Description of The Preferred Embodiment
Stent design
The present invention relates to a radially expandable stent for use in expanding or expanding a target region in a body lumen. In a preferred embodiment of the invention, the assembled stent comprises a tubular member to be inserted into a body lumen of suitable size having a length along the longitudinal axis and a diameter along the radial axis. As discussed below, the length and diameter of the tubular member may vary significantly to facilitate deployment in different selected target body lumens, depending on the number and configuration of the structural members. The tubular member is adjustable from at least a first collapsed diameter to at least a second expanded diameter. One or more stops and engagement elements or tabs are included in the structural member of the tubular member, thereby minimizing "retraction" (i.e., contraction from an expanded diameter to a contracted diameter) to less than about 5%.
The tubular member according to the invention has an "open through lumen", the latter being defined as a structural element which does not protrude into the lumen of the contracted or expanded diameter. Second, the tubular member has smooth edges to minimize damage caused by the edges. The tubular member is preferably thin-walled (wall thickness depends on the material selected, from less than about 0.006 inch for plastic and degradable materials to less than about 0.002 inch for metallic materials) and flexible (e.g., less than about 0.01 newton force/mm deflection) for delivery into small vessels and through tortuous vasculature. The thin-walled design will also minimize the blood turbulence and the resulting risk of thrombus formation. The thin-walled profile of the tubular member deployed in accordance with the present invention also facilitates faster endothelial healing of the stent.
The wall of the tubular part comprises at least one module consisting of a series of sliding elements and radial locking elements. Preferably, a plurality of modules are connected along the longitudinal axis by connecting elements which link radial elements between at least several adjacent modules. The radial elements are shaped to form the circumference of the tubular member in each module. Each radial element in a module is preferably a discrete unitary structure comprising one or more circumferential ribs curved along a radial axis to form a portion of the overall circumference of the tubular member. The radial elements in a module are preferably assembled so that all circumferential ribs are substantially parallel to each other. At least one rib in each radial element has one or more stops disposed along the length of the rib. At least some of the radial elements also have at least one articulating mechanism for slidably engaging ribs from adjacent circumferentially offset radial elements. In one aspect of the invention, the articulating mechanism includes a tab for engaging a stop disposed along adjacent slidably engageable ribs. The articulation between the tabs of one radial element and the stops of an adjacent radial element is such as to form a locking or snap-in mechanism whereby adjacent radial elements can slide circumferentially away from each other but cannot substantially slide circumferentially toward each other. Thus, the tubular element can be radially expanded from a smaller diameter to a larger diameter, but retracted to the smaller diameter is minimized due to the locking mechanism. The amount of retraction can be specifically designed for the application by adjusting the size and spacing between stops along each rib. Preferably, the retraction is less than about 5%.
Some aspects of the present stent are disclosed in U.S. patent No.6,033,436 and pending U.S. application No.09/283,800 issued to Steinke. The disclosure of which is incorporated herein by reference in its entirety.
Referring to fig. 1A-1C, there is illustrated a plan view of a module 10, the module 10 including a sequence of sliding and locking radial elements 20 according to one embodiment of the present invention. The illustrated module is a two-dimensional planar surface. Each radial element has one or more elongated ribs 22 (along the vertical axis) with a substantially vertical end portion 24 (along the horizontal axis) permanently secured to each end of each rib. Each rib has at least one stop 30. The radial elements in the module alternate from a one-rib configuration 20' to a two-rib configuration 20 ". The illustrated one-rib configuration 20' has a single rib with a plurality of stops 30, while the illustrated two-rib configuration 20 "has two ribs, each with a plurality of stops 30. Radial elements according to the present invention may have different numbers of circumferential ribs 22, however, it is preferred that vertically adjacent radial elements alternate between an odd-numbered rib configuration and an even-numbered rib configuration, as shown in FIGS. 1A-1C.
The odd-even alternation in adjacent radial elements facilitates nesting in modules within the circumferential rib 22 while maintaining a constant width (W). However, if the radial elements are made in different shapes, for example parallelograms instead of rectangles, in which the ribs assume a non-circumferential orientation, a change in the axial length of the module will occur upon expansion of the tubular element. Such variations are included in the present invention.
Referring to fig. 1A-1C, some of the end portions 24 of the radial elements 20 in the illustrated design are shown with articulating mechanisms 34, each mechanism 34 including a slot 36 and a tab 32, the slot 36 for slidably engaging a rib of a vertically adjacent radial element, and the tab 32 for engaging a stop 30 in the slidably engaging rib. The end portion 24 of one rib radial element 20' is generally adapted to articulate with each rib 22 of a vertically adjacent two rib radial elements 20 "that are slidably engaged. The end portions 24 of two-ribbed radial elements 20 "are generally adapted to articulate with the individual ribs 22 of a vertically adjacent one-ribbed radial element 20' that can be slidably engaged. The articulating mechanism is shown in more detail in fig. 2A and 2B. The stops 30 may be evenly distributed along the entire length (as shown on the second radial element from the bottom) or the stops may be unevenly distributed along the ribs (as shown in the uppermost radial element).
The articulation between the tab 32 of one radial element and the stop 30 of an adjacent radial element creates a locking or snap-in mechanism such that only one-way sliding (expansion) occurs. Thus, the sequence of radial elements in plan view as shown in FIGS. 1A-1C can be adjusted from the contracted state shown in FIG. 1A to the partially expanded state shown in FIG. 1B to the fully expanded state shown in FIG. 1C. Expansion of the module 10 in plan view may be achieved by applying opposing forces (arrows). The nested sliding and locking radial elements 20 slide away from each other, increasing the height (h) of the series along the vertical axis, without changing the width (W) of the series along the horizontal axis. The locking mechanism formed by the articulation between the tabs 32 and the single stop 30 prevents the expanded series from retracting to a more retracted height.
When the module 10 is rotated to form a tubular component, a slidable articulation may be formed between the ends on the radial elements on the top of the module and the ribs from the radial elements on the bottom of the module. Also, a slidable articulation may be formed between the end on the radial element on the bottom of the module and the two ribs from the radial element on the top of the module. In one variation, after being rotated to form a tubular member, the top and bottom ends can be interconnected using various fastening mechanisms known in the art, including welding, adhesives, mechanical fastening mechanisms, snap fastening mechanisms, or the like. In other words, dedicated structural members may be included to facilitate coupling of the top and bottom portions of the rotating module. Examples of dedicated peripheral coupling elements are detailed below with reference to fig. 4A and 4B.
Referring to fig. 2A and 2B, the individual one-rib 20' and two-rib 20 "radial elements are shown in greater detail, respectively. The one-rib radial element 20' of fig. 2A and the two-rib radial element 20 "of fig. 2B have at least one circumferential rib 22 and one end 24 on each end of the rib. The rib has one or more stops 30 disposed along the length of the rib 22. One end of each of the illustrated radial elements includes an articulating mechanism 34 comprised of a tab 32 and a slot. Also illustrated in fig. 2A and 2B is a connecting element 40 that extends laterally from the end 24 of the radial element. These connection elements 40 are used to link the radial elements between adjacent modules. These connecting elements may extend from one or both ends 24 of either one rib 20' or two rib 20 "radial elements. In a preferred form (as shown), the connecting elements 40 extend from both ends 24 of a rib radial element 20'. The configuration and angle of these attachment elements can vary, depending essentially on the desired attachment distance between the modules and the desired flexibility and surface area of coverage of the stent.
In fig. 3 is shown a tubular component formed from a single module 10 comprising four one-ribbed radial elements 20' and four two-ribbed radial elements 20 "similar to the plan views described with reference to fig. 1A-1D and fig. 2A-2B. These radial elements forming the wall of the tubular part alternate between having an odd number and an even number of circumferential ribs 22. Each rib in the illustrated module has one or more stops 30. An articulating mechanism (shown in more detail in fig. 2A and 2B) has a tab 32, which tab 32 engages the stop and prevents the tubular member from collapsing to a smaller diameter. Each radial element constitutes a portion of the overall circumference of the tubular member (in this case circumferential 1/8). Preferably, the total number of radial elements making up a module varies between about 2 and 12. More preferably, the number of radial elements is 4 to 8. The connecting elements 40 are shown extending laterally from both sides of the module. The connecting element 40 is used to couple the module to a similar module to form a tubular member having a greater longitudinal length.
A variation of the basic module design described above with reference to fig. 1A-1D and fig. 2A-2B is shown in fig. 4A and 4B. The module is illustrated in plan view in both a contracted state (fig. 4A) and an expanded state (fig. 4B). In this variation of the stent, similar to the earlier design, the module 110 includes a sequence of sliding and locking radial elements 120. Each radial element has one or more elongated ribs 122 (along the vertical axis) with a substantially vertical end 124 (along the horizontal axis) permanently affixed to each end of each rib. Each rib has one or more stops 130. The radial elements in the module alternate from one rib configuration 120' to two rib configurations 120 ". One rib configuration 120' has a single rib 122 with one or more stops 130, while the two rib configuration 120 "has two ribs, each with one or more stops 130.
Like the modules previously described, the odd-even alternation in adjacent radial elements facilitates nesting the circumferential rib 122 in a module while maintaining a constant width (W). The ends 124 of the radial elements 120 in the illustrated design are shown with the movement mechanisms 134, each movement mechanism 134 being defined by a slot 136 for slidably engaging a rib from a vertically adjacent radial element and a tab 132 for engaging the stop 130 in the slidably engaging rib. Feathered edges 138 of the articulating mechanism 134 shown in fig. 4A and 4B indicate where the articulating mechanism has been welded to the ends 124 of the respective radial elements, creating slots 136 through which the engaged ribs can slide. The two ends 124 of one rib radial element 120' are generally adapted to articulate with each rib 122 from the vertically adjacent two rib radial elements 120 "that are slidably engaged. The two ends 124 of a two-ribbed radial element 120 "are generally adapted to articulate with the individual ribs 122 of a vertically adjacent one-ribbed radial element 120' that may be slidably engaged. The stops 130 may be evenly distributed along the entire length (as shown), or the stops may be unevenly distributed along the rib, or there may be only a single stop.
In fig. 4A and 4B, a flange 161 is also shown on a rib radial element 120'. The flanges can be included along the length of the rib to provide a temporary stop. During expansion, the rib with flange 161 temporarily stops sliding as flange 161 enters slot 136 of articulating mechanism 138. This temporary stop allows the other elements to fully expand before the temporary stop is overcome by the additional radial expansion force. The inclusion of one or more such flanges in the module facilitates uniform expansion of the radial elements within the module. In addition to or as an alternative to the temporary stop created by the flange 161, some elements may have only one stop, such that the element expands to the stop first, while other elements have multiple stops that provide the preferred expansion step.
The articulation between the tab 132 from one radial element and the stop 130 from an adjacent radial element forms a locking or snap-in mechanism so that only one-way sliding (expansion) occurs. The nested, sliding and locking radial elements 120 slide away from each other, increasing the height of the sequence to along the vertical axis without changing the width of the sequence to along the horizontal axis. The locking mechanism formed by the articulation between the tabs 132 and the single stop 130 prevents the expanded sequence from retracting to a more contracted height.
The module 110 shown in fig. 4A and 4B includes a floating coupling member 150 shaped like the end 124 of the two-ribbed radial member 120 "and having a peripheral rib 122 adapted to slidably engage a ribbed radial member 120'. In a variant of the illustrated embodiment, the floating coupling element may be adapted to float on more than one rib of a radial element having two or more circumferential ribs. Coupling member 150 is also adapted to couple ends 124 of top radial members 121 in the sequence. Both coupling member 150 and end 124 on top radial member 121 are shaped with coupling arms 152, 1543 and 152 ', 154', which may assume a complementary configuration as shown.
Another specific mechanism illustrated in fig. 4A and 4B is a frame member 160 from which the connecting member 140 extends laterally away from the frame member 160. In the module shown in fig. 4A and 4B, the frame element 160 is utilized on only one rib radial element 120'. The illustrated frame member is attached to and extends between the two ends 124 of a rib radial member 120' such that the circumferential rib 122 is surrounded or framed by the two ends 124 and the two frame members 160. The use of frame members to facilitate the coupling of adjacent modules has several advantages. These frame members create additional physical support to the vessel wall. The larger surface area of the individual elements may be desirable in certain circumstances, firstly to provide greater support to the surrounding body cavity, and secondly, to provide a larger carrier for site-directed introduction of the bioactive agent (discussed below). Alternatively, smaller surfaces can be made to minimize the impact of the stent material on the vessel wall, such as with narrow ribs and frame members. By suspending the connecting elements 140 laterally outwardly from the radial elements, these frame elements minimize the length of the connecting elements 140 required to couple adjacent modules while at the same time spacing the sliding ribs of one module from the sliding ribs of an adjacent module. The coupling of connecting elements 140 in adjacent modules forms a very flexible stent. Frame member 160 also carries the bending, allowing much greater movement, thus increasing the degree of flexure. In a variant of this, the frame element can be used in a radial element with more than one rib. See, for example, fig. 5, which shows a modular design comprising a sequence of two-ribbed radial elements, each element having a plurality of frame elements.
Referring to fig. 5, a variation of the odd-even radial elements is shown, wherein each of the two illustrated radial elements 220 has two circumferential ribs 222 and two articulating mechanisms 234 disposed on at least one end 224 of the radial element and including a tab 232 and a slot 236. As in previous versions of the invention, these peripheral ribs may have a plurality of stops 230 disposed along the length of the rib. Each radial element has a frame element 260 which is substantially rectangular in shape (connecting elements not shown). The frame element may be of any shape consistent with the function of surrounding the ribs and providing a connection point for coupling the radial elements of adjacent modules. These frame elements preferably nest the ribs in both the contracted and expanded states without overlapping stent components, which would increase the thickness of the stent.
The shape of these frame elements can be varied to create a circumferential balance of different radial elements with an odd or even number of ribs. For example, referring to FIG. 6, the lateral couplings of a pair of radial elements from one module (a one-rib radial element 320' and a two-rib radial element 320 ") are connected to the connecting elements 340 of another pair of radial elements from an adjacent module. The frame member 360 is illustrated in this embodiment as surrounding only one rib radial member 320'. The frame members 360 are shaped to facilitate nesting (without overlap) of the ribs 322 and frame members 360, minimize lateral space between modules, and facilitate attachment of the peripherally rather than longitudinally oriented connecting elements 340, thereby minimizing peripheral bridging and radial support.
Referring to fig. 7, a variation of the coupling mechanism between adjacent modules is illustrated. No separate connecting element is used. Instead, the frame elements of adjacent modules may be assembled to be interconnected as shown by interweaving. This coupling between adjacent modules allows for a much greater degree of flexibility of the stent.
Referring to fig. 8, another variation of the coupling mechanism between adjacent modules is illustrated. No separate connecting element is used. Instead, the frame members 360 of adjacent modules are coupled to each other as shown. The frame elements of adjacent modules may be attached together by any means suitable for the material, such as welding or the like. In one embodiment, the frame members of adjacent modules may be formed (e.g., cut) from a single piece of material. This direct coupling of the frame elements of adjacent modules advantageously results in a bracket with greater axial strength.
The present invention includes a wide variety of different articulating mechanisms; including, but not limited to, the slot and tab designs disclosed by way of example in fig. 1-8, and the design disclosed in U.S. patent No.6,033,436 to Steinke, the parent version of which is incorporated herein by reference in its entirety.
Those skilled in the art will appreciate that the basic modular design of a sliding and locking sequence of radial elements provides the manufacturer with greater flexibility with respect to the contracted and expanded diameters and longitudinal lengths of the stent. By increasing the number of radial elements in each module, the expansion diameter and expansion ratio can be increased. The longitudinal length can be increased by increasing the number of modules (from one module shown in fig. 9 to six modules shown in fig. 10) that are connected to form the tubular member.
Referring to fig. 9, a tubular component has only one module 410 comprising a sequence of four radial elements (two one-rib radial elements 420' and two-rib radial elements 420 "). In the illustrated module 410, no dedicated coupling elements, such as the floating coupling elements described in fig. 4A and 4B, are used, although such a coupling element may be used without departing from the basic design. The illustrated frame member 460 is rectangular and surrounds only one rib radial member 420'. The module shown in fig. 9 is shown in an expanded state with minimal retraction or contraction (< about 5%) due to the snap-action effect created by the articulation between tabs 432 on the articulating mechanism 434 of one radial element and stops 430 on the slidably engaged ribs 422 of an adjacent radial element. The articulating mechanism is shown as a separate structural member that has been secured, such as by welding, to the end 424 of the corresponding radial element to couple and slidably engage the ribs of the adjacent radial element.
In fig. 10 there is shown a stent according to the invention comprising a tubular member 500 having six modules 510 connected along a longitudinal axis (for clarity, the connecting elements extending between the frame elements of adjacent modules are not shown).
Figure 11 illustrates a radial element sequence of another variation of the invention in which the articulation mechanism is formed by tabs 632 in a one-way locking slot 633. This design does not require the attachment of an overlapping articulating mechanism, such as by welding, to connect and slidably engage the circumferential ribs of adjacent radial elements. As shown in FIG. 11, an entry slot 631 is provided at one end of the central locking slot 633, the central locking slot 633 being provided along at least a portion of the length of each rib in each radial element. The entry slot 631 is adapted to allow a tab 632 on the end 624 of a radial element 620 to fit into and engage the locking slot 633 in the rib. Once the tabs 632 are in place through the inlet slots 631, the radial member 620 can slide away sufficiently to prevent the tabs 632 from returning out of the inlet slots 631. The locking slot 633 is adapted to allow the tab to slide through the slot in only one direction (to a more expanded configuration). For example, as shown, locking slot 633 has a series of saw-tooth shaped cutouts or stops 630 that are offset on either side of the slot and allow tab 632 to move through slot 633 in one direction, but are shaped to engage the tab without allowing the tab to move through the slot in the opposite direction, i.e., to prevent the expanded stent from collapsing. Any of a variety of locking groove and stop configurations are uniformly included in the snap-together design. Some alternative locking groove and stop configurations are disclosed in U.S. patent No.6,033,436 to Steinke, the parent application for which.
The module of the weldless design illustrated in fig. 11 shows a frame element 660 with a connecting element 640 surrounding a ribbed radial element and a floating coupling element 650, element 650 with coupling arms 652 and 654 for mating with complementary coupling arms 652 'and 654' on the end 624 of the top radial element in the series. This increased length makes the stent very flexible in both the contracted and expanded states because of the ability to modularly couple the frame elements.
Another variation of the invention includes varying the configuration of the articulating mechanism and ribs to produce increased friction with progressive expansion. This variant may facilitate a uniform expansion of all radial elements within a module.
In another variation of the present invention, different modules in the stent may exhibit different expanded diameters, allowing the stent to be adjusted to different body lumen states along its length. Thus, the stent may assume a tapered configuration in its expanded state with a larger diameter at one end and a gradually or stepwise decreasing expanded diameter of the module toward its other end. Those skilled in the art will appreciate that the interlocking sliding radial element design of the present invention provides the manufacturer with a significant degree of flexibility in customizing the stent for different uses. Because the overlap of the stent components is minimized due to the nesting of the ribs and frame elements, the contracted profile can be very thin without sacrificing radial strength. Also, during expansion, the degree of overlap does not vary significantly, unlike jelly roll designs that expand by unwinding of the wound sheet. Second, the flexibility of deployment of the stent can be specifically designed by varying the length, configuration and number of all lateral connecting elements. Thus, the flexible and ultra-thin embodiment of the stent is certainly uniquely suited for deployment in small, difficult to reach vessels, such as the intracranial vessels, as far as the carotid artery and more distant coronary arteries.
In another variation, the stent may be used in conjunction with a sheath or sheath to provide a vascular graft, for example, for the treatment of aneurysms. Materials and methods for making vascular grafts (stents and sheaths) including the stent design are described in detail below.
In another variation of the invention, the stops disposed along the elongated ribs may be shaped to facilitate locking of the tabs of the movable connector member within the stops, wherein the apertures are shaped to provide a channel having a biasing force that captures the member (e.g., tab) sliding through the channel. Referring to fig. 12A-12C, steps for forming one embodiment of such a stop tab are illustrated. In fig. 12A, the stent 700 can be eroded from the surface of the top 700' and bottom 700 ". The top and bottom surfaces are coated or masked (e.g., by chemical, laser, etc.) with a corrosion-protective layer in certain areas 702 'and 702 ", respectively, leaving uncoated areas 704' and 704", respectively, on the top and bottom surfaces that are susceptible to corrosion. The two uncoated regions are offset by a distance 706, respectively, which enables some overlap 708 between the top and bottom uncoated regions 704' and 704 ". As shown in fig. 12B, during the erosion process to remove the stent, the uncoated regions 704' and 704 "become cavities 710 extending through the stent material. As shown in fig. 12C, at some point during the etching process, the cavities meet in the overlap region 708 to form a via or channel 712. The stop thus forms a beveled edge that is captively biased against a tab sliding past the stop.
In another embodiment of the present stent, the locking mechanism may be designed as a releasable device, wherein the stent may be collapsed for removal from the body lumen. While other configurations in the present disclosure are designed to permanently lock the components in the expanded state, a mechanism that can be reversed or unlocked may be desirable. The components of one possible release mechanism are illustrated in an exploded view in fig. 13A. Most aspects of the stent according to the invention are as described above. However, the actuator 1034 may be releasably engaged. Tabs 1032 are pre-shaped or biased (due to their resilient material and/or angle of deployment) so as not to lockingly engage a single stop 1030. Instead, a movable slide 1080 and brake plate 1090 are positioned over tab 1032 to deflect the tab downward into a single detent. The shape of tabs 1032 deflected against ribs 1022 by slides 1080 and stop plate 1090 locks ribs 1022 against movement (contraction) in one direction and movement (expansion) in the opposite direction. The slide 1080 has a wide area 1082 that can create a constructive interference with bending the tab 1032 into the locked position. When the broadside 1082 is disposed between the stop plate 1090 and the tab 1032, the tab is forced against the slidably engageable rib 1022 and into the passing stop 1032 as the rib 1022 slides through the activation mechanism. The slide 1080 also has a narrow area 1084 that allows the tab 1032 to release and clear the stop 1030. By pulling the slider 1080 out of the vertical plane of the rib 1020, the narrow region 1084 repositions over the tab 1032, allowing the tab to release the device from the stop 1030 and spring back upward against the stop plate 1090.
Referring to FIG. 13B, a partial view of a module having a one-rib and two-rib radial element and releasable attachment 1034 is shown. The releasable attachment mechanism on one rib radial element is shown engaging two ribs of an adjacent rib radial element. The slider on the releasable attachment mechanism may be modified to have two narrow areas for releasing the two tabs of the device by pulling on one side of the slider.
Manufacture of stents
Preferred materials for making the stents of the present invention include 316 stainless steel, tantalum, titanium, tungsten, gold, platinum, iridium, rhodium, and alloys thereof. Shape memory alloys such as Nitinol may also be used in accordance with the present invention. Preferably, the sheet material is work hardened prior to forming the individual frame members. Methods of work hardening are well known in the art. Rolling the plate under pressure, heating and annealing, and then processing. This may be continued until the desired hardness modulus is obtained. Most stents currently in commercial use 0% to 10% work hardened material to allow for "softer" materials to be deformed to larger diameters. In contrast, because the expansion of the sliding and locking radial elements according to the invention depends on the sliding and not on the material deformation, it is preferable to use a harder material with a preferred range of about 25-95% work hardened material to account for the thinner stent thickness. More preferably the material is 50 to 90% work hardened, and most preferably the material is 80 to 85% work hardened.
The preferred method of forming the individual elements from sheet metal may be laser cutting, laser ablation, die cutting, chemical etching, plasma etching or other methods known in the art capable of producing high resolution parts. In some embodiments, the method of manufacture depends on the material used to form the stent. Chemical etching provides high resolution parts at a lower price, especially compared to the high cost of competitive laser cut products. Tack welding, adhesives, mechanical attachment (snap together), and other attachment methods known in the art may be used to secure the individual elements. Some methods allow for different front and rear erosion workpieces that may form beveled edges that are expected to help improve the locking engagement.
In a preferred form of the invention, the stent is at least partially formed from a degradable polymeric material. The motivation for using degradable stents is that their mechanical support may only take weeks after the vessel formation, especially if it also controls restenosis and thrombosis by delivering pharmacological agents. Degradable polymeric stent materials are well suited for drug delivery.
It is believed that a brachial procedure is required because most heart disease occurs in the first six months, including restenosis within the stent. The permanence of metal stents presents long-term risks and complications. Metal stents can also interfere with re-surgery due to long-term damage and complete coverage. Ideal implant: (1) closely resemble the organization that it is designed to replace in terms of size, shape and material consistency; (2) the placement does not cause infection and foreign body response; (3) is a temporary prosthesis having natural tissue characteristics when the natural tissue disappears; (4) is a biocompatible implant having a smooth surface to minimize thrombosis and macrophage enzyme activity.
Degradable scaffolds have the potential to behave more like an ideal implant. Degradable scaffolds that seamlessly integrate with living host tissues can improve the biocompatibility of the tissues due to their temporary residence. Due to the initial strength of the fixed diseased tissue, such a scaffold can eliminate concerns over product movement over time and long-term product failure. They may also minimize the time, expense and complexity associated with re-surgery at specific and adjacent sites. One significant advantage of degradable stents over metallic stents is that they can be administered to diseased tissue, and that degradable stents can be administered to tissue for a longer period of time than metallic stents coated with a drug.
Unlike restenosis after angioplasty, restenosis within a stent is almost entirely the result of tissue hyperplasia, occurring primarily at those points where the struts of the stent impinge the artery wall. Placement of an overly stiff stent against a flexible vessel creates a mechanical behavior mismatch that creates continuous laterally-expandable stresses on the arterial wall. This stress can promote thrombosis, arterial wall thinning or excessive cell proliferation. Thus, a more flexible polymer material may minimize pathological disease and appear to more closely approximate the mechanical contours of natural tissue.
The undamaged Inner Elastic Layer (IEL) of a healthy artery serves as an effective barrier to (1) protect the underlying Smooth Muscle Cells (SMC) from exposure to proliferation-inducing mitogens; (2) preventing exposure to single cells or lipid-filled macrophages and circulating elastin peptides that promote hard plaque formation and arterial narrowing. A scaffold of biological material can minimize progression of disease states by mimicking the shielding effect of IEL, due to: (1) counteracting the effects of mitogens by delivering a cell cycle inhibitor; (2) by acting as a temporary physical carrier for the passing immune cells.
In the natural disease states of arterial stenosis and atherosclerosis, arteries can have an IEL that is damaged or structurally discontinuous. The cause of such discontinuities is probably not clear. Elastase, circulating elastin peptides and elastin receptors may play a key role in conjunction with endothelial denudation. A stent that does not over-expand the biomaterial of the vessel wall may minimize the risk of further perforation of the IEL. In addition, the surface of the stent can serve as a fixation site for the formation of the endothelial lining and the guardian of blood components and circulating molecules.
In one form of the degradable stent of the present invention, the matrix may be configured to release a pharmacological agent. Mechanical manipulation of diseased vessels by angioplasty and stenting can further damage the arterial wall. Unfortunately, each of these procedures can promote thrombosis and restenosis with 6-24 months post-operative reclosure. These inadequate clinical consequences are the motivation to develop many antagonistic therapies. Some new treatments for restenosis use radioisotopes, Paclitaxel (Paclitaxel) and Rapamycin (Rapamycin), which inhibit vascular cell proliferation.
It is estimated that pharmacological surgery for restenosis requires 2-4 weeks following angioplasty or stent implantation. It is also estimated that a polymeric stent can deliver 10 times the amount of agent delivered systemically. Optimal long-term patency in a diseased vessel can be obtained if a cell cycle inhibitor is released from a degradable stent.
The degradable biomaterial scaffold can improve the long-term safety of the product and the effectiveness for patients. It is believed that a fully degradable drug eluting stent that can remain in the vessel for several weeks after deployment would be effective in controlling restenosis. Thus, the present invention includes a stent having the sliding and locking geometry described above, wherein the components thereof are made of functional biomaterials. According to the invention, the mechanical properties of the degradable biomaterial are selected to have at least one and preferably several of the following characteristics: (1) resist failure due to multi-axial stress-strain behavior of natural vessels and exceed the stress-strain behavior of annealed metals known to be unusable for stent applications; (2) maintaining mechanical strength for weeks or months after deployment; (3) preferably with surface erosion, by hydrolytic or enzymatic degradation, thereby causing the implant to degrade uniformly and to retain its original shape as it degrades; (4) maintaining favorable hemodynamic behavior; (5) presents a hydrophilic, negatively charged, smooth and uniform surface with a low critical surface tension; (6) is beneficial to the healing of endothelium; (7) non-toxic and safely disappear from the body, i.e. there is no systemic effect; (8) comprising an anti-restenosis pharmacological agent; the pharmacological agent may be a cell cycle inhibitor that inhibits SMC proliferation, allows for early or late beneficial regeneration, and is stable in the biomaterial; the degradable biomaterial and pharmacological agent preferably provide a dosage of about 3-4 weeks of disease or degradation cycle through the stent.
Degradable plastics or natural (animal, plant or microbial) or recombinant materials according to one aspect of the invention may include polyglycopeptides, nylon copolyimides, conventional polyamino acid synthetic polymers, pseudopolyamino acids, aliphatic polyesters such as polyglycolic acid (PGA), polylactic acid (PLA), alkylene succinates, Polyhydroxybutyrate (PHB), polybutylene diacetate and polyepsilon-caprolactone (PCL), polydihydropyrans, polyphosphazenes, polyorthoesters, polycyanoacrylates, polyanhydrides, polyketals, polyacetals, polyalpha-hydroxy esters, polycarbonates, polyiminocarbonates, poly-3-hydroxy esters, polypeptides and chemical variants and combinations (mixtures and copolymers) thereof as well as many other degradable materials known in the art (see "synthetic biodegradable polymer scaffolds" such as Atala, a., Mooney, d., in 1997, Birkhauser press, boston, usa; incorporated herein by reference).
In a preferred mode, the degradable substance is selected from the group consisting of: polyalkylene oxalates, polyalkanoates (polyalkanotes), polyamides, polyaspartic acid (polyaspathic acid), polyglutahyrylanic acid (polyglutarenoic acid) polymers, poly-p-diaxanone (such as PDS from Ethicon), polyphosphazenes and polyurethanes.
In a more preferred mode, the degradable substance is selected from the group consisting of: poly (glycolide-trimethylene carbonate); terpolymers (copolymers of glycolide, lactide, or trimethylene carbonate); polyhydroxyalkanoates (PHAs); polyhydroxybutyrate (PHB) and poly (hydroxybutyrate-co-valerate) (PHB-co HV) and copolymers thereof; poly (epsilon-caprolactone) and copolymers (such as lactide or glycolide); poly (epsilon-caprolactone) -trimethylene carbonate dimethyl ester); polyglycolic acid (PGA); poly-L and poly-D (lactic acid) and copolymers and additives (such as calcium phosphate glass) and lactic acid/ethylene glycol copolymers.
In a most preferred form, the degradable material is selected from the group consisting of: polyarylate (L-tyrosine derived) or acid-free polyarylate, polycarbonate (L-tyrosine derived), poly (ester amide), poly (propyl fumarate-co-ethylene glycol ethyl ester) copolymer (i.e. fumaric anhydride), polyanhydride esters (mechanically stronger) and polyanhydrides (mechanically weaker), polyorthoketones, ProLastin or silk elastin polymers (SELP), calcium phosphate (bioglass), magnesium alloys, and commercial polymers of PLA, PCL, PGA alone or in any compound.
Natural polymers (biopolymers) include any protein or peptide. These can be used in mixtures or copolymers with any of the other above-mentioned degradable substances as well as with pharmacological substances or with hydrogels, or alone. Typically, these biopolymers are degraded by enzymes. Preferred biopolymers may be selected from the group consisting of: alginates, cellulose and esters, chitosan (NOCC and NOOC-G), collagen, cotton, dextran, elastin, fibrin, gelatin, hyaluronic acid, hydroxyapatite, spider silk, other polypeptides and proteins, and any combination thereof.
The coating material for degradable and metallic stents may be selected from the group consisting of: hydrogels such as NO-hydroxymethylchitosan (NOCC), PEG diacrylate with drug (intima layer) and drug-free second layer (blood stream contact), polyethylene oxide, polyvinyl alcohol (PVA), PE oxide, polyvinyl pyrrolidone (PVP), polyglutalate such as an engendene (polyglutarunic) acid polymer, DMSO or alcohols and any combination thereof.
Where plastics and/or degradable substances are used, the elements may be manufactured using hot punch molding to produce parts and heat stakes to attach the connecting elements and coupling arms. Other preferred methods include laser ablation using a mask, stencil or mask; solvent casting; forming by stamping, embossing, compression molding, centripetal spin casting, and molding; extrusion and cutting, three-dimensional rapid prototyping using solid intangible manufacturing techniques, stereolithography, selective laser sintering, and the like; etching techniques including plasma etching; textile manufacturing processes including felting, knitting or weaving; molding techniques including fused deposition modeling, injection molding, Room Temperature Vulcanization (RTV) molding, or silicone rubber molding; molding techniques including solvent casting, direct shell production casting, lost wax casting, compression mold casting, resin injection, resin processing by molding or Reaction Injection Molding (RIM). These components may be connected or attached using solvent or thermal bonding or mechanical attachment. Preferred bonding methods include the use of ultrasonic radio frequency or other thermal methods and the use of solvents or adhesives or ultraviolet curing or photoreactive treatments. The elements may be rolled by hot forming, cold forming, solvent weakening and evaporation or by pre-forming before joining. Soluble substances such as hydrogels hydrolyzed with water in the blood, for example, cross-linked poly (2-hydroxyethyl methacrylate) (PHEMA) and its copolymers such as polyacrylamide and polyvinyl alcohol, may also be used.
To facilitate tracking and positioning of the stent, a radioprotectant (i.e., a radiopaque substance) may be added to, absorbed into, or sprayed onto a portion or all of the implant in any manufacturing process. The radiographic sedation contrast can be altered by implant content. The radioprotective properties can be imparted to the polymeric monomeric building blocks of the implant member by covalently bound iodine. Commonly used radiopaque materials include barium sulfate, bismuth subcarbonate, and zirconium dioxide. Other radiopaque elements include cadmium, tungsten, gold, tantalum, bismuth, platinum, iridium, and rhodium. In a preferred embodiment, iodine may be used for its radioprotectant and antimicrobial properties. Radiation sedation performance is typically determined by fluoroscopy or X-ray film.
The stent according to the invention may also be used in a vascular graft, wherein the stent is covered with a sheath consisting of a polymer substance such as expanded PTEE, a degradable polymer or a natural substance such as fibrin, pericardial tissue or derivatives thereof and substances known to the skilled person. Alternatively, the stent may be embedded in the layer of covering material.
Once the stent sections have been cut and assembled into planar modules (see the plan views of fig. 1, 2, 4-8 and 11) and the connecting elements between adjacent modules have been joined (e.g., by welding, interweaving frame members, etc.), the flat sheet of material is wound to form a tubular member. Coupling arms from the coupling element and the end are combined (e.g., by welding) to float to maintain the tubular shape. In embodiments that do not include coupling elements, the ends of the top and bottom radial elements in one module may be joined. Alternatively, where sliding is desired around the entire periphery, a sliding and locking articulation may be made between the ends of the top radial element and the ribs of the bottom radial element (e.g., by tack welding, heat staking or snapping together). Likewise, a corresponding articulation can be made between the end portion of the bottom radial element and the rib of the top radial element.
The modular rolling into a tubular member can be accomplished by any method known in the art, including rolling between two plates, each of which is padded on the sides in contact with the stent element. One plate is held stationary and the other plate is able to move laterally relative to the first plate. The carrier element clamped between the two plates can thus be wound around a mandrel by relative movement of the two plates. Alternatively, the tubular member may be rolled using a three-way mandrel method as is known in the art. Other rolling methods that may be used in accordance with the present invention include those used for "jelly roll" designs, such as those described in U.S. Pat. Nos. 5,421,955; no.5,441,515; no.5,618,299; no.5,443,500; no.5,649,977; no.5,643,314; disclosed in No.5,735,872, the disclosure of which is fully incorporated herein by reference.
The construction of this form of stent provides a number of advantages over the prior art. The configuration of the locking mechanism is largely material dependent. This enables the structure of the bracket to comprise a high strength material, and it is not possible to use the deformation of the material required to complete the design of the locking mechanism. The inclusion of these materials will allow the required thickness of the material to be reduced while retaining the strength characteristics of the thicker stent. In a preferred embodiment, the frequency of the presence of locking holes or stops on selected circumferential ribs prevents unnecessary retraction of the expanded stent.
Drug incorporated in stent
Drugs or other bioactive compounds can be incorporated into the degradable matrix itself or coated onto the non-degradable stent material, thereby providing sustained release of such compounds at the stent site. In addition, degradable biomaterials can be manufactured in various forms and added to the components of the stent. Preferred biomaterials will include an agent mixed with the degradable polymer prior to fabrication of the scaffold. Preferred agents control restenosis (including neointimal thickening, intimal hyperplasia, and in-stent restenosis) or limit the overgrowth of luminal vascular smooth muscle cells of the vessel moving into the stent. Other human uses may require different drugs.
In another aspect of the invention, the biomaterial of the scaffold may also include a hydrogel, such as NOCC and NOCC-G chitosan, to prevent adhesion of blood cells, extracellular matrix or other types of cells. In another aspect, the agent or hydrogel can be coated on the surface of the biomaterial either alone or in a mixture or in combination with other binding agents required to adhere or absorb the agent or hydrogel to the surface of the biomaterial. Additionally or alternatively, the agent or hydrogel or genetic material may be associated with a biomaterial polymer, microsphere or hydrogel.
Synthetic, natural (of plant microbial, viral or animal origin) and reconstituted forms having selected functional or chemical properties can be used in combination with complementary substances (such as antithrombotic and anti-restenosis substances; nucleic acids and lipid complexes). Pharmacological agents may also be used in combination with vitamins or minerals, e.g., those that act directly or indirectly through interactions or mechanisms involving amino acids, nucleic acids (DNA, RNA), proteins or peptides (e.g., RGD peptides), carbohydrate moieties, polysaccharides, liposomes or other cellular components or organelles such as receptors and ligands.
The agent may be polar or have a net charge or a net positive or neutral charge; the agent may be hydrophobic, hydrophilic or zwitterionic or have a great affinity for water. Release may occur by controlled release mechanisms, diffusion, interaction with another agent delivered by intravenous injection, nebulization, or oral administration. The release may also occur by an applied magnetic field, electric field, or using ultrasound.
The classes of compounds that can be used to coat metallic stents or to incorporate degradable stent materials have been disclosed by Tanguay et al, "Heart clinical sciences" (1994) and Nikol et al, "Atherosclerosis" (1996); these references are incorporated herein by reference in their entirety. These compounds include antiplatelet agents (table 1), antithrombin agents (table 2), and antiproliferative agents (table 3). Some preferred agents falling within these classes of compounds are listed in tables 1-3.
TABLE 1 antiplatelet agents
| Compound (I) | Function of |
| Aspirin | Cyclooxygenase inhibition |
| Dipyrimidinol | Phosphodiesterase inhibition |
| Ticlopidine | Blockade of interactions between platelet receptors, fibrinogen and von Willebrand factor |
| C7E3 | Antibodies to single cell lines of glycoprotein IIb/IIIa receptors |
| Integrins | Competitive glycoprotein IIb/IIIa receptor inhibitors |
| MK-852，MK-383 | Glycoprotein IIb/IIIa receptor inhibitors |
| RO-44-9883 | Glycoprotein IIb/IIIa receptor inhibitors |
TABLE 2 antithrombin agents
| Compound (I) | Function of |
| Heparin | Antithrombin HI cofactor |
| Compound (I) | Function of |
| Low Molecular Weight Heparin (LMWH) | Inhibition of factor Xa by antithrombin III |
| R-hirudin | Selected thrombin inhibition |
| Black like Luo Ge (Hirul) | Integrated direct thrombin inhibition |
| Argatroban (Argatroban), Aff Jia Miao Lang (efegatran) | Integrated competitive thrombin inhibition |
| Tick anticoagulant peptides | Specific thrombin inhibition |
| P packing | Irreversible thrombin inhibition |
Supplemental antithrombotic agents and formulations include endothelial derived relaxant factor, prostaglandin 12Blood plasmaZymogen activator inhibitor, tissue-type plasminogen activator (tPA), ReoPro: anti-platelet glycoprotein iib/iiia integrin receptors, heparin, polyamines covalently bound to dextran sulfate and heparin, polymer coatings for endografts (MEDI-COAT by STS biopolymer), polyurethane urea/heparin, hirudin/prostacyclin and analogs, fibrin and fibrinopeptide a, lipid lowering drugs such as omega-3 fatty acids and moth pupal (chrysalin) by moth pupal vascular technique (also known as TRAP 508) (this agent is a peptide part made by the synthesis of the enzyme thrombin of the human body, causing blood clots and promoting cell/tissue repair). Moth pupa element mimics the characteristic properties of thrombin by interacting with receptors on cells involved in tissue repair.
Other anti-restenotic substances according to the invention include integrins from COR therapeutics(INTEGRILIN) (eptifibatide) (prevention of platelet clotting), Resten-NG (neural Gene [ NeuGene ]) by AVI biomedical and transplant sciences (synthetic variant of C-MYC oncogene), BiodivYsio (phosphorylcholine (PC) by Abbott laboratories and by biocompatible International PLC>) Liposomal prostaglandin EI from Endovasc and Collaborative BioAlliance, adenovirus carriers for gene delivery to vascular smooth muscle cells (Boston science and CardioGene therapy), TAXOL from Bristol-Myers Squibb (Paclitaxel) to prevent cell division by promoting assembly and inhibiting microtubule breakdown), and rapamycin or nitric oxide, other drugs including acyl sphingosine, cinnamamic acid, probucol, sitagliptins, cilostazol and low molecular weight variants of heparin.
Various compounds are believed to be useful in controlling vascular restenosis and in-stent restenosis. These preferred antiproliferative agents are listed in table 3 (below).
TABLE 3 antiproliferative agents
| Compound (I) | Function of |
| Angiopeptin (angiopepin) | Growth hormone inhibitor analogs that inhibit IGF-1 |
| Compound (I) | Function of |
| Xiprostene (Xiprostene) | Prostacyclin analogs |
| Calcium blocker | Inhibition of sluggish calcium channels |
| Colchicine | Anti-proliferative and movement inhibition |
| Cyclosporin | Inhibiting immunity and inhibiting intracellular growth signal |
| Cell rabin (Cytorabine) | Anti-tumor, DNA integration inhibition |
| Fusion proteins | Toxin-limiting growth factors |
| Riopsist (lioprot) | Prostacyclin analogs |
| Kataserin (Ketaserine) | Serotonin antagonists |
| Dehydrocortisone | Steroid hormones |
| Azolopyrim | Platelet derived growth factor inhibitors (thromboxane-A2 and/or PDGF receptor antagonists) |
Specific therapeutic agents that may modulate Smooth Muscle Cell (SMC) proliferation have also been identified. The inclusion of such agents may be particularly useful because smooth muscle cell proliferation is associated with atherosclerotic stenosis and post-surgical restenosis. Such agents include, without limitation, SMC mitotic modulators (e.g., TAXOL, rapamycin, or ceramide) with stimulants and triggers for extracellular matrix production such as anti-FGF and TGF-B1Adaptation agents, Tissue Inhibitor Metalloproteinases (TIMP)S) And a substrateA metalloprotease.
Each compound addresses a particular pathological event and/or disease. Some of these therapeutic target compounds are summarized in table 4 (below).
TABLE 4 specific therapeutic target compounds
| Pathological events | Therapeutic target compounds |
| Endothelial dysfunction | Nitric oxide inducers or antioxidants |
| Endothelial injury | VEGF, FGF 'are administered' |
| Cellular activation and phenotypic modulation | MEF-2 and Gax modulators; NFKB antagonists; cell ring inhibitors |
| Pathological events | Therapeutic target compounds |
| Regulating abnormal cell growth | An E2F attractant; an RB mutant; cell ring inhibitors |
| Modulation of aberrant autophagy | Bax or CPP 32 inducer; bc1-2 inhibitors; integrin antagonists |
| Thrombosis | II b/III a blocking agent; a tissue factor inhibitor; anticoagulase agents |
| Plaque rupture | (ii) a metalloprotease inhibitor; leukocyte adhesion blocking agent |
| Abnormal cell movement | Integrin antagonists; a PDGF blocking agent; inhibitors of plasminogen activator; |
| matrix change | (ii) a metalloprotease inhibitor; a plasminogen antagonist; matrix protein cross-linking altering factor |
Therapeutic agents incorporated on or in the scaffold material of the invention may be classified according to their site of action in the host. The following agents are believed to exert their effects extracellularly or on specific membrane receptors. These include corticoids and other ion channel blockers, growth factors, antibodies, receptor blockers, fusion toxins, extracellular matrix proteins, peptides or other biomolecules (e.g., hormones, lipids, matrix metalloproteinases, etc.), radiation, anti-inflammatory agents including cytokinins such as Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-), interferon gamma, and Tranilast, which modulates the inflammatory response.
Other groups of agents exert their influence on the plasma membrane. These include agents involved in signal transduction cascades such as binding proteins, membrane-associated and cytoplasmic protein kinases and effectors, tyrosine kinases, growth factor receptors and adhesion molecules (selectins and integrins).
Some compounds are active in the cytosol, including, for example, heparin, ribozymes, cetoxicines (cytoxins), antiallergic oligonucleotides, and secretory carriers (expressurectors). Other therapeutic approaches are directed to the nucleus. These pathways include gene integration, primary oncogenes, particularly those important for cell division, nucleoproteins, cell-ring genes and transcription factors.
Genetic pathways controlling restenosis include, without limitation: for PDGFR-mThe RNA uses anti-allergic oligonucleotides; the use of antiallergic oligonucleotides for the nuclear antigen C-myb or C-myc oncogenes (Bauters et al, 1997, CV (cardiovascular) medical trends); the use of antiallergic phosphorothioate oligodeoxynucleotides (DDNs) to overcome cdk 2 kinase (cyclin-dependent kinase) to control the cellular loop of vascular SMCs (Morishita et al, 1993, hypertension); the use of the VEGF gene (or VEGF itself) to stimulate reconstructive wound therapy such as endothelial healing and reduction of neointimal growth (Asahara et al, 1995); when delivering nitric oxide synthase radical (eNOS) to reduce vascular SMC proliferation (Yon Der Leyen et al, 1995, Proc Natl Acad Sci); the use of plasminogen activator inhibitor-1 (PAI-1) which secretes adenovirus to reduce vascular SMC migration and thus restenosis (Carmelct et al, 1997, circulation); stimulating apolipoprotein a-1(ApoAl) hypersecretion to rebalance the serum levels of LDL and HDL; use of a gene product for apoptosis (SMC) and use of a gene product for cell sequencing to regulate cell division (tumor suppressor protein p 53 and Gax are homologous)Source heteromorphic box gene products to inhibit rass (ras); p 21 over-secretion); and inhibition of activation of NFKB (e.g., p65) to control SMC proliferation (Autieri et al, 1994, Biochem Biophys Res Commun).
Other therapeutic substances that may be used as a coating for the stent and/or as a reservoir formulation incorporated within a degradable stent include: various antibodies to ICAM-1 for the inhibition of monocyte chemo-sequence recruitment and adhesion, macrophage adhesion and related events (Yasukawa et al, 1996, circulation); various toxin-based therapies such as chimeric toxins or monomeric toxoids that control vascular SMC proliferation (Epstein et al, 1991, circulation); bFGF-saporin (saporin), which selectively stops SMC proliferation in those cells with a large number of FGF-2 receptors (Chen et al, 1995, circulation), suramin inhibits migration and proliferation by preventing PDGF-induced and/or mitogen-activated protein kinase (MAPK-AP-1) -induced signaling (Hu et al, circulation, 1999); chemically stable prostacyclin analogue (PGl)2) Belaprost sodium inhibits intimal thickening and luminal narrowing of coronary arteries (Kurisu et al, J. Guangdong. Med. Sci., 1997); verapamil inhibits the proliferation of neointimal smooth muscle cells (Brauncr et al, j. thorac. cardiovasc, surg., 1997) agents that block CD 154 or CD 40 receptors can limit the progression of atherosclerosis (e.lutgens et al, nature medicine, 1999); the agent for controlling the shear stress response can respond to elements or mechanical stress or strain elements or thermal shock genes; and anti-chemoattractant agents for SMC and inflammatory cells.
Additionally or alternatively, the cells may be encapsulated in a degradable microsphere, or mixed directly with a polymer or hydrogel and used as a drug delivery vehicle. Living cells can be used for the continuous delivery of drug-type molecules such as cytokinins and growth factors. Non-viable cells may also be used as a limited or timed release system. Cells or any source may be used in accordance with this aspect of the invention. Second, preserved or dehydrated cells that retain their viability when rehydrated can be used. Native, chemically modified (treated) and/or genetically engineered cells may be used.
Deployment of stents
The stent can be deployed in the body using a method appropriate to its design. One such method is to mount the collapsed stent on an inflatable balloon catheter component and expand the balloon to force the stent into contact with the body cavity. When the balloon is inflated, the problematic material in the vessel is compressed in a direction generally perpendicular to the walls of the vessel, which in turn causes the vessel to expand to facilitate blood flow within the vessel. Radial expansion of the coronary arteries occurs in several different directions and is related to the nature of the plaque. Soft fatty plaque deposits are collapsed by the balloon and hardened deposits are broken and fragmented to enlarge the body cavity. It is desirable that the stent be radially expandable in a uniform manner.
Alternatively, the stent may be mounted on a catheter which is retained on the stent as it is delivered through the body lumen, and the device stent is released and allowed to self-expand to contact the body lumen. Deployment is complete when the stent has been percutaneously introduced, delivered through a body lumen, and positioned at a desired location with the catheter. The realignment mechanism may include a removable sheath.
The stents most commonly used today are stiffer than desired. The relative flexibility is shown in fig. 14A and 14B. The degree of flexure of the undeployed/mounted stent is shown in fig. 14A. The desired deflection test was performed in saline at room temperature as described in the ASTM standard for stent measurements. The S540 (2.5X 18mm) and S670 (3.0X 18mm) stents were produced by Medtronic, Inc., the TRISTAR(2.5X 18mm) was manufactured by Guidant Corp, the VELOCITY (2.5X 13mm) was manufactured by J&J, and the Nir (2.5X 32mm) is sold by the Boston scientific company. The results shown in fig. 14A (not deployed on a delivery catheter) indicate that the stiffness of the other stents tested was more than twice that of the stent made according to the present invention (MD 3). Has been developedThe difference in the degree of deflection of the open (expanded) stent is even more pronounced as shown in fig. 14B.
Stents made in accordance with the present invention are capable of guiding small or tortuous paths due to the very small profile, small collapsed diameter and large deflection. Thus, the low profile stent of the present invention may be used in coronary arteries, carotid arteries, vascular aneurysms (when covered with a sheath) and peripheral arteries and veins (e.g., renal, iliac, femoral, popliteal, subclavian, aortic, intercranial, etc.). Other non-vascular uses include gastrointestinal, duodenum, bile duct, esophagus, urethra, reproductive tract, trachea and respiratory tract (e.g., bronchi). These uses may or may not require a sheath covering the stent.
The stent of the present invention is adapted to be deployed by conventional methods known in the art and with percutaneous transluminal catheter components. The stent is designed to utilize various in situ expansion mechanisms such as an inflatable balloon or a polymeric plug that expands upon the application of pressure. For example, the body of the stent is first placed around a portion of an inflatable balloon catheter. The stent with the balloon catheter inside is made to be in a first contracted diameter. The stent and inflatable balloon are introduced percutaneously into the body lumen following a pre-set guidewire in an on-line angioplasty catheter system and tracked fluoroscopically until the balloon portion and associated stent are positioned at the point in the body lumen where the stent is to be placed. Thereafter, the balloon is inflated and the stent is expanded from the collapsed diameter to a second expanded diameter by the balloon portion. After the stent has been expanded to the desired final expanded diameter, the balloon is deflated and the catheter is withdrawn, leaving the stent in place. The stent may be covered with a removable sheath during delivery to protect both the stent and the vessel.
The expanded diameter is variable, determined by the desired expanded inner diameter of the body lumen. Thus, controlled expansion of the stent does not cause rupture of the body lumen. Secondly, the stent will resist retraction because the locking mechanism resists sliding of the elongate ribs in the mobility mechanism on the ends of the radial elements. Thus, the stent within the expanded body lumen will continue to exert radial pressure outwardly against the wall of the body lumen and thus will not move away from the desired location.
Although many preferred embodiments of the present invention and variations thereof have been described in detail, other variations and methods of their use and medical use will be apparent to those skilled in the art. It is therefore to be understood that various applications, modifications and substitutions of equivalents may be made without departing from the spirit of the invention and scope of the claims.