Patent Abstract:
According to one aspect of the present invention, a fatigue resistant stent comprises a flexible tubular structure having an inside diameter, an outside diameter, and a sidewall therebetween and having apertures extending through the sidewall. According to other aspects of the invention, processes for making a fatigue resistant stent are disclosed. According to further aspects of the invention, delivery systems for a fatigue resistant stent and methods of use are provided.

Full Description:
RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. Provisional Application Ser. No. 60/840,170 filed Aug. 25, 2006 and U.S. Provisional Application Ser. No. 60/814,437, filed Jun. 16, 2006. The entire contents of both of the above applications is incorporated herein by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to an implant having high resistance to fracture when mechanically cycled at a site in a body lumen. More particularly, this invention pertains to a fatigue fracture resistant vascular implant such as a self-expanding stent. 
       BACKGROUND OF THE INVENTION 
       [0003]    Stents are widely used for supporting a lumen structure in a patient&#39;s body. For example, stents may be used to maintain patency of a coronary artery, carotid artery, cerebral artery, popliteal artery, iliac artery, femoral artery, tibial artery, other blood vessels including veins, or other body lumens such as the ureter, urethra, bronchus, esophagus, or other passage. 
         [0004]    Stents are commonly metallic tubular structures made from stainless steel, Nitinol, Elgiloy, cobalt chrome alloys, tantalum, and other metals, although polymer stents are known. Stents can be permanent enduring implants, or can be bioabsorbable at least in part. Bioabsorbable stents can be polymeric, bio-polymeric, ceramic, bio-ceramic, or metallic, and may elute over time substances such as drugs. Non-bioabsorbable stents may also release drugs over time. Stents are passed through a body lumen in a collapsed state. At the point of an obstruction or other deployment site in the body lumen, the stent is expanded to an expanded diameter to support the lumen at the deployment site. 
         [0005]    In certain designs, stents are open-celled or close-celled cylindrical structures that are expanded by inflatable balloons at the deployment site. This type of stent is often referred to as a “balloon expandable” stent. Stent delivery systems for balloon expandable stents are typically comprised of an inflatable balloon mounted on a multi lumen tube. The stent delivery system with stent crimped thereon can be advanced to a treatment site over a guidewire, and the balloon inflated to expand and deploy the stent. 
         [0006]    Other stents are so-called “self expanding” stents and do not use balloons to cause the expansion of the stent. An example of a self-expanding stent is a tube (e.g., a coil tube, a mesh tube, or an open-celled tube) made of an elastically deformable material (e.g., a superelastic material such a nitinol). This type of stent is secured to a stent delivery device under tension in a collapsed state. At the deployment site, the stent is released so that internal tension within the stent causes the stent to self-expand to its enlarged diameter. 
         [0007]    Other self-expanding stents are made of so-called shape-memory metals. Such shape-memory stents experience a phase change at the elevated temperature of the human body. The phase change results in expansion from a collapsed state to an enlarged state. 
         [0008]    A very popular type of self expanding stent is an open-celled tube made from superelastic nitinol, for example, the Protégé GPS stent from ev3, Inc. of Plymouth, Minn. Open or closed cell tube stents are commonly made by laser cutting of tubes, or cutting patterns into sheets followed by or preceded by welding the sheet into a tube shape, and other methods. Another delivery technique for a self expanding stent is to mount the collapsed stent on a distal end of a stent delivery system. Such a system can be comprised of an outer tubular member and an inner tubular member. The inner and outer tubular members are axially slideable relative to one another. The stent (in the collapsed state) is mounted surrounding the inner tubular member at its distal end. The outer tubular member (also called the outer sheath) surrounds the stent at the distal end. 
         [0009]    Prior to advancing the stent delivery system through the body lumen, a guide wire is first passed through the body lumen to the deployment site. The inner tube of the delivery system is hollow throughout at least a portion of its length such that it can be advanced over the guide wire to the deployment site. The combined structure (i.e., stent mounted on stent delivery system) is passed through the patient&#39;s lumen until the distal end of the delivery system arrives at the deployment site within the body lumen. The deployment system and/or the stent may include radiopaque markers to permit a physician to visualize positioning of the stent under fluoroscopy prior to deployment. At the deployment site, the outer sheath is retracted to expose the stent. The exposed stent is free to self-expand within the body lumen. Following expansion of the stent, the inner tube is free to pass through the stent such that the delivery system can be removed through the body lumen leaving the stent in place at the deployment site. 
         [0010]    In prior art devices, the stent may prematurely deploy as the outer tube is retracted accidentally. Further, once the stent has been deployed, subsequent adjustment of the stent deployment location can be difficult because re-sheathing typically cannot be readily accomplished. To overcome some of these problems some stent delivery systems are comprised of interlocks on the stent and on the inner member. See for example U.S. Pat. No. 6,814,746 to Thompson et. al., entitled “Implant Delivery System With Marker Interlock”, and U.S. Pat. No. 6,623,518 to Thompson et. al., entitled “Implant Delivery System With Interlock”, the contents of both included herein in their entirety by reference. 
         [0011]    A common problem with stents properly deployed in some vessels is that the stents fracture over time. Problems secondary to stent fracture can include pain, bleeding, vessel occlusion, vessel perforation, high restenosis rate, non-uniform drug delivery profile, non-even vessel coverage and other problems, and re-intervention may be required to resolve the problems. Stents are commonly designed for high pulsatile fatigue life, i.e., for resistance to fracture under the diametrical pulsatile movement in an otherwise static blood vessel, as may be appropriate for some implantation sites. Stents however are not usually designed for resistance to fracture under in-patient loading conditions other than pulsatile, as is appropriate for other implantation sites. Stents at implantation sites such as the popliteal artery, iliac artery, femoral artery, tibial artery, and others can suffer from large amounts of axial, bending, or torsional cyclic loading and from large amounts of bending and twisting. It is believed that the high fracture rate of stents implanted in these locations is due to stent designs and stent material mechanical properties that are incapable of withstanding the high mechanical forces applied to the stents by patient activity over and above those forces produced by the beating heart. 
         [0012]    Attempts have been made to improve the fatigue resistance of materials used for implantable medical devices. In U.S. Pat. No. 6,780,261 Trozera proposes use of malleable, recrystallized materials. This approach is unlikely to be suitable for many self expanding stent applications where malleability should be low. In Wu (U.S. Patent Application Publication Number 2004/0241037), Dooley (U.S. Patent Application Publication Number 2004/0216814), and Patel (U.S. Patent Application Publication Number 2005/0090844) the use of cold working or pre-straining is disclosed, and in Walak (U.S. Patent Application Publication Number 2005/0059994) use of a stabilized martensitic surface is disclosed. However, one cannot always uniformly apply these approaches to the surface of an implant because of limiting factors such as access and geometry. 
         [0013]    What is needed is a stent that can be easily manufactured and that will survive without fracture when implanted in locations that experience high mechanical forces produced by patient activity over and above those forces produced by the beating heart. 
       SUMMARY OF THE INVENTION 
       [0014]    In one embodiment, an implant comprising a nickel titanium alloy may be heat set by (a) restraining the implant on a mandrel having a first diameter and annealing the implant within a first temperature range; (b) after (a), restraining the implant on a mandrel having a second diameter and annealing the implant within a second temperature range that is higher than the first temperature range; and (c) after (b), annealing the implant within a third temperature range that is lower than the second temperature range and while the implant is restrained on a mandrel. In some embodiments, the second diameter is larger than the first diameter. Further disclosed are implants made according to the methods disclosed herein, and delivery devices that include a delivery catheter and an implant heat set according to methods disclosed herein. 
         [0015]    In another embodiment an implant comprising a nickel titanium alloy has a bend-rotate fatigue life of at least 1 million cycles to failure. The cycles to failure is the number of full rotations made by the implant before the implant breaks. 
         [0016]    In another embodiment, an implant is disclosed that has a nickel titanium alloy, and a kink radius of no greater than 0.195 inches, wherein the kink radius is half the distance between the implant unkinked ends held parallel to each other when the implant is kinked by bending. The implant may have a kink radius of no greater than 0.189 inches, 0.171 inches, or 0.165 inches. 
         [0017]    In some embodiments, a delivery device includes an implant disclosed herein and a catheter for delivery of the implant. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0018]    The above and further advantages of the invention may be better understood by referring to the following description in conjunction with the accompanying drawings in which: 
           [0019]      FIG. 1  is a side elevation view of one embodiment of a stent delivery system comprised of a fatigue resistant stent having features that are examples of inventive aspects in accordance with the principles of the present disclosure; 
           [0020]      FIG. 2  is an enlarged view of the distal end of the system of  FIG. 1  with an outer sheath shown in phantom line; 
           [0021]      FIG. 3  is the view of  FIG. 2  with the outer sheath retracted; 
           [0022]      FIGS. 4A and 4B  are side elevation views of an alternate embodiment of a stent delivery system comprised of a fatigue resistant stent; 
           [0023]      FIGS. 5 and 6  illustrate plan views of exemplar fatigue resistant stent embodiments. The stents are shown expanded and the stent structures are shown cut longitudinally and laid flat; 
           [0024]      FIGS. 5A and 5B  illustrate plan views of exemplar fatigue resistant stent embodiments. The stents are shown unexpanded and the stent structures are shown cut longitudinally and laid flat; 
           [0025]      FIGS. 7 and 8  illustrate side views of exemplar fatigue resistant stent embodiments. The stents are shown expanded; 
           [0026]      FIG. 9  illustrates a plan view of an exemplar fatigue resistant stent. The stent is shown expanded and the stent and interlock structures are shown cut longitudinally and laid flat; 
           [0027]      FIG. 10  illustrates a plan view of a section of an exemplar fatigue resistant stent. The stent is shown partially expanded and the stent segment and interlock structures are shown cut longitudinally and laid flat; 
           [0028]      FIG. 11  illustrates a plan view of a section of an exemplar fatigue resistant stent. The stent is shown partially expanded and the stent segment and interlock structures are shown cut longitudinally and laid flat; 
           [0029]      FIG. 12  illustrates schematically an exemplar annealing process for a fatigue resistant stent. 
       
    
    
     DETAILED DESCRIPTION 
       [0030]    With reference now to the various drawing figures a description is provided of embodiments that are examples of how inventive aspects in accordance with the principles of the present invention may be practiced. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the broad inventive aspects disclosed herein. It will also be appreciated that the inventive concepts disclosed herein are not limited to the particular stent configurations disclosed herein, but are instead applicable to any number of different stent configurations. 
         [0031]      FIGS. 1-3  show an over-the-wire stent delivery system  10  having distal and proximal ends  11 ,  13 , inner member  14 , and retractable outer sheath  16  that slides over inner member  14 . Stent mounting location  26  is located adjacent distal end  11  of system  10 . Stent  12  (visible in  FIGS. 2 and 3 ) is carried at stent mounting location  26  of stent delivery system  10  in a collapsed (or reduced diameter) state. Stent  12  mounts over inner member  14  and is covered by sheath  16  so as to be retained in the collapsed state (see  FIG. 2 ). Stent  12  is released (i.e., deployed) by retracting sheath  16  to uncover or expose stent  12  (see  FIG. 3 ). System  10  includes proximal interlock structure  27  that prevents stent  12  from prematurely deploying, one or more mid interlock structures  28  that assist with uniform stent deployment and with stent loading, and optional distal interlock structure  29  that assists with uniform stent deployment and with stent loading. Upon release of stent  12  from stent delivery system  10 , stent  12  expands to an enlarged diameter to abut against the walls of the patient&#39;s lumen in order to support patency of the lumen. The expansion of stent  12  also causes stent  12  to disengage from interlock structures  27 ,  28  and  29 . 
         [0032]    System  10  is configured to be advanced through the patient&#39;s body lumen. In use, system  10  may be sufficiently long for distal end  11  to be placed at the deployment site in the patient&#39;s body lumen with proximal end  13  remaining external to the patient&#39;s body for manipulation by an operator. 
         [0033]    Sheath  16  of system  10  may have a variety of different constructions. In certain embodiments, the sheath has a tubular construction of braid-reinforced polyester adapted to resist kinking and to transmit axial forces along the length of sheath  16 . Sheath  16  may be constructed so as to have varying degrees of flexibility along its length. Inner member  14  of system  10  is relatively flexible and can be made of a polymeric material such as nylon. In certain embodiments, inner member  14  has a tubular configuration and defines a lumen that extends through an entire length of inner member  14 . This type of configuration allows the system to be passed over a guidewire for guiding the system to a desired deployment location. However, in other embodiments, inner member  14  can have a solid, non-tubular configuration. 
         [0034]    Distal end  11  of system  10  includes a tapered and flexible distal tip member  30  that is sufficiently flexible to permit advancement of stent deployment system  10  through the patient&#39;s lumen while minimizing trauma to the walls of the patient&#39;s lumen. Tip  30  is connected to inner member  14  adjacent stent mounting location  26 . Proximal end  13  of system  10  includes manifold housing  20  connected to lock housing  22 . Sheath  16  connects to manifold housing  20 . Strain relief jacket  24  surrounds sheath  16  adjacent its connection to housing  20  to provide strain relief for sheath  16 . Inner member  14  passes through both manifold housing  20  and lock housing  22 . Outer reinforcing member  32  surrounds and is bonded to inner member  14  adjacent proximal end  13  of system  10 . Reinforcing member  32  may be made of a relatively rigid material such as stainless steel. Port housing  34  is bonded to reinforcing member  32 . Port housing  34  has a bore aligned with an inner lumen of inner member  14  and functions to facilitate access to the inner lumen. 
         [0035]    Manifold housing  20  carries admission port  42  for injecting a contrast media into the interior of manifold housing  20 . The interior of manifold housing  20  may be in fluid communication with a passage between inner member  14  and sheath  16 . In use, the contrast media can be directed from the passage into the patient&#39;s body lumen through discharge ports (not shown). 
         [0036]    Lock housing  22  carries a threaded locking member (or lock nut)  46  which can be turned to engage reinforcing member  32 . Lock nut  46  selectively permits and fixes axially movement between the inner member and the sheath. Relative movement between the inner member and the sheath is permitted to define a transport position and a deploy position of the system  10 . 
         [0037]    First and second handles  48 ,  50  are secured to lock housing  22  and reinforcing member  32 , respectively. In the transport position, handles  48  and  50  are spaced apart and sheath  16  covers stent mounting location  26  to prevent premature deployment of stent  12 . When handles  48  and  50  are moved toward each other, sheath  16  slides rearwardly or proximally relative to inner member  14 . In other words, relative axial movement between handles  48  and  50  (represented by arrow A) results in relative axial movement between inner member  14  and sheath  16 . In particular, sheath  16  slides rearwardly from the transport position to the deploy position to fully expose stent mounting location  26  and permit stent  12  to freely expand toward its fully expanded diameter. After such expansion, the stent delivery system can be proximally withdrawn through the expanded stent and removed. 
         [0038]    Delivery system  10  may be equipped with an interlock configuration (e.g., interlock structures  27 ,  28 , or  29  of  FIGS. 2 and 3 ) that constrains relative axial movement between stent  12  and inner member  14  until after sheath  16  has been fully retracted. For example, when stent  12  is mounted on inner member  14  and restrained in the compressed orientation by sheath  16 , a proximal interlock geometry located at a proximal end  12   a  of stent  12  interlocks with proximal interlock geometry  27  adjacent the stent mounting location  26 , a mid interlock geometry located at one or more locations along length of stent  12  interlocks with a mid interlock geometry  28  adjacent the stent mounting location  26 , and a distal interlock geometry located at a distal end  12   b  of stent  12  interlocks with a distal interlock geometry  29  adjacent the stent mounting location  26 . The interlock geometries remain interlocked to constrain axial movement of stent  12  until after the sheath has been retracted beyond a predetermined location (e.g., the proximal-most end  12   a  of stent  12 ). When sheath  16  has been retracted beyond the predetermined location, the interlock geometry of stent  12  is allowed to expand. As the interlock geometry of the stent expands, the interlock geometry of stent  12  disengages from the proximal, mid, and distal interlock geometries thereby allowing inner member  14  of system  10  to be moved axially relative to the stent without interference from the interlock geometries. Stent interlocks are further described in co-pending U.S. patent application No. 60/800,106 entitled “IMPLANT AND DELIVERY SYSTEM WITH MULTIPLE MARKER INTERLOCKS” and filed on May 12, 2006, U.S. patent application Ser. No. 10/982,537 entitled “IMPLANT DELIVERY SYSTEM WITH MARKER INTERLOCK” filed on Nov. 4, 2004, U.S. Pat. No. 6,814,746 entitled “STENT DELIVERY SYSTEM WITH RETAINER” which issued on Jun. 28, 2004, U.S. Pat. No. 6,623,518 entitled “IMPLANT DELIVERY SYSTEM WITH INTERLOCK” which issued on Mar. 25, 2003, and U.S. patent application Ser. No. 09/954,555 entitled “IMPLANT DELIVERY SYSTEM WITH INTERLOCK” which was filed on Sep. 17, 2001, each of which is incorporated by reference in their entirety herein. 
         [0039]    Stent  12  has a length L and a circumference C, and includes a plurality of struts  86  (i.e., reinforcing members). At least some of the struts  86  have free terminal ends  72  that define proximal and distal ends  12   a  and  12   b  of the stent  12 . The stent  12  includes interlock geometry in the form of enlargements  47  positioned at the free terminal ends of the struts  86 . As shown in  FIG. 3 , the enlargements are circular enlargements. It will be appreciated that other shapes and interlock configurations could also be used. The enlargements  47  project outwardly from the struts  86  in a circumferential direction (i.e. in a direction coinciding with the circumference C of the stent  12 ). In certain embodiments, the stent  12  can be manufactured by cutting (e.g., laser cutting) the various features from a solid tube of material. When manufactured by this technique, the enlargements  47  do not project radially beyond an inner and outer diameter of the stent. 
         [0040]      FIGS. 4A and 4B  illustrate an alternate embodiment of a stent delivery system. Rapid exchange stent delivery system  60  includes sheath  66  and inner member  64  disposed within sheath. Manifold housing  70  is coupled to sheath  66 . Housing  70  includes side arm  72  and locking member  74 . Push wire  68  is coupled to inner member  64  at its distal end and to handle  80  at its proximal end. Inner member  64  and sheath  66  are axially slideable relative to one another. Push wire  68  and housing  70  are used to facilitate movement of inner member  64  relative to sheath  66 . Locking member  74  can be operated to couple housing  70  to push wire  68  in order to slide both sections along together. Relative movement between the inner member and the sheath is permitted to define a transport position and a deploy position of the system  60 . Stent (not shown) mounts over inner member  64  and is covered by sheath  66  so as to be retained in the collapsed state. The stent is released (i.e., deployed) by retracting sheath  66  to uncover or expose stent. System  60  includes proximal interlock structure (not shown) that prevents stent from prematurely deploying, one or more mid interlock structure (not shown) that assist with uniform stent deployment and with stent loading, and one or more distal interlock structure (not shown) that assist with uniform stent deployment and with stent loading. Upon release of stent from stent delivery system  60 , stent expands to an enlarged diameter to abut against the walls of the patient&#39;s lumen in order to support patency of the lumen. The expansion of stent also causes stent to disengage from proximal, mid, and distal interlock structures. 
         [0041]    Sheath  66  may be made of kink resistant extruded polymer tubing with adequate strength and lubricity for unsheathing a stent. Polymers such as nylon, PEBAX, polyethylene, or polyester may be used. Alternatively, thermoset polymers such as polyimide or braid reinforced polyimide may be used. In some embodiments the distal portion of the outer member is transparent to allow inspection of the stent within. Inner member  64  may be made of flexible kink resistant polymer such as metallic braid reinforced polyimide, although polymers such as nylon, PEBAX, polyethylene, or polyester may be used. Push wire  68  may be constructed of metal. In certain embodiments the proximal portion of push wire is comprised of stainless steel tubing and the distal portion of push wire  68  is comprised of metal wire. This combination provides adequate column strength throughout, good bending resistance proximally, and good bending flexibility distally. Housing  70  and locking member  74  may be comprised of polycarbonate, polystyrene, or other materials, and a sealing gland (not shown) may be used in cooperation with housing  70  and locking member  74  to effect a fluid seal and/or mechanical lock between housing, locking member, and push wire  68  as is well known in the art. Handle  80  may be comprised of polycarbonate, polystyrene, nylon, or other materials. Alternate materials for these components are generally well known in the art can be substituted for any of the non-limiting examples listed above provided the functional requirements of the component are met. 
         [0042]    Guidewire  90  has a nominal outer diameter of 0.010″-0.038″, such as 0.014″. Inner member  64  is dimensioned to allow low friction passage of guidewire  90  within guide wire lumen  95  and through RX port  97 . Guide wire lumen length can vary widely, for example within the range from 5 cm to 50 cm in length. In certain embodiments guide wire lumen  95  is approximately 30 cm in length. Sheath maximum outside diameter can range from about 10 Fr to about 3 Fr. A sheath outside diameter of about 5 Fr is desirable for compatibility with currently popular guide catheter (not shown) dimensions. Sheath length can be varied to suit the application of interest. Sheath lengths of 40 cm-200 cm have been found desirable. In certain embodiment a sheath length of about 145 cm has been used. 
         [0043]      FIGS. 5-9  illustrate a variety of fatigue resistant stents having different characteristics.  FIG. 5  illustrates expanded stent  52  similar to stent  12  shown in  FIGS. 2 ,  3 , and  4  and having enlarged ends  47  and mid-stent retainer pockets  12   y  that both interlock with interlock geometry of a delivery catheter. Stent  52  has cells  18 , each cell comprised of six strut bend regions  19 . Stent cells  18  are connected to adjacent cells  18  by means of interconnection regions  23 . Interconnection regions  23  are not aligned opposite to one another in adjacent cells  18  with regards to the lengthwise axis of the stent. Interconnection regions  23  have lengths along the length of stent  52 . Interconnection region  23  length is between approximately 0.5% and 5% of cell length with respect to the axial direction of stent length L. In certain embodiments interconnection region  23  length is between 0.5% and 3% of cell length. In some embodiments interconnection region  23  length is between 0.5% and 1.5% of cell length. Stent  52  may be comprised of metal, polymer, ceramic, permanent enduring materials, or bioabsorbable materials. Bioabsorbable stents  52  can be polymeric, bio-polymeric, ceramic, bio-ceramic, or metallic, or may be made from combinations of these materials. Bioabsorbable and non-bioabsorbable stents  52  may elute over time substances such as drugs. 
         [0044]      FIGS. 5A and 5B  illustrate unexpanded stent  52   a . Stent  52   a  is similar to stent  52  and has enlarged ends  47  and mid-stent retainer pockets  12   y  that both interlock with interlock geometry of a delivery catheter. Stent  52  has cells  18  (not shown), each cell comprised of six strut bend regions  19 . Stent cells  18  are connected to adjacent cells  18  by means of interconnection regions  23 . Interconnection regions  23  are not aligned opposite to one another in adjacent cells  18  with regards to the lengthwise axis of the stent. Interconnection regions  23  have lengths along the length of stent  52 . Interconnection region  23  length is between approximately 0.5% and 5% of cell length with respect to the axial direction of stent length L. Stent  52   a  may have the specific dimensions as delineated in  FIGS. 5A and 5B , and all such dimensions may be laser cut without any finishing. Stent  52   a  is finished by processes such as microgrit blasting to remove slag, electropolishing to remove stent material having heat affected zone and other imperfections, and surface passivation to render surface of stent  52   a  more resistant to corrosion. The dimensions shown in the figures are merely illustrative and should not be considered limitations of the invention. 
         [0045]      FIG. 6  illustrates expanded fatigue resistant stent  53  comprised of mesh  82 . Mesh  82  may be comprised of intertwined, joined, or non-woven filaments  81 . In some embodiments filaments  81  are braided, woven, knitted, circular knitted, compressed, or otherwise fabricated into a porous mesh structure having cells  18   p . Filaments  81  may be joined at one or more crossings  83  by sintering, bonding, soldering, fusing, welding, or other means. In other embodiments mesh  82  is comprised of a tube having cells  18   p  formed through the wall of the tube, by means such as laser cutting, electrochemical etching, grinding, piercing, or other means. In some embodiments mesh  82  is formed by electroforming. Stent  53  may have one or more enlarged ends  47 . Enlarged ends  47  may be formed integral to the stent, for example in a stent made using electroforming manufacturing methods, or may be joined to stent  53 , for example in a stent made by braiding, using methods known in the art such as welding or fusing. Stent  53  has one or more retainer pockets  12   p . One or more enlarged end  47  and retainer pocket  12   p  together with interlocking structure of a stent delivery catheter may comprise an interlocking stent delivery system. Stent  53  may be comprised of metal, polymer, ceramic, permanent enduring materials, or bioabsorbable materials. Bioabsorbable stents  53  can be polymeric, bio-polymeric, ceramic, bio-ceramic, or metallic, or may be made from combinations of these materials. Bioabsorbable and non-bioabsorbable stents  53  may elute over time substances such as drugs. 
         [0046]      FIGS. 7 and 8  illustrate alternate fatigue resistant stent embodiments. Coil stents  110 ,  120  are comprised of ribbon  111  having widths W and W′, respectively, wound into a hollow cylinder form and having a wind angles A and A′, respectively. Stent  120  is comprised of ribbon  111  having width W′ less than width W of ribbon in stent  110 , and having wind angle A′ greater than wind angle A of ribbon in stent  110 . Ends  112  of ribbon may be rounded to prevent tissue damage or tissue irritation in vicinity of ends  112  when stent  110 ,  120  is implanted into a patient. Ribbon  111  may be comprised of metal, polymer, ceramic, permanent enduring materials, or bioabsorbable materials. Bioabsorbable ribbons  111  can be polymeric, bio-polymeric, ceramic, bio-ceramic, or metallic, or may be made from combinations of these materials. Bioabsorbable and non-bioabsorbable ribbons  111  may elute over time substances such as drugs. 
         [0047]    Ribbon  111  is comprised of an expandable architecture  130  also suitable for use a coiled ribbon illustrates in  FIGS. 7 and 8 . One example of an expandable architecture  130  is illustrated in  FIG. 9 . Ribbon  111  is shown partially expanded and the ribbon and interlock structures are shown cut longitudinally and laid flat. Expandable architecture  130  is comprised of enlarged ends  47 , mid-stent retainer pockets  12   y , struts  86 , bend regions  19 , and one or more interconnection regions  113 . Struts  86  and bend regions  19  together form a zig-zag shaped expandable architecture of ribbon  111 . Other expandable architectures are contemplated for expandable architecture of ribbon  111  such as various serpentine or meandering paths. Interconnection regions  113  join adjacent ribbons  111  and can fracture in a controlled manner such that when fractured interconnection regions  113  no longer join adjacent ribbons  111 . 
         [0048]      FIG. 10  illustrates interconnection regions  113  that comprise holes  114  in bend regions  19  and one or more strand  115 . Strand  115  passes through holes  114  along a pathway that joins together adjacent ribbons  111   a  and  111   b . In the example illustrated in  FIG. 10 , strand  115  passes through holes  114  in adjacent bend regions  19  and forms a closed loop. Many other strand pathways are possible, such as a single strand  115  passing through holes  114  of multiple bend regions  19 , and other configurations as are apparent to those skilled in the art. Strand  115  is comprised of a material that fractures in a controlled manner, and may be formed of biodegradable suture or other materials. In an alternate embodiment interconnection regions  113  are comprised of a biodegradable coupling such as a tube that surrounds bend regions  19 . In another alternate embodiment, interconnection regions  113  are comprised of a biodegradable rivet that passes through holes  114  in adjacent bend regions  19 . 
         [0049]      FIG. 11  illustrates another example of an expandable architecture  130 . A fractional portion of ribbon  111  is shown partially expanded and the ribbon and interlock structures are shown cut longitudinally and laid flat. Expandable architecture  130  is comprised of cells  18 , enlarged ends  47 , mid-stent retainer pockets  12   y , struts  86 , bend regions  19 , and one or more interconnection regions  113 . Struts  86  and bend regions  19  together form a cellular expandable architecture of ribbon  111  with similarities to the cellular structures described in connection with at least  FIGS. 2 ,  3  and  5 . Interconnection regions  113  join adjacent ribbons  111  and can fracture in a controlled manner such that when fractured, interconnection regions  113  no longer join adjacent ribbons  111 . Interconnection regions  113  may be comprised of expanded ends  116  and receiver ends  117 , interdigitating ends  118 , or other structures. 
         [0050]    Coil stent architectures which may be incorporated as part of fatigue resistant stents are further described in U.S. patent application No. 60/674,859 entitled NON-FRACTURE STENT DESIGN which was filed on Apr. 25, 2005, and subsequently also filed as PCT/US06/15596 entitled CONTROLLED FRACTURE CONNECTIONS FOR STENT filed on Apr. 25, 2006, and each which is incorporated by reference in their entirety herein. 
         [0051]    The invention contemplated is suitable for stents in addition to those cited herein. For example, fatigue resistant stents may comprise tapered stents, flared stents, braided stents, bifurcation stents, and other stents as are known in the art. Tapered stents generally have a proximal end of one diameter and a distal end of a second diameter (typically a smaller diameter). Flared stents generally have a short tapered portion at the proximal end of a cylindrical stent, where the flared section is larger in diameter than the cylindrical portion. Braided stents are typically comprised of a tube manufactured by using a braiding method. An example of a braided stent is the Wallstent, sold by Boston Scientific, Natick, Mass. Bifurcation stents are placed in a patient where a vessel branches. Bifurcation stents are generally comprised of a single stent portion that branches into two stent portions and appears similar to a Y-fitting used to connect one piece of tubing to two pieces of tubing. 
         [0052]    In certain embodiments fatigue resistant stents are comprised of superelastic material, such as binary Nitinol alloys with nominal composition of 50-52 atomic percent nickel and the balance of the material comprised of titanium. In some embodiments the superelastic material is comprised of ternary or quaternary nitinol alloys having a nickel/titanium ratio of 1/1 to 1/1.3. In certain embodiments the superelastic material is comprised of binary Nitinol tubing having a composition of about 50.8 atomic percent nickel (about 56 weight percent nickel) and the balance of the material comprised of titanium with small amounts of impurities, the overall composition, structure, and properties falling within the requirements of ASTM Standard F-2063-05. Such material is available under order number SE508 from NDC Corporation of Fremont, Calif. In certain embodiments the superelastic material is comprised of binary Nitinol tubing having a composition of about 50.8 atomic percent nickel (about 56 weight percent nickel) and the balance of the material comprised of titanium with small amounts of impurities. 
         [0053]    In some embodiments, Nitinol is heat treated to improve the fatigue life of the material. One example of a manufacturing process for a 6 mm fatigue resistant stent is illustrated in  FIG. 12  and described below. Cold worked Nitinol tubing (approximately 40% cold work and approximate A F  of −10° C.) having an outside diameter of 0.060″ and a wall thickness of 0.0105″ is optionally stress annealed and then apertures may be laser cut through the wall of the tubing. The cut tube is expanded by forcing the cut tube onto a 2.0 mm outside diameter mandrel having a tapered end (first expansion). After first expansion the tubing is annealed on the 2.0 mm mandrel at 485±3° C. for 1 minute after which the A F  will be approximately +30° C. Intermediate expansions are carried out by forcing the cut tube onto successive 3.0 mm, 4.0 mm, and 5.0 mm outside diameter mandrels, each having a tapered end, with successive anneals of the tubing on each of the 3.0 mm, 4.0 mm, and 5.0 mm mandrels at 485±3° C. for 1 minute for each anneal. After the intermediate expansions the A F  will be approximately +30° C. Final expansion is carried out by forcing the cut tube onto a 6.0 mm outside diameter mandrel having a tapered end and is followed by annealing the tubing on the 6.0 mm mandrel at 600±2° C. for 45-60 seconds and then at 485±3° C. for 5 minutes on the same 6.0 mm mandrel. After the 600° C. anneal the A F  will be approximately +22° C. and after the final 485° C. anneal the A F  will be approximately −15° C. to −20° C. The 485° C. first and intermediate anneals will shape set the Nitinol and raise the austenite finish temperatures (A F ) to a level unsuitable for use as a stent in a patient. The 600° C. anneal will dissolve nickel rich precipitates in the material and the resultant more homogeneous material will be less prone to fatigue fracture. The 600° C. anneal will also lower the A F  somewhat. The final 485° C. anneal will shape set the Nitinol and further lower the A F  to a level suitable for use as a stent in a patient. In certain embodiments, Nitinol tubing having a composition of about 50.8 atomic percent nickel (about 56 weight percent nickel) and the balance of the material comprised of titanium, after being subjected to the heat treatment described above, will have an upper plateau stress of 355±7.2 MPa, a lower plateau stress of 104±7.2 MPa, an ultimate tensile stress of 1,088±51 MPa, and an elongation of 15.4±2.2% (measured in tension). 
         [0054]    Properties of stents can be measured in many ways. Particularly useful measurements include kink radius, flexural peak load, flexural modulus, and bend-rotate fatigue life. Kink radius is measured using the following method. A calibrated ruler is placed on a table and a stent is held by the ends with the long axis of the stent parallel to the table surface and parallel to the ruler. The stent is bent until it kinks. With the un-kinked ends of the stent parallel to each other the distance between the un-kinked parallel ends of the stent is measured using the ruler. The measurement is divided in half to arrive at the stent kink radius. The stents are preconditioned to 37° C. for at least one hour prior to kink testing, and are tested at ambient conditions. 
         [0055]    Flexural peak load and flexural modulus are measured by 3-point bending using the following method. A stent is loaded into a fixture having 3 mandrels oriented parallel to each other and at 90° to the long axis of the stent. Two of the mandrels are aligned horizontally below the stent and the third mandrel is aligned above the stent and midway between the two mandrels below the stent. The separation of the mandrels (span length) below the stent is prescribed according to the table below. 
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 Stent Length (mm) 
                 Span Length (mm) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 10-14 
                 6 
               
               
                   
                 15-19 
                 11 
               
               
                   
                 20-24 
                 16 
               
               
                   
                 25-35 
                 21 
               
               
                   
                 &gt;35 
                 Stent Length minus 4 mm 
               
               
                   
                   
               
             
          
         
       
     
         [0056]    The mandrel above the stent is advanced towards the axis of the stent on a testing machine having tensile and compressive capabilities and a recordation of force and displacement applied to the stent is recorded. The flexural peak load is the maximum force value in the force-displacement curve. The flexural modulus is the slope of the linear portion of the force-displacement curve. The stents are preconditioned to 37° C. in body temperature water bath for at least one minute prior to 3-point bending testing, and are tested at ambient conditions. 
         [0057]    Bend-rotate fatigue life is measured using the following method (the method is based on DIN 50113 (German Institute for Standardization)). Each end of a stent is mounted concentrically on the end of a post and the posts are rotated at the same frequency. The rotational axes of the posts are oriented at an angle of 90° to each other. The distance between the posts is adjusted until the smallest radius along the length of the outer diameter of the stent (worst case bending radius) is 26 mm. The stent is rotated at ≦10 Hz until the stent fractures. The cycles to failure is the number of full rotations made by the stent before the stent breaks. The test environment for bend-rotate fatigue is in air at 37° C. 
         [0058]    Stents manufactured according to the techniques and methods disclosed herein have exceptional fatigue resistance as shown in the examples below. 
       Example 1 
       [0059]    A 6 mm diameter stent having a structure as shown in  FIGS. 5A and 5B  was laser cut from binary nitinol alloy tubing SE508 (NDC Corporation, Fremont, Calif.) and expanded and heat treated using the exemplar processes described in conjunction with  FIG. 12  (hereinafter referred to as “Stent 6X”) to produce material having an upper plateau stress of 355±7.2 MPa and a lower plateau stress of 104±7.2 MPa, an ultimate tensile stress of 1,088±51 MPa, and an elongation of 15.4±2.2%. Stent 6X and competitive 6 mm stents were tested for kink radius, flexural properties, and bend-rotation fatigue endurance. Bend-rotation fatigue endurance subjected the stent struts to a maximum strain of ±3.5%. Percentage strain is defined as change in length divided by original length. Highest strain values are at the stent outer surface, as calculated by finite element analysis using material parameters derived from uncut stent tubing subjected to the same thermomechanical history as stents laser cut from the same tubing. As the table below shows, stent 6X has superior measured characteristics as compared to those of competitive stents. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
               
               
                   
                   
                   
                 Flexural 
                   
               
               
                   
                 Kink Radius 
                 Cycles to 
                 Modulus 
                 Flexural Peak 
               
               
                 Stent 
                 (inches) 
                 Failure (#) 
                 (g/mm) 
                 Load (g) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Competitor B 
                   
                 23,315 
                 10.03 
                 18.18 
               
               
                 Competitor CP 
                 0.375 
               
               
                 Competitor CS 
                   
                 667,974 
                 7.96 
                 15.99 
               
               
                 Competitor CZ 
                   
                   
                 3.56 
                 6.56 
               
               
                 Competitor G 
                   
                 151,371 
                 1.39 
                 3.37 
               
               
                 Stent P 
                 0.494 
                   
                 18.46 
                 36.16 
               
               
                 Stent 6X 1,2   
                 0.189 
                 &gt;20,000,000 
                 4.33 
                 8.63 
               
               
                   
                 0.171 
                   
                 3.90 
                 8.61 
               
               
                   
               
               
                   1 Two data sets for kink radius were generated 
               
               
                   2 Two data sets for flexural properties were generated 
               
             
          
         
       
     
       Example 2 
       [0060]    A 7 mm diameter stent having a structure substantially similar to that shown in  FIGS. 5A and 5B  was laser cut from binary nitinol alloy tubing SE508 (NDC Corporation, Fremont, Calif.) and expanded and heat treated using expansion, annealing, and other processes substantially similar to those described in conjunction with  FIG. 12  to produce material having an upper plateau stress of 355±7.2 MPa and a lower plateau stress of 104±7.2 MPa, an ultimate tensile stress of 1,088±51 MPa, and an elongation of 15.4±2.2%; it is hereinafter referred to as “Stent 7X”. Stent 7X and competitive 7 mm stents were tested for bend-rotation fatigue endurance. As the table below shows, stent 7X has superior measured characteristics as compared to those of a competitive stent. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
               
               
                   
                   
                   
                 Flexural 
                   
               
               
                   
                 Kink Radius 
                 Cycles to 
                 Modulus 
                 Flexural Peak 
               
               
                 Stent 
                 (inches) 
                 Failure (#) 
                 (g/mm) 
                 Load (g) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Competitor B 
                   
                 7,800 
                   
                   
               
               
                 Competitor CS 
                   
                 150,000 
               
               
                 Stent 7X 
                   
                 &gt;10,000,000 
               
               
                   
               
             
          
         
       
     
       Example 3 
       [0061]    An 8 mm diameter stent, having a structure substantially similar to that shown in  FIGS. 5A and 5B  was laser cut from binary nitinol alloy tubing SE508 (NDC Corporation, Fremont, Calif.) and expanded and heat treated using expansion, annealing, and other processes substantially similar to those described in conjunction with  FIG. 12  to produce material having an upper plateau stress of 355±7.2 MPa and a lower plateau stress of 104±7.2 MPa, an ultimate tensile stress of 1,088±51 MPa, and an elongation of 15.4±2.2%. The stent described in the above sentence is hereinafter referred to as “Stent 8X”. Along with competitive 8 mm stents, it was tested for kink radius, flexural properties and bend-rotation fatigue endurance. As the table below shows, stent 8X has superior measured characteristics as compared to those of competitive stents. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
               
               
                   
                   
                   
                 Flexural 
                   
               
               
                   
                 Kink Radius 
                 Cycles to 
                 Modulus 
                 Flexural Peak 
               
               
                 Stent 
                 (inches) 
                 Failure (#) 
                 (g/mm) 
                 Load (g) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Competitor A 
                 0.400 
                   
                   
                   
               
               
                 Competitor B 
                   
                 8,758 
               
               
                 Competitor CP 
                 0.475 
               
               
                 Competitor CS 
                 0.375 
                 12,084 
               
               
                 Competitor G 
                   
                 549,570 
               
               
                 Stent 8X 1   
                 0.195 
                 &gt;10,000,000 
                 4.46 
                 9.10 
               
               
                   
                 0.165 
               
               
                   
               
               
                   1 Two data sets for kink radius were generated 
               
             
          
         
       
     
         [0062]    In certain embodiments of the invention, the stents of the invention may be designed to resist fracture (as measured by bend-rotate fatigue test) over at least 100,000 cycles, at least 200,000 cycles, at least 500,000 cycles, at least 1,000,000 cycles, at least 2,000,000 cycles, at least 5,000,000 cycles, at least 10,000,000 cycles, or at least 20,000,000 cycles. 
         [0063]    An exemplar method of using a stent delivery system to deliver a fatigue resistant stent into a body of a patient is now described. Using techniques well known in the art, a guidewire is percutaneously inserted into a patient&#39;s blood vessel and advanced to a region of interest in the patient&#39;s body. Using imaging techniques such as fluoroscopy the diseased portion of the vessel is identified and a stent having the correct length and diameter for a treatment site is chosen. With reference to  FIGS. 1 ,  2 ,  3 ,  4 A,  4 B,  5 ,  5 A and  5 B self expanding stent delivery system  10 ,  60  is advanced over the guidewire to the treatment site and by using imaging techniques such as fluoroscopy both ends  12   a ,  12   b  of stent  12  are positioned at a correct location relative to the treatment site. 
         [0064]    Inner member  14 ,  64  is held stationary and sheath  16 ,  66  is withdrawn to expose stent  12 . Stent  12  expands into contact with a lumenal wall of the vessel as sheath  16 ,  66  is withdrawn. Distal interlock  26  prevents stent from compressing axially when sheath  16 ,  66  is withdrawn, thereby facilitating deployment of distal end  12   b  of expanded stent at the correct location and reducing forces required to withdraw sheath  16 ,  66 . Mid interlocks  28  (if used) prevent stent from compressing axially when sheath  16 ,  66  is withdrawn thereby reducing forces required to withdraw sheath  16 ,  66 . Proximal interlocks  27  secure stent to stent delivery catheter until sheath  16 ,  66  is withdrawn proximally to stent end  12   a , thereby reducing forces required to withdraw sheath  16 ,  66  and facilitating deployment of proximal end  12   a  of expanded stent at the correct location. After, and optionally, during stent deployment, stent markers  15  are imaged for various reasons including evaluating deployed stent position relative to treatment site, evaluating extent of stent diametrical expansion, and other reasons. 
         [0065]    Following implantation of a fatigue resistant stent into a patient the patient may return to the implanting physician for a followup visit. During followup the markers  15  of implanted stent  12 , stent  12 , or both may be imaged using imaging techniques such as fluoroscopy, ultrasound, or magnetic resonance imaging to assess whether or not stent  12  has fractured, or for other reasons. 
         [0066]    While the various embodiments of the present invention have related to stents and stent delivery systems, the scope of the present invention is not so limited. For example, it will be appreciated that the various aspects of the present invention are also applicable to other types of expandable implants and their delivery systems. By way of non-limiting example, other types of expanding implants that can benefit from application of the invention include anastomosis devices, blood filters, grafts, vena cava filters, percutaneous valves, aneurism treatment devices, or other devices. 
         [0067]    Modifications and equivalents of the disclosed concepts are intended to be included within the scope of the claims. Further, while choices for materials and configurations may have been described above with respect to certain embodiments, one of ordinary skill in the art will understand that the materials and configurations described are applicable across the embodiments.

Technology Classification (CPC): 0