FUNCTION MARKER ELEMENT AND METHOD FOR PRODUCTION THEREOF

Abstract

A marker element for an implant is made from a planar or hollow body-shaped semi-finished product. The semi-finished product is subjected to a plasma-electrolytic treatment on one side, so that a marker element with a surface that is porous on one side is produced.

Claims

1. A method for producing a marker element for an implant, the method comprising: providing a planar or hollow body-shaped semi-finished product consisting of a material of the marker element; cutting out at least one portion from the semi-finished product, in such a way that the portion remains connected via at least one web to a remaining material of the semi-finished product; with the portion still connected to the semi-finished product via the at least one web: covering a first surface of the portion; and subsequently performing plasma electrolytic treatment of a second surface of the portion that is different from the first surface, and thereby forming a porous layer at least on the second surface of the portion by the plasma electrolytic treatment; and separating the portion by severing the at least one web, wherein the separated portion of the semi-finished product forms the marker element.

2. The method according to claim 1, which comprises performing the plasma electrolytic treatment at a maximum bath voltage of more than 180 V with a pulsed voltage source that is electrically conductively connected to the semi-finished product.

3. The method according to claim 1, which comprises forming porous layer also at least in part on a side face of the cut-out portion transverse to the second surface by way of the plasma electrolytic treatment.

4. The method according to claim 1, which comprises subjecting the semi-finished product, in a region of the cut-out portion, to a pickling treatment with an acid prior to covering the first surface of the portion.

5. The method according to claim 1, which comprises, after the plasma electrolytic treatment, firstly immersing the semi-finished product, in a region of the at least one cut-out portion, in a solution comprising a crosslinker and subsequently immersing in a mixture comprising at least one material selected from the group consisting of proteins, further growth factors, enzymes, antibodies and peptides.

6. The method according to claim 1, which comprises immobilizing an organic compound or an inorganic compound capable of elution in a pore structure of the porous layer.

7. A method for producing a framework with a marker element for an implant, the method comprising: producing the marker element by the method according to claim 1; producing a framework for supporting the marker element; introducing the separated portion of the semi-finished product forming the marker element into an opening of the framework and gluing the marker element into the opening.

8. The method according to claim 7, wherein the gluing step comprises applying a polymer solution to the marker element separated from the semi-finished product, applying the polymer solution by pressing in and/or filling the gap between the marker element and an opposite edge of the opening of the framework, and subsequently curing the polymer solution.

9. The method according to claim 7, which comprises providing the framework, at least in a predefined region, with a coating containing a pharmaceutically active substance, prior to the step of gluing the marker element.

10. The method according to claim 7, which comprises providing the framework, at least in a predefined region, with a coating containing a pharmaceutically active substance, after to the step of gluing the marker element.

11. A disc-shaped marker element for an implant, the marker element comprising: a bottom face forming a first surface; a top face forming a second surface; and at least one side face connecting said bottom face and said top face; said top face forming an abluminal face once the marker element has been secured to a framework of the implant; and a porous layer generated by plasma electrolytic treatment covering said top face at least in part.

12. The marker element according to claim 11, wherein said at least one side face is also covered by said porous layer.

13. The marker element according to claim 11, wherein said porous layer is formed with pores having a mean pore diameter between 0.1 m and 2 m and/or a layer thickness between 0.3 m and 10 m.

14. The marker element according to claim 13, wherein said porous layer has a layer thickness between 0.5 m and 4 m.

15. The marker element according to claim 11, wherein said bottom face is formed with a groove-shaped pickling structure.

16. A framework for an implant, comprising a marker element according to claim 11, said marker element being glued into an opening of the framework and a top face of said marker element forming an abluminal face.

17. An implant, comprising a framework formed with an opening, and a marker element according to claim 14 glued into said opening of said framework, with a top face of said marker element forming an abluminal face of the implant.

Description

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

[0073] FIG. 1 is a plan view from above of a portion of a framework of an implant;

[0074] FIG. 2 is a plan view from above of a marker element;

[0075] FIG. 3A and 3B are images recorded by scanning electron microscopy of the outer side (FIG. 3A) and the inner side (FIG. 3B) of a region of a hollow-cylindrical semi-finished product with multiple portions for marker elements following removal of the slag residues and any impurities, in each case in a view from the side in question;

[0076] FIG. 4 illustrates an inner side of the region of the hollow-cylindrical semi-finished product according to FIG. 3B with a portion for a marker element after the pickling step in an image from the side recorded by light microscopy;

[0077] FIG. 5A-5C are images recorded by scanning electron microscopy from above and in different magnifications of regions of an abluminal top face of a marker element after the plasma electrolytic treatment in various magnifications, wherein FIG. 5B and 5C each show a scratch created in the surface by mechanically pressing in a sharp object; and

[0078] FIG. 6A-6B show a region of the abluminal top face and the side face of the marker element in an oblique image from the side, recorded by scanning electron microscopy, in different magnification.

DETAILED DESCRIPTION OF THE INVENTION

[0079] Referring now to the figures of the drawing in detail and first, particularly, to FIG. 1 thereof, there is shown a portion of a framework 10 of an implant according to the invention in the form of a medical stent, for example consisting of the degradable magnesium alloy WE43. The image shows a continuous opening (eyelet hereinafter) 20 arranged for example at the distal or proximal end of the framework 10 and having a rounded rectangular shape. One eyelet 20 or three such eyelets 20 offset by 120 is/are preferably provided at the distal and/or at the proximal end of the framework 10 of the implant as part(s) of the framework, for example on a strut. Here, the framework is preferably formed as a hollow-cylindrical mesh with multiple struts. By way of example, the dimensions of the eyelet 20 are 800 m (dimension 20a in FIG. 1)350 m (dimension 20b in FIG. 1).

[0080] A radiopaque marker element 30, as illustrated in FIG. 2, can be arranged in the eyelet 20. As described hereinafter, it can be secured to the eyelet 20 by means of an adhesive layer.

[0081] The marker element 30 for example is made predominantly of tantalum or a tantalum alloy. The thickness of the marker element 30 is for example 100 m and corresponds preferably to the wall thickness of the framework 10. By way of example, the dimensions of the marker are 750 m (dimension 30a in FIG. 2)300 m (dimension 30b in FIG. 2).

[0082] Referring now to FIG. 3, in order to produce the marker element 30, portions 31 with the shape of the marker element 30 are firstly cut out with the aid of a laser from a semi-finished product in the form of a drawn hollow cylinder 40 made of tantalum or a tantalum alloy, for example having an outer diameter of 2.5 mm. Here, each portion 31 is also connected to the hollow cylinder 40 via two webs 32. Slag residues, laser cutting burrs and any impurities on the hollow cylinder 40 with the portions 31 are then removed by pickling with an acid mixture formed for example of HNO.sub.3 and HF. Subsequently, a multi-stage rinsing step in demineralised water is performed. For the pickling the hollow cylinder with the portions 31 is immersed multiple times into the acid mixture. The condition of the outer side and the inner side of a hollow cylinder 40 of this kind with the portions 31 is shown in FIG. 3A and 3B.

[0083] FIG. 4 shows the inner side of the hollow cylinder 40 with a portion 31 in an enlarged view. The inner side of the portions 31, which is also referred to as the first surface (and therefore the bottom face of the marker element 30 produced therefrom) is characterized by a structure, produced by the drawing process of the hollow cylinder 40 and the subsequent pickling, having a plurality of grooves or furrows. These run, following the arrangement of the marker element 30 in the frame 10, parallel to the axis of the frame or parallel to the flow direction of the blood flowing through the stent. The structure counteracts an adhesion of blood platelets and thus reduces the risk of thrombosis (clotting), also, and in particular, at a time following the dissolution of an optional PLLA layer applied to the surface of the framework.

[0084] A balloon with a diameter of 2.35 mm (after expansion of the balloon) is then introduced into the hollow cylinder 40. The balloon is expanded by means of pressure application. Following the expansion the balloon lies with a form fit against the inner side of the hollow cylinder 40 and seals it fully. The outer, second surface of the portions 31 of the hollow cylinder 40 and the side faces 33 can thus be subjected to further process steps without the first surface of the portions 31 of the hollow cylinder shown in FIG. 4 coming into contact with further media.

[0085] The hollow cylinder with the portions 31 is now subjected to a plasma electrolytic treatment. The oxidation of the chemically stable element tantalum is brought about by the locally limited plasma discharges created at bath voltages>180 V. Here, individual plasma discharges systematically scan the uncovered surface of the portions 31, specifically the outer surface (see FIG. 3A) and at least partially the side surfaces 33 of the portions 31 exposed by the laser cutting.

[0086] The plasma electrolytically treated hollow cylinder 40 with the portion 31 is then rinsed multiple times in demineralised water, and the portions 31 are separated from the hollow cylinder 40 by severing (breaking) the webs 32. Each separated portion forms a marker element 30. The rinsing and breaking of the portion 31 are performed here after the removal from the hollow cylinder 40 of the balloon covering the inner side.

[0087] The marker element 30, due to the plasma electrolytic treatment, obtains a porous surface typical for this process, which consists for the main part of Ta.sub.2O.sub.5. The thickness of the porous layer 35 produced by the plasma electrolytic treatment is for example between 0.5 m and 4 m. Due to the conversion characteristics of plasma discharges, the original outer geometry of the marker element 30 relative to the portion 31 is maintained. The porous layer 35 generated by the plasma electrolytic treatment is shown in FIG. 5A to 5C. The porous layer 35 has a high adhesive strength on account of the material interconnection to the metallic substrate arranged beneath formed from tantalum or a tantalum alloy. This is evident on the basis of the scratches 36 shown in FIG. 5B and 5C, which are produced by pressing in with a sharp object (indenter). The pore structure of the porous layer 35 stops cracks which are produced by mechanical action.

[0088] The surface structuring by the layer 35 also leads to a significant increase of the actual surface of the marker element 30 at least by a factor of 2. This is an essential precondition for a high immobilization capacity of the marker element 30.

[0089] For arrangement on a framework 10, the hollow cylinder 40 is removed from the desiccator, installed in a removal frame and immediately gripped mechanically, with a portion 31 being broken out from the hollow cylinder so that the marker element 30 is created. The framework 10 will have been provided with a polymer active substance coating (for example PLLA/Sirolimus) shortly beforehand. Following the positioning of the marker element 30 in the eyelet 20, the marker element is pressed into the solvent-containing coating (for example PLLA in chloroform 2/98), which is still plastically deformable. In addition, the resultant gap between marker element 30 and framework 10 can be filled with the polymer solution. A sufficient holding force of the marker element 30 in the eyelet 21 is then brought about by the evaporation of the solvent from the solution, as is then also a curing of the polymer coating. Thus, neither the biofunctionalized, abluminal marker side nor the luminal marker side, structured in the blood flow direction, is covered by a polymer layer. The framework 10 with the marker element 30 can then be assembled in the catheter system.

[0090] Due to the porous layer 35, which is formed by the plasma electrolytic treatment, it is ensured that no metal/metal contact between framework 10 and material of the marker element 30 is created, that local element formation is thus inhibited reliably, and that there is no influencing of the further course of degradation of the framework 10.

[0091] In a further, alternative exemplary embodiment the marker element 30 can be immersed in a polymer solution (for example PLLA in chloroform 2/98) prior to the positioning in the eyelet 20. In this embodiment a filling of the gap between marker element 30 and framework 10 is not absolutely necessary. After the positioning of the marker element 30 in the eyelet 20, a sufficient holding force of the marker element 30 in the eyelet 20 is provided by the curing of the polymer coating. The framework 10, inclusive of marker element 30, can then be coated by a polymer active substance layer, and the framework can then be assembled in the catheter system.

[0092] In an alternative exemplary embodiment the plasma electrolytically treated hollow cylinder 40 can be rinsed multiple times in demineralised water following the removal of the balloon and then additionally immersed in a solution containing the crosslinker APTES for example (aminopropyltriethoxysilane). By applying a negative pressure in a desiccator, the pores are saturated with the solution. Here, the reaction on the surface of the portions 31 can also be thermally activated. There is then additionally a reaction with adhesion peptides (for example RGD peptides), which have a particular affinity for the cells of the vessel wall. These bind covalently to the surface activated with APTES. The hollow cylinder 40 with the portions 31 is then rinsed/dried and deposited in a desiccator. During the vascular intervention of the framework 10, the surroundings of the marker element 30 also come into contact with blood. This exemplary embodiment therefore has the advantage that the pores of the abluminal top face of the marker element 30 with the porous layer 35, on account of the adhesion peptides attached by means of APTES, absorb blood constituents that lead to an improved adhesion and healing. It is thus ensured that the marker grows in quickly and remains reliably ingrown in the vessel tissue even after degradation of the framework 10 and the polymer active substance layer.

[0093] In a further alternative exemplary embodiment the hollow cylinder 40 with the portions 31, following the plasma electrolytic treatment, is rinsed multiple times in demineralised water following removal of the balloon and is then additionally immersed in a solution containing the crosslinker APTES (aminopropyltriethoxysilane). By applying a negative pressure in a desiccator, the pores are saturated with the solution. Here, the reaction on the marker surface can also be thermally activated. There is then additionally a reaction with proteins, such as growth factors (for example VEGF) or antibodies, which have a particular affinity to the cells of the vessel wall. These bind covalently to the surface activated with APTES. The hollow cylinder 40 is then rinsed/dried and deposited in a desiccator. In this exemplary embodiment as well, the immobilised proteins cause the marker element 30 to become quickly ingrown into the vessel tissue and to remain in the tissue even after degradation of the framework 10 and the polymer active substance arranged thereon.

[0094] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teaching. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention.