Stentgraft and method for its production

Description

[0001] The present invention relates to a stent graft and a method for its production, wherein in particular a stent structure is applied to a graft by means of an additive process.

[0002] Vessels, especially blood vessels, can change over time due to numerous factors, including aging, diet, stress, and illness. Changes in the elasticity and stability of the vessel walls, which often affect the diameter of the vessels, as well as changes in the function of valves, which act as one-way valves, are particularly risky.

[0003] To reduce the risks posed by vascular changes, various options are available. Vascular implants are frequently used to bypass or replace the affected section of the vessel. For example, a locally narrowed vessel can be replaced by a bypass, or a pathologically dilated vessel can be bypassed or replaced by a stent graft.

[0004] Stent grafts are hollow cylinders with a longitudinal axis and feature a tubular graft and a usually metallic stent structure for stabilizing the graft. The stent structure and graft are typically manufactured in separate processes and then assembled in a relatively time-consuming and costly manner, sometimes through manual steps, such as suturing. Examples of such vascular implants are known from GB 2 347 861 A, US 2004 / 193258 A1, and US 5 911 753 A, and available products are already in routine use.

[0005] However, with regard to individual vascular geometry, patient-specific solutions are desirable in addition to clinically established standard products. These, however, are still associated with comparatively high manufacturing costs and time-consuming production steps.

[0006] A method for creating a vascular support based on a digital 3D model is known from DE 10 2015 207 596 A1. This involves applying a large number of layers, particularly using a (poly-jet) process. However, it seems questionable whether this method can meet the diverse clinical requirements of such a vascular support.

[0007] Furthermore, the production of a hybrid polymer stent is known from US patent 2015 / 0335451 A1. However, these stents have also apparently not become established in practice.

[0008] Further examples of stent grafts and their production are listed below, whereby, according to the state of the art, the stent structure can be produced using an additive process.

[0009] US 2007 / 061004 A1 provides a one-lumen supporting stent with a clear through-lumen for use in a body lumen. This stent is formed from at least one series of sliding and locking radial elements and at least one ratchet mechanism comprising a hinge element and multiple stops. The ratchet mechanism allows the radial elements to slide one-way from a compressed diameter to an expanded diameter, but prevents radial recoil from the expanded diameter.

[0010] US 2009 / 043330 A1 provides a pre-stent comprising a sheath and frame designed to prepare a vessel passage for subsequent stent delivery, wherein the pre-stent can be self-expanding or balloon-expandable. Furthermore, a support system is provided for the safe delivery of the pre-stent, comprising a delivery catheter, one or more occlusion balloons, optionally one or more dilation balloons, and a retention sheath for the self-expanding pre-stent type.

[0011] US 2017 / 333133 A1 provides a method for generating a patient-specific prosthesis, which includes receiving anatomical imaging data representative of a portion of a patient's anatomy. Furthermore, an initial digital representation of the anatomical imaging data is defined, modified, and based on this, a second digital representation of the patient's anatomy is defined. A patient-specific prosthesis template of the patient's anatomy is then generated, at least partially, based on the second digital representation of the anatomical imaging data.

[0012] US 2012 / 197382 A1 provides an endoluminal prosthesis comprising a graft with a tubular body having a proximal and a distal end, and a valve replacement positioned between the proximal and distal ends of the graft. At least one stent is connected to the graft and has a compressed delivery state and an expanded state to maintain patency within a portion of the graft.

[0013] US 2007 / 293936 A1 describes procedures for the production of individual endovascular stents and stent grafts.

[0014] Against this background, the present invention aims to provide an automatable, time- and cost-efficient method that simplifies the production of stent grafts, and in particular individualized stent grafts. The invention also aims to ensure that the produced stent grafts exhibit high biocompatibility and meet the requirements of clinical practice. These requirements include, among others, sufficient crimpability and / or foldability for endovascular insertion and / or sufficient radial stiffness in an expanded state.

[0015] According to the invention, this is achieved by a method and a stent graft according to the attached claims, wherein preferred embodiments are listed in the dependent claims.

[0016] The stent graft according to the invention comprises a graft and a stent structure, which is preferably applied directly to the graft by means of an additive manufacturing process. The stent structure is preferably polymer-based and / or made of a polymeric material.

[0017] The inventive method for producing the stent graft comprises providing a graft, preferably made of a first polymer-based material, and applying a stent structure with a plurality of struts made of a second polymer-based material to the graft by means of an additive process, preferably by means of fused deposition modeling. The graft and the applied stent structure are preferably designed such that the stent graft can be arranged in at least one compressed state and in at least one expanded state, wherein the stent graft has a smaller cross-section in the at least one compressed state than in the at least one expanded state.

[0018] Thus, according to the inventive method, the stent structure is not only produced using an additive process, as is already known from the prior art, but rather the stent structure is applied directly to the graft using an additive process, preferably fused deposition modeling. This allows the production of stent grafts, especially individualized ones, to be automated, time- and cost-efficient, and ensures that the respective stent graft produced, preferably metal-free, meets the requirements of clinical practice particularly well. In particular, methods known from the prior art for applying a stent structure to a graft, such as suturing, gluing, or welding, can be avoided.

[0019] In the context of the present invention, the term "stent graft" refers to an endovascular vascular implant or an endovascular vascular prosthesis comprising at least one stent structure and at least one graft attached thereto. The term "stent structure" here refers to a structure that preferably comprises a plurality of struts. The stent structure is preferably tubular and / or tube-shaped. The term "graft" refers to a structure that guides a medium within a vessel lumen. The graft is preferably associated with a stent structure, for example, in the form of a lining and / or sheathing of the stent structure. Such sheathing is preferably tubular and / or tube-shaped. The sheathing is preferably made of a polymer-based and / or polymeric material.

[0020] The term "stent graft" used here preferably refers to a stent structure with a graft attached to it and thus includes any type of endovascular vascular implant which at least temporarily has at least one preferably tubular structure with a plurality of struts and at least one preferably polymer-based material layer as a sheathing component.

[0021] In the context of the present invention, the term "vessel" refers to any type of tubular body structure, particularly of the human body, that transports at least one fluid, such as a gas and / or a liquid, including, but not limited to, hollow vessels such as blood vessels. The vessel may be located in various regions of the body, for example, in the extremities or the brain, but particularly in the abdomen and / or thorax. In the following, an "affected vessel" is defined as a vessel with a genetically determined and / or acquired vascular wall alteration. The term "affected area" refers to the locally confined region of the vascular wall alteration within the affected vessel and immediately adjacent areas.In the following, the term "intact" refers to the conditions, geometry, and / or properties that the vessel in the affected area would have, or has had, without any changes to the vessel wall, taking into account various factors such as age, sex, and / or body weight. This may also include, for example, the conditions, geometry, and / or properties of the vessel segments immediately adjacent to the area of ​​the vessel wall change. Furthermore, changes to a vessel wall are referred to as aneurysms, and various definitions of the term "aneurysm" are known to those skilled in the art. For example, changes to a vessel wall that lead to an increase in the diameter of the affected vessel, generally an increase of at least 50% compared to the diameter of an intact vessel in the respective area, can be described as an aneurysm.The absolute diameter of a vessel in the area of ​​the vessel wall change can also be used as an indicator of an aneurysm, for example, in the case of an abdominal aorta, 5 cm to 5.5 cm in men and 4.5 cm to 5 cm in women. Similar values, possibly with slight variations, can also be used as an indicator of an aneurysm in other vessels, such as thoracic or thoracoabdominal aortas. The increase in vessel diameter may also be less pronounced, particularly if the change progresses relatively rapidly. For example, an increase in vessel diameter of at least 5 mm within 6 months may indicate an increased risk of rupture or an aneurysm of the affected vessel.

[0022] The stent graft can be designed for the treatment of aneurysms. In particular, the stent grafts according to the invention can be stent grafts for the treatment of aortic aneurysms, such as for the treatment of aneurysms of the thoracic, thoracoabdominal or abdominal aorta.

[0023] According to the invention, the at least one stent structure is applied to the at least one material layer of the graft using an additive manufacturing process. Within the scope of the present invention, the term "additive manufacturing process" includes additive manufacturing processes known to those skilled in the art, or processes for additive or generative manufacturing, in which elements are automatically produced by adding and / or joining materials. Additive manufacturing processes include, for example, 3D printing processes and fused deposition modeling (FDM). In FDM, the preferably polymer-based material of the stent structure is liquefied, for example, by a heated nozzle and applied to the graft in the form of filaments in one or more layers, preferably directly and / or immediately onto the graft. The material can be fed to the nozzle as a filament.Alternatively, the material can be in granular form, which is melted using an extruder and fed into the nozzle.

[0024] The provided graft is preferably tubular and / or tube-shaped, and may be funnel-shaped and / or have diameter discontinuities and / or branches. Preferably, the graft is cylindrical. The stent structure is thus preferably applied to a cylindrical graft. However, the graft could also be provided as a layer of material, e.g., a flat layer. In this case, after the stent structure has been applied, the graft with the applied stent structure could be formed into a tubular shape, for example, by sewing, gluing, welding, or fusing.

[0025] The stent structure is preferably applied to the graft using a rotatable holder, which allows the graft to be held and rotated, preferably about its longitudinal axis. Such a holder can, for example, be a rotating tubular core and / or a rotating tubular scaffold, on the outer surface of which the provided graft rests. In this case, the at least one stent structure is preferably applied to the outside of the graft. If the applied stent structure is to be arranged inside the graft, the method according to the invention can include a further, optional step of inverting the stent graft. The graft of the stent graft according to the invention can therefore be designed to encase the stent structure from the inside or outside.

[0026] Furthermore, the stent graft according to the invention can have at least one stent structure that is arranged at least partially on the inside and outside of the graft. Optionally or alternatively, the stent graft according to the invention can have at least one stent structure arranged on an inside surface of the graft and at least one stent structure arranged on an outside surface of the graft. The respective stent structures can be arranged on a graft such that a respective region of the stent graft according to the invention, which has at least one stent structure on the inside of the graft, also has at least one stent structure on the outside of the graft. Alternatively, the respective stent structures can be arranged on the graft such that at least one region of the stent graft according to the invention, which has at least one stent structure on an inside surface of the graft, also has at least one stent structure on an outside surface of the graft.Alternatively, the respective stent structures can be arranged on the graft such that a region of the stent graft according to the invention, which has a stent structure on an inner surface of the graft, does not have a stent structure on an outer surface of the graft. The respective stent structures arranged on an inner and / or outer surface of the stent graft thus preferably do not overlap, or only partially overlap, in the longitudinal direction of the stent graft. Preferably, the stent graft according to the invention has at least one stent structure arranged on the inner surface of at least one region of a tubular end of the stent graft, and at least one stent structure arranged on the outer surface of at least one central region of the tubular stent graft.

[0027] According to the invention, such stent grafts can be produced, for example, by applying at least one first stent structure to a graft, preferably by using a rotatable holder as also described above. The method according to the invention preferably further comprises a step of inverting the graft with the at least first applied stent structure, followed by at least one further step of applying at least one further stent structure as described above, wherein the respective at least one stent structure can be arranged in one or more regions of the graft or can surround it over its entire length and / or circumference.

[0028] The graft is preferably polymer-based. In the context of the present invention, the term "polymer-based" includes both the expressions "comprising at least one polymer", "consisting of a proportion of at least one polymer", wherein the proportion is up to 50% or up to 70%, preferably up to 75% or up to 80% and particularly preferably up to 90% or up to 95%, as well as "made of at least one polymer" or "consisting of 100% of at least one polymer".

[0029] Alternatively or additionally, the graft is preferably a textile and / or textile-based. Techniques and materials known to those skilled in the art can be used to produce such a textile, wherein the provided graft is preferably made of biocompatible and / or hemocompatible materials, such as polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), polyvinylidene fluoride (PVDF), polyurethane (PU), polylactic acid (PLA), and / or polycaprolactone (PCL). Alternatively or additionally, the provided graft is preferably designed as a woven and / or knitted fabric. A woven fabric is preferably understood to be a woven fabric produced by the right-angled interlacing of at least two yarn systems, while a knitted fabric is a knitted or warp-knitted fabric comprising one or more interlocked threads. For example, monofilament and / or multifilament yarns can be used as threads for the production of the graft.With regard to the overall titer of the thread, the threads can, for example, have a fineness of 1 dtex to 200 dtex, preferably 10 dtex to 60 dtex, according to EN ISO 2060:1995, preferably according to the principle described in point 4, or for monofilaments, for example, according to EN 13392:2001. The graft can, for example, have a material layer thickness of 0.01 mm to 2 mm, preferably 0.1 mm to 0.5 mm, after its fabrication, preferably measured optically on the stent graft.

[0030] The provided graft preferably has a mesh fabric and / or is formed from such a mesh fabric.

[0031] This mesh fabric can be manufactured using a double raschel technique, preferably a Jacquard technique. This allows for particularly flexible adaptation of the graft to the individual patient's anatomy.

[0032] The provided graft preferably has a plurality of pores, for example, more than 100 or more than 1000 pores, formed by the spaces between the threads of the textile, in particular by the meshes between the thread(s), wherein the respective thread(s) may be formed by several filaments. The size and opening area of ​​the pores are therefore easily adjustable. Preferably, the graft has a mesh or pore size of 1 µm to 1000 µm, more preferably of 10 µm to 300 µm. The individual pores can therefore have an opening area of ​​1 to 1,000,000 µm², preferably of 100 to 90,000 µm².

[0033] The pores of the graft can be the same size and / or of different sizes, and may also vary in size along the stent graft in the direction of blood flow. This can, for example, help to secure the graft in the vessel by allowing tissue to grow into the pores.

[0034] The provided graft can be designed to be fluid-permeable. In this case, the graft preferably forms a self-sealing system, whereby the fluid transported in the vessel seals the graft after implantation of the stent graft, for example, by coagulation of components contained in the fluid within and / or on the graft. For this purpose, the pore sizes can be selected such that, upon implantation of the stent graft in a blood vessel, they can be sealed, for example, by the deposition of fibrin on the graft during blood coagulation. However, the provided graft can also be fluid-impermeable, for example, by coating the graft with collagen and / or gelatin. Such a coating can be applied to a graft before a stent structure is attached to it.In this case, the method according to the invention includes a step of coating the graft before applying a stent structure to the graft. Alternatively, a coating can be applied to a graft after a stent structure has been applied to it. In this case, the method according to the invention includes a step of coating the produced stent graft after the stent structure has been applied to the graft.

[0035] The stent structure can support the graft and is preferably compressible to position the stent graft in at least one compressed state, and / or expandable to position the stent graft in at least one expanded state. For this purpose, the stent structure can be elastically deformable and / or incorporate at least one smart polymer. Alternatively or additionally, the stent structure can be mechanically expandable, for example, via a balloon catheter.

[0036] The struts of the stent structure can be arranged in various configurations, preferably forming a compressible helical, zigzag, or mesh structure, and optionally and / or alternatively, meandering rings (crowns). To compress the stent structure, the opening angle between two struts connected at a joint and / or intersection point can preferably be reduced. Such compression of the stent structure can also be referred to as "crimping."

[0037] In the context of the present invention, the term "smart polymer" or "smart polymers" refers to polymers that are characterized by their sensitivity to at least one external factor, such as temperature, humidity, pH value, light intensity, electric fields, and / or magnetic fields, and that change at least one physical property, preferably reversibly and preferably rapidly, in response to at least one of these external factors. Preferred smart polymers include, for example, co-block polymers, which may also be used for drug delivery.

[0038] Preferably, the stent structure comprises at least one shape memory polymer. Shape memory polymers, as smart polymers, have the particular property of changing their shape in a predefined manner in response to at least one of the aforementioned external factors. Examples of preferred shape memory polymers are polyurethane (PU)-based polymers. Preferably, a shape memory polymer is used that springs back to a previously trained shape upon reaching a specific temperature, for example, above 30 °C, above 35 °C, above 37 °C, above 40 °C, or above 45 °C (for example, Yakacki et al., Biomaterials, 2007, 28:2255-63). The return to the trained shape is preferably achieved at a temperature below 55 °C, below 50 °C, below 45 °C, or below 40 °C.

[0039] The stent structure can additionally or alternatively comprise at least one non-smart, biocompatible polymer and / or at least one additive, in addition to or as an alternative to the at least one smart polymer. Within the scope of the present invention, additives are defined as substances known to those skilled in the art that modify the properties of the polymer used, for example, organic fillers, e.g., carbon fibers, or inorganic fillers, e.g., silicates. Within the scope of the present invention, non-smart, biocompatible polymers are defined as polymers known to those skilled in the art that are suitable for use as implants, in particular polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), polyetheretherketone (PEEK), and thermoplastic polyurethane (TPU).By selecting at least one polymer-based material for the stent structure, the compressibility and radial stiffness of the expanded stent graft can be adjusted. The polymer can also be chosen to ensure sufficient adhesion between the stent structure and the graft, depending on the selected additive manufacturing process and the graft material. Alternatively or additionally, the graft and / or the build chamber of the 3D printer can be temperature-controlled to improve adhesion between the stent structure and the graft. The set temperature can, for example, be in the range of the glass transition temperature of the printed polymer. A combination of polymers with different material properties is also possible. Such a combination can be achieved, for example, through compounding.Alternatively and / or additionally, polymers with different material properties can be combined using additive manufacturing, for example, by printing different layers, using multiple nozzles, and / or employing bicomponent nozzles. The material and / or the processing conditions (such as the temperature) can be selected such that the stent structure material flows at least partially into the pores of the graft and / or flows from one side of the graft to the other. Alternatively or additionally, the material and / or its processing conditions (such as the temperature) can be selected such that at least some graft fibers are embedded in the stent structure material and / or completely enclosed by the stent structure material over sections of the fiber length.

[0040] The design of the stent structure can be freely selected and individually customized using additive manufacturing, particularly in the case of fused deposition modeling. The filaments to be melted can, for example, have a diameter of 0.5 mm to 3.5 mm, preferably 1 mm to 3 mm, and particularly preferably 1.75 mm to 2.85 mm.

[0041] The stent structure preferably comprises a plurality of interconnected struts, wherein the struts have a height of at least 0.01 mm, preferably at least 0.05 mm or at least 0.1 mm, in a cross-section perpendicular to the radial direction of the respective strut of the stent graft. For example, the struts can have a height of 0.01 mm to 3 mm, preferably 0.05 mm to 1 mm. Alternatively or additionally, the struts can have a width of at least 0.01 mm, preferably at least 0.05 mm or 0.1 mm, in this cross-section perpendicular to the height. For example, the struts can have a width of 0.01 mm to 5 mm, preferably 0.01 mm to 3 mm, and particularly preferably 0.05 mm to 1 mm.

[0042] The struts can be constructed from multiple layers in a cross-section perpendicular to the direction of travel of the respective strut in the radial direction of the stent graft (vertical direction of the respective strut). The thickness of a single layer can be 0.005 mm to 1 mm, preferably 0.01 mm to 0.7 mm, and particularly preferably 0.02 mm to 0.4 mm. Alternatively or additionally, the struts can be constructed from multiple layers in a cross-section perpendicular to the direction of travel of the respective strut and perpendicular to the radial direction of the stent graft (lateral direction of the respective strut), e.g., from several adjacent extruded lines. The extrusion width of a single line can be 0.01 mm to 5 mm, preferably 0.05 mm to 2 mm, and particularly preferably 0.1 mm to 1 mm or 0.1 mm to 0.5 mm.Alternatively or additionally, the individual extruded lines can overlap in the width direction, for example by a maximum of 70%, preferably by a maximum of 50% and particularly preferably by a maximum of 30%.

[0043] The struts can be arranged in configurations known to those skilled in the art, for example, in zigzag and / or meandering rings (crowns), spirally, and / or in zigzag spirals. The spirals and / or rings can in turn be connected to one another via connectors. The struts can be designed such that, in the expanded state, they cover at most 50%, at most 40%, at most 30%, at most 20%, at most 12%, at most 10%, at most 8%, at most 6%, at most 5%, or at most 3% of the inner surface area of ​​the graft and / or at most 50%, at most 40%, at most 30%, at most 20%, at most 12%, at most 10%, at most 8%, at most 6%, at most 5%, or at most 3% of the outer surface area of ​​the graft.Furthermore, the struts can be designed so that, in the expanded state, they cover at least 12%, at least 10%, at least 8%, at least 5%, at least 3% or at least 1% of the inner surface area of ​​the graft and / or at least 12%, at least 10%, at least 8%, at least 5%, at least 3% or at least 1% of the outer surface area of ​​the graft.

[0044] In the preferred application of Fused Deposition Modeling, the stent structure can furthermore have a structure in which structural elements such as coils are formed without filament crossings. Furthermore, the stent structure preferably does not exhibit any subsequently induced, local changes in material properties, such as seams, weld zones, and / or adhesive residues.

[0045] The stent graft according to the invention is preferably designed to support, bridge, and / or replace the area affected by a change. The stent graft preferably possesses sufficient structural stability and elasticity to ensure the functionality of the vascular implant over a long period, for example, at least 1 year, at least 5 years, at least 10 years, or at least 15 years. The stent graft can be designed so that its diameter can vary with the intact vessel segments during the course of the heart rhythm. However, according to a preferred embodiment, the stent graft is designed so that its diameter does not vary significantly during the course of the heart rhythm. The stent graft is preferably metal-free. Both the graft and the stent structure can be biodegradable, and the graft and the stent structure can be biodegradable at the same or different rates.In a preferred embodiment of the stent graft according to the invention, however, the graft and stent structure are not biodegradable. Furthermore, the stent graft can also comprise several identical or different stent structures and / or grafts and / or include further components applied to the at least one stent structure and / or the at least one graft, such as one or more coatings. Such components can be biodegradable and / or comprise biocompatible materials and / or be coated with them. The stent graft can have one or more coatings, such as silicone, collagen, and / or gelatin.

[0046] The stent graft according to the invention can be inserted into the vessel in question in various ways, in particular endovascularly and / or minimally invasively. Upon insertion into the affected vessel, the stent graft can be in a compressed state, which preferably has a smaller cross-section than the affected vessel and, optionally, any other vessels to be passed through during the insertion of the stent graft. The at least one compressed state has a diameter of 1 to 20 mm, preferably 2 to 15 mm, and particularly preferably 4 to 10 mm. A smaller cross-section can be achieved, in particular, by reducing the cross-sectional area by more than 30%, preferably by more than 50%, and particularly preferably by more than 80% compared to the at least one expanded state.At the target site, the stent graft can be deployed and / or deployed, followed by a preferably reversible change of state into the expanded state, wherein the expanded state has a diameter approximately corresponding to the diameter of the intact vessel in the affected area. The at least one expanded state thus has a diameter of 0.5 cm to 6 cm, preferably 0.7 cm to 5 cm, and particularly preferably 1 cm to 4 cm. The at least one expanded state can have a diameter of at least 0.5 cm, at least 1 cm, at least 2 cm, or at least 3 cm.

[0047] Depending on the individual vessel geometry, for example, the stent graft can have a constant diameter along its longitudinal extent or a diameter that tapers in the direction of flow.

[0048] The transition of the stent graft from the compressed to the expanded state can be achieved by its release from a catheter system that limits its diameter and / or by balloon dilation. Alternatively or additionally, this transition can be triggered by an external factor, such as humidity, pH value, light intensity, electric fields, magnetic fields, and / or, in particular, by a sustained and / or at least brief change in temperature. Such a sustained and / or at least brief temperature change can, for example, be passively achieved by the difference between room temperature and the temperature prevailing in the vessel. Thus, the change from the at least one compressed state to the at least one expanded state is preferably triggered by a brief increase in temperature to values ​​between 30 °C and 60 °C, preferably between 33 °C and 50 °C, and most preferably between 35 °C and 40 °C.This can involve an increase in ambient temperature due to the body temperature itself. A change in temperature can also be actively induced, for example, by flushing a catheter system and / or the vessel with tempered saline solution, e.g., to prevent a premature change in temperature during the insertion and positioning of the stent graft.

[0049] The stent graft is preferably designed such that it rests against the vessel wall, particularly an intact section of the vessel wall, over a sufficient length and is thus securely positioned at the desired location. For this purpose, the stent graft can, for example, have a length of 1 cm to 35 cm, but preferably between 1 cm and 30 cm, and particularly preferably between 5 cm and 25 cm. The length of the stent graft can be at least 3 cm, at least 4 cm, or at least 5 cm. The length of the stent graft can be less than 30 cm, less than 20 cm, or less than 15 cm.

[0050] For secure positioning, contact surfaces for attachment to the intact vessel wall, known as landing zones, can be formed at the end regions of the at least two open ends of the hollow cylindrical shape of the stent graft, but at least at the end region of the end located upwards in the direction of flow. The respective contact surface preferably has a length of between 0.1 cm and 5 cm, more preferably between 0.5 cm and 2 cm. Optionally, the stent graft can also have hooks or other elements for anchoring and / or positioning the stent graft in the relevant area, for example, at the end located upwards in the direction of flow. This allows for particularly strong anchorage.

[0051] Routinely used stent grafts are generally standardized products. These typically require an intact and continuous vessel wall with a length of at least 10 to 15 mm for stable positioning in the immediate vicinity of the altered vessel wall. However, if the vessel wall alteration is located at or near a bifurcation, the use of such standard products may be precluded, as they would interrupt the blood supply to the branching vessel. Abdominal aortic aneurysms (AAA) or thoracic aortic aneurysms (TAA), as well as aneurysms that span both of the aforementioned areas (thoracoabdominal aortic aneurysms (TAAA)), frequently develop near such vessel bifurcations, such as the renal arteries. Therefore, in addition to the open ends of its tubular structure, the stent graft may be designed with further openings, which may also be expandable.

[0052] The provided graft can have one or more scallops and / or fenestrations to form these openings. The term scallop refers to a recess at one end of the preferably tubular and / or tube-shaped graft. Preferably, the term scallop refers to a three-sided, preferably square, or U-shaped recess at the end of the graft located upwards in the flow direction. A scallop has a recess height of 3 mm to 20 mm, preferably 5 mm to 15 mm, measured in the flow direction, and a width (preferably measured transversely to the flow direction or circumferentially) of 2 mm to 15 mm, preferably 7 mm to 12 mm. The term fenestration refers to so-called windows, open zones, or holes in the graft which, after correct positioning of the stent graft in the affected area, are approximately congruent in position and diameter with a respective branching vessel.The fenestrations are preferably oval or round, particularly preferably with a height-to-width ratio between 0.5 and 2.5, preferably between 0.8 and 2, and particularly preferably between 1 and 1.35. Furthermore, scallops and / or fenestrations can be customized to the individual patient.

[0053] The graft may, particularly in cases where the area of ​​vessel wall alteration communicates with another vessel and / or the distance between the area of ​​vessel wall alteration and a communication with another vessel is less than 10 mm, have one or more fenestrations and / or scallops. The number of fenestrations may be between 0 and 10, preferably between 1 and 5. The fenestrations preferably have a diameter between 1 mm and 15 mm, particularly preferably between 3 mm and 12 mm or between 4 mm and 8 mm. The diameter of the one or more fenestrations is preferably at least 2 mm, at least 4 mm, or at least 5 mm.

[0054] The stent structure is preferably positioned on the graft in such a way that the struts do not cross the fenestration(s) and / or scallops and / or impede blood flow through them.

[0055] Smaller fenestrations, for example with a diameter of 5 mm to 8 mm, can be provided between struts of the stent structure in the graft according to the invention. In this respect, a pattern, in particular a regular pattern (e.g., regular in the circumferential direction; e.g., a meander pattern with a specific amplitude and / or interval) of the stent structure in the area of ​​the respective fenestration can be regular and / or unchanged. For example, the amplitude and / or interval of the pattern of the stent structure in the area of ​​the fenestration can remain unchanged. Methods according to the invention can include a step of aligning the stent structure to be applied with the fenestration in the graft. This can in particular be a virtual alignment, which preferably takes place before the stent structure is manufactured, for example in a CAD (Computer-Aided Design) program and / or a CAM (Computer-Aided Manufacturing) program.

[0056] If necessary, fenestrations of struts can be crossed, for example, large fenestrations in the graft with a diameter of, say, 8 mm to 15 mm. Preferably, however, the stent structure—in particular the strut pattern—can be adapted so that crossing and / or impairment of the clear opening of the fenestration is avoided or at least largely avoided. The stent structure and / or the struts of the stent structure can be guided around the fenestration, for example, in the case of a zigzag or meandering strut pattern, by changing (in particular increasing) the amplitude and / or the interval of the pattern in the area of ​​the fenestration.

[0057] Alternatively or additionally, the arrangement of the struts can be designed such that the edges of the fenestration are supported by struts. For example, the struts can run circularly and / or ovally (e.g., ellipsoidally) at least partially (e.g., over an angle of > 90°, > 180° or > 270°) or completely around a respective fenestration.

[0058] Fenestrations and / or scallops can be provided, for example, by punching, perforating, cutting, laser cutting, widening, and / or using, for example, flame shears. Preferably, however, the provided graft has one or more fenestrations and / or scallops that were already provided during its manufacture (e.g., by weaving or knitting the graft accordingly). This avoids the need for subsequent local modification of the material properties and / or the cutting of one or more of the threads that form the graft. This is time-efficient, as no post-processing of the graft is required and no potential weak points are created in the graft. Therefore, the threads of the graft are preferably not cut in the area of ​​the fenestrations and / or scallops and / or run around these fenestrations and / or scallops.

[0059] The stent graft can optionally be branched at at least one end and / or at least one fenestration, with, for example, a stent structure and / or a graft segment projecting into a branching blood vessel (a "bifurcation" or "branch"). The branching segment can be at least 0.5 cm, at least 1 cm, or at least 3 cm long. This can help ensure a stable position for a fenestration and / or bridge, connect, and / or seal the area between the graft and the branching vessel. Alternatively and / or additionally, the stent graft can also be in contact with at least one other stent structure and / or another stent graft that is or will be positioned in another vessel connected to the affected vessel. In the case of such a modular design, the contact can be achieved, for example, by partial overlap.

[0060] The stent graft can be manufactured as a standardized or as a customized product. Particularly in the case of fenestrations and / or bifurcations in and / or near the affected area, it can be advantageous to manufacture the stent graft customized for the specific vessel, as the structure and location of the bifurcation can vary considerably. Preferably, the stent graft is customized based on imaging data of the affected vessel. Specifically, the structure and / or shape of the graft (e.g., the location, shape, and / or size of one or more fenestrations) and / or the structure, shape, and / or pattern of the stent structure (e.g., the course of the struts and / or their cross-section) can be customized and / or manufactured based on such imaging data.

[0061] Information regarding the location of the affected area in the body, the extent of the vessel segment to be supported or replaced, and any possible vessel branches located in or near the affected area can be obtained by medical imaging prior to graft production and / or stent structure application to the graft. This imaging can be performed using computed tomography (CT) and magnetic resonance imaging (MRI), but optionally also using X-ray or ultrasound devices, especially if they are suitable for acquiring a 3D image dataset. As a basis for the production of an individualized stent graft, the image data preferably have a layer thickness of no more than 3 mm, more preferably no more than 2 mm, and most preferably no more than 1 mm. The data are preferably acquired transversely to the flow direction at intervals of 0.05 mm to 10 mm, more preferably at intervals of 0.5 mm to 3 mm.Two successive layers can have an overlap of up to 50%, preferably up to 25%, with the distance between the layers being at most equal to the respective layer thickness. To ensure high-quality information regarding the exact design of the vessel wall, the acquired and / or obtained images are preferably post-processed in a manner known to those skilled in the art, for example by means of multiplanar reconstruction, to provide the highest possible spatial resolution in all directions before being used to produce an individualized stent graft.

[0062] The image data obtained and / or provided may have been created at one or more points in time and are used in a preferred method according to the invention to produce a computer-aided model of the graft, the stent structure and / or the stent graft in order to design an individualized stent graft.

[0063] The computer-aided model(s), in particular a digital 3D model, can include the dimensions, 3D structure, and / or material properties of the stent graft, as well as information regarding its manufacture, for example, which materials are to be processed in which area of ​​the stent graft and how. The model, as a digital representation, is preferably subdivided into cross-sectional layers using a computer system and / or CAD software. These layers are then used to create the vascular implant in an additive manufacturing process. Preferably, the method for producing a stent graft according to the invention and customized based on provided image data is fully automatable. The inventive method, in particular the direct application of the stent structure to the graft, enables optimal customization while significantly reducing production time.

[0064] According to the method of the invention, when defining the geometry of the graft (in particular when creating the computer-aided model of the graft), geometric data of the vessel can be used and, in particular, fed into a computer program. Alternatively or additionally, when defining the geometry of the stent structure (in particular when creating the computer-aided model of the stent structure), geometric data of the vessel and / or geometric data of the graft can be used and, in particular, fed into a computer program. The method can, for example, include a step in which geometric data of the graft and geometric data of the stent structure (e.g., the two computer-aided models) are combined in one program. This can, for example, allow the superimposition of the two computer-aided models, e.g., in a common computer-aided model and / or a common view.

[0065] Preferred embodiments of the invention are described below by way of example with reference to the drawings. These are merely schematic representations, which often omit other (optional) structures to clarify certain aspects or may include various optional, related aspects in a single representation. In this context, identical reference numerals indicate equivalent, similar, comparable, or identical components in the illustrated embodiments.

[0066] The embodiments shown can be modified in many ways within the scope of the claims. The disclosure of the figures is not intended to limit the scope of the invention. It should be noted that the features of the aforementioned embodiments can be combined in a single embodiment. Embodiments of the invention can therefore, depending on the configuration, have all or only some of the aforementioned features. The figures show: Fig. 1 a schematic flowchart of a method according to the invention; Fig. 2 a schematic representation of the application of the stent structure to a graft according to the invention; Fig. 3 a schematic representation of the stent graft according to the invention in a compressed and an expanded state.

[0067] Figure 1 shows in a schematic flowchart the steps of a method according to the invention 100 for the production of a stent graft 1(see also Figure 2 ), where dashed lines indicate optional steps. In a preferred embodiment of the method, pre-operative medical image data of a vessel are first provided (step 1). 110), which were obtained, for example, during computed tomography and / or magnetic resonance imaging. The image data can be processed in a manner known to those skilled in the art to obtain the highest possible 3D resolution and to create a computer-aided model of the graft. 10, the stent structure 20 and / or the stent graft 1 be used (step 120). The production of the stent graft according to the invention and preferably individualized 1 This is done by providing (step 130) a graft, preferably polymer-based 10, on which a stent structure 20applied with a plurality of struts made of a preferably polymer-based material (step 140). This is preferably done using Fused Deposition Modelling as an additive manufacturing process.

[0068] The stent graft 1 according to the invention can be applied in step 1 after the stent structure has been applied. 140, can optionally be turned inside out (step 150), for example, the stent structure 20 within the graft 10 to order.

[0069] Figure 2 The figure schematically shows, in perspective view, the production of the preferably tubular and / or tube-shaped, in particular hollow cylindrical, stent graft. 1, which preferably starts from a first open end 11 to an opposite, second open end 12 extends. The graft, preferably textile-based or consisting of textiles, 10can be slid onto a holder (not shown) and / or rest on it. The holder can be rotatably mounted, for example so that the graft 10 around its longitudinal axis A It is rotatable. The geometry of the holder can be adapted to the geometry of the graft. 10 The outer diameter of a cylindrical holder can be selected according to the diameter of the vessel to be treated.

[0070] The tubular graft shown here as an example 10 has two fenestrations 14 on, which is present in the area of ​​the second end 12 shown. However, these can also be found at other points along the longitudinal axis of the graft. A The graft could be positioned (e.g., in the center). Additionally and / or alternatively, the graft could be... 10 in addition, at least one scallop, further fenestrations, and / or branches, so-called side arm stents ("branches"), along the longitudinal axis Aexhibit. Furthermore, the graft can 10 Additionally and / or alternatively, further openings at the ends 11, 12 exhibit or he could at one of these ends 11, 12 to be branched ("Bifurcation"; not shown).

[0071] The stent structure 20 preferably applied directly to the graft 10 applied by applying a designated polymer-based or polymeric material in a heated nozzle head 70 is heated and one or more liquefied filaments are applied in one or more layers to the graft. 10 be applied 140. This can be achieved, for example, in an automated process following a step-by-step procedure. 120 generated computer-aided model of the stent graft 1 be realized while the nozzle head 70 essentially along the longitudinal direction of the graft 10 moved (see arrow) 71)and the holder rotates as needed. Alternatively, the holder can be moved primarily in the longitudinal direction, or the holder and nozzle head can be moved together. 70. The resulting multiple interconnected struts of the stent structure 20 It can optionally be arranged as rings, zigzags, helixes, spirals, meshes and / or other geometries, whereby, for example, individual segments of the stent structure can be connected directly or indirectly via connectors.

[0072] The stent graft 10 can be inserted into a container in the usual way. Figure 3 This figure shows a schematic overview of the various states that the stent graft can have at a minimum, whereby the change of state is preferably reversible and rapid due to the material and / or material combination of the stent structure. During its fabrication, the stent graft can initially have a first state. ( Fig. 3A ).The stent graft can be manufactured in an expanded state. After its manufacture, but at the latest before its preferably endovascular and / or minimally invasive insertion into the affected vessel, the stent graft is in a compressed, crimped state. ( Fig. 3B ). Depending on the stent geometry, this can be achieved, for example, by reducing the opening angle between two struts connected at a junction and / or intersection point. After the stent graft has been positioned in the affected vessel segment, it is expanded, in which it has a larger diameter than in its crimped state. ( Fig. 3C ),The expanded state can optionally correspond to the first state. This change of state can be brought about by mechanical force or in a predefined manner by changing an external factor if a suitable smart polymer was used to form the stent structure (for example, by springing back into an expanded form upon increasing temperature). In this case, the expanded state is preferably reached by attaining body temperature, i.e., a temperature of 37°C.

[0073] In its expanded state, the stent structure preferably exhibits a radial stiffness sufficient to bridge or replace the affected vessel segment. The graft is preferably designed as a self-sealing system that is initially fluid-permeable and, after implantation of the stent graft, seals itself within a short time through coagulation of components contained in the fluid transported in the vessel and / or their deposition in and / or on the graft.

[0074] Where the preceding description uses the expression "essentially" or similar terms, it also includes embodiments in which the respective feature is fully or completely present. The words "multiple" or "several" are to be understood as "at least two," i.e., two or more. Where specific values ​​are given, these preferably also include minor deviations from these values, such as deviations of + / - 10% or + / - 5% of the respective value.

Claims

1. A method (100) for producing a stent graft (1), which comprises the following steps: providing (130) a graft (10) made of a first polymer-based material; and applying (140) a stent structure (20) comprising a plurality of struts made of a second polymer-based material onto the graft (10) by means of an additive method, preferably by means of fused deposition modeling; wherein the graft (10) and the applied stent structure (20) are configured such that the stent graft (1) is arrangeable in at least one compressed state and in at least one expanded state, wherein the stent graft (1) has a smaller cross-section in the at least one compressed state than in the at least one expanded state.

2. The method (100) according to claim 1, wherein the graft (10) is tubular and / or tube-shaped and wherein the graft (10) optionally comprises diameter changes, bifurcations and / or branches.

3. The method (100) according to claim 1 or 2, wherein the produced stent graft (1) is configured such that the graft (10) is arranged within the stent structure (20).

4. The method (100) according to any one of the preceding claims, wherein the graft (10) is textile and / or textile-based, in particular a weave and / or knitwear; and / or wherein the graft (10) is produced by means of a jacquard technique; and / or wherein the graft (10) has a material layer thickness of 0.01 mm to 2 mm after its production.

5. The method (100) according to any one of the preceding claims, wherein the stent structure (20) comprises a smart polymer, in particular a shape memory polymer, and / or a non-smart, biocompatible polymer; and / or wherein the stent graft (1) is metal-free.

6. The method (100) according to any one of the preceding claims, wherein the provided graft (10) comprises fenestrations (14), wherein the fenestrations (14) preferably have a diameter between 1 mm and 15 mm, more preferably between 3 mm and 12 mm, particularly preferably between 4 mm and 8 mm.

7. The method (100) according to any one of the preceding claims, wherein the provided graft (10) comprises a plurality of pores formed by the mesh structure and having a diameter of 1 to 1,000 µm, and / or wherein individual pores have an opening area of 1 to 1,000,000 µm2.

8. The method (100) according to any one of the preceding claims, wherein the struts, in a cross-section perpendicular to the direction in which the respective strut extends, have a height of at least 10 µm in the radial direction of the stent graft (1) and / or a width perpendicular to the height of at least 10 µm, preferably at least 50 µm, in the cross-section; and / or wherein the struts, in a cross-section perpendicular to the direction in which the respective strut extends, in the radial direction of the stent graft (1), are made from a plurality of layers; and / or wherein the struts, in a cross-section perpendicular to the direction in which the respective strut extends, perpendicular to the radial direction of the stent graft (1), comprise a plurality of layers.

9. The method (100) according to any one of the preceding claims, which further comprises the steps of: obtaining (110) preoperative medical image data of a vessel; and generating (120) a computer-aided model of the graft (10), the stent structure (20) and / or the stent graft (1) by means of the image data.

10. The method (100) according to any one of the preceding claims, wherein the stent structure (20) is applied onto the graft (10) by using a rotatable holder by means of which the graft (10) can be held and rotated.

11. The method (100) according to any one of the preceding claims, wherein the struts configure a compressible helical, zigzag or mesh structure and / or meander-shaped rings.

12. The method (100) according to any one of the preceding claims, wherein the graft (10) comprises one or more scallops and / or fenestrations.

13. The method (100) according to any one of the preceding claims, wherein the provided graft (10) is configured to be permeable to liquid and wherein the graft (10) preferably forms a self-sealing system; or wherein the provided graft (10) is impermeable to liquid, preferably wherein the provided graft (10) is impermeable to liquid by means of a coating, wherein the method (100) comprises a step of coating the graft (10) before the application of a stent structure (20) onto the graft (10), or wherein the provided graft (10) is impermeable to liquid by means of a coating, wherein, after the application of a stent structure (20) onto the graft (10), the method (100) comprises a step of coating the produced stent graft (1).

14. The method (100) according to any one of the preceding claims, wherein the stent graft (1) comprises at least one stent structure (20) that is arranged on the graft (10) at least partially inside and outside, and / or wherein the stent graft (1) comprises at least one stent structure (20) that is arranged on an inner side of the graft (10) and at least one stent structure (20) that is arranged on an outer side of the graft (10).

15. A stent graft (1) produced according to the method (100) according to any one of the preceding claims, preferably wherein the stent structure (20) surrounds the graft (10).