BACKGROUND OF THE INVENTION
The use of stents in various surgical, interventional cardiology, and radiology procedures has quickly become accepted as experience with stent devices accumulates and as the advantages of stents become more widely recognized. Stents are often used in body lumens to maintain open passageways such as in the prostatic urethra, the esophagus, the biliary tract, intestines, and various coronary arteries and veins, as well as more remote cardiovascular vessels such as the femoral artery.
Stents are often used to treat atherosclerosis, a disease in which vascular lesions or plaques consisting of cholesterol crystals, necrotic cells, lipid pools, excess fiber elements and calcium deposits accumulate in the walls of an artery. One of the most successful procedures for treating atherosclerosis is insertion of a deflated balloon within the lumen, adjacent the site of the plaque or atherosclerotic lesion. The balloon is then inflated to put pressure on and “crack” the plaque. This procedure increases the cross-sectional area of the lumen of the artery. Unfortunately, the pressure exerted also traumatizes the artery, and in 30-40% of the cases, the vessel either gradually renarrows or recloses at the locus of the original stenotic lesion. This renarrowing is sometimes referred to as restenosis.
A common approach to prevent restenosis is to deploy a metallic tube or stent to the site of the stenotic lesion. Although metallic stents have the mechanical strength necessary to prevent the retractile form of restenosis, their presence in the artery can lead to biological problems including vasospasm, compliance mismatch, and even occlusion. Moreover, there are inherent, significant risks from having a metal stent permanently implanted in the artery, including erosion of the vessel wall. The stents may also migrate on occasion from their initial insertion location raising the potential for stent induced blockage. Metal stents, especially if migration occurs, cause irritation to the surrounding tissues in a lumen. Also, since metals are typically much harder and stiffer than the surrounding tissues in a lumen, this may result in an anatomical or physiological compliance mismatch, thereby damaging tissue or eliciting unwanted biologic responses. In addition, the constant exposure of the stent to the blood can lead to thrombus formation within the blood vessel. Stents also allow the cellular proliferation of the injured arterial wall to migrate through the stent mesh, where the cells continue to proliferate and eventually lead to the narrowing of the vessel. Further, metal stents typically have some degree of negative recoil. Finally, metallic stents actually prevent or inhibit the natural vascular remodeling that can occur in the organism by rigidly tethering the vessel to a fixed, maximum diameter.
Because of the problems of using a metallic stent, others have recently explored use of bioabsorbable and biodegradable materials stents. The conventional bioabsorbable or bioresorbable materials from which such stents are made can be selected to absorb or degrade over time. This degradation enables subsequent interventional procedures such as restenting or arterial surgery to be performed. It is also known that some bioabsorbable and biodegradable materials tend to have excellent biocompatibility characteristics, especially in comparison to most conventionally used biocompatible metals. Another advantage of bioabsorbable and biodegradable stents is that the mechanical properties can be designed to substantially eliminate or reduce the stiffness and hardness that is often associated with metal stents. This is beneficial because the metal stent stiffness and hardness can contribute to the propensity of a stent to damage a vessel or lumen. Examples of novel biodegradable stents include those found in U.S. Pat. No. 5,957,975 and U.S. application Ser. No. 10/508,739, which is herein incorporated by reference in its entirety.
For both metal and polymer stents, however, it is important to accurately place the stent into the vasculature. To visualize the stent placement, a metal stent can be coated with a radiopaque metal to allow real time visualization of the stent by the cardiologist or interventional radiologist. See, for example, U.S. Pat. Nos. 5,824,045 and 6,099,561. This allows the medical professional to track the delivery catheter through the patient's vasculature and precisely place the stent at the site of a lesion. Gold can be used as the radiopaque metal because gold is non-irritating and substantially non-allergic. Further, gold offers high fluoroscopic visibility in a very thin layer. Use of gold on a metal stent, however, may also result in an increase in corrosion where the two metals meet, thus further increasing thrombosis.
Conventional radiopaque metals, however, have a number of limitations. Completely coating a stent with the radiopaque metal may change the size of the stent, resulting in a less than ideal stent profile. Further, stents are often crimped to a smaller diameter to allow the stent to be easily inserted into the lumen. Once the stent is properly placed in the lumen, an inflatable device expands the stent. In this case, completely coating the stent with a radiopaque metal creates the risk of cracking the metal coating, thereby causing portions of the coating to separate from the underlying substrate. This can create jagged edges on the stent that inflicts increased physical trauma on the lumen wall tissue. Further, this may also induce thrombus formation because of increased turbulence in the blood flow. Finally, any material released can provide blockage and damage at sites distant from the initial stent positioning.
- SUMMARY OF THE INVENTION
Because polymeric stents are not radiopaque, there is no an ideal solution for determining the location, three-dimensional orientation and expansion of the stent in real time.
The present invention is directed to a polymer stent that comprises one or more markers such that when the stent is placed within a lumen, the markers can be detected external to the body. Examples of methods to detect the marker may include, but is not limited to, x-ray or other electromagnetic radiation detection method, magnetic resonance imaging (MRI), and ultrasound.
The markers may be used to track the location of the stent as it travels through the body. This greatly assists the physicians in determining if the stent is traveling the correct path through the vasculature. This further assists the physician in placing the stent at the correct site within the lumen. In some embodiments, these markers can also be used to monitor the stent position after placement and to monitor absorption of bioabsorbable stents.
In certain embodiments, it is contemplated that the stent may comprise at least two markers placed such that the diameter of the stent may be determined in real time. This feature helps to determine if a crimped stent has been properly expanded. The placement of such markers may also determine at any time if the diameter of the stent has increased or decreased.
In certain embodiments, it is also contemplated that the stent may comprise at least three markers. The use of at least three markers enables the three dimensional location of the stent to be determined at any time. This feature can be used to determine if the stent has a rotational motion within the lumen. Rotational motion of the stent within the lumen is disfavored because it increases blood flow turbidity, which increases thrombus formation.
In certain embodiments, it is also contemplated that the stent may comprise markers such that the markers are located in regions with different in vivo lifetimes. Stent regions with different in vivo lifetimes means that the in vivo lifetime of the region is predetermined and found to be different from the in vivo lifetime of a different region. This feature enables one to determine the degradation pattern of the stent in real time.
In certain embodiments, it is contemplated that the pattern and material type of markers on the stent may be such that one can determine the type of stent inserted within a lumen or within a box. This feature may greatly assist in determining and monitoring what type of stents is located within a package as the packages travel through the supply chain. This feature may also assist in determining what type of stent is located within a person post-implantation.
The marker may be any material that is visible within the body by an external means, including but limited to x-ray and MRI. In one embodiment, the stent of the present invention achieves MRI visibility by use of a marker that generates a magnetic susceptibility artifact such as a paramagnetic, ferromagnetic, non-ferromagnetic, ferromagnetic, or superparamagnetic substance. In another embodiment, the test of the present invention achieves visibility by x-ray by use of a radiopaque marker.
DESCRIPTION OF THE FIGURES
The markers may be applied to the stent in any number of ways for insertion or use in the body, including but limited to, application as a ribbon that is crimped onto a strut of the stent and a partially sputter heavy metal coating.
FIG. 1 illustrates a stent comprising one marker.
FIG. 2 illustrates a stent comprising two markers placed such that the diameter of the stent can be determined.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
FIG. 3 illustrates a stent comprising three markers placed such that the three-dimensional orientation of the stent can be determined.
It will be appreciated by those skilled in the art that although the following Detailed Description will proceed with reference being made to preferred embodiments, the present invention is not intended to be limited to these embodiments.
- I. Detectable Marker
In one embodiment, the present invention is directed to a polymer stent that comprises at least one marker, where the marker is provided to track the stent during its placement within the body. The stent of the present invention can have virtually any configuration that is compatible with the body lumen in which it is implanted for the purpose of repairing the same. Typically, stents are composed of an intricate geometric pattern of circumferential and longitudinally extending members. These elements are commonly referred to as struts.
The markers can be made of any material that may be detected external to the body. The only limitation on the type of marker used is that it be visible by external means and may be released safety from the stent as the stent degrades. If the marker is involved in the arterial remodeling, it may be retained by the body at the location of its initial placement. It is readily understood that many factors must be weighed in considering what marker will be used.
In one embodiment, the marker is detected by MRI. An ideal marker detectable by MRI would be one that generates a magnetic susceptibility artifact such as a paramagnetic, ferromagnetic, non-ferromagnetic, ferromagnetic, or superparamagnetic substance. If the marker is metal, then it may be, but is not limited to, ruthenium, rhodium, osmium, silver, palladium, platinum, lead, tin, uranium, molybdenum, brass, copper, tungsten, tantalum, gold, or other paramagnetic or ferromagnetic metals, gadolinium salts, gadolinium complexes, Gd-DTPA (gadolinium diethylenetriaminepentacetic acid), gadopentetate dimeglumine, compounds of copper, nickel, manganese, chromium, dysprosium and gadolinium. The marker may also contain organic components, such as a heme or porphyrin ring.
If the stent is to be viewed via x-ray, then the marker used may be any appropriate radiopaque material, including but not limited to, powder of barium sulfate, bismuth subcarbonate, bismuth trioxide, bismuth oxychloride, tungsten, tantalum, iridium, gold, platinum, palladium or other dense metal. Such radiopaque materials include particles of an iodinated contrast agent and bismuth salts. It is preferred that the radiopaque marker be a metal with a high atomic number element, preferably from the row of the periodic table coincident with the third row of the transition metal block.
The marker may be made by any means. If the marker is a metal, for example, gold, then the marker may be made by mechanically deforming the metal to form a sheet layer or ribbon. Examples of methods to mechanically deform the metal include, but are not limited to, rolling at a high temperature until a desired thickness of the layer is reached, folding the metal, and pounding the metal with heavy objects, heating the metal until the metal melts, then pouring the metal into a mold. If the metal is made into a sheet layer, then it may be cut by any means into any form that conforms to the invention.
It is further understood that the marker may be applied to the stent by any means. If the marker is a ribbon, then it may be placed onto the stent by any means. Preferably, the marker is a ribbon that is crimped upon a strut of the polymer after the stent is formed. Examples include, but are not limited to, crimping, folding, tying, melting, use of a knitten mesh, binding by use of a gluing compound, and winding around the polymer in a helical or zig-zag design. The application of the marker is only limited by the coefficients of expansion. The marker should be such that the coefficient of expansion of the stent is not significantly altered by the application of the marker.
Other methods contemplated for adding the marker to a polymer material include dip coating the marker onto the polymeric structure of a stent. Moreover, the marker, alone or blended with other materials, can be added to the surface of a device by way of a plasma spray or etch or by employing thermal pressure or heat and pressure. Steriolithography and blow molding are other contemplated approaches. In addition, the marker can be mixed with a biocompatible epoxy resin, whereby the marker is blended with another material and coated to the inner diameters, outer diameter or sides of structures defining the stent. The marker can also be chemically bonded to portions of the polymers used in the stents before or after manufacture of the stent. In any event, the metal marker can be applied to an entire surface of a device or in a partial, spot-like manner or as stripes or a series of spots or stripes, or any other combination. Further, it is also contemplated to use more than one type of marker, whereby each type of marker is separately detected by external means.
In addition, the marker may be of any thickness as long as the thickness does not alter the coefficient of expansion of the stent. Preferably, the marker thickness is approximately 0.25 to 30 microns. More preferably, the marker thickness is approximately 5 microns.
It is further contemplated that a polymeric stent may be made radiopaque by any means. For instance, one or more radiopaque materials may be introduced into the polymer solution before the stent is manufactured. In addition, to visualize the stent placement, a polymeric stent can be coated with a radiopaque material to allow real time visualization of the stent by the cardiologist or interventional radiologist. In this situation, it is preferred that the radiopaque material not flake off the polymeric material and have a coefficient of expansion that is consistent with the stent coefficient of expansion, thereby allowing both materials to expand equally.
- II. Stent Fabrication and Properties
Finally, it is contemplated that the marker is placed on the stent to form a pattern such that one can determine the type of stent inserted within a lumen or within the pre-surgery packaging of the stent. The pattern can be a geometric one, or a pattern of using different markers on the same stent, such as gold and platinum, which will provide a unique marker signature. This feature may greatly assist in determining what type of stent is located within a crate as the stent travels through the supply chain. This feature may also assist in determining what type of stent is located within a person post-surgery.
The stents may be formed from any biodegradable, biocompatible, bioresorbable polymer, preferably a thermoplastic polymer. As used herein, a bioresorbable polymer is one whose degradative products are metabolized in vivo or excreted from the body via natural pathways. The polymer of the stent can be a homopolymer or a copolymer. Preferably, the stent is formed from a thin layer of one or more amorphous, bioresorbable polymers, i.e., the polymers used to form the stent preferably are not crystalline. It is also preferred that the polymers used to form the stent do not generate crystalline residues upon degradation in vivo. It is also contemplated that the chains of the polymer may be or may not be cross-linked. Light cross-linking, however, is acceptable provided that thermal and viscoelastic characteristics that allow education, crimping, and deployment of the device are sufficiently maintained.
Appropriate biodegradable polymers may include, but are not limited to, poly(L-lactide), polyglycolide, poly(D,L-lactide), copolymers of lactide and glycolide, polycaprolactone, polyhydroxyvalerate, polyhydroxybutyrate, polytrimethylenecarbonate, polyorthoesters, polyanhydrides, and polyphosphazenes. Examples of the types of preferred polymers for the stent of the present invention include, but are not limited to, lactic acid-based stereocopolymers (PLAx copolymers composed of L and D units, where X is the percentage of L-lactyl units) (55<Tg<60), copolymers of lactic and glycolic acids (PLAxGAy, where X, the percentage of L-lactyl units, and Y, the percentage of glycolyl units, are such that the Tg of the copolymer is above 45° C.), and Poly(lactic-co-glycolic-co-gluconic acid) where the OH groups of the gluconyl units can be more or less substituted (pLAxGayGLx, where X, the percentage of Llactyl units, and Y, the percentage of glycolyl units, and Z the percentage of gluconyl units are such that the Tg of the polymer is above 45° C.). Other suitable polymers include, but are not limited to, polylactic acid (PLA), polyglycolic acid (PGA) polyglactin (PLAGA copolymer), polyglyconate (copolymer of trimethylene carbonate and glycolide, and a copolymer of polyglycolide or lactide acid or polylactic acid with ε-caprolactone), provided that the polymer has a glass transition temperature, Tg, of at least 45° C. or greater.
In one preferred embodiment, the stent comprises a polylactic acid stereocopolymer produced from L and DL lactides. The polymer is designated herein as “PLAX” where X represents the percentage of the L-lactic acid units in the mixture of monomers used to prepare the lactides. Preferably X is in the range of 10 to 90, more preferably 25 to 75. In another preferred embodiment, the stent comprises a poly-lactic acid, glycolic acid copolymer produced from L and DL lactides and glycolides. The polymer is designated herein as “PLAXGAY” where Y represents the percentage of glycolic acid units in the mixture of monomers used to prepare the copolymers. Preferably, the copolymers do not contain glycolyl repeating units since such units are known to be more inflammatory than lactyl repeating units. Preferably, the polymers are prepared using Zn metal or Zn lactate as initiator. To ensure good initial mechanical properties of the stent, the molecular weight of the polymer in the region having the second in vivo lifetime is preferably above 20,000 daltons, more preferably 100,000 daltons or larger. The polydispersity, I=Mw/Mn, is preferably below two and should not greatly reflect the presence of low molecular weight oligomers smaller than 2,000 daltons as determined by size exclusion chromatography. Optionally, the polymeric layer used to make the stent may be impregnated with an anticoagulant agent, such as heparin, anti-oxidants, such as vitamin E, compounds that regulate cellular proliferation, or anti-inflammatory drugs, such as corticosteroids, to provide localized drug delivery. Such drugs are incorporated into the polymeric layer or coated on the layer using techniques known in the art. Agents may also be incorporated into the base polymer that forms the body of the stent, as long as the incorporation does not have significant adverse effects on stent desired physical characteristics such as radial stent deployment and degradation time. For intravascular stents, it is preferred that the film have a thickness of from about 0.05 mm to 0.2 mm.
It is contemplated that the stent may be made by any method. In one preferred embodiment, the stent is a formed from a biodegradable polymeric band comprising a head having a slot and a tongue comprising a catch or locking mechanism proximate the longitudinal edge thereof. The cylindrical element, which has an inner and outer surface, is formed by inserting a portion of the tongue through the slot to provide a cylindrical element having a first reduced diameter configuration. Following deployment, the cylindrical element is in a second expanded diameter configuration wherein the distal catch mechanism engages the inner surface of the head and prevents radial collapse or recoil of the polymeric stent. In a second preferred embodiment, the stent is formed from a plurality of interconnected polymeric bands each of which comprises a head having a slot and a tongue comprising a catch mechanism proximate the longitudinal edge thereof.
In one embodiment, the stent is formed by laser cutting of a cylindrical tube. In another embodiment, the stent is formed by laser cutting a flat polymeric sheet in the form of the stent, and then rolling the pattern into the shape of the cylindrical stent and providing a longitudinal weld to form the stent. In another embodiment, the stents are created by chemically etching a flat polymeric sheet and then rolling and welding it to form the stent, or coiling a polymeric wire to form the stent.
In another preferred embodiment, the stent may also be formed by molding or injection molding of a thermoplastic or reaction injection molding of a thermoset polymeric material. The flat grid is then rolled and extremities are welded or glued to form a cylinder. Filaments of the compounded polymer may be extruded or melt spun. These filaments can then be cut, formed into ring elements, welded closed, corrugated to form crowns, and then the crowns welded together by heat or solvent to form the stent. Lastly, hoops or rings may be cut from tubing stock, the tube elements stamped to form crowns, and the crowns connected by welding or laser fusion to form the stent. In other embodiments, the stent is formed as a cylindrical tube and then a pattern is cut with a laser or other device.
Generally, the struts are arranged in patterns that are designed to contact the lumen walls of a vessel and to maintain patency of the vessel thereby. A myriad of strut patterns are known in the art for achieving particular design goals.
It is contemplated that a crimped stent may incorporate slits or open spaces to allow for the temporary reduction in diameter of the cylindrical tube without substantially altering the wall thickness. Moreover, a stent embodying the present invention can include teeth and corresponding catching structure that operates to maintain an expanded form. Moreover, polymer based stents embodying structure defined by a wire or ribbon coil or helix or a knitted mesh configuration are possible examples of self-expanding stents. Other important design characteristics of stents include radial or hoop strength, expansion ratio or coverage area, and longitudinal flexibility. One strut pattern may be selected over another in an effort to optimize those parameters that are of importance for a particular application.
It is also contemplated that the biodegradable stent may have a programmed pattern of in vivo degradation. Stent polymeric structure allows for differential speed degradation. See, for example, U.S. Pat. No. 5,957,975, the entirety of which is incorporated by reference. In one embodiment, the stent comprises at least one substantially cylindrical element having two open ends and a plurality of regions circumferentially spaced around the cylindrical element and extending from one open end to the other open end of the cylindrical element. Each of the regions is configured or designed to have a desired in vivo lifetime. At least one of the regions is designed to have a shorter in vivo lifetime than the other region or regions. This means that the region having the shorter in vivo lifetime degrades sooner after deployment than the regions having a longer in vivo lifetime. Thus, when stents designed in accordance with the present invention are deployed within the lumen of a vessel of a patient, the cylindrical element acquires one or more fissures which extend from one open end of the cylindrical element to the other open end of the cylindrical element within a desired, predetermined period of time after the stent is deployed in the patient. It has been determined that such fragmentation within a predetermined period of time after deployment allows for enlargement of the lumen of the vessel via the process of arterial remodeling.
The regions of the stent with the different in vivo lifetimes can be made in a variety of ways. Preferably, such stents are made by producing regions having a first in vivo lifetime, i.e., a shorter in vivo lifetime, in a polymeric layer having the predetermined second, or longer, in vivo lifetime. The regions having the first in vivo lifetime are produced by heating the respective regions of the polymeric layer having a second in vivo lifetime for a time and at a temperature sufficient to cause local partial degradation of the polymeric chains. Such treatment, which can be accomplished using a piloted hot needle, laser beam, or flow of hot air, renders the polymer in the heated region more sensitive to hydrolytic degradation. The regions can also be designed with struts of differing thickness where the degradation is thickness dependent. Alternatively, the regions having a first in vivo lifetime may be produced in a polymeric layer having a second in vivo lifetime by incorporating a sufficient number of acidic ions into the respective regions of the polymeric layer. Preferably, the acidic ions are provided by compounds that are not soluble in blood.
Regions having a first in vivo lifetime can also be produced in a polymeric film having a second in vivo lifetime by exposure of the respective regions to beta radiation or gamma radiation for a sufficient time to induce partial cleavage of the polymeric chains within the respective regions. Provided the polymeric layer has a thickness of less than 0.3 mm, regions having a first in vivo lifetime can also be produced in a polymeric film having a second in vivo lifetime by introducing areas of mechanical weakness into the polymer. One method of introducing mechanical weakness is by reducing the thickness of the polymer in the respective region or forming holes therein. Regions having a first in vivo lifetime can also be produced in a polymeric film having a second in vivo lifetime by applying mechanical stress to the respective region. However, this latter process is difficult to control and, thus, is less preferred. Differing lifetimes can also be created by providing one or more different coatings over different regions of the biodegradable stent.
Another method for producing a polymeric layer in which one region or a plurality of spaced apart regions have a first in vivo lifetime and other regions have a second in vivo lifetime is to incorporate strips or fibers of a faster degrading bioresorbable polymer into a film made from a slower degrading polymer. For example, a mesh or a parallel array of fibers or strips of PGA or any other faster degrading bioresorbable polymer can be embedded into the respective regions of a polymeric film of PLA that may be designed to be slower degrading. Embedding can be achieved by inserting the mesh or fibers between two melted sheets of the slower degrading polymer. Provided the relative solubilities are compatible, the fibers or mesh can be placed in an organic solution of the slower degrading polymer and the desired polymeric film formed by evaporation of the organic solvent. One example of a method for embedding a mesh made from one polymer into a polymeric layer made from a second polymer is described in U.S. Pat. No. 4,279,249 issued to Vert et al. on Jul. 21, 1981, which is specifically incorporated herein by reference. A stent having the desired shape and orientation of regions is then formed from the polymeric layer by standard techniques such as stamping, employing a laser beam, or any other technique used in the art to tool a polymeric film.
The initial polymeric cylindrical device that is formed by any of these processes can be configured to have the final predetermined shape, length, wall thickness and diameter, all of which are tailored to the application for which the stent is to be utilized. For example, for cardiovascular applications the initial polymeric device that is formed by these processes can have a final predetermined length ranging from 0.5 cm to approximately 3 cm. For certain applications, the initial polymeric cylindrical device can have a final, predetermined diameter ranging from 0.50 mm to 8.0 mm with a final, predetermined wall thickness ranging from 0.05 to 0.5 mm. Alternatively, the initial cylindrical device that is formed by any of these processes can have a smaller diameter than the final predetermined diameter.
In those instances where the initial polymeric cylindrical device has a smaller diameter than the final predetermined diameter, slits or openings are formed in the cylindrical device as described above, and then the cylindrical device is deformed or expanded to the final shape and diameter. This can be achieved by inserting an expandable device such as a balloon into the stent.
- III. Education and Crimping the Stent
The length, diameter, and strut thickness of the stent can be of any size. However, it is contemplated that these parameters will be limited by the performance features desired. Further, the stent maybe used for any tubular body structure, including but not limited to, coronary, neurological, carotid, renal, iliac, biliary, aortic, femoral, or other peripheral indication.
While it is at the final predetermined shape, size, and diameter, the cylindrical device is educated by heating the device to a temperature above the Tg of the polymer from which the device is formed. The device is heated for a time sufficient to erase any former process-related memory and to impart a new memory of the final predetermined shape and diameter to the polymeric cylindrical device. It is believed that such conditions allow the polymer chains to relax and reorganize themselves from an entanglement typical of the former processing stages to an entanglement typical of the high temperature at which the cylindrical device is compatible with the final or deformed shape and size. When the polymeric cylindrical device has an initial diameter that is less than the final predetermined diameter, it is desired to heat to a temperature well above the Tg of the polymer. This heating step erases the anisotropic stresses promoted by the extrusion or molding process and the former processing-related memory of the polymer chains. Good results have been obtained by heating a laser-precut polymeric cylindrical device formed from PLA75 and deformed from a diameter of 1.0 mm to 4 mm at a temperature of 80° C. for 30 minutes. Temperatures of from about 45° C. to about 120° C. and times of 5 minutes or more should be suitable for educating stents made from PLAx with 0<x<100, PLAxGAy with 0<X<25 and 75<Y<100, or any PLAxGAyGLz.
The polymeric cylindrical device is then crimped. “Crimping” as used herein refers to a process that involves radial pressing on a polymeric cylindrical device having slits, or openings in the wall thereof to allow a decrease in the diameter of the device without substantially affecting the thickness of the wall or struts of the cylindrical device. Such process may also result in an increase in length of the cylindrical device. Examples of crimping may be found in U.S. application Ser. No. 10/541,421, which is incorporated by reference.
To crimp the educated cylindrical device, it is mounted onto a device with a smaller diameter. The diameter of the educated cylinder is reduced by heating the cylinder to a temperature below the Tg of the polymer while evenly applying pressure on the exterior surface of the wall of the cylindrical device.
In some embodiments, the polymeric stent is crimped onto an inflatable device such as an inflatable balloon catheter. In this instance, the stent assembly after crimping comprises an inflatable balloon catheter and an expandable, educated, polymeric stent snugly and stably disposed thereon. Slits or open spaces that allow for a reduction in diameter of the cylindrical device without substantially altering the wall thickness during crimping are incorporated into the cylindrical device prior to the time the cylindrical device is crimped on the inflatable balloon catheter. The temperature at which the cylindrical device is heated during crimping is high enough to allow reduction in diameter of the cylindrical device but low enough to not erase the memory of the final predetermined shape and diameter of the educated cylindrical device. Ideally, the temperature is less than the glass transition state of the polymer. More preferably, the temperature is at about 50° C. Thus, the temperature at which the educated cylindrical device is heated during crimping is less than the temperature at which the cylindrical device is heated during education of the cylindrical device. Further, the time it takes to crimp the educated cylindrical device can vary, depending upon the temperature, size and composition of the stent
In accordance with the present method, expansion of the polymeric stent can be achieved by any means. In one embodiment, a balloon is used merely as a carrier for the stent through the body. In this preferred embodiment, the stent expansion occurs by the positive recoil properties of the stent; thus, the expansion is balloon inflation independent. In another preferred embodiment, a balloon is inflates and/or heated to initiates the stent expansion. It is contemplated that the positive recoil properties of the stent would expand the stent to its final predetermined diameter. The temperature used to initiate the stent expansion may be any temperature at or below the Tg of the polymer. In a less preferred embodiment, a balloon is inflated to expand the polymeric stent to its final predetermined shape.
In another aspect, the method of the present invention starts with a polymeric tube whose diameter initially is less than the final predetermined diameter. Such tube is first heated to a temperature close to or above the Tg of the polymer and expanded to provide a cylindrical device whose diameter is equal to the final desired diameter. Thereafter the cylindrical device is educated as described above to provide an educated cylindrical device having a memory of the final predetermined shape and diameter, and then crimped on a balloon catheter as described above to provide an assembly comprising the balloon catheter and an expandable, educated, polymeric stent snugly and stably disposed thereon.
The present invention also provides an assembly comprising an inflatable balloon catheter and a polymeric stent prepared in accordance with the present method.
Advantageously, the stent of the present invention exhibits little to no relaxation-related negative recoil when deployed in the blood vessel of a subject. Advantageously, the assembly of the present invention has a diameter that allows it to be easily inserted into a blood vessel of the subject and advanced to a target site. Advantageously, the stent of the present invention exhibits expansion (positive recoil) and adaptation to the geometry of the artery when the stent is not fully deployed up to its final diameter during deployment. Positive recoil over several days will create outward radial pressure for long periods of time. This outward radial pressure aids in positive vascular remodeling by assisting stabilizing the injured artery, assist in cellular progress to repair injury of original acute expansion, assist in security of tissue flaps, and the like.
- IV. Stent Placement and Tracking
In addition, the stent of the present invention is stably disposed on the balloon, meaning that a mechanical restraint is not required to prevent the stent from rapidly expanding to its final diameter during storage at room temperature. Thus, although not required, the assembly of the present invention, optionally, also comprises a retractable sheath covering the exterior surface of the stent. Such sheath serves to prevent deformation of the stent and preclude or slow expansion during storage.
The stent may be implanted within the body by any means. For instance, it is contemplated that stent of the invention is mounted upon a catheter having a lumen and an inflation member such as a balloon. The stent and catheter are inserted into the lumen of an arterial wall, duct, or other tubular body structure. The stent may be expanded by any means. After expansion, the stent remains within the body to provide radial support for the treated tubular body structure. For instance, the stent may be used to repair an arterial dissection, or an intimal flap, both of which are commonly found in the coronary arteries, peripheral arteries and other vessels.
However, in all cases, the placement of the stent must be accurate. Therefore, it is critical that the markers on the stent be sufficiently visible external to the body so that the physician can visually locate the stent during the implantation procedure. Because the stent of the present invention can be made visible under, for example, x-ray and MRI, it gives the physician the option of selecting the imaging modality most appropriate for the procedure. It is preferred that the movement of the stent can be detected by the physician in real time as the stent is advanced through the vessel or duct. By knowing the exact location and orientation of the stent at any time, the physician can advance to the stent to the area of the lumen that requires the stent. One embodiment is show in FIG. 1, where by stent (B) comprises one marker (A) which is crimped onto one strut of the stent.
The stent may be delivered to the lumen of the vessel or duct by any means. In one embodiment, an assembly comprising the stent with the markers of the present invention is mounted on an expandable catheter, preferably a balloon catheter, is percutaneously introduced into a vessel. Optionally, if the stent is provided with a membrane that keeps the stent secured to the balloon catheter, the stent may be heated for a time to a temperature sufficient to provide greater malleability to the stent. The catheter is advanced with the aid of a guidewire and under fluoroscopic control to the site of the stenotic lesion. The balloon and stent are then disposed within the constricted portion of the vessel.
After the stent and balloon are delivered to the locus of the stenotic lesion, the optional membrane is removed. The balloon is first heated and then inflated to expand the stent from the first configuration that has a reduced diameter to a second configuration having an enlarged diameter greater than or equal to the interior of the passageway wall so that the stent abuts the wall of the vessel. The diameters of the cylindrical element depend on the size of the passageway into which the stent is introduced. Typically, for coronary arteries, the reduced diameter of the cylindrical element prior to deployment is from about 0.5 to about 1 mm and expanded diameter after deployment is from about 3 mm to about 5 mm.
It is further contemplated that fracturing of the plaque and deployment of the stent may be done concurrently. In such cases, the balloon is inflated to a pressure of about 8 to 12 atmospheres to crack the plaque and expand the stent. Alternatively, the vessel may be pre-dilated using angioplasty without the stent. Thereafter, the stent is introduced into the desired site on a separate expandable catheter, preferably a balloon catheter.
After the stent is positioned at the site but before expansion, the stent is heated to a temperature greater than the glass transition temperature of the polymers used to form the stent. Heating is for less than 30 seconds, preferably less than 10 seconds. Heating of the stent prior to expansion thereof makes the stent more malleable and avoids development of unprogrammed ruptures in the stent. Heating prior to expansion also permits the tongue to go through the slot without breaking, thereby avoiding damage to the locking mechanism. Such heating also gives the polymeric stent a second memory of the second expanded diameter configuration. Such second memory aids in preventing radial collapse of the stent before the time period defined by the first in vivo lifetime. Suitable methods for heating the stent during or after expansion include, for example, use of a laser balloon or a radiofrequency balloon.
In another preferred embodiment, the stent comprises at least two markers placed such that the length of the stent can be determined. The length of the stent may be determined by examining the location of the two markers relative to one another. The determination of the length may be done by any mean, including but not limited to, complex algorithms and software programs. The length of the stent may then be compared to the ideal length of the stent to find if there was any error or issue with the stent deployment.
In another preferred embodiment, the stent comprises at least two markers placed such that the diameter of the stent can be determined. For instance, FIG. 2 illustrates a stent (B) comprising two markers (A) crimped onto the struts of the stent. The two markers (A) placed such that the diameter (X) can be determined. The diameter of the stent may be determined by examining the location of the two markers relative to one another (X). The determination of the diameter may be done by any mean, including but not limited to, complex algorithms and software programs. The diameter of the stent may then be compared to the ideal diameter of the stent to find if there was any error or issue with the stent deployment.
In one preferred embodiment, to determine the length of stent placed within a body lumen of a patient, a first and second marker are upon the struts of a stent so that the markers are spatially oriented such that the markers lie on a line with a component vector parallel to the longitudinal axis of the stent. The polymer stent is then placed within a body lumen of patient and a signal is generated using a machine external to the body lumen. The location of the first and second marker is determined relative to one another and the distance between them is calculated by a software program or algorithm. This method may also be used to determine the diameter of the stent within the body lumen by crimping the first and second marker so that they lie on a line with a component vector perpendicular to the longitudinal axis of the stent.
Once expanded, the stents are ideally retained in position by friction with the inner wall of the vessel and the memory imparted by heating the stent prior to expansion. However, it is also recognized that the three dimensional orientation of a stent with at least three markers can be determined. In one embodiment, the three dimensional orientation of the stent may be determined by crimping a first and second marker upon a stent so that the markers are spatially oriented such that the markers lie on a line with a component vector perpendicular to the longitudinal axis of the stent, and then crimping a third marker upon the stent so that the third marker is spatially oriented such that the third marker lies on a line with a component vector parallel to the longitudinal axis of the stent. For example, FIG. 3 illustrates a stent (B) comprising multiple markers (A) that are crimped onto a strut of the stent. The multiple markers (A) are placed such that they have a different X, Y and Z orientation from each other. By examining the positioning of the markers (A) to one another, one can determine the X, Y and Z coordinates of the stent to find the three dimensional location. Once the three dimensional location is determined, one can find if the stent is correctly retained in position or if the stent is rotating within the lumen. Rotation within the lumen is disfavored as the rotation may increase blood flow turbidity and thus increase thrombis formation. Further, the determination of the three-dimensional orientation of the stent may be done by any means, including but not limited to, complex algorithms and software programs.
It is further contemplated that the markers may be placed such that the in Vivo lifetime of the stent regions can be determined. For instance, in one preferred embodiment the markers are placed within different regions of the stent. In some embodiments, the gold foil or marker can be placed under mechanical tension due to the attachment to the stent walls. As the regions degrade, the markers assume orientation that differ from their original placement. Thus, examining the marker placement over time can show the pattern of degradation of the stent in vivo. Eventually, when the regions having the first in vivo lifetime are degraded, the stent is fragmented and the regions having a second in vivo lifetime are entrapped within the arterial intima.