Devices, systems and methods for the treatment of blood vessels

Abstract

The invention relates to a device (1) for the treatment of a blood vessel (V) of a patient, comprising a filling element (5, 7, 10, 13, 14, 15, 29), a magnetic element (4), a control line (2) and a release mechanism (3). The release mechanism (3) is configured to release the magnetic element (4) and / or the filling element (5, 7, 10, 13, 14, 15, 29) so as to be separated from the control line (2). The magnetic element (4) is configured to be guided by an external actuator (M) to guide at least the filling element (5, 7, 10, 13, 14, 15, 29) along a blood vessel path (V). The filling element (5, 7, 10, 13, 14, 15, 29), when placed in the blood vessel (V) to be treated, is configured to reduce the volume of this blood vessel portion (V). The control line (2) is configured to position the device by being loosened or pulled.

Description

[Technical field]

[0001] The present invention relates to a device, a system and a method for the treatment of blood vessels, which are according to the preambles of the independent claims. [Background technology]

[0002] It is known to use thrombogenic elements to fill aneurysms. For example, U.S. Pat. No. 6,315,709 discloses an apparatus and method for treating vascular injuries by filling the injury, including an aneurysm, with a magnetically controlled device.

[0003] US Pat. No. 6,530,934 discloses an embolic device consisting of a linear array of small flexibly interconnected beads for filling aneurysms.

[0004] However, the devices known in the prior art have several drawbacks, such as being unable to be easily guided in the human body to reach the site to be treated, such as an aneurysm, etc. In addition, the known devices have a rather complicated structure, which poses difficulties in terms of economy and reliability.

[0005] Navigating an aneurysm can be difficult, especially in tortuous arteries, which are common in older patients, potentially increasing treatment times and the risk of arterial injury.

[0006] Additionally, some aneurysms may exhibit complex shapes, making it difficult to achieve sufficient occlusion of the aneurysm while avoiding occlusion of the blood vessel. Summary of the Invention [Problem to be solved by the invention]

[0007] It is therefore an object of the present invention to overcome the shortcomings of the prior art and in particular to provide a device for the treatment of a patient which is reliable, can be easily navigated within the human body, is unlikely to cause tissue damage and generally provides safer treatments and outcomes. [Means for solving the problem]

[0008] This and other objects are achieved by an apparatus and a method according to the features of the independent claims of the present invention.

[0009] A device in the context of the present disclosure may be a particle or composition that provides a function, preferably a controllable function, within the patient's body, however, it is also contemplated that the device may comprise additional features, such as electronics, motors, sensors, actors, etc., to provide more complex functions.

[0010] The device according to the invention is configured for the treatment of a patient's blood vessel. In particular cavities such as aneurysms, such as cerebrovascular or aortic aneurysms, can be treated. The device comprises a filling element, a magnetic element, a control line and a release mechanism. The filling element is preferably an expanding element and / or a thrombus forming element. Preferably, the expanding element is hydrogel based and / or comprises a foam. The release mechanism is configured to release the magnetic element and / or the filling element such that at least the filling element can be separated from the control line. Preferably, upon release, the magnetic element also separates from the control line. Additionally or alternatively, the filling element may be detachable from the control line and / or the magnetic element by the release mechanism. As a result, it may be possible to remove the magnetic element together with the control line, while the filling element remains at the treatment site. The magnetic element is configured to be guided by an external actuator. Guiding the magnetic element allows at least the filling element to be guided along a vascular path. Preferably, the magnetic element and the other parts of the device are also guided along the same path.

[0011] The filling element is configured to reduce the volume of a vascular location where the filling element is placed for treatment, either by occupying the volume or by forming a clot. Preferably, the filling element is activatable, and the reduction in volume occurs after activation. Optionally, the device can include an activation mechanism configured to activate the filling element.

[0012] Preferably, the device is in an inactive state during movement and is activatable at the treatment site, for example by stimulation, which in this context may be, for example, electrical and / or thermal.

[0013] In some embodiments of the device, the protective shell may be removable. Additionally, in some aspects of the invention, the device may be configured to move autonomously, allowing the operator to avoid having to repeatedly push and pull the delivery device to reach the aneurysm, thereby reducing the risk of damage to the tissue wall.

[0014] Accurate delivery is difficult and requires time and extremely well-trained physicians. One of the solutions introduced in this application provides a solution for the gradual and automatic delivery of the filling element.

[0015] The device can be positioned by loosening or pulling the control lines. Additionally or alternatively, the speed of the device may be controllable by the control lines, in particular to release parts of the device (e.g., the filler element and / or the magnetic element) at a particular speed.

[0016] Guidance may include steering (i.e., changing the direction of motion) and / or changing the speed of the object, in particular slowing down, stopping, and / or accelerating. Additionally, guidance may include keeping the position and / or speed constant. Additionally, guidance may include rotating the device.

[0017] Thus, in a preferred embodiment, the device is configured to be carried by the blood flow after insertion into the blood vessel. Magnetic force can be used to guide the device to move along the bifurcation in the blood vessel, while the control line can be used to slow down or stop the device as needed (e.g., before the bifurcation or at the target location for treatment). In addition, while the blood flow may be sufficient in some cases to carry the device to the general location of the aneurysm, magnetic force may be necessary to move the device into the aneurysm. Thus, once located at the treatment site, such as an aneurysm, the device can be moved into the aneurysm. The filling element can be activated by an activation mechanism, e.g., to expand to fill the aneurysm and / or cause the formation of a thrombus, or can be activated passively (e.g., dissolution of a layer in the blood and / or over time). A release mechanism can be used to detach at least a portion of the device from the control line. Release occurs after the device is placed in the aneurysm. However, release may occur at any later time, e.g., before or after activation of the filling element.

[0018] The cables and / or control lines may include wires, monofilament wires, multifilament wires, coiled wires, and / or ribbons. The diameter of the cables may be between 10 and 500 μm, preferably between 20 μm and 70 μm. The cables may comprise or consist of polymers such as nylon, metals such as stainless steel, or hybrid materials made of polymers and metals.

[0019] The control line may have an outer diameter in the range of 10 μm to 1000 μm, preferably 50 μm to 500 μm, preferably 80 μm to 500 μm, particularly preferably 100 to 350 μm, and even more preferably about 200 μm. These values ​​allow for high flexibility, for example to conform to curved areas in a blood vessel, while still providing sufficient mechanical strength for typical control line materials.

[0020] The control line may comprise a string. The string may be formed of monofilaments or multifilaments. Additionally or alternatively, the control line may have a core-shell structure. For example, a monofilament may represent the core of the control line, while a multifilament may be disposed radially outside the monofilament along the longitudinal axis of the monofilament to form the shell. The core may include or be composed of a different material than the shell, and / or may provide a different function. For example, the core may include a nylon filament, while the shell comprises an electrical wire to conduct electricity.

[0021] For example, the control lines may comprise or be constructed of any type of nylon, particularly multifilament nylon.

[0022] The control line may comprise a hollow tube. The hollow tube may allow for the passage of a fluid, such as a gas or liquid, or a wire. The inner wall of the hollow tube may be coated to minimize friction with other elements. For example, a coating made of PTFE may be used.

[0023] To increase the stability of the hollow tube, particularly to withstand internal pressure due to the passage of a fluid, the hollow tube can be reinforced. For example, wires can be placed within, on the interior and / or exterior surfaces of the walls of the hollow tube.

[0024] The control line may comprise wires for conducting electricity and / or heat to each portion of the medical device. Additionally, the control line may comprise two or more wires connected to different portions of the device. The wires may be embedded in the control line. For example, the control line may comprise a core of a multifilament string and the shell may comprise one or more wires. It will be appreciated that a wire may be threaded through the control line at any point during treatment, especially when the control line comprises a hollow tube as described above. The wire may be an electrical wire.

[0025] Additionally or alternatively, the control line may comprise two or more wires arranged substantially along the longitudinal axis of the control line, preferably parallel to one another.

[0026] For example, the control line may comprise a monofilament. The two wires may run substantially along the control line and may be connected to another part of the device, such as a release mechanism. If a multifilament is used, all filaments may be composed of the same material, or filaments made of different materials may be used. In particular, the control line may comprise a structure such as a braided structure and / or a twisted structure.

[0027] It is also contemplated that the control line may have a first portion with different properties compared to a second portion located at a distance from the first portion along the longitudinal axis of the control line. For example, the control line may have a first portion comprising or consisting of a monofilament, located at a more distal position than the second portion. The second portion may comprise or be composed of multifilament nylon. This may provide both flexibility for movement in a tortuous network and high stiffness for removal of the control line. For example, a 2m long control line may have a 0.3m long distal portion made of multifilament, while the remainder of the line is made of monofilament.

[0028] The control line can comprise or be composed of a mixture of materials. Furthermore, there can be a gradient of at least two materials, for example along the longitudinal axis of the control line. For example, a first portion can comprise a first polymer, while a second portion comprises a second polymer. The first and second polymers can be connected via a gradient blend of the first and second polymers.

[0029] The device may in particular not comprise any other elements extending therethrough, such as cables, etc. If the medical device comprises exactly one control line, and this control line is selectively detached from the device, the device floats freely in its environment.

[0030] Preferably, the control line cannot transmit data or energy. It may be made of a non-conductive material or may not be able to conduct electricity along its length, for example due to its structure (such as a sandwich structure with an insulator). The control line may be made of metal, but the connection to the medical device may be unsuitable for the transmission of electricity, for example because the connection is made of or coated with an insulating material. Therefore, in addition or alternatively, the device may not be able to receive data or energy via the control line.

[0031] Preferably, the medical device further comprises a trigger wire. Particularly preferably, the trigger wire is associated with the control line and may be arranged parallel to the longitudinal direction of the control line. For example, it may be arranged inside the control line, in particular inside a hollow tube which is part of the control line, or it may be arranged next to the control line as a separate element, but preferably associated with the control line. The trigger wire is configured to trigger a function of the device.

[0032] The trigger wire can, inter alia, transmit a mechanical or electrical signal to trigger, inter alia, the functions of releasing a drug, activating a filling element, and / or selectively detaching a medical device from the control wire.

[0033] The trigger wire can have a diameter between 10 μm and 150 μm, preferably between 20 μm and 70 μm. The trigger wire can have a cylindrical or strip shape. The trigger wire can be made of a polymer, such as PET, or a metal, such as Nitinol or stainless steel. In some embodiments, the trigger wire can transmit a mechanical force to a portion of the device, in particular a magnetic or filler element, for example to retract a protective coating, for example by breaking and then retracting as a result of the force caused by the trigger wire.

[0034] In certain embodiments, the control line may comprise at least one, preferably a plurality of, optical fibers from UV and / or visible light transmission. The optical fibers may have a diameter of 100 μm or less, preferably less than 30 μm. The delivery of light may be used to expand an expansion material (e.g., a filler element), degrade a protective coating, and / or trigger a release mechanism.

[0035] The device may in particular comprise configurable lines arranged between and capable of connecting the control lines and other parts of the device (eg magnetic elements and / or filler elements).

[0036] In a first preferred embodiment, the configurable wire comprises a shape memory alloy and is configured to be formed into a predetermined shape, allowing the device to have a substantially straight shape for travel and achieve a more spherical (quasi-spherical) shape upon delivery.

[0037] In a second preferred embodiment, the configurable line comprises a thin, flexible material (e.g., a string) connecting two or more magnetic and / or filler elements. Such a configurable line may be referred to as a flexible line. The change from a substantially straight shape to a more spherical (quasi-spherical) shape during delivery may be achieved by auxiliary magnetic elements on the configurable line. The magnetic elements used to change the shape of the configurable line may be the magnetic elements used for guidance and / or additional magnetic elements. In addition to magnetic forces, flow forces due to blood flow may also aid in the movement of the magnetic portions on the configurable line closer to each other.

[0038] The properties of the control lines are configured to allow the device to move along a curved path. In embodiments where a configurable line is present, the configurable line may be more flexible than the control line, i.e., less force may be required for elastic or plastic deformation. Greater flexibility may be achieved through the selection of materials and / or dimensions. For example, the control line and the configurable line may be formed from monofilaments of substantially the same material, but the control line has a diameter of 150 μm and the configurable line has a diameter of 50 μm.

[0039] The control wire may comprise or consist of a biocompatible material, preferably comprising or consisting essentially of a material selected from the group of materials consisting of metals, in particular copper, stainless steel, cobalt-chromium-nickel alloys, titanium, titanium alloys, platinum, platinum alloys, Nitinol, nickel-titanium ternary alloys, nickel-free alloys, metal composites, polymers, carbon fibers, graphene, textiles, raw silk, protein fibers, and carbon nanotubes.

[0040] Particularly suitable polymers are aramids, especially one of Kevlar and Twaron, polyamides (especially nylons, i.e. PA6 and PA66), polytetrafluoroethylene, silicones, polyurethanes, polyvinyl chloride (PVC), bioabsorbable polymers, such as polyglycolic acid (PGA), polydioxanone (PDO), polylactic acid (PLA, especially one of PLLA and PDLA, and / or their corresponding copolymers, such as P(LA-GA)), poly-ε-caprolactone and its corresponding copolymers (e.g. P(LA-CL)). Furthermore, collagen and chitosan are natural polymers that are likewise suitable as materials for the control line.

[0041] It will be appreciated that any of the above polymers may be blended, mixed, or used as copolymers of each.

[0042] Preferably, the control line can be bent into a curve having a radius of curvature of 3 mm, preferably 1 mm, even more preferably less than 700 μm without substantial material stress. Those skilled in the art will appreciate that the above radii of curvature refer to an otherwise straight control line (i.e., a theoretical stress of 0 Pa at a curvature of 0, i.e., an infinite radius). In particular, the control line can be made of a material and / or structure such that the minimum breaking stress (i.e., the mechanical stress in the control line before plastic deformation and / or material failure occurs) is in the range of 0.5-4 MPa. Those skilled in the art will appreciate that the invention can be practiced with control lines having higher breaking stresses (i.e., stronger control lines). However, higher values ​​may not be necessary for the invention to function.

[0043] The elastic modulus of the control line may be in the range of 0.001 to 200 GPa. Preferably, the control line including or made of a polymeric material may have an elastic modulus of 0.001 to 5 GPa. The control line including or made of a metal may have an elastic modulus of 30 to 200 GPa. Of course, it is possible to mix, blend or use combinations of materials, such as composite materials, to achieve any elastic modulus. In particular, a composite material of polymer and metal may be used to achieve an elastic modulus anywhere in the range of 0.001 to 200 GPa.

[0044] Typically, the breaking stress of the control wire is not reached when controlling the medical device. If the control wire is a NiTi wire, the ultimate tensile strength (UTS) can reach 1300±200 MPa, and for polymer wires, the UTS can be between 30-900 MPa.

[0045] The control wire may have a Young's modulus of 0.01 to 50 GPa, preferably 1 to 20 GPa, and particularly preferably 1 to 3 GPa.

[0046] The control wire is 0.001 to 1 N mm 2 , preferably 0.021 to 0.45 N mm 2 It is particularly preferable that the bending rigidity is 0.002 to 0.08 N mm 2 or 0.1~0.3N mm 2 Alternatively, the bending stiffness of the control line is approximately 0.050 N mm 2 may be also possible.

[0047] The control wire may have a breaking stress of 0.1 to 5 GPa, preferably 0.1 to 1 GPa, and particularly preferably 0.3 to 0.7 GPa.

[0048] The control line is 0.001 to 0.1 mm in the plane perpendicular to the longitudinal axis. 2 , preferably 0.004 to 0.1 mm 2 , and particularly preferably 0.01 to 0.05 mm 2The cross-sectional area of ​​the slit may be 0.05 mm or less.

[0049] In particular, the control line may be configured, in particular by the selection of material, diameter and / or cross section in a plane perpendicular to the longitudinal axis, to have a breaking force of at least 8N, preferably at least 12N.

[0050] The surface of the control line can be configured to avoid friction with the vessel wall and / or thrombogenic effects, which leads to a safer treatment since laceration of the vessel wall and / or embolism can be avoided.

[0051] Preferably, the control line comprises a hydrophilic surface, such as a surface functionalized with PEG (polyethylene glycol) or polyvinylpyrrolidone (PVP) or poly(vinyl alcohol) (PVA) or polytetrafluoroethylene (PTFE) or any combination thereof. Such a surface allows wetting by blood and thus easier and safer movement in blood. Furthermore, a hydrophilic surface can limit protein adsorption to the control line, thus preventing, for example, the induction of an immune cascade.

[0052] Preferably, the control line has a surface with antithrombogenicity. For example, it may be coated with a material that does not cause substantial thrombosis. In particular, the surface may comprise at least one of phosphorylcholine, phenox, polyvinylpyrrolidone, and polyacrylamide. Additionally or alternatively, the control line may be coated with a drug with antithrombogenicity.

[0053] Preferably, the control line has a surface coated with a hydrogel. The hydrogel may be a synthetic hydrogel and / or a natural hydrogel. Preferably, a hydrogel selected from the group including elastin-like polypeptide (ELP), polyethylene glycol (PEG), 2-hydroxyethyl methacrylate (HEMA), polyhydroxymethacrylate (PHEMA), polyvinylpyrrolidone, polymethacrylic acid (PMA) (as well as other methacrylate- and methacrylic acid-based polymers), agarose, hyaluronic acid, methylcellulose, elastin, and chitosan is used. Both synthetic hydrogels (ELP, PEG, HEMA, polyvinylpyrrolidone, PMA) and natural hydrogels (agarose, hyaluronic acid, methylcellulose, elastin, chitosan) may be chemically crosslinked and / or physically crosslinked. Other materials that at least partially reduce friction between the control line and the vessel wall may also be used.

[0054] The device may comprise a magnetic portion coated with an expansion material. Additionally or alternatively, the device may comprise expansion beads that can be detached from the magnetic portion after activation at the treatment site. The device may comprise several expansion beads that are carried in one moving step. Additionally or alternatively, the device may comprise a front expansion payload consisting of or comprising expansion beads attached to each other and located at the distal end of the device. Once expanded and delivered at the treatment site, the front expansion payload can be detached from the magnetic portion.

[0055] The expansion material may be activatable by contact with physiological fluids (hydration, chemical reaction) or by application of a stimulus such as heat or electricity.

[0056] Examples of expanding materials are hydrogels such as PVA, PVP, polyacrylamide, superabsorbent polymers such as polyacrylic acid (PAA), or polyurethane foams. PVA hydrogels may be porous.

[0057] Preferably, a hydrogel-based expansion element is used that can expand by stimulation. For example, hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm), poloxamer, and / or poly(organophosphazene) (PPZN) can be used and can expand by increasing temperature. Optionally, any one of these polymers can be filled with magnetic nanoparticles and heated, resulting in heating of the polymer (hyperthermia expansion). Polyelectrolyte hydrogels can be expanded by electricity. Hydrogels containing poly(methacrylic acid-co-acrylamide) can be expanded by changing pH.

[0058] Additionally or alternatively, to increase the volume occupied by the device in the aneurysm, the device can trigger a thrombus forming effect that results in the formation of a thrombus that fills the volume of the aneurysm being treated.

[0059] For example, the device can trigger blood clotting within the cavity. The device can include a thrombus-forming element that can be detached from the magnetic element once thrombus formation is initiated, and the thrombus-forming element is delivered to the treatment site. The thrombus-forming element can remain within the thrombus and contribute to the mechanical properties of the thrombus, such as stiffness or stability.

[0060] Preferably, the thrombogenic elements are thrombogenic beads. Alternatively, other shapes are contemplated, for example ovoid, cylindrical, etc. Preferably, the thrombogenic elements are at least partially curved.

[0061] The thrombogenic elements may include beads (or other shapes) coated with the thrombogenic materials disclosed herein, beads made of the thrombogenic materials disclosed herein (e.g., latex beads), and / or beads made at least in part of a thrombogenic agent, such as beads made of a silicone matrix having tantalum elements, porous thrombogenic beads, expandable thrombogenic beads, etc.

[0062] The release mechanism is used to release at least a portion of the device from the control line to remain at the treatment site (such as an aneurysm). The release mechanism may comprise or consist of, among other things, an element that allows for localized rupture within the device. The device may have one or several release mechanisms.

[0063] To ensure that the device is not further displaced by ambient currents after release, the device may comprise a second release system, which may provide a temporary attachment independent of the first release system and may be activated once stability of the filling element is confirmed. Preferably, the second release system comprises a cable configured to displace the proximal portion from the remainder of the cavity.

[0064] The second release system may be attached or attachable to the filler element and the magnetic element, such as connecting the filler element and the magnetic element. Additionally or alternatively, the second release system may be attached or attachable to the control line and the magnetic element, such as connecting the control line and the magnetic element.

[0065] The second release system may comprise a string, adhesive, or any other element disclosed in the context of the first release system.

[0066] For this purpose, any mechanism known in the art for detaching an element from a string of elements such as a control line can be used. In particular, the selective detachment can be triggered by an electrical stimulus, a rotation of a magnetic part (which can be a magnetic element or another magnetic part), a physical action, and / or a chemical action.

[0067] ] For example, a control wire can be glued to the device, and the glued connection dissolves in blood or another liquid. The glue could be designed to dissolve in blood only above or below a certain temperature. In one embodiment, a metal box can be placed around the glued area. The box can be heated by applying an electric current. The heating causes at least partial, and preferably complete, degradation of the glue.

[0068] In particular, the control wire can be chemically coupled to the device, and this chemical connection can be broken under the influence of an increase in temperature, a change in pH, an electrical stimulus, etc. For example, an electric current can be used to increase the corrosion rate of a magnesium alloy that forms part of the release mechanism and connects the two parts of the device. Additionally or alternatively, an element of the device can be connected to the release mechanism by an adhesive. Additionally or alternatively, the device, and in particular the release mechanism, can be formed at least in part by an iron-based material. Applying an electric current and / or a voltage to the control wire can cause the migration of ferrous ions from the anode to the cathode, which causes the dissolution of the iron-based parts. Additionally or alternatively, the control wire can have an insulating portion to protect the control wire and / or parts of the device from corrosion and dissolution.

[0069] In some embodiments, application of an electric current to the magnetic part may result in biocorrosion of its surface, especially if it is made of iron. Biocorrosion may result in the gradual dissolution of the surface. As a result, the contact surface with the filler element may be removed, thus allowing the two elements to be separated.

[0070] Mechanical release mechanisms are also contemplated. For example, a mechanical interlock can be used, i.e., a first and second contour that interact with each other to connect the two elements. The use of a mechanical interlock mechanism in combination with an adhesive is particularly advantageous because the connection is provided by cohesive forces in the adhesive, rather than adhesive forces between the adhesive surfaces of the device.

[0071] In some embodiments, the control line may be configured to transmit an electrical signal that releases a portion of the device from the control line. This may also be done by magnets and / or electromagnets (e.g., hyperthermia). The medical device may also receive a wireless signal, e.g., via a wireless signal receiver, that selectively triggers the separation of a portion of the device from the control line. In some embodiments, the release mechanism is configured to degrade under irradiation, such as by electromagnetic radiation (e.g., visible light, ultraviolet light, x-rays) and / or ultrasound, which may be transmitted, e.g., via an optical fiber disposed within or adjacent to the control line.

[0072] Additionally or alternatively, the release mechanism may be composed of a biodegradable material such as PGA. A very low molecular weight PGA can be used that loses mechanical integrity when hydrolysis begins, thus ensuring sufficiently fast degradation. Degradation of the biodegradable material can be further accelerated by a stimulus such as heat. The very low molecular weight may be less than 10,000 g / mol, preferably less than 8000 g / mol.

[0073] Preferably, the device moves passively, carried by the body fluid and may be slowed down by a control line, i.e. the device may move at a speed slower than the speed of the flow. Optionally, the device may further comprise a means for propulsion, i.e. an additional device or mechanism allowing for accelerating, maintaining or reducing the speed within the human body. For example, this may be a propeller or impeller.

[0074] The magnetic element may be a single element, for example a particle of one of the above materials. Alternatively, the magnetic element may comprise a plurality of particles and / or an aggregate of particles. The magnetic element may be covered with a coating.

[0075] The magnetic portion may have a spherical, cylindrical, cubic, or ovoid shape (eg, comparable to a rugby ball).

[0076] The magnetic part may be made of hard ferromagnetic materials such as FePt alloys, Nd-Fe-B alloys, SrO6Fe2O3 alloys, soft ferromagnetic alloys such as iron alloys (stainless steel AISI 420C, e.g. Fe covered with a protective shell made of graphite), nickel alloys, or cobalt alloys, or a combination of these magnetic elements, and / or iron oxide (Fe 3 O 4 or Fe 2 O 3 ) can be made of ferrimagnetic materials.

[0077] The magnetic portion may be coated to prevent direct contact with physiological fluids such as blood. Thus, corrosion or cell interaction may be avoided. The protective coating may be made of metals such as titanium, gold, silver, metal oxides, polymers such as polyurethanes, especially polyurethanes with polycarbonate backbones, polymers with siloxane chains to improve resistance to oxidative attack, silicones (parylene, PDMS), polytetrafluoroethylene (PTFE), ceramics such as silica-based ceramics and / or zirconium-based ceramics (e.g. zirconium dioxide). Additionally or alternatively, the protective coating may include graphite or other carbon-based materials.

[0078] The magnetic elements can be fabricated by embedding magnetic particles in a matrix, which can include hard ferromagnetic, ferromagnetic, ferrimagnetic, and / or superparamagnetic materials.

[0079] The magnetic particles may have any suitable shape, in particular cubes, spheres and / or ellipses. The particles may have a characteristic size (eg diameter) of 5 nm to 50 μm, preferably 30 to 100 nm.

[0080] The matrix may comprise or consist of a polymer, such as PLGA, PDMS, polyurethane, and / or a ceramic, such as SiO2.

[0081] The matrix may include or consist of a hydrogel. The hydrogel may be degradable by hyperthermia, resulting in the release of biodegradable magnetic particles. For example, Fe 2 O 4 with a diameter of 5-50 nm, preferably 5-20 nm. 2 O 3 or Fe 3 O 4 The nanoparticles may be released. The integrity of the gel decreases with increasing temperature. Other stimuli disclosed herein may also be used.

[0082] The filling element can include an expansion material. The expansion material can include a hydrogel that swells upon exposure to blood and / or other bodily fluids. Additionally or alternatively, the device can include a scaffold of a shape memory material.

[0083] The expanding material can be used to fill voids in the body, such as aneurysms. Self-expansion can be achieved by hydration, heat, particularly heating to 37°C, and the addition of ions, particularly Fe. 2+ , Na + , Cl - , and / or ions present in human blood, such as phosphate ions.

[0084] Further possible stimuli for the expansion can be chemical stimuli, electricity, electromagnetic radiation, in particular light irradiation, ultrasonic energy, and / or hyperthermia.

[0085] In general, the filler element may include or be composed of an intumescent material. The filler element may be at least partially attached to, attachable to, or formed by the magnetic element. Preferably, the magnetic element and the filler element are fixedly attached or attachable to one another so that they cannot move relative to one another. Alternatively, they are attached or attachable via flexible means, such as, for example, a cord, line, or suture.

[0086] In particular, different elements of the device, such as control lines, filler elements, and / or magnetic elements, may be assembled by chemical connections (e.g., glue), physical connections (e.g., by welding) or mechanical connections (such as screws), and / or release systems, as described herein.

[0087] As a result, the filler elements can be moved very conveniently together with the magnetic elements.

[0088] The filler element may comprise a thrombogenic element comprising at least one of a thrombogenic shape and a thrombogenic material.

[0089] A thrombogenic element is to be understood as any element that causes blood clotting. A thrombogenic element can in principle have any shape and can cause clotting due to its material, shape, specific surface treatment or release of a thrombogenic agent. Of course, these are only non-limiting examples of thrombogenic elements.

[0090] Particularly preferred thrombogenic agents clot blood almost instantly upon contact with the blood, allowing targeted clotting at specific locations and controlled clotting times.

[0091] Preferred thrombogenic agents include biological substances such as thrombin, fibrin, and collagen. Examples of thrombogenic materials are polymers such as nylon or polyethylene terephthalate, polyethylene oxide-based polyurethane PEU-PEO, latex, and metals such as titanium, indium, and tantalum. Additionally or alternatively, the thrombogenic element may include electrical contacts for inducing electrical thrombosis.

[0092] The thrombogenic element may comprise a fiber that may be further coated with a thrombogenic agent, in particular one of thrombin, fibrin, collagen, or latex. The fiber may be a dry fiber and / or may be configured to remain dry during movement through the body.

[0093] In some embodiments, the thrombogenic element can cause the formation of a thrombus with a tailored composition. For example, a coating with a high concentration of thrombin can result in the formation of a large clot with a high fibrin content resulting in more suitable mechanical properties. For example, these mechanical properties can improve the resistance of the thrombus to compression induced by blood flow. Preferably, the thrombin concentration in the thrombogenic element, e.g. the thrombogenic fixed coating, is selected between 100 NIH U / mL and 1000 NIH U / mL. As a result, the activation of fibrinogen can be suitable to achieve a fibrin content in the clot of at least 10%, preferably 50% to 80%.

[0094] Additionally or alternatively, there may be different thrombogenic effects in the first and second states of the thrombogenic element, for example in the first state the thrombogenic effect may be weaker than in the second state.

[0095] A thrombogenic feature is any feature that can cause thrombosis in the blood, for example, a feature having relatively sharp edges, a small radius of curvature, spikes, or other features that can cause a blood clot to form.

[0096] The magnetic elements may in particular be arranged with a thrombogenic shape and constructed as a single element including both the magnetic element and the thrombogenic element.

[0097] The filler element may comprise at least one defined shape, preferably at least a first and a second defined shape. The defined shape is at least partially curved.

[0098] Particularly preferably, the defined shapes are beads or other substantially spherical structures. The defined shapes may have an aspect ratio comprised between 0.5 and 1.5.

[0099] The defined shape preferably has a characteristic length corresponding to 50% to 200% of the characteristic length of the magnetic element.

[0100] The device may further comprise a configurable wire, which particularly preferably forms a connection between the filler element and the magnetic element.

[0101] As a result, the device is configured to change its structure to optimize the filling of a cavity, such as an aneurysm.

[0102] Preferably, the configurable line is formed by a portion of the control line. In these embodiments, it will be appreciated that the portion of the control line may be released with the device by the release mechanism. Thus, the release mechanism may be located along the longitudinal axis of the control line.

[0103] For example, a device having a configurable portion of a control line can partially change its structure under a stimulus. A configurable line, e.g., a configurable portion of a control line, can change its shape from a straight line to a curved shape.

[0104] The configurable wire allows the filler elements to be arranged in a convenient manner by varying its shape and / or size and / or its cross-sectional shape and / or size, for example the cross-sectional shape may vary from circular to flat or ribbon-like.

[0105] The configurable wire may comprise a material that undergoes a structural change, such as a change in crystal structure or alignment of monomers.

[0106] Additionally or alternatively, the configurable wire can change its shape from straight to bent, in particular at an angle between 2° and 160°, preferably between 20° and 120°, or change its radius of curvature by at least 1 mm, preferably 2 mm. In a particular embodiment, the configurable wire comprises first and second magnetic portions that are attracted to each other, thus inducing the bend.

[0107] The configurable line may be configured to be formed into a predetermined shape, where predetermined may be understood as a shape that remains substantially constant, especially after a change in shape.

[0108] The configurable wire may be thrombogenic, particularly in the second configuration, and may be part of the filling element.

[0109] As a result, the configurable wire can be configured to form a larger aggregate fill body comprising multiple filler elements, but still be capable of movement within the vessel in a straight configuration.

[0110] The filling element can comprise a compressed expanding material, such as a foam. The compressed material can be configured to expand to a post-expansion shape. The post-expansion shape can have a size and shape that substantially corresponds to a characteristic size and shape of the aneurysm. Typically, an aneurysm has a characteristic size (e.g., diameter) of 5 mm to several centimeters, particularly 7 to 25 mm.

[0111] Preferably, the filling element comprises an expansion element that can be cut prior to the procedure to fit the size and shape of the aneurysm to be treated. The expansion material may remain compressed for delivery.

[0112] Thus, the foam may be configured to substantially completely fill the aneurysm when expanded therein.

[0113] The device may be provided with a protective coating, particularly as part of the activation mechanism, which may particularly preferably be arranged radially outside the packing element.

[0114] The thickness of the protective coating may be from 20 μm to 400 μm, preferably from 90 μm to 300 μm.

[0115] The protective coating may include or consist of a polymer or a mixture of polymers, such as silicone, polyurethane with a polycarbonate backbone, and / or polytetrafluoroethylene. The protective coating may be disposed with a strain at a distal portion of the microrobot. Additionally or alternatively, the protective coating may include a weakened portion at the distal portion, such as by making a portion of the protective coating thinner than another portion of the protective coating. When the protective coating is to be removed after breaking of the weakened portion, the protective coating may be pulled back to remove the protective coating from the attachment element.

[0116] To break the weakened portion, the protective coating can be retracted proximally, which movement can be accomplished by an electrostrictive material attached to the protective coating.

[0117] For example, piezoelectric ceramics (e.g., lead zirconate titanate and / or barium titanate) or piezoelectric polymers (polyvinylidene fluoride) can be used. Additionally or alternatively, microelectromechanical systems (MEMS) that can be activated by an electric current can be used.

[0118] Particularly preferably, the protective coating is arranged in a sheath-like manner around the filler element and / or the magnetic element.

[0119] Preferably, the protective coating may be configured to dissolve spontaneously in an aqueous fluid or in a manner triggered by a stimulus. The protective coating may be arranged in such a way as to cover the filling element, in particular the thrombogenic element. Dissolution of the protective coating may be achieved, for example, by contacting the thrombogenic element with blood in order to activate the filling element.

[0120] The protective coating may be non-bioabsorbable or bioabsorbable. Preferably, the protective coating is configured to substantially prevent the penetration of liquids to avoid premature activation of the expansion material and / or thrombogenic components.

[0121] In one embodiment, a bioabsorbable protective coating can be fabricated from a biodegradable polymer loaded with nanoparticles. The polymer exhibits a low decomposition temperature (60-40°C). The nanoparticles can be coated with gold, Fe, 2 O 3 , Fe 3 O 4 The protective coating can be made of nanoparticles, nanoparticles, or silver. The protective coating is decomposed by heat generated by the nanoparticles under stimuli such as light or a magnetic field. As a result, the coating breaks down into smaller biodegradable pieces that can be washed away by the bloodstream.

[0122] In another embodiment, the protective coating comprises a membrane. The membrane is substantially composed of magnesium powder in a matrix of a bioabsorbable polymer. The magnesium powder can be degraded, for example, by applying an electric current through a control wire. The magnesium powder particles act as linkers in the membrane, resulting in the membrane rupturing. Thus, the protective coating can disintegrate and be washed away.

[0123] Preferably, the filler elements are arranged radially outside the magnetic elements. This provides a very compact design that allows for advantageous movement. For example, the filler elements may comprise thrombogenic features on the surface of the magnetic elements. Additionally or alternatively, the filler elements may comprise a thrombogenic or expanding coating.

[0124] A release mechanism may be disposed between the control line, preferably a first portion of the control line, and:

[0125] · any one of the filler element and the magnetic element, and preferably the second portion of the control line; any two of the filler element, the magnetic element, and preferably the second portion of the control line; · All three of the filler element, the magnetic element, and preferably the second portion of the control line.

[0126] As a result, the release mechanism can always detach the control line from at least one other part of the device. In a preferred embodiment, at least the filling element is detached from the control line by the release mechanism. This allows a portion of the device, e.g., the filling element, to be released when at least said portion of the device is positioned at the aneurysm. This allows the filling element to fill the aneurysm while at least the control line and optionally other parts of the device are pulled back by the operator.

[0127] The magnetic element can travel to the cavity corresponding to the treatment site and can remain there after treatment or can be detached and removed again, in certain embodiments, the magnetic element does not enter the treatment site.

[0128] For example, a device comprising a configurable wire can be delivered to an aneurysm with at least one expanding bead and a magnetic portion and detached from the control wire as a whole. In another embodiment, a device comprising magnetic beads with a thrombogenic coating can be delivered to an aneurysm and detached from the control wire. The magnetic beads can remain in the aneurysm and be surrounded by the thrombus.

[0129] In yet another alternative embodiment, a device with a front expansion payload may be configured to deliver only the expansion material into the cavity, i.e., the filler element is separate from the remainder of the device (including the magnetic portion) which is then removed.

[0130] Furthermore, the present invention relates to a system for treating a cavity, such as a blood vessel, preferably an aneurysm, of a patient. In particular, the aneurysm may be a cerebrovascular or aortic aneurysm. The system comprises an apparatus as disclosed herein. Furthermore, the system comprises at least one control line driver, a magnetic actuator, and a control unit.

[0131] The control unit may be further configured to actuate the release mechanism and / or trigger an activation mechanism of the device. The control unit may be integrally formed with the control line driver and / or the magnetic actuator. Alternatively, the control unit may be a separate unit operably connected to the control line driver and the magnetic actuator, for example wirelessly or by cable.

[0132] The system may comprise one or several magnetic actuators: in a particular configuration, one magnetic actuator is used to generate a magnetic field that covers the cavity to be treated.

[0133] The system can generate and control stimuli that are used to activate various functions of the device. The stimuli can be generated by control line drivers and communicated to the device via control lines.

[0134] Additionally or alternatively, additional elements may be embedded in the system to generate the stimulation and may be external to the patient, for example an ultrasound probe, preferably mounted on a robotic arm, may be automatically applied to the patient's skin at the appropriate location as determined by the control unit.

[0135] Furthermore, additional elements may be positionable within the patient, preferably in the vascular network. For example, a catheter may be automatically advanced in the vascular network under the control of the control unit and may deliver a stimulus such as light. A robotic pushing system may be present to move the catheter.

[0136] The system may include a system for measuring the flow rate in the cavity. The flow in the cavity may change with the deployment of the device. Monitoring the flow rate and flow perfusion in the cavity therefore allows monitoring the progress of the treatment and possible migration of the device. For example, the attachment of the filling element may be confirmed by a steady flow around the element. To improve the detection of the filling element by ultrasound, the element may be echogenic. For example, air bubbles may be trapped inside the filling element. Alternatively, the surface of the filling element may be coated with hollow particles filled with gas.

[0137] To activate the release mechanism, the magnetic actuator can be rotated. The rotation results in a rotation of the magnetic part of the device. The rotation of the magnetic part results in a twisting of the release system. In this way, the rotation can be performed up to the destruction of the release system. Under rotation, the magnetic part can be moved backwards to contribute to the destruction of the release system.

[0138] The magnetic actuator is configured to generate a magnetic field at a predetermined location. Preferably, the magnetic field is predetermined. The magnetic field exerts a force on the medical device, in particular on the magnetic part of the medical device, e.g., the medical device can be steered in a preferably predetermined direction. The control unit is configured to balance at least three forces acting on the medical device. Preferably, the control unit balances the forces in real time. Preferably, the three forces include at least one of a drag force acting on the medical device due to a flow of a fluid, e.g., blood in a blood vessel, a force due to the control line, and a magnetic force due to the magnetic actuator. Furthermore, the control line operates the magnetic actuator and / or the control line driver.

[0139] Magnetic forces may be primarily used to orient the device in the bloodstream, and thus the device may have embedded magnetic elements that interact with a magnetic field generated external to the patient.

[0140] Drag forces caused by blood flow can include displacement of the device along the vascular network, accomplished primarily by blood flow.

[0141] A control line is attached to the distal portion of the device, and the force exerted by the control line can be used to adjust the speed of the distal portion of the device. The proximal portion of the control line is connected to a control line driver that releases the control line at a target speed. The control line can be very flexible so as not to impair the movement caused by blood flow. As a result, the control line does not have to push against the distal portion of the device.

[0142] Other forces, such as for example gravity acting on the device and / or the control line, may also be taken into account by the control unit.

[0143] The control lines can assist with magnetic guidance. The invention helps to find a good balance between the various forces applied to the medical device, namely flow forces, gravity, control forces, and magnetic or other potential forces acting on the medical device, in order to guide it along a trajectory path. The system, in particular the control unit, can automatically calculate the forces and the relationships between the forces and define the forces generated by the system, in particular the control line forces and the magnetic forces, ensuring that the resulting forces move the medical device along a predefined trajectory, in particular at a controlled speed.

[0144] This balance model also makes it possible to optimize the distribution of forces induced by the magnetic actuators and the control lines. The balance of forces can also be beneficial to optimize system requirements, e.g. weaker magnetic fields and / or smaller control line forces.

[0145] The control line driver may include, and preferably consist of, any one or combination of the following: pulleys, linear actuators, reels, electric motors, spindles, gears, screws and / or nuts, linear gear tracks, and continuous tracks. Additionally, the control line driver may comprise two or more of any one of these elements in combination with one or more of any other elements.

[0146] For example, two pulleys can be connected to two control lines attached to the distal portion of the device, and the synchronization and asynchronous nature of the pulleys can be used to orient the distal portion and / or trigger certain functions of the device.

[0147] Further, the control line driver may additionally or alternatively comprise a control line connector configured to provide an operable connection between the control line driver and the control line.

[0148] Preferably, the control unit may comprise a processor and / or a memory. In a particularly preferred embodiment, the control unit is operatively connected to the electric motor and configured to control at least one of the speed, power, and torque of the electric motor.

[0149] The speed may be at least partially predetermined, automatically determined or manually selected. It is also conceivable to use a combination of predetermined, automatically determined and manually selected speeds. For example, the control unit may calculate an appropriate speed profile based on the planned trajectory in the vessel, taking into account data on the flow of blood in the vessel, and store the speed profile in memory. Additionally or alternatively, the speed of the control line may be adjusted automatically during the intervention, for example via a feedback loop taking into account the planned trajectory and the actual position data, and / or manually by the user. For this purpose, the system may preferably comprise an interface for the user, for example one or more touch screens, knobs, buttons, levers, configured to allow the input of speed parameters. Using the same interface or additional interfaces, it is possible to input further parameters related to the control of the position and speed of the medical device.

[0150] Preferably, the control unit is configured to calculate the magnetic field at the device position in space and / or the force that said magnetic field exerts on the magnetic element when the magnetic element is located at the device position in space. The control unit may in particular take into account at least one of the position, orientation and / or output of the magnetic actuator. Additionally or alternatively, the control unit may be configured to receive data from a sensor at or near the device position, in particular data relating to the magnetic field and / or magnetic force at the device position.

[0151] Additionally or alternatively, the device may calculate at least one of a position, an orientation, and an output of a magnetic actuator suitable for establishing a magnetic field and / or magnetic force at the device location. The magnetic field and / or magnetic force may be calculated qualitatively (e.g., direction only) or quantitatively.

[0152] It is conceivable that the control unit may be configured to perform a closed feedback loop with respect to the magnetic actuator, i.e. to calculate the position, orientation and / or output of the magnetic actuator based on a desired force and / or magnetic field, and to adjust or correct said position, orientation and / or output, e.g. based on an actual measured magnetic field and / or force.

[0153] The control unit may be further configured to calculate and / or determine a force acting on the medical device via the control line. To this end, the control unit may comprise and / or be operatively connected to a force sensor configured to measure the force acting on the medical device. The control unit may control the control line driver to release the control line while keeping the force acting on the medical device via the control line constant. Additionally or alternatively, the control unit may be configured to control the control line driver to release the control line at a constant speed. Additionally or alternatively, the control unit may be configured to control the control line driver to release the control line at a speed and / or pullback force determined based on the magnetic force acting on the medical device.

[0154] Particularly preferably, the control unit is able to control and / or limit one of the speed and the position of the medical device via the control line driver.

[0155] The control unit may further calculate and / or determine drag forces acting on the medical device due to the surrounding blood flow. The system may comprise a sensor configured to measure the velocity of blood flow at the location of the device, for example a Doppler ultrasound device. Additionally or alternatively, force data provided by a force sensor may be taken into account. Additionally or alternatively, the system may comprise a memory device containing flow data as a function of position within the blood vessel obtained before or during the treatment.

[0156] The control unit is therefore configured to balance three forces that may act on the medical device. Balancing the several forces may in particular be understood as adjusting the magnitude of at least one of the several forces in response to and / or based on at least one other force, preferably all other forces.

[0157] The control unit can be configured to increase or decrease the magnetic force acting on the medical device by adjusting at least one of the position, orientation, and / or power of the magnetic actuator in response to the blood flow and / or the force exerted on the medical device by the control lines. For example, if the force exerted on the medical device by the blood flow is too small to move the medical device along the longitudinal axis of the blood vessel, the control unit can adjust the operation of the magnetic actuator to exert a force at least partially in a direction substantially parallel to the longitudinal axis to propel the medical device forward.

[0158] Additionally or alternatively, the control unit may be configured to increase or decrease the speed of the release of the control wires depending on the drag force exerted by the blood flow on the medical device and / or the magnetic force exerted by the magnetic actuator on the medical device. For example, the control unit may determine that the available magnetic force is limited due to spatial constraints or distance between the tissue and the magnetic actuator and / or the drag force exerted by the blood flow is strong enough such that the available magnetic force is not sufficient to move the medical device in the intended direction. Thus, the control unit may operate the control wire driver to slow down and / or stop the release of the control wires, thereby slowing down and / or stopping the medical device. As a result, a smaller magnetic force is sufficient to move the medical device in the desired direction, especially since the medical device has a lower speed compared to the surrounding blood flow.

[0159] The system may comprise an orienting means for orienting the magnetic field. The orienting means may be operatively connected to the control unit. In case of a magnetic field generated by a permanent magnet, the orientation may be performed by moving a magnetic actuator using an orienting means, in particular having an arm, a joint, a telescope, a wheel, a gear, a rail, and combinations thereof, etc. In particular, the orienting means may comprise a robot arm with six degrees of freedom for moving the permanent magnet.

[0160] In the case of magnetic fields generated by non-permanent magnets, orientation of the magnetic field can be achieved by varying the current in an electromagnet and / or by using the orientation means described for permanent magnets.

[0161] In one embodiment according to the invention, the system is additionally or alternatively intended to treat or diagnose a patient by using a medical device, preferably implantable, having a magnetic portion and a shape, size and surface structure that defines a moving component of the medical device when dragged by a bodily fluid. The system comprises a magnetic actuator, a control unit and a control line driver. The control line may be attached to the control line driver. The control line driver is or may be operably connected to the control unit such that at least one of the position, movement and velocity along the axis of the control line when attached to the control line driver is controllable by the control unit via the control line driver. Additionally or alternatively, the control unit may be configured to at least partially control the position and / or velocity of the medical device within a blood vessel when operably connected to the control unit via a control line attached to the control line driver via at least one of the position, velocity and movement of the control line driver.

[0162] The control unit may be further configured to control the position of the medical device within the blood vessel via the magnetic actuator, preferably in a plane perpendicular to the longitudinal axis of the blood vessel and / or in a direction parallel to the longitudinal axis of the blood vessel. Preferably, the control unit is configured to take into account the drag force exerted by the blood flow on the medical device for actuating the magnetic actuator and / or controlling the movement or position of the control line. Additionally or alternatively, the control unit may be further configured to actuate the magnetic actuator based on the velocity of the control line or adjust the velocity of the control line based on the magnetic field generated by the magnetic actuator.

[0163] Particularly preferably, the control unit is configured to determine three force components exerted on the medical device by the blood flow, the magnetic force, and the control line, respectively, and to control the control line driver and the magnetic actuator to balance the three force components to achieve the intended movement of the medical device.

[0164] The control unit may be configured to simulate the progressive filling of the aneurysm by the device and / or the filling element. The simulation may be based on the presence and / or delivery of the filling element and on flow disturbances induced by thrombotic reactions, in particular the activation of the coagulation cascade. The control unit may be configured to monitor the progressive filling of the aneurysm during treatment by image analysis. For this purpose, images obtained by medical imaging systems known in the art may be used to determine the filling state of the aneurysm by the filling element, which can be compared with the simulated state in order to release the filling element at the appropriate time.

[0165] The release of the filler element is triggered by a control unit sending commands to a control line driver having suitable characteristics for generating the various stimuli mentioned above. As an example, the control line driver can have an internal power source connected to the electrical wires of the microrobot.

[0166] Furthermore, the present invention relates to a method for treating a vascular, preferably an aneurysm, in particular a cerebral vascular or aortic aneurysm, wherein a magnetically guideable medical device, preferably a medical device as disclosed herein, is used to carry out the method. The method comprises: -magnetically guiding a medical device through the vasculature to a target site, preferably an aneurysm; activating the filling element, preferably to expand the filling element and / or trigger a thrombus formation action; Releasing at least a portion of the medical device, preferably the magnetic element and / or the filling element, at the target site. Includes.

[0167] Preferably, the steps are performed in this order. The control unit may be capable of simulating a progressive filling of the cavity. In particular, based on flow variations or / and biological reactions induced by at least one device, the control unit can simulate a progressive occlusion and thrombus formation. The simulation allows the determination of a suitable sequence for the delivery of the device. This sequence provides a spatial distribution of the device in the cavity and a time before the release of the filling element.

[0168] To ensure that the filling element is properly secured within the cavity, the magnetic actuator can be moved by 1 mm to 20 mm, preferably 1 mm to 5 mm, and imaging of the device can be performed, for example by fluoroscopy. If no movement of the filling element is detected, a contrast solution can be injected to allow monitoring of the flow within the cavity and around the filling element. If the flow is sufficiently blocked, a release by the release mechanism can be performed. In some embodiments, the control unit can be configured to process the above information and initiate the release.

[0169] Preferably, said steps of the method are repeated at least once, preferably twice.

[0170] When steps of the method are repeated, a set of steps as described above may be performed in a particular order, preferably in the order described above, however, it will be understood that sets of steps may overlap and any step of one set may be in any order relative to any step of another set.

[0171] For example, if the steps are repeated, magnetic guidance may be performed during or after any step of the first repetition of the steps.

[0172] The device, in any of the embodiments disclosed herein, may further comprise fixation elements that ensure attachment of the device at the treatment site, particularly inside the aneurysm and / or vessel wall.

[0173] The fixation element functionally functions to provide an attachment between at least a portion of the device, preferably the entire device, and the vessel wall and / or blood clot.

[0174] For example, the device may include a fixing coating on the expanded beads. Additionally or alternatively, the immobilization element may trigger platelet activation and / or the coagulation cascade. For example, biological elements such as collagen, thrombin, von Willebrand factor (vWF), laminin, thrombospondin, vitronectin, fibrinogen, or thromboxane A2 can be used as immobilization elements, particularly as immobilization coatings.

[0175] Additionally or alternatively, synthetic adhesive materials may be used, such as, for example, cyanoacrylates. The adhesive fixing material may be dried to avoid adhesion to the protective coating. The material may be processed as a fiber, for example to deposit a layer of fiber.

[0176] The filler elements may comprise or consist of Janus beads. The Janus filler elements may have at least two different surfaces. For example, the Janus beads may have an adhesive layer on half of their surface configured to attach to the walls of the cavity. The other half of the surface ensures adhesion to other filler elements.

[0177] For example, Janus beads can have a collagen coating for attachment to the vessel wall, while the other surface may be coated with fibers that increase the contact surface with another filling element.

[0178] Furthermore, specific attachment between two packed beads can be achieved by "click" chemistry and / or by surface properties, such as specific topography and / or positively or negatively charged surfaces, that allow connection between the elements by a click mechanism.

[0179] In some embodiments, the device can be imaged or tracked with imaging modalities such as MRI, CT scanner, echography, X-ray or fluoroscopy, which may be part of the system according to the invention. Imaging allows monitoring, preferably live monitoring, of the device during movement and treatment of the vessel. In particular, the deployment and final positioning of the device can be tracked and verified.

[0180] In particular, a magnetic section, for example made of Nd-Fe-B and having a diameter of 1 mm, can be detected by a C-arm system. Nevertheless, other components of the device may need to be tracked as well, such as control lines, protective coatings and / or filling elements. The device may therefore further comprise at least one tracking element. The tracking element may include or consist of barium compounds, iodine, tantalum, platinum and / or bismuth.

[0181] Preferably, the tracking element is part of the element being tracked, i.e., part of the filler element, magnetic element, control line, protective coating, and / or release mechanism. The tracking element may be disposed within the material, for example, by covalent bonding or grafting. Additionally or alternatively, the tracking element may include or consist of a strip, ring, and / or powder associated with the element being tracked.

[0182] For example, a platinum strip may be placed on the surface of the tracked element. The platinum strip may have a width of 100 μm and / or a thickness of 50 μm. Additionally or alternatively, barium powder may be mixed with a polymer such as polyurethane and applied to the surface of the tracked element. The thickness of such a coating may range from 1 μm to 70 μm, preferably between 5 μm and 15 μm. The particles of the radiopaque powder may have a diameter in the range of 20 nm to 3 μm, preferably 50 nm to 100 nm.

[0183] The invention is explained in further detail in the following figures. [Brief description of the drawings]

[0184] [Figure 1] Figures 1a to 1i show diagrammatically a first method of filling an aneurysm with a device according to the invention. [Diagram 2] 2a-d show diagrammatically a second method of filling an aneurysm with a device according to the invention. [Diagram 3] Figures 3a-3e illustrate generally a third method of treating a vascular site using an apparatus according to the present invention. [Figure 4] Figures 4a to 4e show diagrammatically a fourth method of treating an aneurysm using a device according to the present invention. [Diagram 5] 5a-b show a schematic of the working principle of a configurable wire. [Figure 6] 6a-6c show diagrammatically a method of deploying a device according to the present invention in an aneurysm. [Figure 7] 7a-7d show diagrammatically a fifth method of treating an aneurysm using a device according to the present invention. [Figure 8] Figures 8a to 8e show diagrammatically the closure of a vascular wound with a device according to the invention. [Figure 9] 9a to 9f show a schematic diagram of a method for manufacturing a device according to the invention. [Figure 10]Figures 10a to 10h show embodiments of the device according to the present invention. [Figure 11] Figures 11a to 11b schematically show a first protective coating used with the device. [Figure 12] Schematically shows the device having the protective coating of Figure 11a. [Figure 13] Figures 13a to 13c schematically show the operating principle of a third embodiment of the protective coating. [Figure 14] Schematically shows the operating principle of a fourth embodiment of the protective coating. [Figure 15] Schematically shows the operating principle of a fifth embodiment of the protective coating. [Figure 16] Schematically shows the operating principle of a sixth embodiment of the protective coating. [Figure 17] Schematically shows the operating principle of a seventh embodiment of the protective coating. [Figure 18] Schematically shows the operating principle of an eighth embodiment of the protective coating. [Figure 19] Schematically shows a further embodiment of the device according to the present invention. [Figure 20a] Schematically shows yet a further embodiment of the device according to the present invention. [Figure 20b] Schematically shows yet a further embodiment of the device according to the present invention. [Figure 21] Schematically shows yet a further embodiment of the device according to the present invention. [Figure 22] Schematically shows the operating principle of an embodiment of the filling element. [Figure 23] Figures 23a to 23d schematically show various embodiments of the thrombus-forming element. [Figure 24] Schematically shows another embodiment of the device according to the present invention. [Diagram 25] Figures 25a to 25b schematically show the operating principle of the device of Figure 24. [Figure 26a]13A-13C show diagrammatically the working principle of a further embodiment of the thrombogenic element; [Figure 26b] 13A-13C show diagrammatically the working principle of a further embodiment of the thrombogenic element; [Figure 27] 2 shows a schematic diagram of a manufacturing process for a device according to the invention; [Figure 28a] 2 illustrates a control line driver for a system according to the present invention. [Figure 28b] 2 illustrates a control line driver for a system according to the present invention. [Figure 29] 1 illustrates diagrammatically the working principle of the system according to the invention; [Diagram 30] 1 shows diagrammatically a patient being treated with a system according to the invention; [Diagram 31] 2A-2C show schematic diagrams of forces acting on a device according to the present invention while traversing the vasculature. [Diagram 32] 10A-10C show diagrammatically the progressive delivery of the filling elements; [Diagram 33] 1 shows a schematic representation of an apparatus according to the invention; [Diagram 34] Figures 34a-c show diagrammatically different states of the device during delivery. [Diagram 35] Figures 35a to 35d show diagrammatically different devices according to the invention. [Figure 36a] 2 shows diagrammatically a device according to the invention with an additional release system; [Figure 36b] 2 shows diagrammatically a device according to the invention with an additional release system; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0185] In the following, for the sake of clarity, the same reference numbers referring to the same features are shown only once within the same figure number.

[0186] 1a-1i show diagrammatically the filling of an aneurysm A with a device 1 according to the invention. The device 1 comprises a control wire 2 made of nylon with a diameter of 150 μm, which is attached to the control wire 2 via a release mechanism 3 with a diameter of 100 μm that can be degraded by an electric current. Two electric wires (not shown) with a diameter of 20 μm are further combined with the control wire. A magnetic part 4 having a spherical shape with a diameter of 1 mm containing Nd-Fe-B is provided with a thrombogenic layer made of thrombin with a thickness of 10 μm and further provided with a protective coating 6. The protective coating 6 is arranged radially outside both the magnetic element 4 and the thrombogenic layer 5, and further the protective coating 6 is arranged in a sheath-like manner around the thrombogenic layer 5. The protective coating comprises PTFE and has a thickness of 10 μm.

[0187] Figure 1a shows a first step of a method of using the device 1 according to the invention: The device is guided to an aneurysm A in a vascular network V using an external magnetic flux provided by a magnetic actuator (not shown).

[0188] FIG. 1b shows the device in the general area of ​​aneurysm A. The general area typically refers to the location along the longitudinal axis of the blood vessel where the cavity is located. A magnetic flux is provided by magnet M, which moves the device to the target area, here aneurysm A. The magnetic flux provided by magnet M can further hold device 1 within the aneurysm for as long as necessary.

[0189] 1c shows a subsequent step in the method, where the device 1 has been moved into the aneurysm A and is positioned in the appropriate area within the aneurysm. The protective coating 6 has been dissolved by contact with blood. As a result, blood comes into direct contact with the thrombogenic coating 5 of the device 1.

[0190] As a result, a thrombus T begins to form on the surface of the thrombogenic coating 5 of the device 1. As the thrombus T progresses, the volume of the aneurysm gradually decreases. Optionally, a further stimulus, such as an increase in temperature or exposure to electromagnetic radiation, may be used to assist in dissolving the protective coating 6.

[0191] The control wire 2 is then removed from the device 1 by means of a release mechanism 3, as shown in FIG. 1e.

[0192] Here, the release mechanism 3 is disassembled by applying an electric current through the two wires. When induced, the release mechanism can be protected by a protective coating (see FIG. 1 a), especially if the release system would otherwise be in direct contact with blood.

[0193] In a next step, the control wire 2 is withdrawn from the aneurysm A as shown in FIG. 1f (driven by a control wire driver controlled by a control unit not shown here).

[0194] Optionally, the steps illustrated in Figures 1a-1f can then be repeated to deliver a further device 1' into the aneurysm A. The second device 1' can be attracted to the first device 1 by magnetic forces. In particular, if a hard ferromagnetic material is used, the magnetic attraction of the first device can in some cases be sufficient to attract and hold the second device in place.

[0195] In the illustrated method, a total of seven devices 1, 1', 1" are delivered to the aneurysm, as shown in FIG. 1h. The magnetic force brings the seven devices 1, 1', 1" together inside the aneurysm A. A thrombus T grows and fills the entire aneurysm A. For added safety, the magnet M can be left in place until the thrombus T is fully formed.

[0196] FIG. 1i shows the final stage after completion of the treatment, where the aneurysm is filled by the devices 1, 1', 1'' and the thrombus T. The magnet M is therefore removed.

[0197] Figures 2a to 2d show a method for treating an aneurysm A using another embodiment of a device 1 according to the invention. The device 1 shown here comprises a filling element made of a thrombogenic material formed by beads 7 of polyacrylic acid with a diameter of 800 μm and coated with a protective coating 6. The protective coating is made of polyurethane with a polycarbonate skeleton with a thickness of 20 μm. The beads are attached to a magnetic element 4 via a release mechanism 3.

[0198] The release mechanism 3 comprises a magnesium alloy element which connects the filler element 7 with the magnetic element 4 .

[0199] FIG. 2a shows the delivery of the filling element 7 into the aneurysm A. The steps up to this stage substantially correspond to those shown in FIG. 1a and FIG. 1b. Due to the corrosion of the magnesium alloy, the release mechanism 3 dissolves spontaneously (optionally assisted by an electric current) in the aneurysm, releasing the thrombogenic bead 7 comprising an expanding bead with a 20 μm thick collagen coating as a thrombogenic agent. This method avoids the magnetic element 4 remaining inside the aneurysm A after the completion of the treatment. It is known in the art that magnesium alloys can have an adjustable corrosion rate. Thus, the corrosion rate can be configured such that substantial weakening and dissolution of the release mechanism 3 occurs only after the typical time required to reach the aneurysm A. In parallel with the dissolution of the release mechanism 3, the protective coating 6 arranged around the thrombogenic bead 7 dissolves due to contact with blood, resulting in the activation of the filling element.

[0200] 2b shows the expanding bead 10 after release from the magnetic element 4, dissolution of the protective coating 6, and withdrawal of the control wire and magnetic element 4. The use of a fixation element 8, for example in the form of a thrombin coating, provides attachment to the wall of the aneurysm to stabilize the device 1 within the aneurysm. A thrombus T begins to form around the expanding bead 10 due to stagnation of flow.

[0201] 2a and 2b may be repeated several times to deliver additional thrombus-forming beads 7 to aneurysm A, as shown in FIG. 2c. Repeats may be performed until complete occlusion of aneurysm A is achieved. The cyanoacrylate may also provide attachment to other expanding beads, allowing the expanding beads 7 to be aggregated by fixation elements 8. The formed thrombus T eventually fills the entire aneurysm A.

[0202] Optionally, after complete occlusion of the aneurysm A, the aneurysm can be further closed by a membrane 9 having a magnetic surface 9'. The magnetic surface 9' is advantageous because the membrane can be oriented and positioned using an external actuator (not shown) for optimal closure of the aneurysm. The membrane can adhere to the thrombus T. It will be appreciated that such a membrane 9 can be used in combination with any device or system disclosed herein to close the aneurysm.

[0203] Figures 3a to 3e show diagrammatically the principle of operation of an alternative embodiment of a device 1 similar to that shown in figure 2a. The device comprises an expanded bead 10 coated with a protective coating 6. The expanded bead is connected to a magnetic element 4 via a fixing element 3 substantially corresponding to the embodiment of figure 2a. The fixing element 3 is formed by a collagen layer with a thickness of 10 μm. Additionally or alternatively, a dry cyanoacrylate glue may be used.

[0204] FIG. 3 a shows the device 1 delivered to a treatment site within a blood vessel V. Figure 3b shows diagrammatically the dissolution of the protective coating 6 containing gold nanoparticles (not shown) by irradiation with visible light. The thickness of the protective coating 6 is 20 μm. Debris 6' resulting from the dissolution of the protective coating 6 is washed away by the blood flow. The delivery of light can be achieved via an optical fiber forming part of the control line and / or a light delivery catheter. The optical fiber may optionally pass through the magnetic element 4.

[0205] As shown in Figures 3c and 3d, the expanding bead 10 starts to swell upon exposure to blood and reaches a larger size over time. Its diameter can increase from 0.8 mm to 2.4 mm, i.e. three times. In parallel, dissolution of the fixing element 3 occurs due to corrosion of the magnesium alloy in the blood.

[0206] 3e shows the final stage where the expanding bead 10 has been released from the magnetic element 4 and control wire 2 and has reached its final size. Initial adhesion to the tissue wall may occur by natural thrombus formation, but may also be achieved by an adhesive composition or thrombus forming element as disclosed herein.

[0207] 4a-e show a schematic diagram of a method for occluding an aneurysm using a device 1 with a configurable wire 11. The device comprises a magnetic head portion 4 fixedly attached to a configurable wire made of Nitinol, having a diameter of 1.2 mm, containing Nd-Fe-B and having a diameter of 100 μm. Several expanding beads 10 are attached to the configurable wire 11 and coated with a protective coating. Before expansion, the expanding beads 10 have a diameter of 500 μm. Here, the expanding beads 6 are made of polyurethane foam and are further thrombogenic due to a thrombin coating (not shown) on their surface. The configurable wire in the illustrated embodiment is made of a shape memory alloy.

[0208] Figure 4a shows delivery of the device 1 into the aneurysm. Navigation and movement into the interior volume of the aneurysm can be performed substantially as shown in Figures la and lb. The configurable wire 11 has a straight configuration during delivery and upon entry into the aneurysm 11.

[0209] 4b shows a schematic of a configurable line 11 that spontaneously changes its structure from straight to spiral due to the shape memory effect. It will be understood that other structures are also possible, such as circular, zigzag, or curved. The release mechanism 3 starts to dissolve after the protective coating 6 disposed on the surface of the expanded bead is dissolved, and the expanded bead expands as a result. Here, the expanded bead 10 was compressed by the protective coating 6.

[0210] Figure 4c shows the device 1 after retrieval of the control line 2 following complete dissolution of the release mechanism 3. Upon exposure to blood and dissolution of the protective coating, the expanding beads expand spontaneously. Due to the thrombogenicity of the thrombin coating 10, a thrombus T begins to form.

[0211] In general, blood retention due to occlusion can contribute to thrombus formation. However, such thrombus formation is slow. The use of thrombogenic agents, such as thrombin, can contribute to the formation of thrombi that contain fibrin networks that provide favorable mechanical properties.

[0212] Figure 4d illustrates the delivery of a second device 1', delivered in substantially the same manner as described in the context of Figures 4a-4c.

[0213] FIG. 4e shows complete occlusion of the aneurysm after delivery of both devices 1, 1″ and complete formation of the thrombus.

[0214] FIG. 5a shows the device 1 with a configurable wire 11 inside the aneurysm. The configurable wire 11 in the illustrated embodiment is formed from a nylon multifilament string with a thickness of about 50 μm. For clarity, some features of the device have been omitted, in particular the control wires and the release mechanism. A person skilled in the art will understand that the induction of the illustrated embodiment may be performed in any manner disclosed herein. The device may be combined with any feature of the other disclosed embodiments, in particular the features of FIGS. 4a-4e. The device 1 comprises two polymer beads 10 made of polyacrylate with a diameter of 300 μm, which may be thrombogenic and / or expansible. Arranged in an alternating manner along the longitudinal axis of the configurable wire 11 are two magnetic beads 12 with a diameter of 300 μm. The magnetic beads 12 are made of Fe 3 O 4 The device 1 has a substantially linear configuration that allows convenient guidance to a treatment site A under magnetic guidance using an external magnet M. The magnetic beads 12 and polymer beads 10 are attached to a resin configurable wire 11.

[0215] Figure 5b shows the device 1 of Figure 5a after the configuration of the configurable lines 11 has changed to a substantially elliptical shape. The shape change in this example occurs because the two magnetic beads 12 are magnetically attracted to each other and to the magnetic element 4. As a result, the characteristic volume (e.g., as defined by the hydrodynamic radius) of the device 1 increases, better filling the aneurysm.

[0216] 6a-6c show how the device 1 can be positioned in a particular configuration for convenient treatment.

[0217] Figure 6a shows the first step of the method, in which a device is delivered to isolate a portion of the aneurysm A', thus inducing the formation of a thrombus in this portion (see Figure 6b). The devices are arranged as a substantially flat mass that occludes portion A' of the aneurysm A. The devices are arranged in a preferential orientation, and their accumulation causes the cessation of blood flow in portion A' of the aneurysm A. The change in flow velocity in the region of portion A' causes the formation of a thrombus.

[0218] FIG. 6b shows the formation of a thrombus T that completely occludes portion A'. A second portion A'' of the aneurysm remains unoccluded.

[0219] Thus, FIG. 6c shows the final step where further device 1' is delivered and released into portion A'' to complete the occlusion.

[0220] The method illustrated in Figures 6a-6c is advantageous because it requires less device to be delivered compared to completely filling the aneurysm with the device, resulting in a faster and more economical treatment.

[0221] Figures 7a to 7d show a further method for treating an aneurysm A with a device 1, 1' according to the invention. The device 1 comprises two expanding beads 10 with a protective coating 6, a magnetic element 4 and a release mechanism 3 connecting a first and a second part 2, 2' of a control line. The device 1 is explained in more detail in the context of figure 10e.

[0222] Figure 7a shows the first step where the device is guided into the aneurysm A using an external magnet M. When the protective coating 6 has dissolved, a release mechanism is activated to release the second portion of the control wire 2' in order to retrieve the first portion of the control wire 2.

[0223] FIG. 7 b shows the device 1 after recovery of the first portion of the control wire 2 and expansion of the expansion beads 10 after dissolution of the protective coating 6 .

[0224] Subsequently, a second device 1' is delivered to the same aneurysm A, as shown in FIG. 7c. The second device 1' is expanded and released substantially as described in the context of Figures 7a and 7b, resulting in a more complete filling of the aneurysm shown in Figure 7d.

[0225] Figures 8a to 8e show the treatment of a defect D in a blood vessel wall V with a device 1 according to the invention. The defect may be within an aneurysm.

[0226] FIG. 8a shows the device 1 being moved close to the vessel wall V. The device 1 may be held in place by a magnetic field induced by an external magnet (not shown). The protective coating 6 may be removed once the device 1 is in the vicinity of the defect D.

[0227] Figure 8b shows the device 1 after dissolution of the protective coating 6. The device 1 includes an anchoring coating 8 comprising collagen disposed radially outward of an 800 μm thick expansion coating 13 beneath an 80 μm thick protective coating 6. The anchoring coating provides attachment to the vessel wall through the formation of a thrombus T, as shown in Figure 8c.

[0228] 8d shows the device 1 after the expansion coating 13 and before the control line 2 has been detached from the remainder of the device 2 by the release mechanism 3. The expansion of the expansion coating 13 is caused by exposure to hydration (e.g., from blood) following dissolution of the protective coating 6.

[0229] In a further step, as shown in FIG. 8e, the release mechanism 3 separates the control wire 2 from the other parts of the device that remain to occlude the defect, namely the magnetic element 4, the expanding coating 13 and the fixed coating 8.

[0230] Figures 9a to 9e show a method for manufacturing the device 1 according to the invention. The device resulting from the illustrated manufacturing process is substantially similar to the device shown in the treatment method of Figures 8a to 8e.

[0231] In a first step, shown in Figure 9a, the magnetic part 4 is provided. The magnetic part 4 comprises a stump 4' that can serve as an extension for attaching control lines and / or a release mechanism (not shown here).

[0232] FIG. 9b shows the next step where the magnetic part 4 is coated with a coating 14 having a thickness of 5-15 μm to provide protection against corrosion.

[0233] FIG. 9c shows the device assembly 1 after the intumescent coating 13 has been applied. In a next step, a tie coating 8 is applied onto the expansion coating 13, as shown in FIG. 9d.

[0234] A protective coating 6 is then applied as shown in FIG. 9e. Figure 9f shows the final device 1 after the control lines 2 have been attached via release mechanisms 3 to other parts of the device shown in Figure 9e.

[0235] Fig. 10a shows a first embodiment of a device 1 according to the invention. The device comprises a control line 2, a magnetic part 4 and a release mechanism 3 connecting the control line 2 and the magnetic part 4 and allowing their selective separation. Furthermore, an expansion coating 13 is provided on the surface of the magnetic part 4. Furthermore, a protective coating 6 is provided. It will be appreciated that the protective coating is an optional feature, but may be particularly advantageous in devices 1 having expansion elements whose expansion is caused by contact with blood elements such as water or salts, or in devices 1 in which an anchoring element (not shown here) is embedded in the surface of the expansion coating 13.

[0236] The illustrated device is typically manufactured by providing a short length of control wire 2, which may have a length in the range of 0.2 mm to 20 mm, preferably about 0.5 mm, connected to the magnetic portion 4. The release mechanism 3 may be attached to the short portion of control wire 2 in one manufacturing step, preferably the last manufacturing step. In some embodiments, the release mechanism 3 is arranged to be located on the surface of the expansion element 13 after expansion. Thus, the short portion of control wire 2 that is initially used with the magnetic portion 4 is embedded in the expansion coating 13.

[0237] The magnetic part 4 can then be coated with an expanding polymer. The thickness of the expanding coating can range from 10 μm to 300 μm, preferably from 40 μm to 120 μm. A dip process can be used to apply the expanding coating 13. A surface treatment of the magnetic part 4 can be performed prior to dip coating (or other step of applying the expanding coating 13) to improve adhesion of the expanding material 13 and to prevent corrosion. Thereafter, if necessary, a fixing coating 8 can be placed on the surface of the expanding material 13. The expanding material is both expandable and contractible. The thickness of the fixing coating can range from 5 μm to 60 μm, preferably from 10 μm to 40 μm. Finally, a protective coating 6 can be applied.

[0238] Figure 10b shows a second embodiment of a device 1 according to the invention. The depicted device 1 is similar to the device of Figure 10a, but comprises a thrombogenic coating 5 instead of an expanding coating. The device 1 further comprises a control wire 2, a release mechanism configured to release at least the thrombogenic material 5 from the control wire 2, a magnetic element 4, and a protective coating 6 preventing premature contact between blood and the thrombogenic layer 5.

[0239] The illustrated device 1 would typically be manufactured in a manner substantially similar to that described in the context of the device of FIG. 10a, with the expanding polymer coating being replaced by a coating step with a thrombogenic material.

[0240] To improve the adhesion between the magnetic portion 4 and the thrombogenic coating 5, the surface of the magnetic portion 4 may be pretreated. For example, the surface of the magnetic portion may be functionalized with carboxylic acid groups that can covalently bind to thrombin. Thus, the magnetic portion 4 may be immersed in a thrombin solution at a concentration of 0.4 mg / mL for several hours, typically at least 5 hours. The magnetic portion 4 is then washed to remove unbound thrombin.

[0241] Fig. 10c shows a third embodiment of the device 1 according to the invention. The device 1 comprises a control line 2, a magnetic element 4, an expanding bead 10, a release mechanism 3 connecting the expanding bead 10 and the magnetic portion 4 and allowing one to be released from the other, and a protective coating 6 disposed on the expanding bead. Furthermore, the expanding bead 10 may be coated with a fixation element (8) to provide a more secure attachment at the treatment site after separation from the magnetic portion 4.

[0242] The illustrated device is typically manufactured by attaching a control wire 2 to a magnetic portion 4. Attachment can be accomplished, for example, by gluing, welding, molding, or melting. A release mechanism 3 is then connected to the magnetic portion 4. The release mechanism 3 is preferably positioned opposite the control wire 2, i.e., on top of the magnetic portion 4. An expanding bead 10 is then placed on the release mechanism 3.

[0243] Optionally, the expanded beads 10 may be coated with a fixing coating 8. The thickness of the fixing coating 8 may range from 10 μm to 150 μm, preferably from 20 μm to 50 μm. Alternatively, coating of the expanded beads 10 with the fixing coating 8 may be performed prior to assembling the expanded beads 10 with the release mechanism 3. This approach is advantageous in that it ensures that the entire surface of the expanded beads 10 is covered with the fixing coating 8. The expanded beads may be in an expanded or contracted state when coated with the fixing coating 8.

[0244] A protective coating 3 may then be coated over the release mechanism 3 , the magnetic element 4 , and / or the control wire 2 .

[0245] Figure 10d shows a fourth embodiment of a device 1 according to the invention. The device comprises a control wire 2, a magnetic element 4, a release mechanism 3, thrombogenic beads 14 and a protective coating 6. The device 1 can be manufactured in substantially the same way as described above in the context of Figure 10c, with the expanding beads being replaced by thrombogenic beads 14.

[0246] Fig. 10e shows a fifth embodiment of the device 1 according to the invention. The device 1 comprises a control wire 2, a magnetic element 4 and two expanding beads 10, 10'. A first expanding bead 10 is connected to the magnetic element 4 and a second expanding bead 10' is attached to a portion of the control wire 2'. A release mechanism 3 is arranged on the control wire 2 so as to release both expanding beads 10, 10' together with the magnetic element 4 and also the portion of the control wire 2' to which the second expanding bead 10' is connected. A protective coating is arranged around both expanding beads 10, 10'.

[0247] Optionally, at least one of the expanded beads 10, 10' may be coated with a fastening element (not shown).

[0248] It is contemplated that a first expanding bead 10 may be coated with a different protective coating 6 than a second expanding bead 10' in order to activate the expanding beads 10, 10' at different times. Such a design may be advantageous when further devices 1 are placed in the same cavity.

[0249] It is also conceivable that the first and second expanding beads 10, 10' comprise different materials having different expansion characteristics. For example, one bead 10, 10' may expand more or less at a different rate than the other. This may be advantageous in filling cavities having a complex shape. A complex shape may be understood as a shape lacking symmetry.

[0250] It may be advantageous if the first expanding bead 10 is positioned below the magnetic element 4, i.e. on the side facing away from an external magnet (not shown). Such a positioning facilitates interaction of the magnetic element 4 with a magnetic field generated by another magnetic element or an external magnet. For positioning and orientation in a particular way, the magnetic element 4 may be positioned with its north and south poles pointing in a particular direction, for example along the longitudinal axis of the device or perpendicular to the longitudinal axis of the device.

[0251] It will be appreciated that one or both of the expanding beads 10, 10' may be replaced with thrombogenic beads as shown in Figure 10d, which may accelerate occlusion due to further formation of thrombus (not shown).

[0252] The device 1 shown here is typically manufactured by providing a magnetic element 4 on a portion of a control line 2 (see FIG. 10a). A first expanding bead 10 is placed on the magnetic element 4, preferably on the opposite side of the control line 2 and / or a portion of the control line. Optionally, an electrical wire may be set on the surface of one or both expanding beads 10, 10', for example if necessary for the decomposition of a protective coating. A protective coating 6 is then placed on the expanding beads 10, 10'. A release mechanism 3 is then connected to the control line 2.

[0253] 10f shows a sixth embodiment of the device 1 according to the invention. The device comprises two expanding beads 10 connected by a linker 16 and coated with a fixing coating 8, forming a front expanding payload 15. Furthermore, the device 1 comprises a protective coating 6 around the front expanding payload 15, a control line 2, a magnetic element 4 and a release mechanism 3.

[0254] It will be appreciated that one or both of the expanding beads may be thrombogenic beads. The expanding beads may be arranged in a linear fashion, parallel or perpendicular to the axis of the device. Three expanding beads may be arranged in a triangular configuration.

[0255] The linker 16 provides an attachment between the expanded beads 10 so as to avoid the movement of one bead relative to another. The linker may comprise an elastic string that is stretched upon the expansion of the expanded beads 10. The diameter of the string may be between 30 μm and 200 μm, preferably between 50 μm and 100 μm. The rope is made of a metal, for example Nitinol, or of a polymer, such as polyamide. The string may be connected to the expanded beads by gluing. Furthermore, the linker may comprise a rod that extends at least partially inside the expanded bead 10 used. Additionally or alternatively, the linker may comprise an adhesive, for example a glue or a resin, that connects two expanded beads 10.

[0256] The front expanding payload 15 may be manufactured by connecting two expanding beads 10 together with a string acting as a linker. A fixing coating 8 is then applied to the expanding beads 10 by dip coating. After drying of the fixing coating 8, the first expanding bead is attached to the release mechanism 3. A protective coating 6, for example formed by a polymer film, is placed tightly covering the two expanding beads.

[0257] Figure 10g shows a seventh embodiment of the device 1 according to the invention. The device 1 shown here is substantially identical to the device shown in figure 10e, except that part of the control line 2' is replaced by a configurable line 1.

[0258] The configurable wire 11 can bend under the influence of a stimulus. The diameter of the configurable wire 11 may be between 30 μm and 200 μm, preferably between 50 μm and 100 μm. The configurable wire 11 comprises or consists of a metal and / or a polymer. For example, the configurable wire 11 may be made of Nitinol with a diameter of 100 μm. When a voltage is applied, the configurable wire 11 undergoes an increase in temperature and changes its shape, for example into a bent structure (see FIG. 5b). Alternatively, the configurable wire 11 changes into a spiral shape upon heating.

[0259] The configurable wire 11 may be connected to the electrical wire by low temperature welding, particularly if made of Nitinol. The electrical wire may have a diameter in the range of 30 μm to 70 μm. The release mechanism 3 may be arranged such that the welded electrical connection of the configurable wire 11 is broken down when the configurable wire is released.

[0260] Figure 10h shows an eighth embodiment of the device 1 according to the invention. The device shown here is substantially identical to the device shown in Figure 10g, but further comprises magnetic beads 12 for configuring the configurable line 11. The magnetic beads 12 are attached to the configurable line 11.

[0261] The magnetic beads 12 are configured to assist in changing the structure of the configurable wire 11 as shown in Figures 5a and 5b.

[0262] The configurable wire may exhibit a lower bending stiffness than the control wire, i.e. the Young's modulus of the configurable wire may be lower than the Young's modulus of the control wire 2. Preferably, the Young's modulus of the configurable wire 11 may be in the range of 0.5 GPa to 1 GPA, while the Young's modulus of the control wire may be in the range of 1.5 GPa to 2.5 GPa.

[0263] Additionally or alternatively, the bending stiffness of the configurable wire 11 may be reduced by reducing its cross-sectional area. For example, the diameter of the configurable wire may be 50 μm to 100 μm, while the diameter of the control wire 2 may be 100 μm to 250 μm. The bending stiffness may also be reduced by using a multifilament structure.

[0264] In some embodiments, a portion of the magnetic beads may be coated with a bioabsorbable layer to prevent attraction of the magnetic portions during induction. The bioabsorbable layer can increase the distance between different magnetic elements. Thus, the layer reduces undesired magnetic attraction. When degradation is initiated, a gradual reduction in thickness, preferably within the cavity, ensures a smooth and gradual change in the structure of the configurable line.

[0265] The bioabsorbable layer preferably comprises or consists of a polymer that degrades quickly. Fast degradation can be understood as complete degradation within 1 to 60 minutes, preferably within 2 to 10 minutes. In particular, polymers with low molecular weight, preferably 5,000 to 40,000 M w A bioabsorbable polymer such as PVA or PVP (Da) is used. The biodegradable layer may have a thickness of 10 μm to 500 μm, preferably 50 μm to 200 μm. Additionally or alternatively, the biodegradable layer may be covered with a protective coating that is removed at the treatment site.

[0266] Figure 11a shows an embodiment of a protective coating 6. Although a device is not shown, it will be understood that the protective layer shown can be combined with any device disclosed herein.

[0267] The protective coating 6 is not bioabsorbable and typically requires removal at a control line (not shown). The non-bioabsorbable protective coating 6, having a thickness of 10-100 μm, comprises or consists of silicone, polyurethane with a polycarbonate backbone, PDMS, and / or PTFE.

[0268] To open the coating and expose its interior (i.e. the filling element during treatment) to physiological fluids, the protective coating comprises a disruption system 17. The disruption system 17 is configured to be opened or disassembled, thus resulting in an opening in the protective coating 6. An attachment mechanism 18 is connected or connectable to the control line 2. Thus, the protective coating 18 can be retrieved together with the control line.

[0269] The destruction system 17 can include a degradable material. The degradable material can be a biocorrodible material (e.g., magnesium or a magnesium alloy), a bioabsorbable polymer, and / or a magnetic biodegradable composite. As previously described herein, magnesium alloys can corrode faster when a voltage is applied due to galvanic corrosion.

[0270] The magnetic biodegradable composite material is Fe 2 O 3 or Fe 3 O 4 and may be embedded in a bioabsorbable matrix. The matrix may be degradable by hyperthermia. Magnetic composites are advantageous because they may improve attachment between the disruption system and the magnetic elements of the device.

[0271] Additionally, the destruction system may include or be composed of a bioabsorbable polymer as a matrix containing the magnesium particles.

[0272] In some embodiments, the protective coating 6 is crimped onto an element that is at least partially biodegradable. For example, the protective coating 6 may be crimped onto a cylinder that includes a bioabsorbable portion and exhibits a rupture system 17. Once the bioabsorbable portion is degraded, blood flow enters and hydrates the expansion material.

[0273] Figure 11b shows an embodiment of a biodegradable material that can be used for either the protective layer and / or the release mechanism. The material comprises a biodegradable polymer 19 as a matrix in which nanoparticles 20 are loaded. The polymer can have a low decomposition temperature of 40-60°C. The nanoparticles can be made of gold, Fe 2 O 3 , Fe 3 O 4 , and / or silver. Thus, the biodegradable polymer can be degraded by heat generated by the nanoparticles under stimuli such as light and / or a magnetic field 21.

[0274] Figure 12a shows an embodiment of the device having a non-biodegradable protective layer 6 substantially similar to the embodiment of Figure 11a. The protective layer is crimped onto a degradable element 18. A ring 18 onto which the protective layer 6 is also crimped provides attachment to the control wire 2.

[0275] It is also conceivable that the protective layer comprises areas of reduced mechanical strength as disruptive elements 16. Mechanical stress can be applied to these areas, leading to their rupture and the ingress of blood flow.

[0276] A low mechanical strength can be achieved by reducing the thickness of the material, for example the protective layer may be about 200 μm thick, while the disruptive element may have a low thickness of about 70 μm.

[0277] Additionally or alternatively, the material of the protective layer may be pre-stretched to induce stress in the material, for example to form a fracture element.

[0278] The destruction of the destruction element by applying a force to the protective layer may be accomplished by the expansion of an expanding material, for example, an expanding bead made of foam that can be activated by injecting saline through a control line.

[0279] The disruptive element may, for example, comprise a metallic element that can be heated to locally disrupt the protective coating.

[0280] FIG. 13a shows diagrammatically a protective coating 6 having exactly one destruction system 17 which results in a localized destruction.

[0281] In another embodiment, as shown in FIG. 13b, there are multiple disruption systems 17, disrupting the protective coating 6 into multiple parts.

[0282] FIG. 13c shows a degradable protective coating that provides a slow and gradual ingress of blood at a substantially uniform rate across the entire surface.

[0283] Figure 14 shows an embodiment of the device 1 with a protective coating 6 that breaks under mechanical pressure. The protective coating is configured to break at two breaking points 22, 22'. The mechanical pressure can be achieved by two plates (made of a metal such as stainless steel or a polymer such as PTFE) that are actuated by two rods connected to a release system. The plates have a thickness of 50 μm and a length and width of 100 x 50 μm. The rods are metal rods (nitinol) with a diameter of 50 μm and are actuated by an electric current.

[0284] FIG. 15 illustrates a further embodiment of a protective coating 6 that fails at a failure point 22 due to localized shrinkage in an area 23 opposite the failure point 22 .

[0285] FIG. 16 illustrates another embodiment of a protective coating 6 that fails due to the presence of a localized defect 24 in the protective coating material, which may be triggered by any of the stimuli and / or mechanical stresses disclosed herein.

[0286] 17 shows an embodiment of the protective coating 6 having two disruption systems 17, 17' that can degrade spontaneously or under the influence of light, electricity, ionic solutions, and / or mechanical stress. One disruption system 17, 17' also forms a release mechanism, allowing the device 1 to separate from the control line. The remaining part of the protective coating 6, which comprises a bioabsorbable polymer, can be washed away by blood.

[0287] 18 shows an embodiment of a protective coating 6 that comprises an activatable polymer having a thickness of 10-50 μm and that degrades under the influence of light, electricity, ionic solutions, and / or mechanical stress. Thus, the protective coating 6 degrades into fragments that may be washed away by blood.

[0288] Fig. 19 shows a further embodiment of the device 1 according to the invention. The device is similar to the device shown in Fig. 10g. The device 1 further comprises a rod 25 and a foam neck 26. The rod 25 can connect two different expansion elements. For example, two different expansion materials can be integrated into one expansion bead 10 and connected by a rod 25 to provide different expansion rates. The rod can comprise or be made of stainless steel and can have a diameter of 100 μm and a length of 700 μm. Additionally or alternatively, the shape of the first expansion element can be substantially spherical, while the second expansion and the second expansion elements have a substantially elliptical shape.

[0289] FIG. 20a shows the device 1 having a frame 28 disposed within the expandable bead 10. The frame 28 can be heated when an electric current passes through it, resulting in the expansion of the expandable bead 10. The device 1 further comprises a releasable bullet 27. Additionally or alternatively, the frame 28 increases the stiffness of the expansion material, i.e. the expanding bead 10, to resist compression. For example, the compression can be caused by physiological fluids. The frame 28 can include or be made of Nitinol. The thickness of one arm can be between 20 μm and 500 μm, preferably between 70 μm and 150 μm.

[0290] FIG. 20b shows the device of FIG. 20a as it treats the aneurysm and forms a thrombus during gradual deployment.

[0291] 21 shows an expansion material integrated into a frame having a complex shape, such as an octahedron. Preferably, the expansion material is coated onto the arms of the frame 28. The thickness of one arm may be 20 μm to 500 μm, preferably 70 μm to 150 μm.

[0292] In some embodiments, the expansion material may be integrated into the crimped frame. The crimped frame may have a stent-like shape and be expandable. The crimped frame may be coated with the expansion material, for example, in a layer or as a fabric. Additionally, the crimped frame may be used to break the protective coating by applying inward forces and tensions to the protective coating as described above.

[0293] It is also conceivable that the frame comprises selective parts that can be individually actuated. This design allows the frame to open in a specific user-defined shape that can be adapted to the geometry of the cavity to be occluded. For example, each crimped frame part may be connected to an individual electrical wire. Thus, the frame elements selectively expand when a current is applied to the corresponding element.

[0294] FIG. 22 shows the basic principle of the device 1 with thrombogenic fibers 29 as filling elements. The fibers may be made of a thrombogenic material or may be made of a polymer coated with a thrombogenic material, in particular collagen or latex. The fibers may have a diameter of 0.1 to 500 μm, preferably 10 to 80 μm. Here, the fibers comprise PLGA with a diameter of 20 μm and are coated with collagen. Other suitable coating materials are thrombin and fibrin. The fibers may be dried. When exposed to blood, the thrombogenic fibers cause the formation of a thrombus T around the device 1.

[0295] Figures 23a-d show various embodiments of thrombogenic elements on the device. All devices 1 shown herein include a protective coating 6, which may be any protective coating disclosed herein. It will be understood that the conceptual depiction of device 1 herein may be supplemented by any compatible features disclosed herein.

[0296] Figure 23a shows a device with a thrombogenic material 5 grafted onto the surface of the device. The thrombogenic material 5 may be an enzyme, a protein, a polymer and / or a metal.

[0297] In general, any substance or material that can cause blood clotting and / or platelet activation may be a suitable thrombogenic material.

[0298] For example, biological elements such as collagen, thrombin, von Willebrand factor (vWF), laminin, thrombospondin, vitronectin, fibrinogen, or thromboxane A2 may be used. Thrombin is an enzyme that converts fibrinogen to fibrin through cleavage of fibrinopeptide A. The formed fibrin network can trap red blood cells and platelets, resulting in the formation of a thrombus.

[0299] Polymers may also have a thrombogenic effect. Suitable polymers are PET, PEU-PEO, and / or latex. Coatings of such polymers may be formed by dip coating, spraying, and / or chemical vapor deposition.

[0300] Metals that induce a thrombogenic effect can include titanium, indium, and / or tantalum. The metals can be deposited by CVD, plasma spray, and / or physical vapor deposition.

[0301] Figure 23b shows an embodiment of the device 1 with a thrombogenic element 5, where the thrombogenic effect is due to the shape of the material. The thrombogenic element may therefore be made of any suitable material. It will be appreciated that further thrombogenic materials may be used to enhance thrombogenicity.

[0302] The shape is configured to induce red blood cell hemolysis and thus platelet activation leading to the formation of thrombi, for example grooves with a height of 100 μm to 300 μm. Preferably, a hydrophobic surface is used to increase protein and platelet adhesion.

[0303] Figure 23c shows an embodiment of the device 1 having thrombogenic fibers 29 made of a thrombogenic material. The fibers are deployable upon hydration. The fibers 29 may be attached to the device by grafting, spraying, and / or electrospinning.

[0304] Figure 23c shows an embodiment of the device 1 with thrombogenic fibres 29 which are further coated with a thrombogenic element, in this example thrombin. Such a design is particularly advantageous in that it contributes to retaining the formed thrombus around the device 1. The fibres generally provide an enhanced thrombogenic effect. The fibre diameter may be in the range of 50 nm to 50 μm, preferably between 800 nm to 3 μm.

[0305] FIG. 24 shows an embodiment of the device 1 according to the invention. The device 1 comprises a control line 2 to which is attached a flexible shell 30 closed by a plug 31. The control line 2 comprises a multifilament nylon (diameter 200 μm) with two electric wires (diameter 20 μm) connected to the plug 31. The flexible shell has a thickness of 20 μm and comprises polyurethane. The flexible shell comprises a breaking point with a reduced thickness of 10 μm. The plug 31 is made of a magnesium alloy and is degradable by corrosion upon application of an electric current. In order to adjust the structure of a configurable line (not shown) to which the expanding beads can be attached, a magnetic bead 12 comprising Nd-Fe-B and having a diameter of 1 mm is accommodated in the flexible shell 30. Inside the flexible shell 30, the device 1 comprises a magnetic element for guidance / guidance in the vasculature. Furthermore, three expanding beads 10 with diameters of 400 μm, 500 μm and 600 μm respectively are arranged inside the flexible shell. After degradation of the plug 31, hydration from exposure to blood can cause the expansion beads 10 to expand. 3 O 4 An additional magnetic section with a diameter of 300 μm made of 1000 μm can be used to orient the expanding beads inside the aneurysm. The flexible shell may be made by melting.

[0306] Figure 25a shows the device 1 of Figure 24 after it has been navigated into the aneurysm under magnetic guidance by an external magnet M. Before retrieving the control wire 2, the plug 31 is removed. As a result, the expanding beads become hydrated by exposure to blood.

[0307] Figure 25b shows three expanding beads connected via a configurable line (not visible). At the end of each of the configurable lines there is a magnetic portion formed by a magnetic bead 12 and a magnetic element 4, which ensures a compact overall shape. It will be understood that the order shown here (magnetic element 4, expanding bead 10, magnetic bead 12) is of an exemplary nature and can be changed to any other order without departing from the spirit of the invention.

[0308] Figure 26a shows an embodiment having self-expanding fibers 29. The fibers 29 may include or consist of a self-expanding material, such as a superabsorbent polymer. Additionally or alternatively, the fibers may have a core-shell structure. The thrombogenic material is preferably located within the shell.

[0309] Figure 26b shows the device of Figure 26a after the fibres have self-expanded, resulting in an increase in the hydrodynamic radius R of the device 1.

[0310] 27 shows diagrammatically a method for manufacturing a device 1 according to the invention. A magnetic element 4 is provided and swellable thrombogenic fibres 29 are attached to its surface. The fibres 29 are allowed to swell, for example in saline, and then dried, resulting in a thrombogenic layer 5. A protective coating 6 is provided on the thrombogenic layer 5.

[0311] Control lines may be added to the device at any time. Some embodiments may be configured to increase the blood temperature surrounding the device. For example, a metal piece is placed on the distal portion of the magnetic element. The metal piece may be heated by application of an electric current. Additionally or alternatively, the metal piece may be heated by hyperthermia and / or exposure to electromagnetic radiation or ultrasound. In the case of hyperthermia, the element may be made of superparamagnetic nanoparticles.

[0312] These devices are particularly advantageous since the thrombogenic effect is caused solely by an increase in temperature, thereby allowing the omission of protective coatings.

[0313] In general, it will be understood that any expansion element shown herein can be replaced with a thrombogenic element, and vice versa.

[0314] FIG. 28a shows one embodiment of a control line driver 60. The control line driver 60 comprises an electric motor 62. For clarity, the connection to the control unit (see FIG. 30) has been omitted. It will be understood that the control unit may be connected to the control line driver 60 by any means known in the art, such as a cable or a wireless connection (Bluetooth, Wi-Fi, infrared port, etc.). The control line driver 60 further comprises an axle 61 operably connected to the electric motor 62. The axle is configured to receive the control line 2, and the control line 2 can be wrapped around the axle 61. Rotation of the axle 61 releases or retracts the control line 2. The control line driver 60 further comprises a clamp 63. Here, the clamp 63 is shown in an open state, allowing the control line 2 to move freely through the clamp. Thus, the release, stop, or retraction of the control line 2 is controlled solely by the axle 61. The position of the medical device is controllable by the control line driver 60 and the axle 61 via the movement of the control line 2.

[0315] FIG. 28b illustrates the control line driver 60 of FIG. 1a with the clamp 63 shown in a closed configuration. This allows the control line 2 to be stopped and held independent of the movement of the axle 61. For example, the medical device 1 can be temporarily held and secured without using power to the electric motor 62. Additionally, closing the clamp 63 to hold the control line 2 can be advantageous to secure the medical device 1 via the control line in the event of a malfunction of the control line driver 60. However, the clamp 64 may be used to stop and / or hold the control line 2 at any time and for any reason.

[0316] Figure 29 shows a medical device 1 guided by a system according to the invention. The medical device 1 comprises a control line 2 which exerts a third force F3 on the medical device in addition to the drag force F2 of the blood and the magnetic force F1. As the system detects the drag force F2, it can set, via a control unit (see Figure 9), the pullback force F3 and the magnetic force F1 in balance, such that the total force acting on the medical device 1 moves it to a second position and then to a third position in the direction of the target area G.

[0317] 30 shows a system 100 according to the present invention. Moreover, the system 100 shown here further comprises an imaging system 110. The imaging system may in particular be an ultrasound imaging system, a Doppler ultrasound imaging system, an X-ray fluoroscope, a PET scanner, a CT scanner, an MRI system, or any other imaging system known in the art.

[0318] 31 shows a schematic representation of a force balance model that can be used in devices and systems according to the invention. A medical device 1 including a control line 2 is shown in a blood vessel. The forces acting on the medical device 1 are: -Fluid force F d -Gravity F g -Adhesion F adh -Friction force F f -Normal contact force on the surface F n -Magnetic force F ext - Force F applied by control line 2 line Fluid force F d , gravity F g , and adhesion force F adh , frictional force F f , as well as the normal contact force F n is the force that occurs inherently when the medical device 1 is immersed in the bloodstream. ext and the force F exerted by control line 2 line is artificially influenced and controlled by the system according to the invention.

[0319] The combination of the various forces mentioned above determines the velocity vector (direction and magnitude) and therefore the movement of the medical device 1 within the blood vessel V.

[0320] The motion of the medical device 1 is calculated according to the following equation (where m is the mass of the medical device and v r where is its speed).

[0321]

number

[0322] The purpose of force balance is to determine the necessary forces that the system should exert in combination with the naturally occurring forces to produce a suitable velocity vector to move the medical device 1 along a predetermined trajectory.

[0323] In particular, the balance of forces as described above allows the medical device 1 to stop, retract, branch, and / or steer in low flow vessels.

[0324] The various forces may be predetermined, estimated, directly measured, indirectly measured, or ignored.

[0325] To illustrate the above, two exemplary calculations using the above model are shown. Two sizes of medical devices (1.2 mm and 0.6 mm) are modeled for two different branches (internal carotid artery segment 1 (hereinafter, ICA1-R) to internal carotid artery segment 2 (hereinafter, ICA2); and ICA2 to anterior cerebral artery segment 1 (hereinafter, ACA1)).

[0326] For a medical device 1 having a size of 1.2 mm, a diameter of 400 cm is required to pass through the bifurcation from ICA1-R to ICA2. 3 The magnetic actuator, which has a volume of 2.9·10 -6 It is thought that a magnetic force of 8.9·10 N is required to pass through the branch from ICA2 to ACA1. -5 A force of N and a distance of 17 cm are required.

[0327] A similar calculation for a medical device 1 with a size of 0.6 mm yields 3.7·10 -6 N (ICA1-R to ICA2) and 5.4·10 at 10 cm distance -5 Resulting in N(ICA2 to ACA1).

[0328] The above equation allows for an estimation of the acceleration (ie, velocity fluctuation) of the medical device incorporating various forces acting on the medical device.

[0329] Typically, all forces acting on the device 1 are determined by the force F of the control line 2. line Therefore, the force balance equations can be solved in one of two ways:

[0330] Estimating the force exerted by the control line 2 and calculating the acceleration of the medical device 1; Determine the acceleration of the medical device and calculate the resulting force exerted by control line 2.

[0331] There is an equivalence between the acceleration of the medical device 1 and the force exerted by the control wire 2. It is possible to determine the force exerted by the control wire 2 from the acceleration of the medical device 1 or to determine the acceleration of the medical device 1 from the force exerted by the control wire 2.

[0332] For example, in one configuration of the system, the velocity or acceleration of the medical device can be controlled by controlling the rate of release of control wire 2 by a control wire driver (not shown). The force exerted by control wire 2 can be determined from the velocity / acceleration of the medical device.

[0333] Fig. 32 shows diagrammatically the treatment of aneurysm A with thrombogenic filling elements 7. A device (not shown) was used for autonomous navigation to the aneurysm A in this case. The autonomous navigation is achieved by a navigation system that adjusts the force applied to the device to follow a target trajectory. The forces to be balanced are in particular the magnetic force exerted by the external magnet, the drag force due to the blood in the vessels, and gravity.

[0334] In panel A, a first filling element 105 corresponding to the distal part of the device (not shown, see Figs. 33a-33d) is shown inside the aneurysm A. The filling element 105 is both thrombogenic and inflatable, and is shown here after being released from the proximal part of the device and inflated. A thrombus T has formed due to the thrombogenicity of the filling element 105, providing attachment of the thrombus T to the wall of the aneurysm. Panels B-F diagrammatically show the progressive filling of the aneurysm A with further filling elements 105, which are here identical. However, it will be understood that in some circumstances it may be advantageous to use filling elements of different types. Eventually, as shown in panel F, the entire volume of the aneurysm A is filled with the filling element 105 and the thrombus T.

[0335] FIG. 33 shows a schematic representation of an embodiment of the device 1 according to another embodiment. The device 1 comprises a control line 2 incorporating an electric wire 106. A magnetic portion 4 is attached to the control line 2 and forms the proximal portion of the device 1. A combination thrombus formation and expansion element 105, which forms the distal portion, is attached to the proximal portion by a release mechanism 3 operatively connected to the electric wire 106, which is activatable by the electric wire. This avoids the magnetic element 4 being left permanently in the aneurysm A, since it is removable. The release mechanism 3 is biodegradable when an electric current is applied by the electric wire 106. The filling element 105 is adapted to swell upon hydration and thus self-expands when exposed to blood. The use of an expansion element allows the size of the filling element to be reduced for induction. A protective shell 6 is arranged around the magnetic portion 4 and the filling element 105. Here, an activation mechanism 101 is shown that can be used to selectively open the protective shell 6 to avoid premature activation of the function of the filling element. The activation element 101 here comprises a MEMS that can be activated by an electric current delivered by a wire 106. The protective shell 6 is removable by breaking the shell 6 and pulling it back by the activation element 101. Breaking of the shell 6 is achieved in the distal part (typically in the vicinity of the fixed coating 100; see below) forming a destruction zone. The thickness of the destruction zone is smaller than the general thickness of the shell 6. Here, the thickness of the destruction zone is 70 μm and that of the shell 6 is 200 μm. Alternatively, the shell 6 may be removed using an electrical stimulus generated by an activation system embedded in the distal part of the device 1. Furthermore, a fixed coating 100 is attached to the most distal part of the filling element 105, inside the protective shell 6. The fixed coating provides thrombogenicity in this example and can provide attachment to the vessel wall, thus ensuring that the filling element 105 does not flow out of the aneurysm A. Here, the fixed coating 100 comprises collagen.Additionally or alternatively, the fixative coating 100 may include or consist of thrombin, von Willebrand factor (vWF), laminin, thrombospondin, vitronectin, fibrinogen, thromboxane A2, or any combination thereof. The thrombus T further fills the aneurysm, reducing the required volume of the filling element 105. The fixative coating 100 has a thrombin concentration of 600 NTH U / ml, thus causing the formation of a thrombus T with approximately 60% fibrin content, which provides advantageous mechanical properties of the thrombus, such as less compaction.

[0336] FIG. 34a shows the device 1 of FIG. 33 that can be used to deliver a filling element 105 to an aneurysm (not shown). The device 1 comprises a distal portion made up of a filling element 105 and a proximal portion comprising a magnetic portion 4 and a control wire 2. The filling element 105 is attached to the magnetic portion 4 by a release mechanism 3 and has both expandability and thrombogenicity, i.e. it combines a thrombogenic element with an expanding element. The thrombogenicity is provided by a fixed coating 100. A protective shell 6 is arranged to surround the magnetic element 4 and the filling element 105. The fixed coating 100 is now arranged outside the protective shell 6, since the protective shell 6 has been partially or fully activated to release the fixed coating 100. As shown here, the device 1 may be delivered to the aneurysm. The protective shell 6 starts to dissolve after contact with blood. Alternatively, the shell may be removed by any mechanism described herein, in particular by mechanical or electrical stimulation.

[0337] Figure 34b shows the device 1 in the position of Figure 34a, where the filling element 105 has expanded due to exposure to blood. At the same time, a thrombus T begins to form, resulting in attachment to the vessel wall and allowing the release of the release mechanism 3 by the electrical current supplied by the cable in the control line 2.

[0338] Figure 34c illustrates retraction of the proximal portion of device 1 due to tension applied to control line 2 after release of the biodegradation release mechanism. The resulting configuration of filling element 105 when inside an aneurysm (not shown) may substantially correspond to panel A of Figure 32 shown above.

[0339] Figures 35a-d show diagrammatically various design options for the distal portion of the device 1. All devices 1 shown here have a control wire 2 and a magnetic portion 4 forming a proximal portion, which for clarity will not be described separately hereinafter. Furthermore, for clarity, a release mechanism is not shown, but may be any release mechanism disclosed herein.

[0340] FIG. 35 a shows the device 1 having an expanding element 105 and a anchoring coating 100 that form the distal portion of the device 1 .

[0341] FIG. 35 b shows an example of a device 1 in which the distal portion comprises a thrombogenic element 7 . FIG. 35 c shows an example of a device 1 in which the distal portion comprises an expansion element 10 .

[0342] 35d shows another embodiment in which the distal portion of the device comprises an expansion element 10 attached to a magnetic portion 4 and a thrombus forming element attached distal to the expansion element 10. A release mechanism (not shown) may be disposed between the expansion element and the magnetic portion 4 or between the control wire 2 and the magnetic portion 4.

[0343] FIG. 36a shows an embodiment of the device 1 similar to the device 1 of FIG. 33 and FIG. 34a-c. For clarity, identical features will not be described again, but it will be understood that any functions and features mentioned above in this context may also be present in the device of FIG. 36a. Here, the device 1 further comprises a second release mechanism 107, 107'. The second release mechanism comprises attachment points 104, 104' attached to the magnetic portion 4 and connected to the sutures 102, 102'. The sutures 102, 102' are attached to the filling element 105' by second attachment points 103, 103'. The sutures 102, 102' are configured to temporarily hold the filling element 105 after the release of the first release mechanism (not shown, see reference number 3 in FIG. 33). Thus, after the initial removal of the filling element 105, the proximal part of the device 1 is returned by the control line 2. The position of the filling element 105 may be imaged to confirm that the filling element is indeed attached to the vessel wall.

[0344] Figure 36b shows the final release of the filler element 105 by dissolution of the attachment points 104, 104' (not shown; see Figure 36a). To this end, the attachment points comprise a magnesium alloy which decomposes when an electric current is applied. Alternatively, an iron-based alloy may be used.

Claims

1. A device (1) for the treatment of a blood vessel (V), preferably an aneurysm (A), in particular a cerebrovascular or aortic aneurysm (A) in a patient, comprising: a filling element (5, 7, 10, 13, 14, 15, 29), preferably an expanding element (10, 13, 15) and / or a thrombus-forming element (5, 7, 14, 29), particularly preferably an activatable filling element (5, 7, 10, 13, 14, 15, 29), a magnetic element (4), - control line (2), - Release mechanism (3) and Equipped with the release mechanism (3) is configured to release the magnetic element (4) and / or the filler element (5, 7, 10, 13, 14, 15, 29) to separate them from the control line (2); said magnetic element (4) being configured to be guided by an external actuator (M) to guide at least said filling element (5, 7, 10, 13, 14, 15, 29) along a vascular path (V); said filling element (5, 7, 10, 13, 14, 15, 29) being configured to reduce the volume of said vessel portion (V) when placed in the vessel (V) to be treated, preferably after activation by an activation mechanism; The control line (2) is configured to be loosened or pulled to position the device.

2. 2. The device according to claim 1, wherein the filler element (5, 7, 10, 13, 14, 15, 29) is at least partly attached to, attachable to or formed by the magnetic element (4).

3. 2. The device of claim 1, wherein the filling element (5, 7, 10, 13, 14, 15, 29) comprises at least one of a thrombogenic shape, a thrombogenic material, and a thrombogenic agent.

4. 2. The device according to claim 1, wherein the filler element (5, 7, 10, 13, 14, 15, 29) comprises at least one defined shape that is at least partially curved, preferably at least a first and a second defined shape.

5. Configurable Line (11) Furthermore, 2. The device according to claim 1, wherein the configurable wire (11) preferably forms a connection between the filler element (5, 7, 10, 13, 14, 15, 29) and the magnetic element (4).

6. 6. The apparatus of claim 5, wherein the configurable line (11) is configured to be formed into a predetermined configuration.

7. 2. The device of claim 1, wherein the filling element (5, 7, 10, 13, 14, 15, 29) comprises a compressed foam (26) configured to expand to a post-expansion shape, the post-expansion shape substantially corresponding to the shape of the aneurysm (A).

8. Protective Coating (6) further comprising, particularly as part of the activation mechanism, 2. The device according to claim 1, wherein the protective coating (6) is preferably arranged radially outside the filler elements (5, 7, 10, 13, 14, 15, 29).

9. 2. The device according to claim 1, wherein the filler elements (5, 7, 10, 13, 14, 15, 29) are arranged radially outside the magnetic element (4).

10. 2. The device of claim 1, wherein the release mechanism (3) is disposed between the control line (2) and at least one or two or all of the filler element (5, 7, 10, 13, 14, 15, 29), the magnetic element (4), and the activation mechanism.

11. a fixation element configured to provide adhesion between at least a portion of the device and a blood vessel wall and / or a blood clot; The apparatus of claim 1 further comprising:

12. 1. A system for the treatment of a blood vessel (V), preferably an aneurysm (A), in particular a cerebrovascular or aortic aneurysm (A) in a patient, comprising: A device according to any one of claims 1 to 10, The system further comprises at least one control line driver, a magnetic actuator (M), and a control unit.

13. 13. The system of claim 12, wherein the magnetic actuator (M) is configured to generate a preferably predetermined magnetic field, preferably at a predetermined position, in order to steer the device (1), preferably in a predetermined direction, and wherein the control unit is configured to balance, particularly in real time, at least three forces acting on the medical device, preferably including at least one of a flow drag force, a force from the control line (2), and a magnetic force by the magnetic actuator (M), and to operate the magnetic actuator (M) and / or the control line driver.

14. A method for treating a blood vessel (V), preferably an aneurysm (A), in particular a cerebral or aortic aneurysm (A) of a patient, using a magnetically guideable medical device (1), preferably a device (1) according to any one of claims 1 to 10, comprising: - magnetically guiding said medical device (1) through the vasculature (V) to a target site, preferably an aneurysm (A); - activating said filling element (5, 7, 10, 13, 14, 15, 29), preferably to expand said filling element (5, 7, 10, 13, 14, 15, 29) and / or to trigger a thrombus-forming action; - releasing at least a part of said medical device (1), preferably a magnetic element (4) and / or said filling element (5, 7, 10, 13, 14, 15, 29), at said target site.

15. 15. The method of claim 14, wherein said steps of said method are repeated at least once, preferably twice.

Images