Patent Publication Number: US-9849010-B2

Title: Method of forming a nitinol stent

Description:
RELATED APPLICATIONS 
     This application is a Division of and claims the benefit of U.S. patent application Ser. No. 13/403,784 filed Feb. 23, 2012, now allowed. The disclosures of which are herein incorporated by reference in their entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to methods of making stents, and in particular, to methods of making stents from nitinol wires. 
     BACKGROUND OF THE INVENTION 
     Drug-eluting implantable medical devices have become popular in recent times for their ability to perform their primary function (such as structural support) and their ability to medically treat the area in which they are implanted. Further, stents made from shape memory materials, particularly nitinol, have become popular. 
     Stents formed from nitinol include many characteristics desirable in an effective stent. Nitinol is a nickel-titanium alloy generally containing approximately 55-56% nickel and 44-45% titanium. Nitinol was developed by the Naval Ordinance Laboratory and receives its name from its component parts and the Naval Ordinance Laboratory (Nickel/Titanium/Naval Ordinance Laboratory). Specifically, stents formed from nitinol, with or without special coatings, have been found to be chemically and biologically inert and to inhibit thrombus formation. Nitinol, under certain conditions, is also superelastic, which allows it to withstand extensive deformation and still resume its original shape. Furthermore, nitinol possesses shape memory, i.e., the metal “remembers” a specific shape fixed during a particular heat treatment and can resort to that shape under proper conditions. 
     The superelasticity of nitinol and its shape memory characteristics makes it possible to fabricate a stent having the desired shape and dimensions. Once formed, the stent can be temporarily deformed into a much narrower shape for insertion into the body. Once in place, the stent can be made to resume its desired shape and dimensions. Certain alloys of nickel and titanium can be made which are plastic at temperatures below about 30° C. and are elastic at body temperatures above 35° C. Such alloys are widely used for the production of stents for medical use since these nitinol stents are able to resume their desired shape at normal body temperature without the need to artificially heat the stent 
     While using nitinol for stents is desirable, nitinol material presents some difficulties in the formation of the stent itself. Nitinol materials in either the cold worked or heat-treated state can be easily sheared or stamped, but they are difficult to form to an accurate geometry, whether by forming wire shapes or die pressing. Thus, many nitinol stents are formed from a nitinol tube that is laser cut to the shape of a stent, sometimes also known as a tubular slotted stent. However, many stents are formed by manipulating a wire into a desired stent shape. When forming such a stent from a nitinol wire, complicated or specific design fixtures are required to hold the nitinol wire in the desired pattern throughout the heat setting, or heat treatment, process cycle. Typical process steps when forming a nitinol wire to be used as a stent include: conforming the nitinol wire to the geometry of the fixture; placing the nitinol wire and fixture into a “furnace” or other heating device for a set temperature and duration; removing the nitinol wire and fixture from the heating device and quenching (flash cooling); and removing the nitinol wire from the fixture. Custom fixtures may be required for each particular stent design. It is also often difficult to generate a cost effective fixture for simple and complicated stent patterns. Simpler wire forming methods available for stents made from other materials, where controlled plastic deformation of the wire into the desired shape allows for the wire to hold its shape through further processing, are generally not available for use with nitinol wires. For example, and not by way of limitation, methods and devices for creating waveforms in a wire described in U.S. Application Publication Nos. 2010/0269950 to Hoff et al. and 2011/0070358 to Mauch et al., and co-pending U.S. application Ser. Nos. 13/191,134 and 13/190,775, filed Jul. 26, 2011, may not effectively be used to form nitinol wire stents. 
     Thus, there is a need for an improved method for forming a stent from a nitinol wire, and in particular, and improved method of forming a stent with a hollow nitinol wire. 
     SUMMARY OF INVENTION 
     Embodiments hereof relate to a method of forming a nitinol hollow wire stent. A composite wire including a core member, an intermediate nitinol member, and an outer member is shaped into a stent pattern. The outer member of the composite wire holds the intermediate nitinol member in the stent pattern until a heat treatment step is applied. The composite wire is heat treated to set the stent pattern into the intermediate nitinol member of the composite wire. The composite wire is then processed such that the outer member is removed from around the intermediate member without adversely affecting the intermediate member, such as by chemical etching. Openings may be provided through the intermediate member to a lumen of the intermediate member, or to the core member of the composite wire. The composite wire may also be processed to remove the core member from the lumen of the intermediate member without adversely affecting the intermediate member, and the lumen may be filled with a biologically or pharmacologically active substance. 
     Embodiments hereof also relate to a method of forming a stent with a solid nitinol wire. A composite wire including a solid nitinol inner member and an outer member is shaped into a stent pattern. The outer member of the composite wire holds the inner nitinol member in the stent pattern until the heat treatment step is completed. The composite wire is heat treated to set the nitinol inner member in the stent pattern. The composite wire is then processed such that the outer member is removed from around the inner member without adversely affecting the intermediate member, such as by chemical etching, thus leaving the solid nitinol inner member in the stent pattern. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
       The foregoing and other features and advantages of the invention will be apparent from the following description of the invention as illustrated in the accompanying drawings. The accompanying drawings, which are incorporated herein and form a part of the specification, further serve to explain the principles of the invention and to enable a person skilled in the pertinent art to make and use the invention. The drawings are not to scale. 
         FIG. 1  is a schematic illustration of an exemplary stent in accordance with an embodiment hereof. 
         FIG. 2  is a cross-sectional view taken along line  2 - 2  of  FIG. 1 . 
         FIG. 3  is a longitudinal cross-section of an end of the wire of the stent of  FIG. 1 . 
         FIG. 4  is a schematic illustration of a composite wire including a core member, an intermediate member, and an outer member. 
         FIGS. 5-9  are cross-sectional views of the composite wire of  FIG. 4  at various stages of an embodiment of a method of forming a hollow nitinol wire stent. 
         FIG. 10  is flow chart illustrating an embodiment of a method of forming a hollow Nitinol wire stent. 
         FIG. 11  is a schematic illustration of an exemplary stent in accordance with an embodiment hereof. 
         FIG. 12  is a cross-sectional view taken along line  12 - 12  of  FIG. 11 . 
         FIG. 13  is a schematic illustration of a composite wire including a nitinol core member and an outer member. 
         FIG. 14  is a cross-sectional view of the composite wire of  FIG. 13 . 
         FIG. 15  is flow chart illustrating an embodiment of a method of forming a nitinol wire stent. 
         FIG. 16  is a schematic illustration of a stent in accordance with an embodiment hereof. 
         FIG. 17  is a cross-section view taken along line  17 - 17  of  FIG. 16 . 
         FIG. 18  is a schematic illustration of a composite within including a core member and a nitinol outer member. 
         FIG. 19  is a flow chart illustrating steps in an embodiment of a method of forming a hollow nitinol wire stent. 
         FIGS. 20-23  are cross-sectional views of a composite wire of  FIG. 18  at various stages of the method of  FIG. 19 . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Specific embodiments of the present invention are now described with reference to the figures, where like reference numbers indicate identical or functionally similar elements. 
     An embodiment of a stent  100  disclosed herein is shown in  FIGS. 1-3 . In particular, stent  100  is formed from a hollow wire  102 , in particular, a hollow nitinol wire  102 . The term “wire” as used herein means an elongated element or filament or group of elongated elements or filaments and is not limited to a particular cross-sectional shape or material, unless so specified. In the embodiment shown in  FIG. 1 , hollow wire  102  is formed into a series of generally sinusoidal waveforms including generally straight segments or struts  106  joined by bent segments or crowns  108 . The wire with the waveforms formed therein is helically wrapped to form a tube, as shown in  FIG. 1 . In the embodiment shown in  FIG. 1 , selected crowns  108  of longitudinally adjacent sinusoids may be joined by, for example, fusion points  110 . The invention hereof is not limited to the pattern shown in  FIG. 1 . Wire  102  of stent  100  can be formed into any pattern suitable for use as a stent. For example, and not by way of limitation, wire  102  of stent  100  can be formed into patterns disclosed in U.S. Pat. No. 4,800,882 to Gianturco, U.S. Pat. No. 4,886,062 to Wiktor, U.S. Pat. No. 5,133,732 to Wiktor, U.S. Pat. No. 5,782,903 to Wiktor, U.S. Pat. No. 6,136,023 to Boyle, and U.S. Pat. No. 5,019,090 to Pinchuk, each of which is incorporated by reference herein in its entirety. Further, instead of a single length of wire formed into a stent pattern, a plurality of wires may be formed into a two-dimensional waveform and wrapped into individual cylindrical elements. The cylindrical elements may then be aligned along a common longitudinal axis and joined to form the stent. 
     As shown in  FIG. 2 , hollow wire  102  of stent  100  allows for a biologically or pharmacologically active substance  112  to be deposited within the lumen  103  of hollow wire  102 . Although hollow wire  102  is shown as generally having a circular cross-section, hollow wire  102  may be generally elliptical or rectangular in cross-section. Hollow wire  102  further includes cuts or openings  104  dispersed along its length to permit biologically or pharmacologically active substance  112  to be released from lumen  103 . Openings  104  may be disposed only on struts  106  of stent  100 , only on crowns  108  of stent  100 , or both struts  106  and crowns  108 . Openings  104  may be sized and shaped as desired to control the elution rate of biologically or pharmacologically active substance  112  from stent  100 . Larger sized openings  104  generally permit a faster elution rate and smaller sized openings  104  generally provide a slower elution rate. Further, the size and/or quantity of openings  104  may be varied along stent  100  in order to vary the quantity and/or rate of biologically or pharmacologically active substance  112  being eluted from stent  100  at different portions of stent  100 . Openings  104  may be, for example and not by way of limitation, 5-30 μm in diameter. Openings  104  may be provided only on an outwardly facing or abluminal surface  116  of stent  100 , as shown in  FIG. 2 , only on the inwardly facing or luminal surface  118  of stent  100 , both surfaces, or may be provided anywhere along the circumference of wire  102 . Openings  104  may have a constant diameter through the depth or have a tapered or conical shape. 
     Ends  114  of wire  102  may be closed, as shown in  FIG. 3 . Ends  114  may be closed by crimping excess material of wire  102  to close lumen  103 . Closing ends  114  prevents drug  112  from prematurely releasing from ends  114 . However, closing ends  114  is not required as drug  112  may be dried, provided within a polymer matrix, enclosed within a liner (not shown), or otherwise protected from premature release from ends  114 . Further, ends  114  may be welded, crimped or otherwise connected to other portions of wire  102  such that the ends  114  are not free ends. Ends  114  may alternatively be provided as free ends. Further, ends  114  may be sealed by not removing the core member  120  from the ends of the wire, as shown in  FIG. 3 . 
       FIGS. 4-10  show a method for forming a hollow wire stent in accordance with an embodiment hereof. As shown in  FIG. 10 , step  200  is to utilize a wire having an outer member, an intermediate member, and a central core member. These types of wire are sometimes referred to as core wires, tri-layer wires, or composite wires. Composite wire  170  hereof is formed of an outer member  130 , an intermediate member  102  disposed within a lumen  132  of outer member  130 , and an inner or core member  120  disposed within a lumen  103  of intermediate member  102 , as shown schematically in  FIG. 4 . Intermediate member  102  becomes hollow wire  102  of stent  100 , and thus has been labeled with the same reference number. Composite wire  170  may be formed by any method known in the art, for example and not by way of limitation, a drawn filled tubing process, extrusion, cladding, material deposition, or any other suitable method. Examples of composite wires and methods of forming composite wires can be found in U.S. Pat. No. 5,630,840 to Mayer, U.S. Pat. No. 6,248,190 to Stinson, U.S. Pat. No. 6,497,709 to Heath, and U.S. Pat. No. 7,101,392 to Heath, each of which is incorporated by reference herein in its entirety. 
     Intermediate member  102  in this embodiment is formed from nitinol. Intermediate member  102 , as explained in more detail below, is the surviving material that will become hollow wire  102  of stent  100 . Outer member  130  is formed from a material that is more plastically deformable than the nitinol material of intermediate member  102 , and is sufficiently stiff to hold intermediate member  102  in the stent pattern until the heat treatment step, as described below. Further, the material used for outer member  130  must be able to be removed by a process that does not damage intermediate member  102 . Similarly, core member  120  is made of a sacrificial material that can be removed by a process that does not damage the nitinol material of intermediate member  102 . Core member  120  may be the same material as outer member  130 , or may be a different material. In one non-limiting embodiment core member  120  and outer member  130  are made from tantalum. Examples of other materials for core member  120  and outer member  130  include, but are not limited to, tungsten (W), molybdenum (Mo), niobium (Nb), rhenium (Re), carbon (C), germanium (Ge), silicon (Si) and alloys thereof. 
     A cross-section of composite wire  170  is shown in  FIG. 5 . Intermediate member  102  may have an outer diameter D 2  in the range of 0.0025 inch to 0.010 inch and wall thickness T 2  in the range of 0.0005 inch or larger, depending on the application, for example, in what lumen or organ and for what purpose the stent is to be utilized. Accordingly, core member  120  may have an outer diameter D 1  of 0.0005 inch to 0.0095 inch. Outer member  130  may have a thickness T 3  in the range of 0.0001 inch or larger, depending on the material used for each member of composite wire  170 . In one particular non-limiting example, core member  120  is made from tantalum and has an outer diameter D 1  of 0.0020, intermediate member  102  is made from nitinol and has a thickness T 2  of 0.0025 and an outer diameter D 2  of 0.0070, and outer member  130  is made from tantalum and has a thickness T 3  of 0.0005 and an outer diameter D 3  of 0.0080. The values listed above are merely examples and other diameters and thicknesses may be used depending on, for example, the materials used, the desired stent shape, and the purpose or location of the stent. 
     Referring to  FIG. 10 , step  210  is to shape the composite wire  170  into the stent pattern. As discussed above, the stent pattern can be the pattern shown in  FIG. 1  or any other suitable pattern formed from a wire. Further, although the order of all the steps is not critical, step  210  must be done prior to removing outer member  130 , as explained in more detail below. However, the step of shaping the composite member  170  into the stent pattern does not have to include shaping composite member  170  into the final stent pattern. For example, the step  210  of shaping the composite member  170  into a stent pattern may include only forming the struts  106  and crowns  108  in composite wire  170 , prior to the heat treating step described below. Shaping composite wire  170  into the stent pattern while outer member  130  is disposed around nitinol intermediate member  102  and core member  120  is disposed within intermediate member  102  allows for outer member  130  and core member  120  to “hold” nitinol intermediate member  102  in the stent pattern. As explained above, nitinol members generally must be held in the desired stent pattern using complicated, custom designed fixtures or jigs prior to the heat treating step. Utilizing outer member  130  and core member  120  eliminates the need for such complicated, custom designed fixtures or jigs. This holding function may be primarily accomplished by outer member  130 . Thus, the step  210  of shaping composite wire  170  into the stent pattern can be performed with the same techniques used to shape conventional stents made from stainless steel, MP35N, or other known materials. For example, and not by way of limitation, shaping the composite wire  170  into the stent pattern shown in  FIG. 1  generally includes the steps of forming composite wire  170  into a two dimensional sinusoid pattern followed by wrapping the pattern around a mandrel, as known to those skilled in the art. Forming the composite wire  170  into a two dimensional waveform can be achieved, for example, using techniques described in U.S. Application Publication Nos. 2010/0269950 to Hoff et al. and 2011/0070358 to Mauch et al., and co-pending U.S. application Ser. Nos. 13/191,134 and 13/190,775, filed Jul. 26, 2011, each of which is incorporated in its entirety by reference herein. Other techniques known to those skilled in the art could also be used. 
     Step  220  shown in  FIG. 10  is to heat treat the composite wire  170  while in the shaped stent pattern. Heat treating the composite wire “sets” the nitinol intermediate member  102  in the stent pattern such that nitinol intermediate member  102  “remembers” the stent pattern. Accordingly, when stent  100  with intermediate member  102  as the hollow wire thereof is manipulated into a radially compressed configuration for insertion into a body lumen, such as by a sleeve, the stent  100  will return to the stent configuration of  FIG. 1  upon release from the sleeve, thereby deploying into the radially expanded configuration at the treatment site, as known to those skilled in the art. The heat treatment step  220  may be performed, for example, in a furnace or similar heating equipment. The conditions for heat treatment step  220  are known to those skilled in the art. For example, and not by way of limitation, composite wire  170  may be placed in a furnace at 400° C.-500° C. for 15 minutes. Appropriate temperatures and durations for the heat treatment step are known to those skilled in the art. 
     When the heat treatment step  220  is completed, the composite wire  170  may be removed from the furnace and any fixture to which it was attached, for example, a mandrel. Step  230  is to process the composite wire such that outer member  130  is removed without adversely affecting the intermediate member, such as by chemical etching. Step  230  can be performed by any suitable process for removing outer member  130  while preserving intermediate member  102 . In particular, subjecting composite wire  170  to xenon difluoride (XeF 2 ) gas at low pressure (1-6 Torr) and relatively high temperature (approximately 150° C.) causes the xenon difluoride (XeF 2 ) gas to react with a tantalum (Ta) outer member  103  to form TaF 5  and Xe gases. Xenon difluoride (XeF 2 ) gas reacts similarly with an outer member  130  made from tungsten, molybdenum, niobium, rhenium, carbon, germanium, and silicon. Other methods for removing outer member  130  may used, as described, for example, in U.S. Application Publication no. 2011/0008405 to Birdsall et al. and U.S. Application Publication No. 2011/0070358 to Mauch et al., wherein methods of removing core members are described, each published application incorporated by reference herein in its entirety. Such methods and materials, where appropriate, can be equally applied for removal of outer member  130 . As examples, but not by way of limitation, methods such as wet chemical dissolution, solubilization, sublimation, and melting may be used with appropriate outer member/core member combinations. 
     Upon completion of step  230  to etch outer member  130 , intermediate member  102  and core member  120  remain in the shape of stent  100 . A cross-section of composite member  170  includes intermediate member  102  and core member  120 , as shown in  FIG. 6 . Further processing steps to finish, polish, and sterilize stent  100  may take place at this time, leaving a stent with a nitinol intermediate member  102  and a core member  120 . In such a situation, core member  120  may be selected to improve a characteristic of nitinol intermediate member  102 . For example, and not by way of limitation, core member  120  may be formed from a radiopaque material to improve radiopacity of the stent. For example, and not by way of limitation, core member  120  may be formed of tantalum or platinum, which are considered a radiopaque material, in order to improve the radiopacity of relatively radiolucent nitinol intermediate member  102 . 
     However, in order to provide a stent  100  with a hollow wire  102 , as described above with respect to  FIGS. 1-3 , further processing is required. In particular, step  240  is to provide openings  104  in intermediate member  102  through to lumen  103  of intermediate member  102 . Openings  104  may be laser cut, drilled, etched, or otherwise provided in intermediate member  102 . Step  240  need not be performed after step  230 , nor before step  250 , although it is preferred to be before step  250 , as explained in more detail below. If step  240  is performed after step  230 , a cross-section of composite wire  170  will include intermediate member  102 , core member  120 , and an opening  104 , as shown in  FIG. 7 . It should also be noted that step  240  of forming an opening  104  through intermediate member  102  can be performed prior to step  230  of chemically etching away outer member  130 . In such a situation, the opening  104  may extend through outer member  130  and intermediate member  102  through to lumen  103  of intermediate member  102 . Thus, the step  230  of chemically etching away outer member  130  will be combined with the step  250  of chemically etching away core member  120 , described below. In such a situation, it is preferable that the material of outer member  130  and core member  120  may both be etched by the same etchant, such as, but not limited to, xenon difluoride. 
     Step  250  is to process composite wire  170  such that core member  120  is removed from the lumen  103  of intermediate member  102  without adversely affecting intermediate member  102 , such as by chemical etching. Step  250  can be performed by any suitable process for removing core member  120  while preserving intermediate member  102 . In particular, subjecting composite wire  170  to xenon difluoride (XeF 2 ) gas at low pressure (1-6 Torr) and relatively high temperature (approximately 150° C.) causes the xenon difluoride (XeF 2 ) gas to react with a tantalum (Ta) core member  120  to form TaF 5  and Xe gases, which can be exhausted from lumen  103 . Xenon difluoride (XeF 2 ) gas reacts similarly with a core member  120  made from tungsten, molybdenum, niobium, rhenium, carbon, germanium, and silicon. However, xenon difluoride (XeF 2 ) gas does not react with an intermediate member formed of nitinol. Other methods for removing core member  120  may used, as described, for example, in U.S. Application Publication no. 2011/0008405 to Birdsall et al. and U.S. Application Publication No. 2011/0070358 to Mauch et al., each published application incorporated by reference herein in its entirety. As examples, but not by way of limitation, methods such as wet chemical dissolution, solubilization, sublimation, and melting may be used with appropriate intermediate member/core member combinations. Accordingly, after step  250  is completed, intermediate member  102  remains and core member  120  has been removed, leaving the structure shown in  FIG. 8 . As noted above, openings  104  do not need to be formed prior to the step of removing core member  120  as long as there is a way to expose core member  120  to the etchant. For example, ends  114  of the wire may be open or temporary ports may for formed through intermediate member  102  to expose core member  120  to the etchant. 
     After core member  120  has been removed, biologically or pharmacologically active substance  112  may be introduced into lumen  103  of intermediate member  102 , as shown in step  260  of  FIG. 10 . This produces a hollow wire or intermediate member  102  with biologically or pharmacologically active substance  112  disposed in lumen  103  thereof, and openings  104  through which biologically or pharmacologically active substance  112  may be eluted, as shown in  FIGS. 2 and 9 . Filling lumen  102  with a biologically or pharmacologically active substance may be accomplished by any means known to those skilled in the art. For example, and not by way of limitation, methods for filling lumens of hollow wires described in U.S. Application Publication No. 2011/0070357 to Mitchell et al., each of which is incorporated by reference herein in its entirety; and co-pending U.S. application Ser. Nos. 12/884,362; 12/884,451; 12/884,501; 12/884,578; 12/884,596 each filed on Sep. 17, 2010, and each of which is incorporated by reference herein in its entirety. 
     The biologically or pharmacologically active substance  112  may include, but is not limited to, antineoplastic, antimitotic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antiproliferative, antibiotic, antioxidant, and antiallergic substances as well as combinations thereof. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g., Taxotere® from Aventis S. A., Frankfurt, Germany), methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin® from Pharmacia &amp; Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include ABT-578 (a synthetic analog of rapamycin), rapamycin (sirolimus), zotarolimus, everolimus, angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g., Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &amp; Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor® from Merck &amp; Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suram in, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other biologically or pharmacologically active substances or agents that may be used include nitric oxide, alpha-interferon, genetically engineered epithelial cells, and dexamethasone. In other examples, the biologically or pharmacologically active substance is a radioactive isotope for implantable device usage in radiotherapeutic procedures. Examples of radioactive isotopes include, but are not limited to, phosphorus (P 32 ), palladium (Pd 103 ), cesium (Cs 131 ), Iridium (I 192 ) and iodine (I 125 ). While the preventative and treatment properties of the foregoing biologically or pharmacologically active substances are well-known to those of ordinary skill in the art, the biologically or pharmacologically active substances are provided by way of example and are not meant to be limiting. Other biologically or pharmacologically active substances are equally applicable for use with the disclosed methods and compositions. 
     Further, a carrier may be used with the biologically or pharmacologically active substance. Examples of suitable carriers include, but are not limited to, urea, ethanol, acetone, tetrahydrofuran, dymethylsulfoxide, a combination thereof, or other suitable carriers known to those skilled in the art. Still further, a surfactant may be formulated with the biologically or pharmacologically active substance and the solvent to aid elution of the biologically or pharmacologically active substance. 
     Stent  100  may be used conventionally in blood vessels of the body to support such a vessel after an angioplasty procedure. It is known that certain biologically or pharmacologically active substances eluted from stents may prevent restenosis or other complications associated with angioplasty or stents. Stent  100  may alternatively be used in other organs or tissues of the body for delivery of biologically or pharmacologically active substance to treat tumors, inflammation, nervous conditions, or other conditions that would be apparent to those skilled in the art. 
       FIGS. 11-15  show an embodiment of a stent  300  formed using a solid nitinol wire  302 . In particular, stent  300  is formed from a solid wire  302 , as shown in  FIG. 12 . In the embodiment shown in  FIG. 11 , stent  300  is formed into a series of generally sinusoidal waves including generally straight segments or struts  306  joined by bent segments or crowns  308 . The generally sinusoidal pattern is formed into a tube, as shown in  FIG. 11 . In the embodiment shown in  FIG. 11 , selected crowns  308  of longitudinally adjacent sinusoids may be joined by, for example, fusion points  310 . The invention hereof is not limited to the pattern shown in  FIG. 11 . Wire  302  of stent  300  can be formed into any pattern suitable for use as a stent. For example, and not by way of limitation, wire  302  can be formed into patterns disclosed in U.S. Pat. No. 4,800,082 to Gianturco, U.S. Pat. No. 4,886,062 to Wiktor, U.S. Pat. No. 5,133,732 to Wiktor, U.S. Pat. No. 5,782,903 to Wiktor, U.S. Pat. No. 6,136,023 to Boyle, and U.S. Pat. No. 5,019,090 to Pinchuk, each of which is incorporated by reference herein in its entirety. 
     Ends  314  of wire  302  may be free ends, as shown in  FIG. 11 , or may be fused, crimped, or otherwise connected to other portions of wire  302 , as known to those skilled in the art. Stent  300  may be coated with a biologically or pharmacologically active substance (not shown) or may be a bare stent. A coating may be disposed on a luminal surface  316 , and abluminal surface  118 , or both. 
     As explained above, forming stents from nitinol wire is often difficult due to complicated custom fixtures or jigs required to hold the nitinol wire in place during the heat treatment or heat setting process. In the method described herein with respect to  FIGS. 11-15 , the need for such complicated custom fixtures or jigs is alleviated. In particular, as shown in  FIG. 15 , step  400  is to utilize a wire with an outer member and a central core member. These types of wire are sometimes referred to as core wires or composite wires. Composite wire  370  hereof is formed of an outer member  320  and an inner or core member  302  disposed within a lumen  303  of outer member  320 , as shown schematically in  FIG. 13  and in cross-section in  FIG. 14 . Core member  302  becomes wire  302  of stent  300 , and thus has been labeled with the same reference number. Composite wire  370  may be formed by any method known in the art, for example and not by way of limitation, a drawn filled tubing process, extruding the outer member over the inner member, or any other suitable method. Examples of core wires and methods of forming core wires can be found in U.S. Pat. No. 5,630,840 to Mayer, U.S. Pat. No. 6,248,190 to Stinson, U.S. Pat. No. 6,497,709 to Heath, and U.S. Pat. No. 7,101,392 to Heath, each of which is incorporated by reference herein in its entirety. 
     Core member  302  is a nitinol material. Details regarding nitinol are provided above. Core member  302 , as explained in more detail below, is the surviving material that will become wire  302 . Outer member  320  may be a material that is more plastically deformable than nitinol and is sufficiently stiff to support core member  302  when composite wire  370  is deformed such that core member  302  does not revert back to its non-deformed shape. In particular, outer member  320  is formed from a material and of a selected thickness such that after composite wire  370  is bent into the stent pattern, as explained in more detail below, outer member  320  can “hold” core member  302  in the stent pattern without resort to complicated custom fixtures or jigs. Further, outer member  320  is made of a sacrificial material that can be removed by a process that does not damage the material of core member  302 . Examples of materials for outer member  302  include, but are not limited to, tantalum (Ta), tungsten (W), molybdenum (Mo), niobium (Nb), rhenium (Re), carbon (C), germanium (Ge), silicon (Si) and alloys thereof. 
     A cross-section of composite wire  370  is shown in  FIG. 14 . Core member  302  may have an outer diameter D 1  in the range of 0.0025 inch to 0.0100 inch depending on the application, for example, in what lumen or organ and for what purpose the stent is to be utilized. Outer member  320  may have an outer diameter D 2  in the range of 0.0030 inch to 0.0140 inch and wall thickness T 2  in the range of 0.0002 to 0.0020 inch, depending on the size of core member  302  and the material selected for outer member  330 . The values listed above are merely examples and other diameters and thicknesses may be used depending on, for example, the material used, the desired stent shape, and the purpose or location of the stent. 
     In one example, utilizing an outer member  320  formed from tantalum surrounding the Nitinol core member  302 , the core member  302  may account for up to 90% of the overall outer diameter D 2  and the tantalum outer member  320  would have sufficient stiffness to “hold” the Nitinol core member in place after shaping composite wire  370  into a stent pattern. In particular, the formula for stiffness is as follows: 
               stiffness   ≡     F   δ       =       F     (       FL   3       3   ⁢           ⁢   EI       )       =         3   ⁢           ⁢   EI       L   3       =       3   ⁢           ⁢     E   ⁡     (         1   4     ⁢           ⁢   π   ⁢           ⁢     r   2   4       -       1   4     ⁢   π   ⁢           ⁢     r   1   4         )           L   3                 
where for solid circular cross section (core member  302 ) I=¼πr 4 = 1/64πD 1   4  and for a tubular cross-section (outer member  320 ) I=¼πr o   4 −¼πr i   4 = 1/64πD 2   4 − 1/64πD 1   4 . Thus, stiffness is proportional to EI. The chart below shows the inner diameter D 1  of nitinol core member  302  as a percentage of the overall outer diameter D 2  of the nitinol core member and the tantalum outer member  320 . As can be seen, even with the nitinol core member  302  taking up 90% of the overall diameter D 2 , the outer member  302  (outer shell) is stiffer than core member  302 .
 
     
       
         
           
               
               
               
               
               
               
               
               
               
             
               
                   
               
               
                 D1 as a % of D2 
                 20% 
                 30% 
                 40% 
                 50% 
                 60% 
                 70% 
                 80% 
                 90% 
               
               
                   
               
             
            
               
                 Stiffness (EI) of Nitinol 
                 0.06% 
                 0.33% 
                 1.06% 
                 2.69% 
                 6.01% 
                 12.76% 
                 28.01% 
                 77.02% 
               
               
                 core member as a % of 
               
               
                 stiffness of tantalum 
               
               
                 outer member 
               
               
                   
               
            
           
         
       
     
     Referring back to  FIG. 15 , step  410  is to shape the composite wire  370  into the stent pattern. As discussed above, the stent pattern can be the pattern shown in  FIG. 11  or any other suitable pattern formed from a wire. Further, although the order of all the steps is not critical, step  410  must be done prior to removing outer member  320 , as explained in more detail below. Shaping composite wire  370  into the stent pattern while outer member  320  surrounds core member  302  permits outer member  320  to “hold” core member  302  in the stent pattern until the heat treatment step discussed below is completed. This alleviates the need for complicated custom fixtures or jigs to hold nitinol core member  302  in the stent pattern during the heat treatment step. Shaping the composite wire  370  into the stent pattern shown in  FIG. 11  generally includes the steps of forming composite wire  370  into a two dimensional waveform or sinusoid pattern followed by wrapping the pattern around a mandrel, as known to those skilled in the art. Forming the composite wire  370  into a two dimensional waveform can be achieved, for example, using techniques described in U.S. Application Publication Nos. 2010/0269950 to Hoff et al. and 2011/0070358 to Mauch et al., and co-pending U.S. application Ser. Nos. 13/191,134 and 13/190,775, filed Jul. 26, 2011, each of which is incorporated in its entirety by reference herein. Other techniques known to those skilled in the art could also be used. 
     Step  420  shown in  FIG. 15  is to heat treat the composite wire  370  while in the shaped stent pattern. Heat treating the composite wire “sets” the nitinol core member  302  in the stent pattern such that nitinol core member  302  “remembers” the stent pattern. Accordingly, when stent  300  with core member  302  as the wire thereof is manipulated into a radially compressed configuration for insertion into a body lumen, such as by a sleeve, the stent  300  will return to the stent configuration of  FIG. 11  upon release from the sleeve, thereby deploying to the radially expanded configuration at the treatment site, as known to those skilled in the art. The heat treatment step  420  may be performed, for example, in a furnace or similar heating equipment. The conditions for heat treatment step  420  are known to those skilled in the art. For example, and not by way of limitation, composite wire  370  may be placed in a furnace at 400° C.-500° C. for 15 minutes. Appropriate temperatures and durations for the heat treatment step are known to those skilled in the art. 
     When the heat treatment step  420  is completed, the composite wire  370  may be removed from the furnace and any fixture to which it was attached, for example, a mandrel. Step  430  is to process composite wire  370  such that outer member  320  is removed from around core member  302  without adversely affecting core member  302 , such as by chemical etching. Step  430  can be performed by any suitable process for removing outer member  320  while preserving core member  302 . In particular, subjecting composite wire  370  formed of a nitinol core member  302  and a tantalum outer member  302  to xenon difluoride (XeF 2 ) gas at low pressure (1-6 Torr) and relatively high temperature (approximately 150° C.) causes the xenon difluoride (XeF 2 ) gas to react with the tantalum outer member  302  to form TaF 5  and Xe gases. Xenon difluoride (XeF 2 ) gas reacts similarly with an outer member  302  made from tungsten, molybdenum, niobium, rhenium, carbon, germanium, and silicon. Other methods for removing outer member  320  may used, as described, for example, in U.S. Application Publication no. 2011/0008405 to Birdsall et al. and U.S. Application Publication No. 2011/0070358 to Mauch et al., wherein methods of removing core members are described, each published application incorporated by reference herein in its entirety. Such methods and materials, where appropriate, can be equally applied for removal of outer member  320 . 
     Removing outer member  320  leaves solid nitinol core member  302  formed in a stent pattern, as shown in  FIGS. 11 and 12 . Further processing of stent  300 , such as polishing, sterilizing, and other steps known to those skilled in the art, may be performed to finish stent  300 . 
     An embodiment of a stent  500  disclosed herein is shown in  FIGS. 16-17 . In particular, stent  500  is formed from a hollow wire  502 , in particular, a hollow nitinol wire  502 . The term “wire” as used herein means an elongated element or filament or group of elongated elements or filaments and is not limited to a particular cross-sectional shape or material, unless so specified. In the embodiment shown in  FIG. 16 , hollow wire  502  is formed into a series of generally sinusoidal waveforms including generally straight segments or struts  506  joined by bent segments or crowns  508  and the wire with the waveforms formed therein is helically wound to form a generally tubular stent  500 . In the embodiment shown in  FIG. 16 , selected crowns  508  of longitudinally adjacent sinusoids may be joined by, for example, fusion points  510 . The invention hereof is not limited to the pattern shown in  FIG. 16 . Wire  502  of stent  500  can be formed into any pattern suitable for use as a stent. For example, and not by way of limitation, wire  502  of stent  500  can be formed into patterns disclosed in U.S. Pat. No. 4,800,882 to Gianturco, U.S. Pat. No. 4,886,062 to Wiktor, U.S. Pat. No. 5,133,732 to Wiktor, U.S. Pat. No. 5,782,903 to Wiktor, U.S. Pat. No. 6,136,023 to Boyle, and U.S. Pat. No. 5,019,090 to Pinchuk, each of which is incorporated by reference herein in its entirety. Further, instead of a single length of wire formed into a stent pattern, a plurality of wires may be formed into a two-dimensional waveform and wrapped into individual cylindrical elements. The cylindrical elements may then be aligned along a common longitudinal axis and joined to form the stent. 
     As shown in  FIG. 17 , hollow wire  502  of stent  500  allows for a biologically or pharmacologically active substance  512  to be deposited within the lumen  503  of hollow wire  502 . Although hollow wire  502  is shown as generally having a circular cross-section, hollow wire  502  may be generally elliptical or rectangular in cross-section. Hollow wire  502  further includes cuts or openings  504  dispersed along its length to permit biologically or pharmacologically active substance  512  to be released from lumen  503 . Openings  504  may be disposed only on struts  506  of stent  500 , only on crowns  508  of stent  500 , or both struts  506  and crowns  508 . Openings  504  may be sized and shaped as desired to control the elution rate of biologically or pharmacologically active substance  512  from stent  500 . Larger sized openings  504  generally permit a faster elution rate and smaller sized openings  504  generally provide a slower elution rate. Further, the size and/or quantity of openings  504  may be varied along stent  500  in order to vary the quantity and/or rate of biologically or pharmacologically active substance  512  being eluted from stent  500  at different portions of stent  500 . Openings  504  may be, for example and not by way of limitation, 5-30 μm in diameter. Openings  504  may be provided only on an outwardly facing or abluminal surface  516  of stent  500 , as shown in  FIG. 17 , only on the inwardly facing or luminal surface  518  of stent  500 , both surfaces, or may be provided anywhere along the circumference of wire  502 . Openings  504  may have a constant diameter through the depth or have a tapered or conical shape. 
     Ends  514  of wire  502  may be closed. Ends  114  may be closed by crimping excess material of wire  502  to close lumen  503 . Closing ends  514  prevents drug  512  from prematurely releasing from ends  114 . However, closing ends  114  is not required as drug  512  may be dried, provided within a polymer matrix, enclosed within a liner (not shown), or otherwise protected from premature release from ends  514 . Further, ends  514  may be welded, crimped or otherwise connected to other portions of wire  502  such that the ends  514  are not free ends. Ends  514  may alternatively be provided as free ends. Further, ends  514  may be sealed by not removing the core member  520  from the ends of the wire. 
       FIGS. 18-23  show a method for forming a hollow nitinol wire stent  500  in accordance with an embodiment hereof. As shown in  FIG. 19 , step  600  is to utilize a wire having an outer member  102  and a central core member  120 . These types of wire are sometimes referred to as core wires or composite wires. Composite wire  570  hereof is formed of an outer member  502  and a core member  520  disposed within a lumen  503  of outer member  502 , as shown schematically in  FIG. 18 . Outer member  502  becomes hollow nitinol wire  502  of stent  500 , and thus has been labeled with the same reference number. Composite wire  570  may be formed by any method known in the art, for example and not by way of limitation, a drawn filled tubing process, extrusion, cladding, material deposition, or any other suitable method. Examples of composite wires and methods of forming composite wires can be found in U.S. Pat. No. 5,630,840 to Mayer, U.S. Pat. No. 6,248,190 to Stinson, U.S. Pat. No. 6,497,709 to Heath, and U.S. Pat. No. 7,101,392 to Heath, each of which is incorporated by reference herein in its entirety. 
     Outer member  502  in this embodiment is formed from nitinol. Outer member  502 , as explained in more detail below, is the surviving material that will become hollow nitinol wire  502  of stent  500 . Core member  520  is formed from a material that is sufficiently stiff at the sizes provided to hold nitinol outer member  502  in the stent pattern until the heat treatment step, as described below. Core member  120  may also be formed of a material that is more plastically deformable than nitinol outer member  502 . Further, the material used for core member  520  must be able to be removed by a process that does not damage nitinol outer member  502 . In one non-limiting embodiment core member  520  is made from tungsten. Examples of other materials for core member  520  include, but are not limited to, tantalum, molybdenum, rhenium, and alloys thereof. 
     A cross-section of composite wire  570  is shown in  FIG. 20 . Outer member  502  may have an outer diameter D 2  in the range of 0.0025 inch to 0.010 inch and wall thickness T in the range of 0.0005 inch or larger, depending on the application, for example, in what lumen or organ and for what purpose the stent is to be utilized. Accordingly, core member  520  may have an outer diameter D 1  of 0.0005 inch to 0.0095 inch. In one particular non-limiting example, core member  520  is made from tungsten and has an outer diameter D 1  of 0.0050 and outer member  502  is made from nitinol and has a thickness T of 0.0010 and an outer diameter D 2  of 0.0070. The values listed above are merely examples and other diameters and thicknesses may be used depending on, for example, the materials used, the desired stent shape, and the purpose or location of the stent.
 
 E   core   I   core   &gt;E   outer   I   outer  
 
 E   core   D   1   4   &gt;E   outer ( D   2   4   −D   1   4 )
         where E outer  would be the modulus of elasticity of Nitinol and E core  would be the modulus of elasticity of the inner core material       

     Referring to  FIG. 19 , step  610  is to shape the composite wire  570  into the stent pattern. As discussed above, the stent pattern can be the pattern shown in  FIG. 16  or any other suitable pattern formed from a wire. Further, although the order of all the steps is not critical, step  610  must be done prior to removing core member  520 , as explained in more detail below. However, the step of shaping the composite member  570  into the stent pattern does not have to include shaping composite member  570  into the final stent pattern. For example, the step  610  of shaping the composite member  570  into a stent pattern may include only forming the struts  506  and crowns  508  in composite wire  570 , prior to the heat treating step described below. Shaping composite wire  570  into the stent pattern while core member  520  is disposed in the lumen of nitinol outer member  502  allows for core member  520  to “hold” nitinol outer member  502  in the stent pattern prior to an during the heat treating step described below. As explained above, nitinol members generally must be held in the desired stent pattern using complicated, custom designed fixtures or jigs prior to the heat treating step. Utilizing core member  520  eliminates the need for such complicated, custom designed fixtures or jigs. Thus, the step  610  of shaping composite wire  570  into the stent pattern can be performed with the same techniques used to shape conventional stents made from stainless steel, MP35N, or other known materials. For example, and not by way of limitation, shaping the composite wire  570  into the stent pattern shown in  FIG. 16  generally includes the steps of forming composite wire  570  into a two dimensional sinusoid pattern followed by wrapping the pattern around a mandrel, as known to those skilled in the art. Forming the composite wire  570  into a two dimensional waveform can be achieved, for example, using techniques described in U.S. Application Publication Nos. 2010/0269950 to Hoff et al. and 2011/0070358 to Mauch et al., and co-pending U.S. application Ser. Nos. 13/191,134 and 13/190,775, filed Jul. 26, 2011, each of which is incorporated in its entirety by reference herein. Other techniques known to those skilled in the art could also be used. 
     Step  620  shown in  FIG. 19  is to heat treat the composite wire  570  while in the shaped stent pattern. Heat treating the composite wire “sets” the nitinol outer member  502  in the stent pattern such that nitinol outer member  502  “remembers” the stent pattern. Accordingly, when stent  500  with nitinol outer member  502  as the hollow wire thereof is manipulated into a radially compressed configuration for insertion into a body lumen, such as by a sleeve, the stent  500  will return to the stent configuration of  FIG. 16  upon release from the sleeve, thereby deploying into the radially expanded configuration at the treatment site, as known to those skilled in the art. The heat treatment step  620  may be performed, for example, in a furnace or similar heating equipment. The conditions for heat treatment step  620  are known to those skilled in the art. For example, and not by way of limitation, composite wire  570  may be placed in a furnace at 400° C.-500° C. for 15 minutes. Appropriate temperatures and durations for the heat treatment step are known to those skilled in the art. 
     When the heat treatment step  620  is completed, the composite wire  570  may be removed from the furnace and any fixture to which it was attached, for example, a mandrel. Step  630  is to provide openings  504  in nitinol outer member  502  through to lumen  503  of nitinol outer member  502 . Openings  504  may be laser cut, drilled, etched, or otherwise provided in outer member  502 . Step  630  need not be performed after step  620 , nor before step  640 , although it is preferred to be before step  640 , as explained in more detail below. If step  630  is performed after step  620 , a cross-section of composite wire  570  will include outer member  502 , core member  520 , and an opening  504 , as shown in  FIG. 21 . It should also be noted that step  630  of forming openings  504  through outer member  502  can be performed prior to step  610  of shaping the composite wire  570  into the stent pattern. 
     Step  640  is to process composite wire  570  such that core member  520  is removed from the lumen  503  of outer member  502  without adversely affecting outer member  502 , such as by chemical etching. Step  640  can be performed by any suitable process for removing core member  520  while preserving outer member  502 . In particular, subjecting composite wire  570  to xenon difluoride (XeF 2 ) gas at low pressure (1-6 Torr) and relatively high temperature (approximately 150° C.) causes the xenon difluoride (XeF 2 ) gas to react with a tungsten core member  520  to form TaF 5  and Xe gases, which can be exhausted from lumen  103 . Xenon difluoride (XeF 2 ) gas reacts similarly with a core member  120  made from tantalum, molybdenum, rhenium, and alloys thereof. However, xenon difluoride (XeF 2 ) gas does not react with an intermediate member formed of nitinol. Other methods for removing core member  520  may used, as described, for example, in U.S. Application Publication no. 2011/0008405 to Birdsall et al. and U.S. Application Publication No. 2011/0070358 to Mauch et al., each published application incorporated by reference herein in its entirety. As examples, but not by way of limitation, methods such as wet chemical dissolution, solubilization, sublimation, and melting may be used with appropriate outer member/core member combinations. Accordingly, after step  640  is completed, outer member  502  remains and core member  520  has been removed, leaving the structure shown in  FIG. 22 . As noted above, openings  504  do not need to be formed prior to the step of removing core member  520  as long as there is a way to expose core member  520  to the etchant. For example, ends  514  of the wire may be open or temporary ports may be formed through outer member  502  to expose core member  520  to the etchant. 
     After core member  520  has been removed, biologically or pharmacologically active substance  512  may be introduced into lumen  503  of outer member  502 , as shown in step  650  of  FIG. 19 . This produces a hollow wire or outer member  502  with biologically or pharmacologically active substance  512  disposed in lumen  503  thereof, and openings  504  through which biologically or pharmacologically active substance  512  may be eluted, as shown in  FIGS. 17 and 23 . Filling lumen  503  with a biologically or pharmacologically active substance may be accomplished by any means known to those skilled in the art. For example, and not by way of limitation, methods for filling lumens of hollow wires described in U.S. Application Publication No. 2011/0070357 to Mitchell et al., which is incorporated by reference herein in its entirety; and co-pending U.S. application Ser. Nos. 12/884,362; 12/884,451; 12/884,501; 12/884,578; 12/884,596 each filed on Sep. 17, 2010, and each of which is incorporated by reference herein in its entirety. 
     The biologically or pharmacologically active substance  512  may include, but is not limited to, antineoplastic, antimitotic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antiproliferative, antibiotic, antioxidant, and antiallergic substances as well as combinations thereof. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g., Taxotere® from Aventis S. A., Frankfurt, Germany), methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin® from Pharmacia &amp; Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include ABT-578 (a synthetic analog of rapamycin), rapamycin (sirolimus), zotarolimus, everolimus, angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g., Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &amp; Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor® from Merck &amp; Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other biologically or pharmacologically active substances or agents that may be used include nitric oxide, alpha-interferon, genetically engineered epithelial cells, and dexamethasone. In other examples, the biologically or pharmacologically active substance is a radioactive isotope for implantable device usage in radiotherapeutic procedures. Examples of radioactive isotopes include, but are not limited to, phosphorus (P 32 ), palladium (Pd 103 ), cesium (Cs 131 ), Iridium (I 192 ) and iodine (I 125 ). While the preventative and treatment properties of the foregoing biologically or pharmacologically active substances are well-known to those of ordinary skill in the art, the biologically or pharmacologically active substances are provided by way of example and are not meant to be limiting. Other biologically or pharmacologically active substances are equally applicable for use with the disclosed methods and compositions. 
     Further, a carrier may be used with the biologically or pharmacologically active substance. Examples of suitable carriers include, but are not limited to, urea, ethanol, acetone, tetrahydrofuran, dymethylsulfoxide, a combination thereof, or other suitable carriers known to those skilled in the art. Still further, a surfactant may be formulated with the biologically or pharmacologically active substance and the solvent to aid elution of the biologically or pharmacologically active substance. 
     Stent  500  may be used conventionally in blood vessels of the body to support such a vessel after an angioplasty procedure. It is known that certain biologically or pharmacologically active substances eluted from stents may prevent restenosis or other complications associated with angioplasty or stents. Stent  500  may alternatively be used in other organs or tissues of the body for delivery of biologically or pharmacologically active substance to treat tumors, inflammation, nervous conditions, or other conditions that would be apparent to those skilled in the art. 
     While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of illustration and example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the appended claims and their equivalents. It will also be understood that each feature of each embodiment discussed herein, and of each reference cited herein, can be used in combination with the features of any other embodiment. Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary or the detailed description. All patents and publications discussed herein are incorporated by reference herein in their entirety.