Patent Description:
Stenting of peripheral blood vessels, particularly below-the-knee stenting, presents challenges that are not met by the current use of coronary stent designs applied in a peripheral intervention. Due to particularly difficult device design and delivery requirements of below-the-knee stenting, percutaneous transluminal angioplasty (PTA) also known as balloon angioplasty of the anterior or posterior tibial arteries or the peroneal artery is the current standard intervention protocol for ischemic artery disease in this anatomical region. There is, however, substantial agreement that stand-alone balloon angioplasty of the below the knee arteries is sub-optimal because lesions in this region tend to be highly complex with risk factors including small arterial diameter, lesion length, vascular dissections, diabetes and/or poor arterial run off. It has been observed that after one year post-PTA freedom from amputation, restenosis, or reintervention was only <NUM>%. Feiring reviewed data supporting the overall efficacy of bare metal stents (BMS) and drug-eluting stents (DES) in treating below-the-knee chronic limb ischemia (CLI) and found that the below-the-knee DES registry data report <NUM>,<NUM> DES implanted in <NUM> limbs with CLI. There are an additional <NUM> patients who have been randomized to balloon angioplasty or BMS versus DES. With the exception of a single paclitaxel DES study, all of the reported studies are concurrent in their findings, reporting that DES for CLI is a safe and effective treatment that is superior to either balloon angioplasty or BMS.

Particular study findings included the ACHILLES trial which randomized CLI patients to either the CYPHER DES (Cordis Corporation, Bridgewater, NJ) or percutaneous transluminal angioplasty (PTA). The binary restenosis rates after <NUM> year were <NUM>% with the CYPHER DES and <NUM>% with angioplasty. The DESTINY trial randomized patients to the XIENCE DES (Abbott Vascular, Santa Clara, CA) versus the MULTILINK VISION BMS (Abbott Vascular). Primary patency rates at <NUM> year were <NUM>% versus <NUM>%, and target lesion revascularization was <NUM>% versus <NUM>% with DES versus BMS, respectively. The YUKON-BTK trial compared a proprietary non-polymer sirolimus stent to the same uncoated BMS. The <NUM>-year primary patency rate for DES was <NUM>% versus <NUM>% for the BMS. Thus, after <NUM> year, all three randomized trials strongly endorsed the superiority of DES over balloon PTA or BMS.

While the data suggests that drug-eluting stenting of below-the-knee lesions is desirable, to date the commercially available drug-eluting stents have not achieved commercial success in the marketplace. The CYPHER DES (Cordis Corporation) was discontinued in <NUM> due to poor sales. The XIENCE PRIME DES (Abbott Vascular) is a coronary stent that was not approved by the U. Food and Drug Administration (USFDA) for below-the-knee indications. Similarly, the MULTI-LINK VISION BMS is a coronary stent which also has not been approved by the USFDA for below-the-knee indications.

Additionally, the ZILVER PTX DES (Cook Medical, Bloomington, IN) is a coronary stent design that has been approved by the USFDA for above-the-knee femoropopliteal artery disease. Finally, the STENTYS BTK (Stentys, Paris, France) DES stent has been used in below-the-knee interventions and is the first BTK DES approved by the Notified Body for commercial sale in Europe. The STENTYS BTK has not been approved by the USFDA for below-the-knee interventions.

<CIT> discloses a programmable, variably flexible modular stent that includes: (a) a plurality of basic circular ring units made from a thin malleable material, where each basic ring unit has a recurring sequence of circumferential segments and circumferential/longitudinal segments ; and (b) at least one bridging link that longitudinally connects a circumferential segment of each basic ring unit to a corresponding circumferential segment of an adjacent basic ring unit.

<CIT> discloses an implantable medical device, such as a stent or graft, having asperities on a designated region of its outer surface is disclosed. The asperities can serve to improve retention of one or more layers of a coating on the device and to increase the amount of coating that can be carried by the device. The implantable medical device does not comprise generally sinusoidal circumferential ring members, which are configured to nest with an adjacent generally sinusoidal circumferential ring member when the device is in its diametrically unexpanded state. Also, the implantable medical device does not comprise volume-enhancing features which are configured to add between about <NUM>% to about <NUM>% more surface volume to the outer abluminal surface of the device.

<CIT> discloses an aneurysm occlusion device positionable within a cerebral blood vessel covering a neck of an aneurysm on the blood vessel. The device includes a tubular element having a lumen surrounded by an occlusive sidewall including a plurality of gaps. The gaps are sufficiently small to cause at least partial occlusion against flow of blood from the blood vessel through the side wall into the aneurysm, but are expandable in response to a fluid pressure differential between a first area inside the lumen and a second area outside the lumen to allow flow of fluid through the side wall between the blood vessel and a side branch vessel.

Each of these prior devices have been coronary stent designs that have been employed in peripheral, particularly, below-the-knee vascular interventions. Heretofore, however, it has been unknown to design bare metal and/or drug-eluting stents to have properties that are optimally designed for delivery to and deployment within the below-the-knee vasculature.

A stent having an outer abluminal surface and an inner luminal surface, comprising.

These and other objects, features and advantages of the present invention will be more apparent to those skilled in the art from the following more detailed description of the present invention taken with reference to the accompanying drawings. The above summary is not intended to describe each disclosed embodiment or every implementation of the present invention. The Figures and Detailed Description that follow more particularly exemplify these embodiments.

<FIG> depict embodiments of the invention. The remaining Figures are for comparative purposes.

The device of the present invention will be described with reference to certain exemplary embodiments thereof. These exemplary embodiments are intended to be illustrative and nonlimiting examples of the present invention. The example embodiments are provided so that this disclosure will be thorough, and will fully convey the teaching to those who are skilled in the art. Those of ordinary skill in the art will understand and appreciate that variations in materials, structure, material properties, and tolerances may be made without departing from the scope of the invention, which is defined only by the claims appended hereto and their range of equivalents.

For ease of understanding, the present invention is described with reference to the accompanying Figures. In the accompanying Figures like elements are identified by like reference numerals.

For purposes of clarity, the following terms used in this patent application will have the following meanings:.

"Substantially" is intended to mean a quantity, property, or value that is present to a great or significant extent and less than totally.

"About" is intended to mean a quantity, property, or value that is present at ±<NUM>%. Throughout this disclosure, the numerical values represent approximate measures or limits to ranges to encompass minor deviations from the given values and embodiments having about the value mentioned as well as those having exactly the value mentioned. Other than in the working examples provided at the end of the detailed description, all numerical values of parameters (e.g., of quantities or conditions) in this specification, including the appended claims, are to be understood as being modified in all instances by the term "about" whether or not "about" actually appears before the numerical value. In addition, disclosure of ranges includes disclosure of all values and further divided ranges within the entire range, including endpoints given for the ranges.

"Shape memory alloy" is intended to mean a binary, ternary, quaternary metal alloy that recover apparent permanent strains when raised above an Austenitic transformation temperature (As). Shape memory alloys have two stable phases, i.e., a high-temperature or Austenite phase and a low-temperature or Martensite phase.

"Superelastic" is intended to mean a property of a material characterized by having a reversible elastic response in response to an applied stress. Superelastic materials exhibit a phase transformation between the austenitic and martensitic phases as the applied stress is loaded or unloaded.

"Radiopaque" is intended to mean any material that obstructs passage of radiation and increases contrast to X-ray or similar radiation imaging.

"Sinusoidal" is intended to mean a structure having a wave-form pattern characterized by sine and cosine functions as well as a wave-form pattern that is not rigorously characterized by those functions but nevertheless resemble such in a more general way. As a general example, a waveform pattern includes those characterized as having one or more peaks and valleys that are generally U-shaped, bulbous, or are more triangular in shape, such as V-shaped, zig-zag, or sawtooth shaped, or whose peaks and valleys are generally square or rectangular.

The terms "peak" and "valley" shall be defined with respect to the proximal and distal opposing ends of the stent. Moreover, for the sake of clarity, the terms "peak" and "valley" in reference to circumferential ring member or sub-element thereof are intended to include not only the point(s) of maximum or minimum amplitude on a circumferential ring, but also a small region around the maximum or minimum. More precisely, in the case of peaks, the 'small region' around the maximum is intended to include any point along the ring member which is distal of a line extending through the innermost part of the ring member at the maximum amplitude and perpendicular to the longitudinal axis of the stent up to the peak itself. In the case of valleys, the 'small region' around the minimum is intended to include any point along the ring member which is proximal of a line extending through the innermost part of the ring member at the minimum amplitude and perpendicular to the longitudinal axis of the stent up to the valley itself.

The term "volume-enhancing feature" is intended to mean a topographical feature on or in an abluminal (outer) or luminal (inner) surface of a stent that increases the surface area or surface volume of the stent when compared to a stent surface without the volume-enhancing feature. Examples of such topographical volume-enhancing features include, without limitation, surface depressions such as grooves or trenches and surface protrusions such as pyramidal, conical, columnar, cylindrical, cubic or other polygonal projections. Surface volume may be determined by conventional measurement methods, such as, for example, ISO <NUM>:<NUM> or ASTM D4417. For purposes of this application, the term "groove" or "grooves" is used for ease of reference and illustration and as an example of a volume-enhancing feature. The terms "groove" and "volume-enhancing feature" are used interchangeably in this description.

In accordance with the invention, provided is a stent having an outer abluminal surface and an inner luminal surface, comprising.

The stent of the invention is illustrated in <FIG>. Other Figures are for comparative purposes or refer to the prior art. Several alternative variants of the present disclosure are illustrated in the accompanying Figures. The embodiments of the peripheral below-the-knee stent are characterized by a tubular stent having a plurality of generally sinusoidal circumferential ring members with adjacent ring members being interconnected by at least one bridge member extending between a peak of a first ring member and a peak of an adjacent ring member and at least one bridge member extending between a valley of a first ring member and a valley of an adjacent ring member. The peak-peak bridge members alternate with the valley-valley bridge members along successive circumferential rows along a longitudinal axis of the tubular stent. The ring members each have a plurality of substantially linear strut members with opposing ends of each of the substantially linear strut members begin contiguous with one of a peak or a valley of the circumferential ring member.

The alternative variants disclosed herein differ from each other in one or more of the following general aspects: <NUM>) configuration of the radiopaque markers; <NUM>) surface topography the outer surface of the stent; and/or <NUM>) presence or absence of a drug coating on the outer surface of the stent. The variants of the peripheral below-the-knee stent of the present disclosure include the following:.

In a first comparative embodiment of the disclosure, the stent includes a plurality of projection members at each of the proximal and distal end of the stent. Each of the projection members is contiguous with a peak of a terminal circumferential ring of the stent. Each of the projection members comprises a frame defining a central open region. A radiopaque cuff is joined to each of the plurality of projection members and covers the central open region. The radiopaque cuff preferably wraps around and is secured to the frame of each projection.

In a second comparative embodiment of the disclosure, the stent does not include a plurality of projection members at each of the proximal and distal ends of the stent. Rather in the second embodiment, a radiopaque layer is coated onto an outer surface of the stent only at low-stress regions of the stent. The low-stress regions of the stent are typically the strut regions of the stent between the peaks and the valleys and not on the peaks and valleys or on the bridge members.

In a third comparative embodiment of the disclosure, the stent has a drug-eluting coating on the outer surface of the stent, with the stent being either the first embodiment or the second embodiment described above.

In a fourth comparative embodiment of the disclosure, either the first or second embodiments of the stent, as described above, may be employed. A plurality of surface volume-enhancing features, such as, for example, elongate grooves, are formed in or on the outer surface of the stent about at least a substantial extent of the stent's entire length. The plurality of volume-enhancing features are preferably oriented generally parallel to the longitudinal axis of the stent when the stent is in its diametrically expanded state. The plurality of volume-enhancing features may, optionally, also be formed in the plurality of projection members and radiopaque cuff in accordance with the first embodiment of the invention. Optionally, the plurality of volume-enhancing features may be formed in the outer surface of the stent prior to coating the stent with the radiopaque material in accordance with the second embodiment of the invention described above.

In a fifth embodiment of the disclosure which is in accordance with the invention, the third and fourth embodiments are combined such that the stent has a plurality of volume-enhancing features in or on either the outer surface of the stent or in the outer surface of the radiopaque coating and has a drug-eluting coating on the outer surface of the stent and/or the outer surface of the radiopaque coating. At least a portion of the drug elution coating is disposed within the volume-enhancing features. Those skilled in the art will appreciate that the volume-enhancing features or grooves provide additional surface volume to the stent and, therefore, accommodates a greater volume of the drug-eluting coating and, hence, a greater quantity of the drug than would be present with a drug-eluting coating when compared to a stent having a non-grooved surface.

In a sixth embodiment of the invention, the stent in accordance with the fifth embodiments is provided, with the stent having a hybrid structure of open cells, with a first open cell geometry positioned at proximal and distal ends or regions of the stent and a second open cell geometry begin present at an intermediate region of the stent.

A stent delivery system is described but not claimed. The delivery system comprises, generally, a catheter onto which the inventive stent is mounted toward a distal end of the catheter, an atraumatic tip at the distal end of the catheter, a sheath concentrically engaged about the catheter and configured to enclose the stent between the catheter and the sheath during delivery, a handle coupled to both the catheter and the sheath and having a retraction mechanism operably coupled to the sheath. Actuation of the retraction mechanism, retracts the sheath proximally into the handle, thereby exposing the stent for delivery to a desired site within a body.

The foregoing general descriptions of the variants of the disclosure will be described in greater particularity with reference to the accompanying Figures. While several embodiments are disclosed, only the stent <NUM> of <FIG> is an embodiment of the claimed invention.

Turning to <FIG> and <FIG> (comparative examples), a peripheral below-the-knee stent <NUM> is shown. In accordance with the first embodiment of the disclosure, stent <NUM> is a tubular member having a first end <NUM> and a second end <NUM> corresponding to the proximal and distal ends of the stent. Stent <NUM> also has a longitudinal axis L and a circumferential axis C. Stent <NUM> is composed of a plurality of rings <NUM> extending about the circumferential axis C of stent <NUM>. Laterally adjacent pairs of rings <NUM> are interconnected by at least one of a plurality of bridge members <NUM>. Each of the rings <NUM> has a sinusoidal configuration with a plurality of peaks <NUM> and valleys <NUM>. One of the plurality of bridge members <NUM> interconnects a peak <NUM> of one ring <NUM> to a valley <NUM> of a second adjacent ring <NUM>. More than one bridge member <NUM> preferably interconnects adjacent rings <NUM> about their circumference. The bridge members <NUM> support adjacent rings <NUM> in a spaced apart relationship and define a plurality of cells <NUM>, <NUM> in the space bounded by the bridge members <NUM> and sections of the rings <NUM>.

In each of the embodiments of the stent of the present disclosure, each of the plurality of bridge members <NUM> are substantially linear and, optionally, may have a taper in either width and/or thickness at an end of the bridge member <NUM> that connects to a valley <NUM>. This taper will aid in bend flexibility of the stent <NUM>.

The cells <NUM>, <NUM> are preferably a hybrid of different open cell geometries. As is known in the stent arts, closed-cells are characterized by small free cell areas between struts and bridge members and are constrained from longitudinal flexion about their entire free cell area. In contrast, open-cells have relatively larger free cell areas between struts or bridge members and have unconstrained regions of the free cell area. For purposes of the present application, reference to cell shape or cell area will be made based upon their shape or area when the stent is in its diametrically expanded state. Cells <NUM>, <NUM> are open regions defined between longitudinally adjacent rings <NUM> and extending about the circumferential axis of the stent <NUM>. The bridge members <NUM> delimit circumferentially adjacent cells <NUM>, <NUM>.

In accordance with the first embodiment of stent <NUM>, as depicted in <FIG> and <FIG>, or in accordance with the second embodiment of stent <NUM>, depicted in <FIG> (comparative example), and in the enlarged view of <FIG> (comparative example), first cell <NUM> is an open cell having a substantially V-shape and second cell <NUM> is an open cell having a generally Z-shape. The substantially V-shaped first cells <NUM> are positioned at each of the proximal end <NUM> and the distal end <NUM> of the stent <NUM>, <NUM>, while the substantially Z-shaped second cells <NUM> are positioned along an intermediate region <NUM> of stent <NUM>, <NUM>. This arrangement of open cells <NUM>, <NUM> lends high degrees of longitudinal flexibility and radial expandability to the stent <NUM>, <NUM>.

The stents <NUM>, <NUM> of the present disclosure have a wall thickness between about <NUM> and about <NUM>, with the wall thickness preferably between about <NUM> to about <NUM>. The wall thickness is ideally generally uniform about the longitudinal axis and circumferential axis of the stent <NUM>, <NUM>. The stents <NUM>, <NUM> have an expansion ratio of up to about <NUM>:<NUM> and are capable of being crimped to an outer diameter of about <NUM> outer diameter and radially expand up to an outer diameter of about <NUM>. The crimped diameter of about <NUM> allows for use of a <NUM> French delivery catheter sheath, which is well suited to percutaneous delivery through pedal access. Those skilled in the art will understand that the foregoing dimensions, ratios, sizes and other values are exemplary and that other wall thicknesses, expansion ratios, crimp diameters, expansion diameters, delivery sheath sizes and the like are also intended by the present disclosure.

Stents <NUM>, <NUM> are preferably made of shape memory alloy and/or superelastic alloy. As noted above, shape memory and/or superelastic alloys may be binary, ternary, quaternary, quinary or n-ary, where n-is an integer of the base value metal alloys. While binary nickel-titanium alloys are well known in the art, other alloy additions of platinum, palladium, tantalum, tungsten, zirconium, hafnium and/or gold may also be used. Further, it is preferably that the stents <NUM>, <NUM> be made by physical vapor deposition of shape memory alloy and/or superelastic alloy materials onto a cylindrical mandrel to form a stent hypotube on the cylindrical mandrel. The stent <NUM>, <NUM> pattern geometry then preferably laser cut into the stent hypotube and then removed from the cylindrical mandrel.

Physical vapor deposition of shape memory alloys and/or superelastic alloys onto cylindrical mandrels is known in the art. Such processes are exemplified by <CIT>, <CIT>, <CIT>.

The second embodiment of the stent <NUM> is illustrated with reference to <FIG> (comparative example). Stent <NUM> has the same structure of rings <NUM> and bridge members <NUM>, but lacks the proximal and distal projection members <NUM> or radiopaque cuffs <NUM> coupled to the proximal and distal projection members <NUM>. Instead of the proximal and distal projection members <NUM> and radiopaque cuffs, stent <NUM> has a coating of radiopaque material on portions of the outer or abluminal surface of the stent <NUM> as will be described in greater detail with reference to <FIG> hereinafter. Like stent <NUM>, stent <NUM> is made of a shape memory or superelastic material.

As best seen in <FIG> (comparative example), each peak <NUM> has an innermost part <NUM> and an outermost part <NUM> of the peak <NUM>. The innermost part <NUM> of peak <NUM> lies on a lateral surface of the ring member <NUM> and is positioned in the included angle formed by the adjacent struts <NUM> of which the peak <NUM> is the vertex. The outermost part <NUM> of peak <NUM> lies on an opposing lateral surface of the ring member <NUM> as the innermost part <NUM> and is positioned at the vertex of peak <NUM>. Similarly, an innermost part <NUM> of valley <NUM> lies on a lateral surface of the ring member and is positioned in the included angle formed by the adjacent struts <NUM> of the valley <NUM>. An outermost part <NUM> of valley <NUM> lies on an opposing lateral surface of the ring member as the innermost part <NUM> and is positioned at the vertex of the valley <NUM>.

Again, as best illustrated in <FIG> and <FIG> (comparative examples), each ring <NUM> is comprised of generally linear strut members <NUM> that extend in a generally helical axis, with either a right-handed or a left-handed orientation relative to the longitudinal axis L, of the stent <NUM>, <NUM> and between a peak <NUM> and a valley <NUM> on each of the plurality of rings <NUM>. In this manner, the sinusoidal shape of each ring <NUM> is formed. Optionally, the strut members <NUM> may be provided with an offset section <NUM>, as best illustrated in <FIG>, present at an intermediate point along a length of the strut members <NUM>. The offset section <NUM> is preferably a lateral offset along the circumferential axis of the stent <NUM>. Offset section <NUM> allows adjacent rings <NUM> to nest relative to each other and assists in allowing for the very low crimped profile and low crossing profile of the stent embodiments during delivery.

A first set of bridge members 18a interconnect an outermost portion <NUM> of a valley <NUM> with an innermost portion <NUM> of a valley <NUM> on an adjacent ring <NUM>, while a second set of bridge members 18b interconnect an innermost portion <NUM> of a peak <NUM> with an outermost portion <NUM> of an adjacent ring <NUM>. Optionally, and preferably, the bridge members of the first set of bridge members 18a are in alignment with along the longitudinal axis of the stent <NUM>, <NUM> while the bridge members of the second set of bridge members 18b are in alignment with the longitudinal axis of the stent <NUM>, <NUM>.

As noted above, adjacent rings <NUM> are maintained in spaced apart relationship by bridge members <NUM>. Adjacent rings <NUM> are in substantially synchronous alignment such that the peaks <NUM> and valleys <NUM> of adjacent pairs of rings <NUM> are in substantial alignment about both the circumferential axis C and longitudinal axis L of stent <NUM>, <NUM>. In this manner, a plurality of rows <NUM> are formed between adjacent rings <NUM> along the longitudinal axis of the stent <NUM>, <NUM>. As best illustrated with reference to <FIG>, the plurality of rows <NUM> are denoted as rows 11a, 11b, 11c, 11d, 11e and 11f. While only a few rows are illustrated in the enlarged fragmentary view of <FIG>, those skilled in the art will appreciate, as illustrated in <FIG>, that the plurality of rows <NUM> extend along the entire longitudinal axis of the stent <NUM>, <NUM> ending only with the terminal rings <NUM> at the first end <NUM> and second end <NUM> of the stent <NUM>, <NUM>.

Rows <NUM> are the circumferential spaces between longitudinally adjacent rings <NUM> and include the bridge members <NUM> that maintain spacing between the longitudinally adjacent rings <NUM> forming each row <NUM>. The first set of bridge members 18a and the second set of bridge members 18b are in circumferentially spaced apart relationship relative to one another and staggered in alternating rows <NUM>. This staggered relationship of the first set of bridge members 18a and the second set of bridge members 18b is illustrated in <FIG> wherein the first set of bridge members 18a are in row 11a and the second set of bridge members 18b are in row 11b and are circumferentially offset from the first set of bridge members 18a. The first set of bridge members 18a are generally aligned along the longitudinal axis L of the stent <NUM>, <NUM> and staggered in alternating rows <NUM>. As illustrated in <FIG>, first set of bridge members 18a are found in rows 11a, 11c and 11e. Similarly, the second set of bridge members 18b are generally aligned along the longitudinal axis L of the stent <NUM>, <NUM> and are staggered in alternating rows <NUM>. Also as illustrated in <FIG>, second set of bridge members 18b are found in rows 11b, 11d and 11f. These staggered patterns of bridge members <NUM> along the longitudinal axis L and offset patterns of bridge members <NUM> about the circumferential axis C of stent <NUM>, <NUM> are repeated along the entire intermediate section <NUM> of stent <NUM>, <NUM>.

In accordance with all embodiments of the stent <NUM>, <NUM> of the present disclosure, the terminal end rows <NUM> at each of the first end <NUM> and the second end <NUM> of the stent <NUM>, <NUM> are optionally configured as a circumferential series of V-shaped first open cells <NUM>. As illustrated in <FIG>, <FIG> and <FIG>, the V-shaped open cells <NUM> are formed by adjacent rings <NUM> synchronously positioned with peak <NUM> to peak <NUM> and valley <NUM> to valley <NUM> alignment in the longitudinal axis L of the stent <NUM>, <NUM>. Bridge members <NUM> interconnect adjacent peaks <NUM> and adjacent valleys <NUM> in the adjacent rings <NUM>.

The above-described hybrid combination of first open cells <NUM> and second open cells <NUM> having different open cell geometries, in combination with the shape memory or superelastic alloy construction of stent <NUM>, <NUM>, lends both column and radial strength and longitudinal flexibility to the stent <NUM>, <NUM>. These attributes are crucial to achieve high expansion ratios of up to or greater than <NUM>:<NUM>, crush resistance to at least about <NUM>% of the expanded diameter of the stent, a stent having a crimp diameter down to about <NUM> for low-crossing profile delivery compatible with a <NUM> French delivery system suitable for pedal access, and a uniform radial strength of at least about <NUM>. 5N/mm along the stent's entire circumference and length. These features of the stent <NUM>, <NUM> are all present where the stent <NUM>, <NUM> has a wall thickness between about <NUM> to about <NUM>, more particularly between about <NUM> to about <NUM> and even more particularly between about <NUM> and about <NUM>, and stent <NUM>, <NUM> lengths up to about <NUM>.

Physical vapor deposition of the shape memory or superelastic alloy of the stent <NUM>, <NUM> creates a stent material that is characterized by having at least <NUM>% fatigue resistance and higher corrosion resistance when compared with stents fabricated from the same shape memory or superelastic materials made by wrought material processing, which require secondary passivation to achieve acceptable fatigue and corrosion resistance.

One of ordinary skill in the art is able to readily derive and compare corrosion resistance and fatigue resistance of both the inventive stent and stents made from wrought materials without the exercise of routine experimentation. Ample guidance is available to measure corrosion and fatigue resistance, as well as axial and radial strength and crush resistance with reference to both regulatory guidance and standard test methodologies. For example, corrosion resistance for stents may be determined by ASTM F2129-17b, Standard Test Method for Conducting Cyclic Potentiodynamic Polarization Measurements to Determine the Corrosion Susceptibility of Small Implant Devices, ASTM International, West Conshohocken, PA, <NUM>, www. Fatigue resistance for stents may be determined by ASTM F2477-<NUM>(<NUM>), Standard Test Methods for in vitro Pulsatile Durability Testing of Vascular Stents, ASTM International, West Conshohocken, PA, <NUM>, www. org and/or ASTM F2942-<NUM>, Standard Guide for in vitro Axial, Bending, and Torsional Durability Testing of Vascular Stents, ASTM International, West Conshohocken, PA, <NUM>, www. The United States Food and Drug Administration has also issued a Guidance for Industry and FDA Staff entitled <NPL>) and <NPL>) both of which provide guidance on corrosion and fatigue testing for stents.

When the comparative example stent <NUM>, <NUM> is compared with the ZILVER (Cook Medical) stent, as illustrated in <FIG> (further comparative examples), the ZILVER stent has a single open cell geometry that is uniform throughout the stent. As illustrated in <FIG>, the ZILVER stent has a generally WV-shaped open cell geometry, shaded for reference that is consistent along the entire length of the stent. Moreover, the ZILVER stent has peaks and valleys with enlarged widths that accommodate connection with the bridge members relative to the peaks and valleys that are not connected by bridge members. In contrast, the inventive stent <NUM> has a hybrid open cell geometry with the first open cells <NUM> having a generally V-shape and the second open cells <NUM> having a generally Z-shape, both are shaded for reference.

The basic geometry of stent <NUM>, <NUM> as described above is common to all the following embodiments, which differ only in i) presence or absence surface topographical features; ii) presence or absence of a drug coating; and/or iii) presence or absence of proximal and distal projection members.

Turning to <FIG> in the accompanying Figures there is depicted embodiments of the stent <NUM> of the invention having an outer abluminal surface and an inner luminal surface, comprising.

The stent <NUM> has a plurality of volume-enhancing features <NUM>, such as elongate grooves, formed in the outer surface of the stent <NUM>. The volume-enhancing features <NUM> are preferably, but not necessarily, formed in the entire outer surface of the stent <NUM>, including the rings <NUM> and the bridge members <NUM>. As an alternative to the volume-enhancing features <NUM> being formed in or on the outer surface of the stent <NUM>, the volume-enhancing features <NUM> may be formed in or on an outer surface of a radiopaque coating which is coated onto the outer surface of the stent, as will be described in greater detail hereinafter. Thus, the volume-enhancing features <NUM> may be formed in the outer surface of the tent <NUM> or in the outer surface of a radiopaque layer which, itself, is immediately adjacent the outer surface of the stent <NUM>.

The volume-enhancing features <NUM> may have virtually any transverse cross-sectional shape including, without limitation, V-shape, U-shape, keyhole-shape, or the like. While volume-enhancing features <NUM> are shown as linear grooves in <FIG>, the volume-enhancing features <NUM> may also be sinusoidal, meander or have other curvilinear shapes along the longitudinal axis L of the stent <NUM>. The volume-enhancing features <NUM> each have a width W and a depth D. Depth D and width W may have the same value, e.g., <NUM> depth, <NUM> width, or may have different values, e.g., <NUM> depth, <NUM> width. Adjacent grooves <NUM> further have an inter-groove spacing <NUM> which is a distance between the adjacent grooves <NUM>. The inter-groove spacing <NUM> may either be measured edge to edge or center to center of the adjacent grooves <NUM>. The inter-groove spacing <NUM> may be greater than or equal to the groove <NUM> width W or, alternatively, may be less than or equal to groove <NUM> width W. The volume-enhancing feature <NUM> may have a width to depth ratio been about <NUM>:<NUM> to about <NUM>:<NUM>. The use of the term "groove" intended to be construed as a channel or depression; a notch or indentation that does not pass entirely through the thickness of the material in which the groove is present.

The volume-enhancing features <NUM> of the present invention are configured to add between about <NUM>% to about <NUM>% more surface volume to the outer or abluminal surface of the stent. Those skilled in the art will understand that the degree of added surface volume is a function of the geometry, spacing, width and depth of the volume-enhancing features <NUM> on the surface of stent <NUM>.

, demonstrated that the presence of microgrooves on the luminal surfaces of a MULTI-LINK VISION (Abbott Vascular, Santa Clara, CA) bare metal coronary stent exhibited significantly lower levels of neointimal proliferation and greater mature neointima at a faster rate when compared to flat non-grooved surfaces in humans. Methods of forming the microgrooves on the luminal stent surfaces are found in <CIT>.

Unlike the grooves on the luminal surface of a coronary stent, as described in Vesga, B. or <CIT>, the grooves <NUM> of the present invention are present in the outer surface <NUM> of the stent <NUM>. In accordance with one embodiment of the invention, as illustrated in <FIG>, stent <NUM> has a plurality of grooves <NUM> formed in its outer surface <NUM> and a drug eluting coating <NUM> covering the outer surface <NUM> of the stent <NUM> and at least partially filling each of the plurality of grooves <NUM>. Regardless of the depth D and width W of the grooves <NUM> and regardless of the inter-groove spacing <NUM>, the presence of the grooves <NUM> serves to increase the available surface volume for the drug eluting coating <NUM> when compared to a non-grooved surface. It is within the ordinary skill of one in the art through routine experimentation to determine the desired depth D, width W and inter-groove spacing <NUM> based upon any given specific stent design. Further, one skilled in the art will understand and appreciate that at the position of any given groove <NUM>, the thickness of the drug eluting coating <NUM> is greater than the thickness of the drug eluting coating covering the inter-groove surfaces of the stent <NUM>. The increase thickness of the drug eluting coating <NUM> in the regions of the grooves <NUM> not only increases the amount of drug capable of eluting from those groove <NUM> regions, but also increases the elution time profile overall when compared to non-grooved stent surfaces.

For example, where an individual groove <NUM> has a width of <NUM>, a depth of <NUM> and a length of <NUM>, for example on an individual bridge member <NUM> having a length of <NUM>, the groove <NUM> provides an additional volume of <NUM><NUM>. Where there are three grooves <NUM> on an individual bridge member <NUM>, the total additional volume is <NUM><NUM> when compared to a non-grooved surface for a single individual bridge member <NUM>.

Where the drug eluting coating <NUM> has a thickness of about <NUM>-<NUM> from the outer surface <NUM> of the stent <NUM>, not including the depth of the grooves <NUM>, the drug eluting coating <NUM> will have a thickness of about <NUM> when measured from the bottom surface of the grooves <NUM>.

Turning to <FIG> (comparative examples) in which the end projection members <NUM> are illustrated in greater detail. End projection members <NUM> extend from an outermost portion <NUM> of peak <NUM> and serve as a platform for attaching a radiopaque marker. In accordance with an embodiment of the disclosure invention, the end projection members <NUM> may be a quadrilateral frame defining a central open space <NUM>. The frame has a first end frame member <NUM> that is coupled to peak <NUM> and a second end frame member <NUM> at an opposing end of the end projection <NUM> and in spaced apart relationship to the first end frame member <NUM>. Lateral frame members <NUM> extend between the first end frame member <NUM> and the second end frame member <NUM> and are in spaced apart relationship with one and other. The central open space <NUM> is bounded on its lateral aspects by the lateral frame members <NUM> and on its end aspects by the first end frame member <NUM> and the second end frame member <NUM>. The lateral frame members <NUM> are preferably thinner in wall thickness than the first end frame member <NUM> and the second end frame member <NUM> and are inset from outer lateral edges thereof, thereby defining a first recess <NUM> and a second recess <NUM> relative to the outer lateral edges of the first end frame member <NUM> and the second end frame member <NUM>. Similarly, by having a thinner wall thickness than the first end frame member <NUM> and the second end frame member <NUM>, the lateral frame members also define a third recess <NUM> by this differential thickness.

A radiopaque cuff member <NUM> is coupled to the end projection <NUM>. The radiopaque cuff member <NUM> may be a tubular member that is flattened or crimped onto the end projection <NUM> or it may be a planar member that is wrapped around and secured to the end projection <NUM>. The radiopaque cuff member <NUM> seats within and against first recess <NUM>, second recess <NUM> and third recess <NUM> and covers and at least substantially encloses the open space <NUM> in the end projection <NUM>. Preferably, the radiopaque cuff member <NUM> has a thickness selected to correspond to depths of the first recess <NUM>, second recess <NUM> and third recess <NUM> such that an outer surface of the radiopaque cuff member <NUM> lies substantially co-planar with outer surfaces of the first end frame member <NUM> and the second end frame member <NUM>.

The outer surfaces of the first end frame member <NUM> and the second end frame member are preferably co-planar with the outer surface <NUM> of the stent <NUM>. Similarly, the inner surfaces of the first end frame member <NUM> and the second end frame member are preferably co-planar with the inner or luminal surface of the stent <NUM>. The first end frame member <NUM>, the second end frame member <NUM>, and/or the radiopaque cuff <NUM> may also have grooves <NUM> formed in surfaces thereof. Similarly, the first end frame member <NUM>, the second end frame member <NUM>, and/or the radiopaque cuff <NUM> may also have grooves <NUM> formed in surfaces thereof and may have the drug eluting coating <NUM> over the outer surfaces thereof and at least partially filling the grooves <NUM> formed in surfaces thereof.

<FIG> depicts a variant of the stent <NUM>, <NUM> of the present disclosure which consists of radiopaque coated stent <NUM>. Radiopaque coated stent <NUM> is identical in structure with stent <NUM>, i.e., having sinusoidal rings <NUM> interconnected by bridge members <NUM>, having hybrid open cell structure with first open cells <NUM> with a generally V-shape at the first end <NUM> and the second end <NUM> (not shown) and second open cells <NUM> having a generally Z-shape along the intermediate section of radiopaque coated stent <NUM> and being without end projection members <NUM>. Radiopaque stent <NUM> has the addition of a radiopaque coating <NUM> on the outer surface <NUM> of the radiopaque coated stent <NUM>. Radiopaque coating <NUM> is preferably present only on low-stress or low-strain regions of the radiopaque coated stent <NUM> and forms a discontinuous partial coating along the longitudinal axis L of the radiopaque coated stent <NUM>. As illustrated in <FIG>, the radiopaque coating <NUM> is present only on intermediate sections of the struts <NUM> and not present on the struts at the peaks <NUM>, valleys <NUM> or bridge members <NUM> of the radiopaque coated stent <NUM>. By forming a discontinuous partial coating of the radiopaque coating <NUM> on only the low-stress or low-strain regions of the radiopaque coated stent <NUM>, risk of delamination of the radiopaque coating <NUM> from the outer surface <NUM> of the stent <NUM> during crimping and/or radial expansion of the stent <NUM> is significantly reduced.

Turning now to methods of applying the radiopaque coating <NUM> to the stent <NUM>, <FIG> and <FIG> illustrate alternative systems and methods for applying the radiopaque coating <NUM>. <FIG> illustrates the system and method <NUM> for applying the radiopaque coating <NUM> through a planar mask, whereas <FIG> illustrates the system and method <NUM> for applying the radiopaque coating <NUM> through a cylindrical mask.

The system and method <NUM> for applying the radiopaque coating <NUM> through a planar mask <NUM> is shown in <FIG>. Stent <NUM>, <NUM> is on a mandrel <NUM>. The planar mask <NUM> has a planar mask window <NUM> that has a length that is greater than or equal to the length of the stent <NUM>, <NUM> and a width that is less than or equal to the circumferential width of the radiopaque coating <NUM> to be applied to the low-stress or low-strain regions of the stent <NUM>, <NUM>. In accordance with the method <NUM> of the present invention, the radiopaque coating <NUM> is sputter coated <NUM> through the planar mask window <NUM> and onto the low-stress or low-strain regions of the stent <NUM>, <NUM>. The mandrel <NUM> is rotated about its longitudinal axis and metered so that only the low-stress or low-strain regions of the stent <NUM>, <NUM> are exposed to the planar mask window <NUM> during each sputter deposition run. The mandrel <NUM> also protects the inner surface of the stent <NUM>, <NUM> from the radiopaque coating <NUM> as it is in intimate contact with the inner surface of stent <NUM>, <NUM>. The planar mask <NUM> is maintained in sufficient proximity to stent <NUM>, <NUM> during the sputter deposition run so that there is no or acceptable levels of overspray of the radiopaque coating <NUM> onto undesired stent regions.

The system and method <NUM> for applying the radiopaque coating <NUM> through a cylindrical mask <NUM> is shown in <FIG>. Stent <NUM>, <NUM> is on a mandrel <NUM> and in intimate contact with the mandrel such that the inner or luminal surface of the stent <NUM>, <NUM> is shielded. The cylindrical mask <NUM> has a plurality of cylindrical mask windows <NUM>, has a length that is greater than or equal to the length of the stent <NUM>, <NUM> and a width that is less than or equal to the circumferential width of the radiopaque coating <NUM> to be applied to the low-stress or low-strain regions of the stent <NUM>, <NUM>. In accordance with the method <NUM> of the present invention, the radiopaque coating <NUM> is sputter coated <NUM> through at least one of the plurality of cylindrical mask windows <NUM> and onto the low-stress or low-strain regions of the stent <NUM>, <NUM>. The mandrel <NUM> and stent <NUM>, <NUM> may be rotated, or the entire assembly of the mandrel <NUM>, stent <NUM>, <NUM> and cylindrical mask <NUM> may be rotated about the assembly's longitudinal axis, or the mandrel <NUM> and stent <NUM>,<NUM> may be maintained stationary and the cylindrical mask <NUM> rotated about its longitudinal axis and over the mandrel <NUM> and stent <NUM>,<NUM>. In any case, the rotation is metered so that only the low-stress or low-strain regions of the stent <NUM>, <NUM> are exposed to at least one cylindrical mask window <NUM> during each sputter deposition run. Multiple magnetrons having different angular orientations may be employed to accomplish depositing the radiopaque coating <NUM> without the need for rotation of the stent <NUM>, <NUM> during the deposition run. The cylindrical mask <NUM> is maintained in sufficient proximity to stent <NUM>, <NUM> during the sputter deposition run so that there is no or acceptable levels of overspray of the radiopaque coating <NUM> onto undesired stent regions. In addition or alternatively, an overspray mask (not shown) may be employed such that unacceptable levels of overspray during sputter coating <NUM> of the radiopaque coating <NUM> are avoided.

As an alternative to sputter depositing the radiopaque coating, the radiopaque coating may be applied by selective plating or other methods, including, for example, electroplating, brush plating, electroless chemical plating, or 3D printing.

In accordance with either system and method <NUM> or system and method <NUM> for depositing the radiopaque coating <NUM> onto stent <NUM>, <NUM>, the radiopaque coating <NUM> will have a thickness dependent upon the radiopaque material employed, as different radiopaque materials have differing degrees of opacity under fluoroscopy. Typically, however, the radiopaque coating <NUM> will have a thickness between about <NUM> and <NUM>.

Where the stent <NUM>, <NUM>, <NUM> has grooves <NUM>, the grooves <NUM> may be formed in the outer surface <NUM> of the stent <NUM>, <NUM>, <NUM> and then the radiopaque coating <NUM> is sputter coated onto the outer surface <NUM> and into the grooves <NUM>. Alternatively, the radiopaque coating <NUM> may be sputter coated onto the outer surface <NUM> before the grooves <NUM> are formed into the outer surface <NUM>. In this latter case, the grooves <NUM> will be formed in the radiopaque coating <NUM> and, depending upon the thickness of the radiopaque coating <NUM> and the depth of the grooves <NUM>, the grooves <NUM> may pass through the radiopaque coating and into the outer surface <NUM> of the stent <NUM>, <NUM>, <NUM>.

Additionally, in accordance to the embodiment of the invention where a drug coating <NUM> is employed, the drug-coating <NUM> will be an outermost layer covering the radiopaque coating <NUM> and the grooves <NUM>, if present.

As with all stents, the peripheral stents <NUM>, <NUM>, <NUM>, <NUM> of the present disclosure require a delivery system to introduce and delivery the stent to a desired in vivo position. <FIG> illustrate an embodiment of a delivery system <NUM> in accordance with the present invention. As is common to stent delivery systems, a retractable sheath <NUM> covers a catheter <NUM>. Catheter <NUM> will typically have a guidewire lumen that passes either through its entire length in an over-the-wire version or passes along a more distal portion of the catheter <NUM> length in a rapid-exchange version. A stent mounting region <NUM> is at a distal end of the catheter <NUM> and the catheter <NUM> terminates at its distal end with an atraumatic tip <NUM>. Retractable sheath <NUM> is capable of reciprocal coaxial movement along a portion of the length of the catheter <NUM>. Sheath <NUM> will extend to the distal end of the catheter <NUM> and constrain the stent carried on the catheter <NUM> and typically abuts the atraumatic tip <NUM> in its extended state for delivery. Once positioned at a desired situs in vivo the sheath <NUM> is retracted proximally to expose and deploy the stent.

Handling of the catheter <NUM> and sheath <NUM> typically involves manipulating some sort of mechanism operably coupled to the catheter <NUM> and sheath <NUM> and capable of being controlled by an operator. In accordance with the delivery system <NUM> of the present disclosure, handle <NUM> is provided with a control actuator <NUM> and a flush port <NUM> to allow for flushing fluid to be applied through a lumen, such as the guidewire lumen, in the catheter <NUM>.

Handle <NUM> consists mainly of a housing <NUM> which contains the control actuator <NUM> and into which the catheter <NUM> or a support tube <NUM> coupled to a proximal end of catheter <NUM> on its distal end and to a flush luer <NUM> coupled to the flush port <NUM> in the housing <NUM>. The sheath <NUM> and the catheter <NUM> or support tube <NUM> pass through a strain relief member <NUM> and, optionally, a retaining member <NUM>, both of which allow the sheath <NUM> to pass through and into the housing <NUM>. A carrier member <NUM> is coupled to a proximal end of the sheath <NUM>. The carrier member <NUM> is, in turn, operably coupled to the control actuator <NUM> such that the control actuator <NUM> applies a motivating force to the carrier to retract or extend the sheath <NUM>.

Claim 1:
A stent (<NUM>, <NUM>) having an outer abluminal surface and an inner luminal surface, comprising
a. A plurality of generally sinusoidal circumferential ring members (<NUM>) having peaks (<NUM>) and valleys (<NUM>), wherein each generally sinusoidal circumferential ring member (<NUM>) is configured to nest with an adjacent generally sinusoidal circumferential ring member (<NUM>) when the stent is in its diametrically unexpanded state;
b. A plurality of bridge members (<NUM>) interconnecting adjacent pairs of sinusoidal circumferential ring members (<NUM>);
c. A plurality of volume-enhancing features (<NUM>) formed in or on the outer abluminal surface (<NUM>) of the stent, wherein the volume-enhancing features (<NUM>) are configured to add between about <NUM>% to about <NUM>% more surface volume to the outer abluminal surface of the stent as compared to a stent without the plurality of volume-enhancing features (<NUM>); and
d. A drug eluting layer (<NUM>) covering the entire outer abluminal surface (<NUM>) of the stent and fully filling the plurality of volume-enhancing features (<NUM>).