WO2023075691A2 - Procédés de fabrication d'endoprothèses et endoprothèses associées - Google Patents

Procédés de fabrication d'endoprothèses et endoprothèses associées Download PDF

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Publication number
WO2023075691A2
WO2023075691A2 PCT/SG2022/050766 SG2022050766W WO2023075691A2 WO 2023075691 A2 WO2023075691 A2 WO 2023075691A2 SG 2022050766 W SG2022050766 W SG 2022050766W WO 2023075691 A2 WO2023075691 A2 WO 2023075691A2
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Prior art keywords
stent
printed
feature
overhang
powder
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PCT/SG2022/050766
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English (en)
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WO2023075691A3 (fr
Inventor
Sin Liang SOH
Ying Hsi Jerry FUH
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National University Of Singapore
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Publication of WO2023075691A3 publication Critical patent/WO2023075691A3/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F10/00—Additive manufacturing of workpieces or articles from metallic powder
    • B22F10/20—Direct sintering or melting
    • B22F10/28—Powder bed fusion, e.g. selective laser melting [SLM] or electron beam melting [EBM]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F10/00—Additive manufacturing of workpieces or articles from metallic powder
    • B22F10/40—Structures for supporting workpieces or articles during manufacture and removed afterwards
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/10—Sintering only
    • B22F3/11—Making porous workpieces or articles
    • B22F3/1103—Making porous workpieces or articles with particular physical characteristics
    • B22F3/1115—Making porous workpieces or articles with particular physical characteristics comprising complex forms, e.g. honeycombs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F5/00—Manufacture of workpieces or articles from metallic powder characterised by the special shape of the product
    • B22F5/10—Manufacture of workpieces or articles from metallic powder characterised by the special shape of the product of articles with cavities or holes, not otherwise provided for in the preceding subgroups
    • B22F5/106—Tube or ring forms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P10/00—Technologies related to metal processing
    • Y02P10/25—Process efficiency

Definitions

  • the present invention relates, in general terms, to stents.
  • the stents can have an open cell configuration or a curved profile.
  • the present invention also relates to methods of 3D printing stents.
  • Stents are small tube-like surgical devices used by surgeons to unblock or widen clogged arteries to restore regular blood flow for treatment of patients with vascular diseases.
  • stents are made of a biocompatible Stainless Steel or metal alloy.
  • ISR in-stent restenosis
  • DES drug eluting stents
  • BVS bioresorbable stent
  • stents are fabricated from Nitinol tubular stock and laser cut to the specific design which attribute to the cylindrical profile for most of the stents in the market.
  • AM additive manufacturing
  • additive manufacturing has the capability to deliver customized devices which may not be feasible and cost effective using conventional manufacturing methods. This is favorable for medical applications in which patient-specific implant design can be realized to ensure a better anatomically fit thus promotes faster healing.
  • AM enables accurate stent sizing and apposition have been shown to be important determinants of clinical outcome.
  • using AM to fabricate biomedical components is still challenging. For example, stable process for printing Nitinol has yet to be established. Additional consideration needs to be given to achieve Nitinol's inherent unique properties of shape memory effect and superelasticity, apart from the basic mechanical properties. Further, it is challenging to print overhang features, thus stents with closecell configuration is only achievable via 3D printing.
  • Another challenge to resolve when developing a patient-specific stent is the existence of free hanging or overhang features with the stent having the curvature that conforms to the vascular profile. Even if the stent is a closed-cell design, free hanging or overhang features will be present inevitably when the stent is no longer of a straight profile.
  • This method of removing support by post processing is particularly not ideal for stents with thin strut geometries, as the etching processes further weakens the stent structure.
  • the present invention is predicated on the understanding that additive manufacturing (AM) can be a more economical solution to fabricate a high cost stent than current laser cutting methods.
  • SLM selective laser melting
  • SLM also allows for an entire batch of stents (possibly 100 stents or more, depending on the size of the build platform) to be fabricated in a few hours altogether.
  • customized stents can be fabricated which is favourable for medical applications in which patientspecific implant design can be realised to ensure a better anatomical fit thus promoting faster healing.
  • the present invention provides a method of 3D printing a stent, the stent being 3D printed from a digital model sliced into at least two layers with at least one of the layer having at least one free hanging feature or overhang feature, the method comprising: a) performing selective laser melting on a metal powder to form a support; and b) subsequently performing selective laser melting on the metal powder in step a) to form the free hanging feature or overhang feature such that the support is positioned below the free hanging feature or overhang feature and is not fused with the stent.
  • the support is not directly in contact with the free hanging feature or overhang feature.
  • the support is separated from the free hanging feature or overhang feature by a gap.
  • the gap is about 0.1 mm to about 1 mm.
  • the gap is about 0.1 mm to about 0.5 mm.
  • the 3D printed stent is characterised by an open cell configuration having at least one free hanging and/or overhang feature.
  • the 3D printed stent is characterised by a curvature along its longitudinal dimension when in the expanded state.
  • the 3D printed stent is characterised by a curvature of about 1 ° to about 180 °.
  • the 3D printed stent is characterised by a radius of curvature of about 1 mm to about 200 cm.
  • the metal powder is Nitinol powder, stainless steel powder, cobalt chromium powder, platinum powder, gold powder, tantalum powder, molybdenum powder, magnesium powder, zinc powder or an alloy or combination thereof.
  • the metal powder is characterised by a particle size of about 10 pm to about 60 pm.
  • the selective laser melting is performed with hatch scanning, contour scanning, or a combination thereof.
  • the selective laser melting is characterised by a distance between adjacent laser track paths of about 0.05 mm to about 0.5 mm.
  • the selective laser melting is performed with a layer thickness of about 0.01 mm to about 1 mm.
  • the 3D printed stent has a wire diameter of less than 1 cm, preferably less than 0.5 mm.
  • the method further comprises a step of heat treating the 3D printed stent.
  • stents fabricated using laser cutting require a heat treatment process called shape setting to obtain a superelastic property.
  • shape setting to obtain a superelastic property.
  • heat treatment may be used to further fine-tune the mechanical properties of the 3D printed stents.
  • the heat treating step causes the distribution of nickel and titanium within the stent to be re-distributed. This lowers the M s temperature, thus allowing for a transition from a crimped state to an original un-crimped state at or near human body temperature.
  • the heat treating step comprises heating the 3D printed stent from about 200 °C to about 800 °C.
  • the method further comprises a step of electropolishing the 3D printed stent.
  • the 3D printed stent is characterised by wires of the 3D printed stent having a partially flat cross sectional shape.
  • the 3D printed stent is characterised by wires of the 3D printed stent having an elliptical, tear drop, partially flattened tear drop or circular cross section shape.
  • the present invention also provides a 3D printed stent printed by the method as disclosed herein.
  • the present invention also provides a 3D printed stent, comprising at least one overhang feature, wherein after 3D printing, the overhang is not fused with a support.
  • Figure 1 is a schematic diagram of examples of closed-cell and open-cell stents
  • Figure 2 is a schematic of a stent design with contactless supports for overhang structures
  • Figure 3 illustrates a printed stent having one end of supports connected to the stent and the other end not connected to the stent;
  • Figure 4a-b is a close-up illustration of the ends of the supports which are not connected to the stent of Figure 3;
  • Figure 5 illustrates a 3D printed stent fabricated with contactless support
  • Figure 6 illustrates a stent with a curvature
  • Figure 7 illustrates an overhang feature in a curved stent without contactless support
  • Figure 8 shows the overhang feature of Figure 7 with contactless support (in green);
  • Figure 9a-b are examples of curved stents according to embodiments of the present invention.
  • Figure 10 illustrates an exemplary selective laser melting process
  • Figure 11 illustrates cross-sections of a wire forming the stent
  • Figure 12 illustrates curved stents printed with and without contactless supports.
  • the stents of the present invention can be deployed in many areas within the human body.
  • the femoropopliteal/femoral artery (FPA) is a large artery located in the thigh provides majority of the arterial blood supply to the lower part of the extremity.
  • the FPA undergoes one of the most extensive mechanical deformation in the human body during limb flexion, with twisting, bending and compression.
  • the FPA experiences 2-4°/cm twist, 4-13% axial compression and has 22-72 mm bending radius during limb flexion. Measurements using intra-arterial markers showed even more severe deformation that were 2 to 7 times larger.
  • the average common FPA has a diameter of 6.6 mm (3.9 - 8.9 mm), whereas the superficial FPA and deep FPA have average vessel diameters of 5.2 mm (2.5 - 9.6 mm) and 4.9 mm (2.7 - 7.6 mm) respectively.
  • Current stents used in the FPA generally have diameters between 5 mm and 8 mm and are usually oversized compared to the diameter of the artery. Thus, being able to quickly and accurately fabricate stents with a range of diameters can be advantageous.
  • Additive manufacturing known 3D printing, is defined as "a process of joining materials to make objects from 3D model data, usually layer upon layer, as opposed to subtractive manufacturing methodologies" (ASTM international).
  • Powder bed fusion (PBF) method can be used to melt or fuse powders together in a layer-by-layer approach, and the printing process was named according to the energy types, i.e., E-beam melting (EBM), selective laser melting (SLM), direct metal laser sintering (DMLS) and selective laser sintering (SLS).
  • EBM E-beam melting
  • SLM selective laser melting
  • DMLS direct metal laser sintering
  • SLS selective laser sintering
  • SLM is a laser-powered powder bed fusion process that can produce highly dense metallic parts with delicate geometrical features.
  • Metallurgical bonding of originally loose powders can be achieved by laser melting followed by rapid solidification.
  • the inventors When using AM or SLM, the inventors have found that open-cell stents (in their as is form) are not feasible for 3D printing due to the large overhang surfaces when printing from any orientation. For example, when printing in orientation Y, there are excessive overhang areas which are not supported by the layer below, and which would result in a print failure. When printing in orientation X, there are excessive overhang areas as well, with the addition of curved cross sections in the horizontal plane that would affect the print quality. To this end, the inventors have found a method which allows for printing stents as is and without a subsequent step of removing connected support structures.
  • the present invention provides a method of 3D printing a stent, the stent being 3D printed from a digital model sliced into at least two layers with at least one of the layer having at least one free hanging feature or overhang feature, the method comprising: a) performing selective laser melting on a metal powder to form a support; and b) subsequently performing selective laser melting on the metal powder in step a) to form the free hanging feature or overhang feature such that the support is positioned below the free hanging feature or overhang feature and is not fused with the stent.
  • the printing parameters for the stent and the support can be the same. As such, there is no need to use a specific range of parameters or different sets of parameters for 3D printing. This streamlines the 3D printing process and parameters can be simply set for the different material used (for stents).
  • the method allows for the fabrication of open cell stents which have increased flexibility during navigation/tracking in the blood vessels, and increased conformity when deployed at the targeted location in the blood vessels.
  • the method also allows for customised stents to be printed, of which the design is not restricted by printing, machine or material constrains.
  • the formed stent is not flexible.
  • Post processing such as chemical and electrochemical processing is also required to achieve a more defined overhang features.
  • the presently disclosed method is cleaner (as it does not use ultrasonic cleaning, electropolishing, or chemical polishing to remove the support) and uses less raw material.
  • chemical etching may have an impact on the key mechanical properties, e.g. shape memory and superelastic properties of Nitinol, as well as a potential retention of residual etchant on the stent is not properly processed.
  • Figure 2 shows a CAD design of an open cell stent with supports.
  • the supports are positioned in a manner such that the support structures are right below the free hanging feature and/or overhang features without contacting the free hanging feature and/or overhang features.
  • the gap between the tip of the overhang feature and the top edge of the supporting structure is between 0.1 to 0.5 mm, depending on the size of the stents.
  • Figure 3 shows a 3D printed stent with supports connected at one lower end to the stent.
  • the other upper end of the support as shown generally in 401 and 403, are not fused to or are separated from the overhang features of the stent.
  • Figure 4a shows a close-up view of 401
  • Figure 4b shows a close-up view of 403.
  • the support was clearly observed to be not fused, or not connected, to the overhang features.
  • the overhang features were also observed to be properly formed, without loosing quality of print at these regions.
  • the support is spaced apart from the overhang features by at least about 0.01 mm to about 4 mm, or preferably about 0.1 mm to about 1 mm.
  • Figure 5 shows an exemplary 3D printed stent formed with contactless supports.
  • the stent has an open-cell configuration.
  • the supports are not fused (or separated) at both ends to the stent. In this way, when the 3D printing is complete, the stent can be removed from the metal powder bath without needing post-processing.
  • the stent and the support is printed simultaneously.
  • a main body of the stent is printed concurrently with the support in a layer.
  • the subsequently formed free hanging feature or overhang feature is formed in an overlying layer relative to an underlying layer which comprises the support.
  • the method comprises: a) performing selective laser melting on a metal powder to form a support in an underlying layer; and b) performing selective laser melting on the metal powder in step a) to form the free hanging feature or overhang feature in an overlying layer such that the support is positioned below the free hanging feature or overhang feature and is not fused with the stent.
  • the method comprises: a) performing selective laser melting on a metal powder to form a support in an underlying layer; and b) transiting to an overlying layer; and c) performing selective laser melting on the metal powder in step a) to form the free hanging feature or overhang feature in the overlying layer such that the support is positioned below the free hanging feature or overhang feature and is not fused with the stent.
  • the overlying layer is spaced 1 layer away from the support layer in step a). In other embodiments, the overlying layer is spaced 2 layers away, 3 layers away, 4 layers away, 5 layers away, 6 layers away, 7 layers away, 8 layers away, 9 layers away, or 10 layers away from the support layer.
  • the metal powder in the region between the support layer and overlying layer is unmelted, and hence the support is not fused with the stent.
  • the support and the 3D printed stent are printed as separate entities.
  • the support is not form part of the stent after 3D printing, but is formed as a distinct element on its own. When the stent is removed from the metal powder bath, the support can naturally fall off as it is not connected to the stent.
  • the support while not fused to the free hanging feature or overhang feature and hence the stent, is in contact with the stent.
  • the support is physically separated from the stent, but is touching the free hanging feature or overhang feature.
  • the support is not directly in contact with the free hanging feature or overhang feature of the stent. In some embodiments, the support is separated from the free hanging feature or overhang feature by a gap.
  • the gap can be filled with unmelted metal powder.
  • the gap can be formed, by not melting the metal powder in the region above and/or below the support, during successively printing layers. For example, the metal powder of 3 printing layers above and/or below the support can be un-melted. In other embodiments, at least 3, 4, 5 or 6 layers above and/or below the support is un-melted. In some embodiments, the gap is about 0.1 mm to about 1 mm.
  • the gap is about 0.1 mm to about 0.9 mm, about 0.1 mm to about 0.8 mm, about 0.1 mm to about 0.7 mm, or about 0.1 mm to about 0.6 mm. In some embodiments, the gap is about 0.1 mm to about 0.5 mm, or about 0.2 mm to about 0.5 mm.
  • the gap size can be dependency on the design of the stent.
  • the support has a diameter of less than 1 cm, preferably less than 0.5 mm.
  • the diameter can also be referred to as the support width or thickness.
  • the diameter is less than 0.9 cm, less than 0.8 cm, less than 0.7 cm, less than 0.6 cm, less than 0.5 cm, less than 0.4 cm, less than 0.3 cm, less than 0.2 cm, or less than 0.1 cm.
  • the diameter is about 0.01 mm to about 1 mm, about 0.01 mm to about 0.9 mm, about 0.01 mm to about 0.8 mm, about 0.01 mm to about 0.7 mm, about 0.01 mm to about 0.6 mm, or about 0.01 mm to about 0.5 mm.
  • Free hanging features refers to structures or features which are not attached or connected to a main body formed in the previous printed layer during the 3D printing process.
  • Overhang features in 3D printing are patterns in a 3D print model that extend outwards and past the previous layer. While overhang are partially supported by the previous underlying layers, overhangs lack direct support as they are at least partially extending away from the main body, which makes printing difficult.
  • the overhang feature can be characterised by an angle of the feature relative to a vertical print axis. At certain printing angle (less than 45 degrees), overhang features becomes more challenging to printed as the printed feature is less than 50% supported by the previous layer.
  • the overhang feature is characterised by an angle of less than about 45 °. In other embodiments, the angle is less than about 40 °, about 35 °, about 30 °, about 25 °, or about 20 °.
  • the overhang is spaced apart from an adjacent flex unit in the 3D printed stent by a gap of at least 150 pm.
  • the adjacent flex unit can be circumferentially arranged along a body of the stent such that it is parallel to the overhang.
  • the flex unit can comprise a wire having a wave like structure, for example a sinusoidal wave-like structure.
  • the flex unit can comprise peaks and valleys, from which the overhang (for example valley) is spaced apart by a gap of at least 150 pm (from an adjacent peak or valley).
  • the stent is characterised by an open cell configuration.
  • the open cell configuration has at least one free hanging and/or overhang features.
  • the method may be used for printing curved stents.
  • the contactless support is particularly useful for printing curved stents due to it curvature along its longitudinal dimension resulting in at least one free hanging or overhang feature when printing.
  • Curved stents can be used for the development of patient-specific stent.
  • a curved stent generally refers to a stent with a profile which is not straight.
  • curved stents include stents with a curved design, bifurcated design and/or open-cell design.
  • a curved stent may be specifically designed to suit the tortuous vascular anatomy of a patient to improve clinical outcome is not commercially available.
  • the stent is characterised by a curvature along its longitudinal dimension.
  • the stent can be printed in its expanded state.
  • the stent is characterised by at least one curvature along its longitudinal dimension.
  • the curved stent has at least one free hanging and/or overhang feature to be printed.
  • the stent can be printed in a manner in which a top section is offset from a previous bottom section.
  • the stent has a curvature between its terminal ends of about 1 ° to about 180 °, or about 1 ° to about 160 °.
  • the curvature refers to an angle between two convergent lines extending from an edge of the stent to an opposite edge of the stent.
  • the curvature can be measured between an edge to an inflexion point along the length of the stent or between two adjacent inflexion points.
  • the curvature is about 1 ° to about 150 °, about 1 ° to about 140 °, about 1 ° to about 130 °, about 1 ° to about 120 °, about 1 ° to about 110 °, about 1 ° to about 100 °, about 1 ° to about 90 °, about 1 ° to about 80 °, about 1 ° to about 70 °, about 1 ° to about 60 °, about 1 ° to about 50 °, about 1 ° to about 45 °, about 1 ° to about 40 °, about 1 ° to about 35 °, about 1 ° to about 30 °, about 1 ° to about 25 °, about 1 ° to about 20 °, about 1 ° to about 15 °, or about 1 ° to about 10 °.
  • the stent is characterised by a radius of curvature of about 1 mm to about 100 mm.
  • the radius of curvature is about 1 mm to about 90 mm, about 1 mm to about 80 mm, about 5 mm to about 80 mm, about 10 mm to about 80 mm, about 20 mm to about 80 mm, about 30 mm to about 80 mm, about 40 mm to about 80 mm, about 50 mm to about 80 mm, or about 60 mm to about 80 mm.
  • the stent is characterised by a radius of curvature of about 1 cm to about 200 cm.
  • the radius of curvature is about 1 cm to about 180 cm, about 1 cm to about 160 cm, about 1 cm to about 150 cm, about 1 cm to about 140 cm, about 1 cm to about 130 cm, about 1 cm to about 120 cm, about 1 cm to about 110 cm, about 1 cm to about 100 cm, about 1 cm to about 90 cm, about 1 cm to about 80 cm, about 1 cm to about 70 cm, about 1 cm to about 60 cm, about 1 cm to about 50 cm, about 1 cm to about 40 cm, about 1 cm to about 30 cm, about 1 cm to about 20 cm, or about 1 cm to about 10 cm.
  • radius of curvature means the radius of a circle that touches a curve at a given point and has the same tangent and curvature at that point.
  • the radius of curvature of a stent may refer to the radius of curvature of either side of the stent, or the radius of curvature of the longitudinal axis of the stent graft.
  • the curvature of the stent may be characterised by a curvature of a curved artery, as the stent (when customised to a patient) is likely intended for use in that artery.
  • the curvature may be more than about 45° when measured at end-diastole in an artery.
  • the curvature may be about 90° to about 180° when measured at end-diastole in an artery.
  • the curvature of the stent may be characterised by a tortuosity of an artery. Tortuosity is defined by the presence of >3 consecutive curvatures of 90° to 180° measured at end-diastole in an artery.
  • Severe tortuosity is defined as >2 consecutive curvatures of >180° in an artery.
  • Mild tortuosity is defined as either >3 consecutive curvatures of 45° to 90° in an artery, or >3 consecutive curvatures of 90° to 180° in an artery.
  • the stent can have a curvature at more than one location along its length.
  • Figure 9A shows an example of a curved stent with a single bend (900).
  • the stent 900 has an open cell structure.
  • First end 902 and second end 904 are not aligned along a longitudinal axis, but are displaced relative to each other along that axis to provide a curvature to the stent 900.
  • Figure 9B shows another example of a stent with a double bend.
  • the number of bends is not limited, and can be 3D printed accordingly based on the requirements of the vessel of a patient.
  • Figure 12 shows examples of curved stents printed with and without contactless supports. Stents printed without contactless supports (marked as 1, 2, 3 and 4 in Figure
  • the metal powder is Nitinol powder.
  • Nitinol is a metal alloy of nickel and titanium, where the two elements are present in roughly equal atomic percentages. Different alloys are named according to the weight percentage of Nickel, e.g. Nitinol 55 and Nitinol 60.
  • the nickel content can be from about 40% to about 65%, and the titanium content can be correspondingly be from about 35% to about 60%.
  • Nitinol is used as a powder.
  • the powder can have a particle size from about 10 pm to about 60 pm.
  • the powder shows phase transformation peaks, i.e., the martensite start (Ms) and austenite start (As) temperatures at -17.9 °C and -5.6 °C, respectively.
  • Nitinol alloys exhibit two closely related and unique properties: the shape memory effect and superelasticity (also called pseudoelasticity) at different temperatures.
  • Shape memory is the ability of nitinol to undergo deformation at one temperature (generally a lower temperature), stay in its deformed shape when the external force is removed, then recover its original, undeformed shape upon heating above its "transformation temperature”. This is due to the reversion of martensite to austenite by heating, causing the original austenitic structure to be restored or reversed regardless of whether the martensite phase was deformed.
  • shape memory refers to the fact that the shape of the high temperature austenite phase is "remembered” even though the alloy is severely deformed at a lower temperature.
  • Superelasticity is the ability for the metal to undergo large deformations and immediately return to its undeformed shape upon removal of the external load. Superelastic properties are generally observed when the temperature is above austenite temperature. Nitinol can deform 10-30 times as much as ordinary metals and return to its original shape. At high temperatures, nitinol assumes an interpenetrating simple cubic structure (austenite). At low temperatures, nitinol spontaneously transforms to a more complicated monoclinic crystal structure (martensite). There are four transition temperatures associated to the austenite-to-martensite and martensite-to-austenite transformations.
  • martensite begins to form as the alloy is cooled to the martensite start temperature (M s ), and the temperature at which the transformation is complete is the martensite finish temperature (Mr).
  • M s martensite start temperature
  • Mr martensite finish temperature
  • austenite starts to form at the austenite start temperature (A s ), and finishes at the austenite finish temperature (Ar). This is commonly shown in a cooling/heating cycle as a thermal hysteresis.
  • the hysteresis width depends on the precise nitinol composition and processing. Its typical value is a temperature range spanning about 20-50 K (20-50 °C).
  • the metal powder is stainless steel powder, cobalt powder, chromium powder, or a combination thereof.
  • Other materials such as platinum, gold, tantalum and molybdenum may also be used.
  • Biodegradable materials such as magnesium, zinc, and/or shape memory alloys may also be used.
  • the particle size is about 10 pm to about 50 pm, about 10 pm to about 40 pm, about 10 pm to about 30 pm, or about 10 pm to about 20 pm.
  • the same printing parameters can be used for printing the stent and the support. This can reduce the printing time.
  • different printing parameters can also be used. For example, a different laser power can be used when printing the support. When a weaker laser power is used to print the support, less metal powder material is used which can translate to greater cost savings.
  • volumetric energy density can be defined as:
  • E v energy density (J/mm 3 )
  • P the laser power (W)
  • v is the scan speed (mm/s)
  • h scan spacing or hatch distance or distance between adjacent laser track paths (mm)
  • t layer thickness (mm).
  • the laser power is of about 50 W to about 400 W. In other embodiments, the laser power is about 50 W to about 350 W, about 50 W to about 300 W, about 50 W to about 250 W, about 50 W to about 200 W, about 50 W to about 150 W, or about 50 W to about 100 W.
  • the scan speed is about 50 mm/s to about 2000 mm/s. In other embodiments, the scan speed is about 50 mm/s to about 1800 mm/s, about 50 mm/s to about 1600 mm/s, about 50 mm/s to about 1400 mm/s, about 50 mm/s to about 1200 mm/s, about 50 mm/s to about 1000 mm/s, about 50 mm/s to about 800 mm/s, about 50 mm/s to about 600 mm/s, about 50 mm/s to about 500 mm/s, about 50 mm/s to about 400 mm/s, about 50 mm/s to about 300 mm/s, about 50 mm/s to about 200 mm/s, or about 50 mm/s to about 100 mm/s.
  • Selective laser melting may be performed using a pulsed laser or a continuous wave laser.
  • the selective laser melting is performed with hatch scanning, contour scanning, or a combination thereof.
  • hatch scanning the track paths of the laser are closely drawn parallel lines.
  • contour scanning the track paths of the laser are closed contour lines that may conform to the cross-sectional shape of the stent wires.
  • the laser is characterised by a laser spot size of about 0.03 mm to about 20 mm.
  • the spot size is about 0.03 mm to about 18 mm, about 0.03 mm to about 16 mm, about 0.03 mm to about 14 mm, about 0.03 mm to about 12 mm, about 0.03 mm to about 10 mm, about 0.03 mm to about 8 mm, about 0.03 mm to about 6 mm, about 0.03 mm to about 5 mm, about 0.03 mm to about 4 mm, about 0.03 mm to about 2 mm, about 0.03 mm to about 1 mm, about 0.03 mm to about 0.8 mm, about 0.03 mm to about 0.6 mm, about 0.05 mm to about 0.4 mm, about 0.05 mm to about 0.2 mm, about 0.05 mm to about 0.1 mm, about 0.05 mm to about 0.08 mm, or about 0.05 mm to about 0.07 mm.
  • the distance between adjacent laser track paths is about 0.1 mm to about 0.5 mm. In other embodiments, the distance between adjacent laser track paths is about 0.1 mm to about 0.4 mm, or about 0.1 mm to about 0.3 mm. In some embodiments, the distance between adjacent laser track paths is about 0.1 mm.
  • the selective laser melting is performed with a layer thickness of about 0.01 mm to about 4 mm.
  • the layer thickness is about 0.01 mm to about 3 mm, about 0.01 mm to about 2 mm, about 0.01 mm to about 1 mm, about 0.01 mm to about 0.9 mm, about 0.01 mm to about 0.8 mm, about 0.01 mm to about 0.7 mm, about 0.01 mm to about 0.6 mm, about 0.01 mm to about 0.5 mm, about 0.01 mm to about 0.4 mm, about 0.01 mm to about 0.3 mm, about 0.01 mm to about 0.2 mm, about 0.01 mm to about 0.1 mm.
  • the selective laser melting is performed with a layer thickness of about 0.03 mm.
  • the 3D printed stent has a wire diameter of less than 1 cm, preferably less than 0.5 mm.
  • the wire diameter can also be referred to as the strut width or thickness.
  • the wire diameter is less than 0.9 cm, less than 0.8 cm, less than 0.7 cm, less than 0.6 cm, less than 0.5 cm, less than 0.4 cm, less than 0.3 cm, less than 0.2 cm, or less than 0.1 cm.
  • the wire diameter is about 0.01 mm to about 1 mm, about 0.01 mm to about 0.9 mm, about 0.01 mm to about 0.8 mm, about 0.01 mm to about 0.7 mm, about 0.01 mm to about 0.6 mm, or about 0.01 mm to about 0.5 mm.
  • the laser power can be varied from 50 W to 350 W.
  • the scanning speed can be varied from 50 mm/s to 1,500 mm/s.
  • the energy density can ranged from 11.1 J/mm 3 to 2,333.3 J/mm 3 .
  • the distance between adjacent laser track paths can be at 0.1 mm.
  • the layer thickness can be at 0.03 mm.
  • the oxygen level can be controlled below 100 ppm.
  • the 3D printed stent can have rough surfaces.
  • a post processing step can be added.
  • the method further comprises a step of heat treating the stent.
  • stents fabricated using laser cutting require a heat treatment process called shape setting to obtain its superelastic property.
  • shape setting to obtain its superelastic property.
  • heat treatment may be used to further fine-tune the mechanical properties of the 3D printed stents.
  • the heat treating step causes the distribution of nickel and titanium within the stent to be re-distributed. This lowers the M s temperature, thus allows for a transition from a crimped state to an original uncrimped state at or near human body temperature.
  • the heat treating step comprises heating the stent from about 200 °C to about 800 °C. In other embodiments, the heating is from about 200 °C to about 750 °C, about 200 °C to about 700 °C, about 200 °C to about 650 °C, about 200 °C to about 600 °C, about 250 °C to about 600 °C, about 300 °C to about 600 °C, about 350 °C to about 600 °C, about 400 °C to about 600 °C, or about 450 °C to about 600 °C.
  • the heating step may be performed for about 10 min, about 20 min, about 30 min, about 40 min, about 60 min, or for more than 60 min.
  • the heating step may be performed for about 10 min to about 120 min, about 10 min to about 100 min, about 10 min to about 80 min, about 10 min to about 60 min, about 15 min to about 60 min, about 15 min to about 50 min, about 15 min to about 40 min, or about 15 min to about 30 min.
  • the method further comprises a step of electropolishing the stent.
  • Electropolishing also known as electrochemical polishing or anodic polishing, is an electrochemical process that removes material from a metallic workpiece, reducing the surface roughness by levelling micro-peaks and valleys, improving the surface finish. It is used to polish, passivate, and deburr metal parts.
  • Strut/wire geometry can play an important role in determining blood recirculation zones and shear rates.
  • a streamlined geometry with smaller slopes of cross section morphology (less than about 90°) can be more favourable for endothelialization which decreases the rate of both restenosis and LST.
  • Conventional stents have wires with a rectangular cross section.
  • the inventors have found that the 3D printed stent can be further improved when the wires forming the stent have a partially curved cross sectional shape.
  • these cross sectional shapes for example arc, elliptical or aerofoil
  • these cross sectional shapes also reduce particles adherence to the structure (or less balling). This reduces the risk of tearing or rupturing of the blood vessel during insertion.
  • the 3D printed stent is characterised by wires of the 3D printed stent having a partially flat cross sectional shape. In other embodiments, the 3D printed stent is characterised by wires of the 3D printed stent having a partially curved cross sectional shape. It was found that a partially curved cross sectional morphology such as an arc provides for about a ten times reduction of surface area roughness compared to a circular cross section. The sharp edge of the partially curved cross-section (such as an arc-shape design) reduces the contact surfaces between the particles and the structure at the downskin section. With a reduction of contact surfaces between particles and structure, adherence of partially melted particles to the structure downskin will be weaker thus effort to remove the particles during post processing will be reduced.
  • partially curved geometry can also reduce particle bound to the stent structures (Figure 11).
  • arc, elliptical, tear drop or partially flattened tear drop (such as aerofoil) cross section shape can be used to further improve the surface finishing of the stent.
  • the 3D printed stent is characterised by wires of the 3D printed stent having an elliptical, tear drop, partially flattened tear drop or circular cross section shape.
  • the partially curved cross sectional shape is of an anisotropic shape, it can be characterised by a cross sectional thickness and a cross sectional width.
  • the cross sectional thickness is about 0.01 mm to 0.5 mm, about 0.01 mm to 0.4 mm, about 0.01 mm to 0.3 mm, about 0.01 mm to 0.2 mm, about 0.1 mm to 0.5 mm, or about 0.1 mm to 0.4 mm.
  • the cross sectional width is about 0.1 mm to 0.5 mm, about 0.1 mm to 0.4 mm, or about 0.2 mm to 0.4 mm.
  • the stent is printed in its expanded state, and can be crimped for insertion into a lumen.
  • the stent (especially when formed using Nitinol) has shape memory properties, it can revert back to its expanded state from the crimped state when at least exposed to a temperature above its A s temperature.
  • the stent is flexible due to its open cell configuration, and if 3D printed to be curved, can also conform to the native bends of the targeted lumen.
  • the stent (especially when formed using Nitinol) is superelastic and can revert back to its original expanded state after release of an external force and when exposed to a temperature of about 25 °C to about 50 °C.
  • AM approaches such as laser engineered net shaping (LENS) E-beam melting (EBM), direct metal laser sintering (DMLS) and selective laser sintering (SLS) can also be used.
  • LENS laser engineered net shaping
  • EBM E-beam melting
  • DMLS direct metal laser sintering
  • SLS selective laser sintering
  • the present invention also provides a 3D printed stent printed by the method as disclosed herein.
  • the present invention also provides a 3D printed stent, comprising at least one free hanging feature or overhang feature, wherein after 3D printing, the free hanging feature or overhang feature of the stent is not fused with a support.
  • the 3D printed stent is an open cell stent.
  • the 3D printed stent is a curved stent.
  • the curved stent can be subjected to a crimping process such that its size is reduced and it is straightened. Upon heating to at least body temperature, the crimped stent expands to its original diameter and curved profile.
  • the stent can have a diameter of about 4 mm to about 12 mm. In other embodiments, the diameter is about 5 mm to about 12 mm, about 6 mm to about 12 mm, about 7 mm to about 12 mm, about 8 mm to about 12 mm, or about 9 mm to about 12 mm.
  • the stent can have a length of about 7 mm to about 50 mm. In other embodiments, the length is about 7 mm to about 40 mm, about 7 mm to about 30 mm, or about 7 mm to about 20 mm. The length of stent can be extended depending on a patientspecific scale and requirement.
  • the stent can have a length to diameter aspect ratio of about 15: 1 to about 30:1.
  • the aspect ratio is about 16: 1 to about 30: 1, about 17: 1 to about 30: 1, about 18: 1 to about 30: 1, about 19: 1 to about 30: 1, about 20: 1 to about 30: 1, about 22: 1 to about 30: 1, about 24: 1 to about 30:1, about 26: 1 to about 30: 1, or about 28: 1 to about 30:1.
  • the stent can be fabricated from Nitinol.
  • the elemental composition of Nitinol stent can be within medical grade Nitinol, as defined by ASTM F2063.
  • the stent comprises an elemental composition of: a) nickel of about 54 wt% to about 57 wt% of the composition; and b) titanium of about 43 wt% to about 46 wt% of the composition.
  • the stent can be fabricated using a metal printer such as EOS M 290 3D printer, which has a fibre laser focus diameter of 100pm, estimated laser affected area of 150-200pm and estimated total affected area of 230-280pm, as well as a building volume of 250 x 250 x 535mm.
  • a metal printer such as EOS M 290 3D printer, which has a fibre laser focus diameter of 100pm, estimated laser affected area of 150-200pm and estimated total affected area of 230-280pm, as well as a building volume of 250 x 250 x 535mm.
  • the commercial Ni (55.4 wt%)-Ti powder (size rage 15 - 45 pm) was provided by Advanced Powders and Coating (GE Additive, Canada).
  • the laser power was varied from 50 W to 350 W. Meanwhile, the scanning speed was varied from 50 mm/s to 1,500 mm/s, contributed to an energy density ranged from 11.1 J/mm 3 to 2,333.3 J/mm 3 . Moreover, the default distance between adjacent laser track paths was at 0.1 mm, layer thickness was at 0.03 mm, and the oxygen level was controlled below 100 ppm.
  • the struts can have a diameter of 0.3 mm and height of 15 mm, reached an aspect ratio of 50: 1.
  • a thin layer powder is deposited onto the base substrate (referred to build platform in Figure 10).
  • the base substrate serves a support for the first layer.
  • Energy from the laser source melts the powder and as it cools, it solidifies.
  • the path of the laser is dependent on the cross-section of the structure in the vertical axis (normally the z- axis).
  • After one layer of thin powder (0.01 to 0.04 mm) is exposed to the laser another layer is deposited over the previous layer. The new layer is exposed to the laser energy. As this process repeats, a 3D object will be formed at the layer increases. As shown in figure 10, the solidified part is the fabricated object.
  • the above manufacturing process is applied to the fabrication of the thin stent structure, layer-by-layer to form the desired geometry.
  • the process requires building on the solidified part in the previous layer. Without a solidified base in the previous layer, energy directed onto the powder will 'collapsed', preventing the build to be completed successfully. As such, no free hanging or overhang features should be present for stent designed for additive manufacturing.
  • the 3D printed samples were mounted and ground by SiC 1200 grit sandpaper, and further polished with a grinding-polishing machine.
  • the polished samples were etched for 180 seconds with 'H2O (82.7%), HNO3 (14.1%), and HF (3.2%) solution'.
  • the samples were cleaned with ethanol and pure water, then dried with an air gun.

Abstract

La présente divulgation concerne un procédé d'impression 3D d'une endoprothèse à partir d'un modèle numérique tranché en au moins deux couches, au moins l'une des couches ayant au moins un élément en suspension libre ou un élément en saillie. Le procédé consiste à réaliser une fusion laser sélective sur une poudre métallique pour former un support, puis à réaliser ultérieurement une fusion laser sélective sur la poudre métallique pour former l'élément en suspension libre ou l'élément en saillie de façon à ce que le support soit positionné au-dessous de l'élément en suspension libre ou de l'élément en saillie et qu'il ne fusionne pas avec l'endoprothèse. La présente divulgation concerne également une endoprothèse fabriquée à l'aide du procédé.
PCT/SG2022/050766 2021-10-27 2022-10-26 Procédés de fabrication d'endoprothèses et endoprothèses associées WO2023075691A2 (fr)

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