Methods and apparatus for manufacturing an intravascular stent

Methods and apparatus for manufacturing an intravascular extender

BACKGROUND OF THE INVENTION

1. FIELD OF THE INVENTION

The invention relates to methods and apparatus for the manufacture of intravascular extenders, in which the intravascular extender has its inner surface treated to favor the migration of endothelial cells on the inner surface of the intravascular extender.

two. DESCRIPTION OF THE RELATED TECHNIQUE

Several types of intravascular extenders have been used in recent years. An intravascular extender generally refers to a device used for the support of living tissue during the healing phase, including the support of internal structures. It has been shown that intravascular extenders, or extenders, placed intraluminally, such as through the use of a catheter device, are highly effective in the initial restoration of patenting at vascular occlusion sites. Intravascular extenders, or extenders, may be of the balloon expandable type, such as those of US Pat. No. 4,733,665; 5,102,417; or 5,195,984, which are distributed by Johnson & amp; Johnson Interventional Systems, of Warren, New Jersey, as the expandable balloon extenders Palmaz and the Palmaz-Schatz or expandable balloon extenders from other manufacturers, as is known in the art. Other types of intravascular extenders are known as self-expanding extenders, such as Nitinol coil extenders or self-expanding extenders made of stainless steel wire formed in a tubular zigzag configuration.

Intravascular extenders are used, in general as a mechanical means to solve the most common problems of percutaneous balloon angioplasty, such as elastic recoil and intimate dissection. Another problem with the placement of intraluminal extenders shared with other revascularization procedures, including bypass surgery and balloon angioplasty, is artery restenosis. An important factor contributing to this possible reocclusion at the site of the extensor site is the injury and loss of the natural non-thrombogenic lumen of the artery lumen, the endothelium. The loss of endothelium, exposing the proteins of the thrombogenic arterial wall matrix, together with the generally thrombogenic nature of the prosthetic materials, initiates platelet deposition and activation of the coagulation cascade. Depending on a multitude of factors, such as the activity of the fibrinolytic system, the use of anticoagulants, and the nature of the substrate of the lesion, the result of this process can range from a small wall thrombus to an occlusive thrombus. Second, the loss of the endothelium at the site of the intervention may be critical for the development and extension of eventual intimate hyperplasia at the site. Previous studies have shown that the presence of an intact endothelial layer in an injured arterial site can significantly inhibit the extent of intimate hyperplasia related to smooth muscle cell. Therefore, rapid re-endothelialization of the arterial wall, as well as endothelialization of the prosthetic surface, or internal surface of the extensor, are critical for the prevention of low-flow thrombosis and continued patenting. Unless endothelial cells are somehow introduced from another source and seeded at the site, coverage of an injured endothelial area is achieved primarily, at least initially, by migration of endothelial cells from adjacent arterial areas of intact endothelium.

Although an in vitro biological coating has been previously proposed for an extender in the form of endothelial cells seeded on metal extenders, it is believed that there are serious logistical problems related to the seeding of living cells, which have been shown to be insurmountable. Therefore, it would be advantageous to increase the rate at which endothelial cells migrate from adjacent arterial areas of intact endothelium on the inner surface of the extensor exposed to blood flow through the artery. Currently, most intravascular extenders are made of stainless steel and such extenders are embedded in the arterial wall by tissue growth after weeks to months after placement. This favorable result occurs consistently with any extender design, as long as it has a reasonably low metal surface and does not obstruct the flow of fluid, or blood, through the artery. In addition, due to the dynamics of fluids along the internal arterial walls caused by the pumping of blood through the arteries, together with the interface of the blood and the endothelium, it has been desirable that the extenders have a surface very smooth to facilitate the migration of endothelial cells on the surface of the extensor. In fact, it has been reported that the smoothness of the extensor surface after expansion is crucial for the biocompatibility of an extender and, therefore, no surface topography that is not smooth is desirable. Christoph Hehiein 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 extender has been coated with whey proteins, the endothelium grows on the fibrin-coated metal surface on the inner surface of the extender until a continuous endothelial layer covers the surface of the extender, in days to weeks. The endothelium causes the thrombogenic metal surface to be protected against thrombus deposition, which is likely to form with slow or turbulent flow. Currently, all intravascular extenders made of stainless steel, or other alloys or metals, are provided with an extremely smooth surface finish, such as that normally obtained by electropolishing the metal surface of the extender. Although it has been shown that currently known intravascular extenders, specifically including expandable balloon extenders Palmaz and Palmaz-Schatz are successful in the treatment of coronary heart disease, as an adjunct to balloon angioplasty, intravascular extenders could be even more successful and effective, if the rate and / or speed of migration of endothelial cells on the inner surface of the extensor could be increased. It is believed that the forecast of at least one notch disposed on the inner surface of an extension increases the rate of endothelial cell migration on the inner surface of the extensor, after it has been implanted. Accordingly, the technique has investigated methods and apparatus for manufacturing an intravascular stent with at least one notch disposed on the inner surface of the stent. Known extenders formed by chemical stripping are known from WO 99/23977 and WO 01/00112.

SUMMARY OF THE INVENTION

In accordance with the invention, the foregoing advantage has been achieved through the present methods and apparatus for manufacturing an intravascular extender with at least one notch disposed on the inner surface of the extender.

In one embodiment of the present invention, a method of manufacturing a metal intravascular stent is provided by first forming an extender having an inner surface and an outer surface, and then forming at least one notch on the inner surface of the stent. by chemical stripping of the inner surface with a chemical process. The chemical process comprises the steps of coating the inner surface of the extender with a photosensitive material; insert a mask into the extender; irradiate the inner surface of the extender by a light source; remove the mask outside the extender; and chemically stripping areas exposed to light to produce at least one notch in the inner surface of the extender. The mask may be arranged on a deflated balloon before insertion, and the balloon expands after insertion. The light source can be a coaxial light source with multiple light beams in a single plane, and can be moved along the longitudinal axis of the extender. During the chemical pickling process, either the light source can be driven by a stepper motor for rotation movements, or the mask can be operated for rotation movements with the fixed light source.

It is believed that improvements in the methods and apparatus for manufacturing intravascular extenders of the present invention, when compared to methods currently known for manufacturing such extenders, have the advantage of increasing the migration rate of endothelial cells on the surface inside the intravascular extensor.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

Figure 1 is a perspective view of the partial cross section of a portion of an intravascular stent embedded within an arterial wall of a patient.

Figure 2 is an exploded view of the profiled portion of Figure 1 designated as Figure 2.

Figure 3 is a perspective view of the partial cross section corresponding to Figure 1, after the passage of time.

Figure 4 is an exploded view of the profiled portion of Figure 3 designated as Figure 4.

Figure 5 is a view of the partial cross section of the extensor and of the artery of Figures 1 and 3 after another time step.

Figure 6 is an exploded view of the profiled portion of Figure 5 designated as Figure 6.

Figure 7 is a view of the partial cross-section of the extensor and artery of Figure 5, taken along lines 7-7 of Figure 5, and illustrates the rapid endothelialization resulting in a thin neointimal layer that covers the extender.

Figure 8 is a plan view of an inner portion of an unexpanded intravascular stent in accordance with the present invention.

Figures 9 to 16 are various embodiments of an exploded view of a notch taken along line 9-9 of Figure 8, illustrating various cross-sectional configurations and features of various embodiments of notches. in accordance with the present invention.

Figure 17 is an exploded perspective view of an apparatus that uses a chemical removal method to manufacture extenders in accordance with the present invention.

Figure 17A is an exploded view of the partial cross section of a portion of Figure 17.

Figure 17B is an exploded view of the partial cross section of a portion of Figure 17; and

Figure 18A is an exploded perspective view of an apparatus that uses a rotating coaxial light source to inscribe micro notches into an intact tubular extender in accordance with the present invention.

Figure 18B is an exploded perspective view of an apparatus using a rotating mask and a fixed light source to inscribe micro notches into an intact tubular extender in accordance with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

With reference to Figures 1 and 2, an intravascular extender 200 is illustrated which is disposed within an artery 290 in engagement with the arterial wall 210. For illustrative purposes only, the intravascular extender 200, shown in Figures 1 to 6, is an expandable Palmaz balloon extender, as is known in the art, in which the extender 200 has an inner surface 201 and an outer surface 202. Figures 1 and 2 illustrate the extender 200 shortly after it has been placed inside the artery 290, and after the extender 200 has been embedded inside the arterial wall 210, as is known in the art. Figures 1 and 2 illustrate what can be characterized, in general, as the correct location of an intravascular stent. The extender 200 preferably includes a plurality of metal members, or struts 203, which can be made of stainless steel or other metal materials, as is known in the art. As illustrated in Figures 1 and 2, the correct location of the extender 200 leads to tissue mouths 211 projecting between the struts 203, after the struts 203 have been embedded in the arterial wall 210. The struts 203 also form channels, or linear depressions 204 in the arterial wall 210. Depending on the degree of blockage of the artery 290, and the type and amount of instrumentation used before the location of the extender 200, the tissue mouths 211 can retain endothelial cells (not shown).

With reference to Figures 3 and 4, after the passage of time, a thin layer of thrombus 215 quickly fills the depressions 204 and covers the interior surfaces 201 of the extender 200. As seen in Figure 4, the edges 216 of thrombus 215 they become horizontal towards the tissue mouths 211 projecting between the struts 203. Endothelial cells that were retained on tissue mouths 211 can provide re-endothelialization of the arterial wall 210.

With reference to Figures 5 and 6, endothelial regeneration of the wall of artery 210 is performed in a multi-center manner, as illustrated by arrows 217, in which endothelial cells migrate to and over struts 203 of the Extender 200 covered by thrombus 215. Assuming that extender 200 has been correctly implanted or placed, as illustrated in Figures 1 and 2, satisfactory rapid endothelialization results in a thin layer of tissue 218, as shown in Figure 7. As shown in the art. , to reach the proper location, or embedding, of the extender 200, the extender 200 must be slightly over-expanded. In the case of the extender 200, which is an expandable balloon extender, the diameter of the balloon chosen for the final expansion of the extender 200 must be between 10% and 15% larger than the adapted diameter of the artery, or blood vessel, adjacent to the implant side As shown in Figure 7, the diameter Di of the lumen 219 of the artery 290 is satisfactory. If the re-endothelialization of the wall of the artery 210 is impaired by insufficient expansion of the extensor or by excessive denudation of the arterial wall before or during the location of the extensor, a slower re-endothelialization occurs. This results in an increased deposition of thrombus, proliferation of muscle cells and a reduced luminarium diameter Di, due to the formation of a thicker neointimal layer.

With reference to Figure 8, an intravascular extender 300 in accordance with the present invention is illustrated. For illustrative purposes only, the structure of the intravascular extender 300 is illustrated as an expandable extender with a Palmaz balloon, as is known in the art, illustrated in its initial, non-expanded configuration. It should be understood that the improvement of the present invention is considered suitable for use with any intravascular extender that has any construction or is made of any material, as will be described below. Similarly, the improvement of the present invention in methods for manufacturing intravascular extenders is also considered applicable to the manufacture of any type of intravascular extender, as will also be described later.

As illustrated in Figure 8, the intravascular extender or extensor 300 has an inner surface 301 and an outer surface 302, in which the outer surface 302 is normally embedded in the arterial wall 210 in a buttressing relationship. In accordance with the present invention, the inner surface 301 of the extender 300 is provided with at least one notch 400. If desired, as will be described in more detail below, a plurality of notches 400 could be provided on or on the inner surface 301 of the extender 300. The use of the term "notch" through this specification and in the claims is intended to be interpreted as: a channel or depression; a groove or a V-shaped or rounded indentation; or a scratch or a mark, which has been made with something sharp or jagged. The at least one notch 400 or notches of the present invention are provided on or on the inner surface 301 of the extender 300 by a chemical pickling process that can provide the desired notch or notches 400 on or on the inner surface 301 of the extender 300, as will be described in more detail below.

As shown in Figure 8, the at least one notch or notches 400 may be arranged with its longitudinal axis 410 arranged substantially parallel with the longitudinal axis 305 of the extender 300. Alternatively, the longitudinal axis 410 of the at least one notch 400 may be disposed substantially perpendicular to the longitudinal axis 305 of the extender 300, as shown by the notch 400 ""; or the longitudinal axis 410 of the notch may be arranged at an acute or acute angle with respect to the longitudinal axis 305 of the extender 300, as illustrated by the notch 400 '. The angle that the notch 400 'forms with respect to the longitudinal axis 305 is either an acute angle or an obtuse angle depending on the direction in which the angle is measured with respect to the longitudinal axis 305 of the extender 300. For example, if The angle between the longitudinal axis of the notch 400 'and the longitudinal axis 305 is measured as indicated by the arrows A, the angle is an acute angle. If the angle is measured, as in arrows B, the angle is an obtuse angle.

Still with reference to Figure 8, a plurality of notches 400 may be provided on the inner surface 301 of the extender 300, and that two notches 400 are shown for illustrative purposes only. Instead of a plurality of individual notches, such as notches 400, an individual notch 400 "could be provided in a serpentine shape, to cover as much interior surface 301 of extender 300, as desired. Similarly, the notches could be provided in a cross hatched manner or pattern, as shown by the 400 '' notches. Samples 400, 400 ', 400' ', 400' '' and 400 ”” could be provided alone or in combination with each other, if desired, to provide any desired pattern of notches, including a symmetric or asymmetric pattern of the notches. It should be noted that the arrangement and angular location of the various notches 400 to 400 "" will vary and will be altered after the expansion of the extender 300 into the artery 201 (Figure 1), the extender 300 being illustrated in its non-expanded configuration in the figure 8. Similarly, if the extender 300 were an extender made of wire or wire lengths, the arrangement and angular orientation of the samples formed from said wire or wire members, will be similarly altered after the expansion and implantation of said extender. It should also be noted, as described above, that the notch or notches may be disposed on or on the inner surface of any intravascular extender to increase the rate of endothelial cell migration on or above the inner surface of the intravascular extender.

With reference to Figures 9 to 16, various embodiments of the notch 400 will be described in more detail. In general, as seen in Figure 9, the notch 400 has a width W, a depth D and a length L (Figure 8). The width W and depth D may be the same and may not vary along the length L of the notch

400 Alternatively, the width W of the notch may vary along the length L of the notch 400. Alternatively, the depth D of the notch may vary along the length L of the at least one notch. Alternatively, both the width W and also the depth D of the notch 400 may vary along the length of the at least one notch. Similarly, as with the location and angular arrangement of the notch or notches 400 as described in connection with Figure 8, the width W, the depth D and the length L of the notch or notches 400 may vary as desired, and different types or patterns of notches 400 could be arranged on the inner surface 301 of the extender 300.

As shown in Figures 9 to 16, the notch 400 may have a variety of different cross-sectional configurations. As desired, the configuration of the cross-section of the notch or notches 400 may vary along the length L of the notch; or the notch cross section configuration may not vary along the length of the at least one notch 400. Similarly, combinations of such cross-section configurations could be used for the notches. The cross-sectional configuration of the notch or notches 400 may be substantially symmetrical about the longitudinal axis 410 of the notch 400 as illustrated in Figures 8 and 9; or the cross-sectional configuration of the at least one notch can be substantially asymmetric about the longitudinal axis 410 of the at least one notch, as illustrated in Figures 14 and 16. The cross-sectional configuration of the groove 400 may take a variety of forms, some of which are illustrated in Figures 9 to 16, and include those cross-sectional configurations that are substantially: square in shape (Figure 9); U-shaped (figure 10); triangular or V-shaped (figure 11); rectangular in shape (figure 12); and triangular or cotter-shaped (figure 13). The surface of the wall 303 of each sample 400 may be substantially smooth, as illustrated in Figures 9 to 13, or the surface of the wall 303 may be serrated, or rough, as illustrated in Figures 14 and 16 As illustrated in Figure 15, the surface of the wall 303 could also be provided with at least one projection 304 and at least one indentation 305, if desired, and additional projections and indentations 304, 305 could be provided, if desired.

The depth D of the notch or notches 400 may fall within a range of about half to about ten microns. The width W of the notch or notches 400 may fall within a range from about two to about forty microns. Naturally, the width W and the depth D could vary with respect to the previous ranges, as long as the migration rate of endothelial cells on the extender 300 is not impaired. The length L of the notch 400 may extend the total length of the extender 300, such as the notch 400 of Figure 8; or the length L 'of a notch may be less than the total length of the extender 300, such as the notch 400 "" in Figure 8. The notch or notches of the present invention may be continuous or discontinuous along the surface interior 301 of extender 300.

The portion of the inner surface 301 of the extender 300, which has not been provided with a notch or notches 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 can be provided with any finish or surface coating, as desired. It is believed that when at least one notch in accordance with the present invention is provided, or provided on or on the inner surface 301 of an intravascular extender 300, after implantation of extender 300, the rate of migration of endothelial cells on the inner surface 301 of the extender 300 will be increased above the migration rate that would be obtained if the inner surface 301 was not provided with at least one notch in accordance with the present invention.

To manufacture intravascular extenders with at least one notch arranged on the inner surface of the extender, the best current technology to enroll micro notches on metals seems to be the chemical pickling photo. The present invention provides improved methods of inscribing notch patterns within an intact tubular extender.

With reference to Figures 17, 17A and 17B, a chemical removal technique and apparatus 600 for forming the desired notch or notches 400 on or on the inner surface 301 of the extender blank 300 is illustrated. A retention device of the extender 601, which is arranged with the extender blank 300, is provided with an orientation groove or location groove 469 '. A mask photo 602 is formed from a metal, such as Mylar film. The dimensions of the mask 602 correspond to the area of ​​the inner surface 301 of the extender 300. The mask 602 is formed in a cylindrical orientation to form a mask sleeve 603, which is wound on a deflated balloon 605, such as a balloon of a conventional balloon angioplasty catheter. A conventional photo-resistant material is coated by rotation on the inner surface 301 of the extender blank 300. The mask sleeve 603, disposed on the balloon 605, is inserted into the extender 300, and the balloon 605 is expanded to form the mask sleeve 603 at a butt joint relationship with the inner surface 301 coated photo-resistant of the extender 300 The balloon 605 can be provided with an orientation pin 606 corresponding to an orientation notch 607 on the mask sleeve 603, which, in turn, is aligned with a location groove 469 'on the blank of the extender 300. The expansion of the balloon 605 is sufficient to insert the mask sleeve 603 in abutment contact with the inner surface 301 coated photo-resistant of the extender 300; however, the balloon 605 is not sufficiently inflated to crush the photo-resistant material outside the extender 300. The inner surface 301 of the extender 300 is then irradiated through the inside of the balloon 605 through the wall of the balloon, such as by a suitable light source 610. The balloon 605 is then deflated and the mask sleeve 603 is removed from inside the extender 300. The non-polymerized photo-resistant material is removed by rinsing and the polymerized resistant material is hardened by cooking on the inside of the extender 300. The notch or notches 400 are then chemically stripped on the unprotected metal surface on the inner surface 301 of the extender 300. The cooked photo-resistant material is then removed by conventional chemical or mechanical techniques.

Alternatively, instead of using a Mylar layer as a mask 602 to form the mask sleeve 603, the mask 602 can be formed directly on the outer surface of the balloon 605, as shown in Figure 17A. The production of the mask 602 directly on the outer surface of the balloon can be carried out by physical adhesion of the mask 602 on the outer surface of the balloon 605, or by forming the mask 602 on the surface of the balloon 605 by deposition of the desired notch pattern 468 by deposition of UV light absorbing material by thin film methods. In the case of using the mask sleeve 603 as shown in Figure 17B, the material of the balloon must be sufficiently elastic to prevent creases from the wall of the balloon, which can mask the resulting mask 602. In the event that the mask 602 is formed on the balloon 605 as shown in Figure 17A, a non-elastic balloon 605 would be used, so as not to distort the resulting image by stretching the elastic wall of the balloon. If, on the other hand, the mask 602 physically adheres to the outer wall of the balloon 605, an elastic balloon 605 can be used, provided that the mask 602 adheres to the balloon 605 when the balloon 605 is in its fully expanded diameter.

With reference to Figures 18A and 18B, a method for creating notches inside an intact tubular extender 300 is shown, which involves the projection of light modeled into an extender 300 previously coated with photosensitive material, as described, for example. , in connection with Figure 17 (PSM). Areas exposed to light are subjected to chemical pickling to produce a pattern of notches. This method involves using a coaxial light source 800 with multiple small beams 801 of light in an individual plane. The light source 800 could travel along the longitudinal axis of the tube or extender 300, at a rate consistent with the proper exposure of the photosensitive material. Step-by-step motors could be used in order to drive the light source in the x and y planes, which would allow interlacing notches (see Figure 18A). A pass would create a spacing of 1 mm, while the next pass creates 500 m, and so on.

Rotational movements could introduce variability in the direction of the notch for zigzag, spiral or undulating patterns. Alternatively, the light source 800 could be fixed as shown in Figure 18B, and the beams would be as narrow and long as the necessary notches on the inner surface of the mask

602 The staggering of the mask 602 would allow narrow spacing of the notches.