# Patent

## Title
Deformable underlayer for stent

## Abstract

An endoprosthesis includes a brittle layer, e.g. a ceramic and an underlayer to accommodate dimensional changes as the endoprosthesis is flexed.

## Background
TECHNICAL FIELD
This invention relates to an elastic underlayer for a stent.
BACKGROUND
The body includes various passageways such as arteries, other blood vessels, and other body lumens. These passageways sometimes become occluded or weakened. For example, the passageways can be occluded by a tumor, restricted by plaque, or weakened by an aneurysm. When this occurs, the passageway can be reopened or reinforced with a medical endoprosthesis. An endoprosthesis is typically a tubular member that is placed in a lumen in the body. Examples of endoprostheses include stents, covered stents, and stent-grafts.
Endoprostheses can be delivered inside the body by a catheter that supports the endoprosthesis in a compacted or reduced-size form as the endoprosthesis is transported to a desired site. Upon reaching the site, the endoprosthesis is expanded, e.g., so that it can contact the walls of the lumen. Stent delivery is further discussed in Heath, U.S. Pat. No. 6,290,721, the entire contents of which is hereby incorporated by reference herein.
The expansion mechanism may include forcing the endoprosthesis to expand radially. For example, the expansion mechanism can include the catheter carrying a balloon, which carries a balloon-expandable endoprosthesis. The balloon can be inflated to deform and to fix the expanded endoprosthesis at a predetermined position in contact with the lumen wall. The balloon can then be deflated, and the catheter withdrawn from the lumen.
SUMMARY
In an aspect, the invention features an endoprosthesis including a stent wall having a stent body and ceramic having a defined grain or globular morphology and an underlayer between the stent body and the ceramic. The underlayer is more easily deformed than the ceramic and the stent body.
In an aspect, the invention features an endoprosthesis including a stent wall having a stent body formed of metal and ceramic formed of an oxide and a metal underlayer between the stent body and ceramic. The underlayer has a bulk modulus that is about 75% or less than the modulus of the stent body and the ceramic has a globular morphology.
In another aspect, the invention features a method of forming an endoprosthesis including providing a substrate, providing on a first surface of the substrate a metal layer, the metal layer having a first thickness less than the thickness of the substrate, providing a ceramic on the metal layer, providing a metal layer on a second surface of the substrate, the metal layer having a second thickness less than the thickness of the substrate, and different than the first thickness, providing a ceramic on the first metal layer, and utilizing the substrate in a stent.
Embodiments may include one or more of the following features. The underlayer can have a bulk modulus that is about 75% or less than the modulus of the stent body. The underlayer can have a thickness of about 1% or less than the stent body and 200% to 1% of the thickness of the ceramic. The underlayer can be a metal. The underlayer can be more dense than the stent body. The underlayer may include a polymer. The ceramic can form a relatively continuous layer having a globular morphology. The ceramic can have a defined grain morphology. The ceramic can be in particulate form. The underlayer may include a drug. The ceramic can be iridium oxide (IROX). The underlayer can include a higher density radiopaque component. The ceramic and underlayer can be on the abluminal surface only. The ceramic and underlayer can be on the abluminal and adluminal surfaces. The underlayer on the abluminal and adluminal surfaces can have different thicknesses or compositions. The ceramic on the abluminal and adluminal surfaces can have different morphologies or compositions. The ceramic can be directly atop the underlayer and the underlayer can be directly atop the stent body. The stent body can be stainless steel.
Embodiments may include one or more of the following features. The first surface can correspond to the luminal surface and the second surface can correspond to the adluminal surface. The first thickness can be greater than the second thickness.
Embodiments may include one or more of the following advantages. Stents can be formed with brittle coatings, e.g. ceramics, with reduced cracking or fracture on expansion or bending, e.g. around a curvature in a blood vessel. An undercoating is provided between the stent body and coating. The undercoating can have greater deformation or elasticity than the stent body and/or the brittle coating such that it absorbs strains of expansion, compression and bending during stent use without substantially modifying the mechanical performance of the stent body. The thickness of the undercoating and its elasticity are selected in coordination with the amount of stent body deformation upon expansion.
Still further features, aspects, and advantages follow.



DESCRIPTION OF DRAWINGS
FIGS. 1A-1C are longitudinal cross-sectional views illustrating delivery of a stent in a collapsed state, expansion of the stent, and deployment of the stent
FIG. 2 is a perspective view of a stent.
FIG. 3A is a cross-sectional view of a stent wall prior to expansion.
FIG. 3B is a cross-section of a stent wall after expansion.
FIG. 4 is a cross section of a stent wall.
FIGS. 5A-5C are views of ceramic morphologies.
FIGS. 6A-6C are schematics of morphologies.



DETAILED DESCRIPTION
Referring to FIGS. 1A-1C, a stent 20 is placed over a balloon 12 carried near a distal end of a catheter 14, and is directed through the lumen 16 (FIG. 1A) until the portion carrying the balloon and stent reaches the region of an occlusion 18. The stent 20 is then radially expanded by inflating the balloon 12 and compressed against the vessel wall with the result that occlusion 18 is compressed, and the vessel wall surrounding it undergoes a radial expansion (FIG. 1B). The pressure is then released from the balloon and the catheter is withdrawn from the vessel (FIG. 1C).
Referring to FIG. 2, the stent 20 includes a plurality of fenestrations 22 between struts defined in a wall 23. Stent 20 includes several surface regions, including an outer, or abluminal, surface 24, an inner, adluminal, surface 26, and a plurality of cutface surfaces 28. The stent can be balloon expandable, as illustrated above, or self-expanding stent. Examples of stents are described in Heath '721, supra.
Referring to FIG. 3A, an end on cross-sectional view of a strut region, a stent wall 23 includes a stent body 25 formed, e.g. of metal, and includes a first coating 32 of a relatively stiff or brittle material such as a ceramic, and a relatively flexible undercoating or underlayer 34 between the brittle coating 32 and the body 25. Referring as well to FIG. 3B, during use, e.g. on expansion (arrows) of the stent, the dimensions of the stent body 25 are changed, in this example reduced, as the body material is stretched. The strain induced by the change in geometry of the stent body 25 is substantially absorbed by the undercoating 34, which stretches to a larger thickness, thus limiting a dimensional change in the first coating 32. As illustrated, the thickness of T34 of the undercoating 34 is less than the thickness of T34E after expansion. The thickness T25 of the stent body before expansion is greater than the thickness T25E. The thickness T32 of the coating 32 is substantially constant before and after expansion.
The undercoating 34 is relatively deformable, elastically or plastically, compared to the coating 32 and as deformable or more deformable than the stent body 25. In embodiments, the modulus of elasticity and/or the bulk modulus (volumetric elasticity) of the undercoating is lower than the coating and the same as or less than the stent body. In embodiments, the modulus of elasticity and/or bulk modulus of the undercoating is about 75% of less, e.g. about 10% of the modulus of the stent body. In embodiments, the modulus of elasticity is about 186 GpA or less. The thickness of the undercoating is selected in coordination with the deformability of the undercoating material and the degree of deformities (e.g. due to stent expansion) that will be accommodated during stent use. In embodiments, the thickness of the undercoating is small compared to the thickness of the stent body, e.g. 10% or less, e.g. 1% or less than the thickness of the stent body. The thickness of the undercoating can be greater than or less than the thickness of the brittle coating. In embodiments, the thickness of the undercoating is about 100% or more, e.g. 200% of the thickness of the brittle coating. In other embodiments, the thickness of the undercoating is about 50% or less, e.g. 10% or less of the thickness of the coating. In some embodiments, the thickness of the undercoating can also be selected in coordination with the stent geometry. For example, the deformation of the stent wall may be concentrated in certain areas of the stent wall which exhibit high bending or deflection upon stent expansion. In embodiments, an undercoating can be used only in high deflection areas or the thickness can be increased in those areas. Suitable undercoatings include, e.g. malleable metals, e.g. gold, which may also be radiopaque materials, as described below. Suitable metals are described in Heath '720, supra.
Referring to FIG. 4, the underlayer can be tailored in coordination with the type of ceramic. For example, the underlayer can have different thicknesses on different surfaces of the stent. A stent body 25 includes on its abluminal side a ceramic layer 40 that has a relatively rough surface characterized by particulates or crystalline grains. The rough surface facilitates bonding of a polymer layer 42 including drug. The abluminal side also includes an underlayer 44. The ceramic layer 40, while brittle, is not susceptible to cracking or, cracking would not produce deleterious effects. As a result, the underlayer 44 is relatively thin to accommodate some dimensional change while keeping the overall wall thickness small.
The stent body 25 includes on its luminal side a ceramic coating 46 that is relatively thin, continuous, less rough than ceramic 40 and does not include a polymer layer over it. The ceramic coating 46 may have a morphology or roughness optimized to encourage endothelialization. The abluminal side also includes an underlayer 48 which is highly deformable, e.g. thicker than underlayer 44 to further protect ceramic 46.
The undercoating can be formed of a metal, metal matrix composite, a polymer, a ceramic, or a polymer ceramic composite. Multiple undercoating layers can be provided. In embodiments, suitable metals include relatively malleable metals such as silver or gold or highly elastic metals such as superelastic metals. In embodiments, the metal is relatively radiopaque compared to stent body. The metals can be deposited by, e.g. physical vapor deposition (PVD). Suitable metals are described in Heath '721, supra. Suitable polymers include drug eluting polymers. Suitable polymers include styrene-isobutylene styre, urethanes, and synthetic rubbers. Other suitable polymers are described in U.S. Ser. Nos. 11/752,736 and 11/752,772 filed May 23, 2007. Suitable ceramics include metal oxides and nitrides, such as of iridium, zirconium, titanium, hafnium, niobium, tantalum, ruthenium, platinum and aluminum. The ceramic can be crystalline, partly crystalline or amorphous. The ceramic can be formed entirely of inorganic materials or a blend of inorganic and organic material (e.g. a polymer). In embodiments, the thickness of the coatings is in the range of about 50 nm to about 2 um, e.g. 100 nm to 500 nm. The undercoating can also be selected as a tie layer to chemically enhance bonding between brittle coating and the stent body. Suitable materials are discussed in U.S. application Ser. Nos. 11/776,320, filed Jul. 11, 2007 and 11/776,304, filed Jul. 11, 2007.
The morphology and composition of the ceramic is selected for its mechanical characteristics, to enhance adhesion to the stent body and enhance adhesion of a polymer coating, for example, and/or to enhance therapeutic function such as reducing restenosis and enhancing endothelialization. Certain ceramics, e.g. oxides, can reduce restenosis through the catalytic reduction of hydrogen peroxide and other precursors to smooth muscle cell proliferation. The oxides can also encourage endothelial growth to enhance endothelialization of the stent. When a stent is introduced into a biological environment (e.g., in vivo), one of the initial responses of the human body to the implantation of a stent, particularly into the blood vessels, is the activation of leukocytes, white blood cells which are one of the constituent elements of the circulating blood system. This activation causes a release of reactive oxygen compound production. One of the species released in this process is hydrogen peroxide, H2O2, which is released by neutrophil granulocytes, which constitute one of the many types of leukocytes. The presence of H2O2 may increase proliferation of smooth muscle cells and compromise endothelial cell function, stimulating the expression of surface binding proteins which enhance the attachment of more inflammatory cells. A ceramic such as iridium oxide (IROX) can catalytically reduce H2O2. The morphology of the ceramic can enhance the catalytic effect and reduce growth of endothelial cells. Iridium oxide (IROX) is discussed further in Alt, U.S. Pat. No. 5,980,566. Defined grain morphologies may also allow for greater freedom of motion and are less likely to fracture as the stent is flexed in use and thus the coating resists delamination of the ceramic from an underlying surface and reduces delamination of an overlaying polymer coating. The stresses caused by flexure of the stent, during expansion or contraction of the stent or as the stent is delivered through a tortuously curved body lumen increase as a function of the distance from the stent axis. As a result, in embodiments, a morphology with defined grains is particularly desirable on abluminal regions of the stent or at other high stress points, such as the regions adjacent fenestrations which undergo greater flexure during expansion or contraction.
The morphology of the surface of the ceramic is characterized by its visual appearance, the size and arrangement of particular morphological features such as local maxima, and/or its roughness. In embodiments, the surface is characterized by definable sub-micron sized grains. Referring particularly to FIG. 5A, for example, in embodiments, the grains have a length, L, of the of about 50 to 500 nm, e.g. about 100-300 nm, and a width, W, of about 5 nm to 50 nm, e.g. about 10-15 nm. The grains have an aspect ratio (length to width) of about 5:1 or more, e.g. 10:1 to 20:1. The grains overlap in one or more layers. The separation between grains can be about 1-50 nm. In particular embodiments, the grains resemble rice grains.
Referring particularly to FIG. 5B, in embodiments, the surface is characterized by a more continuous surface having a series of shallow globular features. The globular features are closely adjacent with a narrow minima between features. In embodiments, the surface resembles an orange peel. The diameter of the globular features is about 100 nm or less, and the depth of the minima, or the height of the maxima of the globular function is e.g. about 50 nm or less, e.g. about 20 nm or less.
Referring to FIG. 5C, in other embodiments, the surface has characteristics between high aspect ratio definable grains and the more continuous globular surface and/or has a combination of these characteristics. For example, as shown in FIG. 4C, the morphology can include a substantially globular base layer and a relatively low density of defined grains. In other embodiments, the surface can include low aspect ratio, thin planar flakes. The morphology type is visible in FESEM images at 50 KX.
Referring to FIGS. 6A-6C, morphologies are also characterized by the size and arrangement of morphological features such as the spacing, height and width of local morphological maxima. Referring particularly to FIG. 5A, a coating 40 on a substrate 42 is characterized by the center-to-center distance and/or height, and/or diameter and/or density of local maxima. In particular embodiments, the average height, distance and diameter are in the range of about 400 nm or less, e.g. about 20-200 nm. In particular, the average center-to-center distance is about 0.5 to 2× the diameter.
Referring to FIG. 6B, in particular embodiments, the morphology type is a globular morphology, the width of local maxima is in the range of about 100 nm or less and the peak height is about 20 nm or less. In particular embodiments, the ceramic has a peak height of less than about 5 nm, e.g., about 1-5 nm, and/or a peak distance less than about 15 nm, e.g., about 10-15 nm. Referring to FIG. 6C, in embodiments, the morphology is defined as a grain type morphology. The width of local maxima is about 400 nm or less, e.g. about 100-400 nm, and the height of local maxima is about 400 nm or less, e.g. about 100-400 nm. As illustrated in FIGS. 6B and 6C, the select morphologies of the ceramic can be formed on a thin layer of substantially uniform, generally amorphous IROX, which is in turn formed on a layer of iridium metal, which is in turn deposited on a metal substrate, such as titanium or stainless steel. The spacing, height and width parameters can be calculated from AFM data. A suitable computational technique and further discussion of morphologies and layer form is provided in U.S. Ser. Nos. 11/752,736 and 11/752,772 filed May 23, 2007. The ceramic can also be provided in the form of particulates by, e.g., kinetic spraying. Kinetic spraying is described in U.S. Ser. No. 11/934,463 filed Nov. 2, 2007.
The stents described herein can be configured for vascular, e.g. coronary and peripheral vasculature or non-vascular lumens. For example, they can be configured for use in the esophagus or the prostate. Other lumens include biliary lumens, hepatic lumens, pancreatic lumens, and uretheral lumens. Any stent described herein can be dyed or rendered radiopaque by addition of, e.g., radiopaque materials such as barium sulfate, platinum or gold, or by coating with a radiopaque material. The stent can include (e.g., be manufactured from) metallic materials, such as stainless steel (e.g., 316L, BioDur® 108 (UNS S29108), and 304L stainless steel, and an alloy including stainless steel and 5-60% by weight of one or more radiopaque elements (e.g., Pt, Ir, Au, W) (PERSS®) as described in US-2003-0018380-A1, US-2002-0144757-A1, and US-2003-0077200-A1), Nitinol (a nickel-titanium alloy), cobalt alloys such as Elgiloy, L605 alloys, MP35N, titanium, titanium alloys (e.g., Ti-6Al-4V, Ti-50Ta, Ti-10Ir), platinum, platinum alloys, niobium, niobium alloys (e.g., Nb-1Zr) Co-28Cr-6Mo, tantalum, and tantalum alloys. Other examples of materials are described in commonly assigned U.S. application Ser. No. 10/672,891, filed Sep. 26, 2003; and U.S. application Ser. No. 11/035,316, filed Jan. 3, 2005. Other materials include elastic biocompatible metal such as a superelastic or pseudo-elastic metal alloy, as described, for example, in Schetsky, L. McDonald, “Shape Memory Alloys”, Encyclopedia of Chemical Technology (3rd ed.), John Wiley & Sons, 1982, vol. 20. pp. 726-736; and commonly assigned U.S. application Ser. No. 10/346,487, filed Jan. 17, 2003.
The stent can be of a desired shape and size (e.g., coronary stents, aortic stents, peripheral vascular stents, gastrointestinal stents, urology stents, tracheal/bronchial stents, and neurology stents). Depending on the application, the stent can have a diameter of between, e.g., about 1 mm to about 46 mm. In certain embodiments, a coronary stent can have an expanded diameter of from about 2 mm to about 6 mm. In some embodiments, a peripheral stent can have an expanded diameter of from about 4 mm to about 24 mm. In certain embodiments, a gastrointestinal and/or urology stent can have an expanded diameter of from about 6 mm to about 30 mm. In some embodiments, a neurology stent can have an expanded diameter of from about 1 mm to about 12 mm. An abdominal aortic aneurysm (AAA) stent and a thoracic aortic aneurysm (TAA) stent can have a diameter from about 20 mm to about 46 mm. The stent can be balloon-expandable, self-expandable, or a combination of both (e.g., U.S. Pat. No. 6,290,721). The ceramics can be used with other endoprostheses or medical devices, such as catheters, guide wires, and filters.
All publications, patent applications, patents and other references mentioned herein are incorporated by reference herein in their entirety.
Still other embodiments are in the following claims.

## Claims

1. An endoprosthesis, comprising:
a stent wall including
a stent body,
a ceramic coating having a defined grain or globular morphology, and
an underlayer between the stent body and the ceramic coating, the underlayer comprising a polymer and being more easily deformed than the ceramic coating and the stent body and having a thickness selected in coordination with deformability of the underlayer and degree of deformity of the stent body to be accommodated due to expansion of the stent body during use, such that the ceramic coating remains substantially dimensionally constant during expansion of the stent body.

2. The endoprosthesis of claim 1 wherein underlayer has a bulk modulus that is about 75% or less than the modulus of the stent body.

3. The endoprosthesis of claim 1 wherein the thickness of the underlayer is about 1% or less than the stent body and 200% to 1% of the thickness of the ceramic.

4. The endoprosthesis of claim 1 wherein the underlayer is comprises a metal.

5. The endoprosthesis of claim 1 wherein the underlayer is more dense than the stent body.

6. The endoprosthesis of claim 1 wherein the ceramic coating forms a relatively continuous layer having a globular morphology.

7. The endoprosthesis of claim 1 wherein the ceramic coating has a defined grain morphology.

8. The endoprosthesis of claim 1 wherein the ceramic coating is in a particulate form.

9. The endoprosthesis of claim 1 wherein the underlayer includes comprises a drug.

10. The endoprosthesis of claim 1 wherein the ceramic coating is iridium oxide.

11. The endoprosthesis of claim 1 wherein the underlayer includes comprises a higher density radiopaque component.

12. The endoprosthesis of claim 1 wherein the stent wall comprises an abluminal surface and an adluminal surface, and the ceramic coating and underlayer are on the abluminal surface only.

13. An endoprosthesis, comprising:
a stent wall including
a stent body,
a ceramic coating having a defined grain or globular morphology, and
an underlayer between the stent body and the ceramic coating, the underlayer being more easily deformed than the ceramic coating and the stent body and having a thickness selected in coordination with deformability of the underlayer and degree of deformity of the stent body to be accommodated due to expansion of the stent body during use, such that the ceramic coating remains substantially dimensionally constant during expansion of the stent body, and

wherein the stent wall defines an abluminal surface and an adluminal surface, and the ceramic coating and underlayer are on the abluminal surface and on the adluminal surface.

14. The endoprosthesis of claim 13 wherein the underlayer on the abluminal surface and the underlayer on the adluminal surface have different thicknesses or compositions.

15. The endoprosthesis of claim 1 wherein the ceramic coating is directly atop the underlayer and the underlayer is directly atop the stent body.

16. The endoprosthesis of claim 1 wherein the stent body is stainless steel.

17. An endoprosthesis, comprising:
a stent wall including
a stent body formed of a metal,
a ceramic coating formed of an oxide and having a globular morphology, and
an underlayer formed of another metal between the stent body and the ceramic coating, the underlayer having a bulk modulus that is about 75% or less than the modulus of the stent body and having a thickness selected in coordination with deformability of the underlayer and degree of deformity of the stent body to be accommodated due to expansion of the stent body during use, the thickness of the underlayer being less than the thickness of the ceramic coating and the underlayer having a density greater than the density of the stent body, such that the ceramic coating remains substantially dimensionally constant during expansion of the stent body.

18. An endoprosthesis, comprising:
a stent wall including
a stent body,
a ceramic coating having a defined grain or globular morphology, and
an underlayer comprising a polymer, the underlayer being between the stent body and the ceramic coating and being more easily deformed than the ceramic coating and the stent body.

19. An endoprosthesis, comprising:
a stent wall having an abluminal surface and an adluminal surface, the stent wall including
a stent body,
a ceramic coating having a defined grain or globular morphology, and
an underlayer between the stent body and the ceramic coating, the underlayer being more easily deformed than the ceramic coating and the stent body, the ceramic coating and the underlayer being on the abluminal surface and on the adluminal surface, and the ceramic coating on the abluminal surface and the ceramic coating on the adluminal surface have different morphologies or compositions.