WO1999015104A1

WO1999015104A1 - Non-thrombogenic stent jacket

Info

Publication number: WO1999015104A1
Application number: PCT/IB1998/000499
Authority: WO
Inventors: Carlos Vonderwalde Freidberg
Original assignee: Carlos Vonderwalde Freidberg
Priority date: 1997-09-23
Filing date: 1998-04-06
Publication date: 1999-04-01
Also published as: AU6416298A

Abstract

A jacketed stent assembly comprising a tubular, expandable stent, preferably having a metallic framework, jacketed with a cylinder of biocompatible, non-thrombogenic expandable material, such as heterologous tissue, which, in a preferred embodiment, contains a therapeutic or diagnostic agent. In a preferred embodiment, the jacket of the expandable stent is formed of bovine or porcine pericardial tissue. A delivery catheter having an expandable member on its distal extremity may be used to deliver the stent assembly to a desired region in a lumen of a patient. The jacketed stent is expanded to be seated within the body lumen. Self-expanding jacketed stents are also contemplated.

Description

NON-THROMBOGENIC STENT JACKET

BACKGROUND OF THE INVENTION

This invention relates to the field of expandable intraluminal support devices such as stents and the like. Typically, stents are expandable, tubular metallic devices that are positioned within a patient's vasculature or other body lumen and expanded in order to support a vessel or body lumen at a desired intraluminal location to allow the flow of blood or other body fluids therethrough, Often, the stents are formed from a deformable metal and delivered to the desired intraluminal location by mounting the stent onto an expandable portion, e.g. a balloon, on the distal extremity of a delivery catheter. By advancing the catheter through the body lumen, the stent may be delivered to a desired position and expanded therein by expanding the expandable member, e.g. the balloon to an expanded configuration, seating it within the artery or other body lumen. Other implementations make use of a self-expanding stent formed from a suitable material such as psuedoelastic material that is delivered in a constricted condition and when released spontaneously expands to an enlarged configuration. In other embodiments, a stent made of shape memory alloy (e.g. NiTi alloy) may be inserted into the body lumen in a martensitic phase and transformed to an austenite phase which has an expanded memory when raised to a temperature above the transformation temperature, usually less than 45°C.

Stents are often used in conjunction with an intravascular treatment for obstructive coronary artery disease. For example, ablation, atherectomy, balloon dilation, laser treatment or other procedures are among the methods used to widen a stenotic region of a patient's vasculature. However, restenosis occurs in large percentage of percutaneous transluminal coronary angioplasty (PTCA) patients and rates can be even higher with other procedures. The prior art has employed a number of mechanical and pharmacological strategies to reduce the restenosis rate, but none have been particularly effective. Accordingly, stents have been proposed to maintain the patency of a treated vessel and prevent restenosis. Using stents, restenosis rates have fallen to less than 20%.

Restenosis is thought to be a natural healing reaction provoked by injury from the intravascular procedure. The healing process frequently causes thrombosis and may lead to intimal hyperplasia that occludes the vessel.

Although helpful in reducing restenosis, stents do not represent a complete solution. The framework of the stent may still allow migration and proliferation of the smooth muscle cells, while the stent itself can be thrombogenic. To address these problems, stents have been covered with DACRON, PTFE and autologous vein and the stent surface has been seeded with endothelial cells or otherwise treated. Each of these solutions suffer from certain drawbacks, such as not being biocompatible, lacking sufficient mechanical strength, having a surface that is difficult to prepare, lack of ready availability and being thrombogenic. Antithrombotic drug regimens, in which anticoagulants and thrombolytic agents are administered during and after deployment of the stent, have also been employed to reduce the risk of thrombosis.

Thus, there remains a need for a stent capable of minimizing restenosis while having a consistency similar to the native artery, a non-thrombogenic surface and sufficient mechanical strength as well as being biocompatible and readily available. This invention satisfies these and other needs.

SUMMARY OF THE INVENTION The invention is directed to a stent assembly suitable for maintaining the patency of a bodily lumen, generally comprising an expandable stent and an expandable, biocompatible, non-thrombogenic jacket such as heterologous tissue disposed about the exterior of the expandable stent. Preferably, the heterologous tissue is selected from the group consisting of bovine pericardium, porcine pericardium, aortic leaflet and other suitable heterologous tissue. The stent may be an expandable, tubular framework and may be a conventional self expanding or balloon expandable stent. The jacket is disposed about either or both of the outer and inner surfaces of the stent. In a preferred embodiment, the jacket is generally cylindrical for corresponding to the tubular framework or the stent.

This invention is also directed to a method for maintaining the patency of a bodily lumen generally comprising providing a delivery catheter having an expandable member on the distal extremity thereof, mounting the stent assembly, including a tubular stent with a jacket of biocompatible, non- thrombogenic expandable material such as heterologous tissue disposed about at least part of the stent, on the expandable member on the distal extremity of the delivery catheter. The catheter is advanced through the body lumen within the patient until the distal extremity of the catheter having the stent assembly is positioned at a desired location therein. The stent assembly is expanded by expanding the expandable member onto which the stent assembly is mounted to anchor the stent assembly within the body lumen. Once the stent assembly is effectively positioned within the body lumen, the expanded expandable member may be contracted, e.g. by deflating the balloon, and then the delivery catheter may be withdrawn.

A presently preferred embodiment of the invention is directed to a stent assembly suitable for expansion within a body lumen and delivery of a therapeutic or diagnostic agent therein, generally comprising an expandable stent and an expandable, biocompatible, non-thrombogenic jacket such as heterologous tissue, which contains the therapeutic or diagnostic agent and which is disposed about the expandable stent. The jacket releasably contains at least one therapeutic or diagnostic agent.

A wide variety of therapeutic or diagnostic agents for a variety of indications can be used, including angiogenesis agents and antithrombotic agents. The term "antithrombotic agents" is meant to include various agents for reducing the risk of thrombosis, including anticoagulants such as heparin, thrombolytic agents such as urokinase, streptokinase, tissue plasminogen activator (ACTIYSE), monoclonal antibodies such as abciximab (REOPRO), fibrinolytic agents, and the like. In a presently preferred embodiment, the jacket is impregnated with a liquid containing the therapeutic or diagnostic agent. For example, a jacket formed from heterologous tissue which is submerged in a solution of the therapeutic agent will absorb the solution. Thereafter, the stent assembly can be positioned at a desired site within the patient's body lumen, where the jacket will release the therapeutic agent. The jacket on the stent assembly may be impregnated just before use, or alternatively, stored in the therapeutic or diagnostic agent so that the stent assembly is preimpregnated.

The invention is also directed to a method for delivery of a therapeutic or diagnostic agent within a body lumen. The stent assembly including a tubular stent with a jacket of biocompatible, non-thrombogenic expandable material, such as heterologous tissue, containing a therapeutic or diagnostic agent is positioned within the bodv lumen as outlined above. With the stent assembly positioned at a desired location, the therapeutic or diagnostic agent is released from the jacket into the body lumen and thereby delivered at and around the location of the stent assembly within the body lumen.

The expanded jacket of biocompatible, non-thrombogenic expandable material such as heterologous tissue should extend over a substantial portion, preferably all, of the stenotic region in which it is disposed in order to minimize the restenosis.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is an isometric view, partially in section, of a stent assembly of the invention showing a tubular, expandable stent with an expandable biocompatible non-thrombogenic cylindrical exterior jacket. Figure 2 is an elevational view, partially in section, of a delivery catheter having a jacketed stent mounted on an inflatable balloon on the distal extremity of the catheter.

Figure 3 is a transverse cross sectional view of the stent assembly shown in Figure 1 , taken along lines 3-3. DETAILED DESCRIPTION OF THE INVENTION

In the embodiment of the invention shown in Fig. 1 , stent assembly 10 comprises a tubular, expandable metallic framework forming the stent 12 with an exterior jacket 14 of heterologous tissue. Preferably, metallic stent 12 extends about 1 mm beyond each end of jacket 14 to prevent prolapse of the tissue into the lumen of the stent when it is expanded. Jacket 14 may be secured to metallic framework 12 by any suitable means. For example, four radially spaced sutures 16 may be placed at each end of jacket 14.

In a presently preferred embodiment of the stent assembly illustrated in Fig. 1 , the jacket 14 contains a therapeutic or diagnostic agent, as shown in Fig. 3, illustrating a transverse cross section of the stent assembly shown in Fig. 1 , taken along lines, 3-3. Exterior jacket 14 preferably comprises bovine pericardium, a material shown to resist suture line bleeding, require no pre-clotting, support endothelialization and have an excellent host-tissue response. Further, bovine pericardial tissue has an elasticity of up to about 30% which allows the tissue cylinder to conform to both the unexpanded and expanded configurations of the stent 12 with out adding a great deal of bulk which increases the profile on the balloon. Other heterologous tissue suitable in the practice of the invention includes porcine pericardium, aortic leaflet, veins and arteries, and others. Useful heterologous tissue is relatively impervious and impenetrable so as to prevent tissue build up and the migration of smooth muscle cells through the stent framework. A particularly preferred bovine pericardium has cross-linked collagen and is available from Bio Vascular. Bovine pericardium tissue is available in a thickness ranging from about 0.25 mm to about 0.75 mm, with an average of about 0.45 mm. Thicknesses of 0.45 mm and less are preferred, so long as the mechanical strength remains sufficient. Metallic stent 12 may comprise any suitable conventional stent. For example, Micro Stent II and GFX stents available from Arterial Vascular Engineering, and Multi-Link, available from Guidant, have proven useful. Other stents that may be used in the practice of this invention include the Palmaz-Shatz stent from Johnson and Johnson, the Gianturco stent from Cook Incorporated and other commercially available stents. Conventional balloon expandable stents are preferred, but, as previously mentioned, self-expanding stents, such as those formed from shape memory materials, are also suitable. The cylinder of heterologous tissue forming the jacket 14, may be formed by cutting a rectangle of tissue having a length about 2 mm shorter than the stent on which it is to be mounted and a width about equal to the circumference of the expanded stent. The two sides corresponding to the length of the stent then may be secured together, such as by sewing with 6-

0, 7-0, 8-0 or 10-0 polypropylene sutures. Other means for securing the sides of the stent cover together include mechanical means such as staples, adhesive or chemical bonding and the like. It may be desirable to support the tissue while manipulating it. For example, a 9 French introducer dilator may be used to support a 3 mm diameter cylinder, an 1 1 French dilator for a 3.5 mm cylinder and a 12 French dilator for a 4 mm cylinder. Depending upon the jacket material, the tissue may be kept wet at all times during manipulation or it may be dry until advanced into the patient's blood stream. Additionally, radio-opaque markers, such as rings of gold or platinum, may be added to the outer layer of the tissue so that the integrity of the cylinder may be assured before deployment within the body lumen. The cylinder of heterologous tissue is configured to be mounted onto a stent and generally has a length of about 5 to greater than about 80 mm, typically about 5 to about 80 mm, preferably about 10 to about 50 mm, and a diameter of about 2 to about 35 mm, typically about 2 to about 6 mm, preferably about 2.5 to about 5 mm.

The jacketed stent assembly 10 is inserted into the body lumen in the following fashion. A guidewire 20 is backloaded into a delivery catheter 22 having the jacketed stent assembly 10 mounted over an inflatable balloon 24 on the distal extremity of the delivery catheter (as schematically shown in Fig. 2) or on a self expanding stent delivery system (not shown). The catheter 22 and guidewire 20 are percutaneously introduced by means of a conventional Seldinger technique and a 9 or 10 French guiding catheter (not shown) into the patient's arterial system. The guidewire 20 is advanced out delivery catheter 22 through the vasculature under fluoroscopic imaging until it crosses a stenotic region. Then the catheter 22 is advanced over the guidewire 20 until the stent assembly 10 is positioned at the desired location within the stenotic region. Then, the balloon 24 is inflated or the securing mechanism of the self expanding stent is released to expand the stent 12 and cylindrical jacket 14, seating the assembly 10 within the vessel. The balloon 24 is then deflated and the catheter 22 is removed, leaving the expanded stent assembly 10 in place.

Although primarily described with respect to preventing restenosis in angioplasty patients, the covered stents of this invention may be used in a number of coronary artery, peripheral artery and non-vascular applications. For example, coronary artery applications include use in ectatic arteries and ectatic arteries containing an obstructive lesion, aneurismatic arteries, saphenous vein grafts and native arteries, coronary perforation, coronary fistula, and ostial coronary lesions. Peripheral artery applications include aortic abdominal aneurysm and other aneurismatic peripheral arteries, transjugular intrahepatic portal shunt, percutaneous transluminal angioplasty, fistula closing and neuro interventions (such as aneurysms and arterial-venous malformations), small vessel intraluminal grafting, and ostial renal artery lesions. Finally, the covered stents of this invention may be used in urological, gastroenterological, respiratory, neurological, and other non- vascular applications. For example, urological field applications include urethral stenting for stenosis due to tumors, fibrous tissue and perforation.

Gastroenterological field applications include fistula closing, reconstruction such as esophagus reconstruction, and esophageal bleeding. Respiratory field applications include tracheal and bronchial obstructions, and neurological field applications include carotid angioplasty not involving branches. A general description of the device of the present invention as well as a preferred embodiment of the present invention has been set forth above. One skilled in the art will recognize and be able to practice many changes in many aspects of the device described above, including variations that fall within the teachings of this invention. The spirit and scope of the invention should be limited only as set forth in the claims which follow.

Claims

WHAT IS CLAIMED IS:

1 . A stent assembly for maintaining the patency of a body lumen comprising an expandable stent with a cylindrical jacket formed of biocompatible, non-thrombogenic expandable material.

2. The stent assembly of claim 1 wherein the cylindrical jacket is formed of heterologous tissue.

3. The stent of claim 2, wherein the heterologous tissue is selected from the group consisting of bovine pericardium, porcine pericardium, and aortic leaflet, veins and arteries.

4. The stent of claim 3, wherein the heterologous tissue comprises bovine pericardium with cross-linked collagen.

5. The stent of claim 2 including at least one therapeutic or diagnostic agent releasably contained in the cylindrical jacket.

6. A method for maintaining the patency of a body lumen comprising the steps of: a) mounting on a delivery catheter a stent assembly comprising a tubular expandable stent with a cylindrical jacket formed of biocompatible, non-thrombogenic expandable material; b) advancing the delivery catheter through the body lumen until the stent assembly is positioned at a desired location; c) expanding the stent assembly to anchor it within the bodily lumen; and d) withdrawing the delivery catheter.

7. A cylindrical jacket formed of heterologous tissue configured to fit over a portion of an intraluminal stent.

8. The cylindrical jacket of claim 7 having a length of about 5 to about 80 mm.

9. The cylindrical jacket of claim 7 having a length of about 10 to about 50 mm.

10. The cylindrical jacket of claim 7 having a diameter of about 2 to about 35 mm.

1 1. The cylindrical jacket of claim 10 having a diameter of not greater than about 6 mm.

12. The cylindrical jacket of claim 7 having a diameter of about 2.5 to about 5 mm.

13. The cylindrical jacket of claim 7 configured to fit over an outer portion of the intraluminal stent.

14. The cylindrical jacket of claim 7 configured to cover an inner portion of the intraluminal stent.

15. A method of treating a patient, comprising: a) providing an elongated delivery catheter having an expandable member on a distal extremity thereof; b) mounting an expandable stent having a cylindrical jacket formed of biocompatible, non-thrombogenic expandable material onto the expandable member on the distal extremity of the delivery catheter; c) advancing at least the distal extremity of the catheter within a body lumen of the patient until the jacketed stent is disposed at a desired location within the body lumen; d) expanding the expandable member on the distal extremity of the catheter to expand the jacketed stent mounted thereon and fix the expanded jacketed stent within the body lumen; and e) contracting the expanded expandable member so the elongated delivery catheter can be removed from the patient.

16. An expandable jacketed stent comprising a metallic tubular member and an outer jacket formed of heterologous tissue.

17. The expandable jacketed stent of claim 16 wherein the heterologous tissue is selected from the group consisting of bovine pericardium, porcine pericardium, and aortic leaflet, veins and arteries.

18. A stent assembly for maintaining the patency of a body lumen comprising an expandable stent with a cylindrical jacket formed of biocompatible, non-thrombogenic expandable material containing a therapeutic or diagnositic agent.

19. The stent assembly of claim 18 wherein the therapeutic agent is an antithrombotic agent.

20. The stent assembly of claim 18 wherein the therapeutic agent is selected from the group consisting of heparin, urokinase, streptokinase, tissue plasminogen activator, and abciximab.

21. A method for maintaining the patency of a body lumen comprising the steps of: a) mounting on a delivery catheter a stent assembly comprising a tubular expandable stent with a cylindrical jacket formed of biocompatible, non-thrombogenic expandable material containing a therapeutic or diagnositic agent; b) advancing the delivery catheter through the body lumen until the stent assembly is positioned at a desired location; c) expanding the stent assembly to anchor it within the bodily lumen and deliver the therapeutic or diagnostic agent to the desired location within the body lumen; and d) withdrawing the delivery catheter.

22. A cylindrical jacket formed of heterologous tissue containing a therapeutic or diagnostic agent, configured to fit over at least one of an outer surface and an inner surface of an intraluminal stent.

23. A method of treating a patient, comprising: a) providing an elongated delivery catheter having an expandable member on a distal extremity thereof; b) mounting an expandable stent having a cylindrical jacket formed of formed of biocompatible, non-thrombogenic expandable material containing a therapeutic or diagnostic agent onto the expandable member on the distal extremity of the delivery catheter; c) advancing at least the distal extremity of the catheter within a body lumen of the patient until the jacketed stent is disposed at a desired location within the body lumen; d) delivering the therapeutic or diagnostic agent to the desired location within the patient by expanding the expandable member on the distal extremity of the catheter to expand the jacketed stent mounted thereon and fix the expanded jacketed stent within the body lumen; and e) contracting the expanded expandable member so the elongated delivery catheter can be removed from the patient.

24. An expandable jacketed stent comprising a metallic tubular member and a jacket formed of heterologous tissue containing a therapeutic or diagnostic agent.

25. A stent assembly for maintaining the patency of a body lumen comprising an expandable stent with a cylindrical exterior jacket formed of biocompatible, non-thrombogenic expandable material.

26. A stent assembly for maintaining the patency of a bodily lumen comprising an expandable stent disposed within a cylinder of biocompatible, non-thrombogenic expandable material.

27. The stent of claim 26 wherein the cylinder of biocompatible, non- thrombogenic expandable material contains a therapeutic or diagnostic agent.

28. A cylinder formed of heterologous tissue containing a therapeutic or diagnotic agent, configured to fit over an intraluminal stent.