US20230277345A1

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Publication number: US20230277345A1
Application number: US18/313,393
Authority: US
Inventors: BenZion SPECTOR; Juan Jose RIGLA CROS
Original assignee: InspireMD Ltd
Current assignee: InspireMD Ltd
Priority date: 2018-10-19
Filing date: 2023-05-08
Publication date: 2023-09-07
Also published as: EP3866732A1; CN112839612A; WO2020079621A1; JP2022511315A; CN114732579A; CN112839612B; US11684498B2; US20200121482A1; EP3866732A4

Abstract

A method of using a self-adjusting stent assembly includes estimating body lumen diameter(s) associated with a portion of a body lumen in which a stent assembly will be placed; determining, based on the estimated diameter(s), target expanded stent diameter(s) of the stent assembly which is to be placed in the portion of the body lumen; selecting the stent assembly for stenting the portion of the body lumen, wherein the stent assembly is configured to: expand from an initial to expanded diameters within a range of expanded diameters; wherein the range of expanded diameters is from about 9 mm to about 5.5 mm; and wherein the target expanded stent diameter(s) is/are within the range of expanded diameters; and apply a chronic radial force to a wall that forms the portion of the lumen, wherein the radial force is less than about 0.33 N/mm.

Description

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No. 16/260,427, filed Jan. 29, 2019, which claims the benefit of the filing date of, and priority to, U.S. Application No. 62/747,800, filed Oct. 19, 2018, the entire contents of which is hereby incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to stent devices and methods and, specifically, to the use of a self-expanding one-size-fits-all stent assembly for any body lumen diameter within a range of body lumen diameters, kits containing such stent assembly, and instructions to stent with such a stent assembly.

BACKGROUND

Self-expanding stents generally have a tubular shape cut in a pattern that results in spring-like movement of the stent assembly in the radial direction. The stents are placed in a vessel and the spring-like movement acts as a scaffold to support lesions, thereby hopefully restoring an adequate lumen in a vessel. Currently these devices are designed to fit a specific vessel diameter, and the indication of use is usually within 1-2 mm of the nominal diameter of the designed stent to minimize or avoid damage to the vessel wall. However, the variances in vessel diameters may be 5 mm or larger. Thus, the physician or other medical practitioner is required to use various imaging techniques to determine which size of stent assembly is required. Additionally, the stent assembly may need to be placed in a portion of a vessel that has a varied vessel diameter. In this instance, the physician must choose a size that corresponds to only one of the vessel diameters and place it in that diameter portion of the vessel, or use a tapered stent assembly to span the portion of the vessel that has a varied vessel diameter. Often, the physician might incorrectly choose the stent size, which results in an oversizing of the stent or under sizing of the stent. Under sizing may result in shifting of the stent or failure to achieve full stent apposition, raising the risk of thrombosis or mobilization over the stent edges. Oversizing may result in stressing the walls of the vessel and generating re-stenosis or perforation.

SUMMARY

One aspect of the disclosure details a method of using a stent assembly adapted to stent a range of body lumen sizes, which includes: providing stenting instructions that include instructions to: estimate body lumen diameter(s) associated with a portion of a body lumen in which the stent assembly will be placed, determine, based on the estimated body lumen diameter(s), target expanded stent diameter(s) of the stent assembly, select the stent assembly for stenting the portion of the body lumen based on the target expanded stent diameter(s), wherein the stent assembly is configured to expand from an initial diameter to one or more expanded diameters within a range of expanded diameters while applying a radial force of about 0.20 N/mm to about 0.33 N/mm, wherein the range of expanded diameters is from about 5.5 mm to about 9 mm, and wherein the target expanded stent diameter(s) is/are within the range of expanded diameters; and providing the selected stent assembly in association with the stenting instructions. In a preferred embodiment, the stent assembly is implanted in the portion of the body lumen.

In one embodiment, the stent assembly is configured to expand to all diameters within the range of expanded diameters. In another embodiment, the portion of the body lumen in which the stent assembly will be placed includes a lesion; and wherein the estimated body lumen diameter(s) include: a first estimated body lumen diameter that is spaced in a first direction from the lesion, and a second estimated body lumen diameter that is spaced in a second direction from the lesion, wherein the first direction is opposite the second direction. In another embodiment, the instructions further include instructions to: when the portion of the body lumen defines varying body lumen diameters, allow a first portion of the stent assembly to expand to a first expanded diameter that is within the range of expanded diameters and allow a second portion of the stent assembly to expand to a second expanded diameter that is within the range of expanded diameters. In a preferred embodiment, the first expanded diameter is different from the second expanded diameter. In yet another embodiment, the stent assembly includes a knitted stent jacket, including an expansible mesh structure formed from fibers having a diameter between about 7 micrometers and about 40 micrometers, and an expansible stent, operatively associated with the knitted stent jacket, wherein the expansible mesh structure includes a retracted state that is associated with the initial diameter and a deployed state that is associated with the one or more expanded diameters, wherein the expansible mesh structure defines apertures having a minimum center dimension greater than about 100 micrometers and no more than about 300 micrometers before implantation and when the expansible mesh structure is in the deployed state, wherein the expansible mesh structure has a thickness of greater than about 12.5 micrometers to no more than about 100 micrometers.

In another aspect, the disclosure encompasses a method of increasing the intraluminal expansion range of a stent assembly to one or more expanded diameters from about 5.5 mm to about 9 mm, under conditions effective to extend the expansion range of the stent where the chronic radial force applied is about 0.20 N/mm to about 0.33 N/mm. In a preferred embodiment, the stent assembly includes a knitted stent jacket that includes an expansible mesh structure formed from fibers having a diameter between about 7 micrometers and about 40 micrometers, and an expansible stent, operatively associated with the knitted stent jacket, wherein the expansible mesh structure includes a retracted state that is associated with the initial diameter and a deployed state that is associated with the one or more expanded diameters, wherein the expansible mesh structure defines apertures having a minimum center dimension greater than about 100 micrometers and no more than about 300 micrometers before implantation and when the expansible mesh structure is in the deployed state, wherein the expansible mesh structure has a thickness of greater than about 12.5 micrometers to no more than about 100 micrometers.

In another aspect, the disclosure encompasses a method of stenting, which includes: estimating a base reference diameter(s) associated with a portion of a body lumen in which a stent assembly will be placed, determining, based on the estimated base reference diameter(s), target expanded stent diameter(s) of the stent assembly which is to be placed in the portion of the body lumen, selecting the stent assembly for stenting the portion of the body lumen, wherein the stent assembly is configured to: expand from an initial diameter to one or more expanded diameters within a range of expanded diameters, wherein the range of the one or more expanded diameters is from about 5.5 mm to about 9 mm, and wherein the target expanded stent diameter(s) is/are within the range of the one or more expanded diameters, apply a chronic radial force to a wall that forms the portion of the body lumen in which the stent assembly will be placed, wherein the chronic radial force is less than about 0.33 N/mm. In one preferred embodiment, the stent assembly is implanted in the portion of the body lumen.

In one embodiment, the method includes implanting the stent assembly in the portion of the body lumen includes allowing the stent assembly to expand to an expanded diameter within the range of expanded diameters such that the stent assembly applies the chronic radial force to the wall that forms the portion of the body lumen in which the stent assembly will be placed, and wherein the chronic radial force is greater than about 0.20 N/mm. In one preferred embodiment, the stent assembly is a configured to expand to all diameters between about 5.5 mm and about 9 mm. In another preferred embodiment, when the portion of the body lumen defines varying body lumen diameters, implanting the stent assembly in the portion of the body lumen includes: allowing a first portion of the stent assembly to expand to a first expanded diameter that is within the range of the one or more expanded diameters such that the first portion of the stent assembly applies the chronic radial force to the wall that forms the portion of the body lumen in which the stent assembly will be placed, and allowing a second portion of the stent assembly to expand to a second expanded diameter that is within the range of the one or more expanded diameters such that the second portion of the stent assembly applies the chronic radial force to the wall that forms the portion of the body lumen in which the stent assembly will be placed, and wherein the chronic radial force is greater than about 0.20 N/mm. In another preferred embodiment, the first expanded diameter is different from the second expanded diameter. In another preferred embodiment, the method includes allowing the first portion of the stent assembly to expand to the first expanded diameter and allowing the second portion of the stent assembly to expand to the second expanded diameter occurs simultaneously. In another embodiment, the stent assembly includes: a knitted stent jacket, including an expansible mesh structure formed from fibers having a diameter of about 7 micrometers to about 40 micrometers, and an expansible stent, operatively associated with the knitted stent jacket, wherein the expansible mesh structure includes a retracted state that is associated with the initial diameter and a deployed state that is associated with the expanded diameter(s), wherein the expansible mesh structure defines apertures having a minimum center dimension of at least about 100 micrometers to no more than about 300 micrometers before implantation and when the expansible mesh structure is in the deployed state, wherein the expansible mesh structure has a thickness of at least about 12.5 micrometers to no more than about 100 micrometers.

In another aspect, the disclosure encompasses a method of stenting a plurality of body lumens, which includes: positioning a first stent assembly in a retracted state within a first body lumen, expanding the first stent assembly to place the first stent assembly in a deployed state within the first body lumen, wherein, when the first stent assembly is in the deployed state, the first stent assembly has a first expanded diameter and applies a first radial force to a first wall that forms the first body lumen, positioning a second stent assembly in a retracted state within a second body lumen that is different from the first body lumen, and expanding the second stent assembly to place the second stent in a deployed state within the second body lumen, wherein, when the second stent assembly is in the deployed state, the second stent assembly has a second expanded diameter and applies a second radial force to a second wall that forms the second body lumen, wherein the first and second stent assemblies are at least substantially identical, and the second expanded diameter is greater than the first expanded diameter, wherein the second expanded diameter is between about 220% to about 110% of the first expanded diameter, and wherein the second radial force is greater than about 50% of the first radial force.

In one embodiment, the method includes expanding the second stent assembly to place the second stent assembly in the deployed state within the second body lumen includes, when the second body lumen defines varying body lumen diameters: expanding a first portion of the second stent assembly to the second expanded diameter that is within a range of expanded diameters, and expanding a second portion of the second stent assembly to a third expanded diameter that is within the range of expanded diameters, and wherein the range of expanded diameters is from about 9 mm to about 5.5 mm. In another embodiment, each of the first and second stent assemblies includes: a knitted stent jacket, including an expansible mesh structure formed from fibers having a diameter of about 7 micrometers to about 40 micrometers, and an expansible stent, operatively associated with the knitted stent jacket: wherein the expansible mesh structure transitions from the retracted state to the deployed state, wherein the expansible mesh structure defines apertures having a minimum center dimension of at least about 100 micrometers to no more than about 300 micrometers before implantation and when the expansible mesh structure is in the deployed state, wherein the expansible mesh structure has a thickness of at least about 12.5 micrometers to no more than about 100 micrometers.

In another aspect, the disclosure encompasses a kit including: a stent assembly including: a knitted stent jacket, including an expansible mesh structure formed from a single fiber having a diameter from about 7 micrometers to about 40 micrometers, and an expansible stent, operatively associated with the knitted stent jacket: wherein the expansible mesh structure includes a retracted state and a deployed state, wherein the expansible mesh structure defines apertures having a minimum center dimension of at least about 160 micrometers in the deployed state, and wherein the expansible mesh structure has a thickness of at least about 12.5 micrometers to no more than about 100 micrometers, and instructions for use setting forth a method for expanding the stent assembly to any expanded diameter in a range from about 5.5 mm to about 9 mm while applying a chronic radial force of about 0.2 N/m to about 0.33 N/mm.

In one embodiment, the instructions include instructions to: estimate body lumen diameter(s) associated with a portion of a body lumen in which the stent assembly will be placed, determine, based on the estimated body lumen diameter(s), target expanded stent diameter(s) of the stent assembly, select the stent assembly for stenting the portion of the body lumen based on the target expanded stent diameter(s), wherein the stent assembly is configured to expand from an initial diameter to any expanded diameter within the range of expanded diameters while applying a radial force of about 0.20 N/mm to about 0.33 N/mm, wherein the target expanded stent diameter(s) is/are within the range of expanded diameters, and implant the stent assembly in the portion of the body lumen. In another embodiment, the stent assembly is a configured to expand to all diameters within the range of expanded diameters. In yet another embodiment, the instructions further include instructions to: when the portion of the body lumen defines varying body lumen diameters, allow a first portion of the stent assembly to expand to a first expanded diameter that is within the range of expanded diameters and allow a second portion of the stent assembly to expand to a second expanded diameter that is within the range of expanded diameters. In yet another embodiment, the first expanded diameter is different from the second expanded diameter.

Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the disclosure, example methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

Example non-limiting embodiments of the disclosure are described in the following description, read with reference to the figures attached hereto. In the figures, identical and similar structures, elements or parts thereof that appear in more than one figure are generally labeled with the same or similar references in the figures in which they appear. Dimensions of components and features shown in the figures are chosen primarily for convenience and clarity of presentation and are not necessarily to scale. The attached figures are:

FIG.1 is a perspective view of an enhanced stent apparatus, in an open, non-crimped mode, in accordance with an example embodiment of the disclosure;

FIG.2 is a cross-sectional side view of an enhanced stent apparatus, in accordance with an example embodiment of the disclosure;

FIG.3 is an illustration of an enhanced stent apparatus in an open mode in situ, in accordance with an example embodiment of the disclosure;

FIG.4 is a perspective view of an enhanced stent apparatus, with multiple helical coils in an open mode, in accordance with an example embodiment of the disclosure;

FIG.5 is a perspective view of an enhanced stent apparatus, in a crimped, closed mode, in accordance with an example embodiment of the disclosure;

FIG.6A is a perspective view of a knitted porous structure enhanced stent apparatus in an open mode, in accordance with an example embodiment of the disclosure;

FIG.6B is a detailed view of a knitted porous structure, in accordance with an example embodiment of the disclosure;

FIG.7 is a perspective view of a braided porous structure enhanced stent apparatus, in accordance with an example embodiment of the disclosure;

FIG.8 is a perspective view of an enhanced stent apparatus, provided with longitudinal non-stretchable wires, and horizontal stretchable elastomers in accordance with an example embodiment of the disclosure;

FIG.9 is a perspective view of an enhanced stent apparatus, wherein porous structure is longer than the support element, in accordance with an example embodiment of the disclosure;

FIG.10 is a perspective view of an enhanced stent apparatus, wherein porous structure is significantly greater in diameter than a crimped support element, and is folded on itself for insertion into a lumen, in accordance with an example to embodiment of the disclosure;

FIG.11 is a perspective view of a porous structure significantly greater in diameter than an at least partially deflated balloon wherein the porous structure is folded on itself for insertion into a lumen, in accordance with an example embodiment of the disclosure;

FIG.12 illustrates the use of a funnel to reduce the diameter of at least a porous structure, in accordance with an example embodiment of the disclosure;

FIG.13 illustrates using a stretchable rubber tube for manufacturing a compressed porous structure, in accordance with an example embodiment of the disclosure;

FIG.14 is a graph showing fiber thickness vs. percentage of porous structure surface area that is structure, in accordance with an example embodiment of the disclosure;

FIG.15 is a detailed illustration of a threading method for securing a porous structure to a support element, in accordance with an example embodiment of the disclosure;

FIG.16 is a detailed illustration of a knotting method for securing a porous structure to a support element, in accordance with an example embodiment of the disclosure;

FIG.17 is a cross-section view of an enhanced stent apparatus showing a porous structure folding technique, in accordance with an example embodiment of the disclosure;

FIG.18 is a schematic showing a method for manufacturing a porous structure, in accordance with an example embodiment of the disclosure;

FIG.19A is an illustration of a typical aneurism;

FIG.19B is an illustration of a prior art technique for treating an aneurism;

FIG.19C is an illustration of a technique for treating an aneurism, in accordance with an example embodiment of the disclosure;

FIG.20 is a graphic illustration of a reaction force of prior art stents through crimping and then deployment, in accordance with an example embodiment of the disclosure;

FIG.21 is a graphic illustration of a reaction force of the stent apparatus ofFIG.1 through crimping and then deployment, in accordance with an example embodiment of the disclosure;

FIG.22 is a table detailing reaction forces of the stent apparatus ofFIG.1 through crimping and then deployment, in accordance with an example embodiment of the disclosure

FIG.23 is a flow chart illustrating a method of operating the apparatus ofFIG.1, in accordance with an example embodiment of the disclosure;

FIG.24 is a cross-sectional view of a vessel, in accordance with an example embodiment of the disclosure;

FIG.25 is a cross-sectional view of the stent apparatus ofFIG.1 in a retracted state and extending within the vessel ofFIG.24, in accordance with an example embodiment of the disclosure;

FIG.26 is a cross-sectional view of the stent apparatus ofFIG.1 in a deployed stated and extending within the vessel ofFIG.24, in accordance with an example embodiment of the disclosure;

FIG.27 is a table detailing aggregated, de-identified patient information relating to an experimental test of one embodiment of the stent assembly ofFIG.1, in accordance with an example embodiment of the disclosure;

FIG.28A is a cross-sectional view of a slip ring in a reduced profile configuration, in accordance with an example embodiment of the disclosure;

FIG.28B is a cross-sectional view of a slip ring in a deployed configuration, in accordance with an example embodiment of the disclosure;

FIG.29 is cross sectional view of a porous structure with an endothelium cell layer overgrowing it, in accordance with an example embodiment of the disclosure;

FIG.30 is an illustration of a prior art situation in which a clump of endothelial cells detaches from a stent strut;

FIGS.31a-31dshow deployment of a self-expanding stent, according to embodiments of the disclosure;

FIGS.32-35 show in situ details of a typical stent jacket material in the art, in situ; and

FIG.36 shows a portion of the knitted stent jacket, according to embodiments of the disclosure;

FIG.37 shows a plan view of the knitted stent jacket ofFIG.36, according to embodiments of the disclosure;

FIGS.38-39 show details of the material including the knitted stent jacket ofFIG.36, according to embodiments of the disclosure; and

FIG.40 shows in situ details of the material shown inFIG.9, according to embodiments of the disclosure.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

Aspects of the present disclosure address shortcomings of the prior art, which are noted above, by providing a so-called one-size-fits-all stent assembly. The one-size-fits-all stent assembly is configured for use in a wide range of body lumen diameters regardless of whether the body lumen is a straight body lumen (having a generally consistent diameter) or a varied diameter body lumen (having changes in the diameter), or even a branched or bifurcated body lumen. As such, use of the one-size-fits-all stent assembly eliminates or reduces sizing errors and reduces the number of different sized stent assemblies required to be available on-hand at a patient treatment or prevention facility, e.g., a hospital.

The instant application is divided into a number of labeled sections which generally include, in order, descriptions of apparatuses (e.g. porous structures, stents, etc.), materials and methods for manufacturing the apparatuses, the usage of pharmaceuticals with the apparatuses, and methods of using the apparatuses. It should be understood that the section headings are for clarity only and are not intended to limit the subject matter described therein. Furthermore, some of the subject matter described in a particular section may belong in more than one section and therefore, some of the material could overlap between sections.

INTRODUCTION

Aspects of the present disclosure successfully address shortcomings of the prior art by providing a stent assembly that is configured to expand to any diameter within a range of diameters to provide a chronic radial force between about 0.33 N/mm and about 0.20 N/mm.

In accordance with some embodiments of the present disclosure, the stent assembly reduces risks and errors associated with choosing a specific stent assembly size.

In accordance with some embodiments of the present disclosure, the stent assembly reduces the amount of stent assemblies required to remain on-hand. This can advantageously permit smaller medical institutions to carry the cost of having stent assemblies on hand that work for a variety of body lumen sizes, and more generally minimize the cost of having a large inventory of different devices on hand for emergencies.

In accordance with some embodiments of the present disclosure, the stent assembly provides a known predefined radial force expectancy for all diameters in the range.

In accordance with some embodiments of the present disclosure, the stent assembly provides better adaptation to varying diameters of a body lumen, such as a vessel, over the length of the implantation mesh.

In accordance with some embodiments of the present disclosure, the stent assembly includes a fiber having a low diameter that allows each endothelial cell to fully cover and overlap one or more fibers, thereby forming a layer of endothelial cells that adhere to tissue on either side of such fibers. The thus formed endothelial layer is substantially stable with a substantially reduced tendency to break away and form emboli, which can provide improved patient outcomes.

In accordance with some embodiments of the present disclosure, the mesh fiber includes material that encourages adherence of endothelial cells, thereby encouraging endothelial layer stability.

In accordance with some embodiments of the present disclosure, the mesh is not secondarily processed, for example, with a chemical coating that may diminish endothelial adherence. Additionally, the absence of chemical coatings serves to maintain low bulk fibers and fiber junctions, where a first fiber passes over or under a second fiber—another feature that contributes to endothelial layer stability. In such embodiments, it is possible to have one or more pharmaceutical agents imbued within a fiber, or in another layer or portion of the stent assembly, to provide the benefit of such an agent while avoiding the deficiencies of a chemical coating.

In accordance with some embodiments of the present disclosure, each mesh fiber is spaced a distance from a neighboring fiber thereby minimizing the risk of, or preventing, a single endothelial cell from adhering to more than one fiber, thereby reducing the chance that endothelial cells will break free of the stent, for example as a result of natural stent pulsation during blood flow.

In accordance with some embodiments of the present disclosure, the stent jacket optionally includes a mesh that is knitted. In accordance with some embodiments of the present disclosure, the stent jacket mesh is optionally formed from a single fiber or a single group of fibers.

Overview of Enhanced Stent Apparatus

The present disclosure, in some embodiments thereof, relates to stent assemblies, as presented in PCT Patent Application PCT/IB2006/051874, the disclosure of which is hereby incorporated herein by express reference thereto. The methods and kits disclosed herein may, e.g., use various stent assemblies disclosed in that PCT application.

In an example embodiment of the disclosure, an apparatus is provided which includes a porous structure and, optionally, an underlying support element, such as a stent (wherein underlying means the porous structure is between the support element and a lumen wall).

In some example embodiments of the disclosure, an enhanced stent apparatus, including the porous structure and a stent, is used to treat stenosis and/or restenosis. In some example embodiments of the disclosure, the enhanced stent apparatus furnishes at least one of a multiplicity of benefits over a conventional arterial stent. For example, the enhanced stent apparatus is optionally used to prevent plaque from getting into the blood stream to cause embolism, since the porous structure is made with small enough apertures (sizes indicated below) to hold detached plaque in place. In an embodiment of the disclosure, use of a porous structure replaces the use of an embolism protection device during stent implantation. Optionally, the “umbrella” type embolism protection device is not used. Optionally, the porous structure is used in conjunction with an embolism protection device for enhanced protection over the method of using an embolism protection device during the implantation of a conventional arterial stent. In an embodiment of the disclosure, the enhanced stent apparatus delivers more comprehensive pharmacological assistance to a treated area than conventional stents. In some embodiments of the disclosure, the enhanced stent apparatus is optimized to encourage endothelial cell growth and/or migration. For clarity, the porous structure may be the mesh stent jacket described herein.

FIG.1 shows a perspective view of an enhanced stent assembly orstent apparatus100, in an example embodiment of the disclosure. Asupport element102 is designed and constructed to expand a blood vessel in a radial fashion from acentral axis106 of theenhanced stent apparatus100. Optionally,support element102 is tubular in shape. In some example embodiments of the disclosure,support element102 is constructed of a flexible, biocompatible material. Optionally,support element102 is constructed of stainless steel, nitinol, and/or cobalt chromium and/or other metal alloys (e.g. magnesium alloy). Optionally,support element102 is constructed of polymer either biostable or bioresorbable. In some example embodiments of the disclosure,support element102 is a vascular stent, such as those made by Cordis®, Boston Scientific® and/or Medtronic®, for example.

In an example embodiment of the disclosure,support element102 is covered by at least oneporous structure104. Optionally,support element102 acts as a support structure forporous structure104, for example to provide radial support and or to maintain a desired shape ofporous structure104.FIG.2, shows a cross-sectional view of an enhanced stent apparatus. In this embodiment,support element102 supplies structural support toporous structure104, which is located on the exterior ofsupport element102.

In some example embodiments of the disclosure,porous structure104 is laid on the exterior ofsupport element102 and thereby overlaps gaps in support element102 (making the aperture sizes of the device as a whole smaller, for example 150 microns), since conventional stent construction usually results in multiple gaps in the structure of the stem, typically several millimeters. In other example embodiments of the disclosure,porous structure104 covers only a portion ofsupport element102. For example, only a portion ofsupport element102 is covered to avoid restricting luminal flow to a branching vessel.

In some example embodiments of the disclosure,porous structure104 extends past at least one end ofsupport element102. This can, for example, better treat the inside surface of a blood vessel at an edge ofenhanced stent apparatus100, where it is more likely to have restenosis. In an example embodiment of the disclosure,porous structure104 pads and/or treats trauma caused by the edge ofsupport element102 by extending past at least one end ofsupport element102. Optionally,porous structure104 extends no more than 1 mm past the end ofsupport element102. Optionally,porous structure104 extends over 1 mm past the end ofsupport element102. Optionally,porous structure104 extends past only one end or both ends (as shown inFIG.9) ofsupport element102.

In some example embodiments of the disclosure,porous structure104 is attached to supportelement102 to preventporous structure104 from unraveling and/or causing tissue irritation and/or avoiding dislodgment of the porous structure from the support element during deployment. Optionally, the end ofporous structure104 is folded over the end ofsupport element102 and attached, providing padding to a potentially trauma causing edge. Optionally, the end ofporous structure104 is folded under itself and is held folded due to the pressure between the support element and the lumen. In an embodiment of the disclosure, a treatment, such as heat, is used to make the fold sharp and/or permanent.

It should be understood that while an example configuration of enhanced stent apparatus is shown inFIGS.1 and2, other configurations could possibly be used, including: aporous structure104 over a pharmaceutical eluting support element; a pharmaceutical eluting porous structure over asupport element102; a pharmaceutical to eluting porous structure over a pharmaceutical eluting support element; a support element in between at least two porous structures, optionally some or all eluting pharmaceuticals; and, an enhanced stent including a plurality of layers which exhibit different optional characteristics such as degradation time and/or pharmaceutical elution. It should be understood that any of the above configurations include biodegradable and/or bioresorbable materials. Optionally, configurations are chosen for specific treatment regimens indicated by the condition of the patient.

In some example embodiments of the disclosure,porous structure104 is used to control the local pressure exerted by the enhanced stent apparatus on the body lumen wall. For example, by increasing or decreasing the coverage area of the porous structure as it at least partially covers the stent, the pressure exerted by the enhanced stent apparatus per unit area can be altered. In some embodiments of the disclosure, modification of the coverage area considers factors such as the stiffness ofsupport element102 and the geometry and/or coverage area of the support struts ofsupport element102. In an embodiment of the disclosure, pressure control is used to reduce the likelihood of the enhanced stent apparatus causing plaque to break off of the lumen wall. In some embodiments of the disclosure, pressure control is used to reduce tissue trauma typically caused by stent implants, thereby enhancing protection against stenosis/restenosis. Furthermore, in some embodiments of the disclosure,support element102 struts which could not be used previously due to the likelihood of trauma to the lumen tissue can optionally be used in combination withporous structure104.

In some example embodiments of the disclosure, bile ducts are treated using at least a porous structure as described herein. For example, the bile ducts often become congested with debris (e.g. cholesterol) which restricts flow. Treatment of the bile ducts using enhanced stent apparatus may increase the diameter of the bile ducts, improving their operation.

It is known that varying types of body lumens possess varying surface textures, both varying from each other, and sometimes within one type of lumen. Thus, in some example embodiments of the disclosure, different porous structures with varying surface texture configurations are manufactured and/or used depending on the interior surface texture of a lumen being treated. For example, peaks and valleys in a body lumen are fitted with counter peaks and valleys of a porous structure (i.e. porous structure counter peak goes into lumen valley and porous structure counter valley accepts lumen peak). Optionally, the counter peaks and valleys are of the same magnitude as the peaks and valleys found in the lumen being treated.

It should be understood that the aperture size, the porous structure thickness, the fiber thickness (or French), and/or the coverage area are varied for different applications. For example, when treating the carotids, debris of more than 100 microns should be prevented from reaching the brain, thus the porous structure is designed such that when stent is expanded, usually to about 8 millimeters, the majority of aperture sizes are less than 100 microns. As another example, when treating the coronaries larger debris (>100 microns) is not as problematic, while the endotheliazation process and the non-restriction of flow to side branches is more important. Thus, for coronary artery applications, when thesupport element102 is in an expanded position, usually about 3 millimeters in diameter, the apertures in the porous structure are optionally larger than 100 microns and below 300 microns. In some embodiments of the disclosure, the rate of endothelium cell growth over porous structure may be modified by increasing and/or decreasing fiber thickness and porous structure thickness.

In an example embodiment of the disclosure,porous structure104 is under 100 microns in thickness. In some example embodiments of the disclosure, the porous structure is less than 30 microns thick. Optionally, the porous structure is less than 10 microns in thickness. For example, the porous structure is less than 5 microns or 1 micron thick.Porous structure104 optionally includes at least one fine, thread-like fiber. In some example embodiments of the disclosure,porous structure104 includes at least one fiber that is 40 nm to 40 microns thick. Optionally, to the fiber thickness is similar to or less than the diameter of an endothelial cell to encourage endothelial cell growth between fibers and/or around at least one fiber. In an example embodiment of the disclosure, a super-fiber is used to constructporous structure104, wherein the super-fiber is made of multiple fibers braided together. Optionally, super-fibers are used to enhance the strength ofporous structure104.

In an example embodiment of the disclosure, the fibers ofporous structure104 are spun and/or knitted and/or woven and/or braided to provide structure to andapertures110 inporous structure104. Optionally, the porous structure is woven in an even pattern. Optionally, the porous structure is constructed so that the fibers are randomly positioned inporous structure104. Optionally, polymer fibers are used to constructporous structure104. Optionally, polymer coverings are applied toporous structure104 and/orsupport element102. Example porous structure manufacture is described in more detail in the “Methods of Manufacture” section below.

In an example embodiment of the disclosure, the polymer coveredporous structure104 is optionally made out of a closed interlocked design and/or an open interlocked design, or semi open design, similar totypical support element102 designs. The open interlocked design has an advantage when side branching is needed. When treating a junction of two blood vessels, there is sometimes a need to introduce one stent through the side of another one. An open interlocked design allows such a procedure, and when the porous structure is made of metal mesh, an open interlocked design is utilized in order to allow easy side branching stents. Optionally, using a biodegradable polymer coating on anon-biodegradable support element102 leaves thesupport element102 embedded after the biodegradable polymer has degraded.

In an example embodiment of the disclosure,porous structure104 is crimped to a small diameter while still maintaining its flexibility, to enable successful maneuverability through a patient's blood vessels to the site whereenhanced stent apparatus100 is to be implanted. In an example embodiment of the disclosure,porous structure104 is expandable to enable expansion ofporous structure104 withsupport element102 upon deployment at a treatment site within a patient's blood vessel. Optionally, expansion ofporous structure104 along the longitudinal axis matches the expansion ofsupport element102 along the longitudinal axis.

In an example embodiment of the disclosure, at leastporous structure104 is expandable without significant foreshortening or elongation of the length ofporous structure104. For example, and in some embodiments, at least theporous structure104 is expandable with less than about 20% foreshortening, with less than about 15% foreshortening, with less than about 10% foreshortening, or with less than about, or about, 6% foreshortening. Generally, a percent of foreshortening is defined as 100×(change in length÷loaded or final length). Optionally,porous structure104 expands differently thansupport element102, for example using sliding connections described herein. As described elsewhere herein, in a knitted embodiment ofporous structure104, expansion occurs at least partially as a result of the knitted structure, and not necessarily because of the elasticity of the fiber used in constructingporous structure104. In an embodiment of the disclosure, at least one fiber which includesporous structure104 is provided with slack during manufacture to provide additional fiber material whenporous structure104 expands.FIG.8 shows a perspective view of anenhanced stent apparatus900.Enhanced stent apparatus900 is provided withnon-stretchable wires902, andstretchable elastomer fibers904, in accordance with an example embodiment of the disclosure. Such an embodiment assists with the preservation ofoverall apparatus900 length while allowing expandability and flexibility during implantation.

In an example embodiment of the disclosure, an enhanced stent apparatus is provided which includes at least an expandable support element and an expandable porous structure. The support element is optionally a stent, examples of which are known in the art for providing treatment to a wide range of body lumens. In an embodiment of the disclosure, the porous structure has structure which resembles to fishing net. In an embodiment of the disclosure, the porous structure is knitted from a fiber approximately 15-20 microns in diameter, has a coverage area of less than 20%, and which has aperture sizes approximately 150×200 microns. In some embodiments of the disclosure, the porous structure is at least temporarily attached to support struts of the support element by stitching. Optionally, the stitches are loose, allowing the porous structure to slide on the support struts, for example to provide extra expandability as described herein with respect toFIG.15. In some embodiments of the disclosure, the stitching is biodegradable. In some embodiments of the disclosure, the support element and/or the porous structure are adapted to elute pharmaceutical agents into the body lumen being treated.

In some embodiments of the disclosure, different characteristics of the enhanced stem apparatus are chosen based on the intended use or treatment to be rendered. For example, aperture sizes are optionally chosen based on a desire to provide embolic shower protection against debris of a certain size. As another example, coverage area is optionally selected for modifying local pressure on the lumen being treated. Many of these characteristics are interrelated, as described herein and shown inFIG.14, for example.

In an embodiment of the disclosure,porous structure104 is flexible to allow the lumen to naturally change its diameter, to account for pressure changes in the lumen and/or to respond to muscular activity. In some embodiments of the disclosure, theporous structure104 divided into a plurality of semi-independent sectors, which react differently to stimuli within or from the lumen. Optionally, the sectors are used to prevent banding of the lumen across the entire length of theporous structure104.

Example Characteristics and Performance of Porous Structure

Manufacturing techniques, described in more detail below, such as knitting which provide slack to individual fibers, or sections, ofporous structure104, enableporous structure104 to optionally expand upon deployment up to 10 times its diameter at insertion (insertion diameter is described in more detail below), in an embodiment of the disclosure. For example, in coronary applicationsporous structure104 may expand from 1 mm to 3 mm in diameter. In other examples,porous structure104 may expand from 2 mm to 8 mm in carotid applications, while in brain applicationsporous structure104 may expand from 0.3 mm to 2.5 mm. These numbers are approximate and are by way of example only. In an embodiment of the disclosure, expansion ofporous structure104 is effectuated in at least one of three ways: 1) the knitted/braided/woven structure of porous structure104 (including slack in the fibers and curly fibers); 2) the fiber from which theporous structure104 is made is at least slightly elastic; 3) sliding connections (described below) betweenporous structure104 andsupport element102 permit shifting ofporous structure104 during expansion with respect to supportelement102, within certain limits. In an embodiment of the disclosure, the fiber from whichporous structure104 includes from about 2% to about 80% of non-elastic materials. In some embodiments of the disclosure, the elastic material of the fiber from whichporous structure104 is made allows for expansion up to 1000% its original size.

In some example embodiments of the disclosure,porous structure104 exhibits a high durability when subjected to twisting, turning, compression and/or elongation, which allowsporous structure104 to withstand the delivery process through the patient's vasculature to a treatment site. In an embodiment of the disclosure,porous structure104 can be loosely attached to asupport element102 at several locations and folded for insertion into a lumen. The foldedporous structure104 provides a reduced diameter apparatus for easier insertion into body lumen(s) of the patient.

In some example embodiments of the disclosure, 20% of the total area ofporous structure104 includes apertures having an approximate diameter no greater than 50, 200 or more than 200 microns in an expanded configuration. It is recognized that during the course of manufacturing the porous structure, for example with certain manufacturing techniques like electrospinning and/or knitting, apertures created within the porous structure may overlap. This overlap effectively creates an aperture size which is smaller than specified. However, in some example embodiments of the disclosure, the effective, nominal aperture size is no greater than 50, 200 or more than 200 microns in diameter. In some embodiments of the disclosure, aperture sizes are selected to encourage endothelial cell overgrowth at a certain rate.

It should be noted that shapes of apertures are likely to vary at least somewhat as a result of manufacture and/or desired properties ofporous structure104. For example, in a knitted porous structure, apertures are most likely to be roughly square. In contrast, use of a weaving technique to manufacture porous structure likely produce square and/or rectangular shaped apertures whereas a braided porous structure is likely to exhibit quadrilateral shaped apertures, such as inFIG.7. In describing an approximate “diameter” of an aperture, it should be recognized that all, some or none of the apertures will be actual circles, squares, rectangles and/or quadrilaterals capable of simplistic area measurement using diameter. Therefore, description using diameter is merely an approximation to convey example aperture sizes. For example, “diameter” could be the distance between two parallel sides of a quadrilateral, such as a square or rectangle.

In some parts of the following description, aperture sizes described herein are in reference to their size upon porous structure deployment in a lumen. In other parts, the sizes refer to the aperture sizes when crimped. Sometimes, the aperture sizes described herein refer to their size in a state intermediate a crimped and deployed configuration. In context, it should be easily perceived which of the above configurations applies, however, in the event it is not clear the aperture sizes could be considered as applying to expanded, crimped or intermediate configurations. When a fiber diameter is referred to, it relates to the fiber used to construct theporous structure104. For example, ifporous structure104 is constructed from a super-fiber including a bundle of 10 fibers each 2 microns in diameter, the overall super-fiber diameter is about 20 microns. Furthermore, it should be understood that references to fiber diameter are for approximation and convenience only and does not imply that the fiber is necessarily round. Optionally, fiber sizes are measured in French sizes, for example 0.003 Fr.

Referring toFIG.14, agraph1500 is shown which correlates fiber thickness of porous structure with percentage of the coverage area of a support element, for a porous structure with a fishing net type configuration. It can be seen that the general trend is that as the fiber sizes get thinner, the amount of porous structure surface area dedicated to structure is reduced. In an embodiment of the disclosure, it is desirable to have under 25% coverage area. Optionally,porous structure104 exhibits less than 20% coverage area. In an embodiment of the disclosure, the coverage area of the porous structure is adapted to be minimized while still performing an intended lumen treating function, such as those described herein. In some embodiments of the disclosure, the coverage area ofporous structure104 is minimized in order to avoid undesirable clinical side effects. For example, lumen tissue irritation and pyrogenic effects are considerations for minimizing the coverage area and optionally other characteristics such as aperture size, porous structure thickness and/or fiber thickness, ofporous structure104.

In some example embodiments of the disclosure, the proportion of structure to apertures ofporous structure104, fiber size and/or apertures are sized in order to allow easy diffusion throughporous structure104 and to facilitate growth of endothelial cells. Since thefiber2202 diameters used in construction ofporous structure104 are on the order of the size of theendothelial cells2204, or smaller, as shown inFIG.29, the integrity of the cells grown over the porous structure will be much better than what is achieved in the prior art. An individual cell, statistically, will have a firm connection to the blood vessel wall, since it is of the same order or larger than the fiber diameter, thus anchoring itself, in an embodiment of the disclosure, in more than one location to its native basalamina intimal layer and enabling better growth conditions. It is thus expected that the chance of late or sub-acute thrombosis can be reduced over what is currently achieved when treatment is performed using a pharmaceutical eluting stent. In addition,porous structure104 effectively acts as an embolic shower protection device, holding detached plaque in place, preventing it from traveling from the vessel wall into the blood stream. It should be noted thatporous structure104 is configured, accounting for fiber thickness, porous structure thickness and/or aperture size such that endothelial cells will overgrowporous structure104, and optionally supportelement102, in order to secure the enhanced stent in place and/or insulate the foreign material ofsupport element102 and/orporous structure104 from the bloodstream. In an example embodiment of the disclosure, endothelial cell layer overgrowth ofporous structure104 is established within hours of implantation. In an embodiment of the disclosure, overgrowth is accomplished within this time frame due to characteristics ofporous structure104 as they relate to endothelial cells, for example, the overall thickness being on the same order of, or smaller, than an individual endothelial cell. In some embodiments of the disclosure, it is conceived that a patient's average stay in the hospital after a stenting procedure can be reduced as a result of the speed of endotheliazation using enhanced stent apparatus. In addition, the speed and efficacy of pharmaceutical treatment can expected to be enhanced as a result of the rapid endotheliazation over at leastporous structure104 ofenhanced stent apparatus100.

FIG.30 shows a disadvantage of using prior art drug eluting stents wherein a clump of endothelium cells has become detached from thestent strut2304, revealing an exposed “island”2302 of the stent. Sometimes a clump falls offstrut2304 due to poor adhesion of the endothelium cells to the polymer coating of thestrut2304. Contributing to this poor adhesion, thestent strut2304 is typically an order of magnitude larger than a single endothelium cell, thereby necessitating the creation of a large endothelium cell bridge to cross the strut. The exposedisland2302 can serve as a seed for thrombosis development. In some embodiments of the disclosure,porous structure104 is constructed to reduce the likelihood of endothelial cells falling from the porous structure, thereby reducing the chance of development of late or sub-acute thrombosis and exposure ofsupport element102 to substances within the lumen. For example, endothelial cell retention is optionally encouraged by constructingporous structure104 from at least one fiber of a thickness and with aperture sizes (to permit growth of endothelial cell therethrough), such as described herein. Optionally, endothelial cells are encouraged to remain on the porous structure by using a fiber layer of a thickness such as those described herein. Optionally, the linear nature of a single fiberporous structure104, such as shown inFIG.29, reduces the possibility of a large clump of endothelial cells becoming dislodged. In an embodiment of the disclosure,porous structure104, optionally imbued with a pharmaceutical, is placed on the interior of a bare metal or drug eluting support element in order to reduce the thrombogenicity of the support element. For example, by encouraging endothelial cell growth thereover and/or by reducing the exposed surface area of the support element by covering a portion of it up.

In an embodiment of the disclosure, the reduced risk of late or sub-acute thrombosis by usingporous structure104 for pharmaceutical elution optionally allows for a duration and/or dosage reduction in the use of anti-coagulants by the patient.

In some example embodiments of the disclosure, fiber thickness, porous structure thickness and/or aperture size are all separately varied depending on the application ofporous structure104 and the needs of the patient. For example, in the coronary arteries it is sometimes helpful to provide for good pharmaceutical dispersion. In such an example, fibers includingporous structure104 are optionally located closer together in order to allow for more complete transmission of a pharmaceutical to patient.

In some example embodiments, when large molecule drugs, which have a poor diffusion into the tissue, are used to fight restenosis, the porous structure can be soaked and/or imbued with an appropriate drug in order to better diffuse it. The maximum concentrations of most of the drugs used are rather limited due to side effects and over toxicity, and at the same time the concentration is not enough in order to allow the optimum pharmacokinetics in areas not covered by the stent struts. The porous structure mesh, having a better geometrical cover of the stent area, provides a better and more optimum pharmacokinetics to the whole area covered by the stent. For example, when high Dalton-large molecule drugs are used, or when liposomes are the carriers of the treatment agents, or when the stereo-chemical structure of the drug is large and/or complicated, and/or when the drug is hydrophobic, relatively even distribution of the drug is highly desirable. In some example embodiments of the disclosure, pharmacokinetics is also optimized because the drug is located on/in the fibers ofporous structure104, and is covered and sealed within an endothelium layer, which helps the drug from being washed away by the blood.

In some example embodiments of the disclosure, such as in a bypass vein graft, side branching is not an issue, therefore aperture sizes are optionally made smaller, but not so small as to prevent endothelial cell growth therethrough. In another example embodiment of the disclosure, such as in the carotid arteries, side branching is not generally considered a problem, but catching debris is. Therefore, in some example embodiments of the disclosure, the aperture sizes ofporous structure104 are decreased to as little as 20 microns in diameter. In other applications, the aperture size can be increased to 50, 100, 200 or even more then 200 microns, depending on the application ofenhanced stent apparatus100.

In some example embodiments of the disclosure, a plurality of porous structures is used. Optionally, at least one porous structure is located on the interior ofsupport element102, inside the lumen ofsupport element102. Optionally, more than one porous structure is located on the exterior surface ofsupport element102. In some example embodiments of the disclosure, at least some of the porous structures located onsupport element102 are configured to be “in-phase” where the apertures of the porous structures coincide with one another. Optionally, the porous structures are “out-of-phase” where the apertures are configured to not coincide with one another. In an example embodiment of the disclosure, an “out-of-phase” configuration is used to improve contact surface area between porous structures and the lumen interior surface. In an embodiment of the disclosure, increased contact surface area can improve pharmacokinetics, reduce local pressure exerted byporous structure104 on the lumen wall, improve embolic shower protection and/or realize other advantageous effects. In some example embodiments of the disclosure,porous structure104 is constructed in the same shape and pattern assupport element102, but on a smaller scale.

Example Materials of Manufacture

It should be noted that in some example embodiments of the disclosure, a stretchable and/or expandableporous structure104 is desired. Therefore, in some embodiments of the disclosure, materials are chosen which are either a) stretchable and/or b) can be used to manufacture a porous structure which is stretchable (e.g. a knitted structure). In some example embodiments of the disclosure, biodegradable (i.e. are broken down by the body) and/or bioresorbable (i.e. are absorbed into the body) materials are used. In addition, blends of materials are used in accordance with some embodiments of the disclosure. In an embodiment of the disclosure, a material is chosen because it exhibits durability during manufacture, deployment and/or use despite being thin. In an embodiment of the disclosure, other considerations for the material to be used are their biocompatibility, toxicity, hemocompatibility, and thrombogenicity.

Example materials for manufacturingporous structure104 include natural-based materials such as modified cellulose and/or collagen. In some embodiments of the disclosure, metal fibers are used to construct porous structure, optionally constructed of stainless steel, and/or CoCr and/or CoNi alloy among other possibilities. Optionally, the metal fibers used are coated with at least one polymer. In some embodiments of the disclosure, porous structure is manufactured from a shape memory alloy, such as nitinol. Optionally, carbon fiber is added toporous structure104 in order to improve strength characteristics ofporous structure104. Optionally, glass fiber is added toporous structure104 in order to improve strength characteristics ofporous structure104. Optionally, a durable, resorbable and/or degradable fiber is added toporous structure104 in order to improve strength and durability characteristics of the fiber during manufacture, which is degraded or resorbed or washed away to leave a thinnerporous structure104.

In an embodiment of the disclosure, some polymer fibers are chosen for use in constructingporous structure104 because they are elastic, biocompatible, hemocompatible, can be made not to stick to endothelium tissue, are selectably bio-stable and/or biodegradable, exhibit the requisite mechanical strength, are sterilizable, have a high temperature transformation zone (solid and non-sticky at 37° C.), are capable of hosting an effective amount of pharmaceuticals, and/or can release embedded pharmaceuticals at a controlled rate. In some example embodiments of the disclosure, other materials which exhibit some or all of these properties are optionally used to constructporous structure104. Optionally, coatings are put onporous structure104, including materials which exhibit some or all of these properties.

Polymer fibers are optionally made out of any of the following materials: thermoplastic polymers for example polyethylene terephthalate (PET), polyolefin, oxidized acrylic, PTFE, polyethylene co-vinyl acetate, polyethylene elastomer, PEO-PBT, PEO-PLA, PBMA, polyurethane, Carbosil (PTG product), medical grade polycarbonate urethanes, Nylon, PEEK-Optima, carboxylic acid moiety including one or more of a poly acrylic acid, a poly methacrylic acid, a maleic acid, a helonic acid, a taconic acid and/or combinations and/or esters of these monomers, thermoplastic polymers, thermosetic polymers, polyolefin elastomers, polyesters, polyurethanes, polyfluoropolymers, and/or nylon. Optionally, the fibers are constructed of an elastomer. Optionally, the fibers are constructed of a coated fiber with a drug and polymer coating mixed to get a predetermined drug release characteristic, either coating over a metal and/or over a polymer fiber. Optionally, the fibers are constructed of other materials than the example materials listed above. Example polymers which are optionally used for this purpose are manufactured by Cordis®, Surmodix®, Boston Scientific®, Abbott® and Hemoteq® Polymers. Optionally, these polymers are selected for at least one of the reasons specified in the paragraph above. Optionally, the coating is used to facilitate the elution of pharmaceuticals fromporous structure104.

In some embodiments of the disclosure, the porous structure is made out of a resorbable/degradable polymer such as poly lactic-co-polyglycolic (“PLGA”) copolymers, or any other degradable copolymeric combination, such as polycaprolactone (“PCL”), polygluconate, polylactic acid-polyethylene oxide copolymers, poly(hydroxybutyrate), polyanhydride, poly-phosphoester, poly(amino acids), poly-L-lactide, poly-D-lactide, polyglycolide, poly(alpha-hydroxy acid) and combinations thereof.

Example Methods of Manufacture

Many of the methods and orientations described herein are designed to provide a porous structure which exhibits at least some expandable quality.Porous structure104 is optionally adapted and constructed to stretch as it is being deployed within the lumen being treated. In some example embodiments of the disclosure,porous structure104 is provided with stretchability in order to ease positioningporous structure104 relative to supportelement102 or another intervening layer, such as a graft or buffering elements.

In an example embodiment of the disclosure, weaving, braiding and/or knitting results in some or all the elasticity of the porous structure being achieved due to the structure of the interlaced and/or crimped and/or textured fibers (curly, slack). This can be achieved by material elongation properties securing the porous structure to the stent. In some example embodiments of the disclosure, a porous structure is made by combining several interlacing techniques such as knitting over a braided porous structure or braiding over a knitted porous structure. In some embodiments of the disclosure, multiple layers are combined and/or created using these techniques. In some example embodiments of the disclosure, a warp knitted porous structure with “laid in” yarns is used. In some example embodiments of the disclosure, a porous structure is woven using elastomeric or crimped weft to obtain radial elasticity.

In some example embodiments of the disclosure, the porous structure is manufactured by combining several techniques such as knitting over a braided porous structure or braiding over a knitted porous structure. In some example embodiments of the disclosure, a weft knitted porous structure with “laid in” yarns is used. In some example embodiments of the disclosure, a porous structure is woven using elastomeric and/or crimped weft to obtain radial elasticity. Optionally, porous structure includes at least one fiber oriented generally parallel to the support element's longitudinal axis.

In an example embodiment of the disclosure, a manufactured porous structure is added as a cover to supportelement102. Optionally,porous structure104 is used separately fromsupport element102, which is optionally not used for stenting. In some example embodiments of the disclosure,porous structure104 is manufactured directly ontosupport element102.

In an example embodiment of the disclosure,porous structure104 is manufactured by a knitting technique known to those of ordinary skill in the knitting art for non-analogous arts, such as clothing manufacturing and textiles. Knitting ofporous structure104 is optionally performed by heads having between 20 and 35 needles. Optionally, the head used has between 30 and 45 needles. Optionally, the head used has between 35 and 80 needles. An example of the effect of head size on the porous structure can be seen inFIG.14, described above, in which a 22 size head and a 35 size head are graphed. InFIG.14, the needle gauges are 40.

In some embodiments of the disclosure, the shape and/or size of the knit is controlled by controlling the tension on the fiber being used for knitting. For example, to create a knit with larger eyes, slack is provided to the fiber during knitting. Optionally, the fiber is controlled during knitting to achieve a circular shaped eye whenporous structure104 is expanded. In an embodiment of the disclosure, pre-tension on the fiber during knitting is approximately 10-20 grams. In some embodiments of the disclosure, post-tension on the fiber during knitting is 15-25 grams. The stitch length is between 300 and 400 microns, in an example embodiment of the disclosure. In some embodiments of the disclosure, the knitting machine is run at a relatively slow speed. For example, the knitting machine is run at 10% of speed capacity using a Lamb Knitting Machine Corp. System Model WK6 with a special modification of speed operation measured by percentage.

In an example embodiment of the disclosure, a fiber or a super-fiber yarn with a specific fineness, or a range of fineness, between 5 and 100 microns is used to manufacture a knit porous structure. Optionally, yarn with a fineness of 10 to 20 microns is used to manufacture a knit porous structure. Optionally, the yarn is finer than 5 microns. Yarn fineness is often referred to in textile terms by “Tex”. This is the weight in grams of 1000 meters of the yarn. In an example embodiment of the disclosure, yarn ranging from 0.3 Tex to 10 Tex is used to manufacture porous structure. In some embodiments of the disclosure, a specific yarn fineness is chosen based on the desiredporous structure104 characteristics. For example, a 0.5 Tex yarn using a 22 gauge needle head will, in some embodiments, produce a porous structure with approximately 12% coverage area.

An example resulting porous structure using the above components and techniques, should have 5 to 50 courses per cm. Optionally, 20 to 45 courses per cm are manufactured. Optionally, a porous structure with 30-35 courses per cm is manufactured.FIG.5 illustrates a knittedporous structure104 andsupport element102 in a crimped, closed position.FIG.6A illustrates a knittedporous structure104 laid on top of asupport element102 in an open position.FIG.6B shows example knitting in detail.

In another example embodiment of the disclosure, weaving techniques are used to manufactureporous structure104. Narrow needle looms as well as conventional narrow looms can be configured to produce woven tubular structures. In weaving, at least two layers of warp yarns are interlaced with intersecting fill yarns.

By carrying the fill yarn alternately back and forth across two layers of warp yarns, a tubular shape is created. The size and shape of the weave are optionally controlled by determining the warp and/or fill density, the interlacing pattern and/or frequency, the yarn tension and/or the yarn dimensions and/or elastic properties. The types of weaves used for a porous structure are optionally one of “plain”, “basket”, “twill”, “sateen”, “leno” and/or “jacquard”. Optionally, all of the fibers of porous structure are the same. Alternatively, warp and weft fibers of a weave are not constructed of the same materials. Optionally, different materials are used to take advantage of the inherent properties of the different materials, for example one material may be elastic and a different material may have a high tensile strength. Optionally, warp fibers are coated and/or are pharmaceutical eluting while the weft fibers are not, or vice versa.

In another example embodiment of the disclosure, braiding techniques are used to manufactureporous structure104, for example as described in Knitting Technology, D. J. Spencer—ed., Woodhead Publishing Limited, Abington Hall, Abington, Cambridge, CB1 6AH, England, the disclosure of which is incorporated herein by express reference thereto. Braiding machines are optionally used to interlace yarns at a variety of intersecting angles. In braiding, multiple yarns are fed to an interlacing zone. Interlacing is optionally achieved by rotation of the yarn spools or by a reciprocating needle bed. The size and shape of the braid is optionally controlled by the number of yarns, the interlacing pattern and/or angle and/or the yarn dimensions and/or elastic properties. Optionally, all of the fibers of porous structure are the same. Optionally, warp and weft fibers of a braid are not constructed of the same materials, for example where weft fibers are used to provide strength and warp fibers are used to provide stretchability of the braid.

In another example embodiment of the disclosure,porous structure104 is manufactured by an electrospinning process. Electrospinning is a technique which utilizes a charged polymer solution (or melt) that is fed through a small opening or nozzle (usually a needle or pipette tip). Because of its charge, the solution is drawn toward a grounded collecting plate (usually a metal screen, plate, or rotating mandrel), typically 5-30 cm away, as a jet. Optionally,support element102 is placed on a delivery catheter which is used as a mandrel. During the jet's travel, the solvent gradually evaporates, and a charged polymer fiber is left to accumulate on the grounded target. The charge on the fibers eventually dissipates into the surrounding environment. The resulting product is a non-woven fiber porous structure that is composed of tiny fibers with diameters between approximately 40 nanometers and 40 microns (e.g. a felt), depending on the size of the fibers input into the system. If the target is allowed to move with respect to the nozzle position, such as by rotating and/or moving the mandrel along its longer axis, specific fiber orientations (parallel alignment or a random alignment, as examples) can be achieved. In some example embodiments of the disclosure,porous structure104 is spun in a helical coil pattern onto the mandrel orsupport element102. Optionally,porous structure104 includes a plurality of helical coil patterns, constructed by moving the mandrel back and forth, such as depicted inFIG.4. Optionally,porous structure104 is constructed with fibers oriented substantially parallel tocentral axis106. Optionally,porous structure104 is constructed with fibers oriented substantially perpendicular tocentral axis106. Optionally,porous structure104 is constructed with fibers oriented in a combination of any of the orientations described or suggested herein. The mechanical properties of the porous structure are optionally altered by varying the fiber diameter and orientation depending on the requirements for treating a patient. For example, in some embodiments of the disclosure, a laser is used to cut specific aperture sizes and/or to ensure that the apertures traverse from the exterior side ofporous structure104 to the interior side ofporous structure104. Optionally, solvent is used to modify aperture sizes.

Optionally, portions of catheter are masked in order to prevent accidental coverage of the delivery catheter byporous structure104. Optionally,support element102 is coated with an adhesive and/or a pharmaceutical agent prior to putting theporous structure104 on the top ofsupport element102. In some example embodiments of the disclosure, the material used to produce theporous structure104 is imbued with pharmaceutical agents. Optionally, pharmaceutical agents are embedded in the material coating theporous structure104. In an example embodiment of the disclosure,porous structure104 includes at least one inner coating proximal to supportingstructure102 which exhibits different properties than an external coating proximal to patient's blood vessel. For example, the inner coating is optionally configured to avoid adhesion to the delivery catheter and/or support structure. Optionally, inner coating is configured to adhere to supportelement102, but not to delivery catheter.

In some embodiments of the disclosure,porous structure104 is designed to be less sensitive to foreshortening and elongation forces asporous structure104 expands upon deployment. This is in part due to the knitted nature ofporous structure104, in some embodiments. This property allowsporous structure104 to be secured to supportelement102 at its ends, rather than in another location, such as the middle as described in U.S. App. No. 2005/0038503 to Greenhalgh et al., the description of which is incorporated herein by express reference thereto.

In some example embodiments of the disclosure, a porous structure is manufactured in an at least partially open, wide diameter, condition. In some example embodiments of the disclosure, the at least partially stretched porous structure is reduced to a smaller diameter, by heat-setting, crimping and/or folding, after manufacture.

In an embodiment of the disclosure, the diameter of the at least partially stretched porous structure is reduced mechanically. Optionally, afunnel1304 shown inFIG.12, is used to reduce the diameter of the knitted porous structure1302, during the manufacture the porous structure. A knitted porous structure1302 is drawn down from the knitting zone into a narrowing bore,funnel1304. This results in a final porous structure diameter that is controllably smaller than the diameter of the needle bed.FIG.13, illustrates how a porous structure is manufactured using a stretchedrubber tube1402. In this method, theporous structure1400 is tightly inserted onto a pre-radially stretchedtube1402, and then the tube is relaxed, compressing the porous structure and creating a smaller aperture sized porous structure, the size of which is controlled by the stretch ratio of the rubber tube.

Referring toFIG.17, an embodiment is shown in whichporous structure104 is folded in “n” substantially folds, the folds used to reduce the overall diameter ofenhanced stent apparatus100 for easier insertion and navigation through the patient. Optionally, the folds are towards the same direction. In an embodiment of the disclosure, a foldedporous structure104 is at least temporarily secured to supportelement102.FIG.10 shows an alternate folded configuration from a perspective view.

An additional or alternative embodiment to folding includes heat setting a polymer includesporous structure104 to supportstructure102. In an embodiment of the disclosure, heat setting is used whenporous structure104 includes at least one polymer material. Determination of heat setting conditions is related to the polymer's heat transition temperatures, in an embodiment of the disclosure. Heat setting is performed in the temperature range between T_gand T_mof the polymer. At this range the polymer becomes amorphous and is shrunk to supportelement102, establishing an overallenhanced stent apparatus100 radius that is not much more than thesupport element102 radius. For example,porous structure104 adds less than 10 microns in diameter total to supportelement102 which is 1 mm in diameter, in some embodiments of the disclosure. At T_mthe polymer turns into a viscous liquid which loses its mechanical integrity and will stick to supportelement102 surface. For example, polyethyleneterephthalate (PET) has a T_gof 70° C. and a T_mof 265° C., therefore the heat set temperature somewhere within that range, in an embodiment of the disclosure, is 200° C. Using temperatures higher than T_mfor heat setting can cause thermal degradation, which results in polymeric chain scission, unzipping of the polymer and/or producing a large array of oligomeric material that changes the mechanical properties ofporous structure104 and/or releases poisonous and/or non-biocompatible materials, causing an inflammatory reaction in the patient. Other example polymers which can be used in heat setting are below in Table 1 (not an exhaustive list):

TABLE 1

TABLE-US-00001 Example polymers and
temperatures for heat setting Material name

Material name	T_g	T_m	set temp.

PP	18° C.	165° C.	140° C.
NYLON 6,6	80° C.	256° C.	210° C.
PTFE	150° C.	330° C.	300°C.
PVA
100° C.	230° C.	190° C.
Polyurethanes	70° C.	120° C.	100° C.
PLLA	60° C.	175° C.	100° C.

Another additional or alternative embodiment to folding includes crimping using at least acrimped support element102 in combination withporous structure104. In some embodiments of the disclosure,porous structure104 is crimped withsupport element102. In an embodiment of the disclosure, crimping ofporous structure104 andsupport element102 is performed when it is desirable to reduce the overall diameter ofenhanced stent apparatus100. For example, a reduced diameter enhancedstent apparatus100 allows for easier insertion and navigation of the apparatus to the treatment site. In some embodiments of the disclosure, at least acrimped support element102 provides an object with relatively stable mechanical properties for more predictable movement during insertion and navigation.

Optionally,porous structure104 is made on anon-crimped support element102. Anon-crimped support element102 can be expanded or semi-expanded during manufacture. In an example embodiment of the disclosure,porous structure104 andsupport element102 are crimped together. Optionally, excessporous structure104 material, which is created as a result of reducing the profile ofsupport element102 during crimping, is folded withsupport element102, such as shown inFIG.17. In some example embodiments of the disclosure,porous structure104 is made on a crimped or partially crimpedsupport structure102. When manufacturing a porous structure for placement on an already crimped support structure, consideration may be given to providing a porous structure which is sufficiently stretchable to expand with the radial expansion of the support structure, when implanted at a treatment site within a lumen.

Example Methods for Coating a Fiber

In another example embodiment of the disclosure, a manufacturing technique is used to cot a fiber thatporous structure104 includes with at least one polymer layer. For example, a dipping technique, shown inFIG.18, using a biocompatible, hemocompatible, biostable and/or biodegradable polymer dissolved in an organic solvent is utilized to create a dipping solution1906 for use in coating the fiber includingporous structure104. The fiber to be coated is optionally placed in aspool1902, from which thefiber1904 is drawn to formporous structure104. Additives such as drugs, biological components, enzymes, growth factors, and/or any other additive mentioned herein or known in the art, may be incorporated intofiber1904 during the manufacturing process, for example by placing them in solution1906 and passingfiber1904 through solution1906. In an embodiment of the disclosure, at least one layer is used in order to control the drug/biological additive's release. For example, more than one solution tank may be provided forfiber1904 to pass through during manufacture.Fiber1904 is optionally moved into a drying oven1908 with an operational temperature range from 37-70° C. (in some embodiments of the disclosure) depending on the drug used, to dry solution1906 ontofiber1904. In an example embodiment of the disclosure,fiber1904 is then used by a knitting system to1910 to manufactureporous structure104. Optionally,knitting system1910 is the Lamb Knitting Machine Corp. System Model WK6. Optionally,porous structure104 is coated with a polymer layer after it has been manufactured.

In some example embodiments of the disclosure,support element102 andporous structure104 are coated with an additional substance. Optionally, the additional substance is a polymer. Optionally, the additional substance is drug eluting. Optionally, the coating is hyaluronic acid. Alternatively or additionally, the coating is hyaluronan. Optionally, a different non-woven technology such as wet and/or dry spinning is used to manufactureporous structure104. In some embodiments of the disclosure, additional coatings are added to achieve different effects, for example timed release of pharmaceutical agents and/or release of a plurality of agents at different times.

Example Methods for Mounting Porous Structure to Support Element

In some embodiments of the disclosure,porous structure104 is at least temporarily secured to supportelement102. Advantages of securingporous structure104 to supportelement102, at least temporarily, include: prevention of unraveling and/or run out of fiber from the porous structure weave, dislodgement and/or slipping ofporous structure104 with respect to supportelement102 during insertion, delivery and/or deployment. Optionally,support element102 andporous structure104 are not secured together using an adhesive and/or other securing means despite being in a coaxial and proximate relationship in many embodiments.

In some example embodiments of the disclosure, wheresupport element102 is optionally coated with a polymer,support element102 andporous structure104 are attached together by curing at the same time the polymer support element coating and the polymer includes porous structure, and/or coated porous structure, thus adhering the polymers together. Optionally, pressure and/or heat is used to adhere a polymer coatedsupport element102 to a non-coated or polymer coatedporous structure104, for example when they are both hot. In some example embodiments of the disclosure,porous structure104 includes two components, an external component and an internal component, relative to supportelement102. Upon the simultaneous curing of the external and internal components, the polymers of which both adhere together, thereby securingporous structure104 to supportelement102, which is located between the components.

In an example embodiment of the disclosure,porous structure104 is secured to supportelement102 in order to avoid porous structure migration, but not limitporous structure104 and/orsupport element102 expandability.

In some example embodiments of the disclosure, an adhesive is used tobond support element102 andporous structure104 together. Optionally,porous structure104 is glued to supportelement102 utilizing any natural and/or synthetic biocompatible adhesive, such as cyanocrylate, thermo plastic elastomers, silanes, laminin, albumin and/or fibrinogen and/or PEG-PEG adhesive, and/or polyurethane adhesive and/or any other suitable compatible polymeric material. Optionally, whenporous structure104 is glued to supportelement102, wherein thesupport element102 is a drug eluting stent, the same polymer as used for the elution of the drug is used for attachment ofporous structure104 to supportelement102.

In an embodiment of the disclosure,porous structure104 is attached to supportelement102 at a plurality of points. Optionally, the plurality of points defines a pattern, such as a line or zigzag of points. Optionally,porous structure104 compresses ontosupport element102 to maintain an attachment to supportelement102. Optionally, the porous structure is held in place on support element at least partially by frictional forces. Optionally,porous structure104 is sewn and/or mechanically entangled ontosupport element102. Optionally, heating, pressure, laser welding, UV curing and/or ultrasound are used as techniques to secureporous structure104 to supportelement102. Optionally, a primer, such as parylene, is used onsupport element102 prior to adheringporous structure104 to it in order to enhance cohesion.

Referring toFIG.15, an embodiment of the disclosure is shown in whichporous structure104 is attached to supportelement102 using a sliding connection1602. In an example embodiment of the disclosure, the sliding connection is established by attaching at least one loop1604 ofporous structure104 to supportelement102 in a condition that prevents the two from becoming separated, but is loose enough to allow sliding ofporous structure104 with respect to supportelement102. In an embodiment of the disclosure, a loose stitch is used to attachporous structure104 to supportelement102 in a sliding connection. In an embodiment of the disclosure, expansion ofporous structure104 is assisted by utilizing the sliding nature of the connection1602. For example,porous structure104 is secured to theoutermost strut1606 ofsupport element102 at its most outlying position1608. In an embodiment of the disclosure, on the other side ofsupport element102

porous structure

104 is also attached to the outermost strut at its most outlying position. Whensupport element102 andporous structure104 are expanded during deployment,porous structure104 is afforded additional expandability, in relation to a pre-expanded configuration, as the sliding connection1602 moves from the most outlying position1608 onoutermost strut1606 to aninnermost position1610. Thedistance1612, about 1 mm to 6 mm in an embodiment of the disclosure, from the most outlying position1608 toinnermost position1610 provides additional expandability toporous structure104. Optionally, sliding is prevented by securingporous structure104 to strut1606 atinnermost position1610 as well as most outlying position1608. Optionally, sliding is prevented by tightening the connection between the two, for example by providing a tighter stitch.

In some embodiments of the disclosure,porous structure104 is tied to supportelement102 using any one of thumb, square, reef, or double surgeon's knots. Optionally, the at least one fiber used to constructporous structure104 is used to tieporous structure104 to supportelement102.FIG.16 shows an example method for attachingporous structure104 to supportelement102 using knotting. It can be seen that a knotting fiber1702 is used to secureporous structure104 to supportelement102 at various points along asupport element strut1704. Optionally, knotting fiber1702 is threaded through a plurality ofeyes1706 and oversupport element strut1704 wherein aknot1708 is tied to secureporous structure104 to supportelement102 at least some of the eyes.

As mentioned above, in some embodiments of the disclosure, securingporous structure104 to supportelement102 is also used to reduce the likelihood of run outs and/or porous structure unraveling. In an embodiment of the disclosure, run outs and/or porous structure unraveling are to be avoided for at least the reasons of: avoiding porous structure protrusion into the lumen and/or rendering porous structure ineffective for intended treatment of the lumen. In an embodiment of the disclosure,porous structure104 is secured to supportelement102 at the ends ofsupport element102, at least some intersections whereporous structure104 andsupport element102 overlap, or both and/or every eye at both ends. Any of the methodologies of securing described above are optionally used to secureporous structure104 to supportelement102 to prevent run outs and/or unraveling.

In an example embodiment of the disclosure,porous structure104 is treated to supply temporary enhanced adhesion to supportelement102 during implantation.

For example,enhanced stent apparatus100 is optionally dipped in a liquid which causesporous structure104 to adhere to supportelement102. Optionally, this adherence is due to surface tension of the liquid. Optionally, this adherence is due to temporary shrinkage ofporous structure104, which secures it to supportelement102 more tightly. In some example embodiments of the disclosure, temporary cohesion is used to preventporous structure104 from slipping off ofsupport element102 as a result of frictional stress experienced during navigation of the vasculature during implantation.

General Pharmacological Usage

Alternatively or additionally to the physical prevention of debris from entering the bloodstream,porous structure104 optionally contains pharmaceuticals designed to treat a variety of ailments. In some example embodiments of the disclosure, pharmaceuticals are optionally provided including one or more pharmacological agents for encouraging cell and/or liposomal growth and/or other endothelial cell growth factors, anti-proliferative, anti-thrombotic, anti-coagulant and/or anti-platelet effects, tissue engineering factors, immunomodulators, antioxidants, antisense oligonucleotides, collagen inhibitors, hydrophobic pharmaceuticals, hydrophilic pharmaceuticals and/or endothelial cell seeding substances. Optionally, pharmacological therapy rendered from a porous structure is used to accelerate vein to artery conversion. Specific examples of pharmaceuticals that are optionally used withporous structure104 include: anti-proliferative agents like sirolimus, zolimus or zotarolimus (ABT-578®), paclitaxel and other taxanes, tacrolimus, everolimus, vincritine, viblastine, HMG-CoA reductase inhibitors, doxorubicin, colchicine, actinomycin D, mitomycin C, cycloporine, and/or mycophenolic acid, triazolopyrimidine and its derivatives (i.e. Trapidil®, a coronary vasodilating drug); intrapide, glucocorticoids like dexamethasone, methylprednisolone, and/or gamma interferon; antithrombotics like heparin, heparin-like dextran derivatives, acid citrate dextrose, coumadin, warfarin, streptokinase, anistreplase, tissue plasminogen activator (tPA), urokinase and/or abciximab; antioxidants like probucol; growth factor inhibitors like tranilast and/or angiopeptin; antisense oligonucleotides like c-myc and/or c-myb; collagen inhibitors like halofuginone and/or batimistat; liposomes; gemcitabine (i.e. Gemzar®); steroids and corticosteroids for example cortisone and prednisone; cortisone, prednisone; sirolimus (Rapamycin®); statin drugs like lovastatin and/or simvastatin (i.e. Zocor®); VEGF; FGF-2; micro carriers containing endothelial cells; genes; DNA; endothelial cell seeds; and/or hydrogels containing endothelial cells.

Typically, stents (i.e. support elements) which provide pharmaceutical treatment only have the pharmaceutical embedded on the structure of the stent, in particular on the stent struts. This structure is typically minimized in order to provide flexibility and reduce cost, among other reasons. As a result of a minimized support element structure, the struts of the structure are usually spaced widely apart. Thus, when the stent is in situ, and pharmaceuticals are released into the patient from the stent, the pharmaceutical is only diffused from the widely spaced struts. This prevents even distribution of the pharmaceutical over the entire length of the stent. In addition, stent struts are typically large in relation to endothelial cells and therefore formation of a covering endothelial cell layer typically takes on the order of days or weeks, rendering pharmaceutical elution into body tissues delayed and/or ineffective (due to a number of reasons, including the pharmaceutical being washed away by fluids flowing in the lumen before the endothelial cell layer covers the stent).

In contrast, usage of a pharmaceutical enhanced porous structure, such as described herein, to cover the stent, including the struts, provides far more surface area in contact with the inner wall of the patient's blood vessel, thereby enabling more diffusion to take place. In comparison to conventional techniques for stent delivered pharmaceuticals, lower concentrations of pharmaceutical are optionally used with the present disclosure because of its improved therapy-rendering surface area. In an embodiment of the disclosure, improved delivery by the presently described disclosure allows for lower doses of pharmaceutical to be used in order to render the same relative amount of treatment, and reduce the overall dosage needed in order to obtain the same results, thus reducing possible side effects. For example, a currently recommended concentration of taxol on a drug eluting stent is around 1 μg/mm²of stent surface. In contrast, a concentration of 0.5 μg/mm²is optionally used withporous structure104, due to its increased treatment rendering surface area. Optionally, the concentration is less than 0.5 μg/mm². As another example, typical concentrations of rapamycin and ‘limus drugs today are around 140 μg/mm², however, using the herein described porous structure104 a concentration of 80 μg/mm²is optionally used to achieve the same therapeutic effect. In some example embodiments of the disclosure, as little as 10 μg/mm²is optionally, used to achieve the same therapeutic effect. In some example embodiments of the disclosure, concentrations of pharmaceutical embedded on porous structure are up to 15 times less than conventionally used today.

In conventional stents, at the struts, the pharmaceutical may not propagate far enough and/or without effect into the vascular wall, or may overdose a particular section of the vascular wall, without sufficient propagation laterally to the rest of the inner surface where it is needed. Having additional surface area more evenly covering the stent surface area,porous structure104 can deliver drugs in a more locally homogenous way. Optionally, there is an axial profile change in dosage. Since distribution of the drug into the tissue is governed by diffusion, and since the amount of dosage concentration on the struts is limiting due to over toxicity and side effects, spreading the drug in a more even manner is very helpful for obtaining better pharmacokinetics.

In an example embodiment of the disclosure, pharmaceuticals to be administered to patient are located in and/or on the fibers ofporous structure104. Examples of where and how pharmaceuticals are optionally located in and/or on the fibers ofporous structure104 and/or eluted include:

- 1. depositing pharmaceutical in the apertures of porous structure;
- 2. mixing pharmaceutical particles into fibers of porous structure at fiber creation;
- 3. applying pharmaceutical topically to the porous structure, such as by spraying;
- 4. dipping porous structure into a solution containing a pharmaceutical additive, thereby depositing the additive on and/or in the fibers of the porous structure;
- 5. encapsulating a pharmaceutical additive on porous structure, optionally using a thermal process;
- 6. grafting a pharmaceutical additive onto porous structure using plasma treatment;
- 7. etching a pharmaceutical additive into porous structure, for example via spattering or coating;
- 8. transferring a pharmaceutical additive to porous structure using concentration differences between the porous structure and an additive containing substance, for example by adhering micro carriers containing to pharmaceutical additive to a porous structure allowing their migration into the porous structure;
- 9. any method known to those of ordinary skill in the art, such as shown in U.S. Pat. App. No. 2004/0030377 to Dubson et al., U.S. Pat. App No. 2005/0187140 to Hunter et al., U.S. Pat. App. No. 2004/0236407 to Fierens et al., U.S. Pat. No. 6,902,522, to Walsh, et al., U.S. Pat. No. 6,669,961 to Kim, et al., U.S. Pat. No. 6,447,796 to Vook et al., U.S. Pat. No. 6,369,039 to Palasis et al., U.S. Pat. No. 6,939,374 to Banik, et al., and U.S. Pat. No. 6,919,100 to Narayanan, the contents of which are incorporated herein by express reference thereto;
- 10. elution of the drug from a polymer coating the porous structure fibers;
- 11. elution of the drug from the polymer from which the porous structure is constructed; and,
- 12. incorporating the drug in a biodegradable polymer.

Optionally, embedding of the pharmaceutical occurs before (e.g. mixing pharmaceutical particles into fibers of porous structure at fiber creation), during (e.g. using the dipping method ofFIG.18) and/or after (e.g. a spray on pharmaceutical after apparatus is made) the manufacture ofenhanced stent apparatus100. In some example embodiments of the disclosure, a pharmaceutically embeddedporous structure104 is placed on top of a pharmaceutically treatedsupport element102. In some example embodiments of the disclosure,porous structure104 is coated with at least a polymer. In some example embodiments of the disclosure, a porous structure is provided with a polymer coating which contains a pharmaceutical which elutes from the coating.

Pharmaceuticals are optionally embedded intoporous structure104 such that they are released into the patient over an approximate predetermined amount of time. For example, pharmaceuticals are optionally embedded intoporous structure104 for release over the course of a week. Other pharmaceuticals are optionally embedded intoporous structure104 for release over the course of months. Factors which vary according to the release schedule of the pharmaceutical include the type of material used to constructporous structure104, the type of pharmaceutical being used, the manner in whichporous structure104 is constructed, and/or the amount of coverage ofsupport element102 thatporous structure104 provides.

In some example embodiments of the disclosure, 1 microgram of pharmaceutical per square centimeter of fiber surface coverage (not the area of the fiber themselves, but the area of the tissue it treats) area is embedded on the fibers. Optionally, up to 200 micrograms of pharmaceutical per square centimeter of fiber surface area is embedded on the fibers. Optionally, a higher or lower concentration of pharmaceutical is used depending on the therapeutic needs of the patient and depending on the type of drug used.

Large and/or Complicated Stereochemistry Molecule Pharmaceutical Usage

In some example embodiments of the disclosure, usage ofporous structure104 for enhanced pharmaceutical delivery allows for effective dispersion and delivery of large molecule and complex stereochemistry pharmaceuticals. Traditionally, large molecule pharmaceuticals are not used with drug eluting stents because they don't diffuse very well, and the widely spaced struts of traditional stents do not facilitate even and/or widespread diffusion of the large molecule, as described above. In contrast, use of a device with more extensive coverage of a vascular wall would make treatment using large molecule pharmaceuticals more feasible. This is optionally accomplished by providingporous structure104 and/orsupport element102 with large molecule pharmaceuticals for elution and taking advantage of the increased vascular wall coverage ofporous structure104, due to the smaller aperture sizes in some example embodiments. Alternatively or additionally, due to the overgrowth ofporous structure104 by cells from the body, large molecule pharmaceuticals are more efficiently delivered to the patient as pharmaceuticals are delivered into tissue, rather than being washed away in the blood stream, for example. Optionally, pharmaceuticals larger than 700 Dalton, 1,000 Dalton, 3,000 Dalton or up to 50,000 Dalton are dispersed and delivered evenly into patient's vasculature.

Optionally, liposomes are eluted from at least oneporous structure104 and/orsupport element102. Optionally, steroids, statins, anticoagulants, gemcitabine (Gemzar®), zolimus or zotarolimus (ABT-578®), sirolimus (e.g. Rapamycin®), taxol/paclitaxel, and/or other large or complex molecule pharmaceuticals are eluted from at least oneporous structure104 and/orsupport element102. Referring toFIG.3,pharmaceutical agents406 are shown eluting fromenhanced stent apparatus100 intoartery400 fromlumen wall404. Optionally,agents406 elute from porous structure after at least some growth ofendothelial cells408 through enhancedstent apparatus100, for example the time determined by experimental endothelial cell growth data. As described elsewhere herein,porous structure104 optionally acts to trapdebris402 between the exterior surface ofenhanced stent apparatus100 andlumen wall404.

Timed Release Pharmaceutical Usage

In an example embodiment of the disclosure, pharmaceuticals are eluted from an enhanced stent apparatus into overgrown endothelial tissue and not merely into the interior surface of the lumen being treated. In an example embodiment of the disclosure, pharmaceutical release is thus optimized by ensuring that only a pre-defined amount of drug is lost into the bloodstream and/or into other non-therapeutic media. In some example embodiments, including, for example, in conjunction with BBB treatment as described below, endothelial cell growth can assist with pharmaceutical therapy by providing a transfer medium for the pharmaceutical from an implanted stent to the body area being treated.

In some example embodiments of the disclosure, pharmaceuticals are eluted depending on the extent of endothelial tissue growth. Optionally, pharmacological treatment commences after some endothelial cell growth is exhibited through and/or around the enhanced stent apparatus. Optionally, pharmacological treatment begins upon implantation without regard to endothelial cell growth. In some example embodiments of the disclosure, the enhanced stent apparatus is adapted and constructed to time-release pharmaceuticals in accordance with a predetermined treatment schedule. Optionally, the predetermined treatment schedule accommodates anticipated and/or actual endothelial cell growth rates by utilizing a coating with a predetermined breakdown rate. Optionally, release of pharmaceuticals is determined by time in situ. For example, if it is estimated that it would take 8 hours for endothelial cell growth to completely encapsulate the implanted stent, pharmaceuticals located in the porous structure of the stent optionally have a predetermined 8 hour delay prior to release and/or elute at a low rate to prevent inefficient or undesirable (i.e. toxic overdose) use of the pharmaceutical. In an embodiment of the disclosure, it takes only few hours for the endothelial cells to cover the thin porous structure, therefore the time release delay is adapted to match. This may be achieved by coatingporous structure104 with a “diffusion barrier” layer that to inhibits the diffusion of drug for a predefined period. Optionally this may be achieved by using a controlled degradable matrix. Optionally, pharmaceutical release occurs after only partial growth of endothelial cells around and/or through porous structure and/or stent. Optionally, pharmaceuticals begin to elute immediately upon insertion and/or implantation into a body lumen. Optionally, it is sufficient for pharmaceutical therapy thatporous structure104 has any biological covering, such as mucus, etc. In some embodiments of the disclosure, delay is determined according to the material that is expected to overgrowporous structure104.

In an example embodiment of the disclosure, timed release of pharmaceuticals is accomplished by coating and/or constructingporous structure104 and/orsupport element102 of multiple biodegradable/resorbable layers. By using layers which offer different performance characteristics (e.g. different pharmaceutical, different degradation time, stickiness to the body lumen, surface treatment modifications (e.g. treatment to make it non-sticky to the lumen)), enhancedstent apparatus100 can be tailored to perform a specific treatment schedule. For example, layer #1 (the external layer) includes a material which degrades in 2 hours, layer #2 (an inner layer) includes a pharmaceutical for elution into the patient and which degrades in 10 hours minutes, layer #3 (an inner layer) includes a different pharmaceutical for elution into the patient which degrades in 6 hours, and so on. Naturally, depending on the therapy desired for the patient, the layers and/or performance characteristics of those layers are changed to provide the desired treatment. It should be noted that a biodegradable layer can be placed in the outermost position which is timed to the expected endothelial cell growth, as described above. In such an embodiment, the degradation of the outermost layer is completed at approximately the same time as the completion of the endothelial cell layer overgrowth ofenhanced stent apparatus100, enabling a pharmaceutical to be eluted directly into endothelial tissue from a second layer ofenhanced stent apparatus100.

In an example embodiment of the disclosure,support element102 elutes pharmaceuticals, but treatment is assisted byporous structure104 which encourages endothelial cell growth oversupport element102. Optionally, the pharmaceutical located onsupport element102 elutes slowly to allow for endothelial cell growth. In some embodiments of the disclosure, the rate of elution depends on the local concentration and the anticipated diffusion rate of the pharmaceutical through the surrounding body tissue.

In some embodiment of the disclosure, a first pharmaceutical agent is eluted, which is designed to encourage endothelial cell overgrowth, followed by a second pharmaceutical agent designed to treat a malady of the patient.

In some embodiments of the disclosure, at leastporous structure104 is attached to the lumen using an adhesive which is impermeable to the pharmaceutical inporous structure104. However, timed release is achieved by allowing the endothelial layer to overgrowporous structure104, such that the pharmaceutical will elute into the endothelial layer that is not proximal to the adhesive. Optionally, the adhesive is biodegradable and/or bioresorbable and merely delays elution.

Blood Brain Barrier (BBB) Therapy

The BBB is the specialized system of capillary endothelial cells that protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. Unlike peripheral capillaries that allow relatively free exchange of substance across/between cells, the BBB strictly limits transport into the brain through both physical (tight junctions) and metabolic (enzyme) barriers. Thus the BBB is often the rate-limiting factor in determining permeation of therapeutic drugs into the brain.

In some example embodiments of the disclosure, a pharmaceutical eluting porous structure is used to enable treatments through the BBB. As described herein, pharmaceutical therapy is often enhanced by endothelial cell growth through and/or around an implanted drug eluting stent. Use ofporous structure104 in brain arteries, allows the endothelium cells to grow over theporous structure104, thus embeddingporous structure104 into the arterial tissue. The end result, after the previous endothelial cell layer has been absorbed by the body is thatporous structure104, which contains a brain treating pharmaceutical, is on the other side of the endothelium layer, thus on the other side of the BBB, with no significant impediment betweenporous structure104 and the brain tissue. In addition, some example embodiments ofporous structure104 are suitably sized to be used in the narrow lumens found in the brain. Example pharmaceuticals suitable for use withporous structure104 in treating through the BBB include gemcitabine (Gemzar®), and enzastamin, dopamine and dopamine derivatives, and anti-cancer drugs. In some embodiments of the disclosure,porous structure104 elutes anti-BBB materials for lowering resistance to transmission of substances through the BBB.

Pharmaceutical Treatment of Small Lumens

Currently, small lumens such as small coronary or brain arteries are treated only with a balloon type catheter. These treatments are short term and do not lend themselves to rendering pharmaceutical treatment to the lumen, as is sometimes desired. Traditional stenting is not often performed at the very least due to the difficulty of navigating a stent into the small spaces of these arteries. In an example embodiment of the disclosure, lumens smaller than 2 mm in diameter are treated with pharmaceuticals using at least a pharmaceutical elutingporous structure104, and optionally a support element. Optionally, the support element is a stent. Optionally, the support element is a balloon on whichporous structure104 is placed. In an example embodiment of the disclosure, a balloon-type catheter is used to insertporous structure104 in a small lumen. The balloon is expanded to causeporous structure104 expansion and to instigate contact betweenporous structure104 and the lumen wall to be treated. In an embodiment of the disclosure,porous structure104 at least partially adheres to the lumen wall. Optionally, a biocompatible adhesive is used to adhereporous structure104 to the lumen wall. In several preferred embodiments of the disclosure,porous structure104 is self-expandable.

In some embodiments of the disclosure, small lumens are treated long term, which is not performed currently. For example, by implanting at least the porous structure of anenhanced stent apparatus100, treatment can last on the order of months (e.g. a month or more). Optionally, treatment can last on the order of weeks (e.g. a week or more).

Example Treatment Methods

In an example embodiment of the disclosure,enhanced stent apparatus100 is used for treating, dilating, drugging and/or supporting body lumens, such as blood vessels. In some example embodiments of the disclosure,enhanced stent apparatus100 is used for treatment of disorders in the carotid arteries. In some embodiments of the disclosure,enhanced stent apparatus100 is used for treatment of disorders in the coronary arteries. As described above, treatment can be rendered through the BBB.Stent apparatus100 can be a self-expandable stent or use any other expansion method. Generally, thesupport element102 and/orporous structure104 are self-expandable. Optionally, pharmaceuticals are used to treat a patient via body lumens, for example, as described herein. In some embodiments of the disclosure,enhanced stent apparatus100 is used for treatment of aneurisms (described below), for example in the brain. In some embodiments of the disclosure,enhanced stent apparatus100 is used for preventative treatment of vulnerable plaque.

In operation,enhanced stent apparatus100 is navigated to the area in abody lumen400, as shown inFIG.3, where theenhanced stent apparatus100 is to be emplaced, using techniques known in the art. Optionally,enhanced stent apparatus100 can be expanded withinbody lumen400 using self-expandable techniques known in the art. Optionally,support element102 and/orporous structure104 are constructed of a thermo-sensitive, shape memory alloy which, when exposed to a patient's natural body temperature, assumes an expanded shape withinbody lumen400 at some time after situation in the appropriate location to render treatment. Alternatively, super-elastic or elastic release is used for placing a stent in a treatment area. In some example embodiments of the disclosure, a balloon is used topre-dilate body lumen400 at a treatment area prior to implantation ofenhanced stent apparatus100 at that area, in an at least a two-step (1. pre-dilate, 2. implant apparatus100) procedure. Optionally, onlyporous structure104 is implanted and not the wholeenhanced stent apparatus100. In some example embodiments of the disclosure, a balloon is used topost-dilate body lumen400 at a treatment area after implantation ofenhanced stent apparatus100 at that area, in an at least a two-step (1.

implant apparatus

100, 2. post-dilate) procedure. This kind of procedure is commonly used whenimplant apparatus100 is a self-expandable stent, such as for carotid applications.

In some example embodiments of the disclosure, the porous structure mesh is filled with a material which improves the stiffness of the porous structure temporarily until it arrives at a treatment site in a lumen. In some embodiments of the disclosure, the material is dissolved by naturally occurring substances in the body, such as enzymes. Optionally, the dissolving is timed to the anticipated overgrowth ofporous structure104 by the endothelial cell layer. Optionally the material is fibrogane. Optionally, the material is albumin fibrogane helonic acid laminin.

Example Treatment of Embolic Showers at Insertion and/or Deployment

It is commonplace in stenting procedures to use an embolic shower protection device which is situated only during the stenting procedure downstream from the treatment area, the idea being that the protection device will trap debris which falls from the blood vessel walls during the stenting procedure. In an example embodiment of the disclosure, usage ofenhanced stent apparatus100 withporous structure104 obviates the need for an embolic shower protection device. The small aperture size ofporous structure104 is designed to traparterial wall plaque402 and other debris of a particular size that becomes dislodged during and/or after the stenting procedure, betweenporous structure104 and thelumen wall404. In an example embodiment of the disclosure, debris greater than the size of the apertures in diameter is prevented from entering the bloodstream in this manner.

An additional advantage of using implantedporous structure104 instead of a conventional embolic shower protection device is that it remains in place after the procedure. That is, debris which becomes dislodged at some time after the stenting is performed still becomes trapped byporous structure104. This is an improvement over the embolic shower protection device conventionally used, which is removed at the conclusion of the stenting procedure. Optionally,enhanced stent apparatus100 is used with an embolic shower protection device as reassurance during the stenting procedure. Optionally,porous structure104 filters a particular type or types of debris whilesupport element102 filters another type or types.

It should be noted further that in an example embodiment of the disclosure the aperture sizes of theporous structure104 are designed and constructed to permit the passage of blood therethrough. This prevents the “jailing” of branching blood vessels which prevents the passage of critical blood components, such as red blood cells from passing into the branching vessel. In an example embodiment of the disclosure, the aperture size ofporous structure104 is larger than the average size of a red blood cell, or about 7 microns, allowing throughput of red blood cells without the risk of producing significant hemolysis. In some example embodiments of the disclosure, the approximate aperture diameters are greater than 20 microns. In some example embodiments of the disclosure, the approximate aperture diameters are smaller than 100 microns thus allowing blood to flow through while holding large debris (>100 microns) in place.

Carotid stenting is rarely performed currently, due to the high risk of debris becoming dislodged during the stenting procedure. This dislodged debris then travels to the brain where it often causes serious injury to the patient. In order to combat this problem of dislodged debris,enhanced stent apparatus100, which includesporous structure104, is used for stenting in the carotid arteries in some example embodiments of the disclosure.

Example Treatment of Aneurisms

Referring toFIG.19A, atypical aneurism volume2002 is depicted promulgating from abody lumen2004.FIG.19B shows a current method of treating an aneurism called coil embolization. Coil embolization is particularly indicated for treatment of cerebral aneurisms. Coil embolization of cerebral aneurisms involves the insertion of a catheter through the groin with a small microcatheter navigated to the aneurism itself through the cerebral arteries. Acoil2006 is then deployed into the aneurism filling it from within and thus disturbing the blood flow in the aneurism volume. This effect that leads to the creation of blood clot, which is trapped inaneurism volume2002 and which eventually turns into a more solid structure, thus reducing the risk of rupture of the aneurism. In some treatments, astent2008 is also used in order to keepcoil2006 from falling out ofaneurism volume2002 and into the blood stream. However, in some cases parts ofcoil2006 protrude throughstent2008 and are therefore exposed to the blood flow within thelumen2004. Additionally, safe insertion ofcoil2006 intoaneurism volume2002 can be a complicated procedure. Additionally, the blood clot produced might grow through the stent struts into the blood vessel lumen, narrowing it possibly to the point of complete occlusion.

Referring toFIG.19C, an embodiment of the disclosure is shown in whichporous structure104 located onenhanced stent apparatus100 is used to treat an aneurism while preventingcoil2006 from protruding intolumen2004. Optionally, a cerebral aneurism is treated by this method.Porous structure104 is adapted to have aperture sizes which are small enough to preventcoil2006 from protruding intolumen2004, in accordance with an embodiment of the disclosure. Optionally, a plurality of porous structures is used at least slightly out of phase in order to prevent at least a portion ofcoil2006 from protruding intolumen2004. In some example embodiments of the disclosure,coil2006 is covered with a porous structure (separate from porous structure104), thereby creating more surface area for the blood to stick to, enhancing the creation of a blood clot within theaneurism volume2002. In some embodiments of the disclosure,porous structure104 is manufactured using an electrospinning technique.

In an example embodiment of the disclosure,enhanced stent apparatus100 is used to treat an aneurism without the need forcoil2006. In some embodiments of the disclosure,porous structure104 is adapted to restrict blood flow intoaneurism volume2002, thus causing the trapped blood inaneurism volume2002 to clot, which in time will solidify and create a solid tissue structure thus reducing the likelihood of aneurism rupture or expansion as a result of increased blood flow thereto. For example, the aperture sizes inporous structure104 may be small or spaced widely apart. Optionally, a plurality of “out of phase” porous structures are used together to restrict blood flow intoaneurism volume2002. Optionally,porous structure104 has apertures smaller than 20 microns. Eliminating the need ofcoil2006 is advantageous, as it makes the procedure faster, safer, and simplifies the delivery catheter that can be used to perform the procedure.

In some example embodiments of the disclosure,porous structure104 is shorter thansupport element102. A shorterporous structure104 is optionally used so that only the aneurism is treated and not a healthy portion of the lumen. Optionally, a shorterporous structure104 is used to avoid restricting blood flow to a branching vessel. Optionally,porous structure104 has small aperture sizes on the aneurism side for restricting flow therethrough, while the other side has larger apertures to avoid restricting blood flow to a branching vessel.

In some example embodiments of the disclosure,porous structure104 includes a self-expanding material, such as nitinol, having enough radial force to hold itself in place within the lumen. Optionally, asupport element102 is not used at all andporous structure104 provides the necessary treatment to the aneurism. Optionally, the radial pressure applied byporous structure104 is equivalent to about 1 atmosphere. Optionally, the aperture diameters for aneurism treatments are smaller than 30 microns.

In some embodiments of the disclosure,porous structure104 also prevents blood clots and/or other embolism-causing debris from entering thelumen2004 fromaneurism volume2002.

Example Treatment of Vulnerable Plaque

Identification of vulnerable plaque areas allows prophylactic treatment of these areas before they can create problems for the patient. In an embodiment of the disclosure, anenhanced stent apparatus100 is used to preemptively treat lumen areas expected to trigger problematic conditions for the patient in the future. For example, plaque often builds up in blood vessels which in some cases breaks off in a clump or partially tears, causing a thrombosis. The downstream movement of the plaque or thrombosis is a potential cause of a heart attack, stroke or other malady in the patient. In some embodiments of the disclosure, an enhanced stent apparatus, including at leastporous structure104 is implanted at a potentially problematic location within a lumen, preventing the plaque from rupturing and, thus, from entering the bloodstream. In some embodiments of the disclosure,porous structure104 elutes at least one pharmaceutical used for treating the condition affecting the lumen, such as those described herein. In some embodiments of the disclosure,porous structure104 is made of nitinol as a self-expandable stent, having enough radial force to hold itself in place, without thesupportive element102.

Example Method of Implantation

In some example embodiments of the disclosure,porous structure104 is positioned on a catheter for implantation in a lumen separately from or withoutsupport element102. Treatment with a catheter is optionally provided by using the catheter to implantporous structure104 adapted and constructed for rendering treatment to a lumen over time. Optionally, pharmaceuticals or other therapeutic agents are embedded withinporous structure104, such as described herein. Positioning, in an example embodiment of the disclosure, entails inserting the catheter at least partially through the interior ofporous structure104 alongcentral axis106. During delivery ofporous structure104 to a treatment site within a lumen, a balance is optionally struck between securingporous structure104 to the catheter during delivery, but not so securely as to prevent implantation ofporous structure104 at the treatment site and pulling the catheter out while leaving theporous structure104 inside the lumen intact. For example,porous structure104 is optionally adhered to catheter at selected points using an adhesive such as loctite instant adhesive number 40340, 40840, 46040 or 3411-UV curable. The adhesive is strong enough to prevent any attachedporous structure104 from slipping off the catheter during delivery, however upon self-expansion or other expansion, the bonds betweenporous structure104 and the catheter are broken, allowing for implantation ofporous structure104 at a treatment site within a lumen. In some embodiments of the disclosure, delivery lasts for 6 hours or less. Optionally, delivery lasts for 3 hours or less. Optionally, delivery lasts for 1 hour or less.

In some example embodiments of the disclosure, the catheter is treated with an anti-sticking agent such as Parylene-c, silicon coating and/or Teflon® (PTFE) coating, to help preventporous structure104 from staying fastened to catheter after deployment at treatment site. Optionally, a thin film is coated onto the catheter which securesporous structure104 to the catheter during the delivery, but dissolves upon an approximate lapsing of time, allowingporous structure104 to be removed from the catheter. Optionally, the thin film includes albumin fibrogane helonic acid laminin. Optionally, the thin film layer is up to a few microns thick. Alternatively, the thin film layer is 0.1 microns in thickness.

In some example embodiments of the disclosure, the mesh-like structure ofporous structure104 is filled and/or encapsulated with a gel type material, such as fibrogane, fibrinogen and/or hyaluronic acid and/or laminin. The gel material stiffensporous structure104 for delivery, however, upon extended exposure to intra-lumen conditions, the gel dissolves leaving onlyporous structure104 after some period of time, for example a few hours or days.

In an embodiment of the disclosure, an adhesive material which is sensitive to a certain threshold (e.g. 1 atm. up to 20 atm.) of pressure is placed onporous structure104 such that when theporous structure104 is present and pressed against the lumen, theporous structure104 adheres to the lumen. In an example embodiment of the disclosure, whenporous structure104 is coated with the pressure sensitive adhesive it is only coated on the lumen side ofporous structure104. Optionally,porous structure104 is covered with a selectively adhesive material which has a high affinity for adhering to body tissue, for example fibrin sealant, biological glue, collagen, hydrogel, hydrocolloid, or collagen algirate, but limited affinity for adhesion to other substances, such as a delivery catheter.

Optionally,porous structure104 is at least temporarily fastened to the interior surface of the lumen with the assistance of an adhesive. In some example embodiments of the disclosure,porous structure104 is at least temporarily attached using at least one barb or pin located on an exterior surface ofporous structure104 facing the inside surface of the blood vessel. Optionally, the adhesive is applied to the exterior surfaces ofporous structure104 prior to insertion into the lumen. In some example embodiments of the disclosure, onceporous structure104 is placed at the treatment site within the lumen, asupport element102 is implanted at the same site interior ofporous structure104 in relation to the interior surface of the lumen, thus sandwichingporous structure104 betweensupport element102 and the lumen.

In some example embodiments of the disclosure,porous structure104 provides mechanical support to a blood vessel wall. Optionally,porous structure104 support is in addition to support rendered bysupport element102. Alternatively,porous structure support104 is in lieu of support rendered bysupport element102. In some example embodiments of the disclosure,support element102 provides no or minimal support to the blood vessel wall while supportingporous structure104. Optionally,porous structure104 provides pharmacological treatment to blood vessel while providing no or minimal support to blood vessel. Optionally,porous structure104 is implanted along withsupport element102, howeversupport element102 degrades in situ, leavingporous structure104. Optionally,porous structure104 preventssupport structure102 from falling apart in large pieces, permitting release of piece ofsupport structure102 only when below a certain threshold size, for example under 20 microns in diameter. Optionally,porous structure104 is implanted along withsupport element102, howeverporous structure104 degrades in situ, leavingsupport element102. This last configuration is sometimes indicated whenporous structure104 is made of a polymer containing a pharmaceutical. Eliminating the polymer and the pharmaceutical after period of time has an advantage because it reduces the likelihood of long term side effects such as thrombosis associated with the presence of the polymer and the pharmaceutical.

Stent assemblies, with or without jackets, are used in opening vessel lumens in a variety of vascular tissue including, inter alia, stenotic coronary arteries, stenotic carotid arteries and stenotic organ vasculature.

Prior Art Radial Force and Stent Diameter Compromise

As noted above, self-expanding stents generally have a tubular shape cut in a pattern that results in spring-like movement of the stent assembly in the radial direction. These stents are preloaded into delivery systems by crimping them to a small diameter, then during the procedure the stents are deployed and expand to the vessel diameter gradually. The stent acts as a scaffold based on the stent geometry, and a radial force exerted on the vessel walls by the stent is regarded as radial force (RF).

FIG.20 includes agraphic illustration2050 of the reaction force of conventional stents through crimping and then deployment (e.g., change in stent diameter). Generally, theline2052 represents the amount of equivalent linear force required to crimp the stent to a specific diameter within a 4-12 face polygonal cavity, whileline2054 represents the amount of force exerted on the vessel walls by the stent while the stent diameter increases.

Generally, theline2054 passes through afirst zone2056 and asecond zone2058 during expansion. Thefirst zone2056 is the radial force zone, which delivers high radial force until the minimal determined size (radial expansion) of the stent and any other stent assembly component(s), such as an associated stent jacket. Thezone2056 is designed to initiate the expansion of the lesion site or otherwise contact the portion of the body lumen that is damaged. Thezone2056 corresponds to the opening of the stent from 0 to 5 mm with relatively high radial force. Thesecond zone2058 is the conformability zone, that achieves diameters up to 11 mm with relatively lower radial force. Generally, conventional stents have higher radial force from 0 to 5 mm, and then a lower radial force from about 6 to 11 mm. Conventional stents have a very high change in radial force across thezone2058. Thus, the radial force at 5 mm diameter is much higher than the radial force at 9.5 mm. As such, conventional stents do not typically provide a wide range of size (i.e., vessel diameter) coverage, as the stents are designed to give scaffold coverage proportional to the diameter of the target reference site while avoiding a maximum radial force that could damage a vessel wall. For example, when thesecond zone2058 includes diameters between 5.5 mm to 9 mm (e.g., 163% change from initial diameter), the reduction of radial force is greater than 50% and so high that if a designed expanded stent diameter is +/−1 to 2 mm compared to the vessel diameter, an inappropriate radial force is applied to the vessel wall. As such, and to help ensure that an appropriate radial force is applied to the vessel wall, the physician must choose a size of stent that is usually within 1-2 mm of the vessel wall. In other words, with conventional stents, the stent has a designed expanded stent diameter that is acceptable within a very small window of vessel diameters. In some applications, the portion of the vessel to be stented has varying diameters along the length of that portion, with differences of 5 mm or more. Vessels between different patients have differences of 5 mm or more, and/or vessels within one patient may have differences of 5 mm or more. Thus, there is a wide array of vessel sizes and varying vessel diameters to be stented, with different stent sizes expected to be required for each application. Often, the physician might incorrectly choose the stent size, leading to a situation where under-sizing or oversizing occurs. Under sizing may result in shifting of the stent or not achieving full stent apposition, raising the risk of thrombosis or mobilization over the stent edges. Oversizing may result in stressing the walls and generating re-stenosis or perforation. Oversizing and under-sizing are thus undesirable and the stent apparatus, methods, and kit described herein avoid these undesirable outcomes and the associated risks and costs.

Example Stenting of Various Vessel Diameters Using One Embodiment of theStent Apparatus100

FIG.21 includes agraphic illustration2060 of the reaction force of one embodiment of thestent apparatus100 through crimping and then deployment (e.g., change in stent diameter). The one embodiment of thestent apparatus100 included an open-cell Nitinol stent with the outerporous structure104 being woven from a single strand of 20 μm diameter PET. Thegraphic illustration2060 includes the

lines

2052 and2054 and thesecond zone2058.FIG.22 includes a table2062 detailing the chronic outward force during expansion of the one embodiment of thestent apparatus100. For the one embodiment of the sentapparatus100 tested, the radial force was determined with a segmented head radial force test device (Blockwise Engineering LCC, Tempe, Ariz., USA). The one embodiment of the sentapparatus100 was released directly into the test device at a start diameter of 5 mm. The test was conducted at a temperature of 37±2° C. to approximate body temperature. The diameter of the test stent assembly device was then increased with a speed of 0.2 mm/s up to a diameter of 11 mm (full expansion of the one embodiment of the stent apparatus100) while constantly measuring the radial force, representing the chronic outward force of the one embodiment of the sentapparatus100. Afterwards the diameter of the test device was decreased down to 5 mm while constantly measuring the radial force, representing the radial resistive force of the one embodiment of the sentapparatus100. All radial force values were normalized by the length of the one embodiment of the sentapparatus100. Defining the radial force at the lowest allowed diameter (i.e., 5.5 mm) as 100%, the radial force at the maximum allowed diameter (i.e., 9 mm) was 59% of the maximum radial force. The radial resistive force during compression was about twice of the chronic outward force with a similar progression in the diameter range tested. In some embodiments, the chronic radial force is the radial force applied to the vessel wall by thestent apparatus100 over an extended period of time, such as for example over the course of the useful or design life of thestent apparatus100.

As can be seen, the diameter of the one embodiment of the sentapparatus100 increased from 5.5 mm at 0.330 N/mm outward force to 9 mm at 0.195 N/mm outward force, which is a 163% increase in diameter with only a 41% decrease in outward force. Stated differently and when a second expanded diameter is less than the first expanded diameter, a ratio between the first expanded diameter and the second, different expanded diameter of the stent apparatus is less than about 1.65 and greater than about 1 with the second radial force being within about 170% of the first radial force. This large range of diameters with a generally small decrease in outward force results in expansion of the lesion segment while applying minimal residual radial force to adjacent healthy segments of the vessel. When used to treat an aneurism, thestent apparatus100 applies an acceptable residual radial force to the wall of the lumen for any lumen diameter within a range of lumen diameters, such as for example the range between about 5.5 mm to about 9 mm. The relevant sizing for aneurism treatment often depends on the size of the index artery. Thestent apparatus100 is configured to provide adequate chronic radial forces to all diameters within the range that includes a first expanded diameter to a second expanded diameter. This avoids permanent trauma to the stented portions and adjacent portions of the vessel. That is, thestent apparatus100 opens the lesion to its original diameter or base reference diameter, resists collapse, and provides a safe coverage of the target lesion/reference site without overexerting on the luminal walls. Moreover, thestent apparatus100 conforms to various vessel diameters over short distances without causing trauma in any area. As such, thestent apparatus100 is configured to expand to any diameter within the range of diameters that includes from about 5.5 mm to about 9 mm.

In some embodiments, thestent apparatus100 is configured for use in a variety of body indications. For example, thestent apparatus100 is configured and sized for body lumens that includes arteries, veins, bronchial lumens, biliary lumens, hepatic lumens, any digestive related lumen, Otorhinolaryngology related lumen, etc. Generally, thestent apparatus100 provides similar radial forces (e.g., less than 50% reduction) at variate final reference normal diameters or base reference diameters. Examples of regions in which thestent apparatus100 is configured for use, associated minimum and maximum reference diameters, associated percent increase of minimum and maximum diameters, and associated percent decrease of radial force are below in Table 2 (not an exhaustive list):

TABLE 2

Example Regions of Use

				Percent
				Decrease of
				Radial Force
				associated
			Percent	with Min.
			Increase	Diameter
			from Min.	Ref. to
	Min.	Max.	Diameter	Radial Force
	Diameter	Diameter	Ref to Max.	associated
	Reference	Reference	Diameter	with Max.
Region	(mm)	(mm)	Ref	Diameter Ref.

Femoral	4	7	175%	≤50%
Renal	5	6	120%	≤50%
Iliac	7	14	200%	≤50%
Fistula AV	5	6	120%	≤50%
Bronchial
	10	12	120%	≤50%
Aorta
	20	44	220%	≤50%
Biliar
	10	14	140%	≤50%
Veins	14	20	142%	≤50%
Common	5.5	9	163%	≤50%
Carotid
Artery

In an example embodiment, as illustrated inFIG.23 amethod2070 of stenting includes estimating body lumen diameter(s) associated with a portion of a body lumen in which thestent apparatus100 will be placed atstep2072; determining, based on the estimated body lumen diameter(s), target expanded stent diameter(s) of the stent assembly which is to be placed in the portion of the vessel atstep2074; selecting thestent apparatus100 for stenting the portion of the body lumen atstep2076; and implanting thestent assembly100 in the portion of the body lumen atstep2078.

Atstep2072, body lumen diameter(s) associated with a portion of the body lumen in which the stent assembly will be placed is estimated. Often, a physician uses imaging techniques to determine the estimated body lumen diameter(s) of the portion of the body lumen that needs to be stented. In some embodiments, the portion of the body lumen to be stented has, or ideally should have, a generally consistent vessel diameter (e.g., within 10% variance in diameter). However, in other embodiments, the portion of the body lumen has, or should have, a varied body lumen diameter, which in some cases may be a variation of up to 5 mm or about 160% variance in diameter. Thus, in some embodiments, multiple body lumen diameters are estimated during thestep2072. As illustrated inFIG.24, multiple body lumen diameters such as2080aand2080bof a portion of avessel2082 are estimated atstep2072. In some embodiments, thevessel diameter2080ais associated with a first portion of thebody lumen2082 while the body lumen diameter2080bis associated with a second portion of thebody lumen2082. In some embodiments, a lesion2084 creates a narrowing of the body lumen diameter. In some embodiments and as noted above, thediameters2080aand2080bare different while in other embodiments thediameters2080aand2080bare generally the same. Generally, thediameters2080aand2080bare base reference diameters associated with the area that is to be stented. This avoids mismeasurement in that some lumen diameters can appear smaller when the lumen is restricted in any way, e.g., due to a lesion. In some embodiments, thediameter2080ais spaced from the lesion2084 in a first direction and the diameter2080bis spaced from the lesion2084 in a second direction that is opposite the first direction.

Atstep2074, the target expanded stent diameter(s) of thestent apparatus100 is determined based on the estimated body lumen diameter(s). Generally, the target expanded stent diameter of thestent apparatus100 coincides with the unaffected areas of the body lumen. That is, the target expanded stent diameter is the diameter of the vessel at locations adjacent the lesion2084 or are thediameters2080aand2080b. In some embodiments, the expanded diameter of the stent assembly is generally consistent. However, in some embodiments and as illustrated inFIG.24, there are multiple target expanded stent diameters.

Atstep2076, thestent apparatus100 is selected for stenting the portion of thebody lumen2082. In some embodiments, thestent apparatus100 is selected regardless of whether the target expanded stent diameter is generally consistent or whether there are multiple target expanded stent diameters over a range of expanded diameters. Moreover, thestent apparatus100 is selected when the target expanded stent diameter is any diameter within the range of about 5 mm to about 10 mm. In some embodiments, thestent apparatus100 is selected when the target expanded stent diameter is any diameter within the range of about 5.5 mm to about 9 mm.

At thestep2078, thestent apparatus100 is implanted in the portion of thebody lumen2082. As illustrated inFIG.25, the stent assembly is positioned within the portion of thebody lumen2082 in a retracted or crimped state (deployment tools are not illustrated inFIGS.25 and26). When positioned within the portion of thevessel2082, thestent apparatus100 is allowed to expand. As illustrated inFIG.26, the stent assembly expands to open the body lumen at the site of the lesion2084. Moreover, thestent apparatus100 self-adjusts to the adjacent portions of the body lumen such that the expanded diameter of thestent apparatus100 is the same as or substantially similar to the estimatedbody lumen diameters2080aand2080b. That is, thestent apparatus100 self-adjusts and provides an appropriate radial force to the body lumen portions adjacent the lesion2084.

While a lesion2084 is illustrated inFIGS.24-26, themethod2070 is also applicable for the treatment of aneurisms. In those instances, the portion of the body lumen that is to be stented includes an aneurism instead of a lesion. The stent assembly of the present disclosure may be used in other indications and applications.

Moreover, while thestent apparatus100 described above inmethod2070 is designed for use in a common carotid artery to expand to any diameter from about 5.5 mm to about 9 mm, themethod2070 is also applicable for use in each region detailed above in Table 2. In those instances, and for example when thestent apparatus100 is designed and sized for use in an aorta, thestent apparatus100 is configured to expand to any diameter from about 20 mm to about 44 mm while having equal to or less than about a 50% decrease in chronic radial force between the 20 mm expanded diameter and the 44 mm expanded diameter.

Thestent apparatus100 and/or themethod2070 reduces or eliminates risk of sizing choice errors. That is, errors relating to under sizing or oversizing of stent assemblies are minimized or prevented, as thestent apparatus100 configured for common carotid artery use is configured to expand to the range of diameters that includes 5.5 mm to 9 mm and in some cases from 5 mm to 10 mm. Similarly, and as provided in Table 2, when thestent apparatus100 is configured for use in the aorta, thestent apparatus100 is configured to expand to any diameter from about 20 mm to about 44 mm while having equal to or less than about a 50% decrease in chronic radial force between the 20 mm expanded diameter and the 44 mm expanded diameter. Moreover, thestent apparatus100 and/or themethod2070 reduces the number of stent assemblies required to be stored on-hand. Thestent apparatus100 and/or themethod2070 ensures a known predefined radial force expectancy for all diameters in the range and results in better adaptation to varying diameters over the length of the implantation. As such, the use of a stent assembly that is configured specifically for vessels having variations in diameters, such as a tapered stent, is no longer required. Instead, thestent apparatus100 is configured for use in portions of body lumens having varied diameters, and for use in a range of vessel sizes having generally consistent diameters. Thestent apparatus100 eliminates the compromise of selecting stents for different body lumen diameters based on maximum radial force and desired stent diameter. As thestent apparatus100 self-adjusts, the stent assembly automatically gains optimal expansion and apposition with minimal residual radial force that does not exceed a maximum safe radial force that avoids or minimizes damage to a body lumen wall.

In some embodiments and when the outerporous structure104, being woven from a single strand of 20 μm diameter PET, is placed onto the outside of the stent, the scaffold coverage increases without the need for additional metal struts. This interface increases target lesion coverage and allows more flexibility with less metal implanted. The benefit of full coverage with the outerporous structure104 being woven from a single strand of 20 μm PET placed over a nitinol stent, allows for a superior treatment giving coverage across a variety of diameters within the same site, rather than oversizing in certain areas, or indeed under sizing in some. In some embodiments, the sentapparatus100 is composed of or includes a super elastic memory material such as nickel titanium alloys or super elastic polymers such as for example Memory Ultem® by SABIC of Riyadh, Saudi Arabia, or cobalt chromium stents, or other stent materials.

In some embodiments, themethod2070 also includes providing stenting instructions and providing thestent apparatus100 in association with the instructions. In some embodiments, the stenting instructions include instructions to: estimate body lumen diameter(s) associated with a portion of a body lumen in which the stent assembly will be placed; determine, based on the estimated body lumen diameter(s), target expanded stent diameter(s) of the stent assembly; select the stent assembly for stenting the first portion of the body lumen, wherein the stent assembly is configured to expand from an initial diameter to expanded diameters within a range of expanded diameters while applying a radial force of about 0.20 N/mm to about 0.33 N/mm; and implant the stent assembly in the portion of the body lumen.

In some embodiments, the instructions and thestent apparatus100 are provided in a kit.

In some embodiments, thestent apparatus100 includes theporous structure104 and thesupport structure102 as described above. In other embodiments, theporous structure104 is omitted and thesupport structure102 includes or is a single-component cut stent.

Experimental Data Relating to One Embodiment of theStent Apparatus100

Thirty (30) consecutive eligible patients were enrolled and treated with one embodiment of thestent apparatus100 having a free diameter of 10.5 mm. All patients had high grade stenosis and/or symptomatic stenosis of the internal carotid artery. The modified Rankin Scale of the symptomatic patients was 1.4±0.7. The key inclusion criteria included high grade of stenosis and/or symptomatic stenosis; clinical symptoms of carotid stenosis less≤1 month prior to intervention; and vessel diameters between 4.7 and 9.0 mm. The key exclusion criteria included asymptomatic stenosis<80%; simultaneous acute occlusion of intracranial artery; intracranial bleeding; and previous ipsilateral stent implantation. The patient and lesion characteristics are listed in table2090 ofFIG.27. The lesions characteristics showed a step-in diameter from common carotid artery (CCA) of 8.4±0.6 mm to internal carotid artery (ICA) of 5.8±0.6 mm. Twenty-one (21) arteries were with elongations and six (6) of these had severe tortuosity, while nine (9) arteries were relatively straight. All patients underwent duplex ultrasound (DUS) and CT or MRI before intervention. Each of the one embodiment of thestent apparatus100 were implanted by a transfemoral approach using local anesthesia. After placing a long (i.e., 90 cm) support sheath (6F, Destination, Terumo Europe, Leuven, Belgium) in the common carotid artery, a distal embolic protection device (FilterWire EZ™ of Boston Scientific, Natick Mass., USA) was used in twelve out of thirty (12/30) patients. Primary stenting was performed without predilatation in all patients. The one embodiment of thestent apparatus100 was implanted (10×40 mm (n=25) and 10×30 mm (n=5)) in the patients. All patients received 0.5 mg Atropine I.V. (Braun, Germany) and postdilatation was performed with a 5×30 mm balloon (Sterling™ Monorail of Boston Scientific, Natick Mass., USA) at 10 atm. All the cases were documented at baseline, including stenting, postdilation and following this, removal of the distal filter with an intracranial digital subtraction angiography (DSA) in two projections. In the puncture site a clip-based closure device was used (StarClose SE of Abbott Vascular, Santa Clara, Calif., USA). After intervention, all patients were referred to the stroke unit and had neurological monitoring. DUS was repeated after intervention and after 30 days. In a subgroup, a 30 day diffusion-weighted magnetic resonance imaging (DW-MRI) was performed. All patients were preloaded the day before the intervention with acetylsalicylic acid (ASA) 500 mg andClopidogrel 300 mg (Sanofi Aventis of Germany). During the intervention between 5,000 to 10,000 IU heparin were given depending on the active clotting time (ACT), that had to be 250 to 300 s. From the intervention, 75 mg clopidogrel (Sanofi Aventis of Germany)/day was given for a minimum of 6 weeks, and ASA (100 mg/day) permanently. The technical success rate was 100%. No pre-dilatation prior to stent placement was performed in any case. In twelve out of thirty (12/30) cases a distal filter was used. After retrieving the filter no debris was observed. There were no cases of relevant spasm, distal embolization or dissection. The median treatment time from puncture to vessel closure was 37.4±8.7 min. The ACT during intervention was in median 266.3 sec. There were no cases of death or major adverse events (MAE). No incidence of minor or major stroke occurred peri-procedural or during the 30 days follow-up period. No patients developed new neurological symptoms. The modified Rankin Scale was 0. In the DUS post-procedural and after 30 days, all stents were patent with normalized doppler speeds. At 30d, the median peak systolic velocity (PSV) was 75.8±9.1. The external carotid artery was patent in all patients. DW-MRI was performed in ten out of thirty (10/30) patients after 30 days, without detection of new ipsilateral lesions.

The high incidence of postprocedural embolizations with conventional stents (e.g., ⅔ of CAS major adverse cardiac and cerebrovascular events (MACCE) at 30 days) justified the introduction of the one embodiment of thestent apparatus100, which includes theporous structure104, to offer a permanent protection upon the stent implantation as it is designed to prevent peri-procedural and late embolization by trapping potential emboli against the arterial wall, while maintaining perfusion to the external carotid artery and branch vessels.

In some embodiments, the small pore size of theporous layer104 provides neuroprotection with a significant reduction of the incidence and volume on DW-MRI new lesions at 30 days after CAS vs. conventional stents historical data.

In terms of clinical performance, a review of 550 patients treated with the one embodiment of thestent apparatus100, demonstrated an overall complication rate of 1% after 30 days with a near elimination of post-procedural events. In a prospective all-referral-study of 101 patients treated with the one embodiment of thestent apparatus100, only one periprocedural minor stroke was found without any other related complication at one-year follow-up, with a single case of intrastent restenosis. No complications and no minor or major strokes were observed in thirty patients in the follow-up.

The step differences were in median more than 2 mm. In previous approaches, tapered stents (TS) implanted in a swine model displayed that the low radial force reduces intimal hyperplasia leading to significantly less restenosis. The TS confirmed a lower rate of restenosis in comparison to straight stents in clinical trials, without prevention in peri-procedural events. However, and as noted above, the one embodiment of thestent apparatus100 eliminates and superates the need for any tapered stent assembly. The one embodiment of thestent apparatus100 stent demonstrates an extreme adaptability with a near flat chronic outward force profile in the range of 5.5 to 9.0 mm (i.e., only about 40% drop force).

In this series of otherwise routine CAS in consecutive patients, the one embodiment of thestent apparatus100 demonstrates that it can be safely implanted with respect to the vessel architecture, providing a near flat chronic outward force profile in in the range of 5.5 to 9.0 mm. Experimental data relating to the use of the one embodiment of thestent apparatus100 demonstrate prevention of post-procedural embolic events.

In some embodiments, and for thestent apparatus100 used in themethod2070, theporous structures104 described herein can be replaced with a polymer stent jacket or polymeric graft jacket. In some embodiments, theporous structure104 is omitted.

In some embodiments, thestent apparatus100 is a dual therapy stent, a bioresorbable vascular scaffold, a bio-engineered stent, a drug eluting stent, and/or a bare metal stent.

Prior Art Stent and Jacket Configurations

Referring toFIG.31a, astent apparatus100 includes a stand-alonetubular stent202, without a jacket, hereinbare stent202.Bare stent202 typically includes a metal or polymer tubular structure having large, mesh-like, apertures270.Bare stent202 is shown encircling aballoon260 and, upon expansion ofballoon260,bare stent202 expands radially outward.

As seen inFIG.31b,bare stent202 has expanded radially invessel lumen125 to press against a stenotic area oftissue240, thereby compressing and crackingstenotic area240 radially outward. Following deployment ofstent apparatus100,vessel lumen125 expands, allowing better circulation throughlumen125.

Deployment ofbare stent202, however, causes damage to abasalamina intimal layer127 resulting in the formation ofscars242,plaques244 and newstenotic lesions240 that protrude throughapertures270. Over the long-term, a large percentage of the recipients ofbare stents202 will develop significantstenotic lesions240 that blockvessel lumen125, causing what is known as restenosis.

To prevent restenosis, (FIG.31c),stent assemblies200 have been developed includingstents202 with an internal orexternal jacket204 having small apertures.Stent assembly200 is shown in position around aspindle holder180, emerging from acompression sheath182, withstent202 andstent jacket204 in substantial tubular alignment. Typically, the jacket is formed of a polymer.

During expansion,jacket204 preventsembolitic debris121 generated from plaques along basalaminaintimal layer127 from enteringvessel lumen125.

InFIG.31d,stent assembly200 is expanded radially invessel lumen125 so thatjacket204 pressesstenotic tissue240 radially outward. Following deployment of thestent assembly200, stent jacket substantially preventsscars242,plaques244 andstenotic lesions240 from protruding throughapertures270. In spite of substantially preventing restenosis,stent jacket204 creates its own set of problems related to formation of anembolism300.

As noted above, to provide sufficient strength,stent jacket204 may be made of interlacing knitted fibers, and/or fibers subject to chemical or heat treatments, all of which tend to increase the thickness offibers210 and bulk ofjacket204, seen inFIG.32.

Within 48 hours following implantation of stent assembly200 a layer ofendothelial cells220 coatstent jacket fibers210 and basalaminaintimal layer127, as seen inFIG.32.

Endothelial cells

220 have a diameter222 of approximately 20 micrometers and maintain adherence to basalaminaintimal layer127 but generally do not substantially adhere tojacket fibers210.

Fibers

210 in stent jacket typically have athickness212 of 20 micrometers so thatendothelial cell220 that straddlesfiber210, will have no attachment to basalaminaintimal layer127 and will easily dislodge fromfiber210.

Additionally,fibers210 are typically spaced adistance218 of less than 20 micrometers so thatendothelial cell220 that straddles between twofibers210, will attach to the twoadjacent fibers210 and will have a marginal attachment to basalaminaintimal layer127 therebetween; again resulting in acell220 that is easily dislodged fromfibers210.

Singleendothelial cells220 that become detached from basalaminaintimal layer127, are not large enough to be recognized by platelets as foreign bodies around which to aggregate. However, as seen inFIG.33, during natural movement offibers210, for example during regular pulsation of blood in circulation, a release of multipleinterconnected cells220 occurs.

In this case fourendothelial cells220, have broken loose from basalaminaintimal layer127, and are freely floating in vessel lumen. Aplatelet310, having adiameter320 of between four to ten times the diameter ofendothelial cells220, is attracted to masses that include at least twoendothelia cells220 andendothelial cells220 provide an excellent attractive target forplatelet310.

As seen inFIG.34, asingle platelet310 has adhered to dislodgedendothelial cells220. As seen inFIG.35, as a result of chemotaxis,additional platelets310 have aggregated aroundendothelial cells220 to form anembolism300.

As noted above,embolism300, including aggregatedplatelets310, presents a health threat that can form at any time following implantation ofstent jacket204 causing an estimated 2% of all recipients of jacketedstents204 to eventually develop necrosis of vital organs and/or die.

The tremendous and constant threat ofemboli300 from stent-and-jacket assembly204 (FIG.33) has resulted in lifetime administration of platelet aggregation reduction APIs. There are many life-threatening sequelae associated with Clopidogrel and there are many clinical trials being conducted on alternative platelet aggregation reducing APIs, including: Ticlopidine, Cangrelor, ARMYDA-2, and Prasugrel.

(Journal of Interventional Cardiology “TCT Annual Meeting: Antiplatelet Agents”; Volume 19 Page 193—April 2006.)

As noted above, lifetime administration of platelet aggregation reducing APIs, herein Clopidogrel, present problems to many sectors of the population.

For example, many jacketed stent recipients develop reactions that require cessation of Clopidogrel, such reactions include: ulcers, skin rashes, and syncope. With high bulk jacketed stents, Cessation of Clopidogrel puts the patient at risk for developing alife threatening embolus300.

In addition to the hazards ofembolus300, there are patients who, not only must cease taking Clopidogrel and its accompanying risks, but may also develop conditions that are life threatening of themselves, including myelotoxicity, acquired hemophilia and TTP.

Additionally, there are the conditions that the patient may have that prevent the administration of Clopidogrel, including unresponsiveness to a platelet aggregate reducing API, an antithrombin deficiency, hereditary antithrombin deficiency (HD), immune depression, low CCR5 Delta 32 homozygous genotype (CCR5), acquired hemophilia, AIDS, HIV.

Moreover, there are risks presented to virtually every person receiving a jacketed stent. To prevent excessive bleeding in conjunction with virtually any surgery, Clopidogrel administration must be ceased for a significant period of time both pre-operatively and post-operatively. As a result, a patient who has received a stent and is a candidate for an elective surgery, for example prostate removal, is presented with a Hobson's choice of ceasing Clopidogrel administration and risking death from emboli, or taking Clopidogrel and risking embolism-free bleeding, hemorrhage and death.

Optimized Stent Assemblies

It has been found that specific configurations of the above-noted stents and jackets appear to provide advantages as is explained in the “Experimental Data” section. The specific features of these configurations will now be addressed.

Single fiber knits have been used in pantyhose since 1939, and include a plurality of interconnected loops known for strength, elastic qualities and thinness. Single fiber knit fabrics would be desirable as lowbulk jackets600 were it not from the problem that any loop along the edge of the nylon material can flip 180 degrees and form a run.

FIG.36 shows aknitted stent jacket600 including knittedfibers620 formingapertures110. To prevent flipping infibers620, anelastomeric belt640 has been passed throughapertures110 at the distal end ofstent jacket600. Optionally, anelastomeric belt640 is similarly passed through loops at the proximal end of stent jacket600 (not shown).

As used herein, any reference to a “knitted material” includes any material that is manufactured by a knitting process, including, inter alia: a material knitted from a single fiber, including either monofilament or multifilament fiber. The single fiber may include, inter alia, polyethylene, polyvinyl chloride, polyurethane, nylon, stainless steel, nitinol, or any other metal.

The biostable polymer includes, inter alia, any one of a polyolefin, a polyurethane, a fluorinated polyolefin, a chlorinated polyolefin, a polyamide, an acrylate polymer, an acrylamide polymer, a vinyl polymer, a polyacetal, a polycarbonate, a polyether, an aromatic polyester, a polyether (ether keto), a polysulfone, a silicone rubber, a thermoset, and a polyester (ester imide).

The natural polymer includes, inter alia, a polyolefin, a polyurethane, a Mylar, a silicone, a polyester and a fluorinated polyolefin.

As seen inFIG.37, knittedstent jacket104 includesapertures110 that are maximized so thatfibers620 provide a small total coverage area in whichstent jacket104 covers astent102.

In accordance with some embodiments of the present disclosure, in an expanded state, the area ofaperture110 is between about 50,000 square micrometers and about 70,000 square micrometers. In alternative embodiments,aperture110 has an area of between about 40,000 square micrometers and about 60,000 square micrometers. In other embodiments,aperture110 has an area of between about 30,000 square micrometers and about 50,000 square micrometers.

Withknitted stent jacket104 havingfibers620 presenting a small total coverage, crimpingstent102 for insertion into compression sheath,182 (FIG.31c) for example, is relatively simple.

Additionally, a small total coverage allows crimpedstent102 to have a small profile, allowing easy maneuverability throughlumen125.

Moreover, withknitted stent jacket104 having minimal thickness offibers620,stent jacket104 substantially has a minimal influence on the mechanical properties of the stent during the delivery and expansion.

The location ofjacket104 externally onstent102 protects basalaminaintimal layer127 from damage during expansion ofstent102. Additionally, the location ofjacket104 externally onstent102 provides substantial protection againstdebris121, seen inFIG.31d, enteringvessel lumen125 during expansion ofstent102.

In accordance with some embodiments of the present disclosure, a proximal portion ofjacket104 is attached to a proximal aspect ofstent102 using a process selected from the group consisting of: sewing, adhesion, gluing, folding, suturing, riveting and welding. Such an attachment, for example, allowsstent102 to expand with a typically different coefficient of expansion than that ofjacket104 without causing damage to basalaminaintimal layer127.

As seen in a plan view ofknitted stent jacket600 inFIG.37, knittedstent jacket104 includes a small coverage area, for example about 9%, or about 10%, or about 11%, or about 12% of the surface area of associated self-expandingstent102. In general, the coverage area is less than 16%. Hence, in spite of crimpingstent102 prior to deployment, there is no need to fold knittedjacket104 to fit into sheath182 (FIG.31c) prior to deployment; thereby reducing bulk and increasing maneuverability ofstent assembly200.

The above-noted parameters of a knitted jacket on a self-expanding stent can be easily attained in the present disclosure using a fiber diameter of about 12.5 micrometers.

FIG.38 shows details ofknitted jacket600 in whichapertures110 have alongitudinal length650 of greater than about 160 micrometers. In other embodiments,longitudinal length650 is greater than about 180 micrometers. In other embodiments,longitudinal length650 is greater than about 200 micrometers.

In accordance with some embodiments of the present disclosure,apertures110 have atransverse length642 of greater than about 250 micrometers. In other embodiments,transverse length642 is greater than about 240 micrometers. In other embodiments,transverse length642 is greater than about 230 micrometers.

It will be appreciated that the shorter one of thelongitudinal length650 and thetransverse length642 defines the minimum center dimension630 (D) which must be greater than about 230 micrometers, and preferably, greater than 240 micrometers, and still more preferably, greater than 250 micrometers.

FIG.39 shows thatfibers620 have adiameter662, optionally in a range of between about 7 micrometers and about 18 micrometers. In other embodiments,diameter662 is in a range of between about 10 micrometers and about 15 micrometers. In still other embodiments,diameter662 is in a range of between about 11 micrometers and about 14 micrometers. In still other embodiments,diameter662 is in a range of between about 12 micrometers and about 13 micrometers. In still other embodiments,diameter662 is in a range of between about 12.25 micrometers and about 12.75 micrometers. In still other embodiments,diameter662 of about 12.5 micrometers.

Substantially inherent advantages of the measurements ofknitted jacket600 become readily apparent inFIG.40 in whichendothelial cells220 are well adhered and stable against basalaminaintimal layer127 due to the thinness offibers620.

As a result of such spacing, a typicalendothelial cell220 will have substantial contact with basalaminaintimal layer127 asendothelial cell220 is prevented from adhering to more than one column offibers620 due to the distance therebetween.

A group of threeendothelial cells220 is seen adhering to a portion ofknitted stent jacket600.Endothelial cells220 have an amoeba-like movement so that at afiber junction692,cell220 will typically touch down onjunction692 and move until a substantial portion ofcell220 is in substantial contact with basalaminaintimal layer127. In rare cases where a cell228 fails to properly anchor into basalaminaintimal layer127, that specific single cell228, alone, may have a tendency to dislodge due to movement offibers620 during normal pulsation in the blood circulation cycle. Due to the stability ofadjacent cells220 resulting from substantial contact with basalaminaintimal layer127,multiple cells220 will not dislodge together with single cell228.

As shown, single endothelial cell228 has separated from basalaminaintimal layer127. However, single cell228 does not have the necessary mass to be recognized byplatelet310 as a body worthy of adherence. As a result, there is no formation of the above-noted life-threatening embolism300 associated with aggregation ofplatelets310.

Typically, to ensure stability ofendothelial cells220, a patient receivingstent jacket100 will be given a platelet aggregation reducing API, for example Clopidogrel, for no more than six months, and possibly less. For example, the patient may receive Clopidogrel for no more than for five months, no more than for four months, no more than for three months, no more than for two months, or no more than for one month.

At times, the patient receivingstent jacket100 will not be given a platelet aggregation reducing API, the unique property of the fiber diameter, as illustrated inFIG.30, and the advantage of the aperture minimum center dimension D, alone or in combination, relieving the need for the platelet aggregation reducing API, altogether. Thus, if the patient is scheduled to undergo elective surgery during the six-month administration, Clopidogrel may be discontinued without substantial fear of platelet aggregation.

Further, if, during a six-month administration period, the recipient ofstent jacket600 has any reaction, including ulcers, skin rashes, syncope, myelotoxicity, and TTP, Clopidogrel may be immediately ceased without substantial fear of embolism generation.

Further, Clopidogrel administration may be ceased or not initiated in the face of patient unresponsiveness to Clopidogrel, an antithrombin deficiency, HD, immune depression, low CCR5, acquired hemophilia, AIDS, and HIV.

Experimental Data

Reference is now made to the chart below showing experimental data, which together with the above description, illustrate the disclosure in a non-limiting fashion.

Optimization of jacket stent fiber thickness and aperture square area reduces the need for an anti-coagulation agent, for example Clopidogrel.

Maintaining small total coverage areas provides several additional advantages:

- 1. crimping the stent for insertion is relatively simple;
- 2. profile of the crimped stent is small;
- 3. stent jacket substantially has a minimal influence on the mechanical to properties of the stent during the delivery and expansion; and
- 4. jacket does not require folding during crimping when the coverage area of the stent is about 9%, or about 10%, or about 11%, or about 12% in self-expanding stent. In general, the coverage area is less than 16%.

The chart below provides support that the above-noted parameters of jacket coverage on a stent can be easily attained in the present disclosure using a fiber diameter of about 12.5 micrometers.

TABLE-US-00003

Stent	Fiber	Head	Apertures Size	Covered

Size	size	Needle	Aperture	Transverse	Longitudinal	area
[mm]	[μ]	No.	No.	[μ]	[μ]	[%]

2.5	12.5	22	44	166	291	11%
2.75	12.5	22	44	184	291	10%
3	12.5	22	44	202	291	10%
3.5	12.5	22	44	237	291	9%
4	12.5	35	70	167	291	11%
4.5	12.5	35	70	189	291	10%
5	12.5	35	70	212	291	9&
5.5	12.5	35	70	234	291	9%

It is understood that the phraseology and terminology employed herein is for descriptive purpose and should not be regarded as limiting.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure belongs. In addition, the descriptions, materials, methods, and examples are illustrative only and not intended to be limiting. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure.

As used herein, the terms “comprising” and “including”, or grammatical variants thereof are to be taken as specifying the stated features, integers, steps or components but do not preclude the addition of one or more additional features, integers, steps, components or groups thereof. This term encompasses the terms “consisting of” and “consisting essentially of”.

As used herein, “a” or “an” mean “at least one” or “one or more”. The use of the phrase “one or more” herein does not alter this intended meaning of “a” or “an”.

It is expected that during the life of this patent many relevant stent jacket materials will be developed and the scope of the term stent jacket is intended to include all such new technologies a priori.

As used herein, the term “about” refers to no more than ±10% of a given numerical value, as applicable.

Additional objects, advantages, and novel features of the present disclosure will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting. Additionally, each of the various embodiments and aspects of the present disclosure as delineated hereinabove and as claimed in the claims section below finds experimental support in the following examples.

It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub combination.

Although the disclosure has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those of ordinary skill in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present disclosure.