JP7414243B2 - thin wall scaffold - Google Patents

Description

[0001] The present invention relates to bioabsorbable scaffolds, and more particularly, the present invention relates to bioabsorbable scaffolds for treating anatomical lumens of the body.

[0002] A radially expandable endoprosthesis is an artificial device adapted to be implanted within an anatomical lumen. "Anatomical lumen" refers to the lumen or duct of a tubular organ, such as a blood vessel, urinary tract, or bile duct. A stent is an example of an endoprosthesis that is generally cylindrical and that holds open and optionally expands a portion of an anatomical lumen. Stents are often used in the treatment of atherosclerotic stenosis within blood vessels. "Stenosis" refers to a narrowing or constriction of the diameter of a body passageway or orifice. In such treatments, stents reinforce the walls of blood vessels and prevent restenosis after angioplasty in the vasculature. "Restenosis" refers to the recurrence of stenosis in a blood vessel or heart valve after apparently successful treatment (by balloon angioplasty, stenting, or valvuloplasty).

[0003] Treatment of an affected area or lesion with a stent involves both introduction and deployment of the stent. "Introducing" refers to introducing and delivering a stent through an anatomical lumen to a desired treatment site, such as a lesion. "Deployment" corresponds to expansion of the stent within the lumen of the treatment area. Stent introduction and deployment involves positioning the stent around one end of a catheter, inserting the end of the catheter through the skin and into an anatomical lumen, and moving the catheter within the anatomical lumen toward the desired treatment. This is accomplished by advancing the catheter into position, expanding the stent at the treatment location, and removing the catheter from the lumen.

[0004] Scaffolds and stents traditionally fall into two general categories: balloon-expandable and self-expandable. The latter type expands (at least partially) within the vessel to an expanded or expanded state when the radial constraint is removed, whereas the former utilizes externally applied forces to expand itself from a crimp or retracted state to a unfolded or expanded state.

[0005] Self-expanding stents are designed to expand significantly once the radial restraints are removed and often do not require a balloon to deploy the stent. Self-expanding stents do not undergo, or are relatively susceptible to, plastic or inelastic deformation when stored within a sheath (with or without an auxiliary balloon) or expanded within a lumen. Balloon expandable stents or scaffolds, in contrast, undergo significant plastic or inelastic deformation both when crimped and later when deployed by a balloon.

[0006] For balloon expandable stents, the stent is attached around the balloon portion of a balloon catheter. The stent is compressed or crimped onto the balloon. Crimping may be accomplished through the use of an iris-type or other form of crimper, such as the crimping machine disclosed and illustrated in US Patent Application No. 2012/0042501. A significant amount of plastic or inelastic deformation occurs both when a balloon expandable stent or scaffold is crimped and later deployed by a balloon. At the treatment site within the lumen, the stent is expanded by inflating a balloon.

[0007] A stent must be able to meet several basic functional requirements. The stent (or scaffold) must be able to sustain radial compressive forces while supporting the vessel wall. Therefore, the stent must have adequate radial strength. After deployment, the stent must maintain its size and shape properly throughout its useful life despite the various forces that may be placed on the stent. In particular, the stent must adequately maintain the blood vessel at a defined diameter for the desired treatment period despite these forces. The treatment period may correspond to the period required for the vessel wall to remodel, after which the stent is no longer needed.

[0008] Examples of bioabsorbable polymer scaffolds include Limon, US Pat. No. 8,002,817, Lord, US Pat. No. 8,303,644, and Yang, US Pat. 388,673. Figure 1 shows the distal region of a bioabsorbable polymer scaffold designed to be introduced through an anatomical lumen using a catheter and expanded plastically using a balloon. The scaffold has a cylindrical shape with a central axis 2 and includes a pattern of interconnecting structural elements called bar arms or struts 4. The axis 2 extends through the center of the cylindrical shape formed by the struts 4. The stresses involved during compression and deployment are widely distributed throughout the strut 4 but concentrated at the bending elements, apexes or strut joints. The strut 4 includes a series of ring struts 6 connected to each other at the top 8. The ring struts 6 and the top 8 form a sinusoidal ring 5. The ring 5 is arranged longitudinally around the axis 2. The struts 4 also include link struts 9 that connect the rings 5 to each other. The rings 5 and link struts 9 collectively form a tubular scaffold 10 having an axis 2 that represents the lumen or longitudinal axis of the scaffold 10. Ring 5d is located at the distal end of the scaffold. The apex 8 forms a smaller angle when the scaffold 10 is crimped to the balloon and a larger angle when expanded plastically by the balloon. After deployment, the scaffold is subjected to static and cyclic compressive loads from the surrounding tissue. The ring 5 is configured to maintain the radially expanded state of the scaffold after deployment.

[0009] Scaffolds can be made from biodegradable, bioabsorbable, bioresorbable, or bioerodible polymers. The terms biodegradable, bioabsorbable, bioresorbable, biosoluble or bioerodible refer to the property of a material or stent being degraded, absorbed, reabsorbed or eroded away from the implantation site. Scaffolds may also be constructed of bioerodible metals and alloys. Scaffolds, in contrast to durable metal stents, are intended to remain in the body only for a limited period of time. In many therapeutic applications, the presence of a stent within the body may be required for a limited period of time until its intended function is achieved, such as maintaining vascular patency and/or drug delivery. Additionally, biodegradable scaffolds have been shown to enable improved healing of anatomical lumens compared to metal stents, which may lead to a lower incidence of late thrombosis. . In these cases, treat the blood vessel using a polymer scaffold, especially a bioabsorbable or bioresorbable polymer scaffold, rather than a metal stent, so that the presence of the prosthesis in the blood vessel is temporary. It is desired to do so.

[0010] In some of the methods below, polymeric materials contemplated for use as polymer scaffolds, such as poly(L-lactide) ("PLLA"), poly(D,L-lactide-co-glycolide) ) (“PLGA”), poly(D-lactide-co-glycolide) or poly(L-lactide-co-D-lactide) with less than 10% D-lactide (“PLLA-co-PDLA”), poly( L-lactide-co-caprolactone), poly(caprolactone), PLLD/PDLA stereocomplex, and blends of the above polymers may be described by comparison to metallic materials used to form stents. Polymeric materials typically have a lower strength-to-volume ratio compared to metals, which means more material is required to provide equivalent mechanical properties. Therefore, the struts must be thicker and wider in order for the stent to have the necessary strength to support the lumen wall at the desired radius. Scaffolds made from such polymers also tend to be brittle or have limited fracture toughness. The inherent anisotropic and rate-dependent inelastic properties of the material (i.e., the strength/stiffness of the material varies with temperature, degree of hydration, thermal history, as well as the rate at which the material deforms) , only exacerbates this complexity when working with polymers, especially bioabsorbable polymers such as PLLA and PLGA.

[0011] An additional challenge with using bioabsorbable polymers (and generally polymers consisting of carbon, hydrogen, oxygen, and nitrogen) in scaffold structures is that the materials are radiolucent and not radiopaque. be. Bioabsorbable polymers tend to have X-ray absorption similar to body tissue. A known method to address this problem is to attach radiopaque markers to structural elements of the scaffold, such as struts, bar arms, links, etc. For example, in FIG. 1 a link element 9d is shown that connects the distal end ring 5d to the adjacent ring 5. Link element 9d has a pair of holes. Each hole holds a radiopaque marker 11. There are problems in using the marker 11 in combination with the scaffold 10. A reliable way to attach the marker 11 to the link element 9d so that it does not separate from the scaffold during processing steps such as crimping the scaffold to a balloon or when the scaffold is balloon expanded from a crimped state. is necessary. These two events, crimping and balloon expansion, are particularly problematic for marker attachment to the scaffold because both events induce significant plastic deformation in the scaffold body. If this deformation causes significant out-of-plane or irregular deformation of the struts supporting or near the marker, the marker may fall off (e.g., the struts holding the marker are crimped). (If it twists or bends inside the hole, the marker may fall out of the hole). Scaffolds with radiopaque markers and methods for attaching the markers to the scaffold body are discussed in US Patent Application No. 2007/0156230.

[0012] There is a need to improve the reliability of fixation of radiopaque markers to the scaffold for thin-walled scaffolds. Related to this need is a need to improve the performance characteristics of scaffolds, particularly thin-walled scaffolds made of bioabsorbable materials that must be routed around tortuous anatomical structures.

[0013] Disclosed are radiopaque markers and tortuous anatomical structures carrying such radiopaque materials and having reduced crimp profiles and/or scaffolds attached to the catheters. A bioabsorbable scaffold having a scaffold structure that allows improved conformability to the catheter when pushed through the catheter.

[0014] The scaffolds disclosed herein are suitable for meeting one or a combination of the following objectives.
(i) Thinning the crimp profile of the thin scaffold supporting the radiopaque marker.
(ii) fixing the marker to the thin-walled scaffold;
(iii) reducing strain energy accumulation in the marker-retaining structure when the thin-walled scaffold is deformed during crimping, balloon expansion at the target vascular site, or during introduction of the scaffold into the target site;
(iv) reducing flaring of the end ring at the distal end of the scaffold for thin-walled scaffolds, or scaffolds comprising PLLA and having a wall thickness greater than 125 microns (μm);

[0015] Through testing, it has been recognized that thin walls require modification of certain critical areas of the scaffold that were not previously an issue when larger wall thicknesses were used. An example of a scaffold with a larger wall thickness of 158 microns (μm) is described in US Patent Application No. 2010/0004735. When a significant reduction in wall thickness is made, compared to existing bioabsorbable scaffolds (e.g., from 160 microns (μm) wall thickness to 100 microns (μm) wall thickness), the placement of ring and link elements It has been found that the shape and dimensions require improvement, especially at the distal end of the scaffold.

[0016] Thin wall scaffolds are desired because of the clinical need to maintain a low profile of exposed struts in the bloodstream. Blood compatibility, also called hemocompatibility or clot resistance, is a desirable property for scaffolds and stents. Although the adverse events of scaffold thrombosis are very infrequent events, they are associated with high morbidity and mortality. Dual antiplatelet therapy is administered with all coronary scaffold and stent implantations to reduce the risk of thrombosis. This is to reduce blood clot formation due to the procedure, vascular damage, and the implant itself. Scaffolds and stents are foreign materials, and they all have some degree of thrombogenicity. Thrombogenicity of a scaffold refers to its tendency to form blood clots, which is determined by strut thickness, strut width, strut shape, total scaffold surface area, scaffold pattern, scaffold length, scaffold diameter, surface This is due to several factors including roughness and surface chemistry. Some of these factors are interrelated. A low strut profile also leads to reduced neointimal proliferation. This is because the new internal wall will proliferate to the extent necessary to cover the struts. Covering is therefore a necessary step for completion of healing. It is believed that thinner struts also result in faster endothelialization and healing.

[0017] According to various aspects of the invention, a thin-walled scaffold (“scaffold”), a medical device, a method for making such a scaffold, a method for making a marker, a strut of the scaffold, There are methods for attachment to links or bar arms, methods for crimping, or methods for assembling medical devices comprising such scaffolds, which include one or more of the following (1) to (15): , or any combination thereof.

(1) The scaffold is crimped to the theoretical minimum crimp diameter (D-min).

(2) the scaffold wall thickness is less than 125 microns (μm), less than 100 microns (μm), about 100 microns (μm), or about 93 microns (μm);

(3) the wavelength of the ring coupled to the marker link is greater than the wavelength of another ring not coupled to the marker link, and/or the wavelength of the ring coupled to the marker link has a wavelength of a different length;

(4) The distance from the top of W to the top of adjacent U is greater than the distance from the top of Y to the top of adjacent U.

(5) The scaffold is made of tubing containing poly(L-lactide).

(6) a scaffold crimped to a balloon, the scaffold configuring the crimped state illustrated and described in connection with FIG. 4D, FIG. 6A, or FIG. 7A;

(7) A method of crimping any of the scaffolds described in connection with FIG. 3, FIG. 4, FIG. 5, FIG. 6, or FIG.

(8) Methods for attaching radiopaque markers to scaffolds.

(9) Marker links illustrated and described in connection with FIG. 2C.

(10) The ring has n peaks, where n is greater than 5, or greater than 6 and less than or equal to 12.

(11) The ring has two wavelengths of a first size and n-3 wavelengths of a second size, the first size being larger than the second size.

(12) The ring connected to the marker link at the w top has a first width, and the adjacent ring connected to the marker link has a second width that is greater than the first width.

(13) The ring connected to the marker link at the W top has a wider flat portion than the Y top flat portion connected to the marker link and connected to the first ring.

(14) The first distance between the marker link and the adjacent ring is greater than the second distance between the rings connected by the marker link.

(15) A first distance between rings joined by a nonlinear link marker link is greater than a second distance between rings not joined by a nonlinear marker link.

(16) D-min is about 1 mm or less.

(17) The aspect ratio (AR) of the marker link in the thin-walled scaffold is about 4–5, or about 4.5, where AR is defined as the maximum width of the marker link divided by the wall thickness at the marker link. be done.

(18) The first wavelength or half wavelength of the first ring is greater than the second wavelength or half wavelength of the coupled second ring.

(19) The first wavelength or half wavelength between two peaks of a ring is different from the second wavelength between two other peaks of the same ring.

(20) The ring is sinusoidal or zigzag shaped.

(21) For a marker link with a maximum width approximately 200% larger than the maximum width of a non-marker link, the half wavelength measured from the top of the W formed between the marker link and the first ring is This is about 15% larger than the half wavelength measured from the top of the Y formed between the first ring and the second ring.

(22) For a marker link that has a maximum width approximately 200% larger than the maximum width of a non-marker link, the wavelength measured from the top of the W formed between the marker link and the first ring is is approximately 5% to 10% larger than the wavelength measured from the top of the Y formed between the ring and the second ring coupled to the second ring.

(23) For a marker link with a maximum width approximately 200% larger than the maximum width of a non-marker link, the wavelength measured from the W peak/peak formed between the marker link and the ring will be Approximately 5% to 10% greater than the measured measured wavelength.

(24) Top width B1 larger than top width B2, for example, top width B1 about 350% to 400% larger than top width B2.

(25) The ring spacing A12 between the first ring and the second ring is larger than the ring spacing A23 between the second ring and the third ring, for example, A12 is about 40% larger than A23. .

(26) The link is a straight link or a non-linear link. For example, link 20 and link 636.

(27) Length c1 approximately 36% larger than marker link length c2.

(28) The length c1 is about 36% larger than the length c2 of the nonlinear link.

(29) A thin-walled scaffold having a network of rings interconnected by links, each ring having a plurality of peaks, the peaks comprising a U-top, a Y-top, and a W-top. one of a plurality of thin-walled scaffolds extending circumferentially in an undulating manner along a vertical axis (B-B) perpendicular to the longitudinal axis (A-A); a marker link extending between a first ring and a second ring of the rings, the marker link including a structure having a hole, the hole including a radiopaque material; , a marker link, the marker link forms a first ring and a W apex of the first ring, a second ring and a Y apex of the second ring, and a W apex of the first ring. The 1/2 wavelength of the first ring measured from the top to the next U top in the first ring is measured from the Y top of the second ring to the next U top in the second ring. A medical device that is larger than 1/2 wavelength of the second ring.

(30) The medical device according to (29), which is combined with one or more of the following items (a) to (g), or any combination thereof.
(a) The length of the marker link is greater than the length of the link connecting the second ring to a third ring coupled with the second ring.
(b) the marker link includes a first link portion extending from the structure to the W top of the first ring; a second link portion extending from the Y top of the second ring to the structure; The width of one link portion is shorter than the length of the second link portion.
(c) the length of the first link portion is less than the length of the second link portion;
(d) the structure includes a first hole and a second hole each containing a radiopaque material, the first hole and the second hole being arranged parallel to the axis A-A; There is.
(e) The first ring includes a first peak, a second peak, and a third peak, the first peak corresponding to the W top of the first ring, and the second peak corresponding to the top of the first ring. A third wavelength is next to the first peak, a third peak is next to the second peak, and a second wavelength that extends from the second peak to the third peak is a second wavelength that extends from the first peak to the second peak. smaller than the wavelength of 1.
(f) The flat portion of the W top of the first ring is the flat portion of the W top of the third ring of the third ring combined with the second ring, and/or the flat portion of the W top of the third ring combined with the second ring. It is larger than the flat part at the top of W.
(g) The wavelength of the first ring forming the W top of the first ring is longer than the wavelength of the second ring forming the Y top of the second ring.

(31) A medical device comprising a thin-walled scaffold having a proximal end portion and a distal end portion formed by a network of a plurality of rings interconnected by links, each ring having a plurality of ridges. , the peak is one of a U-top, a Y-top, and a W-top, and each ring has a vertical axis (B-B) perpendicular to the longitudinal axis (A-A). a thin-walled scaffold extending circumferentially in a wavy manner and a marker link extending between a first ring and a second ring of the plurality of rings, the marker link having a structure having a hole; a marker link comprising a radiopaque material in the hole, the marker link forming a first ring and a W top of the first ring, and a second ring and a second ring; form the Y top of the ring, and the W top of the first ring corresponds to the first peak, measured from the first peak to the second peak of the first ring next to the first peak. the first wavelength of the first ring that is greater than the second wavelength of the first ring measured from the second peak to the third peak adjacent to the first ring.

(32) The medical device according to (31), which is combined with one or more of the following items (a) to (c), or any combination thereof.
(a) the first ring has n peaks and n-1 wavelengths, where n is at least 6 and not more than 12, and the first wavelength and the second wavelength are different from each other; The first peak is larger than the remaining n-3 wavelengths measured between the n-1 peaks.
(b) The remaining n-3 wavelengths all have the same length.
(c) The length of the marker link is approximately equal to the length of the link connecting the second ring to the third ring.

(33) A medical device formed by a balloon catheter having a balloon having a distal balloon end and a proximal balloon end, and a network of rings interconnected by links, the proximal end portion and the distal a thin-walled balloon-crimped scaffold having an end portion, each ring having a plurality of peaks, the peak being one of a U-top, a Y-top, and a W-top, and each ring having a , a thin-walled scaffold extending circumferentially in an undulating manner along a vertical axis (B-B) perpendicular to the longitudinal axis (A-A); a marker link extending between the ring and the marker link, the marker link including a structure having a hole, the marker link including a radiopaque material within the hole; The first ring and the W top of the first ring are formed, the second ring and the Y top of the second ring are formed, the W top of the first ring corresponds to the first mountain, and the W top of the first ring corresponds to the first mountain. The first wavelength of the first ring measured from the peak to the second peak next to the first peak is measured from the second peak to the third peak next to the second peak. the thin-walled scaffold has an outer diameter of about D-min, where D-min=(1/π)×[(n×strut_width)+(m×link_width) )]+2*t, a medical device.

(34) The medical device according to (33), which is combined with one or more of the following items (a) to (d), or any combination thereof.
(a) The maximum width of the structure, measured along axis BB, is greater than the maximum width of the link extending between the second ring and the third ring coupled to the second ring.
(b) The marker link includes a first link portion extending from the structure to the W top and a second link portion extending from the Y top to the structure, and the width of the first link portion is equal to the width of the second link portion. It is larger than the width of the link part.
(c) the length of the first length portion is less than the length of the second link portion;
(d) the structure includes a first hole and a second hole comprising a radiopaque material, the first hole and the second hole being arranged parallel to the axis A-A; .

(35) A method for making a medical device, the steps comprising using a tube comprising poly(L-lactide) and forming a thin-walled scaffold pattern from the tube, the thin-walled scaffold having a link formed by a network of a plurality of rings interconnected by a proximal end portion and a distal end portion, each ring having a plurality of ridges, the ridges being formed by a network of a plurality of rings interconnected by a U-top, a Y-top and a W-top. one of the rings, each ring extending circumferentially in an undulating manner along a vertical axis (B-B) perpendicular to the longitudinal axis (A-A), the thin-walled scaffold comprising a plurality of forming a thin-walled scaffold pattern including at least one marker link extending between a first of the rings and a coupled second ring, the marker link including a structure having a hole; , placing a radiopaque material in the marker hole, the hole having a first size before material placement and a second size greater than the first size after material placement; The construction includes placing a radiopaque material having a width measured along axis B--B and crimping the thin-walled scaffold to the balloon catheter, the thin-walled scaffold being approximately theoretically A method in which the top of the structure is crimped to the minimum crimp diameter (D-min) so that none of the tops above or below the structure overlap the structure.

(36) The medical device according to (35), which is combined with one or more of the following items (a) to (c), or any combination thereof.
(a) The marker link forms the first ring and the W top of the first ring, the second ring and the Y top of the second ring, and the W top of the first ring forms the W top of the first ring. The first wavelength of the first ring corresponding to the peak and measured from the first peak to the second peak next to the first peak is the first wavelength measured from the second peak to the third peak next to the first peak. greater than the second wavelength of the first ring measured up to.
(b) The marker link forms a first ring and a W top of the first ring, a second ring and a Y top of the second ring, and a first U top and a second U top. are respectively above and below the W top of the first ring, the first strut extends from the W top of the first ring to the first U top, and the second strut extends from the W top of the first ring to the first U top. extending from the W apex to the second U apex, and the distance between the first U apex and the second U apex or the distance from the second strut to the first strut is is greater than or equal to the maximum width of the marker structure measured along.
(c) The width of the marker structure is greater than the maximum width of the link connecting the second ring to the adjacent third ring.

(37) A medical device comprising a thin-walled scaffold having a proximal end portion and a distal end portion formed by a network of a plurality of rings interconnected by links of the thin-walled scaffold, wherein each ring has a plurality of crests including a U crest and at least one of a Y crest and a W crest, each ring having a vertical axis (B-B ), the proximal end portion includes an outermost proximal ring coupled to the first proximal ring by a first proximal link; , the first proximal ring is coupled to the second proximal ring by a second proximal link, and the distal end portion is coupled to the first distal ring by the first distal link. an outermost distal ring, the first distal ring being coupled to the second distal ring by a second distal link, the first proximal link comprising a radiopaque material; A medical device including a proximal marker link with a proximal hole, the first distal link lacking a link retaining radiopaque material.

(38) The medical device according to (37), which is combined with one or more of the following items (a) to (i), or any combination thereof.
(a) The outermost proximal ring is connected to the first proximal ring only by a first proximal link, two of the first proximal links relative to axis AA. They extend parallel to each other and have a constant moment of inertia.
(b) the outermost distal ring is coupled to the first distal ring only by a first distal link, each first distal link being a non-linear link strut;
(c) the proximal marker link has a first end and a second end, the first end forming one of a W apex and a Y apex with the outermost proximal ring; , forming the other of the W apex and the Y apex with the first proximal ring.
(d) the first distal ring and the second distal ring are coupled by a distal marker link;
(e) the distal marker link includes structure surrounding the two holes, and the first distal ring and the second distal ring are further coupled by one or more marker links.
(f) the distal marker link has a first end and a second end, the first end forming one of a W apex and a Y apex with the first distal ring; , forming the other of the W apex and the Y apex with the second distal ring, the W apex being wider than the Y apex.
(g) the proximal marker link is a periphery generally surrounding the hole and defining the hole wall and the strut periphery, the distance between the wall and the periphery being D; a radiopaque marker comprising a head having a peripherally disposed flange, the flange having a radial length from 1/2D to less than D; The thin scaffold thickness (t) is related to the marker length (L) measured between the abluminal and luminal sides of the marker by 1.1≦(L/t)≦1.8. are doing.
(h) the distal marker link forms one of the W apex and Y apex of the first distal ring and the second distal ring, and the W apex, measured from the adjacent apex of the first; The 1/2 wavelength of a ring with a Y top is greater than the 1/2 wavelength of a ring with a Y top.
(i) the length of the first proximal link is less than the length of the first distal link, and/or the length of the second distal link is less than the length of the first distal link;

(39) A medical device formed by a balloon catheter having a balloon having a distal balloon end and a proximal balloon end, and a network of a plurality of rings interconnected by links of a thin-walled scaffold; a thin-walled balloon-crimped scaffold having a portion and a distal end portion, each ring having a plurality of crests including a U-top and at least one of a Y-top and a W-top; , each ring comprises a thin-walled scaffold extending circumferentially in an undulating manner along a vertical axis (B-B) perpendicular to the longitudinal axis (A-A), the proximal end portion having a , including an outermost proximal ring crimped to the proximal balloon end and connected to the first proximal ring by a first proximal link, the first proximal ring being connected to the second proximal link. a second proximal ring, the distal end portion being crimped to the distal balloon end, and an outermost distal end portion being connected to the first distal ring by a first distal link. the first distal ring is coupled to the second distal ring by a second distal link, the first proximal link having a proximal hole containing a radiopaque material. the first distal link is devoid of links carrying radiopaque material, the first distal link comprises a non-linear link, and the thin-walled scaffold is approximately D-min. A medical device having an outer diameter of D-min=(1/π)×[(n×strut_width)+(m×link_width)]+2*t.

(40) The medical device according to (39), which is combined with one or more of the following items (a) to (i), or any combination thereof.
(a) the outermost proximal ring is connected to the first proximal ring only by a first proximal link, each first proximal link extending parallel to axis AA; and has a constant moment of inertia.
(b) The non-linear link is a U-shaped link.
(c) the proximal marker link has a first end and a second end, the first end forming one of a W apex and a Y apex with the outermost proximal ring; , forming the other of the W apex and the Y apex with the first proximal ring, and the marker link includes structure surrounding the hole.
(d) a first link portion of the proximal marker link extends from the W top to the structure, a second link portion of the proximal marker link extends from the Y top to the structure, and the length of the first link portion; The length is greater than the length of the second link portion.
(e) The length of the first link portion is approximately equal to twice the ring width plus the length of the strut extending between the U-top and the U-top, Y-top, or W-top of the ring.
(f) the nonlinear link has a first end and a second end, the first end forming one of a W apex and a Y apex with the outermost proximal ring; and the other of the W apex and the Y apex, and the nonlinear link includes a U-shaped structure between the W apex and the Y apex.
(g) a first link portion of the proximal U-shaped link extends from the W top to the U-shaped structure; a second link portion of the proximal marker link extends from the Y top to the structure; The length of the section is greater than the length of the second link section.
(h) The length of the first link portion is approximately equal to twice the ring width plus the length of the strut extending between the U-top and the U-top, Y-top, or W-top of the ring.
(i) the distal marker link has a first end and a second end, the first end forming one of a W apex and a Y apex with the first distal ring; , forming the other of the W apex and the Y apex with the second distal ring.

(41) A medical device comprising a thin-walled scaffold having a proximal end portion and a distal end portion formed by a network of a plurality of rings interconnected by links of the thin-walled scaffold, wherein each ring has a plurality of crests including a U crest and at least one of a Y crest and a W crest, each ring having a vertical axis (B-B ), the proximal end portion includes an outermost proximal ring coupled to the first proximal ring by a first proximal link; , the first proximal ring is coupled to the second proximal ring by a second proximal link, and the distal end portion is coupled to the first distal ring by the first distal link. an outermost distal ring, the first distal ring being coupled to the second distal ring by a second distal link, the first proximal link comprising a radiopaque material; a proximal marker link with a pair of proximal holes disposed along axis A-A, and a first distal link with a pair of distal markers comprising a radiopaque material. and a distal marker link with a distal hole disposed along axis BB.

(42) The medical device according to (41), which is combined with one or more of the following items (a) to (i), or any combination thereof.
(a) The outermost proximal ring is connected to the first proximal ring only by a first proximal link, two of the first proximal links relative to axis AA. They extend parallel to each other and have a constant moment of inertia.
(b) the outermost distal ring is coupled to the first distal ring only by the first distal marker link and the nonlinear link strut;
(c) the proximal marker link has a first end and a second end, the first end forming one of a W apex and a Y apex with the outermost proximal ring; , forming the other of the W apex and the Y apex with the first proximal ring.
(d) The width of the W apex formed by the first end is greater than the width of the Y apex formed by the second end, so that the wavelength of the ring forming the W apex forms the Y apex. longer than the wavelength of the ring.
(e) the distal marker link has a first end and a second end, the first end forming one of a W apex and a Y apex with the outermost distal ring; , forming the other of the W apex and the Y apex with the first distal ring.
(f) The distal marker link includes a first link portion extending from the hole to the W top and a second link portion extending from the hole to the Y top, the first link portion having a length of It is longer than the length of the link part of 2.
(g) the proximal marker link is a periphery generally surrounding the hole and defining the hole wall and the strut periphery, the distance between the wall and the periphery being D; a radiopaque marker comprising a head having a peripherally disposed flange, the flange having a radial length from 1/2D to less than D; The thin scaffold thickness (t) is related to the marker length (L) measured between the abluminal and luminal sides of the marker by 1.1≦(L/t)≦1.8. are doing.
(h) a radiopaque material is contained within the hole, the radiopaque material having a frustum shape;
(i) the hole has a first aperture and a second aperture located on the first and second sides of the marker link, respectively, the first aperture being larger than the second aperture; is substantially on the same plane as the first opening and the second opening.

(43) A medical device formed by a balloon catheter having a balloon having a distal balloon end and a proximal balloon end and a network of a plurality of rings interconnected by links of a thin-walled scaffold; a thin-walled balloon-crimped scaffold having a portion and a distal end portion, each ring having a plurality of crests including a U-top and at least one of a Y-top and a W-top; , each ring comprises a thin-walled scaffold extending circumferentially in an undulating manner along a vertical axis (B-B) perpendicular to the longitudinal axis (A-A), the proximal end portion having a , including an outermost proximal ring crimped to the proximal balloon end and connected to the first proximal ring by a first proximal link, the first proximal ring being connected to the second proximal link. a second proximal ring, the distal end portion being crimped to the distal balloon end, and an outermost distal end portion being connected to the first distal ring by a first distal link. a first distal ring coupled to a second distal ring by a second distal link; (1) the first proximal link includes a proximal marker link comprising a structure; (2) the first distal link includes a distal marker link comprising a structure, the structure extending parallel to axis AA and including a radiopaque material; Extending parallel to axis B-B and comprising radiopaque material, the thin-walled scaffold has an outer diameter of approximately D-min, where D-min=(1/π)×[(n× strut_width)+(m×link_width)]+2*t.

(44) The medical device according to (43), which is combined with one or more of the following items (a) to (i), or any combination thereof.
(a) the outermost proximal ring is connected to the first proximal ring only by a first proximal link, each first proximal link extending parallel to axis AA; and has a constant moment of inertia.
(b) the first distal link includes a non-linear link;
(c) the proximal marker link has a first end and a second end, the first end forming one of a W apex and a Y apex with the outermost proximal ring; , forming the other of the W apex and the Y apex with the first proximal ring, and the marker link includes structure surrounding the hole.
(d) a first link portion of the proximal marker link extends from the W top to the structure, a second link portion of the proximal marker link extends from the Y top to the structure, and the length of the first link portion; The length is greater than the length of the second link portion.
(e) The length of the first link portion is approximately equal to twice the ring width plus the length of the strut extending between the U-top and the Y-top, U-top or W-top of the ring.
(f) the first distal link comprises a non-linear link having a first end and a second end, the first end being connected to the outermost proximal ring and one of the W apex and the Y apex; forming the first proximal ring and the other of the W apex and the Y apex, the nonlinear link including a U-shaped structure between the W apex and the Y apex.
(g) a first link portion of the non-linear link extends from the W-top to the U-shaped structure; a second link portion of the non-linear link extends from the Y-top to the U-shaped structure; and the second link portion of the non-linear link extends the length of the first link portion; The length is greater than the length of the second link portion.
(h) The length of the first link portion is approximately equal to twice the ring width plus the length of the strut extending between the U-top and the Y-top, U-top or W-top of the ring.
(i) The hole in the distal marker link is between and between the U-top next to the W-top of the outermost distal ring and the U-top next to the Y-top of the first distal ring. Neither overlap nor underlap.

[Incorporated by reference]
[0018] All publications and patent applications mentioned herein are incorporated herein by reference, as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. It is used in To the extent there is conflicting usage of terms between a referenced document or patent and this specification, those terms have the meaning consistent with their usage herein.

1 is a perspective view of a portion of a prior art scaffold, with the scaffold shown in a crimped state (balloons not shown); FIG. FIG. 3 is a top partial view of a scaffold having holes for retaining radiopaque material and showing marker links connecting adjacent rings. 3 is a reproduction of FIG. 2 showing additional dimensional characteristics and/or features of the link for holding two markers; FIG. FIG. 6 illustrates an alternative embodiment of a marker link. 3 is another reproduction of FIG. 2 with markers attached to links; FIG. 3 illustrates distal and proximal end portions of a scaffold according to one embodiment, including marker links of the coupling ring of FIG. 2; FIG. 4 shows section IIIA of the scaffold of FIG. 3. FIG. 4 shows section IIIB of the scaffold of FIG. 3. FIG. Figure 4 shows the scaffold of Figure 3 in a crimped state. Figure 4 shows the scaffold of Figure 3 crimped to a balloon of a balloon catheter. the end portion connects adjacent rings and includes a link containing a marker, the ring has a W apex formed in part by the marker link, the W apex being modified to accommodate the marker structure; FIG. 6 illustrates an end portion of a scaffold according to another embodiment. 5 is a section IV view of the scaffold of FIG. 4. FIG. Figure 4 shows the distal end ring of the scaffold of Figure 3 with the distal end ring of the scaffold of Figure 4 shown in dotted lines to illustrate the difference between the two rings. 5 is a diagram illustrating section IVC of the scaffold of FIG. 4. FIG. Figure 5 shows the scaffold of Figure 4 in a crimped state. FIG. 7 is a partial view of a distal end portion of a scaffold according to another embodiment. A scanner according to another embodiment, wherein the distal end portion is different from the proximal end portion, the nonlinear link strut connects the outermost distal ring to the inner ring, and the marker link is between the inner rings at the distal end portion. It is a figure which shows the edge part of a fold. Figure 7 is a partial view of the scaffold of Figure 6 in a crimped state; FIG. 3 is an image of the distal end of the catheter in a bent configuration showing the distal ring of the scaffold flaring or protruding outward from the distal end of the balloon. 7 is an image of the catheter distal end in a bent configuration showing the distal ring of the scaffold according to FIG. 6, where the distal end ring no longer flares when the catheter is placed in the bent state; FIG. FIG. 7 shows an end portion of a scaffold according to another embodiment, wherein the proximal end portion is different from the distal end portion, and nonlinear link struts and modified marker links connect the outermost distal ring to the inner ring; be. Figure 8 is a partial view of the scaffold of Figure 7 in a crimped state; 8 is a partial view of the scaffold of FIG. 7 taken in section VII of FIG. 7; FIG. 8 is an image of the catheter distal end in a flexed configuration showing the distal ring of the scaffold according to FIG. 7, where the distal end ring does not flare outward when the catheter is placed in the flexed configuration; FIG. FIG. 6 is a side view of a marker according to another embodiment. FIG. 6 is a top view of a marker according to another embodiment. 8A-8B is a cross-sectional view of a link having a hole in which the marker of FIGS. 8A-8B is embedded; FIG. FIG. 3 is a side cross-sectional view of a first die for forming rivet markers from radiopaque beads. 11 is a side view of a rivet marker formed using the die of FIG. 10. FIG. FIG. 11A is a side cross-sectional view of the scaffold strut after the marker has been deformed during the forming process to create a peripheral edge and a lower peripheral edge that retain the marker within the hole, with the marker of FIG. 11A engaging the hole in the strut; be. FIG. 3 is a side cross-sectional view of a second die for forming rivet markers from radiopaque beads. 13 is a side view of a rivet marker formed using the die of FIG. 12. FIG. FIG. 3 is a perspective view illustrating one aspect of a process for deforming a rivet packed into a scaffold hole to strengthen engagement with the hole to resist dislodgement forces associated with crimp or balloon expansion. FIG. 3 is a perspective view illustrating another aspect of a process for deforming a rivet packed into a scaffold hole to strengthen engagement with the hole to resist dislodgement forces associated with crimp or balloon expansion. FIG. 12 is a perspective view illustrating yet another aspect of a process for deforming a rivet packed into a scaffold hole to enhance engagement with the hole to resist dislodgement forces associated with crimp or balloon expansion. FIG. 14C is a side cross-sectional view of the deformed rivet marker and scaffold hole after the steps described in connection with FIGS. 14A-14C. FIG. 15B is an illustration of the modified marker shown in FIG. 15A. 15A is a side cross-sectional view of the rivet and marker hole of FIG. 15A after a heating step; FIG. FIG. 4 illustrates the steps associated with removing the formed rivet marker from the die and placing the rivet marker in a hole in the scaffold. FIG. 4 illustrates the steps associated with removing the formed rivet marker from the die and placing the rivet marker in a hole in the scaffold. FIG. 4 illustrates the steps associated with removing the formed rivet marker from the die and placing the rivet marker in a hole in the scaffold. FIG. 3 illustrates a process for crimping thin-walled scaffolds according to the present disclosure. FIG. 3 illustrates a process for crimping thin-walled scaffolds according to the present disclosure.

[0056] Like reference numbers in the drawings and the specification herein designate corresponding or similar elements in different figures.

[0057] The following terms and definitions apply to this disclosure.

[0058] The terms "about," "approximately," "generally," or "substantially" mean 30%, 20% less than a stated value, range, or each endpoint of a stated range. %, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1%, 1-2%, 1-3%, 1-5%, or 0.5-5% means less or more, less or more, or a variance (Gaussian distribution) of 1 sigma, 2 sigma, 3 sigma from the stated mean or expected value. For example, d1 is about d2 means that d1 is 30%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1%, 0%, or It means different from d2 by 2%, 1-3%, 1-5%, or 0.5-5%. If d1 is a mean value, then d2 is about d1 meaning that d2 is within a variance or standard deviation of 1, 2, or 3 sigma from d1.

[0059] Any number, range, or range endpoint in this disclosure preceded by the word "about," "approximately," "generally," or "substantially" (e.g., "approximately") (including "nothing," "substantially nothing," "substantially all," etc.) is preceded by the word "about," "approximately," "generally," or "substantially." It is to be understood that the same numerical value, range, or range endpoint is also described or disclosed.

[0060] "Glass transition temperature", TG, is the temperature at which the amorphous domains of a polymer change from a brittle glass state to a solid deformable or ductile state at atmospheric pressure. In this application, the method of finding the TG, or TG-low (lower limit of the TG range) of a polymer, is defined in the same manner as in US patent application Ser. No. 14/857,635 (Docket Number: 62571.1216).

[0061] "Stent" generally means a permanent, durable, or non-degradable structure consisting of a non-degradable metal or alloy structure, whereas "scaffold" refers to a A temporary device comprising absorbable or biodegradable polymers, metals, alloys or combinations thereof and capable of radially supporting the blood vessel for a limited period of time, e.g. 3, 6 or 12 months after implantation. It means a structure. However, it should be understood that the art often uses the term "stent" to refer to either type of structure.

[0062] "Inflated diameter" or "expanded diameter" refers to the inner or outer diameter that a scaffold acquires when its support balloon expands the scaffold from its crimped configuration for implantation of the scaffold within a blood vessel. Inflated diameter may refer to the balloon diameter after inflation above the nominal balloon diameter, for example, a 6.5 mm balloon (i.e., a nominal diameter of 6.5 mm when inflated to a nominal balloon pressure, such as 6 times atmospheric pressure). The expanded diameter of a 6.0 mm balloon is approximately 7.4 mm, and the expanded diameter of a 6.0 mm balloon is approximately 6.5 mm. The balloon's nominal to post-inflated ratio may range from 1.05 to 1.15 (ie, the post-inflated diameter may be 5% to 15% larger than the nominal inflation balloon diameter). Scaffold diameter is determined by the recoil effect, which is primarily related to any or all of the following: the way the scaffold was manufactured and processed, the scaffold material, and the scaffold design after obtaining the expanded diameter by balloon pressure. This results in a certain reduction in diameter.

[0063] Reference to diameter shall mean an inner diameter or an outer diameter, unless otherwise specified or the context of the description suggests otherwise.

[0064] Reference to scaffold struts also applies to links and bar arms.

[0065] The "post-expanded diameter" (PDD) of a scaffold refers to the inner diameter of the scaffold after it has been increased to its expanded diameter and the balloon has been removed from the patient's vasculature. PDD takes into account recoil effects. For example, acute PDD refers to the scaffold diameter that takes into account acute recoil in the scaffold.

[0066] "Pre-crimp diameter" means cut from a tube of the material from which the scaffold is made (e.g., dip coated, injection molded, extruded, radially expanded, die drawn and/or annealed tube). OD) or the outer diameter (OD) of the scaffold before being crimped to the balloon. Similarly, "crimp diameter" refers to the OD of the scaffold when crimped onto a balloon. "Pre-crimp diameter" is approximately 2 to 2.5 times, 2 to 2.3 times, 2.3 times, 2 times, 2.5 times, 3.0 times the crimp diameter, expanded diameter, nominal It can be about 0.9 times, 1.0 times, 1.1 times, 1.3 times, and about 1-1.5 times the balloon diameter, or the expanded diameter. By crimp, in this disclosure, we mean a diameter reduction of a scaffold that is characterized by significant plastic deformation, i.e., a diameter reduction of more than 10%, or more than 50%, in a wavy ring pattern, such as in FIG. attributable to plastic deformation, such as at the top in the case of a stent or scaffold with a When the scaffold is deployed or expanded by the balloon, the inflated balloon plastically deforms the scaffold from its crimp diameter. A method for crimping scaffolds made in accordance with the present disclosure is described in US Patent Application No. 2013/0255853 (Docket No. 62571.628).

[0067] Materials "comprising" or "comprising" poly(L-lactide) or PLLA include PLLA polymers, blends or mixtures containing PLLA and another polymer, and PLLA and another polymer. including, but not limited to, copolymers of Thus, struts comprising PLLA mean that the struts can be made from materials comprising either PLLA polymers, blends or mixtures comprising PLLA and another polymer, and copolymers of PLLA and another polymer. .

[0068] The bioabsorbable scaffold made of biodegradable polyester polymer is radiolucent. Radiopaque markers are placed on the scaffold to allow fluoroscopy. For example, the scaffold described in U.S. Pat. It has two platinum markers 206.

[0069] When we refer to a direction perpendicular to axis AA (as shown in FIG. 3) or parallel to axis AA and/or parallel to axis AA, we are referring to the axial direction of the scaffold or tube. means perpendicular to or parallel to the axial direction. Similarly, when we refer to a direction perpendicular to axis B-B or parallel to axis B-B (as shown in Figure 3, for example), we are referring to a direction circumferentially of the scaffold or tube. It means perpendicular to the circumferential direction or parallel to the circumferential direction. Thus, the sinusoidal rings of the scaffold extend (periodically) parallel to the circumferential direction and/or parallel to the axis B-B and perpendicular to the axis A-A, while the links in one embodiment extends parallel to the axial direction or axis AA of the scaffold or tube and perpendicular to axis BB.

[0070] Whenever the same element number is used in more than one drawing, unless otherwise noted, the same description originally used for the element in the first drawing appears in the implementation in the later drawing. It should be understood that it applies to the form.

[0071] Thickness dimensions (eg, wall, strut, ring or link thickness) refer to dimensions measured perpendicular to both axis AA and axis BB. Width dimensions are measured in the planes of axis AA and axis BB. More specifically, width is the cross-sectional width from one side of a continuous structure to the other, so U-shaped link 636 has a constant link width, just as link 334 has a constant link width. It has a constant link width over its length. Furthermore, it should be noted that the so-called planes of axis A-A and axis B-B are not technically planes, since they describe the surface of a tubular structure with a central lumen axis parallel to axis A-A. I want to be understood. Therefore, axis B-B may alternatively be considered as the angular component if the scaffold position were described using a cylindrical coordinate system (i.e., axis A-A is the Z-axis and the top , links, rings, etc., are found by angular and radial coordinate constants).

[0072] "Thin wall thickness", "thin wall scaffold", "thin wall" refers to struts, rings made of polymers, including poly(L-lactide), having a wall thickness of less than 125 microns (μm); Refers to the link or bar arm. Here we discuss the challenges encountered when working with thin-walled scaffolds, including maintaining markers with the same volume of radiopaque material.

[0073] FIG. 2 is a top view of a portion of a polymer scaffold, eg, a polymer scaffold having a pattern of rings interconnected by links. Marker link 20 (“link 20”) extends between rings 312a, 312b in FIG. Links 20 form left and right structures or strut portions 21b, 21a, respectively, for holding radiopaque markers. The marker can be held in the hole 22 formed by the structures 21a, 21b. Surface 22a corresponds to the abluminal side of the scaffold.

[0074] FIG. 2A is a reproduction of FIG. 2 showing additional dimensional features, particularly distinctive dimensional features D0, D1, and D2. The diameter of the hole 22 is D0. The distance between adjacent holes 22 is greater than or equal to D1. The width of either or both edges of the hole 22, ie, the distance from the inner wall surface surrounding either or both of the holes 22 to the edge of the link 20, is greater than or equal to D2.

[0075] FIG. 2B shows the dimensions described in connection with FIG. 2A for a marker link 720 oriented such that structures 21a, 21b are offset along axis BB rather than axis AA. Show characteristics. Marker 720 connects ring 312a and ring 312b. A scaffold embodying this marker is shown in FIG.

[0076] In FIG. 2C, a rivet-type marker 127'/137' is shown secured to the hole 22. The dimensions indicated are used to evaluate the ability of the marker link (after the radiopaque material has been connected) to resist forces that would tend to dislodge the rivet 127'/137' from the hole 22. Refers to parameters that can be used to test. These shedding forces can be caused by deformation of the pressurized balloon surface or nearby scaffold structure that tends to deform the holes 22 as the scaffold is crimped or balloon expanded. According to one aspect, the rivet heads and/or rivet tips of the rivet 127'/137' pair may be inspected to determine whether minimum distances δ1, δ2, and δ3 (FIG. 2C) are met. . Distances δ1, δ2, and δ3 reflect the minimum size of either or both of the head and/or tip of the rivet pushed into the hole, which size the rivet should be retained within the hole 22. Both the head and tip diameters are too small to resist shedding forces and the excess rivet material can lead to problems such as balloon puncture and vascular irritation when the scaffold is implanted into a blood vessel. It instructs both that it not cause According to embodiments, the minimum distance from the end of the marker head/tip to the edge of the strut (or link) portion 21a/21b, i.e. δ2, is approximately 10%, 25% and up to 50% of D2. It can be done. Above 50% means the head or tip is too small to hold the rivet in place. For heads/tips of D2 and above, the head may or may extend beyond the edges of the struts/links, which may damage the balloon or irritate adjacent tissue. This can lead to problems such as the formation of relatively sharp edges. The minimum distance between the marker head/tip, ie δ1, is 0% or up to 25% of the distance D1. If the edges or heads of the markers overlap each other, this can exceed the maximum height required for the strut (approximately 160 microns (μm)). The minimum length of the head/tip extending to the right or left of the hole 22, ie δ3, is greater than 50% of D2.

[0077] Methods for inserting radiopaque markers into holes generally utilize cylindrical holes to retain the marker. Most of the holding force comes from the friction between the wall and the marker material. The marker material is securely retained in the scaffold holes in this manner when the scaffold has a wall thickness of 150 microns (μm) or more. However, when the wall thickness is reduced to 100 microns (μm) or less, it becomes much more difficult to retain the marker material within the hole. Coating materials for drug delivery may also help hold the marker in place, but coatings such as everolimus/PDLLA tend to be very thin, on the order of 3 microns (μm); This limits the out-of-plane shear strength to resist the marker falling out of the hole.

[0078] There are several desirable properties or capabilities that result from reducing the wall thickness of the scaffold struts. Advantages of using reduced wall thickness include a lower profile and therefore better introduceability, reduced acute thrombogenicity, and potentially improved healing. In some embodiments, it is desirable to use the same size markers on scaffolds with thinner struts so that there is no difference, ie, decrease, in radiopacity between the two types of scaffolds. However, reducing the strut thickness while keeping the marker hole 22 the same size may result in the marker protruding above and/or below the strut surface due to the reduced hole volume. It is desirable to keep the abluminal and luminal sides 25a and 25b of the marker coplanar with the corresponding abluminal and luminal sides of the strut, in which case the hole 22 diameter (d) is smaller than that of the thinner strut. It may be increased to partially compensate for the resulting reduction in hole volume.

[0079] Paragraphs [0073] through [0083] of U.S. patent application Ser. and the special challenges faced when the wall thickness is less than 160 microns (μm) or less than 125 microns (μm). According to some embodiments, when the wall thickness is less than 125 microns (μm), i.e., when the scaffold is thin-walled, friction alone ensures that the marker is retained in the hole. It turns out that it is not possible. In preferred embodiments where the wall thickness is less than 100 microns (μm), the marker material comprises a rivet-shaped marker, briefly described above in connection with FIG. 2C, and described in more detail in connection with FIGS. 8-16. Used to be held within the hole.

[0080] Below, embodiments of scaffold patterns are described that are suitable for meeting one or a combination of the following objectives.
(i) Thinning the crimp profile of the thin scaffold supporting the radiopaque marker.
(ii) fixing radiopaque markers within the thin-walled scaffold;
(iii) Reduce strain energy accumulation in the marker-retaining structure when the thin-walled scaffold is deformed during crimping, balloon expansion at the target vascular site, or introduction of the scaffold into the target site.
(iv) Avoiding protrusion or flaring of end rings at the distal end of the scaffold for thin-walled scaffolds or scaffolds that include PLLA and have a wall thickness greater than 125 microns (μm).

[0081] It will be appreciated that the above objectives are interrelated and that a single change can address multiple objectives. For example, by making marker links more flexible, both objective (iii) and objective (iv) can be met. Scaffolds according to these embodiments may be made from thin-walled tubes or sheets of material comprising poly(L-lactide) (PLLA), such thin-walled tubes or sheets producing the patterns shown in FIGS. 3-7. laser cutting from the tubular body. Methods of making tubes include one or more of extrusion, injection molding, solid state processing, and biaxial expansion as described in U.S. patent application Ser. No. 14/810,344 (62571.1212). may include.

[0082] Scaffolds according to embodiments, such as scaffolds 300, 400, 500, 600 or 700, are preferably crimped to a balloon catheter as shown in FIG. 3D. The scaffold may be crimped using any of the crimping methods described in U.S. Patent Application No. 2013/0255853, specifically paragraphs [0068] to [0073] of U.S. Patent Application No. 2013/0255853; [0077] to [0099], [0111] to [0126], [0131] to [0146] and in FIGS. 1A, 1B, 4A, 4B, 5A, 5B, 8A and 8B. The balloon may be attached to the balloon using any of the following crimping methods and devices for crimping to ensure a desired crimp diameter, such as D-min (defined below).

[0083] FIG. 3 shows a partial top view of an end portion of a scaffold, scaffold 300, according to one embodiment. The left or distal end portion 302 (ie, the left side in FIG. 3) includes sinusoidal rings 312a, 312b, and 312c, with ring 312a being the outermost ring. Ring 312a and ring 312b are connected by two links 334 and marker link 20. Ring 312c and ring 312d are connected by three links 334 extending parallel to axis AA. Link 334 extends parallel to axis AA and has a constant moment of inertia over its length, which means that link 334 has constant width and thickness and its center of gravity or means that the location of the geometric center (or longitudinal axis) is parallel to axis AA wherever it is located. The right or proximal end portion 304 (ie, the right side in FIG. 3) includes sinusoidal rings 312d, 312e, and 312f, with ring 312f being the outermost ring. Ring 312d and ring 312e are connected by three links 334. Ring 312e and ring 312f are connected by two links 334 and marker link 20. Thus, the scaffold 300 has marker links 20 extending between the outermost link and the adjacent inner ring and connecting the outermost link with the adjacent inner ring. Scaffold 300 may have 15, 18 or 20 rings 312 interconnected to each other by links 334.

[0084] The ring 312, e.g. ring 312b, is sinusoidal, which means that the curvature of the ring along the axis BB is most pronounced by the sine wave, where the wavelength of the sine wave is equal to the distance between adjacent peaks 311a of the ring. It means that it is well explained. The ring has a constant width at both the peaks 307, 309, 310 and the struts 330 connecting the peaks to adjacent peaks.

[0085] Each inner ring 312b-312e has three types of tops: a U-top, a Y-top, and a W-top. The outermost ring has only Y top type or W top type and U top type. The mountain or peak 311a (or the valley or valley 311b) may correspond to a U-top, a Y-top, or a W-top. The outermost ring 312a has only a U top type and a W top type. The outermost ring 312f has only a U top type and a Y top type. Marker link 20 connects the rings by forming a W top with a first ring (eg, ring 312e) and a Y top with a second ring (eg, ring 312f).

[0086] Link 334 connects to ring 312f at Y top 310. "Y-top" refers to the top of ring 312 where the angle extending between struts 330 and links 334 is obtuse (greater than 90 degrees). Link 334 connects to ring 312a at W top 309. “W top” refers to a top where the angle extending between strut 330 and link 334 is an acute angle (less than 90 degrees). The U top portion 307 is a top portion to which no links are connected. Marker link 20 connects to the ring at W top 314 and Y top 316.

[0087] In the scaffold 300, there are six ridges or peaks 311a and six valleys or valleys 311b per ring 312. Valley 311b always follows mountain 311a. Ring 312b has twelve peaks, three W peaks 309, three Y peaks 310, and six U peaks 307.

[0088] Figures 3A and 3B show enlarged partial views of scaffold 300. FIG. 3A shows section IIIA of FIG. 3, and FIG. 3B shows section IIIB of FIG. The following description will be made with reference to FIGS. 3A-3B, with the understanding that in the case of link 20, the Y top 316 connects to the outermost ring 312f, and the W top 314 connects to the adjacent ring 312e. , similarly applies to portions 302 and 304 of scaffold 300.

[0089] Referring to FIG. 3A, the successive wavelengths of the outermost ring 312a have lengths L1 and L2, i.e., the distance (along axis BB) from apex 314 to U-apex 307. is L1, and the distance from the U top 307 to the Y top 309 is L2. The same distances apply to ring 312b, with apex 316 to W apex 309 and W apex 309 to Y apex 310 being L1 and L2, respectively. In scaffold 300, L1=L2=constant for rings 312a, 312b. That is, the distance or wavelength from one mountain to another is the same. Furthermore, in the scaffold 300, L1+L2 is also constant everywhere. That is, for all rings, the distance between the W top and the Y top is the same, as is the distance between adjacent peaks of rings 312a to 312f. The distance X in FIG. 3A refers to the half period or half length of the sine wave, ie, 1/2 of L1. The distance X is equal to the distance from the top 314 to the U top 307 of the adjacent top 312a. X is the same for ring 312b. In other embodiments, L1 is not equal to L2 and X is different between the outermost ring 312a and the adjacent ring 312b.

[0090] In alternative embodiments, including scaffold 400, scaffold 500, or scaffold 700 described below, the ring may be zigzag rather than sinusoidal ring shaped. An example of a zigzag shaped ring is shown in FIGS. 5A and 6A of US Patent Application No. 2014/0039604. A zigzag ring may be described as a non-curved strut element centered at the top that is shaped to have an inner top radius and an outer top radius. The same description applies, ie the ring can be described in terms of wavelength, struts and tops, except that the shape is zigzag rather than sinusoidal. The term "wavy" refers to both zigzag and sinusoidal ring types.

[0091] Referring to FIG. 3B, the distance along axis AA from the peak or peak of ring 312a to the peak or peak of adjacent ring 312b, that is, the length of marker 20 (plus width t1) is A12. be. The distance along axis AA from the peak or peak of ring 312b to the peak or peak of adjacent ring 312c, that is, the length (plus width t2) of marker 334 between these rings is A23. In scaffold 300, A12=A23. The width of the left link 20 of the marker structure 21a is tm1, and the width of the right marker link 20 of the structure 21b is tm2. The width of link 334 is tl1. The tops 307, 310, 309, 314 of ring 312a and struts 330 have a constant width t1. The tops 307, 310, 309, 314 of ring 312b and struts 330 have a constant width t2. The tops 307, 310, 309, 314 of ring 312c and struts 330 have a constant width t3. In scaffold 300, t1 is less than t2 and t2=t3. Dimensions B1 and B2 are the top surfaces of rings 312a and 312c that extend parallel to axis BB, or uncurved or flat top surface portions. In scaffold 300, B1=B2.

[0092] Referring to FIG. 3C, a scaffold 300 is shown having markers 20 in a crimped state. The crimp diameter performed on the scaffold 300 is such that the same top is the theoretical minimum crimp diameter at which struts converging on each other touch each other. The formula for the theoretical minimum crimp diameter (D-min) under these conditions is shown below.
D-min=(1/π)×[(n×strut_width)+(m×link_width)]+2*t
and in the formula,
"n" is the number of struts in the ring (12 struts in scaffold 300);
“strut_width” is the width of the strut (170 microns (μm) for Scaffold 300);
"m" is the number of links connecting adjacent rings (3 in the scaffold 300),
“link_width” is the width of the link (127 microns (μm) for scaffold 300);
"t" is the wall thickness (93 microns (μm) for scaffold 300).

[0093] Therefore, for scaffold 300, D-min=(1/π)×[(12×170)+(3×127)]+2×(93)=957 microns (μm).

[0094] In the distal end 302 coupled ring pair 312a, 312b and the distal end coupled ring pair 312e, 312f, the marker link 20 is positioned closer to the link 334 (axis B) to accommodate the marker. - along B) wide. As a result, adjacent struts 330 can often overlap links 20 to achieve the same D-min throughout. This situation is shown in FIG. 3C. Such a condition of the crimped scaffold raises concerns about the local strength of the rings and links that hold the markers. As shown in FIG. 3C, overlapping (the struts push against the abluminal side of the marker) or underlap (the struts push against the abluminal side of the marker) by struts 330a, 330b and/or the associated U apices associated with these struts (pushing the surface) exists. It is preferred to eliminate this overlap/underlap when the scaffold is crimped.

[0095] Scaffold struts, particularly the struts and links of thin-walled scaffolds, are not designed to twist or to support large torsions. Twisting occurs when the struts touch and overlap each other. The higher the width-to-thickness aspect ratio of a scaffold strut, the greater the tendency for the strut to twist when it contacts an adjacent structure, e.g. (with higher aspect ratio, strut width for the same vascular tissue coverage compared to the flesh scaffold). As can be seen from the deformed state in FIG. 3C compared to FIG. 3, torsion is introduced into the ring structure and possibly also into the marker link struts. This type of abnormal deformation can lead to crack propagation or reduced fatigue life of the ring and/or link 20 during balloon expansion within a blood vessel.

[0096] FIG. 3D shows a medical device comprising a balloon catheter and a scaffold 300 crimped to the balloon 15. The distal end 302 of the scaffold 300 is closest to the distal end 17b of the balloon 15, and the proximal end 304 is closest to the balloon proximal end 17a. The tip or most distal end 12 of the balloon catheter is shown. A guidewire or mandrel 8 extends from the tip 12 and emerges from the lumen of the catheter shaft 2. The scaffold crimped to the balloon (according to D-min or other minimum crimp diameter) can be scaffold 300 or scaffold 400, discussed below. Scaffold 500, scaffold 600, and scaffold 700 may be used in place of scaffold 300.

[0097] As mentioned above, when compared to scaffolds with relatively thick walls, such as the scaffolds described in U.S. Patent Application No. 2010/0004735 and the ABSORB GT1 bioabsorbable scaffold, similar Thin-walled scaffolds with scaffold patterns were found to exhibit a significantly higher incidence of strut overlap or underlap (hereinafter referred to as MBOL) similar to that shown in Figure 3C. MBOL rates are likely to be higher when the width of the link containing the marker is widened to accommodate the same overall volume of marker material used in scaffolds with larger wall thickness struts. be. MBOL can also be higher if a more aggressive crimp is used, for example with a D-min crimp profile.

[0098] Additionally, if the same volume of marker beads is attached to both thin-walled and thick-walled scaffolds and the marker is coplanar with the abluminal and luminal sides of the link, the marker bead area A flat, wide shape must be used, and this forced shape deforms structures 21a and 21b, increasing the tendency for strut overlap in the marker bead area. This is because the marker structure may have a higher aspect ratio to accommodate the marker and/or distortion from the marker upsetting process may remain, causing the marker structure 21 to become out-of-plane. This is because it becomes more susceptible to twisting. Table 1 summarizes these findings.

[0099] Paragraphs [0073] through [0083] of U.S. patent application Ser. and the special challenges faced when the wall thickness is less than 160 microns (μm) or less than 125 microns (μm). Additionally, in the '710 application, the markers optionally remain coplanar with the abluminal side of the strut (thus having a higher aspect ratio and less tendency for torsional movement and overlap during crimping). It is also discussed how wide the marker holding structure must be for a reduced wall thickness and the same volume of radiopaque material if A wider, flatter marker structure increases the aspect ratio (AR) of the link width to wall thickness, thereby increasing the likelihood that the link will twist when in contact with an adjacent strut or apex.

[0100] In one example, the aspect ratio (AR) of the marker link of a thin-walled scaffold having a wall thickness of 93 microns (μm) is, for example, as described in U.S. Patent Application No. 2010/0004735. Compared to the AR of a scaffold with a larger wall thickness of 158 microns (μm), when the same volume of marker material is retained in both the 93 micron and 158 micron marker structures, it is approximately 4.5 (AR=ts/t=419 microns (μm)/93 microns (μm)=4.5). For a scaffold with a total thickness of 158 microns (μm), the AR is approximately 2 (AR=ts/t=322/158). Therefore, if the wall thickness is reduced from 158 microns (μm) to 93 microns (μm) for the same volume of marker material, the AR increases by a factor of 2.5. Given this significant increase in aspect ratio, there is a tendency for the marker link to twist when it contacts an adjacent strut or apex during crimping, and/or for the strut to overlap/underlap the marker link. Let it be understood that it is understandable.

[0101] It is known that during crimping the scaffold bar arm angle decreases and the adjacent bar arm struts naturally move towards the w-top link. In this crimp event, the "outer radius" of the w-top and its center point (usually located on the outside of the link) play an important role in guiding the way the scaffold strut crimps. In fact, the center point of this outer radius tends to act as a pivot point that guides the initial behavior of the strut and limits the extent of strut movement towards the marker linkage. At this second point, the MBOL that occurs between the strut and the marker linkage is closely related to this outer radius and the location of the pivot point. For the w-top with marker links 20 and thin scaffold design, the center point of the w-top was initially positioned within the marker structure 21 area. Therefore, during crimping, the closing behavior of the struts was not kinematically restricted, resulting in frequent overlaps/underlaps with the marker links. In order to reduce the MBOL incidence, the center point of the top of the W with the marker structure 21 can be moved to an area outside the marker structure 21. Therefore, during crimping, as the struts of the w-top move toward the marker structure 21, the struts are pushed and slipped into an overlapping or underlapping condition that induces twisting of the w-top and/or links. should be avoided.

[0102] FIG. 4 shows a partial top view of an end portion of a scaffold, scaffold 400, according to another embodiment. The left or distal end portion 402 (ie, the left side in FIG. 4) includes sinusoidal rings 412a, 312b, and 312c, with ring 412a being the outermost ring. Ring 412b and ring 312c are connected by two links 334 and marker link 20. Ring 312c and ring 312d are connected by three links 334 extending parallel to axis AA. The right or proximal end portion 404 (ie, the right side in FIG. 4) includes sinusoidal rings 312d, 412b, and 312f, with ring 312f being the outermost ring. Ring 312d and ring 412b are coupled by three links 334. Ring 412b and ring 312f are connected by two links 334 and marker link 20. Thus, the scaffold 400 has marker links 20 extending between the outermost link and the neighboring ring and connecting the outermost ring with the neighboring ring. Scaffold 400 may have 15, 18, or 20 rings 312 interconnected to each other by links 334.

[0103] Scaffold 400 has the same features as described above for scaffold 300, except as follows. Rings 412a and 412b are sinusoidal and are coupled to neighboring rings by W apex 414 and Y apex 416 (as in rings 312a and 312e), but ring 412a and ring near marker 20 The ring structure of 412b has been modified to avoid strut overlap when the scaffold is crimped to the minimum theoretical crimp diameter (D-min), as described above.

[0104] Referring to FIGS. 4A and 4C, enlarged views of the scaffold 400 in sections IVA and IVB of FIG. 4 are shown, respectively. To avoid the overlap described above, the spacing between the w top strut portions at the markers of rings 412a and 412b is increased. This modification is shown at w top 414 in the drawings. The extended top (along axis B-B) provides more spacing between struts 430 and marker structures 21a, 21b to avoid overlap (with this resulting change The crimp shape is shown in Figure 4D). w apex 414, in contrast to apex 309 that is not associated with marker link 20, modifies the scaffold structure near marker 20 in at least one of the following ways: (1), (2), and (3). ing.
(1) The flat or uncurved surface portion B1 of the top increases in the direction BB over the flat surface portion B2 of the other w top 309, which is, for example, the non-marker link width (tL ) is about 350% to about 400% greater than the maximum width (ts) of the marker link.
(2) The distance from the w top 414 (mountain) to the adjacent u top 407 (valley) is the distance from the y top 316 (mountain) of the ring 312b to the adjacent u top 307 (valley), and/or It increases compared to the distance from either the w top 309 (mountain) or the y top 310 (mountain) of the ring 312 to the adjacent u top 307 (valley). This is shown in the figure by comparing distance X412 and distance X312, which are measured lengths from the center of the peak to the center of the valley of ring 412 and ring 312, respectively. Distance X 412 is approximately 15% larger than X 312 of the marker link maximum width (ts), which is approximately 200% larger than the non-marker link width (tL).
(3) The distance from mountain 414 to neighboring mountain 407 is greater than the distance from mountain 407 to mountain 409, that is, L1 is longer than L2 in FIG. 4A, for example, L1 is about 10% longer than L2. , and/or L1 is a ridge next to any of rings 312a, 312b, 312d, 312f and a ridge next to any marker link maximum width (ts) that is approximately 200% greater than the non-marker link width (tL). approximately 5% longer than the distance between

[0105] The characteristics of ring 412a apply equally to ring 412b within the vicinity of marker link 20. FIG. 4B shows a view of portion 302 where ring 412a is shown in dotted lines from scaffold 300 onto ring 312a. The added spacing between marker link 20 and strut 430 is represented by "increased spacing" in the drawings. In this figure, the half-period difference in the sinusoidal ring portions (X412, X312) extending between the y and w apexes of the marker link, respectively, can also be seen. Additionally, the feature of the ring 412a is that it is symmetrical about the w top 414. Therefore, at least one of the changes (1), (2), and (3) described above applies to both sides of the w top 414.

[0106] According to another aspect of the scaffold 400 related to "increased spacing" shown for the MBOL or overlap-avoiding scaffold 400, scaffold marker links are created to avoid overlap. However, in some embodiments of interlocking rings, it is also beneficial to take into account the deformation of the structures 21a, 21b when marker elements, rivets or beads are swaged into the holes.

[0107] FIG. 4D shows a portion of the scaffold 400 in a crimped state where the scaffold has been crimped to D-min. As shown, the added spacing between the strut portions 430a, 430b of the w-top 414 in the marker link 20 also allows for overlap when the scaffold is crimped to the theoretical minimum crimp diameter, D-min. No underlap occurs either. Specifically, FIG. 4D shows that by modifying the ring 412 with the W top 414 connection to the marker link 20, the struts and/or U tops that are vertically adjacent to the marker structure can be scaffolded to It is shown that they are separated by a distance that is greater than or equal to the maximum width (ts) of the marker structure when crimped to min. No overlap occurs when the scaffold with ring 412 is crimped to D-min. The marker link is between the top and the strut wherever the scaffold is crimped to about D-min.

[0108] When a thin-walled scaffold similar to Scaffold 300 followed a simulated calcified serpentine anatomical model, the distal end ring due to struts being lifted and caught on obstacles along its path. It has been found that distortion was observed. In addition, there was also the possibility that the marker structure 21 and hole 22 would deform/stretch, resulting in the marker material falling off. To address this concern of separation of the marker material from the thin-walled scaffold, by extending the marker link and/or narrowing the width of the link portion connecting the structure 21 to the adjacent Y-top or W-top. The bending flexibility of the marker link can be increased. As a result of this modification, the hinge region next to the marker structure 21 becomes more flexible, thereby localizing the deformation to a point away from the structure 21 and protecting the marker hole 22 from significant deformation. This modification also allows the distal and/or proximal ends of the scaffold to be more flexible and conform to the balloon, thereby preventing the struts from lifting and catching on obstacles while being introduced to the target site. The possibility is reduced.

[0109] FIG. 5 shows an enlarged view of another embodiment of a scaffold, scaffold 500. The illustration of FIG. 5 is the same as section IVC of FIG. 4, except that the scaffold 500 has been modified in the marker links connecting rings 412a and 312b and the marker links connecting rings 412b and 312f. Scaffold 400 has all the features of scaffold 400 except . Marker link 520 differs from marker link 20 in that an additional link 520b has been added, ie the existing link on the right side of marker structure 21b (see marker link 20) has been extended. This added or extended marker link portion results in an increase in distance A12 compared to when marker 20 is used. The distance A12 is also longer than the distance A23 separating rings that are not connected by a marker link, such as ring 312b and ring 312c in FIG. The same modification marker link 520 that replaces marker link 20 is made to the marker link extending between ring 412b and ring 312f. Marker link 520 may replace marker link 20 of scaffold 300 (at both the proximal and distal ends). In such a case, the same features discussed with respect to scaffold 400 with links 520 also apply to scaffold 300 with links 520.

[0110] Replacing link 20 with marker link 520 allows the radiopaque material carried by marker structure 21 to fall off the scaffold as it is crimped, balloon expanded, or follows a tortuous blood vessel. , or were found to have less tendency to separate. The reason for the improved retention can be understood by considering the strain energy distribution on the links as the scaffold is deformed or as the y-top 316 of ring 312b moves relative to the w-top of ring 412a. Good morning.

[0111] If the top 316 of the ring 312b moves radially outward or inward relative to the top 414 of the ring 412a, or if the top moves in the opposite direction along axis BB, the marker link 20 deforms. do. A significant portion of the strain energy in the link 20 resulting from this deformation is retained in the marker structures 21a, 21b because the left and right link portions of the structure 21 are relatively short and thick (thus, this portion of the marker link There is little deformation and therefore less strain energy is retained here). The load must be counteracted somewhere along the marker link when ring movement is forced (i.e., ring movement is caused by forced displacement or overwhelming force, e.g. by the jaws of the crimper on the scaffold). (due to the closure of It is held in a marker structure 21 that is more easily deformed than the marker structure 21. This deformation may change the shape of the hole in which the marker material is located, resulting in a loss of retention force. retained in the structure 21 by extending the link portion of the marker 20 or by adding a link 520b that is significantly longer than the link 520a representing the length of the link portion of the link 20 between the left and right sides of the structure 21. Rather, the strain energy is reduced and more strain energy is retained by link 520b. As a result, the marker holes 22 retain their shape during these loading events so that the marker material is less likely to fall off during crimping or bending of the scaffold. In other words, most of the deformation of the link occurs in the elongated portion 520b so that the hole 22 can retain its shape. Additionally, link 520b increases the flexibility of the link, thereby allowing ring 312b or ring 312f to move more easily relative to ring 412a and ring 412b, respectively. This aspect is advantageous to avoid the problem of the distal end ring flaring or protruding from the balloon when the catheter is routed around dense vasculature (objective (iv) above). It should also be noted that marker 720, discussed in connection with FIG. 7, similarly addresses objective (iv) and objective (iii).

[0112] According to one example, the links 520b that form the y-top 316 have a thickness (tm2) that is approximately 60% less than the thickness (tm1) of the link portions 520a that form the w-top 414. Additionally, length A12 is approximately 27% longer than length A23 to accommodate link 520 with additional link portion 520b.

[0113] When a thin-walled scaffold crimped into the delivery system was followed through a simulated calcified serpentine anatomical model, distortion of the distal end ring due to struts catching obstacles along their path was observed. observed. To understand the possible causes of strut snagging, thin-walled scaffolds were crimped into an introduction system of the same morphology and placed in a flexion condition similar to that present in the anatomical model observed under the microscope. The balloon was observed to be compressed in the inner curve of the bend and under tension in the outer curve of the bend. Under tension, the balloon stretched and conformed to the curve. If the w-crest associated with the marker link were accidentally positioned in the outer curve of the bend, the w-crest would swivel outward rather than conform to the underlying curved balloon material at the distal end 15a. It flares out (see Figure 6B). The w-top portion of the scaffold remains straight because it is rigid due to the marker material and structure 21.

[0114] FIG. 6 shows a partial top view of an end portion of a scaffold, scaffold 600, according to another embodiment. The left or distal end portion 602 (ie, the left side in FIG. 6) includes sinusoidal rings 312a, 412b, and 312c, with ring 312a being the outermost ring. The right or proximal end portion 604 (ie, the right side of FIG. 6) includes sinusoidal rings 312d, 412b, and 312f, with ring 312f being the outermost ring. As can be seen in FIG. 6, distal end portion 602 is different from proximal end portion 604. This modification to scaffold 300 or scaffold 400 is to address the occurrence of non-conforming distal outermost end rings when scaffolds mounted on balloon catheters are routed around sharp turns within the vasculature. It is something that is done.

[0115] Proximal end portion 604 of scaffold 600 is the same as proximal end portion 304 or proximal end portion 404 associated with scaffold 300 and scaffold 400, respectively. Distal end portion 602 is modified from distal end portion 302 or distal end portion 402 as follows.

[0116] The (distal) marker link 20 or marker link 520 is in contrast to the (proximal) marker link 20 or 520 located between the outermost distal ring 312f and the inner ring 412b. Located between the proximal end ring 412a and the inner distal end ring 312c. This modification to distal end 602 is desirable for at least one of the following reasons (a) and (b).
(a) Improved compatibility with the distal end balloon: The marker link 20 has a higher bending stiffness than the link 634, or link 334 for that matter, resulting in increased distal compliance from the distal end of the balloon. This can result in separation of the outermost ring. If it is undesirable to change the marker link structure or (e.g. because the structure is needed to provide sufficient surface area to hold the desired volume of radiopaque material), it is realized If not, significantly reducing the bending stiffness of the links connecting the outermost ring 312a to the inner ring 412a can be achieved by moving the marker links 20 between the inner rings. It is then addressed that the bending stiffness between the two outermost rings 312a can be dramatically reduced (objective (iv)).
(b) Reducing strain on the marker holding structure: When the scaffold is fed through a sharp turn, it is the outermost ring that experiences the most strain due to the scaffold flexing. In embodiments of the scaffold where it is undesirable to reduce the bending stiffness of the outermost ring relative to the adjacent inner ring (as can occur, for example, if the connecting links are lengthened to make both more flexible) If it is important to avoid reducing the radial stiffness of the outermost ring or increasing the spacing between the rings for drug coverage or vascular support), the marker link 20 is placed between the inner rings. The movement avoids or reduces bending strains on the link 20 that could cause the marker material to fall off. That is, the bending strain of the scaffold (which occurs when the catheter is turned sharply) is greater between the outermost ring and the adjacent inner ring than between the inner rings (by changing the marker link structure). By locating the links 20 between the inner rings (unnecessarily), bending strains on the marker structure 21 are reduced. Objective (ii) and objective (iii) are met.

[0117] Scaffold 600 is also differentiated between scaffold 300 and scaffold 400 by the link type used to connect the outermost ring to the inner ring, i.e., link 634 that connects ring 312a to ring 412a. different. The outermost distal ring 312a is connected to ring 412a with three nonlinear link struts 634 that have significantly more bending flexibility than the link struts 334 connecting the inner rings. This also contributes to reason (a) for using the scaffold 600 pattern at the distal end.

[0118] Nonlinear link struts can take on a variety of shapes, but with some constraints, such as providing sufficient spacing for the crimp, such as a D-min crimp profile. The type shown in Figure 6 has a U-shaped intermediate section 636 connected to respective y- and w-tops by short and long straight link sections, respectively. Link portion 632a connecting portion 636 to the w top is longer than link portion 632b connecting to the y top to provide sufficient clearance for the ring struts during crimping (as described below). Because this gap is provided, the w top portion 309 formed by the link portion 632a prevents the U-shaped portion 636 from interfering with the strut 330 or the strut 330 from overlapping the U-shaped portion 636 in the crimped state. It can be crimped to D-min.

[0119] Referring to FIG. 6A, a crimp side profile of scaffold 600 is shown. A long straight link portion 632a and a short straight link portion 632b of link 634 are shown along with a U-shaped intermediate portion 636. Length A12 (measured with respect to axis A-A) exceeds length A23 by approximately the length of U-shaped portion 636, or the sum of the lengths of portions 632a and 632b equals the strut width of the ring. It is approximately equal to A23 minus . In one example, length A12 is approximately 40% longer than length A23.

[0120] In other embodiments, the U-shaped portion 636 is a link having a smaller moment of inertia in the area between portions 632a and 632b, an S-shaped cutout portion that replaces the U-shaped portion, or a narrowed portion. Can be replaced. Examples of these link types are described in FIGS. 14B, 14C, 14D, 14E, and 14F and accompanying paragraphs [0223]-[0229] of U.S. Patent Application No. 2014/0039604. ing. By "non-linear" link strut is meant any of these links.

[0121] FIG. 6B is an image showing a modified distal end of a medical device including a balloon catheter having a shaft 2 and a scaffold 10 crimped to a balloon 15. As can be seen from this figure, when the catheter is guided through a sharp turn (as it traces over the guidewire), the distal end of the balloon and the shaft adjust to the angle of the turn, but the distal end of the scaffold 7 does not adapt. More specifically, the outermost ring 5 flares or protrudes outwardly from the distal end. This protruding structure 5 may get caught on the wall of the vascular system. The most immediate concern with this orientation of the scaffold relative to the distal end of the balloon is damage that could be caused by the ring 5 catching on the vasculature (due to excessive bending strain) and damaging the scaffold. Possible damage has been discussed above. First, the marker link structure may be deformed, resulting in shedding of the marker material. Second, the strain may result in destruction of the ring 5 or breakage or crack propagation within the ring 5.

[0122] One solution to this problem is to increase the bending stiffness of the end ring so that vessel occlusion creates space at the flared or protruding scaffold ends. For example, the end rings could be made thicker or the number of connecting links between the outermost ring and the inner ring could be increased. However, it is preferred instead to reduce the stiffness of the ring so that the scaffold end is more compliant with the distal end of the balloon. Also, for the reasons mentioned above, it is also preferable to limit the load applied to the marker link. Scaffold 600 (or scaffold 700 below) meets this need.

[0123] FIG. 6C is an image of the scaffold distal end 602 attached to the distal end 15a of the balloon 15 as the catheter makes a similar sharp turn in the vasculature. As shown, end ring 312a conforms to the shape of balloon distal end 15a by reducing the bending stiffness of ring 312a relative to the inner ring (ring 312b). The end ring 312a does not flare or protrude as in the case of the scaffold 5. Link 632 acts as a hinge to accommodate the compression and tension forces that the bend would exert on the distal end ring when the crimped scaffold is placed in the bend.

[0124] Distal end scaffold conformability with the balloon distal portion may also be achieved by modifying the marker link structure to provide greater bending flexibility. In fact, the w-crest formed by the marker link according to the present considerations can significantly reduce the stiffness in the w-crest associated with the marker link 314. The thin-walled scaffold design then allows the marker link to connect to the outermost ring without the flaring problems mentioned above.

[0125] FIG. 7 shows a partial top view of an end portion of a scaffold, scaffold 700, according to another embodiment. The left or distal end portion 702 (ie, the left side in FIG. 7) includes sinusoidal rings 312a, 312b, and 312c, with ring 312a being the outermost ring. The right or proximal end portion 704 (ie, the right side of FIG. 7) includes sinusoidal rings 312d, 412b, and 312f, with ring 312f being the outermost ring. As can be seen in FIG. 7, the distal end portion 702 is different from the proximal end portion 704. This modification to scaffold 300 or scaffold 400 also addresses the occurrence of non-conforming distal outermost end rings when scaffolds mounted on balloon catheters are routed around sharp turns within the vasculature. It is done for the purpose of

[0126] Proximal end portion 704 of scaffold 700 is the same as proximal end portion 304 or 404 associated with scaffolds 300 and 400, respectively. Additionally, distal end portion 702 shares some of the characteristics of scaffold 600 in distal end portion 602, except as follows.

[0127] Marker link 720 (FIG. 2B) is located between outermost ring 312a and inner ring 312b, as opposed to marker link 20 or 520, which is located between the inner links in the case of scaffold 600. do. The marker links of scaffold 700 are also different from those of the previous embodiments. Marker link 720 has marker structure 21 oriented vertically, rather than horizontally as in marker link 20 or link 520. That is, marker structure 21a is offset from marker structure 21b along axis BB rather than axis AA. There is a long straight link section 732a connecting the structures 21 at one end to form the w-top 314 and a short link 732b at the opposite end forming the y-top 316.

[0128] The outermost ring 312a of the scaffold distal end portion 702 is connected to the inner ring 312b by one marker link 720 and two non-linear links 634 used in the scaffold 600. The bonded inner rings are not connected by marker links 720 or links 634. Link 334 is used. Marker link 720, in contrast to marker link 20, has more bending flexibility due to the length of portion 732a and is the outermost ring for easier positioning of the ends of the scaffold under fluoroscopy. and the adjacent inner ring. Additionally, when marker 720 is used, one or more of the following advantageous functional orientations exist. First, the marker is more flexible so that the outermost ring conforms to the balloon more easily when the catheter is routed around sharp turns within the vasculature. In this sense, marker 720 has some of the same advantages as marker 520 (objective (ii) and objective (iii)). Also, no changes need to be made to the ring structure to allow crimping of the ring with a w-top formed by the marker link. Since structure 21 does not interfere with ring structure 21, ring 312a can be crimped to D-min (objective (i)).

[0129] FIGS. 6A and 7A show the crimped condition of scaffold 700 near marker 720 and link 634, and the lengths A12, A23 between the rings. As can be seen from these figures, marker and link portions 732a and 632a, respectively, allow outer ring 312a to be crimped to D-min without interference from U-shaped portion 636 or from marker structure 21. It has a length of As can be seen from these figures, the structure 21 with hole 22 and U-shaped structure 636 has a U-top next to the W-top of the left ring and a U-top next to the Y-top of the right ring. between.

[0130] Referring to FIG. 7B, an enlarged view of section VII of FIG. 7 is shown. As shown, the lengths of portions 732a and 732b are c1 and c2, respectively. The lengths of portion 632a and portion 632b are also c1 and c2. Length A12 and length A23 of scaffold 700 are also shown (length A12, length A23, length c1 and length c2 are also the lengths and ring spacing of portions 632a and 632b of scaffold 600. apply). The sum of length c1 and length c2 is equal to A12 minus the length of U-shaped portion 636 and the width of the top. In some embodiments, A12 is about 40% larger than A23 and c1 is about 36% longer than c2. Length c1 is the distance between the adjacent apex valley and the w peak formed by section 732a or section 632a, minus the width of apex 314 or strut 330 when the scaffold is in the crimped state. (see FIGS. 6A to 7A). The marker structure is located to the right of the U top next to the W top formed by the marker link.

[0131] FIG. 7C is an image of the scaffold distal end 702 attached to the distal end 15a of the balloon 15 as the catheter makes a similar sharp turn in the vasculature. As shown, end ring 312a conforms to the shape of balloon distal end 15a by reducing the bending stiffness of ring 312a relative to the inner ring (ring 312b). The end ring 312a does not flare or protrude as in the case of the scaffold 5.

[0132] Table 2 shows the dimensions associated with examples of fabricated scaffolds corresponding to the illustrated scaffold embodiments (where an entry is "-" it means the same value as the adjacent column to the left). Therefore, the value of tm2 for scaffold 400 is 217, and the length B1 of scaffold 500 and scaffold 700 are 374 and 78, respectively).

[0133] Referring to Table 2, as understood from the examples above and as described above with respect to scaffold 300 in comparison to scaffolds 400, 500, 600, 700, scaffolds through crimped and/or tortuous arteries. wavelength, half-wavelength, marker link thickness, length, and orientation, non-marker link type and length, ring spacing, and top width at the marker link, respectively, as needed related to the introduction of has been changed. These relationships apply to thin-walled scaffolds, whether in the crimped state or prior to the crimped configuration. Thus, when referring to crimped scaffolds, the above relationships also apply. It should also be appreciated that features of scaffold 400 and/or scaffold 500 that are different from scaffold 300 can be incorporated into scaffold 600 and scaffold 700. Alternatively, features of scaffold 400 and/or scaffold 500 may not be included in the pattern of scaffold 600 and scaffold 700.

[0134] The following discussion is primarily concerned with fulfilling objective (ii): fixing the radiopaque material in the scaffold holes provided by the marker structures 21a, 21b. As previously mentioned, it has been discovered that thin-walled scaffolds cannot reliably retain marker material in the marker holes through frictional engagement with the walls of the cylindrical holes. In order to satisfy objective (ii), in a preferred embodiment, the radiopaque material is capable of forming a rivet-like body of marker material without interfering with any of the other objectives (i), (iii) or (iv). It is secured to either scaffold 300, 400, 500, 600 or 700 by upsetting marker structure 20, 520 or 720. Attachment and fixation of the marker, in some embodiments, does not involve the addition of any polymer, adhesive, or reshaping of the cylindrical hole (other than the deformation that occurs during the upsetting process). In a preferred embodiment, the drug polymer coating is applied after the marker is placed in the hole.

[0135] Instead of a spherical marker 25 for a cylindrical hole, a rivet-shaped marker is used. A side view and a top view of the rivet-shaped marker 27 are shown in FIGS. 8A and 8B. Head 28 may include an abluminal side 27a or a luminal side 27b of rivet 27. In the figures, head 28 includes an abluminal side 27a. It may be preferable for the head 28 to be the luminal side portion of the rivet 27 for assembly purposes. This is because the scaffold can then be placed over the mandrel and the tip portion of the rivet that has been deformed by a tool (such as a pin) applied externally to the abluminal side of the scaffold. be. The rivet 27 has a head diameter d1, and the diameter d2 of the shank 27c is approximately equal to the diameter of the hole 22. The height of the head 28 is h2, which is the amount that the head 28 will extend beyond the abluminal side 22a of the strut portion 21a. Although undesirable, the head 28 of the strut does not extend more than about 25 microns (μm), i.e., from about 5-10 microns (μm) to about 25 microns (μm) from the abluminal side 22a. Head protrusions extending no more than about 25% of the thickness may also be acceptable. Regarding the deformation of the tip of the rivet, the same degree of protrusion beyond the lumen side surface 22b may be allowed.

[0136] Referring to FIG. 9, a rivet within hole 22 is shown. The rivet 27 is fixed in the hole 22 by the deformed tip 27b'. The overall height h1 is preferably about 40% or about 10% to 40% or less of the strut thickness (t), and the tip height is about the same as the head height h2 or The size is within 5 to 20 microns (μm) compared to the height h2 of the head.

[0137] The rivet 27 is inserted into the strut portion 21a by first inserting the rivet 27 into the hole 22 from the lumen side of the scaffold so that the head 28 rests on the lumen side 22b of the strut portion 21a. can be attached to the hole 22 of. The scaffold is then slid over the interference fit mandrel. With the mandrel surface pressed against the head 28, a tool (such as a pin) is used to deform the tip 27b to produce the deformed tip 27b' of FIG. In some embodiments, rivet 27 may be inserted into hole 22 from the abluminal side first such that head 28 rests on abluminal side 22a of strut portion 21a. With the head 28 held in place by a tool or flat surface applied to the abluminal side, the tip 27b is inserted into the lumen or removed from an adjacent position on the abluminal side. Deformed by tools, pins, or mandrels passed through the scaffold pattern. In some embodiments, the rivet 27 may be a solid body (FIGS. 8A-8B) or a hollow body, for example, the shank is a hollow tube and the opening extends through the head 28 of the rivet. and extend.

[0138] In some embodiments, the rivet is a hollow or solid cylindrical tube without a prefabricated head 28. In these embodiments, the tube (solid or hollow) may be first fitted into the hole and then the rivet head and tip portion formed using a tightening tool. According to a preferred embodiment, there is a method for making a radiopaque marker as a rivet and attaching the rivet to a scaffold, and a scaffold attached with such a marker. First, a method for producing a rivet-shaped marker from beads will be described.

[0139] As mentioned above, the head and tip portion of the marker may be damaged when an external force is applied to the rivet, when the link structure is deformed during crimping or balloon expansion, or when the scaffold undergoes sudden turns in the vasculature. This helps hold the marker in place, such as when performing However, in some embodiments, the tip portion of rivet 27' of FIG. 9, such as tip 27b', is not present. Alternatively, the shank portion of the rivet is deformed to have a trapezoidal or frustoconical shape, or to have an enlarged end (eg, rivet 137' shown in FIG. 15A). This type of marker has been found to have increased resistance to being forced out of the holes in the struts or links when the scaffold is subjected to external forces that deform the links or struts holding the marker.

[0140] It is desirable to select the appropriate size of beads to form the rivet. According to some embodiments, the bead size, or bead volume, to be used depends on the thickness (t) of the struts of the scaffold structure to which the rivets are attached, the hole diameter (D2), the distance between the holes (D1), and Depending on the thickness of the periphery (D2) (eg link struts with holes 22 in FIG. 2A or FIG. 2B). The raw material may be spherical or cylindrical. Raw materials made of radiopaque materials can be obtained from commercial sources.

[0141] According to the present disclosure, raw beads are used to create rivet markers for attachment to scaffold holes 22. In preferred embodiments, rivet markers are attached to or engaged with scaffold holes in thin walled struts or links, preferably having a thickness (t) of less than about 100 microns (μm). The rivet making process and scaffold attachment steps can be summarized as a six-step process.

[0142] Step 1: From among the raw materials, have a diameter or volume within the desired range, i.e., a diameter or volume suitable for attachment to the scaffold according to the dimensions D0, D1, D2 and t (Figure 2B). Select marker beads. Selection of marker beads with a desired diameter or volume, or removal of beads that are too small from a lot, can be done using a mesh sieve. A set of beads is sieved on a mesh sieve. Beads that do not have the smallest diameter or volume fall through the openings of the mesh sieve. Alternative methods known in the art may be used to remove unwanted beads or select beads of appropriate size.

[0143] Step 2: Place the selected beads from Step 1 onto the die plate.

[0144] Step 3: Cold form the rivet from the beads by pressing the beads into a die plate. Reshape the beads by forcing them through a die (e.g., using a plate, mandrel head, pin, or tapered ram head) at near ambient temperature to achieve the shape of the die and the die receiving the beads. into a rivet defined by the volume of the bead relative to the volume of .

[0145] Step 4: Remove the formed rivet from the die plate. The formed rivet has an overall length of about 190-195 microns (μm), a diameter of about 300-305 microns (μm), and is removed using a tool with a vacuum tube. Air pressure is adjusted to grip the rivet or move the rivet away from the tip. Rivets are die-cut by placing the opening of the vacuum tube over the head of the rivet, lowering the air pressure in the tube to cause the head to adhere (by pressure difference) to the tube tip, or suction, and lifting the rivet from the die. removed from.

[0146] Step 5: With the rivet still attached to the tip of the tube, move the rivet to position it above the hole in the scaffold, use the same tool to place the rivet in the hole, and then Raise air pressure to ambient air pressure. The rivet separates from the tool.

[0147] Step 6: Deform the rivet and/or hole to enhance engagement or resistance to dislodgement of the marker from the hole, eg, FIGS. 14A-14C.

[0148] It will be appreciated that according to steps 1-6, the problem of handling non-spherical beads is overcome. For example, steps 1 through 6 above overcome the problem of orienting the spherical beads so that they can be aligned and placed in the holes without the need for reorientation after the rivet is formed from the spherical beads. Ru.

[0149] Referring to FIGS. 16A, 16B, and 16C, transferring the formed rivet 127' (or 137') from the die 200 (or 205) to the scaffold strut hole 22 using the vacuum tool 350. The steps associated with are shown. As will be appreciated, the formed radiopaque marker 127' is extremely small, i.e. less than 1 millimeter in its largest dimension, and therefore handling and orientation of the marker 127' for placement in the hole 22 is It is complicated by the need to properly orient the shank relative to the hole (as opposed to placing the ball in the hole). Thus, the upsetting or forging process involves removing the rivet 127' from the hole 200 using the tool 250, FIG. 16A, keeping the rivet 127' attached to the tool and maintaining its orientation, FIGS. 16B-16C, and then placing the rivet 127' in the hole 22a, combined with placement in the scaffold hole according to FIG. 16C.

[0150] Referring to FIGS. 10 and 11A, a first embodiment of a die 200 and a marker 127 formed using the die 200 are shown, respectively, in accordance with the present disclosure. The die is a flat plate having an upper surface 201 and a through hole extending from the upper end 201 to the lower end. The hole has a top diameter dp2 and a bottom diameter dp1 that is less than dp2. Although the hole 202 is preferably circular throughout, in other embodiments the hole may be rectangular or hexagonal throughout the thickness tp, in which case dp1 and dp2 are the hole (rather than diameter) It is the transverse length or size. Further, the plate 200 has a height tp. The taper angle is related to dp2 and dp1 by the formula tanФ=(1/2(dp2-dp1)/tp), where in preferred embodiments φ is 1-5 degrees, 5-10 degrees, 3-5 or 2- It is 4 degrees. The shape of die 200 produces a frustoconical shank, as shown in FIG. 18A. Beads are placed at the top of opening 202 such that source beads (not shown) are partially located within hole 202 . A plate, mandrel or pin (“ram head”) is then pushed onto the top of the bead so that the bead is pushed into the hole 202. The bead is forced into the hole until the ram head is about a distance HH from the surface 201. The rivet 127 formed from the above-described forming process has a taper angle Τ over the entire or substantial portion of the shank height SH, and the shank shape is frustoconical. The overall height of the rivet is HR, the head thickness is HH, and the head diameter is HD. In some embodiments, the angle Τ may be small enough such that the shank is treated as a cylinder or such that Τ is approximately zero.

[0151] Referring to FIGS. 12 and 13A, a second embodiment of a die 205 and a marker 137 formed using the die 205 are shown, respectively, in accordance with the present disclosure. The die is a flat plate having a top surface 206 and a hole extending from the top end 301 to the bottom end. The hole has a constant diameter dcb1 throughout. A counterbore is formed in the upper end 206. The counterbore diameter is dcb2. Hole 207 is preferably circular throughout, but in other embodiments hole 207 may be rectangular or hexagonal, in which case dcb1 is the length or size across the hole (rather than the diameter). be. The shape of die 205 produces a cylindrical shank with a rivet or head having a stepped cylindrical shape, as shown in FIG. 13A. Beads are placed at the top of opening 207 such that source beads (not shown) are partially located within hole 207 . The ramhead is then pushed onto the top of the bead so that the bead is pushed into the hole 207. The bead is forced into the hole until the ram head is approximately HH distance from surface 206. The rivet 137 formed from the above-described forming process takes the shape shown in FIG. 13A. The overall height of the rivet is SH+HH, the head thickness is HH, the shank height is SH, and the head diameter is HD.

[0152] Tables 3 and 4 below provide examples of rivet dimensions for rivets for securing within link holes 22 as shown in FIG. 2A. In this example, the thickness of the link is 100 microns (μm), and the values of D0, D1, and D2 in microns (μm) are 241, 64, and 64, respectively.

[0153] The values of dimensions tp, dp2 and dp1 of die 200 are 178, 229 and 183. The dimensions of the formed rivets obtained using die 200 are shown in Table 3. As can be seen from the results, the shank length (or height) is greater than 150% of the link thickness and the rivet head diameter (HD) is significantly greater than the hole 22 diameter. The lower part of the shank is used to form the tip of the rivet. The mean values and standard deviations for HD, SD, and SL are based on "n" samples of rivets each measured.

[0154] The values of dimension dcb2 and dimension dcb1 of die 205 are 305 and 203. The dimensions of the formed rivets obtained using die 300 are shown in Table 4. The mean values and standard deviations for HD, SD, HH and SL are based on "n" samples of each rivet measured.

[0155] In Tables 3 and 4, "OD. Rivet head diameter after upsetting" refers to the outer diameter of the rivet marker head after the rivet marker is pushed into the scaffold hole.

[0156] Next, consider an example process for attaching either rivet 127, 137 to scaffold hole 22. According to some embodiments, the rivet shank is placed in the hole 22 from the abluminal side or outside of the scaffold, so that the head is located on the abluminal side 22a. The rivet may alternatively be placed from the luminal side of the hole. The rivet is firmly pushed into the hole so that the largest portion of the shank extends from the luminal or abluminal side, respectively.

[0157] After the rivet 127 is placed in the hole 22, the opposite side of the head is subjected to an upsetting process. Referring to FIG. 11B, a cross section of a deformed rivet 127' within hole 22 is shown. Rivet 127' has a head 127a' extending an amount h2 from surface 22a. Length h2 may be about 25 microns (μm), 25-50 microns (μm), or 5-50 microns (μm). The same dimensions apply to the tip 127b' extending from the opposite surface (eg, the luminal side) of the link. The diameter of the head 127a' may be larger than that of the tip, and the diameter of the tip 127b' may be larger than the diameter of the head 127a'. The tip portion is formed from an extended shank length that projects from the link surface by upsetting. The tip portion 127b' is formed by upsetting. For example, rivets 127 are placed from surface 22a (abluminal) such that a significant portion of the shank length, eg, 50% of the strut thickness, extends from the luminal side. A cylindrical mandrel (not shown) is placed through the lumen of the scaffold. This mandrel has an outer diameter slightly smaller than the inner diameter of the scaffold and provides an upsetting surface that forms tip 127b'. The mandrel is rolled back and forth over a shank portion extending from the side of the lumen. This action flattens the shank material around the hole to create tip portion 127b'. The resulting rivet 127' is driven, at least in part, by the resistance of the tip portion 127b' which tends to push the rivet towards the abluminal side of the bore and which tends to push the rivet towards the luminal side of the bore 22. and the resistive force of the head portion 127a' to secure it in place. As shown, the deformation of the shank produces a tip 127b' having a flange disposed on surface 22b. The flange may be circular like the head and may have a flange radial length that is greater or less than the radial length of the flange of the head 127a'.

[0158] Referring to FIGS. 15A and 15B, a stepped mandrel is used with a ram head to produce rivet 137' from rivet 137. The rivet has a shank 137' that has been reshaped, for example, from a generally cylindrical shape when using die 205 of FIG. 12 to the shape shown in FIGS. 15A-15C. This shank shape can be characterized by a taper angle θ on the order of about 5-15 degrees, 5-9 degrees, or about 3-8 degrees. The shank according to some embodiments of the rivet in hole 22 is frustoconically shaped, with the shank end opposite or distal to head 137a', i.e. end 137b' being proximal or distal to head 137a'. It has a larger or larger diameter than the shank portion closest to section 137a'. The deformed shank 22' has a shank diameter S2 closest to one of the luminal or abluminal openings of the hole 22' that is larger than the shank diameter S1 closest to the other of the luminal or abluminal openings. In other words, S2>S1. According to some embodiments, as shown in FIG. 15A, the cylindrical hole 22 is also transformed into a hole 22' having a larger opening in surface 22b than the hole opening in surface 22a. According to some embodiments, hole 22 and rivet 137 are deformed when rivet 137 is attached to the scaffold.

[0159] The structure shown in FIG. 15A may be created by a second step of attaching rivet markers to the scaffold holes 22. In contrast to the first step, the tool is not rolled over the entire surface over which the shank tip protrudes from the hole opening. Instead, the shank tip is pressed directly into a non-compliant surface, which can be the surface of a metal mandrel. The rivet is deformed by compressive forces between the surface of the mandrel and the head of ram 234, forcing the rivet into the mandrel surface. The first step of producing a deformed rivet 127', in contrast, is formed by a combination of rolling a hard surface into the shank and restraining the head 127a, which causes the tip 127b to become upset. The rivet head is held against the surface 22a during the process. Under the second step, the line of force is completely along the axis of the rivet, or perpendicular to the rivet head. The result is that the shank portion is leveled or widened and the hole is deformed, with little or no flange or periphery formed from the distal end portion of the shank.

[0160] Next, the second step will be described in more detail with reference to FIGS. 14A to 14C. Scaffold 400 is placed on stepped mandrel 230. The mandrel has a first outer diameter and a second outer diameter that is smaller than the first outer diameter. The scaffold portion holding the marker 137 is placed over the small diameter portion of the mandrel 230. The larger diameter portion of mandrel 230 holds adjacent portions of the scaffold. The smaller diameter portion of mandrel 230 has a surface 230a and the larger diameter portion has a surface 230b. As shown in FIGS. 14B and 14C, the ram 234 forces the scaffold portion 230a carrying the marker 137 into the mandrel surface 230a with a force F (FIG. 14B), causing the scaffold end to move a distance " d” (FIG. 14A). After the scaffold reaches the surface 230a, the ram 234 continues to force the marker-bearing scaffold portion (by pushing directly on the head 137a), leaving the deformed marker 137' and the hole as shown in FIG. 15A. 22' is generated. The selected surface 230a is smooth or free of grooves, pitting, dents, or other surface irregularities (other than the cylindrical surface) that would impede material flow during upsetting. Good too. In a preferred embodiment, the mandrel surface is smooth compared to the surface of the head 234 pressed into the rivet marker 137. That is, the coefficient of friction (Mu) between head 234 and surface 137a' is greater than Mu between surface 230a and surface 137b' of mandrel 230.

[0161] The deformed shank 137' and hole 22' geometry shown in FIG. (meaning great power). Indeed, unexpectedly, the deformed rivet 137' and hole 22' have greater resistance to dislodgement than a marker fitted to a link with 50% greater thickness, with or without head 137a'. It was discovered that. For example, a test for the minimum shedding force required to force a rivet 137' out of the side 22a of a 100 micron (μm) thick strut hole 22' is described in U.S. Patent Application No. 2007/0156230 (FIG. 8A, 8B, or when the sphere deforms more into a cylindrical shape during storage, increasing surface-to-surface contact to a maximum), with holes in the struts having approximately 50% greater thickness (158 microns (μm) vs. 100 microns ( μm)) was higher than the shedding force required to extrude the attached marker. As shown in Table 4.

[0162] Scaffold B has a greater extrusion force even though Scaffold A has more surface area for contact with the marker and thus has a greater frictional force to resist shedding. This result shows that the deformation that occurs during the upsetting process that results in the deformed rivet marker and hole in Figure 15A has a significant impact on the extrusion force (note: the gravimetric grams reported in Table 4 The extrusion force was applied to the luminal side 22b of scaffold B). Considering the 50% greater wall thickness, scaffold A should have had a greater shedding force (same bead material, bead volume and poly(L-lactide) scaffold for scaffold A and scaffold B). material). The greater dislodgement force can be explained by the modified shank and hole shape essentially creating a lower portion 137b' that is significantly larger than the opening 22a of the strut 22. Thus, the dislodging force is applied to the aperture 22a' and the aperture 22a' in order to dislodge the marker from the 22a side of the aperture 22' (in addition to essentially overcoming the frictional forces between the material and the wall of the hole). and/or must be large enough to deform the shank portion 137b'.

[0163] The shape 137' of FIG. 15B may be formed by an upset process that deforms the rivet while it is located inside the hole 22. The rivet may have the shape and/or characteristics of rivet 27, rivet 127 or rivet 137 prior to upsetting. Lateral flow of rivet material during upsetting near tip portion 137b' (shear flow) expands the rivet material and brings the strut hole closer to opening 22b' (enlarges). This creates a trapezoidal or frustoconical shape of the rivet shank and hole. The upsetting process of Figures 14A-14C applies equal and opposite forces approximately collinear with the axis of symmetry of the rivet (rather than rolling motion on one side). Instead, a cylindrical or ball (rather than a rivet) is placed in the hole 22 and is placed between the upsetting surface 230a and the tip 137b approximately equal to the coefficient of friction (COF) between the upsetting surface 234 and the head 137a. If the same COF were present but otherwise the same upsetting process as in Figures 14A-14C, the result would be a more symmetrical shape, such as the shape shown in US Patent Application No. 2007/0156230. It is considered that the marker has become a deformed marker, for example, a cylindrical or barrel-shaped marker that has been crushed depending on the COF. This result is reported in Kajtoch, J Strain in the Upsetting Process, Metallurgy and Foundry Engineering, Vol. 33, 2007, No. 1 (discussing the effect of the coefficient of friction between the ram and the ingot on the resulting shape for slenderness ratios greater than 2). The shape of the radiopaque material pushed into the hole, such as rivet 137 versus sphere (scaffold A), is also a factor. The presence of the head on one side causes the shank to form an asymmetrical shape about the strut midplane axis. It is thought that the combination of rivet shape and friction coefficient difference produced the favorable results.

[0164] In a preferred embodiment, the smooth mandrel 230 surface 230a presses against the surface 137b compared to the rougher surface of the head 234 that presses against the surface 137a. In a preferred embodiment, the abluminal coefficient of friction was greater than 0.17, ie, Mu>0.17, while the luminal coefficient of friction was less than 0.17, ie, Mu<0.17. Ta. As mentioned above, the effect of differences in friction coefficients can be explained by constraints on shear flow or subsequent material flow near the ends that contact the respective upsetting heads. If the coefficient of friction is low enough, the surface area expands laterally rather than remaining relatively constant. Therefore, since Mu is small on the luminal side, there is more lateral flow than on the abluminal side. The result, when combined with the use of a rivet shape, is believed to be the disclosed frustoconical shape, as shown in FIGS. 15A-15B, for example, which can be thought of as a shank with a fixed angle θ.

[0165] There may be a heating step for the scaffold after marker placement. In some embodiments, this heating step may correspond to a recovery step of the scaffold polymer prior to crimping that removes aging effects of the polymer.

[0166] Thermal recovery (including heat treatment of the bioabsorbable scaffold above the TG but below the melting temperature (Tm) of the polymer scaffold) prior to the crimp step reverses physical aging of the polymer scaffold or can be removed, reducing the number of crimp damage and/or marker dislodgements (eg, in scaffold piles).

[0167] According to some embodiments, immediately before crimping the scaffold to the balloon and after placing the marker, the scaffold is heat treated, mechanically strained, or solvent treated to restore polymer aging or Induce erasure. Restoration erases or reverses changes in physical properties caused by physical aging by returning the polymer to a less aged or even unaged state. Physical aging brings the polymer closer to thermodynamic equilibrium, while recovery moves the material away from thermodynamic equilibrium. Restoration can therefore change the properties of the polymer in the opposite direction to that produced by physical aging. For example, recovery may cause the polymer to decrease its density (increase its specific volume), increase its elongation at break, decrease its modulus, increase its enthalpy, or any combination thereof. .

[0168] According to some embodiments, recovery is desirable for reversal or erasure of physical aging of previously treated polymers. However, recovery is not intended to remove, reverse, or erase memory of previous processing steps. Therefore, recovery does not train the scaffold or tube, nor does it impart memory to the scaffold or tube. Memory can refer to the transient polymer chain structure and transient polymer properties provided by previous processing steps. This includes a processing step to radially strengthen the tube to form a scaffold by inducing biaxial orientation of polymer chains in the tube as described herein.

[0169] Regarding the integrity or resistance to shedding of the marker scaffold during crimping, a heating step has been found to help reduce the instances where crimping causes marker shedding. According to some embodiments, any of the foregoing embodiments of markers retained within scaffold holes 22 may be subjected to a heating step immediately before crimping, such as within 24 hours after crimping, after the marker has been placed in the hole. can include. It has been found that the scaffold can better retain the marker within the hole 22 after heating. Mechanical strain, e.g. limited radial expansion, or thermal recovery (which raises the scaffold temperature above the glass transition temperature (TG) of the load-bearing portion of the scaffold polymer for a short period of time) may occur after crimping. and/or may have a beneficial effect on the structural integrity of the scaffold after balloon expansion from the crimped state.

[0170] In particular, these strain-inducing steps tend to beneficially affect the dimensions of the hole 22 surrounding the marker when the hole is deformed as described above in connection with FIGS. 15A-15B.

[0171] According to some embodiments, the scaffold after marker placement is heated to a temperature of about 20 or 30 degrees above the glass transition temperature of the polymer for 10-20 minutes. More preferably, the load-bearing structure of the scaffold (e.g., a portion made from a polymer tube or sheet of material) is a polymer comprising poly(L-lactide) and the temperature is maintained at about 10 to 20 minutes after marker placement. Heat to 80-85°C.

[0172] According to some embodiments, increasing the temperature of the scaffold after marker placement causes portions of the hole 22 to reshape to improve the fit of the marker within the hole. ing. Referring to FIG. 15C, after the rivet marker 137 is placed in the hole 22 according to the second step, the hole shape is deformed to create a lip or edge 140 at the end 137b'', which is processed in the recovery step. The surface 140a of the lip 140 resists marker shedding more strongly when the force is directed toward the end 22b'.

[0173] In accordance with the foregoing objective of achieving the desired crimp profile of a thin-walled scaffold, there is a method for crimping such a scaffold into a balloon that meets the following needs:
Structural integrity: Avoiding damage to the structural integrity of the scaffold when it is crimped to or expanded by a balloon.
Safe introduction to the implantation site: Avoid dislodgement or separation of the scaffold from the balloon during transfer to the implantation site.
Uniformity of Expansion: Avoiding uneven expansion of the scaffold ring that can lead to structural failure and reduced fatigue life.

[0174] As previously reported in US Patent Application No. 2014/0096357, scaffolds are not as elastic as more ductile metallic stents. Therefore, the need to meet all of the above needs is particularly for thin-walled scaffolds that can be more easily damaged during crimping or balloon expansion.

[0175] FIGS. 17A-17B illustrate the steps associated with a crimping process for crimping a thin-walled scaffold 300, 400, 500, 600 or 700 to a balloon catheter (FIG. 3D) according to the present disclosure. It has been found that this crimping process can meet all the above requirements for scaffolds crimped to D-min. In this example, a crimping process for crimping a 3.5 mm scaffold to a 3.0 mm semi-compliant PEBAX balloon is described. FIG. 17B shows the flow of the crimp portion of the flow of FIG. 17A in graphical form, i.e., a balloon pressure of about 20 to 70 psi (or 1 atm to fully inflated or overinflated balloon pressure) is applied throughout most of the crimp process. A graph of scaffold diameter versus time is shown. For example, the balloon pressure is maintained at 70 psi during steps A through G, and then the pressure is decreased (or deflated) to 50 psi (or 1 atmosphere) over periods GH. Balloon pressure is removed at point H. Steps H to J do not use balloon pressure in order to achieve a low transverse profile or crimp to D-min and avoid balloon damage.

[0176] FIG. 17A shows three possible methods of crimping, depending on your needs. First, two balloons, Balloon A and Balloon B, are used. Balloon B is used for the pre-crimp step(s) and balloon A (used with the introduction system) is used for the final crimp. Second, only one balloon is used for the entire crimp process, including alignment confirmation testing (Balloon A). In this case, the scaffold inner diameter is larger than fully inflated or overinflated balloon A. Therefore, misalignment can occur on the balloon before crimping. Third, only one balloon is used for the entire crimping process (Balloon A) without final alignment confirmation inspection. In this case, the balloon for the introduction system has a fully inflated or overinflated state approximately equal to the inner diameter of the scaffold inner diameter.

[0177] Stage I: Place the scaffold supported on the fully inflated balloon of the balloon catheter into the crimp head. The balloon, when inflated and supporting the scaffold in this state, has substantially all creases removed. In a preferred embodiment, the catheter balloon (ie, the final product, the balloon used in the stent introduction system) is used for Stage I to Stage II. In other embodiments, it may be preferable to use a second, larger balloon for Stage I and Stage II (as detailed below). The crimper blade is heated to raise the temperature of the scaffold to the crimp temperature. In a preferred embodiment, the crimp temperature is between the lower limit of the glass transition temperature (TG) of the polymer and 15 degrees between TG.

[0178] After the scaffold reaches the crimp temperature, the iris of the crimper closes, reducing the scaffold inner diameter (ID) to a diameter slightly smaller than the outer diameter (OD) of the fully inflated or overinflated balloon. (For example, 3.45 mm to about 3.05 mm for a PEBAX 3.0 mm semi-compliant balloon inflated to a diameter of about 3.2 mm). In this example, Balloon B would be used for diameter reduction to a 3.0 mm balloon size, or Balloon A size (eg, a 3.0 mm balloon).

[0179] Stage II: Hold the crimper jaws at a diameter of 3.05 mm and maintain this diameter for a second rest period at the crimp temperature. After Stage II, the scaffold has approximately 90% of its pre-crimped diameter.

[0180] In Steps I-II above, the scaffold diameter is reduced to the size of the fully inflated balloon (ie, Balloon A) of the stent delivery system. During the initial alignment test (before crimping), the scaffold inner diameter was greater than the fully expanded diameter of the balloon (e.g., the scaffold diameter was approximately the fully expanded diameter of a balloon with a diameter of 3.0 mm to 3.2 mm). 109%-116%), so there is potential for longitudinal displacement (relative to the balloon) while the scaffold is crimped to the balloon size. Considering this possibility, remove the scaffold from the crimper and inspect the alignment of the scaffold on the balloon with respect to the proximal and distal balloon markers.

[0181] "Final alignment confirmation" step: When the scaffold needs to be adjusted on the balloon, the technician makes manual adjustments to move the scaffold into position. However, it has proven difficult to make these fine adjustments while the scaffold is resting on a fully inflated balloon and has an inner diameter slightly smaller than the outer diameter of the balloon. To address this need, the balloon pressure is reduced slightly or the balloon is temporarily deflated to make realignment easier. Once the scaffold is properly realigned between the balloon markers, return the scaffold and fully inflated balloon to the crimper. Now that the scaffold inner diameter and balloon size are approximately equal, the final crimping of the scaffold to the balloon of the catheter can begin. In order to prevent further longitudinal movement of the scaffold relative to the balloon, it is preferred that the scaffold diameter is made slightly smaller than the fully inflated diameter of the balloon before the start of stage III. As mentioned above, if two balloons are used, replace balloon B with balloon A, align against balloon A, and crimp the scaffold to the final diameter of balloon B.

[0182] Stage III: Return scaffold and balloon to crimper. The jaws close to approximately the same diameter as Stage II or slightly larger (taking into account the recoil that occurs during alignment testing). The crimper jaws are held at this diameter for a third rest period, which may be the time required for the scaffold to return to the crimping temperature.

[0183] The iris diameter is then reduced to an ID approximately equal to, or slightly less than, the OD of the balloon if it were unpressurized and had randomly distributed folds. That is, the scaffold is crimped to the approximate OD of the balloon when it is pressurized and deflated so that nearly all prefabricated folds are replaced with random folds. For example, the iris diameter is reduced to approximately 1.78 mm for a 3.5 mm scaffold. After this diameter reduction, the scaffold OD is about 60% of its diameter at stage III and about 50% of its starting or pre-crimp OD.

[0184] Stage IV: After reducing the scaffold OD to approximately 50% of its starting diameter, the crimper jaws are held at this diameter for a third rest period. In a preferred embodiment, balloon pressure decreases slightly during this pause. For example, in a 3.0 mm semi-compliant PEBAX balloon, the pressure decreases from 70 psi to 50 psi during the Stage IV pause. This reduction is preferred to achieve a lower transverse profile and/or protect the balloon material from overstretching.

[0185] After the Stage IV rest period, the balloon is deflated or returned to atmospheric pressure and the crimper iris is reduced to the final crimp OD, eg, 1.01 mm or about 30% of its pre-crimp OD. This balloon deflation may be performed by opening a valve that supplies pressurized gas to the balloon while or just before the iris diameter is reduced to the final crimp diameter.

[0186] The jaws of the crimper are then opened for a pause of about 170 seconds with or without maintaining the crimp temperature (i.e., the scaffold temperature is between 15 degrees below TG and approximately TG). Hold at the final crimp diameter for a period of time, or 100-200 seconds. This final rest period is intended to reduce the amount of scaffold recoil when the crimped scaffold is removed from the crimper. Immediately after the 170 second pause, the scaffold is removed and a retaining sheath is placed over the scaffold to further reduce recoil. A leak test may be performed after the final stage of crimping.

[0187] It may be necessary to provide an auxiliary pressure source for the balloon to maintain a relatively constant pressure throughout the diameter reduction and rest periods (as shown in the example above). Indeed, in one embodiment, it was found that a pressure drop occurred in the balloon during diameter reduction. To account for this pressure drop, a secondary pressure source was used to maintain the same pressure during diameter reduction as during the rest period.

[0188] The above-described example of a preferred crimping process that selectively pressurizes the balloon throughout the crimping step is expected to provide three advantages while minimizing possible hyperextension of the balloon. The first advantage is increased scaffold balloon retention. By maintaining a relatively high pressure in the balloon throughout most of the crimp step, the balloon material is more likely to be placed on the scaffold than if the crimp were performed without balloon pressurization or only after the scaffold diameter has been substantially reduced. More balloon material should be placed between the struts of the scaffold as it will be forced into the fold more. Additionally, by substantially eliminating folds prior to diameter reduction, it is also expected that the balloon material will be more compliant. Thus, more balloon material can extend between the struts rather than being forced between the scaffold and the catheter shaft when the scaffold is crimped.

[0189] A second advantage of balloon pressurization is a more uniform expansion of the crimped scaffold as the balloon is expanded. If the balloon is initially inflated, and there is maximum space available for the balloon to expand within the attached scaffold before the crimping is done, the balloon material will be tighter around the catheter shaft after crimping. evenly distributed. In a preferred embodiment, the balloon is fully inflated and held in this inflated state for at least 10 seconds before crimping to ensure that all pre-existing creases are removed. If the balloon is only partially expanded and the creases If the line or balloon memory is not removed by balloon pressure, the presence of folds or partial folds will result in slippage or displacement of the balloon material during crimping, thereby reducing the distribution of balloon material around the catheter shaft after crimping. is expected to become more uneven.

[0190] A third advantage is the avoidance of out-of-plane twisting or overlap of the scaffold struts, which can result in strength loss, cracking, or failure of the struts. As discussed above, it is believed that by supporting the scaffold within the crimper with inflated balloons, the tendency of the struts to drift out of alignment is suppressed or minimized.

[0191] The aforementioned advantages may be achieved without the risk of overstretching the balloon material in a crimping process where balloon pressure is selectively controlled. Referring to FIG. 3B, the pressure range provided is 20-70 psi. The upper end of this pressure range forms a fully inflated balloon in the case of the balloon used in the example and can be maintained over the first three stages. Balloon pressure is then reduced to 50 psi and 20 psi in stage IV. Several tests have shown that a constant and consistent fully inflated balloon pressure is maintained until the beginning of stage IV, or after the crimped scaffold reaches approximately 1/2 of the original scaffold diameter, followed by a slight decrease in pressure. was found to provide a good balance of stent retention, uniform expansion, low cross-sectional profile, uniform crimp and avoidance of damage to the balloon material.

[0192] As mentioned above, there are three possible methods of crimp. Two balloons, Balloon A and Balloon B, are used. Balloon B is used for pre-crimp step (a) and balloon A (used with the introduction system) is used for the final crimp. Second, only one balloon is used for the entire crimp process, including alignment confirmation testing (Balloon A). In this case, the scaffold inner diameter is larger than fully inflated or overinflated balloon A. Therefore, misalignment can occur on the balloon before crimping. Third, only one balloon is used for the entire crimping process (Balloon A) without final alignment confirmation inspection. In this case, the balloon for the introduction system has a fully inflated or overinflated state approximately equal to the inner diameter of the scaffold inner diameter. These different embodiments are further described below.

[0193] In some embodiments, the process is described above by the example of FIGS. 17A-17B, with the following exceptions. Use two balloons. That is, instead of just Balloon A as in the above example of the preferred embodiment, a sacrificial or secondary balloon (Balloon B) is used in addition to the balloon of the catheter (Balloon A). Balloon B is a balloon that has a larger nominal inflation balloon diameter than Balloon A, or that can be overinflated to a larger diameter than Balloon A. Balloon B is used for Stage I and Stage II. Balloon B is selected to have a fully expanded diameter that is the same as or slightly larger than the original inner diameter of the scaffold. One advantage of this alternative embodiment is that (as opposed to the above example where balloon A could provide little or no radial support for the scaffold due to the gap at stage I), the scaffold is It is to be supported by a balloon through. After stage II, the scaffold is removed from the crimper and balloon B is replaced with balloon A. The crimping process then continues as described above.

[0194] The above description of illustrated embodiments of the invention, including what is described in the Abstract, is not intended to be exhaustive or to limit the invention to the form disclosed. isn't it. Although specific embodiments of the invention and examples thereof are described herein for purposes of illustration, those skilled in the art will appreciate that various modifications are possible within the scope of the invention.

[0195] These modifications can be made to the invention in light of the above detailed description. The terminology used in the claims should not be construed to limit the invention to the particular embodiments disclosed herein.

Claims (2)

A medical device, the medical device comprising:
A thin-walled scaffold having a network of rings interconnected by a plurality of links, each ring having alternating peaks and valleys , the peaks being at the U-top, Y-top or W-top. a thin-walled scan in which the valley is the U-top and each ring extends circumferentially in an undulating manner along a vertical axis (BB) perpendicular to the longitudinal axis (A-A). Fold and
a marker link extending between a first ring and a second ring of the network of a plurality of rings, the marker link including a structure having a hole in which a radiopaque material is received;
The marker link forms, together with the first ring, a W apex of the first ring, and together with the second ring, forms a Y apex of the second ring, and the W apex of the first ring. The distance is the dimension along the vertical axis from the top of the Y that is the valley in the first ring to the top of the next U that is the valley in the second ring. greater than a distance that is the dimension along said vertical axis to the top;
The length of the marker link is longer than the length of a link connecting the second ring to a third ring adjacent to the second ring,
The first ring includes a first peak, a second peak, and a third peak, the first peak corresponds to the top of the W of the first ring, and the second peak corresponds to the top of the W of the first ring. The third peak corresponds to the U top of the first ring, the second peak corresponds to the W top of the first ring, the second peak is next to the first peak, and the third peak corresponds to the W top of the first ring. is next to the second peak, and a second wavelength extending from the second peak to the third peak is shorter than a first wavelength extending from the first peak to the second peak. ,
the thin-walled scaffold is configured to have an outer diameter of D-min, where:
D-min=(1/π)×[(n×strut_width)+(m×link_width)]+2×t,
"n" is the number of struts in the ring,
"strut_width" is the width of the strut,
"m" is the number of links connecting adjacent rings,
"link_width" is the width of the link,
"t" is the wall thickness,
medical equipment. The structure includes a first hole and a second hole each housing the radiopaque material, the first hole and the second hole being parallel to the longitudinal axis (A-A). The medical device according to claim 1, which is arranged in a row.

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