An absorbable intravascular device that shortens when expanded to create space for vasomotion

Abstract

Multi-element vascular stents can be used to maintain or enhance vascular patency. The stents can be used in peripheral vessels that may be long and / or tortuous. By using multiple, separate balloon-expandable stent elements, multi-element stents can be stronger than conventional self-expanding stents, but due to their multi-element configuration, they can be more flexible than conventional balloon-expandable stents. The individual stent elements shorten upon expansion, creating spaces between them. When deployed, the distance between the stent elements can be adjusted based on the stent's characteristics and the target vessel location to prevent the stent elements from contacting each other during skeletal movement. Therefore, the multi-element vascular stents described herein can be particularly advantageous for treating long lesions in tortuous peripheral vessels. [Selected figure] Figure 2

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 682,727, filed June 8, 2018, entitled "ABSORBABLE INTRAVASCULAR DEVICES THAT SHORTEN UPON EXPANSION CREATING SPACE FOR VASCULAR MOVEMENT."

[0002] This application relates generally to the field of medical devices. More specifically, this application relates to the design and manufacture of intravascular stents intended to maintain patency (blood flow) of blood vessels (arteries and veins). [Background technology]

[0003] Atherosclerosis is the leading cause of death and disability worldwide, accounting for nearly one-third of all human mortality. Although some developed countries have made significant progress in risk factor modification and lifestyle behavior changes, some estimates predict that the global prevalence of atherosclerosis is still rising, resulting in more than 23 million deaths per year by 2030. The economic burden is staggering, with estimated annual costs of treating atherosclerosis and its sequelae exceeding $200 billion in the United States alone.

[0004] Atherosclerosis is a pathological process of arterial aging. In early life, supple elastin fibers within the arterial media provide the structural elasticity and adaptability required for arterial pulsation and pulse wave transmission. Over decades, however, sustained pressure and motion slowly denature the structural matrix proteins, causing elastin fatigue and destruction. The result is a slow but inexorable loss of compliance and a chronic stiffening of the arterial wall. Loss of pulsatility and pulse wave reflection leads to a sluggish flow velocity profile, loss of flow reversal, and attenuation of the antegrade flow coefficient. This results in long periods of relative stagnation during diastole, with increased residence time in wall particles and cells. The dysfunctional wall beneath the stagnant boundary layer begins to accumulate circulating atherogenic cholesteryl fatty acyl ester and triglyceride particles, especially apolipoprotein B-containing lipoproteins. Oxidative modification of lipoproteins activates the overlying endothelium to secrete chemokines, which attract blood-borne monocytes that roll along the endothelium and tether them to the vascular surface made sticky by the exposure of adhesion molecules and tissue factors. Extravasation of firmly attached monocytes traps the cells within the thickened subendothelial space. The ongoing pathological process thus initiated generates fatty occlusive lesions through continued recruitment and infiltration of cholesterol-laden foam cells, inflammatory and hematopoietic cells, as well as progressive accumulation of lipid matrix and smooth muscle proliferation, which slowly ascend the endothelium and begin to invade the arterial lumen. When atherosclerotic plaques grow large enough to reduce the flow of blood and oxygen to vital organs, they cause a chronic clinical syndrome of chest pain (angina pectoris), mini-strokes (transient ischemic attacks), and circulatory failure (claudication). More complex plaques with a stiffened core and a degenerated fibrous cap can suddenly rupture, leading to acute occlusion of the artery in which they reside. These can result in serious life-threatening clinical events including heart attack (myocardial infarction), stroke (cerebrovascular accident) and gangrene (critical limb ischemia).

[0005] The first stent type widely applied to treat atherosclerotic plaque was the balloon-expandable stent (BES), designed as an open mesh tube made of stainless steel. When crimped onto an angioplasty balloon, it could be advanced coaxially through the arterial tree and deployed directly into the plaque. Stent implantation created a larger, more durable flow channel compared to balloon angioplasty alone.

[0006] Today, balloon-expandable stents are deployed in nearly all percutaneous coronary intervention (PCI) cases and approximately half of all peripheral intervention procedures.

[0007] To support the open large arteries and avoid excessive recoil and deformation, peripheral BES are rigid medical devices. They are typically 0.5-2x10 5 Pa(375~1500mmHg, 0.05~0.2N / mm 2 ) pressures, non-physiological forces far exceeding any intravascular or extravascular pressures observed in the human body. In fact, BES are more than 10 times stiffer than the blood vessels they occupy. Because they are so stiff, BES can only be implanted in a limited number of anatomical locations, namely those with minimal or easily predictable arterial motion, such as the coronary, renal, and common iliac arteries. As such, implantation of BES is definitely not recommended for many important peripheral vascular beds, including the carotid, subclavian, external iliac, common femoral, superficial femoral, and popliteal arteries.

[0008] The stiffness of BES also severely limits the length that can be used. If a stent is implanted for too long, it will kink or tear the moving artery, leading to restenosis, thrombosis, pseudoaneurysm formation, and possibly device breakage and migration. Stent manufacturers, aware of the risks, make devices available in limited lengths. Although atherosclerotic lesions in peripheral arteries can be hundreds of mm long, the longest available BES are only 60 mm long. They are clearly insufficient for interventions in the leg, where lesions over 200 mm occur routinely.

[0009] As early as 1969, it was theorized that intravascular stents should be flexible rather than rigid. An equiatomic alloy of nickel-titanium called Nitinol, originally developed for aerospace applications, was thought to exemplify ideal mechanical properties for vascular scaffolding. One property was superelasticity, the ability of the metal to return to its original shape after significant deformation. This ensured flexibility within arteries moving within the human body. The other property was shape memory, the ability of the alloy to be annealed at one temperature, sufficiently deformed at a lower temperature, and then return to its original shape when heated. This allowed Nitinol stents to be compressed at low temperatures into a delivery system, then released and expanded within a warm mammalian environment upon implantation.

[0010] The first self-expanding nitinol stent (SES) approved for clinical use was a simple coiled wire made of nitinol. It was introduced to the US market in 1992. The availability of seamless tubes of nitinol soon allowed the development of laser-cut tubular nitinol stents. In modern times, tubular nitinol SES are the most common devices deployed in long, flexible vessels such as the external iliac and superficial femoral arteries.

[0011] Because SES do not generate as much force as BES, they rarely fully dilate vessels. To dilate them more completely, SES are routinely post-dilated with a larger diameter balloon after deployment. However, even after repeated balloon dilations, the relatively weak SES is unable to overcome the inward force of the recoil artery, resulting in an insufficient post-procedure diameter. This occurs surprisingly frequently after SES deployment, especially in peripheral arteries suffering from significant atherosclerotic disease. In one study, underdilation of the target lesion (residual stenosis of 30% or more) was observed in 70% of cases after SES implantation in calcified arteries.

[0012] A second drawback to the use of nitinol SES is their disturbing propensity to fracture. Although only occasionally observed with BES, SES fracture is surprisingly common, as high as 65% in one clinical report. Although not fully understood, one attractive hypothesis for this phenomenon is that fracture may be a function of the inherent biomechanical forces imposed on the stent in the lower extremity. Leg kinematics are complex movements, and the hip and knee loading during walking can repeatedly compress the artery axially and even generate multidimensional bending, twisting, and kinking. This can result in single or multiple strut fractures, or in severe cases, complete severing of the stent. Fractures are more common after implantation of long and / or overlapping stents, and perhaps in more active patients. Endovascular stent fracture is clearly associated with restenosis, although whether the relationship is associative or causal is controversial.

[0013] The unique mechanism and design of the SES ensures that the chronic force pattern on a stented artery is significantly different than that of a BES. After BES deployment, the forces on the artery are static and temporary. The artery is perturbed by the initial stretch and stent deployment, but upon recovery, it heals completely and returns to a quiescent state. However, the vessel housing the Nitinol SES is continually exposed to a chronic outward force (COF) exerted by the ever-expanding, twisted device. COF accompanies all SES implantations, since by definition, the SES must be “oversized” at the time of implantation. That is, the nominal diameter of the stent must, in all cases, exceed the reference vessel diameter (RVD) of the target lesion, so that the flexible, unfixed device will remain in place after deployment. The final diameter of the device is always smaller than its nominal “shape memory” diameter as manufactured, and so will continue to exert an outwardly expanding force on the vessel wall until, at which point, its nominal diameter is reached (which is extremely rare). Combined with the movement of the blood vessels into which SES are typically implanted, this ensures continued and chronic perturbation of the vessel wall for many years after deployment of the device. The artery responds with chronic inflammation, foreign body reaction, smooth muscle cell proliferation and restenosis. This is particularly troublesome in anatomical areas that are prone to bending and tortuosity, such as the common femoral artery. The problem is so prevalent that implantation of a nitinol SES at the hip or knee is surgically discouraged.

[0014] Finally, although Nitinol SES are much more flexible than their BES counterparts, continued thickening of SES-treated arteries does ultimately cause the stented artery to become stiffer. Even arteries treated with so-called "flexible" stents develop significant foreign body reactions, stiffening and inducing kinking and twisting of the unstented portion. Although exaggerated motion of the remaining artery may still allow limited motion and maintain patency, the resulting abnormal flow patterns and compliance very often lead to thrombosis and failure.

[0015] Given the nonphysiologic nature of SES in the high-resistance peripheral vasculature, their overall poor efficacy is not surprising. One-year primary patency of superficial femoral arteries treated with SES remains dismal at 60% and continues to decline with each passing year.

[0016] To address the myriad of issues associated with permanent metallic implants, stents that slowly dissolve after deployment have long been envisioned. So-called “bioresorbable vascular scaffolds” (BVS) potentially offer several important biological and physiological advantages, including (1) effective scaffolding without the permanence of metallic implants, (2) attenuation of inflammation and chronic foreign body reaction leading to reduced restenosis and enhanced long-term patency, (3) support of adaptive vascular remodeling, (4) restoration of physiological vasoactive function, and (5) facilitation of imaging and monitoring during follow-up.

[0017] The original bioabsorbable device was the "gut" surgical suture, the first evidence of which in historical records dates back approximately four millennia. Gut sutures are derived from the dried intestines of sheep, goats, or cows, but the name "gut" probably persisted because they were also used as strings for musical instruments, sometimes called "kits". Gut sutures can be classified as bioabsorbable because they can be enzymatically degraded and reabsorbed in vivo. More modern bioabsorbable surgical sutures are synthetic. Other recently developed bioabsorbable medical devices include bioabsorbable screws and fracture plates for the treatment of traumatic injuries, indwelling scaffolds that serve as the basis for tissue engineering and regenerative medicine, chemotherapy-loaded polymers for tumor treatment, inert synthetic wraps for the prevention of postoperative peritoneal adhesions, bioabsorbable scaffolds for stenting of the upper airway and Eustachian tube, and bioabsorbable endovascular scaffolds (stents). Unfortunately, recent longer-term results have raised questions regarding the safety and efficacy of first-generation absorbable coronary stents.

[0018] It would therefore be advantageous to have a stent for use in the vascular system that is stiff when implanted to maximally expand and scaffold the artery, but that slowly loses stiffness to allow the vessel to return to its original healthy, flexible state. At least some of these objectives will be met by the embodiments described below. Summary of the Invention

[0019] Embodiments herein describe a device for placement within a blood vessel to maintain or enhance blood flow through the vessel. The device may include a plurality of balloon expandable bioabsorbable vascular stent elements configured to be implanted within the vessel as a multi-element stent. The stent elements may be positioned consecutively along the length of the balloon with spacing of 1 mm or less between the stent elements in a non-expanded state. The stent elements may be configured to shorten to an expanded state at the target vessel location upon balloon expansion, creating spacing between the stent elements in the expanded state such that the stent elements do not contact each other at the target vessel location during skeletal movement. The stent is configured to be radially rigid and longitudinally flexible after implantation at the target vessel location.

[0020] The cell pattern of the stent elements may be configured to shorten the stent elements upon expansion and provide spacing between the stent elements in the expanded state. In one embodiment, the stent elements include one or more shortened sections configured to shorten upon expansion to the expanded state and one or more extended sections configured to extend to the expanded state. The shortened sections may include closed cells. Additionally or alternatively, the shortened sections may include open cells having one or more struts connecting one or more crests of the first ring to one or more crests of the second ring. The extended sections may include open cells having one or more struts connecting one or more valleys of the first ring to one or more valleys of the second ring.

[0021] In some embodiments, the stent is made of poly(L-lactic acid) (PLLA), poly(D-lactic acid) (PDLA), poly(D,L-lactic acid) (PDLLA), semicrystalline polylactide, polyglycolic acid (PGA), poly(lactic acid-co-glycolic acid) (PLGA), poly(iodized desaminotyrosyl-tyrosine ethyl ester) carbonate, polycaprolactone (PCL), salicylate-based polymers, polydioxanone (PDS), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoesters, polyanhydrides, poly(glycolic acid-co-trimethylene carbonate), poly(iodized desaminotyrosyl-tyrosine ethyl ester) carbonate, polyphosphoesters, polyphosphoester urethanes, poly(amino acid ), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonates), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, polyurethanes including polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicones including polysiloxanes and substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, PLLA-co-PCL, polyacrylates, polyvinylpyrrolidone, polyacrylamide, or combinations thereof.

[0022] In one embodiment, the stent includes a therapeutic agent that can prevent or attenuate inflammation, cell dysfunction, cell activation, cell proliferation, neointima formation, hyperplasia, late atherosclerotic changes, or thrombosis.

[0023] In one embodiment, the radial stiffness of the stent slowly decays as its structural polymer bonds are broken and metabolized, so that the stent slowly becomes more flexible, inducing vascular adaptation and remodeling and restoration of vascular elasticity.

[0024] A method for manufacturing an intravascular stent may include loading a multi-element stent including a plurality of individual stent elements onto an inflatable balloon in an expanded state such that the stent elements are positioned sequentially along the longitudinal length of the balloon and the stent elements do not contact one another. The stent elements may be spaced apart such that the stent elements do not contact one another at the target vascular location during skeletal movement. The balloon may be deflated to crimp the multi-elements to a non-expanded state, thereby elongating each stent element and reducing the spacing between the stent elements to 1 mm or less.

[0025] This and other aspects of the disclosure are described herein. [Brief description of the drawings]

[0026] The present embodiments have other advantages and features that will become more readily apparent from the following detailed description and the appended claims, when taken in conjunction with the accompanying drawings. [Figure 1] 1 illustrates typical radial forces of an intravascular stent. [Figure 2A] 1 illustrates one embodiment of a multi-element stent. [Figure 2B] FIG. 2B is an enlarged view of the stent element of FIG. 2A. [Figure 3A-C] 1 depicts the deployment of a balloon expandable multi-element stent. [Figure 4A] 1 shows a multi-element stent implanted in the popliteal artery with the hip and knee in full flexion. [Figure 4B] 4B depicts the implanted device of FIG. 4A shown in three dimensions. [Figure 5A-C] FIG. 13 is a side view of a self-expanding nitinol stent placed in the distal SFA and popliteal artery illustrating various amounts of leg flexion. [Figure 6] Depicts the angle created between the stent elements during maximum flexion of the target vessel location during scaffolding movement. [Figure 7A-D]

[0033] Figure 7 shows one embodiment of a stent pattern: Figure 7A is a two-dimensional depiction of an element; Figure 7B shows an enlarged view of a cell of Figure 7A; Figures 7C and 7D show the stent element of Figure 7A in a cylindrical shape. [Figure 8A-D] 1 shows a cell diagram of a pattern of stent elements that shorten upon expansion. [Figure 9] 1 shows a laser cut stent. [Figure 10A-E] 1 shows a multi-element stent mounted on an angioplasty balloon. [Figure 11A-F] A finite element analysis (FEA) of a bioabsorbable polymer stent cell that lengthens when crimped and shortens when expanded is shown. [Figure 12A-D] 4 shows cell patterns for various connector configurations. [Figure 13A-C] Shown is a two-segment device deployed in the left iliac-femoral artery. [Figure 14] Shown is an optical coherence tomography (OCT) image of a bioabsorbable stent deployed in a porcine iliac-femoral artery. [Figure 15A-C] 13 shows micro-CT images of the scaffold arteries. [Figure 16A-B] Shown is eight consecutive balloon-expandable stent segments implanted along the entire length of a porcine iliac-femoral artery. [Figure 17] FIG. 1 is a schematic diagram of a microstereolithography machine used to create a stent, according to one embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] While the invention has been disclosed with reference to particular embodiments, it will be understood by those skilled in the art that various modifications can be made and equivalents substituted without departing from the scope of the invention. In addition, many modifications can be made to adapt a particular situation or material to the teachings of the invention without departing from its scope.

[0028] Throughout this specification and the claims, the following terms take on the meanings expressly associated therewith, unless the context clearly dictates otherwise. The meanings of "a," "an," and "the" include plural references. The meaning of "in" includes "in" and "on." With reference to the drawings, like numbers indicate like parts throughout the figures. Additionally, reference to the singular includes reference to the plural unless otherwise expressly stated or inconsistent with the disclosure herein.

[0029] The word "exemplary" is used herein to mean "serving as an example, instance, or illustration." Any implementation described herein as "exemplary" is not necessarily to be construed as advantageous over other implementations.

[0030] Various embodiments are described herein with reference to the figures. The figures are not drawn to scale and are intended only to facilitate the description of the embodiments. They are not intended as an exhaustive description of the invention or as limitations on the scope of the invention. In addition, an illustrated embodiment need not have all aspects or advantages shown. An aspect or advantage described in connection with a particular embodiment is not necessarily limited to that embodiment and may be implemented in any other embodiment even if not so illustrated.

[0031] FIG. 1 shows a typical radial force of an intravascular stent. A typical "bioabsorbable vascular scaffold" (BVS) or absorbable stent has a radial force of less than 2 N / cm. Similarly, a typical self-expanding metal stent (SES) has a radial force of less than 2 N / cm. A typical balloon expandable metal stent (BES) has a much higher radial force, which can exceed 18 N / cm.

[0032] Embodiments herein describe a novel intravascular absorbable device design that maintains long vascular flow paths (patency) by providing temporary rigid radial support that is much greater than that provided by typical absorbable or self-expanding metal stents (SES) and comparable to that provided by balloon-expandable metal stents (BES). When implanted, the absorbable device exerts a high degree of radial force to hold open diseased arteries, nearly equivalent to that of a large diameter peripheral balloon-expandable metal stent.

[0033] In contrast to most stent patterns designed to combine both radial force and longitudinal flexibility, the patterns described herein are specifically tailored to maximize radial force and stiffness and eliminate longitudinal and axial flexibility.

[0034] The devices described herein are multi-element vascular stents (or "vascular scaffolds") that are composed of multiple short, rigid, cylindrical stent segments or elements that are separate from one another but are sometimes collectively referred to as multi-element stents.

[0035] Generally, at least two of the elements of the multi-element stents described herein are sufficiently stiff to provide a desired level of strength to withstand the stresses of the vessels in which they are deployed, such as tortuous peripheral vessels. At the same time, the multi-element stents are also flexible because they are composed of multiple separate elements, and therefore can be deployed in curved and tortuous vessels. In some embodiments, at least two of the elements vary in stiffness or radial strength in the multi-element stent. In one embodiment, the outer element may have a lower radial strength than the inner element in the multi-element stent. In another embodiment, the multi-element stent includes elements with continuously increasing radial strength along the length of the multi-element stent, such as in an AV fistula. Thus, the radial strength of the elements can be different and tailored according to the known characteristics of the target artery.

[0036] Additionally, since balloon expandable stents are typically stronger than self-expanding stents, the multi-element stents described herein will generally be balloon expandable rather than self-expanding. Each balloon expandable element of the stent may have a relatively high radial force (stiffness) due to the structures and materials described. A stent element is defined as being radially stiff if it has significantly higher radial strength than a self-expanding stent of similar or greater magnitude than a conventional balloon expandable metal stent, such as steel or cobalt chrome.

[0037] When mounted in series on an inflatable balloon, they can be implanted side-by-side in long vessels at the same time. During organism movement, the elements can move independently and maintain their individual shape and strength, while the unstented intervening elements of the vessel can twist, bend, and rotate unhindered. The result is a treated vessel with a rigidly maintained flow path, yet unlimited flexibility during organism movement.

[0038] The described embodiments utilize the principles that (1) a rigid device deployed via balloon expansion represents an optimal design for an endovascular stent that takes into account the temporary effects on the arterial wall and the relative ease of precise implantation, (2) a long rigid device cannot be safely implanted in an artery that bends and twists with skeletal motion, (3) long arteries that bend and twist can be effectively treated with multiple short BES that allow unstented intervening arterial elements to move unhindered, (4) the length, number, and spacing of stent elements can be determined by the known and predictable bending characteristics of the target artery, and (5) the artery only needs scaffolding temporarily, with delayed dissolution of the stent having little effect on the long-term efficacy of the treatment.

[0039] One embodiment of the fully assembled device is shown in FIG. 2A. A single balloon inflation and device deployment can treat long segments of diseased arteries while maintaining the artery's critical ability to bend with skeletal movements such as sitting or walking. The multi-element stent 200 includes multiple stent elements 201. The individual balloon expandable stent elements 201 are crimped to an inflatable balloon 203 to facilitate delivery. FIG. 2B is an enlarged view of the stent elements 201 of FIG. 2A. The individual elements 201 are positioned sequentially along the longitudinal length of the balloon 203 and are spaced apart such that the stent elements 201 do not touch each other. Furthermore, the spacing is such that the stent elements 201 do not touch or overlap during skeletal movements after deployment. The number of elements 201, the length of the elements, and the gaps 202 between the elements 201 can vary depending on the target vessel location. In one embodiment, each element 201 in the multi-element stent 200 has the same length. In a multi-element stent having more than two elements 201, and therefore more than two gaps 202, the gaps may be of the same length.

[0040] Figures 3A-C depict the deployment of a balloon-expandable multi-element stent. In Figure 3A, the balloon-mounted multi-element stent is advanced to the lesion. In Figure 3B, the balloon and stent are expanded. In Figure 3C, the balloon is withdrawn, leaving the multi-element stent still in the artery.

[0041] Figure 4A shows a multi-element stent implanted in the popliteal artery with the hip and knee in full flexion. Figure 4B depicts the implanted device of Figure 4A shown in three dimensions. The individual stent elements 401 are spaced apart so that they do not overlap even when the artery is highly curved. Unhindered arterial movement is provided by bending or stretching of the unstented gaps 402.

[0042] Given the length and constant motion of limb arteries, proper stent element length and spacing between stent elements are important. If the stent elements are too long, the stent will lack sufficient longitudinal flexibility. If the elements are too close together, they may overlap during motion, also leading to a lack of sufficient longitudinal flexibility. This may lead to breakage of the stent elements. Breakage of intravascular stents is clearly associated with restenosis. Similarly, if elements are too short or spaced too far apart, the lesion may not adequately contact the target lesion. The appropriate length and spacing of the elements may be determined by known characteristics of the target artery.

[0043] 5A-5C are side views of a self-expanding nitinol stent 500 placed in the distal SFA and popliteal artery, illustrating various amounts of leg flexion. FIG. 5A illustrates the stent 500 with the leg in a neutral position and minimal / mostly extended. FIG. 5B shows the stent 500 in partial flexion (70° / 20° knee / hip flexion), with the circle and bend diameter 502 illustrating the bend angle and curved deformation of the stent 600. FIG. 5C illustrates the stent 500 in greater flexion (90° / 90° knee / hip flexion). As FIGS. 5A-5C illustrate, the stent 500 deforms significantly with leg movement. The drawn circle illustrates the use of the bend diameter 502 to describe the degree of deformation. A stent that bends around a smaller circle (with a smaller diameter 502) deforms more. For example, the more deformed stent of Figure 5C has a smaller bend diameter 502 than the less deformed stent 500 of Figure 5B. The nearly straight stent of Figure 5A has a very large bend diameter that is too large to accurately estimate.

[0044] Stent deformation after implantation in the femoropopliteal artery is shown in Table 1. Perfect straightness is assigned a value of 180°. Deflection (°) is calculated as the difference in bending angle at various degrees of limb flexion. Note the greater bending of the popliteal stent compared to the SFA stent. [Table 1]

[0045] The length and spacing of the individual elements are determined in part by the planned anatomical location of the device. For example, according to available anatomical and physiological data, the superficial femoral artery (SFA) undergoes minimal bending and compression during thigh and knee flexion (approximately 7° of flexion and approximately 5% compression), so individual stent elements in devices targeted to the SFA can therefore be spaced fairly narrowly and do not overlap when the leg is flexed. In contrast, the popliteal artery deforms more severely when the hip and knee are flexed (approximately 60° of flexion and approximately 8% compression). Thus, individual stent elements in devices targeted to the popliteal artery must be spaced more widely to avoid overlapping during skeletal motion.

[0046] 6 depicts the angle θ (25.609° for the example embodiment shown in FIG. 6) created between stent elements 601 during maximum bending of the target vessel location during skeletal movement. The angle θ is a calculated angle governed by the maximum bending diameter and maximum length of the individual stent elements 601 for each anatomical location. For the SFA, the angle θ is calculated to be 8.473°. For the popliteal fossa, the angle θ is calculated to be 25.609°.

[0047] In one embodiment, the minimum required gap between elements may be calculated using the planned stent diameter (D) in the expanded state at the target vessel location and the angle (θ) created between the stent elements during maximum vessel bending at the target vessel location. The gap (G) may be calculated using the following formula:

number

[0048] The ideal gap length between stent elements may also be influenced by axial stent compression or shortening during limb flexion. Table 3 shows the axial stent compression after implantation in the femoropopliteal artery. The amount of axial compression is calculated as the difference in stent length measured at various degrees of limb flexion. [Table 3]

[0049] The ideal gap length, taking into account axial compression, can be calculated using the following formula: Gap=((LEC+GEC-GC) / (e-1))+G L is the length of the stent element. E is the number of stent elements. G is the gap length calculated using the previous formula. C is the maximum axial compression percentage of the target vessel location. For the SFA, C is approximately 5%. For the popliteal fossa, C is approximately 8%.

[0050] As can be seen from this formula, if all other factors remain the same, the distance between each stent element increases as the length of the stent element increases. Similarly, if all other factors remain the same, the distance between each stent element decreases as the number of elements in a multi-element stent increases. Similarly, if all other factors remain the same, the distance between each stent element increases as the maximum axial compression percentage of the stent element at the target vessel location increases. Table 4 shows the approximate relationship of device diameter, length, number of elements, and element spacing for devices intended for the superficial femoral artery. Table 5 shows the approximate relationship of device diameter, length, number of elements, and element spacing for devices intended for the popliteal artery. [Table 4] [Table 5]

[0051] The stents described herein can be formed from a variety of different materials. In one embodiment, the stent can be formed from a polymer. In various alternative embodiments, the stent or stent elements can be made from any suitable bioabsorbable material that is non-toxic and dissolves in the human body, such as, but not limited to, poly(L-lactic acid) (PLLA), polyglycolic acid (PGA), poly(iodized desaminotyrosyl-tyrosine ethyl ester) carbonate, etc. In one embodiment, at least two of the elements comprise different materials. For example, the outer element can be made of a bioabsorbable material that degrades faster than the inner element of the bioabsorbable multi-element stent.

[0052] In alternative embodiments, any suitable polymer can be used to construct the stent. The term "polymer" is intended to include the product of a polymerization reaction, including homopolymers, copolymers, terpolymers, etc., whether natural or synthetic, including random, alternating, block, graft, branched, crosslinked, mixtures, compositions of mixtures, and variations thereof. The polymer can be in true solution as particles, saturated or suspended, or supersaturated with beneficial agent. The polymer can be biocompatible or biodegradable. By way of example and not limitation, polymeric materials include poly(D-lactic acid) (PDLA), poly(D,L-lactic acid) (PDLLA), poly(iodized desaminotyrosyl-tyrosine ethyl ester) carbonate, poly(lactic acid-co-glycolic acid) (PLGA), salicylate-based polymers, semicrystalline polylactide, phosphorylcholine, polycaprolactone (PCL), poly-D,L-lactic acid, poly-L-lactic acid, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone (PDS), polyorthoesters, polyanhydrides, poly(glycolic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), cyanoaromatic polysaccharides, and the like. These may include, but are not limited to, acrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, polyurethanes including polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicones including polysiloxanes and substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, PLLA-co-PCL, polyacrylates, polyvinylpyrrolidone, polyacrylamides, and combinations thereof.Non-limiting examples of other suitable polymers include thermoplastic elastomers in general, polyolefin elastomers, EPDM rubber, and polyamide elastomers, as well as biostable plastic materials including acrylic polymers and their derivatives, nylons, polyesters, and epoxies. In some embodiments, the stent may include one or more coatings with materials such as poly(D,L-lactic acid) (PDLLA). However, these materials are merely examples and should not be considered as limiting the scope of the invention.

[0053] The stent elements may include a variety of shapes and configurations. Some or all of the stent elements may include closed cell structures formed by intersecting struts. The closed cell structures may include diamond, square, rectangular, parallelogram, triangular, pentagonal, hexagonal, heptagonal, octagonal, cloverleaf, circular, elliptical, and / or oval shapes. The closed cells may also include slot-type shapes, such as H-slots, I-slots, J-slots, etc. Additionally or alternatively, the stent may include open cell structures, such as helical, serpentine, zigzag, etc. The intersection of the struts may form cell corners that are sharp, perpendicular, rounded, blunt, flat, beveled, and / or chamfered. In one embodiment, the stent may include a plurality of different cells having different cell shapes, orientations, and / or sizes. Various cell structures are described in PCT International Application No. PCT / US16 / 20743, entitled "MULTI-ELEMENT BIORESORBABLE INTRAVASCULAR STENT," the entire disclosure of which is incorporated herein by reference.

[0054] Returning to FIG. 2B, in this exemplary embodiment, the stent element 201 has a diamond-shaped closed cell pattern. The element 201 includes mixed diamond-shaped closed cells 204, 205. The diamond-shaped cells 204 can be aligned longitudinally and / or circumferentially in a repeating pattern. Similarly, the diamond-shaped cells 205 can be aligned longitudinally and / or circumferentially in a repeating pattern. Additionally or alternatively, the diamond-shaped cells 204 and the diamond-shaped cells 205 can be aligned helically in an alternating pattern. In one embodiment, the diamond-shaped cells 204 and the diamond-shaped cells 205 are offset circumferentially. Additionally, the diamond-shaped cells 205 can be formed at a central location between four adjacent diamond-shaped cells 204. The width of the strut 206 between two corners of the longitudinally aligned diamond-shaped cells 204 is greater than the width of the strut 207 between two corners of the longitudinally aligned diamond-shaped cells 205.

[0055] In contrast to most balloon expandable stent patterns, which are designed to minimize foreshortening upon stent expansion, the various patterns described herein are specifically designed to foreshorten upon expansion, such that the length of the deployed elements is significantly shorter than the length of the elements when crimped. Although previously felt to be an undesirable characteristic of intravascular stents, the patterns described herein are actually intended to foreshorten, ultimately resulting in discontinuity of the fully deployed device within the vessel.

[0056] One embodiment of a stent pattern designed to foreshorten upon expansion is shown in Figures 7A-7D. The structure of the stent pattern may be designed for maximum radial force and stiffness, stretching when crimped and foreshortening when expanded. Stent element 701 has a diamond-shaped closed cell pattern with relatively thick strut width and diagonally angled links. Element 701 includes diamond-shaped closed cells 704. Element 701 may include struts 706 with widths of 225 microns or more. Element 701 may similarly include struts 706 with thicknesses of 225 microns or more. In one embodiment, element 701 includes struts 706 with widths and / or thicknesses of about 250 microns. The width and / or height of struts 706 between the two corners of the diamond-shaped cell 704 may be greater or less than the widths and / or heights of the struts 706 that form the sides of the diamond-shaped cell 704.

[0057] 8A-8D show cell diagrams of patterns of stent elements that shorten upon expansion. The individual cell patterns of absorbable intravascular stents are designed for maximum radial force and stiffness, elongating when crimped and shortening when expanded. The stent elements can have a diamond-shaped closed cell structure with relatively thick strut widths and diagonally angled links.

[0058] An example of an actual laser cut stent designed herein is shown in FIG. 9. FIGS. 10A-10E show two such segments mounted on a standard angioplasty balloon. FIG. 10A shows two segments crimped onto the angioplasty balloon. The segments were applied with an intervening space that was eliminated as the stent stretched during crimping. To the naked eye, the device appears as a single continuous stent. However, when the balloon is subsequently inflated, the two rigid stent segments shorten to create an intervening space between them (FIGS. 10B-10E). Because the segments are rigid, the intervening space allows the artery to flex with normal skeletal motion.

[0059] There are several parameters that can be manipulated to engineer the desired spacing between elements. Examples of seven of these parameters are provided here.

[0060] Parameter 1: Stent pattern The stent pattern generally influences the amount of foreshortening that the stent undergoes during expansion. The more foreshortening a given stent pattern, the more spacing is created between elements. Many features of the stent pattern can be manipulated to achieve the desired amount of foreshortening and spacing between elements.

[0061] One feature that can be manipulated is the change in angle that the struts undergo during expansion. The change in angle can be seen in Figures 11A-11F. Figures 11A-11F show a finite element analysis (FEA) of a bioabsorbable polymer stent cell that elongates when crimped and shortens when expanded. The stress scale is shown on the left. Figures 11A-11F show the progressive crimping of a single cell 1104. Note that even when fully crimped, there is a maximum stress of 156 von Mises (Figure 11F), demonstrating that the device can be effectively crimped without undue strain or failure. In 11F, the struts are in a crimped configuration prior to expansion, with each strut essentially horizontal. In 11A, the struts are in a fully expanded configuration, with each strut rotated from the horizontal to a more upright orientation. The greater this change in angle, the more the pattern will shorten for a closed cell pattern. Changing the length of the struts or the number of cells around the stent element can affect the change in angle.

[0062] For open cell patterns, depending on the configuration of the connectors between the rings, greater strut angle change during expansion may increase, decrease, or have no effect on shortening. Figures 12A-12D show cell patterns with various connector configurations. When connector 1201 connects crest 1202 of one ring to crest 1202 of another ring (Figure 12A), that portion of the pattern acts like a closed cell pattern, and increasing strut angle change increases shortening and increases spacing between elements. When connector 1201 connects valley 1203 of one ring to valley 1203 of another ring (Figure 12B), increasing strut angle change causes elongation during expansion, and that portion of the pattern causes decreased spacing between elements. When connector 1201 connects valley 1203 of one ring to crest 1202 of another ring (Figure 12C), increasing strut angle change does not affect the length of the stent during expansion.

[0063] The various connector configurations described above may be used in combination with each other and / or with the closed cell pattern to manipulate the amount of foreshortening and the size of the spacing between elements. For example, the pattern shown in FIG. 12D combines one ring of an open cell pattern with every two rings of a closed cell pattern. The particular connector 1201 configuration of the open cell portion contributes to elongation upon expansion, while the closed cell portion foreshortens upon expansion. The foreshortening partially offsets the foreshortening, thus resulting in a smaller amount of foreshortening than would result from using only the closed cell pattern.

[0064] Parameter 2: Element length Given a constant amount of foreshortening per unit length of a stent element, the absolute amount of foreshortening is proportional to the length of the element, and since the spacing between elements is determined by the amount of foreshortening, it is also proportional to the length of the element.

[0065] Parameter 3: Unfolded diameter For stent elements that foreshorten during deployment, creating a space to the next element, the larger the diameter to which the element is expanded, the greater both the foreshortening and the space created.

[0066] Parameter 4: Crimp Spacing Spacing between elements after deployment can be directly manipulated by changing the pre-deployment spacing when the elements are crimped to the balloon. In the exemplary device shown in Figures 10A-10F, the elements are crimped so that they touch, and all of the spacing between the elements is created by shortening and / or movement of the elements. However, this is not required. Elements can also be crimped with pre-existing spacing that increases during deployment. In one embodiment, elements can be crimped with pre-existing spacing of 1 mm or less.

[0067] Parameter 5: Stent material The stent material can affect the amount of spacing created in two ways. First, the material used affects the design of the stent pattern because different materials may undergo different amounts of strain prior to fracture and different stent patterns will cause the material to undergo different amounts of strain during deployment. Second, even when the same stent pattern is used, different materials may react differently to both the crimping and deployment processes, thereby affecting different amounts of foreshortening and the size of the inter-element spacing.

[0068] Parameter 6: Crimping process variables Balloon expandable bioabsorbable stents may be initially manufactured with a diameter close to the final deployed diameter and then crimped onto a balloon or collapsed to a smaller diameter via a crimping process. Stent elements that foreshorten during deployment elongate during the crimping process. Both the amount of elongation and deformation of the stent pattern that occurs during crimping can be affected by several variables of the crimping process. The amount of elongation that the stent elements undergo during crimping affects the amount that the elements foreshorten during deployment and the size of the spacing between elements that is created. Variables that affect elongation during the crimping process include the temperature at which the crimping is performed, the time that the crimping occurs, the presence or absence of an inflated balloon during parts of the crimping process, and the pressure of the balloon. For example, if a higher temperature is used during crimping, the material may become softer during crimping and the stent struts may deform more, leading to a reduced amount of elongation, which in turn leads to less foreshortening during deployment.

[0069] Parameter 7: Balloon material The material of the balloon used to deploy the stent can affect the size of the spacing between the elements, as different balloon materials generate different amounts of friction between the balloon and the stent. Thus, different balloon materials may allow more or less movement of the entire stent element or only a portion of the element relative to the balloon. This can affect the size of the spacing between the elements in two ways. First, the allowed motion affects the amount of elongation that occurs in the element during crimping and the amount of shortening that occurs during deployment. Second, the allowed motion can affect the overall movement of the element during deployment. For example, if the spacing between two elements increases during deployment, the elements may slide apart from each other, increasing the size of the spacing. The amount that the elements slide apart will be affected by the balloon material.

[0070] Device embodiments were acutely tested by implantation in laboratory animals. Domestic farm pigs were anesthetized with intramuscular administration of ketamine, azaperone, and atropine. Via surgical exposure, a sheath was placed in the right common carotid artery and wire access was secured in the left iliac-femoral artery system under fluoroscopic control. A two-segment device was deployed in the left iliac-femoral artery as shown in Figures 13A-C. In Figure 13A, the left hindlimb is stretched. Figure 13B shows the animal's hindlimb bent to simulate the bending of the human superficial femoral artery. The artery bends in the interval intervening between the two stents, while the scaffold segment itself remains rigid and straight. Figure 13C shows the extreme non-physiological bending of the hindlimb. The stented artery remained patent by bending in the interval intervening between the two rigid stents.

[0071] After deployment, optical coherence tomography (OCT) imaging was performed using an Illumien Optis imaging system (Abbott Laboratories, Abbott Park, IL). The OCT catheter was advanced into the vessel distally beyond the device and pulled back to a point proximal to the device. An optical coherence tomography (OCT) image of a bioabsorbable stent deployed in a porcine iliac-femoral artery is shown in Figure 14. Due to the high radial strength of the device, all scaffolding struts are perfectly opposed to the arterial wall.

[0072] Following deployment and imaging, animals were euthanized by lethal injection of saturated potassium chloride while maintaining deep anesthesia. The lower body was perfused with lactated Ringer's solution, followed by neutral buffered formalin. The scaffold artery was excised, processed through graded alcohols, and then scanned using a Nikon XT H225 micro-computed tomography device. Micro-CT images are shown in Figure 15A-C. The scaffold artery is shown intact in Figure 15A. The anterior arterial wall is subtracted in Figure 15B. Figure 15C shows the entire arterial wall subtracted. The device shortens upon expansion, creating an intervening space around which the pliable artery hinges.

[0073] Eight consecutive balloon expandable stent segments were implanted along the entire length of a porcine iliac-femoral artery. The results are shown in Figures 16A and 16B. A total of eight segments were implanted along the entire length of the iliac-femoral artery, approximately 12 cm. Figure 16A shows that the animal's hind limb was stretched. Aortic injection shows wide patency of the stented artery. Patency is again shown when the hind limb is manually flexed (Figure 16B). Although the artery has been treated with multiple consecutive stiff stents, its ability to move is maintained by the intervening intervals created by the shortening of the stents.

[0074] The devices described herein may include the incorporation of a therapeutic agent into one or more stent elements of a multi-element stent. In one embodiment, the therapeutic agent may be intended to prevent or attenuate pathological consequences of intraluminal intervention, such as inflammation, cellular dysfunction, cellular activation, cellular proliferation, neointima formation, hyperplasia, late atherosclerotic changes, and / or thrombosis. In various embodiments, any suitable therapeutic agent (or "drug") may be incorporated into, coated on, or otherwise attached to the stent.Examples of such therapeutic agents include antithrombotic agents, anticoagulants, antiplatelet agents, antilipid agents, thrombolytic agents, antiproliferative agents, anti-inflammatory agents, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters, antimitotic agents, antifibrin, antioxidants, antitumor agents, agents that promote endothelial cell recovery, matrix metalloproteinase inhibitors, antimetabolites, antiallergic agents, viral vectors, nucleic acids, monoclonal antibodies, tyrosine kinase inhibitors, antisense compounds, oligonucleotides. , cell permeation enhancers, hypoglycemic agents, lipid lowering agents, proteins, nucleic acids, agents useful for stimulating erythropoiesis, angiogenic agents, antiulcer / antireflux agents, and antiemetic / antiemetic agents, PPAR alpha agonists such as fenofibrate, selected PPAR-gamma agonists such as rosiglitazone and pioglitazone, heparin disodium, LMW heparin, heparoids, hirudin, argatroban, forskolin, bapriprost, prostacyclin, and prostacillin analogs, dextran, D-p he-pro-arg-chloromethylketone (synthetic antithrombin), glycoprotein IIb / IIIa (platelet membrane receptor antagonist antibody), recombinant hirudin, thrombin inhibitors, indomethacin, phenylsalicylate, beta-estradiol, vinblastine, ABT-627 (astrasentan), testosterone, progesterone, paclitaxel, methotrexate, fotemusine, RPR-101511A, cyclosporine A, vincristine, carvedilol, vindesine, dipyridamole, These include, but are not limited to, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexol, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, and iotrolan, antisense compounds, smooth muscle cell proliferation inhibitors, lipid lowering agents, radiopaque agents, antineoplastic agents, HMG CoA reductase inhibitors such as lovastatin, atorvastatin, simvastatin, pravastatin, cerivastatin, and fluvastatin, and combinations thereof.

[0075] Examples of antithrombotic, anticoagulant, antiplatelet, and thrombolytic agents include, but are not limited to, heparin sodium, unfractionated heparin, low molecular weight heparins such as dalteparin, enoxaparin, nadroparin, reviparin, aldoparin, and sertaparin, heparinoids, hirudin, argatroban, forskolin, bapriprost, prostacyclin, and prostacillin analogs, dextran, thrombin inhibitors such as D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb / IIIa (platelet membrane receptor antagonist antibody), recombinant hirudin, and bivalirudin, thrombin inhibitors, and thrombolytic agents, and thrombolytic agents such as urokinase, recombinant urokinase, prourokinase, tissue plasminogen activator, ateplase, and tenecteplase.

[0076] Examples of cytostatic or anti-proliferative agents include, but are not limited to, rapamycin and its analogs, including everolimus, zotarolimus, tacrolimus, novolimus, and pimecrolimus; angiotensin-converting enzyme inhibitors such as angiopeptin, captopril, cilazapril, or lisinopril; calcium channel blockers such as nifedipine, amlodipine, cilnidipine, lercanidipine, benidipine, trifluperazine, diltiazem, and verapamil; fibroblast growth factor antagonists, fish oil (omega-3-fatty acids), histamine antagonists, topoisomerase inhibitors such as lovastatin, etoposide, and topotecan; and antiestrogens such as tamoxifen.

[0077] Examples of anti-inflammatory agents include, but are not limited to, colchicine and glucocorticoids such as betamethasone, cortisone, dexamethasone, budesonide, prednisolone, methylprednisolone, and hydrocortisone. Nonsteroidal anti-inflammatory agents include, but are not limited to, flurbiprofen, ibuprofen, ketoprofen, fenoprofen, naproxen, diclofenac, diflunisal, acetominophen, indomethacin, sulindac, etodolac, diclofenac, ketorolac, meclofenamic acid, piroxicam, and phenylbutazone.

[0078] Examples of antineoplastic agents include, but are not limited to, alkylating agents including altretamine, bendamusine, carboplatin, carmustine, cisplatin, cyclophosphamide, fotemustine, ifosfamide, lomustine, nimustine, prednimustine, and threosulfin; mitotic inhibitors including vincristine, vinblastine, paclitaxel, docetaxel; antimetabolites including methotrexate, mercaptopurine, pentostatin, trimetrexate, gemcitabine, azathioprine, and fluorouracil; antibiotics such as doxorubicin hydrochloride and mitomycin; and agents that promote endothelial cell recovery, such as estradiol.

[0079] Anti-allergy agents include, but are not limited to, pemirolast potassium nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidines, and nitric oxide.

[0080] The beneficial agent may include a solvent, which may be any single solvent or combination of solvents. By way of example and not limitation, examples of suitable solvents include water, aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ketones, dimethylsulfoxide, tetrahydrofuran, dihydrofuran, dimethylacetamide, acetate, and combinations thereof.

[0081] Stents may be manufactured using addition or subtraction. In any of the described embodiments, the stent or stent elements may be manufactured as a sheet and rolled into a cylinder. Alternatively, the stent or stent elements may be manufactured in a cylindrical shape using an additive manufacturing process. In one embodiment, the stent may be formed by extruding material into a cylindrical tube. In some embodiments, a longer stent element may be formed during the manufacturing process and then cut into smaller stent elements / elements to provide a multi-element stent. In one embodiment, the stent tube may be laser cut with a pattern to form the stent elements.

[0082] 17, in one embodiment, the stent may be manufactured using a micro-stereolithography system 100 (or "3D printing system"). Some examples of currently available systems that may be used in various embodiments include, but are not limited to, the MakiBox A6 (Makible Limited, Hong Kong), CubeX (3D Systems, Inc., Circle Rock Hill, SC), and 3D-Bioplotter (EnvisionTEC GmbH, Gladbeck, Germany).

[0083] The micro-stereolithography system may include an illuminator, a dynamic pattern generator, an imager, and a Z-stage. The illuminator may include a light source, a filter, an electronic shutter, a collimating lens, and a reflector that projects uniformly intense light onto a digital mirror device (DMD) that creates a dynamic mask. FIG. 10 shows some of these components of one embodiment of a micro-stereolithography system 100, including a DMD board, a Z-stage, a lamp, a platform, a resin vat, and an objective lens. Details of 3D printing / micro-stereolithography systems and other additional manufacturing systems are well known in the art and will not be described here. However, according to various embodiments, any additional manufacturing system or process, whether now known or later developed, can potentially be used to manufacture stents within the scope of the present invention. In other words, the scope of the present invention is not limited to any particular additional manufacturing system or process.

[0084] In one embodiment, the system 100 may be configured to fabricate a stent using dynamic mask projection micro-stereolithography. In one embodiment, the fabrication method may include first generating a 3D microstructured scaffold by slicing a 3D model with a computer program and solidifying and stacking the images layer by layer in the system. In one embodiment, the reflector of the system is used to project a uniformly intense light onto the DMD, which generates a dynamic mask. The dynamic pattern generator creates an image of the sliced ​​section of the fabrication model by generating black and white areas similar to the mask. Finally, to stack the images, a resolution Z-stage moves up and down to refresh the resin surface for the next cure. In one embodiment, the Z-stage build subsystem has a resolution of about 100 nm and includes a platform for mounting the substrate, a vat for containing the polymer liquid solution, and a hot plate for controlling the temperature of the solution. The Z-stage creates a new solution surface with the desired layer thickness by moving deep down, moving up to a predetermined position, and then waiting a certain time until the solution is evenly distributed.

[0085] While specific embodiments have been shown and described, they are not intended to limit the invention. Various changes and modifications can be made to any of the embodiments without departing from the spirit and scope of the invention. The invention is intended to cover alternatives, modifications, and equivalents.

Claims

1. 1. A device for placement within a blood vessel to maintain or enhance blood flow through the vessel, comprising: a plurality of balloon-expandable, bioabsorbable vascular stent elements configured to be implanted in the vessel as a multi-element stent; the plurality of stent elements contact one another while being positioned successively along the longitudinal length of the balloon in an unexpanded state; a cell pattern of the plurality of stent elements configured to shorten the stent elements to an expanded state at a target vessel location upon balloon expansion and to separate the stent elements that contact one another in the expanded state to create spaces between the stent elements such that the plurality of stent elements do not contact one another at the target vessel location during skeletal movement; A device, wherein the stent is configured to be radially rigid and longitudinally flexible after implantation at the target vascular location.

2. 2. The device of claim 1, wherein the stent elements include one or more shortening sections configured to shorten to the expanded state upon expansion and one or more elongation sections configured to elongate to the expanded state upon expansion, wherein the elongation of the one or more elongation sections is less than the shortening of the one or more shortening sections and configured to partially offset the shortening of the stent elements by the one or more shortening sections, wherein a combined effect of the one or more shortening sections and the one or more elongation sections shortens the plurality of stent elements upon expansion to the expanded state and separates the stent elements that contact each other in the expanded state, creating spaces between the stent elements.

3. The device of claim 2 , wherein the shortened section comprises a closed cell.

4. The device of claim 2 , wherein the shortened section includes an open cell having one or more struts connecting one or more peaks of a first ring to one or more peaks of a second ring.

5. The device of claim 2 , wherein the extension section includes open cells having one or more struts connecting one or more valleys of the first ring to one or more valleys of the second ring.

6. 10. The device of claim 1, further comprising a therapeutic agent, wherein the therapeutic agent prevents or attenuates inflammation, cellular dysfunction, cellular activation, cellular proliferation, neointima formation, hyperplasia, late atherosclerotic changes, or thrombosis.

7. The stent element is formed from a bioabsorbable polymeric material, the bioabsorbable polymeric material being selected from the group consisting of poly(L-lactic acid) (PLLA), poly(D-lactic acid) (PDLA), poly(D,L-lactic acid) (PDLLA), semicrystalline polylactide, polyglycolic acid (PGA), poly(lactic acid-co-glycolic acid) (PLGA), poly(iodized desaminotyrosyl-tyrosine ethyl ester) carbonate, polycaprolactone (PCL), salicylate-based polymers, polydioxanone (PDS), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoesters, polyanhydrides, poly(glycolic acid-co-trimethylene carbonate), poly(iodized desaminotyrosyl-tyrosine ethyl ester) carbonate, polyphosphoesters ...

10. The device of claim 1, comprising urethanes, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonates), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, polyurethanes including polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicones including polysiloxanes and substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, PLLA-co-PCL, polyacrylates, polyvinylpyrrolidone, polyacrylamide, or combinations thereof.

8. 10. The device of claim 1, wherein the radial stiffness of the device slowly decays as its structural polymer bonds are broken and metabolized, causing the device to slowly become more flexible, causing adaptation and remodeling of the blood vessel and restoration of elasticity of the blood vessel.

Images