant after it has been partially positioned in the blood vessel.

[0168] It is understood that features, materials, properties, or groups described in connection with a particular aspect, implementation, or example are applicable to other aspects, implementations, or examples described herein, except where inconsistent therewith. All of the features disclosed in this specification (including the accompanying claims, abstract, and drawings), or all of the steps of the methods or processes so disclosed, may be combined in any combination, except combinations in which at least some of such features or steps are mutually exclusive. Protection is not limited to the details of the foregoing implementations. Protection extends to novel or novel combinations of features disclosed in this specification (including the accompanying claims, abstract, and drawings), or novel or novel combinations of steps of the methods or processes so disclosed.

[0169] Although specific implementations have been described, these implementations are presented as examples only and are not intended to limit the scope of protection. Indeed, the novel methods and systems described herein may be embodied in a variety of other forms. Furthermore, various omissions, substitutions, and changes in the form of the methods and systems described herein may be made. Those skilled in the art will appreciate that in some implementations, the steps actually taken in the illustrated or disclosed processes may differ from those illustrated. In some implementations, some of the steps described above may be omitted, and other steps may be added. For example, the steps or order of steps actually taken in the disclosed steps may differ from those illustrated. In some implementations, some of the steps described above may be omitted, and other steps may be added. Furthermore, the features and attributes of the specific implementations disclosed above may be combined in different ways to form additional implementations, all of which are within the scope of the present disclosure.

[0170] Although the present disclosure includes specific implementations, examples, and applications, those skilled in the art will appreciate that the present disclosure extends to other alternative implementations or applications beyond the specifically disclosed implementations, including implementations that do not provide all of the features and advantages set forth herein, and obvious modifications and equivalents thereof. Thus, the scope of the present disclosure is not intended to be limited by the implementations described, but may be defined by the claims presented herein or presented in the future.

[0171] Conditional language such as "can," "could," "might," or "may," unless specifically stated otherwise or understood otherwise within the context in which it is used, is generally intended to convey that a particular implementation includes a particular feature, element, or step, and that other implementations do not include the particular feature, element, or step. Thus, such conditional language is not generally intended to imply that a feature, element, or step is somehow required for one or more implementations, or that one or more implementations necessarily include logic for determining, with or without user input or prompting, whether those features, elements, or steps are included in or performed in any particular implementation. Terms such as "comprising," "including," "having," and the like, are synonymous and are used in an inclusive, open-ended manner and do not exclude additional elements, features, acts, operations, etc. Additionally, the term "or" is used in an inclusive (and not exclusive) sense, so that, for example, when used to connect a list of elements, the term "or" may mean one, some, or all of the elements in the list. Similarly, the term "and / or" in reference to a list of two or more items covers all interpretations of this word: any one of the items in the list, all of the items in the list, and any combination of the items in the list. Furthermore, as used herein, the term "each" can refer to any subset of the set of elements to which the term "each" applies, in addition to its ordinary meaning. Furthermore, the words "herein," "above," "below," and words of similar import, when used in this application, refer to this application as a whole and not to particular portions of this application.

[0172] Conjunctive expressions such as "at least one of X, Y, and Z" are to be understood in context as being commonly used to convey that an item, term, etc. may be either X, Y, or Z, unless otherwise noted. Thus, such conjunctive expressions do not generally imply that a particular implementation requires the presence of at least one of X, at least one of Y, and at least one of Z.

[0173] Language of degree used herein, such as the terms "approximately," "about," "generally," and "substantially," refers to a value, amount, or characteristic that is close to a stated value, amount, or characteristic that performs a desired function or achieves a desired result. For example, the terms "approximately," "about," "generally," and "substantially" can refer to an amount that is within less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of a stated amount. As another example, in certain implementations, the terms "generally parallel" and "substantially parallel" refer to a value, amount, or characteristic that deviates from perfect parallelism by 15 degrees or less, 10 degrees or less, 5 degrees or less, 3 degrees or less, 1 degree or less, or 0.1 degrees or less.

Claims

1. 1. A self-expanding, thrombophilic intraluminal implant, said implant comprising a generally tubular frame; The tubular frame is a proximal portion comprising a ring extending around the circumference of the tubular frame, the ring comprising a plurality of ring struts, adjacent pairs of the ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern; a distal portion comprising a ring extending around the circumference of the tubular frame, the ring comprising a plurality of ring struts, adjacent pairs of the ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern; a central portion between the proximal and distal portions, The central portion is a plurality of longitudinally spaced rings extending around the circumference of the tubular frame, each ring having a plurality of ring struts, adjacent pairs of the ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern; a plurality of connecting struts extending at least partially around the circumference of the tubular frame, each connecting strut of the plurality of connecting struts connecting a distal apex of one ring of the plurality of rings to a proximal apex of an adjacent ring of the plurality of rings; Intraluminal implants.

2. each connecting strut of the plurality of connecting struts connects each one of the distal apexes of one ring of the plurality of rings of the central portion to each one of the proximal apexes of an adjacent ring of the plurality of rings of the central portion, except for each one of the distal apexes of the most distal ring of the central portion and each one of the proximal apexes of the most proximal ring of the central portion, such that the central portion does not have a free apex; The intraluminal implant of claim 1 .

3. a distal apex of each of the plurality of distal apexes of the distal-most ring of the central portion connects to a proximal apex of each of the plurality of proximal apexes of the ring of the distal portion, and a proximal apex of each of the plurality of proximal apexes of the proximal-most ring of the central portion connects to a distal apex of each of the plurality of distal apexes of the ring of the proximal portion. The intraluminal implant of claim 2 .

4. a distal apex of each of the plurality of distal apexes of one ring of the plurality of rings of the central portion is rotationally offset from a proximal apex of each of the plurality of proximal apexes of an adjacent ring of the plurality of rings of the central portion such that at least a portion of each linking strut of the plurality of linking struts extends along an at least partially helical path around the circumference of the tubular frame; The intraluminal implant of claim 1 .

5. at least a portion of each connecting strut of the plurality of connecting struts connecting a distal apex of the plurality of distal apexes of one ring of the plurality of rings in the central portion to a proximal apex of the plurality of proximal apexes of an adjacent ring of the plurality of rings in the central portion extends along a helical path in a first helical direction at least partially around the circumference of the tubular frame; Each distal apex of the plurality of distal apexes of an adjacent ring of the plurality of rings in the central portion is connected to each proximal apex of a plurality of proximal apexes of another adjacent ring of the plurality of rings in the central portion. at least a portion of each of the plurality of connecting struts connecting the tubular frame to the portion extends at least partially around the circumference of the tubular frame along the helical path in a second helical direction generally opposite to the first helical direction; The intraluminal implant of claim 4.

6. one or more struts extending generally proximally from one or more proximal apexes of each of the plurality of proximal apexes of the ring of the proximal portion, each of the one or more generally proximally extending struts including a neck portion and a connecting portion, the connecting portion configured to connect to a radiopaque marker; one or more radiopaque markers configured to connect to the one or more generally proximally extending struts at the connection portion. The intraluminal implant of claim 1 .

7. one or more struts extending generally distally from one or more distal apexes of each of the plurality of distal apexes of the ring of the distal portion, each of the one or more generally distally extending struts including a neck portion and a connecting portion, the connecting portion configured to connect to a radiopaque marker; one or more radiopaque markers configured to connect to the one or more generally distally extending struts at the connection portion. The intraluminal implant of claim 1 .

8. the proximal portion flaring radially outward in a proximal direction and / or the distal portion flaring radially outward in a distal direction; The intraluminal implant of claim 1 .

9. The plurality of connecting struts do not overlap each other. The intraluminal implant of claim 1 .

10. the intraluminal implant is configured such that a malapposition between the intraluminal implant and the inner wall of a blood vessel is less likely when the intraluminal implant is disposed on the inside of a bend in the blood vessel than when the intraluminal implant is disposed on the outside of a bend in the blood vessel. The intraluminal implant of claim 1 .

11. The implant does not include a graft, covering, or liner. The intraluminal implant of claim 1 .

12. further comprising a heparin coating; The intraluminal implant of claim 1 .

13. 1. A self-expanding, thrombophilic intraluminal implant comprising: the implant comprises a generally tubular frame; The tubular frame is a plurality of longitudinally spaced rings extending around the circumference of the tubular frame, each ring having a plurality of ring struts, adjacent pairs of the ring struts joining at a plurality of proximal apices and a plurality of distal apices to form a chevron pattern; a plurality of connecting struts extending at least partially around the circumference of the tubular frame, each connecting strut of the plurality of connecting struts connecting a distal apex of one ring of the plurality of rings to a proximal apex of an adjacent ring of the plurality of rings; the tubular frame has a wall thickness of about 45 μm or less; the implant comprises a heparin coating. Self-expanding thrombophilic intraluminal implant.

14. the heparin coating has a thickness of about 30 nm or less; The intraluminal implant of claim 13

15. the heparin coating has a mass of about 1.0 μg or less; The intraluminal implant of claim 13.

16. The ratio of the mass of the heparin coating to the total surface area of ​​the implant is about 0.007 μg / mm ２ That's all. The intraluminal implant of claim 13.

17. the ratio of the thickness of the heparin coating to the wall thickness of the tubular frame is greater than or equal to about 0.00016; The intraluminal implant of claim 13.

18. The particle size corresponding to the entire heparin coating is about 101 μm or less in diameter. The intraluminal implant of claim 13.

19. The ratio of heparin activity of the heparin coating to the wall thickness of the tubular frame is about 0.30 pmol AT / cm ２ / μm or more, The intraluminal implant of claim 13.

20. The implant does not include a graft, covering, or liner. The intraluminal implant of claim 13.

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