Abstract:
The invention relates to an intravascular stent wherein the intravascular stent has its inner surface treated to promote the migration of endothelial cells onto the inner surface of the intravascular stent. Particularly, the inner surface of the intravascular stent includes at least one groove. Methods for manufacturing an intravascular stent are also disclosed.

Description:
RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Application No. 60/064,916, filed Nov. 7, 1997. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The invention relates to an intravascular stent and method for manufacturing an intravascular stent, wherein the intravascular stent has its inner surface treated to promote the migration of endothelial cells onto the inner surface of the intravascular stent. 
     2. Description of Related Art 
     Various types of intravascular stents have been used in recent years. An intravascular stent generally refers to a device used for the support of living tissue during the healing phase, including the support of internal structures. Intravascular stents, or stents, placed intraluminally, as by use of a catheter device, have been demonstrated to be highly efficacious in initially restoring patency to sites of vascular occlusion. Intravascular stents, or stents, may be of the balloon-expandable type, such as those of U.S. Pat. Nos. 4,733,665; 5,102,417; or 5,195,984, which are distributed by Johnson &amp; Johnson Interventional Systems, of Warren, N.J., as the Palmaz™ and the Palmaz-Schatz™ balloon-expandable stents or balloon expandable stents of other manufacturers, as are known in the art. Other types of intravascular stents are known as self-expanding stents, such as Nitinol coil stents or self-expanding stents made of stainless steel wire formed into a zigzag tubular configuration. 
     Intravascular stents are used, in general, as a mechanical means to solve the most common problems of percutaneous balloon angioplasty, such as elastic recoil and intimal dissection. One problem intraluminal stent placement shares with other revascularization procedures, including bypass surgery and balloon angioplasty, is restenosis of the artery. An important factor contributing to this possible reocclusion at the site of stent placement is injury to, and loss of, the natural nonthrombogenic lining of the arterial lumen, the endothelium. Loss of the endothelium, exposing the thrombogenic arterial wall matrix proteins, along with the generally thrombogenic nature of prosthetic materials, initiates platelet deposition and activation of the coagulation cascade. Depending on a multitude of factors, such as activity of the fibrinolytic system, the use of anticoagulants, and the nature of the lesion substrate, the result of this process may range from a small mural to an occlusive thrombus. Secondly, loss of the endothelium at the interventional site may be critical to the development and extent of eventual intimal hyperplasia at the site. Previous studies have demonstrated that the presence of an intact endothelial layer at an injured arterial site can significantly inhibit the extent of smooth muscle cell-related intimal hyperplasia. Rapid reendothelialization of the arterial wall, as well as endothelialization of the prosthetic surface, or inner surface of the stent, are therefore critical for the prevention of low-flow thrombosis and for continued patency. Unless endothelial cells from another source are somehow introduced and seeded at the site, coverage of an injured area of endothelium is achieved primarily, at least initially, by migration of endothelial cells from adjacent arterial areas of intact endothelium. 
     Although an in vitro biological coating to a stent in the form of seeded endothelial cells on metal stents has been previously proposed, there are believed to be serious logistic problems related to live-cell seeding, which may prove to be insurmountable. Thus, it would be advantageous to increase the rate at which endothelial cells from adjacent arterial areas of intact endothelium migrate upon the inner surface of the stent exposed to the flow of blood through the artery. At present, most intravascular stents are manufactured of stainless steel and such stents become embedded in the arterial wall by tissue growth weeks to months after placement. This favorable outcome occurs consistently with any stent design, provided it has a reasonably low metal surface and does not obstruct the fluid, or blood, flow through the artery. Furthermore, because of the fluid dynamics along the inner arterial walls caused by blood pumping through the arteries, along with the blood/endothelium interface itself, it has been desired that the stents have a very smooth surface to facilitate migration of endothelial cells onto the surface of the stent. In fact, it has been reported that smoothness of the stent surface after expansion is crucial to the biocompatibility of a stent, and thus, any surface topography other than smooth is not desired. Christoph Hehriein, et. al.,  Influence of Surface Texture and Charge On the Biocompatibility of Endovascular Stents, Coronary Artery Disease , Vol. 6, pages 581-586 (1995). After the stent has been coated with serum proteins, the endothelium grows over the fibrin-coated metal surface on the inner surface of the stent until a continuous endothelial layer covers the stent surface, in days to weeks. Endothelium renders the thrombogenic metal surface protected from thrombus deposition, which is likely to form with slow or turbulent flow. At present, all intravascular stents made of stainless steel, or other alloys or metals, are provided with an extremely smooth surface finish, such as is usually obtained by electropolishing the metallic stent surfaces. Although presently known intravascular stents, specifically including the Palmaz™ and Palmaz-Schatz™ balloon-expandable stents have been demonstrated to be successful in the treatment of coronary disease, as an adjunct to balloon angioplasty, intravascular stents could be even more successful and efficacious, if the rate and/or speed of endothelial cell migration onto the inner surface of the stent could be increased. Accordingly, the art has sought an intravascular stent, and method for manufacturing an intravascular stent, which may increase the rate of migration of endothelial cells upon the inner surface of the stent after it has been implanted. 
     SUMMARY OF THE INVENTION 
     In accordance with the invention, the foregoing advantage has been achieved through the present intravascular stent having an outer surface and an inner surface. The present invention includes an improvement in such intravascular stents, and an improvement in the method for manufacturing such intravascular stents, by providing at least one groove disposed in the inner surface of the stent. A further feature of the present invention is that the at least one groove may have a width, a length, and a depth, and the width and depth may not vary along the length of the at least one groove. Further features of the present invention are that: the width of the groove may vary along the length of the at least one groove; the depth of the groove may vary along the length of the at least one groove; and both the width and the depth may vary along the length of the at least one groove. 
     Another feature of the present invention is that the at least one groove may have a length, a longitudinal axis, and a cross-sectional configuration, and the cross-sectional configuration of the at least one groove may vary along the length of the at least one groove. An additional feature of the present invention is that the cross-sectional configuration of the at least one groove may not vary along the length of the at least one groove. Further features of the present invention are that the cross-sectional configuration of the at least one groove may be: substantially symmetrical about the longitudinal axis of the at least one groove; substantially asymmetrical about the longitudinal axis of the at least one groove; substantially triangular shaped; substantially rectangular shaped; substantially square shaped; substantially U shaped; or substantially V shaped. 
     A further feature of the present invention is that the longitudinal axis of the at least one groove may be disposed: substantially parallel with the longitudinal axis of the stent; substantially perpendicular to the longitudinal axis of the stent; at an obtuse angle with respect to the longitudinal axis of the stent; or at an acute angle with respect to the longitudinal axis of the stent. An additional feature of the present invention is that the groove may have a depth within a range of approximately one-half to approximately ten microns, and the at least one groove may have a width within a range of approximately two to approximately forty microns. 
     It is believed that the improvements in intravascular stents and in methods for manufacturing intravascular stents of the present invention, when compared with presently known intravascular stents and methods for manufacturing such stents, has the advantage of increasing the rate of migration of endothelial cells upon the inner surface of the intravascular stent. 
    
    
     BRIEF DESCRIPTION OF THE DRAWING 
     In the drawing: 
     FIG. 1 is a partial cross-sectional, perspective view of a portion of a intravascular stent embedded within an arterial wall of a patient; 
     FIG. 2 is an exploded view of the outlined portion of FIG. 1 denoted as FIG. 2; 
     FIG. 3 is a partial cross-sectional, perspective view corresponding to FIG. 1 after the passage of time; 
     FIG. 4 is an exploded view of the outlined portion of FIG. 3 denoted as FIG. 4; 
     FIG. 5 is a partial cross-sectional view of the stent and artery of FIGS. 1 and 3 after a further passage of time; 
     FIG. 6 is an exploded view of the outlined portion of FIG. 5 denoted as FIG. 6; 
     FIG. 7 is a partial cross-sectional view of the stent and artery of FIG. 5, taken along lines  7 — 7  of FIG. 5, and illustrates rapid endothelialization resulting in a thin neointimal layer covering the stent; 
     FIG. 8 is a plan view of an interior portion of an unexpanded intravascular stent in accordance with the present invention; and 
     FIGS. 9-16 are various embodiments of an exploded view of a groove taken along line  9 — 9  of FIG. 8, illustrating various cross-sectional configurations and characteristics of various embodiments of grooves in accordance with the present invention. 
    
    
     While the invention will be described in connection with the preferred embodiment, it will be understood that it is not intended to limit the invention of that embodiment. On the contrary, it is intended to cover all alternatives, modifications, and equivalents, as may be included within the spirit and scope of the invention as defined by the appended claims. 
     DETAILED DESCRIPTION OF THE INVENTION 
     With reference to FIGS. 1 and 2, an intravascular stent  200  is illustrated being disposed within an artery  290  in engagement with arterial wall  210 . For illustrative purposes only, intravascular stent  200 , shown in FIGS. 1-6 is a Palmaz™ balloon-expandable stent, as is known in the art, stent  200  having an inner surface  201  and an outer surface  202 . FIGS. 1 and 2 illustrate stent  200  shortly after it has been placed within artery  290 , and after stent  200  has been embedded into arterial wall  210 , as is known in the art. FIGS. 1 and 2 illustrate what may be generally characterized as correct placement of an intravascular stent. Stent  200  preferably includes a plurality of metal members, or struts,  203 , which may be manufactured of stainless steel, or other metal materials, as is known in the art. As illustrated in FIGS. 1 and 2, correct placement of stent  200  results in tissue mounds  211  protruding between the struts  203 , after struts  203  have been embedded in the arterial wall  210 . Struts  203  also form troughs, or linear depressions,  204  in arterial wall  210 . Dependent upon the degree of blockage of artery  290 , and the type and amount of instrumentation utilized prior to placement of stent  200 , the mounds of tissue  211  may retain endothelial cells (not shown). 
     With reference to FIGS. 3 and 4, after the passage of time, a thin layer of thrombus  215  rapidly fills the depressions  204 , and covers the inner surfaces  201  of stent  200 . As seen in FIG. 4, the edges  216  of thrombus  215  feather toward the tissue mounds  211  protruding between the struts  203 . The endothelial cells which were retained on tissue mounds  211  can provide for reendothelialization of arterial wall  210 . 
     With reference to FIGS. 5 and 6, endothelial regeneration of artery wall  210  proceeds in a multicentric fashion, as illustrated by arrows  217 , with the endothelial cells migrating to, and over, the struts  203  of stent  200  covered by thrombus  215 . Assuming that the stent  200  has been properly implanted, or placed, as illustrated in FIGS. 1 and 2, the satisfactory, rapid endothelialization results in a thin tissue layer  218 , as shown in FIG.  7 . As is known in the art, to attain proper placement, or embedding, of stent  200 , stent  200  must be slightly overexpanded. In the case of stent  200 , which is a balloon-expandable stent, the balloon diameter chosen for the final expansion of stent  200  must be 10% to 15% larger than the matched diameter of the artery, or vessel, adjacent the site of implantation. As shown in FIG. 7, the diameter Di of the lumen  219  of artery  290  is satisfactory. If the reendothelialization of artery wall  210  is impaired by underexpansion of the stent or by excessive denudation of the arterial wall prior to, or during, stent placement, slower reendothelialization occurs. This results in increased thrombus deposition, proliferation of muscle cells, and a decreased luminal diameter Di, due to the formation of a thicker neointimal layer. 
     With reference to FIG. 8, an intravascular stent  300  in accordance with the present invention is illustrated. For illustrative purposes only, the structure of intravascular stent  300  is illustrated as being a Palmaz™ balloon-expandable stent, as is known in the art, illustrated in its initial, unexpanded configuration. It should be understood that the improvement of the present invention is believed to be suitable for use with any intravascular stent having any construction or made of any material as will be hereinafter described. Similarly, the improvement of the present invention in methods for manufacturing intravascular stents, is also believed to be applicable to the manufacturing of any type of intravascular stent as will also be hereinafter described. 
     As illustrated in FIG. 8, intravascular stent, or stent,  300  has an inner surface  301 , and an outer surface  302 , outer surface  302  normally being embedded into arterial wall  210  in an abutting relationship. In accordance with the present invention, the inner surface  301  of stent  300  is provided with at least one groove  400 . If desired, as will be hereinafter described in greater detail, a plurality of grooves  400  could be provided on, or in, inner surface  301  of stent  300 . The use of the term “groove” throughout this specification and in the claims is intended to be construed as: a channel or depression; a notch or a V-shaped or rounded indentation; or a scratch, or a mark, having been made with something sharp or jagged. The at least one groove  400 , or grooves, of the present invention may be provided in, or on, the inner surface  301  of stent  300  in any suitable manner, such as by: abrading the inner surface  301  of stent  300  to provide the at least one groove  400 ; a chemical or mechanical etching process; use of a laser or laser etching process; use of a diamond-tipped tool; use of any suitable abrasive material; or use of any tool or process, which can provide the desired groove, or grooves,  400  in, or on, the inner surface  301  of stent  300 , as will be hereinafter described in greater detail. 
     As shown in FIG. 8, the at least one groove, or grooves,  400  may be disposed with its longitudinal axis  410  being disposed substantially parallel with the longitudinal axis  305  of stent  300 . Alternatively, the longitudinal axis  410  of the at least one groove  400  may be disposed substantially perpendicular to the longitudinal axis  305  of stent  300 , as illustrated by groove  400 ″″; or the longitudinal axis  410  of the groove may be disposed at an obtuse, or acute, angle with respect to the longitudinal axis  305  of stent  300 , as illustrated by groove  400 ′. The angle that groove  400 ′ makes with respect to longitudinal axis  305  is either an acute or an obtuse angle dependent upon from which direction the angle is measured with respect to the longitudinal axis  305  of stent  300 . For example, if the angle between the longitudinal axis of groove  400 ′ and longitudinal axis  305  is measured as indicated by arrows A, the angle is an acute angle. If the angle is measured, as at arrows B, the angle is an obtuse angle. 
     Still with reference to FIG. 8, a plurality of grooves  400  may be provided on the inner surface  301  of stent  300 , two grooves  400  being shown for illustrative purposes only. Instead of a plurality of individual grooves, such as grooves  400 , a single groove  400 ″ could be provided in a serpentine fashion, so as to cover as much of the inner surface  301  of stent  300  as desired. Similarly, the grooves could be provided in a cross-hatched manner, or pattern, as shown by grooves  400 ′″. Grooves  400 ,  400 ′,  400 ″,  400 ′″, and  400 ″″ could be provided alone or in combination with each other, as desired, to provide whatever pattern of grooves is desired, including a symmetrical, or an asymmetrical, pattern of grooves. It should be noted that the angular disposition and location of the various grooves  400 - 400 ″″ will vary and be altered upon the expansion of stent  300  within artery  201  (FIG.  1 ), stent  300  being illustrated in its unexpanded configuration in FIG.  8 . Similarly, if stent  300  were a stent made of wire or lengths of wire, the disposition and angular orientation of the grooves formed on such wire, or wire members, would similarly be altered upon the expansion and implantation of such stent. It should be further noted, as previously discussed, that the groove, or grooves, of the present invention may be provided in, or on, the inner surface of any intravascular stent, so as to increase the rate of migration of endothelial cells on, and over, the inner surface of the intravascular stent. 
     With reference to FIGS. 9-16, various embodiments of groove  400  will be described in greater detail. In general, as seen in FIG. 9, groove  400  has a width W, a depth D, and a length L (FIG.  8 ). The width W and depth D may be the same, and not vary, along the length L of the groove  400 . Alternatively, the width W of the groove may vary along the length L of the groove  400 . Alternatively, the depth D of the groove may vary along the length L of the at least one groove. Alternatively, both the width W and the depth D of the groove  400  may vary along the length of the at least one groove. Similarly, as with the location and angular disposition of groove, or grooves,  400  as described in connection with FIG. 8, the width W, depth D, and length L of the groove, or grooves,  400  can vary as desired, and different types and patterns of grooves  400  could be disposed on the inner surface  301  of stent  300 . 
     As shown in FIGS. 9-16, groove  400  may have a variety of different cross-sectional configurations. As desired, the cross-sectional configuration of the groove, or grooves,  400  may vary along the length L of the groove; or the cross-sectional configuration of the groove may not vary along the length of the at least one groove  400 . Similarly, combinations of such cross-sectional configurations for the grooves could be utilized. The cross-sectional configuration of the groove, or grooves,  400  may be substantially symmetrical about the longitudinal axis  410  of groove  400  as illustrated in FIGS. 8 and 9; or the cross-sectional configuration of the at least one groove may be substantially asymmetrical about the longitudinal axis  410  of the least one groove, as illustrated in FIGS. 14 and 16. The cross-sectional configurations of groove  400  can assume a variety of shapes, some of which are illustrated in FIGS. 9-16, and include those cross-sectional configurations which are substantially: square shaped (FIG.  9 ); U shaped (FIG.  10 ); triangular, or V shaped (FIG.  11 ); rectangular shaped (FIG.  12 ); and triangular, or keyway shaped (FIG.  13 ). The wall surface  303  of each groove  400  may be substantially smooth, such as illustrated in FIGS. 9-13, or wall surface  303  may be jagged, or roughened, as illustrated in FIGS. 14 and 16. As illustrated in FIG. 15, wall surface  303  could also be provided with at least one protrusion  304  and at least one indentation  305  if desired, and additional protrusions and indentations  304 ,  305  could be provided as desired. 
     The depth D of groove, or grooves,  400  may fall within a range of approximately one-half to approximately ten microns. The width W of groove, or grooves,  400 , may fall within a range of approximately two to approximately forty microns. Of course, the width W and depth D could be varied from the foregoing ranges, provided the rate of migration of endothelial cells onto stent  300  is not impaired. The length L of groove  400  may extend the entire length of stent  300 , such as groove  400  of FIG. 8; or the length L′ of a groove may be less than the entire length of stent  300 , such as groove  400 ′″″ in FIG.  8 . The groove, or grooves, of the present invention may be continuous, or discontinuous, along inner surface  301  of stent  300 . 
     The portion of the inner surface  301  of stent  300  which has not been provided with a groove, or grooves,  400  in accordance with the present invention, may have any suitable, or desired, surface finish, such as an electropolished surface, as is known in the art, or may be provided with whatever surface finish or coating is desired. It is believed that when at least one groove in accordance with the present invention is disposed, or provided, on, or in, the inner surface  301  of an intravascular stent  300 , after the implantation of stent  300 , the rate of migration of endothelial cells upon the inner surface  301  of stent  300  will be increased over that rate of migration which would be obtained if the inner surface  301  were not provided with at least one groove in accordance with the present invention. 
     It is to be understood that the invention is not limited to the exact details of construction, operation, exact materials, or embodiments shown and described, as obvious modifications and equivalents will be apparent to one skilled in the art. Accordingly, the invention is therefore to be limited only by the scope of the appended claims.