WO2007095233A2 - Thin film metal alloy covered stent - Google Patents

Thin film metal alloy covered stent

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Publication number
WO2007095233A2
WO2007095233A2 PCT/US2007/003792 US2007003792W WO2007095233A2 WO 2007095233 A2 WO2007095233 A2 WO 2007095233A2 US 2007003792 W US2007003792 W US 2007003792W WO 2007095233 A2 WO2007095233 A2 WO 2007095233A2
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WO
Grant status
Application
Patent type
Prior art keywords
stent
thin
film
sheet
nitinol
Prior art date
Application number
PCT/US2007/003792
Other languages
French (fr)
Other versions
WO2007095233A3 (en )
Inventor
Daniel Steven Levi
Gregory P. Carman
Original Assignee
The Regents Of The University Of California
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/92Stents in the form of a rolled-up sheet expanding after insertion into the vessel, e.g. with a spiral shape in cross-section
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, E.G. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0014Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof using shape memory or superelastic materials, e.g. nitinol

Abstract

A stent has a structure including a generally rectangular thin film sheet of shape memory alloy wrapped into a generally tubular shape.

Description

THIN FILM METAL ALLOY COVERED STENT

BACKGROUND

[0001] The present invention relates to an implantable medical device for treating diseases and disorders of blood vessels.

[0002] Although traditional stents consist of non-occlusive metal scaffolds, the treatment of many disease processes relies on the ability to use a "covered stent." These stents are able to both open vessels and provide a circumferentially occlusive boundary between the stent and the vessel. Thus, covered stents are ideal for re- establishing the integrity of aneurysmal vessels at risk for rupturing or for minimizing the risk of in-stent stenosis (1-3). The potential applications of such covered stents are wide-ranging and include the treatment of carotid and coronary artery disease, aortic and central nervous system vascular aneurysms, carotid artery or pulmonary artery stenoses, carotid artery atheromas, and even treatment of ruptured vessels (1-7). In the palliation of congenital heart disease, the appropriate covered stent would be of tremendous value in stenting the ductus arteriosus, coarctation of the aorta, or potentially in the treatment of pulmonary artery stenoses and in the stenting of pulmonary veins, an intervention often plagued by in-stent stenosis. Various materials have been used to cover stents, including silicone, polyurethane, and polytetrafluoroethylene (1-2,8). Examples of commercially available covered stents include the polytetrafluoroethylene (PTFE) covered JoStent made by JoMed and the CP covered stent that is available from NuMed. There are self-expanding covered stents intended for the treatment of abdominal aortic aneurysms. U.S. Patent No. 6,533,905 presents stents that include nitinol. However, to date, the production of a highly flexible, durable, and thrombus-resistant stent material has not been achieved for all applications. Furthermore, prior art covered stents generally have a thick covering, making the profile of the stent unacceptably large for certain applications, such as implantation in small blood vessels. Therefore, there is a need for covered stents which are highly flexible, durable, and thrombus-resistant and have small profiles. SUMMARY OF THE INVENTION

[0003] In an embodiment of the invention, the stent includes a structure that includes a generally rectangular thin film sheet of shape memory alloy wrapped into a generally tubular shape. The sheet can have two distal edges of the sheet that define two ends of the tubular shape. The sheet can have two longitudinal edges that overlap when wrapped. The structure can have a compacted form with a first diameter and a deployed form with a second diameter larger than the first diameter. The thin film sheet can be nonperforated, have a tubular support, or both. The compacted form can be, for example, a folded configuration, a spiral, a star spiral, a twisted star spiral, a keyed wheel spiral, an inner loop tab-and-slot, or an outer loop tab-and-slot. In an embodiment, the generally rectangular thin film sheet of shape memory alloy can have a slot.

[0004] In an embodiment of the invention, the stent can include a tubular support for the thin film sheet. The sheet can be perforated or nonperforated. The tubular support can have an outer surface and can have a hollow inside. The thin film sheet can be wrapped around the outer surface or wrapped within the hollow inside of the tubular support. In an embodiment, a first thin film sheet can be wrapped around the outer surface, and a second thin film sheet can be wrapped within the hollow inside of the tubular support. The first thin film sheet and the second thin film sheet can be bonded to each other and can enclose the tubular support.

[0005] In an embodiment of the invention, a stent can be formed by wrapping a nonperforated, thin film sheet of shape memory alloy into a generally tubular shape and forming the tubular shape into a compacted form. The wrapping can include coiling the sheet into a spiral. The thin film sheet can be produced by sputtering, for example, by sputtering from a heated target. The thin film can be shaped by photolithography and etching. For example, photolithography and etching can be used to form a tab proximal to a first longitudinal edge and to form a slot proximal to a second longitudinal edge.

[0006] In an embodiment of the invention, the stent can be inserted in a compacted form into a body cavity, such as a blood vessel, and the stent can be allowed to expand to its deployed form. The stent can be inserted in its compacted form through or on a catheter into the body cavity. In an embodiment, the stent can be expanded to its deployed form without the application of extrinsic force. For example, the stent's expansion can be driven by a phase change of or by super- elasticity of the shape memory alloy. In another embodiment, the stent can be expanded to its deployed form with the application of extrinsic force. For example, the extrinsic force can be provided by a balloon and the shape memory alloy can exhibit detwinning behavior.

[0007] In an embodiment of the invention, the stent includes a structure that includes an endless loop of shape memory alloy having a generally tubular shape. The structure can have a compacted form with a first diameter and a deployed form with a second diameter larger than the first diameter. The compacted form can be, for example, a star, twisted star, or keyed wheel. The deployed form can be, for example, a tube, e.g., an elliptical tube or a spiral having a generally tubular shape.

BRIEF DESCRIPTION OF THE FIGURES

[0008] Figure 1 shows a tubular structure formed as a spiral from a sheet having ends.

[0009] Figure 2 shows a tubular structure having a belt cover design (inside roll).

[0010] Figure 3 shows a tubular structure having a belt cover design (outside roll).

[0011] Figure 4 shows an end-on view of a tubular structure having the compacted form of a star.

[0012] Figure 5 shows an end-on view of a tubular structure having the compacted form of a twisted star.

[0013] Figure 6 shows a perspective view of a tubular structure.

[0014] Figure 7 shows an end-on view of a tubular structure having the compacted form of a keyed wheel.

[0015] Figure 8 presents a graph of a stress-strain curve of a thin film of nitinol similar to that used for stent covering.

[0016] Figure 9 presents a graph of a curve from differential scanning calorimetry of thin film nitinol.

[0017] Figure 1OA shows apβn self-expanding stent spiral wrapped with a nitinol sheet with the assembly placed inside a 10 mm tube.

[0018] Figure 1OB shows a.pβn self-expanding stent spiral wrapped with a nitinol sheet with the assembly placed inside a 10 mm tube.

[0019] Figure 1 IA shows a mesh stent sandwiched between an inner spiral nitinol sheet and an outer spiral nitinol sheet. [0020] Figure HB shows a mesh stent sandwiched between an inner spiral nitinol sheet and an outer spiral nitinol sheet.

[0021] Figure 11C shows a mesh stent sandwiched between an inner spiral nitinol sheet and an outer spiral nitinol sheet.

[0022] Figure 12 shows a Palmaz Genesis balloon expandable stent spiral wrapped with a nitinol sheet inside an opened swine descending aorta.

[0023] Figure 13A shows apfin self-expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine descending aorta.

[0024] Figure 13B shows apfin self-expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine descending aorta.

[0025] Figure 14 shows apfin self-expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine superior vena cava.

[0026] Figure 15 shows apfin self-expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine inferior vena cava.

[0027] Figure 16 shows a PFM self-expanding stent covered with a nitinol sheet of the inside roll tab-and-slot design inside an opened swine descending aorta. Neointimal proliferation is observed in uncovered stent portions. Uncovered portions were adherent to the vessel wall; covered portions were not adherent to the vessel wall.

[0028] . Figure 17 shows an angiogram of stents covered with a spiral wrapped nitinol sheet implanted in the swine arterial and venous circulation. Contrast has been injected into the superior vena cava, significant neointimal hyperplasia is evident. Covered stents are also observed in the swine descending aorta. An uncovered stent is also present as a control.

[0029] Figure 18A shows an image of a vessel wall treated by hematoxylin and eosin staining which previously contained uncovered stent portions. Significant neointimal hypeφlasia and endothelial injury is noted in vessels previously housing uncovered stent portions.

{0030] Figure 18B shows an image of a vessel wall treated by hematoxylin and eosin staining which previously contained covered stent portions.

DETAILED DESCRIPTION

[0031] Embodiments of the invention are discussed in detail below. In describing embodiments, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected. A person skilled in the relevant art will recognize that other equivalent components can be employed and other methods developed without parting from the spirit and scope of the invention. AU references cited herein are incorporated by reference as if each had been individually incorporated.

[0032] Material used in a stent must meet a number of criteria. Materials must not cause an excessive inflammatory response, must not be toxic to the body and should not cause clotting in the blood stream. For example, nickel-titanium alloys (NiTi or nitinol) can be used in stents and for covering stents. NiTi is a well-known biocompatible material (9-10) used in many implantable medical devices, including stents and atrial septal defect occlusion devices. NiTi is biologically inert in physiological solutions, a titanium oxide layer forms on the metal's surface which prevents corrosion of the bulk material (9-11, 21-24). Furthermore, nitinol is resistant to thrombus formation and does not calcify (12-13). When implanted within blood vessels and within the heart itself, NiTi has proven to be nontoxic, biocompatible, and non-thrombogenic.

[0033] The thin films that can be used to cover stents in accordance with the present invention may be made from thin films of metal alloys that are phase transforming and/or exhibit twin boundary motion. For example, NiTi and other similar metal alloys exhibit a thermally induced crystalline transformation between a ductile martensite phase at low temperatures and a rigid austenite phase at high temperatures. NiTi exhibits both shape-memory and super-elastic properties. These metal alloys are referred to herein as thin-film memory or shape memory metal alloys. Upon cooling below the martensite temperature, unstrained NiTi has a twinned martensite structure. When placed under stress, the twin orientation is reorganized along the direction of stress. When heated above the austenite temperature, the material regains its rigid highly-ordered austenite phase and recovers the original shape in which it was crystallized. In the low temperature martensite phase, nitinol is exceedingly malleable and can be compressed into catheters. Upon heating (in many cases simply to body temperature), nitinol transforms into its austenite parent phase and recovers from the deformation induced in the martensite state. Thus, stents with a cover made from thin film NiTi (or other similar metal alloy) and stents only made of thin film NiTi can make use of these shape memory properties. However, this does not preclude the use of purely martensite NiTi or possible other acceptable shape memory or psuedoelastic material.

[0034] Alternatively, a stent can be designed which does not require the phase transformation, but rather solely relies on the malleability of the nitinol. In other words, the stent would produce the restoring deformation. The nitinol film can be in its martensitic state and rely solely on twin boundary motion.

[0035] Exemplary thin-film memory metal alloys useful in any embodiment of the invention include the nickel-titanium alloys (NiTi), as well as alloys having the desired properties selected from the following: nickel-titanium-copper alloys (NiTiCu) and other copper-based alloys; gold-cadmium and other cadmium-based alloys (AuCd); nickel-titanium-platinum (NiTiPt) and other platinum-based alloys; nickel-titanium-palladium (NiTiPd) and other palladium-based alloys; nickel- titanium-hafnium (NiTiHf) and other hafnium-based alloys; and nickel-magnesium- gallium alloys (NiMgGa)5 nickel-manganese-gallium alloys (NiMnGa) and other gallium-based alloys.

[0036] These thin film metal alloys may be produced with various percentages of the constituent elements. For example, nickel-titanium alloys, such as nitinol, that contain about 50 atom percent nickel and about 50 atom percent titanium can be used. As another example, NiTi alloys that include from about 45 to about 55 atom percent nickel and from about 45 to about 55 atom percent titanium can be used. Nickel- titanium alloys with other atom percentages can also be used.

[0037] Although fabrication of thin film nitinol (about 8 microns in thickness) has been attempted since the early 1990's using flash and vacuum evaporation, ion beam sputtering, and laser ablation, most of these fabrication methods have been unsuccessful in producing high quality uniform film required for medical applications (14-17). DC magnetron sputter deposition under ultra-high vacuum is a preferred method for the production of medical quality thin film nitinol as it allows for high levels of process controllability and "batch-to-batch" consistency (18). In brief, sputter deposition involves ejecting atoms from a target material and directing them to form a thin film on a substrate. Target heating during sputtering creates films of uniform thickness and composition not achieved with conventional sputtering processes (19-20). This allows for precise process control of film composition. For example, a film having a compositional variation of no more than about 1 atom percent can be produced. For example, the target can be heated to a temperature of from about 200 0C to about 800 0C. The target can be heated to a temperature of from about 400 0C to about 700 0C. The target can be heated to a temperature of from about 550 0C to about 650 0C. The effects of target composition and annealing temperatures on thin film nitinol transition temperatures are described in several documents (19-20). A hot target sputtering method (19) was used to produce thin films used in studies described in this application.

[0038] For example, hot target sputtering was carried out as follows. A residual gas analyzer (Stanford Research Systems, Sunnyvale, CA) was used to monitor residual gas contamination levels prior to sputtering. Residual gases can deplete the amount of titanium reaching the substrate. The combined pressure of water, carbon dioxide, and carbon monoxide gases were maintained below 10"9 Torr during sputtering. An argon scrubber further cleaned the argon to 99.999% purity as required for the sputtering process. Sputtering of thin film nitinol onto a silicon wafer with 500 nm thick wet thermal oxide was accomplished with a 3-inch DC magnetron gun (MeiVac. Inc. San Jose, CA). One of the targets consisted of bulk nitinol cut from a three inch boule of nitinol containing 48% nickel and 52% titanium (SCI Engineering, Columbus, OH). All films were deposited at base pressures below 5x10" Torr. The substrate-to-target distance was 4 cm and a sputtering power of 300 Watts was used. During deposition the substrate was translated back and forth in relation to the target at 45° arcs with 80 mm length to minimize compositional variation. The deposited amorphous film was crystallized by heating to 500 degrees Celsius for 120 minutes prior to removal from the sputtering system.

[0039] The thin memory metal alloy films can be manufactured with thicknesses of from about 0.1 to about 30 microns. For example, the thin films can have a thickness ranging from about 0.1, 1, 2, 4, 5, 10, 15, 20, or 25 microns to about 4, 5, 10, 15, 20, 25, or 30 microns. For example, the thin films can have a thickness of from about 4 microns to about 10 microns.

[0040] Thus, covering stents with the thin memory metal films described in this application will cause a minimal and inconsequential increase in the size of the device. For example, thin film NiTi can be manufactured in films of 5-8 micron thickness, so that covering a stent with thin film NiTi adds very little bulk to the devices. For children, for neurointerventional applications, and for coronary applications, it is essential that covered stents maintain a very low profile. Many applications require that stents can be delivered through very small catheters even after covering them. f

[0041] Thin memory metal alloy films can be produced in a range of shapes and sizes. For example, thin memory metal alloy films can be made square or rectangular. Each dimension of such a square or rectangle can be selected from a wide range, for example, from about 0.1 mm to about 100 mm, from about 0.5 mm to about 25 mm, or from about 3 mm to about 20 mm.

[0042] Thin memory metal alloy films can be made in a wide variety of shapes other than square or rectangular. For example, thin memory metal alloy films may be made to resemble other polygons, circles, ovals, crescents, or an arbitrary shape.

[0043] A generally tubular shape can be other than a perfectly cylindrical shape. That is, a generally tubular shape can be distorted somewhat from a cylindrical shape. In a generally tubular shape, the inside is hollow, so that, for example, a fluid can travel into the shape through one distal end, through the shape (along the central axis), and out of the other distal end of the shape.

[0044] A spiral can be formed by curling a sheet, so that if the sheet is traced from one end, a path around a central axis is followed. As the path goes around the central axis, the path generally moves either continuously inward toward the central axis or continuously outward away from the central axis. The path may have excursions from such continuously inward or continuously outward movement.

[0045] A broken ring is similar to a spiral, except that there is no overlap, i.e., the winding number is 1 or less. That is, a broken ring can have the ends just touching, or can have the ends separated.

[0046] A star is a shape resembling a concave simple polygon, which if a path is traced around its perimeter, the path segments alternate between moving generally, not necessarily directly, toward the centroid of the polygon and moving generally, not necessarily directly, away from the centroid of the polygon. Pentagrams, hexagrams, and heptagrams are examples of stars. A pair of path segments, the first one of which moves generally away from the centroid of the polygon and the other of which moves generally toward the centroid of the polygon can be termed radiant regions. Between two radiant regions may be a path segment which stays at a constant distance (or moves toward or away from the centroid). Thus, for example, the star may resemble a disk with radiant regions jutting away from the center of the disk. A twisted star can have a pair of line segments bounding a radiant region curved clockwise or counterclockwise.

[0047] A keyed wheel can have the general form of a circle from which keystone shaped regions jut away from the center.

[0048] Compacted can mean that an object, for example, a sheet, is temporarily shaped so that at least one dimension of the object is smaller than in the deployed form of the object.

[0049] For children or adults, requiring neurointerventional applications and for coronary applications, it is essential that covered stets maintain a very low profile. Many application require that the stents be delivered through very small catheters even after they are covered. The use of thin film metal alloy to cover stents in accordance with the present invention allows for the construction of very low profile covered stents for use in the treatment of congenital heart disease (including percutaneous treatment of aortic coarctations and pulmonary artery stenoses at risk for rupture), coronary disease, coronary artery disease, carotid artery disease, treatment of coronary blood vessels including, for example, the aorta, superior vena cava, inferior vena cava, pulmonary artery, and pulmonary vein, aneurysms of the central nervous system vasculature, brain vessel aneurysms, percutaneous Fontan Conduit, carotid artery atheromas and, aortic aneurysms.

[0050] Thin films of metal alloys having shape-memory properties, for example, shape-memory properties associated with a phase change, super-elastic properties, or detwinning properties can be anchored to a stent, for example, to a self- expanding or a balloon inflatable stent, to form a covered stent. In one embodiment, an appropriately sized, rectangular thin film of thin film memory metal alloy is trained to be flat and then is anchored on one side of the stent by laser welding, mechanical clamping (that is, by use of a mechanical clamp), atomic bonding, or another acceptable bonding technique. The remaining length of the rectangular thin film nitinol is wrapped circumferentially around the stent or folded in an accordion fashion. In an embodiment, the thin film memory metal can be woven through the lumen of the stent. For example, the thin film memory metal can be woven through holes, spokes, or mesh in the wall of a conventional stent. Woven can mean that the thin film passes through an opening in the conventional stent from outside of the conventional stent to the inside of the conventional stent, and then the thin film passes through a second opening in the conventional stent from the inside of the conventional stent to the outside of the conventional stent.

[0051] In other words, either shape-memory or super-elastic NiTi thin film can be anchored to, for example, a self-expanding or balloon inflatable stent to form a covered stent. Appropriately sized, rectangular thin film nitinol can be trained to be flat and then can be anchored on one side by laser welding or mechanical means to a stent. The remaining length of the rectangular thin film nitinol can be wrapped circumferentially around the stent. The composite apparatus, the stent with the thin film wrapped tightly around it, can then be advanced into a catheter. When the apparatus is advanced into position within the body, the thin film NiTi covering the stent can unravel as it was trained to do and the stent can then be expanded without damaging the tightly wrapped thin film NiTi.

[00521 A mesh stent is formed of a lattice of wires, struts, or a scaffold of metal or other material.

[0053] For some applications, a supporting stent may not be required and the thin film memory metal alone, after being appropriately compacted, can be used as a stent.

[0054] The composite apparatus (the stent with the thin film wrapped around it) can then be advanced into a catheter. When the apparatus is advanced into position within the body, the thin film memory metal covering the stent unravels as it is trained to do (as it is heated or as it simply uses twin boundary motion forced by the stent) and the stent can then be expanded without damaging the tightly wrapped thin film of memory metal.

[0055] The thin film can be nonperforated. For example, the thin film can be solid, without holes, pores, or open slots. The thin film can be impermeable to body tissue and fluids. The tab-and-slot embodiment described herein can be nonperforated, meaning that other than the tab-constraining slot, there are no perforations. Alternatively, the thin film can be perforated as appropriate for particular applications.

[0056] Standard photolithography and etching techniques can be used to generate precise two-dimensional shapes required to produce thin film nitinol sheets for covering the stents. In the studies described in the application, a positive photoresist (Clariant AZ 4620, Muttenz, Switzerland) was spin coated onto an 8- micron thin film nitinol coated silicon oxide wafer. The photoresist (PR) was exposed through a patterned glass mask (Computer Circuit Inc, Gardena, CA) and developed, leaving the desired PR pattern on the nitinol film. The unprotected portions of the thin film nitinol (areas without PR) were etched away in a 1:1:15 HNO3:HF:H2θ solution, and the remaining PR was removed with acetone. The fabricated thin film nitinol sheets were mechanically removed from the silicon oxide wafer. This photolithography approach reduced the number of imperfections on the edges of the thin film nitinol, thereby reducing/eliminating the incidence of tearing as compared to mechanical mechanisms.

[0057J In an alternative approach, cylinders of thin-film nitinol were manufactured for covering stents. In order to sputter cylinders of thin-film nitinol, a new sputtering system was assembled in the UCLA Active Materials Laboratory (Denton Vacuum, Moorestown, NJ). This multi-target system allows an operator to sputter shape memory alloys onto a rotating substrate within the sputtering chamber. It consists of an ultra high vacuum chamber with 3 magnetron sputtering guns, three 4" wafer holders with rotation and z-motion facility, rotation facility for tube/rod shaped substrates, and an in situ annealing facility able to achieve crystallization temperatures of 8000C. A residual gas analyzer (RGA) monitors the partial pressure of the contamination levels, particularly water and carbon dioxide pressure prior to the sputtering, and a load lock chamber with high vacuum to load the samples without breaking the main chamber vacuum. Sputtering is performed in the same manner as described for 2-dimensional thin film nitinol. Copper tubes (10 cm in length with diameters of 3 and 10 mm) were rotated at 4 rpm within the sputtering chamber and act as the substrate. The tubes were first mechanically polished to provide a smooth target surface. Once the thin-film nitinol was sputtered onto the tube, the entire tube was placed in a chemical bath to chemically etch away the copper. In this manner, the copper was removed leaving behind a cylinder, or tube, of thin-film nitinol that can be used for covering stents.

[0058] Figures 1 through 7 illustrate several different configurations of stents formed from sheets or endless loops.

[0059] Figure 1 presents a spiral stent embodiment of the invention. A sheet of a thin film of memory metal 100 is shown. If laid flat, the sheet 100 has a thickness dimension much smaller than the length and width directions. The thickness of the sheet 100 is approximately constant. The thin film of which the sheet is formed is sufficiently thin that it can readily be curved, bent, or folded. The sheet 100 shown is generally rectangular, that is, when laid flat, the sheet has the appearance of a rectangle with a longer length dimension and a shorter width dimension. Adjacent sides need not be perpendicular. The sheet 100 is not an endless loop; rather, the sheet 100 has two longitudinal edges as ends of the sheet, bounding the length dimension.

[0060] The sheet 100 is shown wrapped around an implantable medical device that is a conventional stent 102, for example, a mesh stent. A stent is a framework, generally having a tubular shape. A stent can be used, for example, to support a body cavity or to maintain a passage through a body cavity. For example, a stent implanted into a blood vessel can act to prevent the closing of the blood vessel. The conventional stent 102 shown in Fig. 1 is hollow, so that fluid can travel through it along its central axis. The medical device formed by the sheet 100 and the conventional stent 102 as a whole can be used as a covered stent. For example, the covered stent can be implanted in body cavities, such as blood vessels supplying the central nervous system, in peripheral blood vessels, and in coronary blood vessels, in order to treat diseases and disorders of the blood vessels. The covered stent formed by the sheet 100 and the conventional stent 102 as a whole is generally tubular. That is, from the exterior, the covered stent formed by the sheet 100 and the conventional stent 102 as a whole has an approximately cylindrical shape. The inside is hollow, so that fluid can travel into the stent through one distal end, through the stent (along the central axis), and out of the other distal end of the stent.

[0061] However, when a stent is deployed or placed inside a body cavity, for example, a blood vessel, it will often distort somewhat. For example, the sheet 100 and/or the conventional stent 102 will not have a perfectly cylindrical shape, but will be distorted from this ideal shape, e.g., to conform to an underlying support on the walls of the vessel.

[0062] In being wrapped around the conventional stent 102, the sheet 100 envelops the conventional stent 102. However, in the covered stent shown in Fig. 1, the sheet 100 does not entirely enclose the conventional stent 102, that is, portions of the conventional stent 102 are exposed to the environment. Furthermore, the sheet 100 overlaps itself. That is, more than one layer of the sheet lies between a portion of the conventional stent 102 and a portion of the environment. In other words, the winding number of the sheet 100, which corresponds to the number of revolutions of the sheet about the conventional stent 102, is greater than 1.

[0063] In other words, Fig. 1 presents a schematic of a thin film memory metal alloy covered stent. The thin film can be wrapped around the stent. As the stent expands, the film can unravel.

[0064] In addition to the embodiment shown in Fig. 1, an implantable stent can be formed with a sheet of thin film memory metal alloy alone, that is, without a conventional stent. The sheet can be wrapped around itself into a spiral. A spiral can be formed by curling the sheet, so that if the sheet is traced from one end, a path around a central axis is followed. As the path goes around the central axis, the path generally moves either continuously inward toward the central axis or continuously outward away from the central axis. The path may have excursions from such continuously inward or continuously outward movement. Thus, an implantable stent formed with a sheet 100 alone would look like the depiction in Fig. 1, but without the conventional stent 102. Fluid can travel into a distal end of the stent, the distal end formed by one edge bounding the width dimension of the sheet 100, along the central axis associated with the spiral formed sheet 100, and out of the other distal end formed by the other.edge bounding the width dimension of the sheet 100.

[0065] Fig. 2 shows an embodiment of a tab-and-slot stent according to the present invention. The stent is formed of a sheet 200, which includes tabs 206 projecting in the width direction, that is, perpendicular to the length dimension of the sheet 200. The tabs 206 are proximal to a first end 104 of the sheet. The sheet 200 includes a slot 210 proximal to the second end 208 of the sheet. The end 104 with the tabs 206 can be inserted through the slot 210. Furthermore, sheet 200 can be wrapped around itself to have a spiral form, as shown in Fig. 2, with the second end 208 representing an excursion in that it is slightly closer to the central axis of the spiral than the immediately preceding portion of the sheet 200 on the other side of the slot

210. The form of the sheet 200 in Fig. 2 can be termed a tab-and-slot design.

Furthermore, because the second end 208 lies closer to the central axis of the spiral than other portions of the sheet 200, the form of the sheet in Fig. 2 can be termed an inside roll tab-and-slot design. The sheet 200 has a generally tubular structure. [0066] The spiral formed sheet 200 may be used alone as a stent.

Alternatively, the spiral formed sheet 200 may be used to cover a conventional stent 102, to form a covered stent which can be implanted.

[0067] In other words, in the device shown in Fig. 2, the cover, i.e., the sheet of thin film memory metal alloy, can unroll in a belt/buckle design. The buckle maintains the cover's alignment, and prevents the cover from unraveling too far. The device shown in Fig. 2 has the cover unraveling from the inside out, assuring proper stent coverage and alignment.

[0068] The sheet of thin film memory metal alloy can be formed to have only one perforation. For example, this perforation can be a slot 210, as in the sheet 200 shown in Fig. 2.

[0069] An alternative embodiment of a sheet 300 formed into a tab-and-slot design is shown in Fig. 3. Tabs 310 proximal to a second end 308 of the sheet, and a slot 306 proximal to a first end of the sheet 104 are shown. Because the second end 308 lies farther from the central axis of the spiral than other portions of the sheet 300, the form of the sheet in Fig. 3 can be termed an outside roll tab-and-slot design.

[0070] In other words, in the device shown in Fig. 3, the cover, i.e., the sheet of thin film memory metal alloy, can unroll in a belt/buckle design. The buckle maintains the cover's alignment, and prevents the cover from unraveling too far. The device shown in Fig. 3 has the cover unraveling on the outside of the belt, assuring proper stent coverage and alignment.

[0071] The sheet, whether in the form of a spiral as in Fig. 1, an inside roll tab-and-slot design as in Fig. 2, or an outside roll tab-and-slot design as in Fig. 3, or in another form not shown, can have a compacted form to facilitate its delivery into a body cavity, for example, either inside or on a catheter. Compacted means that the sheet is temporarily shaped so that at least one dimension of the generally tubular structure formed by the sheet is smaller than in the deployed form. For example, the sheet 100 in Fig. 1 can be wrapped tightly, so that it has a large winding number, or the sheet 100 can be wrapped loosely. If the sheet 100 in Fig. 1 is wrapped tightly, so that it has a large winding number, it is in a compacted form, because the diameter of the generally tubular structure formed by the sheet 100 is smaller than it would be if the sheet 100 were wrapped loosely. If the sheet 100 in Fig. 1 is wrapped loosely, so that it has a small winding number, it is in a deployed form, because the diameter of the generally tubular structure formed by the sheet 100 is larger than it would be if the sheet 100 were wrapped tightly.

[0072] The sheet in its deployed form can be impermeable to body tissue and fluids.

[0073] A sheet formed of a thin film memory metal alloy can be induced to transition from its compacted form to its deployed form by a change in temperature. Alternatively, a sheet which is held under tension in its compacted form, say because it is inside a catheter, can be induced to transition to its deployed form by a release of the tension, say, after the sheet is placed in a blood vessel and the catheter is removed. When the sheet is induced to transition from its compacted form to its deployed form by a change in temperature or by a release of tension, no extrinsic force is required to expand the sheet to its deployed form.

[0074] The expansion of the sheet to its deployed form can be driven by a phase change of the shape memory alloy, and can be driven by super-elasticity of the shape memory alloy.

[0075] In an embodiment, extrinsic force can be required to expand the stent to its deployed form. The extrinsic force can be provided by a balloon and the shape memory alloy can exhibit detwinning behavior.

[0076] In its deployed form, a sheet formed of a thin film memory metal alloy can, for example, have the form of a spiral, an inner loop tab-and-slot design, an outer loop tab-and-slot design, a broken ring, or another configuration. A broken ring is similar to a spiral, except that there is no overlap, i.e., the winding number is 1 or less. That is, a broken ring can have the ends just touching, or can have the ends separated.

[0077] However, when a stent is deployed inside a body cavity, for example, a blood vessel, it will often distort somewhat. For example, the sheet and any conventional stent with which it is associated will not have a perfectly cylindrical shape, a perfect spiral shape, or another idealized shape for which it was designed. Rather, the sheet and/or the conventional stent will be distorted from this ideal shape.

[0078] In another embodiment, a tubular structure 402, that is, a structure having a similar topology as a hollow cylinder with thin walls, can be used to form a stent 400. Generally, such a stent can be formed from a sheet, an endless loop, or a tube. Such a stent is shown in its compacted form in Fig. 4. The compacted form shown is termed a star. A star is a shape resembling a concave simple polygon, which if a path is traced around its perimeter, the path segments alternate between moving generally, not necessarily directly, toward the centroid of the polygon and moving generally, not necessarily directly, away from the centroid of the polygon. Pentagrams, hexagrams, heptagrams are examples of stars. A pair of path segments, the first one of which moves generally away from the centroid of the polygon and the other of which moves generally toward the centroid of the polygon can be termed radiant regions. Between two radiant regions may be a path segment which stays at a constant distance (or moves toward or away from the centroid). Thus, for example, the star may resemble a disk with radiant regions jutting away from the center of the disk. When the stent 400 shown in Fig. 4 is induced to transition to its deployed form, it may assume the shape, for example of a hollow cylinder without path segments jutting away from the central axis.

[0079] In other words, in the device shown in Fig. 4, the sheet of thin film memory metal alloy is folded into a star shape.

[0080] An embodiment of tubular structure 502 having a different compacted form is shown in Fig. 5. The tubular structure 502 can be used to form a stent 500. Generally, such a stent can be formed from a sheet, an endless loop, or a tube. The compacted form shown is termed a twisted star. A twisted star has a pair of line segments bounding a radiant region curved clockwise or counterclockwise. In other words, the leaflets of the cover, i.e., the radiant regions of the sheet of thin film memory metal alloy, can be folded down or compressed to fit inside a catheter. When the stent 500 shown in Fig. 5 is induced to transition to its deployed form, it may assume the shape, for example of a hollow cylinder without path segments jutting away from the central axis. [0081] The tubular structure 502 can be used alone to form a stent 500.

Alternatively, a conventional stent 102 can be enveloped by a tubular structure 602 to form a covered stent 600, shown in Fig. 6. Figure 6 shows how the compacted form of a twisted star can be made, by folding down the radiant regions as indicated by the arrows. In other words, in the design shown in Fig. 6, leaflet covers, i.e., the radiant regions, can be folded down to fit inside a catheter. By the thin film memory metal alloy being folded, the cover is presented from unraveling too far, and the amount of unraveling that needs to occur is minimized.

[0082] An embodiment of a tubular structure 702 having a compacted form is shown in Fig. 7. The tubular structure 702 can be used to form a stent 700.

Generally, such a stent can be formed from a sheet, an endless loop, or a tube. The compacted form shown is termed a keyed wheel. A keyed wheel has the general form of a circle from which keystone shaped regions jut away from the center. When the stent 700 shown in Fig. 7 is induced to transition to its deployed form, it may assume the shape, for example, of a hollow cylinder without path segments jutting away from the central axis.

[0083] A stent formed from a sheet, an endless loop, or a tube can have a compacted form with a shape with radial points selected from the group consisting of a spiral, star, twisted star, and keyed wheel. A stent formed from a sheet, an endless loop, or a tube can have a deployed form selected from the group consisting of a tube, an elliptical tube, or a spiral.

[0084] A stent formed of a sheet of thin film memory metal alloy is not limited to a spiral, inside roll tab-and-slot, or outside roll tab-and-slot design as shown in Figs. 1-3. For example, a sheet of thin film memory metal alloy can be used to form a stent having a compacted form with any means for packaging the area of the sheet into a smaller circumference than the deployed circumference, such as folds, coiling, and layers. These include packaging means like a spiral, but also having outward protrusions to resemble a star, a twisted star, a keyed wheel, or other configurations. [0085] Furthermore, even though the stent may be designed to have a particular shape for its compacted form, often, when the stent is placed in or on a catheter, the compacted form may be distorted from the designed shape. For example, a sheet of thin film memory metal and any conventional stent 102 with which it is associated, when placed in or on a catheter, will not have the ideal shape of a spiral, tab-and-slot, star, twisted star, keyed wheel, or other configuration. Rather, the sheet and/or the conventional stent 102 will be distorted from this ideal shape.

[0086] In an embodiment, a first sheet of a thin film memory metal alloy is wrapped around the outer surface of a conventional stent, and a second sheet of a thin film memory metal alloy is wrapped around the hollow inside of the conventional stent. The first sheet and the second sheet can be formed of the same material or of different materials. The first sheet and the second sheet can have the same compacted form or different compacted forms. The first thin film sheet and the second thin film sheet can be bonded to each other. Bonded can mean that the material of the first sheet has bonds at the atomic level with the material of the second sheet. For example, annealing or welding can be used to bond a first sheet to a second sheet. If a third structure is bonded to both the first sheet and the second sheet, e.g., if the sheets are soldered together, then the sheets are also bonded to each other.

[0087] In an embodiment, the first thin film sheet and the second thin film sheet enclose the conventional stent, in that there is no path from the conventional stent to the outside environment which does not pass through the first sheet or the second sheet. In other words, the bonded first sheet and second sheet isolate the conventional stent from the biological environment. Such a configuration can be useful, for example, because the material of which the conventional stent is formed can be selected for its mechanical properties alone, without regard to its biocompatibility.

[0088] Several studies, presented in the Examples below, support the use of thin-film nitinol in producing novel, low profile, covered stents.

[0089] In addition to its shape-memory and super-elastic properties, thin film nitinol possesses remarkably high tensile strength. These properties make it particularly amenable for use in transcatheter devices. Furthermore, thin film nitinol allows for the construction of extremely low profile covered stents. Because this material is manufactured as a thin film, there is little room for fluctuations in surface texture, resulting in an extremely smooth surface. In contrast to bulk nitinol currently utilized in multiple biomedical applications, the DC hot target sputtering process used in our laboratory produces thin films of nitinol which are free of contaminants and uniform in composition. Thin film nitinol has also been shown to be more resistant to corrosion in a biological environment than bulk, i.e., commercially available, nitinol.

[0090] In the in vivo studies presented in Example 8, all stents were able to be delivered with their recommended delivery sheathes (i.e. the thin film nitinol coverings did not significantly increase the device size). The stents were found to become covered in neointima within the first month after implantation. There were no indications of thrombosis or embolic phenomenon following stent implantation.

There was no device-related injury noted on histology or pathology of vessel walls previously containing covered stent portions; the thin film nitinol formed a barrier between the vessel wall and the stent which allowed for very rapid removal of the stent from the arteries.

[0091] Thin-film nitinol covered stents may have application in preventing in- stent stenosis secondary to direct neointimal hyperplasia. Covered stents are able to prevent vessel growth into the lumen of a stent by forming a mechanical barrier to directly prevent neointimal proliferation into the stent's lumen. However, intima may still grow into a covered stent's lumen from its edges. The studies presented in Example 8 indicated that in the arterial circulation, the thin film nitinol cover did prevent in-growth of neointima and supported growth on endothelial cells over the first month after implantation. These studies suggested covering both the outside and inside of the stent with thin film nitinol to prevent neointimal growth. Thus, in an embodiment, the medical device can have a layer of thin film nitinol on the inside of the stent and a layer of thin film nitinol on the outside of the stent. The stent embodiments described herein have application in the stenting of coronary arteries, pulmonary and systemic veins, the neonatal patent ductus arteriosus, and for the treatment of peripheral and central nervous system aneurysms. [0092] In several embodiments, thin film memory metal alloy can be used to cover a variety of stent devices. For example, thin film memory metal alloy can be used to cover a balloon stent, a self-expanding stent, or another type of stent.

[0093] Used alone as a stent, the sheet of thin film memory metal alloy can be housed in a catheter or sheath and delivered to the place in the body, e.g., a part of a blood vessel, where it is to be deployed. The stent can then be unsheathed, so that the sheet of thin film memory metal alloy expands into its deployed form. The expansion can be driven, for example, by a temperature induced phase change in or by the super- elasticity of the sheet.

[0094] Used to cover a stent, the sheet of thin film memory metal alloy, with the stent, can be housed in a catheter or sheath and delivered to the place in the body, e.g., a part of a blood vessel, where it is to be deployed. The covered stent can then be unsheathed, so that the sheet of thin film memory metal alloy expands into its deployed form. The expansion can be driven, for example, by a temperature induced phase change in or by the super-elasticity of the sheet. As another example, expansion can be driven by force imposed on the sheet of thin film memory metal by the stent, which may be self-expanding or may be a balloon which is inflated. The material of which the sheet of thin film memory metal alloy is formed can be selected, so that the sheet exhibits detwinning behavior and can expand with the stent.

[0095] When the sheet of thin film memory metal alloy is used to cover a balloon stent, the covered stent can be inserted into the body without use of a catheter or sheath. After being maneuvered to the part of the body where the stent is to be deployed, the balloon can be inflated. The material of which the sheet of thin film memory metal alloy is formed can be selected, so that the sheet exhibits detwinning behavior and can expand with the stent. EXAMPLES

Example 1: Stress-Strain Testing

[0096] To characterize the stress-strain and shape memory properties of the thin film nitinol, an MTS Tytron (MTS, Eden Prairie, MN) was used. The MTS Tyron has a displacement resolution of 0.1 μm and a minimum force of 0.01 N. Thin film nitinol was removed from the wafer on which it was formed using a crack and peel method to produced a free-standing film. Tensile samples were fabricated using a razor blade and a straight edge to produce strips of thin film nitinol with dimensions of 3 mm by 20 mm. The specimens were arranged in the grips such that the length of the specimen was 10 mm. All tests were conducted at room temperature. Prior to testing, a small load (.01 lbs) was applied to eliminate slack in the test setup. The load on the thin film nitinol sample was ramped from 0.22-15.5 N (.05-3.5 lbs) at a rate of 0.35 N/sec (0.08 lbs/sec). The load was then returned to 0.22 N and the film was heated to above the austenite finish temperature in order to record strain recovery.

[0097] A stress-strain curve quantifying the ductility and shape memory behavior of the thin film is shown in Fig. 9. The modulus of the film was calculated to be 17.8 GPa and the stress to induce twin boundary motion in the material was 136 MPa. The film withstood tensile forces above 425 MPa and was strained to above 5%. Upon unloading and heating, the thin film nitinol sample exhibited complete strain recovery showing excellent shape memory behavior.

Example 2: Differential Scanning Calorimetry

[0098] A Shimadzu DSC-50 (Shimadzu, Kyoto, Japan) differential scanning calorimeter (DSC) was used to determine the transformation temperatures of the thin film nitinol formed for this study. Thin film nitinol was mechanically removed from the wafer and a sample weighing 19 mg was cut from the freestanding film. The film was cut into small sections to reduce internal stresses that may develop in the film during DSC testing. The specimen was heated to 1500C and then cooled to -200C at a constant rate of 100C min'1. Transformation temperatures were determined from the endothermic and exothermic peaks of the heating and cooling curves. The curves obtained from the differential scanning calorimetry testing are shown in Fig. 10. The start and finish transition temperatures of thin film nitinol for the martensite (Ms, Mf) and austenite (As, Af) phases were determined from the exothermic and endothermic peaks of the cooling and heating curves. The Af , As, Mf, and Ms temperatures were found to be 86.80C, 69.3°C, 26.6°C and 44.3°C respectively. A rhombohedral phase is also observed during cooling.

Example 3

[0099] Both self-expanding nitinol stents and balloon-inflatable stainless steel stents were mechanically covered with thin film nitinol. Specifically, balloon- inflatable PGl 91 OB and PG2910B stents from Cordis (Johnson and Johnson, Miami, FL), and prototype nitinol pfm ipfin AG5 Homburg, Germany) self-expanding stents (8-10 mm diameter) were used for laboratory and animal testing. Figures 1OA and 1OB show a PFM self-expanding stent spiral wrapped with a nitinol sheet with the assembly placed inside a 10 mm tube.

Example 4

[00100] Several nitinol cover designs were examined, including an outer wrap design and a design using a tube of cylindrical thin film nitinol. The simplest spiral cover was ultimately employed for most laboratory and animal testing (see Fig. 1). A two-dimensional piece of thin film nitinol was wrapped circumferential Iy around the stent, with the end able to unravel freely upon stent expansion.

[00101] A tab-and-slot design was employed to attach the thin film nitinol to the stent (see Fig. 2). A piece of thin film nitinol was shaped in a rectilinear fashion, with protruding tabs on either end. One 'tab' end of this piece was fitted through a slot created toward the proximal portion of the thin film nitinol cover. The second 'tab' end was then woven through the lumen of the stent, around the stent strut, back out to the exterior of the stent, and finally through the same slotted thin film nitinol cover. In this manner, a ring composed of thin film nitinol was created that mechanically coupled the thin film cover with the stent.

Example S

[00102] Thin film covered stents were made having thin film nitinol on both the outer and inner walls of a conventional stent. In other words, the stent is covered on the outside as well as the inside in order to produce most favorable results. For example, this type of stent can be produced by annealing two thin film nitinol cylinders together. In this configuration, the stent is sealed between two flexible pieces of thin film nitinol. This approach is illustrated in Figures 1 IA-11C.

Example 6

[00103] Covers were affixed to balloon-inflatable Cordis stents. In order to cover the pfin self-expanding stents, each stent was cooled with liquid nitrogen to -195.95 degrees Celsius and compressed into 5 French sheaths. The thin film nitinol cover was then wrapped around this sheath. The 5 French sheath wrapped in nitinol was subsequently placed into a larger 7 French sheath. Finally, the 5 French sheath was then pulled back, leaving the thin film cover in place while simultaneously exposing the stent. The stent became covered by self-deploying into the thin-film nitinol wrap. The final 7 French sheath was then attached to a modified version of a pfin stent delivery system. In later trials, the thin film nitinol cover was first attached to the stent in the manner previously described, and then compressed into the 7 French sheath using liquid nitrogen.

Example 7: In Vitro Testing

[00104] In vitro testing of the thin film nitinol covered stents was designed primarily to demonstrate the feasibility of successful stent deployment, and to test the success of different covered stent designs. A pulsatile flow loop was constructed using a Harvard Apparatus Pulsatile Blood Pump (Harvard Bioscience, Holliston, MA) and clear PVC tubing (10 mm diameter). A 7 French sheath was used as an introductory port for the insertion of catheters and balloons for stent deployments. Results were recorded on both digital video and still images with pulsatile flow of 1.5 L/min through the system.

[00105] Thin film nitinol covered stents deployed successfully in our flow loop in multiple consecutive trials. Upon deployment, all stents expanded with ease and remained in place throughout each trial. After both the self-expanding and balloon expandable thin film nitinol stents were shown to deploy in a consistent fashion in the laboratory flow loop, animal studies, discussed in Example 8, below, were begun.

Example 8: In Vivo Testing

[00106] A swine animal model was used for the in vivo testing of the thin film nitinol covered stents. A total of four animals were used.

[00107] The following table lists several of the in vivo trials in which thin-film

NiTi covered stents were implanted and explanted in swine animal models.

Notes: PG1920B: Palmaz-Genesis 19 x 20 mm balloon expandable stent

PG2920B: Palmaz-Genesis 29 x 10 mm balloon expandable stent

Pfin: pfm Inc. self- expanding stent (10 mm in diameter, various lengths)

"Trial Length" indicates the time between stent implantation and explantation

DAO = Descending aorta

IVC = Inferior vena cava

SVC = Superior vena cava

[00108] Results from animal studies indicate that the most effective thin film covered stents have thin film nitinol on both the outer and inner walls of the stent.

[00109] After appropriate anesthesia and endotracheal intubation, thin-film nitinol covered stents were percutaneously implanted into appropriately sized vessels of each swine. All arterial implantations were performed in the descending aorta (DAO). Venous implants were performed in either the superior vena cava (SVC), right femoral vein, or inferior vena cava (IVC). In all animals, percutaneous vascular access was obtained via the Seldinger technique and 7 French sheathes were placed in the right or left femoral artery and contralateral vein. A 5 French pigtail catheter was advanced into the proposed site of implantation and cineangiograms were performed with machine injections of contrast solution (1.5 cc/kg). Appropriately sized vessels were evaluated via catheter calibration prior to stent implantation. 50 Units/kg was administered prior to stent deployment.

[00110] In the first animal implantation, only one thin film nitinol covered

Genesis PG1910B stent was deployed in the descending aorta (DAO). This animal was re-catheterized and euthanized two weeks later. The three subsequent animals had a combination of balloon expandable and self-expanding thin film nitinol covered stents placed in the DAO5 SCV, and/or IVC. Control stents without thin film nitinol coverings were also implanted in each swine. As below, swine were euthanized 2, 3, 4, and 6 weeks after stent implantation.

[00111] Amplatzer 0.035" super stiff wires (AGA Inc., Golden Valley, MN) were used to guide all stent deliveries. Balloon expandable stents were delivered in the usual fashion by manual inflation via an insufflator (6-9 atm). Self-expanding stents were delivered by unsheathing the devices after appropriate positioning. Cineangiograms were performed after each stent's deployment to demonstrate proper stent placement and function. Following the procedure, animals were continuously monitored until they are able to ambulate unaided. Animals were treated for pain as needed for up to seven days post-operatively. Animals were not further anticoagulated after recovery.

[00112] AH swine were re-catheterized under general anesthesia at two, three, four, and six weeks after the initial catheterization procedure and cineangiograms of stent implantation sites were performed. Each swine was euthanized with pentobarbitol immediately following this catheterization procedure.

[00113] Following euthanization of the swine models, stent-containing vessels were harvested, as well as specimens from major organs (liver, heart, lungs, stomach, kidney, pancreas, and spleen). Light microscopy was employed to analyze the covered and uncovered portions of the harvested stents. Gross examination, trichrome staining, and hematoxylin and eosin staining (H&E) were used to analyze the recovered organ specimens and stent implantation sites.

[00114] A total of four animal trials were performed, resulting in the successful implantation of ten thin film nitinol covered stents (4 Palmaz and 6 pfiri). Figure 12 shows a Palmaz Genesis balloon expandable stent spiral wrapped with a nitinol sheet inside an opened swine descending aorta. Figure 13 A shows a pfm self-expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine descending aorta. Figure 13B shows B. pβn self-expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine descending aorta. Figure 14 shows a pfin self- expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine superior vena cava. Figure 15 shows a. pfm self-expanding stent covered with a spiral wrapped nitinol sheet inside an opened swine inferior vena cava.

[00115] In angiograms taken 2 to 6 weeks after the initial implantation

(immediately prior to euthanization), the thin-film nitinol covered stents placed in the descending aorta showed absolutely no in-stent stenoses. At two and three weeks, minimal neointimal obstruction was seen in the thin film nitinol covered stents placed in the venous circulation, while moderate-to-severe neointimal obstruction was observed in the uncovered portions of the stents (see angiogram of Fig. 17). [00116] Upon post-mortem dissection, the covered portions of all implanted stents were easily removed, while uncovered portions were adherent to the vessel walls (see Fig. 16). Post-mortem analysis correlated with the radiographic findings. No significant in-stent neointimal hyperplasia was found on covered thin film nitinol stents placed in the arterial circulation.

[00117] Scanning electron microscopy (SEM) was utilized to determine the surface characteristics of the thin films following post-mortem explantation. The samples were air dried, sputtered with gold and examined using a Cambridge Stereoscan 250 (Cambridge Instruments, Cambridge, MA).

[00118] Scanning electron microscopy of nitinol coverings removed from stents placed in the arterial circulation revealed a thin film of endothelial cells coating the entire surface of the nitinol film by 21 days post implantation. On microscopic examination, no endothelial injury was noted in vessel walls previously housing covered stent portions (see Fig. 18B), as compared to significant endothelial injury and neointimal proliferation observed in vessel walls housing uncovered stent portions. Figure 18A shows an image of a vessel wall treated by hematoxylin and eosin staining which previously contained uncovered stent portions. Significant neointimal hyperplasia and endothelial injury is noted in vessels previously housing uncovered stent portions. Microscopic examinations of organ tissues showed no evidence of device-related abnormalities.

[00119] AH references cited herein are incorporated by reference as if each had been individually incorporated. The embodiments illustrated and discussed in this specification are intended only to teach those skilled in the art the best way known to the inventors to make and use the invention. Figures are not drawn to scale. In describing embodiments of the invention, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected. Nothing in this specification should be considered as limiting the scope of the present invention. All examples presented are representative and non-limiting. The above-described embodiments of the invention may be modified or varied, without departing from the invention, as appreciated by those skilled in the art in light of the above teachings. It is therefore to be understood that, within the scope of the claims and their equivalents, the invention may be practiced otherwise than as specifically described.

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23. Rocher P., El Medawar L., Hornez J.C., "Biocorrosion and cytocompatibility assessment of NiTi shape memory alloys," Scripta Materialia, 50(2), pp. 255-260. 24. Stepan L.L., Levi D.S., Gans E., Panduranga M.K, Ujihara M., Carman G.P., "Biocorrosion investigation of two shape memory nickel based alloys: Ni-Mn-Ga and thin film nitinol," J Biomed Mat Res., Accepted for publication.

Claims

WHAT IS CLAIMED IS:
1. A stent, comprising: a structure comprising a generally rectangular thin film sheet of shape memory alloy wrapped into a generally tubular shape; two distal edges of the sheet defining the two ends of the tubular shape; two longitudinal edges of the sheet overlapping; and the structure having a compacted form with a first diameter and a deployed form with a second diameter larger than the first diameter, wherein the thin film sheet is nonperforated, has a tubular support, or both.
2. The stent of claim 1 , wherein the generally rectangular thin film sheet of shape memory alloy is nonperforated.
3. The stent of claim 2, wherein the compacted form is a spiral.
4. The stent of claim 2, wherein the compacted form is a spiral having a winding number greater than one.
5. The stent of claim 2, wherein the compacted form is selected from the group consisting of a star spiral, twisted star spiral, and keyed wheel spiral.
6. The stent of claim 2, wherein the deployed form is tubular.
7. The stent of claim 2, wherein the deployed form is a spiral.
8. The stent of claim 2, wherein the deployed form is a spiral having a winding number greater than one.
9. The stent of claim 2, wherein the deployed form is a broken ring.
10. The stent of claim 1 , wherein the shape-memory alloy is selected from the group consisting of nickel-titanium alloy, nickel-titanium-copper alloy, gold-cadmium alloy, nickel-titanium-platinum alloy, nickel-titanium-palladium alloy, nickel-titanium-hafnium alloy, nickel-magnesium-gallium alloy, and nickel-manganese-gallium alloy.
11. The stent of claim 1, wherein the shape-memory alloy is selected from the group consisting of nickel-titanium-copper alloy, gold-cadmium alloy, nickel-titanium-platinum alloy, nickel-titanium-palladium alloy, nickel-magnesium-gallium alloy, and nickel- manganese-gallium alloy.
12. The stent of claim 2, wherein the shape-memory alloy is a nickel-titanium alloy having from about 45 to about 55 atom percent nickel.
13. The stent of claim 2, wherein the shape-memory alloy is a nickel-titanium alloy having about 50 atom percent nickel.
14. The stent of claim 2, wherein the sheet has a compositional variation of no more than about 1 atom percent.
15. The stent of claim 1 , wherein the generally rectangular thin film sheet of shape memory alloy has a slot.
16. The stent of claim 15, wherein the compacted form is selected from the group consisting of a spiral, star spiral, twisted star spiral, keyed wheel spiral, inner loop tab- and-slot, and outer loop tab-and-slot.
17. The stent of claim 15, wherein a first longitudinal edge of the thin film sheet defines a tab, and a second longitudinal edge of the thin film defines a slot.
18. The stent of claim 1, further comprising a tubular support for the thin film sheet.
19. The stent of claim 18, wherein the sheet is perforated.
20. The stent of claim 18, wherein the sheet is nonperforated.
21. The stent of claim 18, wherein the tubular support has a hollow inside and an outer surface.
22. The stent of claim 21, wherein the thin film sheet is wrapped around the outer surface of the tubular support.
23. The stent of claim 21 , wherein the thin film sheet is wrapped within the hollow inside of the tubular support.
24. The stent of claim 21, wherein a first thin film sheet is wrapped around the outer surface of the tubular support and a second thin film sheet is wrapped within the hollow inside of the tubular support.
25. The stent of claim 24, wherein the first thin film sheet and the second thin film sheet are formed of different materials.
26. The stent of claim 24, wherein the compacted form of the first thin film sheet is different than the compacted form of the second thin film sheet.
27. The stent of claim 24, wherein the first thin film sheet and the second thin film sheet are bonded to each other.
28. The stent of claim 27, wherein the first thin film sheet and the second thin film sheet enclose the tubular support.
29. The stent of claim 18, wherein the sheet is woven through the lumen of the tubular support.
30. A method of forming a stent, comprising: wrapping a nonperforated, thin film sheet of shape memory alloy into a generally tubular shape; and forming the sheet into a compacted form.
31. The method of claim 30, wherein the wrapping comprises coiling the sheet into a spiral.
32. The method of claim 30, wherein forming the sheet into a compacted form comprises forming a spiral.
33. The method of claim 30, wherein forming the sheet into a compacted form comprises folding.
34. The method of claim 30, wherein the thin film sheet is produced by sputtering.
35. The method of claim 34, wherein the thin film sheet is formed by sputtering from a heated target.
36. The method of claim 35, wherein the heated target has a temperature of from about 200 0C to about 800 0C.
37. The method of claim 35, wherein the heated target has a temperature of from about 400 °C to about 700 0C.
38. The method of claim 35, wherein the heated target has a temperature of from about 550 0C to about 650 0C.
39. The method of claim 30, wherein the wrapping comprises overlapping the two longitudinal edges of the sheet.
40. The method of claim 39, wherein the overlapping defines a shape selected from the group consisting of a spiral, star spiral, twisted star spiral, and keyed wheel spiral.
41. The method of claim 34, further comprising shaping the thin film by photolithography and etching.
42. A method of forming a stent, comprising: wrapping a thin film sheet of shape memory alloy into a generally tubular shape; and forming the sheet into a compacted form, the sheet having no perforations, or having a tubular support, or both.
43. The method of claim 42, wherein the compacted form is a shape selected from the group consisting of a spiral, star spiral, twisted star spiral, keyed wheel spiral, inner loop tab-and-slot, and outer loop tab-and-slot.
44. The method of claim 42, further comprising shaping the thin film by photolithography and etching, forming a tab proximal to a first longitudinal edge, and forming a slot proximal to a second longitudinal edge.
45. The method of claim 44, further comprising inserting the first longitudinal edge through the slot.
46. A method comprising: inserting the stent of claim 1 in its compacted form into a body cavity; and allowing the stent to expand to its deployed form.
47. The method of claim 46, wherein the stent is inserted in its compacted form through or on a catheter into a body cavity.
48. The method of claim 46, wherein no extrinsic force is required to expand the stent to its deployed form. λ
49. The method of claim 48, wherein the stent's expanding to the deployed form is driven by a phase change of the shape memory alloy.
50. The method of claim 48, wherein the stent's expanding to its deployed form is driven by super-elasticity of the shape memory alloy.
51. The method of claim 46, wherein an extrinsic force expands the stent to its deployed form.
52. The method of claim 51, wherein the extrinsic force is provided by a balloon and the shape memory alloy exhibits detwinning behavior.
53. The method of claim 46, wherein the stent consists essentially of the thin film sheet.
54. The method of claim 46, wherein the body cavity is a blood vessel.
55. The method of claim 54, wherein the blood vessel is located within the central nervous system.
56. The method of claim 54, wherein the blood vessel is part of the peripheral vascular system.
57. The method of claim 54, wherein the blood vessel is a coronary blood vessel.
58. A kit comprising: the stent of claim 1 ; means for inserting the stent into a body cavity; and means for expanding the stent to its deployed form.
59. A medical device comprising: a thin film sheet of a shape memory alloy wrapped into a tubular shape, having a compacted form with a compacted circumference and having a deployed circumference; and the compacted form comprising means for packaging a portion of the thin film sheet corresponding to the difference between the deployed circumference and the compacted circumference.
60. The medical device of claim 59, wherein the packaging means comprises folds or a spiral.
61. The medical device of claim 59, further comprising means for inserting the thin film sheet wrapped into the tubular shape, in the compacted form, into the body of a subject.
62. The medical device of claim 59, further comprising a mesh stent.
63. A stent, comprising: a structure comprising an endless loop of shape memory alloy having a generally tubular shape; and the structure having a compacted form with a first diameter and a deployed form with a second diameter larger than the first diameter, wherein the compacted form is selected from the group consisting of a star, twisted star, and keyed wheel.
64. The stent of claim 63, wherein the deployed form is tubular.
65. The stent of claim 63, being in compacted form.
66. The stent of claim 63, wherein the compacted form has a shape with radial points selected from the group consisting of a spiral, star, twisted star, and keyed wheel and wherein the deployed form is selected from the group consisting of a tube, an elliptical tube, or a spiral having a generally tubular shape.
PCT/US2007/003792 2006-02-10 2007-02-12 Thin film metal alloy covered stent WO2007095233A3 (en)

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US60/771,863 2006-02-10

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CN105126636A (en) * 2015-09-06 2015-12-09 中国船舶重工集团公司第七一二研究所 Preparation method for support-type tubular palladium membrane or palladium alloy membrane
WO2014134568A3 (en) * 2013-03-01 2016-05-12 The Regents Of The University Of California Apparatus and methods for bidirectional hyperelastic stent covers
DE102015121531A1 (en) * 2015-12-10 2017-06-14 Acandis Gmbh & Co. Kg Medical system for treating aneurysms

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US20020193864A1 (en) * 1998-03-25 2002-12-19 Endotex Interventional Systems, Inc. Coiled sheet graft for single and bifurcated lumens and methods of making and use
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US20050119719A1 (en) * 1996-12-09 2005-06-02 Micro Therapeutics, Inc. Intracranial stent and method of use

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US5984963A (en) * 1993-03-18 1999-11-16 Medtronic Ave, Inc. Endovascular stents
US20050119719A1 (en) * 1996-12-09 2005-06-02 Micro Therapeutics, Inc. Intracranial stent and method of use
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WO2014134568A3 (en) * 2013-03-01 2016-05-12 The Regents Of The University Of California Apparatus and methods for bidirectional hyperelastic stent covers
CN105126636A (en) * 2015-09-06 2015-12-09 中国船舶重工集团公司第七一二研究所 Preparation method for support-type tubular palladium membrane or palladium alloy membrane
DE102015121531A1 (en) * 2015-12-10 2017-06-14 Acandis Gmbh & Co. Kg Medical system for treating aneurysms

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