Patent Application
20210128793
The present invention relates to the field of medicine and is more particularly concerned with biodegradable temporary structures such as stents, membranes, mesh, clips, sutures and implants.
Obstructive coronary diseases may be caused by a stable or an unstable plaque. An unstable atherosclerotic plaque is vulnerable to rupture and to subsequent thrombogenic reaction, which can lead to sudden death. In general, when the associated stenosis of a stable plaque reaches a certain threshold, it may cause a lack of myocardium perfusion and associated chest pain or angina pectoris.
Historically, the first endovascular mechanical treatment was introduced in 1977 by Andreas Gruentzig who introduced the angioplasty balloon. Percutaneous angioplasty was however associated with a phenomenon called restenosis. Restenosis is essentially the re-obstruction of the vessel caused by vessel recoil, remodeling and hyperplasia. In order to treat the acute recoil and limit the restenosis process, Palmaz-Schatz introduced a new medical implant, the stent, in 1986. A new phenomenon was then observed, in-stent restenosis, or the re-obstruction inside the stent. However, the restenosis rates associated with balloon angioplasty (40-60%) were greatly improved with the advent of stents in 1986 (20-30%) which nevertheless still constitutes a relatively high rate. In order to treat the in-stent restenosis process, Drug Eluting Stents (DES) were introduced. DES were initially coated with antiproliferative and anti-thrombotic compounds. The first DES (Cypher, Cordis) was approved in Europe in 2002. DES initially were effective in limiting restenosis with reported rates between 0 and 16%. However, a few years following their introduction, a serious phenomenon was reported. Late thrombosis (reported by Camenzin on the “Black Sunday” in 2006) was demonstrated to be associated with DES. It was subsequently shown that the rate of late thrombosis continues to increase with time following the implantation. This is phenomenon is of great concern since thrombosis is a life threatening event possibly leading to myocardium infarction.
The causes of late thrombosis are not fully elucidated but processes like chemical compound effect, chronic inflammation and vessel wall injury are reported in the literature. Concerning chronic inflammation and vessel wall injury, a direct link was demonstrated between stent fracture and In-Stent Restenosis (ISR) and thrombosis. ISR is observed both with bare metal stents (BMS) and DES with respective rates of 20-25% and 0-16.7%. The relation with DES fracture was shown to be more frequent than previously thought. The reason is that most of the time stent fracture is clinically silent. However, with imaging modalities, the reported incidence is 1-2% and pathologic investigations reported an incidence of 29% with about 5% associated with adverse effects: inflammation, ulceration, avulsion, ISR, thrombosis.
Furthermore, it was also shown that stent fractures are correlated with anatomical location (tortuosity), with stent fractures more common in the Right Coronary Artery (RCA) with a rate of 57% than in the Left Anterior Descending (LAD) with a rate of 34%, and stent design and lesion types. In addition, stress fractures are also strongly correlated with time: stents may get fully broken over long periods of time. For example, a few broken struts have been reported after implantation times of about 172 d and full stent fracture after implantation times of 1800 d.
This problem is inherently a mechanical problem linked to the notion of fatigue of material. Every material subjected to cyclic loading, such as heart beats, will fatigue and eventually fail. Possible solutions for stent design include developing a superior material for manufacturing the stent for higher longevity and biodegradable stents. Indeed, a biodegradable stent would essentially disappear once it has performed its temporary scaffolding task and thus avoid being subjected to cyclic fatigue.
It is with this perspective that the lgaki-Tamai stent, the first polymeric biodegradable stent made of poly-L-lactide polymer, was introduced in 2003. Since polymers have mechanical properties that are about 2 orders of magnitude lower than metals, mechanical integrity problems were reported, including acute recoil. Given their relative weaker mechanical properties, larger struts are required to ensure proper scaffolding of the vascular wall. The thicker struts, in turn, may cause more resistance to blood flow and may be too large to implant in many blood vessels. Their capacity to properly scaffold plaques with calcification was also mentioned. In addition, larger struts were also associated with more vessel injuries, thus potentially leading to more vessel response and hyperplasia.
At about the same time, biodegradable metallic stents were investigated. The principle was to exploit the property of reactive metals to corrode for biodegradation. The initial selected metal was magnesium. The concept of biodegradation has been shown to work. However, there are several limitations associated with the use of magnesium (WE magnesium). Similarly to polymers, magnesium has mechanical properties that are much lower than the current super alloys used for commercial stents (such as 316L stainless steel, L605 cobalt-chromium alloy). As a consequence, thicker struts are also required, and these are associated with the same problems of possible flow disturbances and wall injury. Indeed, negative remodelling was recently demonstrated with the use of the magnesium-based stent.
More recently, other reactive metal alloys were investigated, including iron-manganese alloys and electroformed iron. These alloys have relatively better mechanical strength than magnesium-based alloys. However, the iron-manganese alloys have quite large metallic grains (100 microns), which is an issue given that a stent strut dimension is below 100 microns. Electroformed irons have much smaller grain sizes (2-8 microns) but have limited ductility. Furthermore, control of the degradation rate of these alloys is a challenging task.
Some stents, such as the stent proposed in US Pat. No. 8,080,055 by Atanasoska et al. and issued Dec. 20, 2011, use galvanic corrosion between a core of a stent and a coating made of a different material to promote degradation of the stent in situ. However, such stents require thick struts having a layered structure. This structure also results in heterogeneous degradation as the cathodic layers will remain uncorroded and the anodic layer will also degrade non-homogeneously.
Accordingly, there is a need in the industry to provide an improved bioresorbable stent and other bioresorbable medical devices, along with methods of manufacturing such medical devices. An object of the present invention is therefore to provide such devices and methods.
In a broad aspect, the invention provides a bioresorbable stent, the bioresorbable stent comprising: a bioresorbable material, the bioresorbable material being an intermixed particulate material including cathodic particles and anodic particles bound to each other. The anodic particles are made of an anodic material and the cathodic particles are made of a cathodic material, the anodic and cathodic materials forming a galvanic couple with the anodic material being electropositive and the cathodic material being electronegative. The anodic and cathodic particles are present in a predetermined ratio in the bioresorbable material. The anodic particles, cathodic particles and predetermined ratio are such that bioresorption of the stent is promoted by galvanic corrosion between the anodic and cathodic materials.
For the purpose of this document, the terminology “stent” refers to structures to be used during medical interventions, on humans or animals, to maintain open or to open a cavity in biological tissues. For example, a stent could be used, among other uses, to maintain an artery open. Stents therefore also include devices referred to in the current literature as “scaffolds”.
In some embodiments, the cathodic and anodic particles are substantially homogeneously dispersed in the bioresorbable material.
In some embodiments, the anodic and cathodic materials are metallic.
Typically, the anodic and cathodic materials are biocompatible.
In some embodiments, the anodic material is selected from the group consisting of iron, iron alloys and vanadium and the cathodic material is selected from the group consisting of cobalt-chromium alloys, stainless steel, tantalum, titanium and platinum-steels.
In some embodiments, the anodic material and cathodic material are selected from the group of couples consisting of iron/stainless steel and iron/tantalum.
In some embodiments, the anodic and cathodic particles are from about 1 μm to about 30 μm in average size.
In some embodiments, the stent is bioresorbable at a predetermined rate; and the anodic particles, cathodic particles and predetermined ratio are selected such that the stent is bioresorbable at the predetermined rate due to galvanic corrosion between the anodic and cathodic materials.
In some embodiments, the bioresorbable material further includes rate control particles made of a rate control material and dispersed in the bioresorbable material; and the rate control particles affect the galvanic corrosion to change the predetermined rate in accordance with a predetermined rate change.
In some embodiments, the rate control particles increase the predetermined rate. In other embodiments, the rate control particles decrease the predetermined rate. For example, the rate control material is selected from the group consisting of: salts, acids, solid electrolytes, ceramics, dielectrics and metal oxides.
In some embodiments, the bioresorbable material is an annealed material.
In some embodiments, the anodic and cathodic particles include grains of about 1 μm or less in average size. In some embodiments, the anodic and cathodic particles include grains of about 4 μm or less in average size. In some embodiments, the anodic and cathodic particles include grains of about 10 μm or less in average size.
In some embodiments, the anodic and cathodic materials have bulk specific weights that differ by about 50% or less. In some embodiments, the anodic and cathodic materials have bulk specific weights that differ by about 20% or less.
In some embodiments, the anodic and cathodic materials have hardnesses that differ by about 50% or less. In some embodiments, the anodic and cathodic materials have hardnesses that differ by about 20% or less.
In some embodiments, the predetermined ratio is about 4:1 w/w (weight to weight) or more in the anodic particles with respect to the cathodic particles. In some embodiments, the predetermined ratio is about 8:1 w/w or more in the anodic particles with respect to the cathodic particles. In some embodiments, the predetermined ratio is about 20:1 w/w or more in the anodic particles with respect to the cathodic particles.
In some embodiments, the cathodic material is stainless steel and the anodic material is iron.
In some embodiments, the bioresorbable material is substantially non-porous. For example, the bioresorbable material has a porosity of about 0.2% or less.
In some embodiments, the stent is entirely made of the bioresorbable material. In other embodiments, the stent further comprises a non-bioresorbable portion.
In another broad aspect, the invention provides a method for manufacturing a bioresorbable stent, the method comprising: providing an anodic powder including anodic particles made of an anodic material; providing a cathodic powder including cathodic particles made of a cathodic material, the anodic and cathodic materials forming a galvanic couple; mixing the anodic and cathodic powders together in a predetermined ratio to obtain a mixed powder; cold spraying the mixed powder on a substrate to obtain a bioresorbable material; and processing the bioresorbable material to form the bioresorbable stent. The anodic particles, cathodic particles and predetermined ratio are selected so that bioresorption of the stent is promoted by galvanic corrosion between the anodic and cathodic materials.
The specific details regarding some embodiments of the stent described hereinabove apply to the present method.
In some embodiments, the method further comprises providing a bioresorption rate control powder including rate control particles made of a rate control material. Mixing the anodic and cathodic powders together includes also mixing a rate control quantity of the bioresorption rate control powder with the anodic and cathodic powders to obtain the mixed powder. The bioresorption rate control powder affects the galvanic corrosion to change the predetermined rate in accordance with a predetermined rate change.
In some embodiments, the substrate has a substantially planar form, or cylindrical form, or thick plate form, or thin sheet form.
In some embodiments, processing the bioresorbable material to form the bioresorbable stent includes taking a slice of a predetermined thickness of the bioresorbable material and shaping the slice to form the bioresorbable stent, the slice including substantially opposed slice first and second side edges.
In some embodiments, taking the slice of the predetermined thickness of the bioresorbable material includes cutting the slice with electrical discharge machining methods (EDM). The EDM methods can be also used to cut the shape of the final stent blank in a tubular form.
In some embodiments, processing the bioabsorbable material to form the tubular stent blanks includes CNC machining methods such as CNC Turning operations or CNC Milling operations.
In some embodiments, taking the slice of the predetermined thickness of the bioresorbable material includes cutting the slice with electrical discharge machining methods (EDM). The EDM methods can be also used to cut the shape of the final stent blank in a tubular form.
In some embodiments, shaping the slice includes folding the slice to form a cylinder so that the slice first and second side edges are substantially adjacent to each other and welding the slice first and second side edges to each other.
In some embodiments, shaping the slice includes embossing the slice to form a half-cylinder and welding a similar half-cylinder thereto to form a complete cylinder.
In some embodiments, shaping the slice to form the stent includes forming a substantially cylindrical stent blank and cutting out portions of the stent blank to define stent struts.
In some embodiments, cutting out portions of the stent blank includes laser cutting the portions of the stent blank under conditions maintaining the stent blank under an annealing temperature of the anodic and cathodic materials.
In some embodiments, cutting out portions of the stent blank includes laser cutting the portions of the stent blank using picosecond or femtosecond laser equipment.
In some embodiments, the method further comprises annealing the bioresorbable material.
In some embodiments, the bioresorbable material is annealed under conditions resulting in grains of the anodic and cathodic materials in the anodic and cathodic particles to remain below about 1 μm in average size. In some embodiments, the bioresorbable material is annealed under conditions resulting in grains of the anodic and cathodic materials in the anodic and cathodic particles to remain below about 4 μm in average size. In some embodiments, the bioresorbable material is annealed under conditions resulting in grains of the anodic and cathodic materials in the anodic and cathodic particles to remain below about 10 μm in average size. In some embodiments, the bioresorbable material is dynamically annealed. In some embodiments, the bioresorbable material is annealed at a temperature between 70% and 90% of a melting temperature of a lowest melting temperature material selected from the anodic and cathodic materials.
In some embodiments, the substrate is substantially planar and processing the bioresorbable material to form the bioresorbable stent includes cutting a cylinder in the bioresorbable material and emptying the cylinder to form a stent blank.
In yet another broad aspect, the invention provides a bioresorbable material, the bioresorbable material being an intermixed particulate material comprising cathodic particles and anodic particles bound to each other. The anodic particles are made of an anodic material and the cathodic particles are made of a cathodic material, the anodic and cathodic materials forming a galvanic couple. The anodic and cathodic particles are present in a predetermined ratio in the bioresorbable material. The anodic particles, cathodic particles and predetermined ratio are such that bioresorption of the bioresorbable material is promoted by galvanic corrosion between the anodic and cathodic materials.
The specific details regarding some embodiments of the stent and the bioresorbable material from which the stent is made as described hereinabove, apply to some embodiments of the present bioresorbable material.
In yet another broad aspect, the invention provides an intermixed particulate material comprising: cathodic particles and anodic particles bound to each other, the anodic particles being made of an anodic material and the cathodic particles being made of a cathodic material, the anodic and cathodic materials forming a galvanic couple.
The specific details regarding some embodiments of the stent and the bioresorbable material from which the stent is made, as described hereinabove, apply to some embodiments of the present particulate material.
In yet another broad aspect, the invention provides a method for manufacturing an intermixed particulate material, the method comprising: providing an anodic powder including anodic particles made of an anodic material; providing a cathodic powder including cathodic particles made of a cathodic material, the anodic and cathodic materials forming a galvanic couple; mixing the anodic and cathodic powders together in a predetermined ratio to obtain a mixed powder; and cold spraying the mixed powder on a substrate to obtain the intermixed particulate material.
The specific details regarding some embodiments of the stent and the bioresorbable material from which the stent is made, as described hereinabove, apply to some embodiments of the present method.
In yet another broad aspect, the invention provides a method for manufacturing a bioresorbable medical device, the method comprising: providing an anodic powder including anodic particles made of an anodic material; providing a cathodic powder including cathodic particles made of a cathodic material, the anodic and cathodic materials forming a galvanic couple; mixing the anodic and cathodic powders together in a predetermined ratio to obtain a mixed powder; cold spraying the mixed powder on a substrate to obtain a bioresorbable material; and processing the bioresorbable material to form the bioresorbable medical device. The anodic particles, cathodic particles and predetermined ratio are such that bioresorption of the stent is promoted by galvanic corrosion between the anodic and cathodic materials.
The specific details regarding some embodiments of the stent and the bioresorbable material from which the stent is made, as described hereinabove, apply to some embodiments of the present method.
In some embodiments, the medical device is selected from the group consisting of stents, scaffolds, markers, anchors, clips, occluders, sutures, surgical devices and orthopedic support devices.
In yet another broad aspect, the invention provides a method of implanting a bioresorbable stent in a patient, the method comprising: determining a desired resorption rate of the bioresorbable stent based on the satisfaction of predetermined criteria by the patient; selecting a patient stent from a set of predetermined stents, the predetermined stents being as defined above, the patient stent having the desired resorption rate when implanted in the patient; and implanting the patient stent in the patient. In some embodiments, the method further comprises resorbing the stent in the patient at the desired resorption rate.
Advantageously, in some embodiments of the invention, a relatively small bioresorbable stent that is nevertheless strong and ductile enough can be manufactured using the proposed material.
In yet another broad aspect, there is provided a method for manufacturing a bioresorbable stent, the method comprising: providing a mixed powder including anodic particles made of a metallic anodic material and cathodic particles made of a metallic cathodic material, the anodic and cathodic materials forming a galvanic couple; cold spraying the mixed powder on a substrate to obtain an amalgamated material; forming a substantially tubular stent blank made of the amalgamated material by machining the amalgamated material using electrical discharge machining (EDM); removing selected portion of the stent blank to form the stent; wherein the anodic particles, cathodic particles and predetermined ratio are selected so that bioresorption of the stent is promoted by galvanic corrosion between the anodic and cathodic materials.
The material formed through cold-spray is an amalgamated material in which the various particles contained in the mixed powder have been amalgamated, or in other words stuck to each other, using cold spraying.
There may be provided a method further comprising removing the amalgamated material from the substrate and annealing the amalgamated material removed from the substrate before forming the stent blank.
There may be provided a method wherein the amalgamated material is annealed under conditions resulting in grains of the anodic and cathodic materials in the anodic and cathodic particles to remain below about 1 μm in average size.
There may be provided a method wherein the amalgamated material is annealed under conditions resulting in grains of the anodic and cathodic materials in the anodic and cathodic particles to remain below about 4 μm in average size.
There may be provided a method wherein the amalgamated material is annealed under conditions resulting in grains of the anodic and cathodic materials in the anodic and cathodic particles to remain below about 10 μm in average size.
There may be provided a method wherein the amalgamated material is annealed at a temperature below a sintering temperature of the amalgamated material.
There may be provided a method wherein the amalgamated material is annealed at a temperature between 70% and 90% of a melting temperature of a lowest melting temperature material selected from the anodic and cathodic materials.
There may be provided a method wherein the cathodic material is stainless steel and the anodic material is iron.
There may be provided a method wherein the amalgamated material is annealed at an annealing temperature of between 800° C. and 1400° C. for an annealing duration of 30 minutes to 4 hours.
There may be provided a method wherein the annealing temperature is between 1100° C. and 1300° C. and the annealing duration is between 1 and 3 hours.
There may be provided a method wherein the amalgamated material is brought from room temperature to the annealing temperature at a predetermined heating rate.
There may be provided a method wherein the predetermined heating rate is between about 100 and about 400° C./hr.
There may be provided a method wherein the amalgamated material is brought from annealing temperature to the room temperature at a predetermined cooling rate.
There may be provided a method wherein the predetermined cooling rate is between about 100 and about 400° C./hr.
There may be provided a method wherein the anodic material is selected from the group consisting of iron, iron alloys and vanadium and the cathodic material is selected from the group consisting of cobalt-chromium alloys, stainless steel, tantalum, titanium and platinum-steels.
There may be provided a method wherein the anodic material and cathodic material are selected from the group of couples consisting of iron/stainless steel and iron/tantalum.
There may be provided a method wherein the stent blank defines a longitudinally extending stent passageway, the stent passageway being formed in the amalgamated material before a peripheral surface of the stent blank is machined.
There may be provided a method wherein forming the stent passageway includes forming a pilot hole in the amalgamated material, inserting an EDM wire in the pilot hole, and enlarging the pilot hole to a predetermined diameter using wire EDM.
There may be provided a method wherein the anodic and cathodic particles are from about 1 μm to about 30 μm in average size.
There may be provided a method wherein the anodic and cathodic particles include grains of about 1 μm or less in average size.
There may be provided a method wherein the anodic and cathodic particles include grains of about 4 μm or less in average size.
There may be provided a method wherein the anodic and cathodic particles include grains of about 10 μm or less in average size.
There may be provided a method wherein the anodic and cathodic materials have bulk specific weights that differ by about 50% or less.
There may be provided a method wherein the anodic and cathodic materials have bulk specific weights that differ by about 20% or less.
There may be provided a method wherein the anodic and cathodic materials have hardnesses that differ by about 50% or less.
There may be provided a method wherein the anodic and cathodic materials have hardnesses that differ by about 20% or less.
There may be provided a method wherein the predetermined ratio is about 4:1 w/w or more in the anodic particles with respect to the cathodic particles.
There may be provided a method wherein the predetermined ratio is about 8:1 w/w or more in the anodic particles with respect to the cathodic particles.
There may be provided a method wherein the predetermined ratio is about 20:1 w/w or more in the anodic particles with respect to the cathodic particles.
There may be provided a method wherein the mixed powder includes rate control particles made of a rate control material, the rate control material affecting the galvanic corrosion to change the predetermined rate in accordance with a predetermined rate change.
There may be provided a method wherein the bioresorption rate control powder increases the predetermined rate.
There may be provided a method wherein the bioresorption rate control powder decreases the predetermined rate.
There may be provided a method wherein the rate control material is selected from the group consisting of: salts, acids, solid electrolytes, ceramics, dielectrics and metal oxides.
There may be provided a method wherein the EDM is performed with the amalgamated material immersed in an oil-based dielectric fluid. The oil-based dielectric fluid is a fluid that will not promote corrosion of the amalgamated material.
There may be provided a method wherein the oil-based dielectric fluid is actively circulated to promote heat removal from the amalgamated material during machining.
In yet other embodiments, bioresorbable stents are manufactured from wires or stacked and folded sheets of material including a mix of anodic and galvanic material building elements. For example, a wire or set of wires may be braided or twisted together using smaller filaments of an anodic material and filaments of a cathodic material. Such wires can then be used to manufacture wire stents and other medical devices. Braiding is performed so that the cathodic and anodic material are in contact with each other at multiple locations there along with specific and predetermined alternating of the filaments. Such a wire or individual filaments may be used to make a bioresorbable fabric. In other embodiments, thin foils or cathodic and anodic materials are stacked and bonded to each other. Folding the foils allows to the anodic and cathodic alternation to make bioresorbable structures.
In yet another broad aspect, the invention provides a bioresorbable stent, comprising: an anodic material in filament form and a cathodic material in filament form, the anodic and cathodic materials being metallic and forming a galvanic couple, the anodic and cathodic materials being distributed in the stent so that the anodic and cathodic materials contact each other at a plurality of junctions; wherein bioresorption of the stent is promoted by galvanic corrosion between the anodic and cathodic materials at the junctions.
There may also be provided a bioresorbable stent wherein at least one anodic filament made of the anodic material and at least one cathodic filament made of the cathodic material are braided together in a wire, the wire including at least some of the plurality of junctions.
There may also be provided a bioresorbable stent wherein the anodic and cathodic filaments are also braided with a carrier filament.
There may also be provided a bioresorbable stent wherein the carrier filament is metallic.
There may also be provided a bioresorbable stent wherein the carrier filament is made of a material that differs from the anodic and cathodic materials.
There may also be provided a bioresorbable stent wherein the anodic and cathodic filaments have different pitches relative to the wire.
There may also be provided a bioresorbable stent wherein the bioresorbable stent is a wire stent made of one or more of the wires.
There may also be provided a bioresorbable stent wherein a plurality of anodic filament segments made of the anodic material and a plurality of cathodic filament segments made of the cathodic material are weaved together in a fabric, the fabric including at least some of the plurality of junctions.
There may also be provided a bioresorbable stent wherein the anodic filament segments are substantially parallel to each other in the fabric and the cathodic filament segments are substantially parallel to each other in the fabric, the anodic filament segment being substantially perpendicular to the cathodic filament segments.
There may also be provided a bioresorbable stent wherein one of the anodic and cathodic materials forms a base grid defining a plurality of grid apertures and another one of the anodic and cathodic materials is crocheted into the base grid through the apertures.
There may also be provided a bioresorbable stent wherein at least one of the cathodic and anodic materials are in beaded filament form.
There may also be provided a bioresorbable stent wherein both the cathodic and anodic materials are in beaded filament form.
There may also be provided a bioresorbable stent wherein the cathodic and anodic filaments are under tension and the junctions are created due to normal forces between the filaments at locations where the filaments intersect.
There may also be provided a bioresorbable stent wherein the cathodic and anodic materials are sintered to each other.
There may also be provided a bioresorbable stent wherein the anodic material is selected from the group consisting of iron, iron alloys, mild steel and vanadium and the cathodic material is selected from the group consisting of cobalt-chromium alloys, stainless steel, mild steel, tantalum, titanium and platinum-steels.
There may also be provided a bioresorbable stent wherein the anodic material and cathodic material are selected from the group of couples consisting of iron/stainless steel, two different mild steels and iron/tantalum.
There may also be provided a bioresorbable stent wherein the cathodic and anodic materials have different diameters.
There may also be provided a bioresorbable stent wherein a total length of the anodic material in the bioresorbable stent differs from a total length of the cathodic material in the bioresorbable stent.
In yet another broad aspect, there is provided a bioresorbable stent, comprising a plurality of layers alternating between cathodic layers and anodic layers forming alternating galvanic couples promoting galvanic corrosion between the anodic and cathodic layers.
There may also be provided a bioresorbable stent wherein all the cathodic layers are made of a same cathodic material and all the anodic layers are made of a same anodic material, the anodic and cathodic materials forming a galvanic couple.
There may also be provided a bioresorbable stent wherein the anodic material is selected from the group consisting of iron, iron alloys, mild steel and vanadium and the cathodic material is selected from the group consisting of cobalt-chromium alloys, stainless steel, mild steel, tantalum, titanium and platinum-steels.
There may also be provided a bioresorbable stent wherein the anodic material and cathodic material are selected from the group of couples consisting of iron/stainless steel, two mild steels of different compositions and iron/tantalum.
There may also be provided a bioresorbable stent wherein the anodic layers are thinner than the cathodic layers.
There may also be provided a bioresorbable stent wherein the anodic layers are thicker than the cathodic layers.
There may also be provided a bioresorbable stent wherein the anodic layers and cathodic layers define concentric cylindrical layers.
There may also be provided a bioresorbable stent wherein the anodic layers are formed by a cathodic spiralling sheet made of the cathodic material an the anodic layers are formed by an anodic spiralling sheet made of the anodic material and parallel to the cathodic spiralling sheet.
There may also be provided a bioresorbable stent wherein the cathodic material includes a plasma deposited layer deposited the anodic material.
There may also be provided a bioresorbable stent wherein the anodic material includes a plasma deposited layer deposited the cathodic material.
In yet another broad aspect, there is provided a method of manufacturing a bioresorbable wire, the method comprising braiding together at least two metallic filaments having different galvanic potentials. For example, the two filaments are different mild steels.
Other objects, advantages and features of the present invention will become more apparent upon reading of the following non-restrictive description of preferred embodiments thereof, given by way of example only and in relation with the following Figures.
The present invention relates to novel materials and to bioresorbable, or biodegradable, medical devices including this material. Also, as detailed hereinbelow, methods of manufacturing the materials and medical devices are provided. While the following description mostly refers to a stent manufactured using the proposed material, it is within the scope of the invention to manufacture any suitable medical device using this material, such as, for example, orthopedic devices used as temporary support while tissues heal. Also, while the proposed material is well suited to the manufacture of bioresorbable medical devices, any other medical devices can be manufactured using the proposed material. Finally, while specific methods of manufacturing the proposed medical devices is proposed, in an alternative embodiment of the invention, the medical devices are manufactured using any other suitable method.
Returning to the specific case of a stent, the ideal mechanical properties for stent design are: high Elastic modulus E (to limit stent recoil), low yield strength Sy (to lower balloon pressure for stent expansion), high ultimate strength SUT (for stent longevity), high ductility (for stent longevity and the capacity to withstand deformation under heart pulsation), a high value of the equation E·t3 (for buckling resistance, t being the strut thickness) and the capacity of the stent to withstand a sufficiently large number of cycles.
It is in order to alleviate the limitations mentioned above in the background section that the proposed invention is put forward. One objective was to develop a bioresorbable stent with a new material having a small grain size, the highest possible ductility, high strength and a controllable degradation rate.
Small grain size is advantageous given the size of the stent struts and to avoid a discontinuous material and stress concentration at the interface of grains. It should be noted that grain size should not be confused with particle size, as the proposed material is particulate. The material is made of particles, and the particles each include a plurality of grains. It is also known that for a given material, small grain sizes favor strength and fatigue resistance (basically linked to the Hall-Petch effect: strength ˜1/d1/2 with d the grain size). Apart from increasing strength and fatigue resistance, a smaller grain size has a definite advantage in wear properties. Stents and other medical devices may thus benefit from a significant reduction in grain size. To achieve this result, a cold spray process is proposed to manufacture the novel material.
Indeed, conventional techniques to reduce the grain size, such as cold work, usually make the material too brittle. We propose using the cold gas-dynamic spraying (CGDS) process, referred herein as “cold spray”, to generate improved materials with smaller grain sizes. The cold spray process essentially uses the energy stored in a high pressure gas to propel ultra-fine powder (nano-powder) particles at supersonic velocities (300-1500 m/s). The compressed gas is preheated (to a temperature lower than the powder melting temperature) and exits through a nozzle at high velocity. The compressed gas is also fed to a powder feeder which introduces the ultrafine powder in the gas stream jet. The nano-structured powder impacts with a substrate and the particles deform and adhere to form a coating on the substrate. The particles remain relatively cold and retain their submicron to micron range dimensions. No melting is observed and, interestingly, particles flow and mix under very high strain rates generating complex microstructures. Therefore, unwanted effects of high temperatures, such as oxidation, grain growth and thermal stresses, are absent.
The proposed material achieves bioresorption through the use of a mixture of two powders in the manufacturing process. More specifically, the bioresorbable material is an intermixed particulate material comprising cathodic particles and anodic particles bound, or amalgamated, to each other. The anodic particles are made of an anodic material and the cathodic particles are made of a cathodic material, the anodic and cathodic materials forming a galvanic couple, the anodic material being electropositive relative to the cathodic material, which is therefore electronegative. The anodic and cathodic particles are present in a predetermined ratio in the bioresorbable material. The anodic particles, cathodic particles and predetermined ratio are such that bioresorption of the stent is promoted by galvanic corrosion between the anodic and cathodic materials. Also, conventional passive oxidation of the cathode and anode occurs, which further enhances bioresorption.
In some embodiments, the proposed material and medical devices are made entirely of the cold-sprayed material, that is the bioresorbable material. Therefore, in opposition to some medical devices that may include a cold-sprayed coating of cold-sprayed particles, the proposed medical device is made entirely of the cold-sprayed material, or includes a bulk, structural, portion thereof that is made entirely of the cold-sprayed material. A structural portion is a portion of the medical device that by itself provides for example support to tissues when implanted in the body or that maintains integrity of the device. In some embodiments, the proposed medical devices are made entirely of metal particles.
It should be noted that the terminology “particles” relates to elements that are smaller than most (or all) of the details of the structure to manufacture. In the case of a stent, the particles have a size that is smaller than the thickness of the stent struts, so that each strut includes many particles. Bioresorption is not achieved by sudden detachment of large elements from the stent, but by gradual disintegration of the stent struts.
It should be noted that this approach is to be contrasted with, for example, the medical devices described in US Patent Application Publication 20100249927 of Yang et al. published on Sep. 30, 2010, in which all the particles have a centre of a first material and a coating of a second material. Such devices are not bioresorbable and the galvanic cells formed are used to generate a current to enhance antiseptic properties of the devices. In these devices, all the particles forming the stent have the same composition. In contrast, the proposed bioresorbable material stent includes two different types of particles. Also, the proposed material and devices manufactured therewith differ greatly from the stents described in U.S. Pat. No. 7,854,958 in the name of Kramer issued Dec. 21, 2010 in which a single material is cold-sprayed to obtain a porous stent. Once again, the devices described in this patent are not bioresorbable. In addition, due to their porous nature, they are relatively fragile.
Also, particulate materials, such as those manufactured using cold spray, are conventionally used to prevent corrosion and wear. As such, only one material is used, often to form a coating on the object to protect. It is contrary to the conventional wisdom in this field to instead promote galvanic corrosion within the material. Also, other techniques described herein, including folding laminates or braiding and weaving wires of different compositions do not require the cold spray process and may use any suitable conventional metal wires and films.
The anodic and cathodic particles form a plurality of galvanic pair cells or structures. The proposed mechanism of bioresorption for the new biodegradable material is similar to the concept of sacrificial anode used in the ship industry to protect boat hulls from corroding, but with the distinction that corrosion of the anode is a desired effect that will lead to loss of cohesion of the proposed material at a desired controlled rate. Two (or more) dissimilar powders are thoroughly mixed prior to the cold spray. Anodic particles (less noble metal) and cathodic particles (more noble metal) are substantially homogeneously mixed using known methods. When in the presence of an electrolyte, current will flow between the anodic and cathodic particles in the cold-sprayed material, which will lead to corrosion of the anodic material, which, in turn, will allow resorption of the medical devices manufactured using the proposed material. In typical embodiments, this resorption will occur substantially homogeneously.
More generally speaking, there is proposed an intermixed particulate material comprising cathodic particles and anodic particles bound, or amalgamated, to each other, the anodic particles being made of an anodic material and the cathodic particles being made of a cathodic material, the anodic and cathodic materials forming a galvanic couple. While bioresorption is a useful property of the proposed material, in alternative embodiments, the proposed material is manufactured such that bioresorption proceeds at such a small rate that it does not occur during the lifetime of the patient. In this case, it is the other properties of the proposed material, such as mechanical properties, that are advantageously used. Typically, when the manufacturing process described hereinbelow is used, the cathodic and anodic particles are randomly and substantially homogeneously dispersed in the bioresorbable material. However, it is possible to have non-random distribution of the anodic and cathodic particles, for example if self-assembling materials are used.
In the case in which a bioresorbable stent is manufactured, the stent includes the bioresorbable material. The stent may be entirely made of the bioresorbable material, or the stent may also include a non-bioresorbable portion made of a non-bioresorbable material, such as pure stainless steel, among other conventional possibilities. In the latter embodiments, a portion of the stent remains in the patient after the remainder of the stent has been resorbed. For example, the non-resorbed portion could include a marker usable to locate the stent implantation site after most of the stent has been resorbed, for example for follow up exams. In another example, the non-resorbed portion could be a stent graft anchoring, a valve anchoring, a clip or a suture that anchors another structure. In these embodiments, the other structure remains in place even after a portion of the stent, which was useful to support the vessel during a healing process, has been resorbed.
When the proposed material is used to manufacture a medical device, the anodic and cathodic materials or a combination of them are biocompatible, typically during the entire life cycle of the device. Typically, the anodic and cathodic materials are metallic.
In some embodiments of the invention, the anodic material is selected from the group consisting of iron, iron-alloys and vanadium, and the cathodic material is selected from the group consisting of cobalt-chromium alloys, stainless steel, tantalum, titanium and platinum-steels. In more specific embodiments of the invention, the anodic material and cathodic material are selected from the group of couples consisting of iron/stainless steel and iron-tantalum. However, other possibilities are within the scope of the invention.
The anodic and cathodic particles are in some embodiments from about 1 μm to about 30 μm in average size, which is advantageous in the manufacture of devices including sub-millimeter sized elements. Average size is defined as a mean value in a Gaussian distribution of sizes, as assessed using microscope imaging. For example, the anodic and cathodic particles are produced by melting the anodic and cathodic materials and pouring the molten materials on a spinning wheel, which creates a rain of small droplets of molten material. Cold water is sprayed afterwards on the resulting droplets, which solidifies the anodic and cathodic particles. The resulting shape is substantially spherical and size refers to the diameter of the particles. In another example, the anodic and cathodic particles are created by grinding the anodic and cathodic materials in bulk form to make powders. The resulting particles are irregular. These irregular particles are then heated, which again produces substantially spherical anodic and cathodic particles, and size refers again to the diameter of the particles.
The anodic and cathodic particles each include grains. The grains typically have much smaller dimensions than the particles. In some embodiments of the invention, the grains are about 1 μm or less in average size. In other embodiments, the grains are about 4 μm or less in average size. In yet other embodiments, the grains are about 10 μm or less in average size. Relatively small grain size promotes ductility of the devices manufactured using the proposed devices, which is often advantageous.
When a cold spray process is used, it is useful in some embodiments to have anodic and cathodic particles with some properties that are similar to promote good material properties. For example, the anodic and cathodic materials have bulk specific weights that differ by about 50% or less, and in more specific examples, the anodic and cathodic materials have bulk specific weights that differ by about 20% or less. This promotes good mixing of the particles to ensure homogeneous and random distribution of the anodic and cathodic particles in the proposed material. The bulk specific weight refers to the specific weight of the material in bulk form, not to the specific weight of the material in particulate powder form. In the context of this document, “differing by X %” is to be interpreted as meaning that the largest property is X % larger than the smallest property. For example, a material having a specific weight of 2 g/cm3 and a material having a specific weight of 3 g/cm3 differ in specific weight by 50%.
In some embodiments of the invention, the anodic and cathodic materials have hardnesses that differ by about 50% or less, and in more specific examples, the anodic and cathodic materials have hardnesses that differ by about 20% or less. This promotes good adhesion between the particles.
One could hypothesize that a ratio of 1:1 w/w between the number of cathodic and anodic particles would be desired so that the same number of electron receiving and releasing particles are provided. While this ratio can provide bioresorbable materials, it was found that, surprisingly, a predetermined ratio of about 4:1 w/w or more in the anodic particles with respect to the cathodic particles provides faster corrosion, which is advantageous in some situations. It is believed that in more extreme examples, a predetermined ratio of about 8:1 w/w or more in the anodic particles with respect to the cathodic particles, or even a predetermined ratio of about 20:1 w/w or more in the anodic particles with respect to the cathodic particles is also achievable while preserving the bioresorption properties.
In some embodiments, the proposed material is a dynamically annealed material in which the material has been heated at a time varying temperature to correct defects within the particles without promoting large grain growth. This preserves ductility while increasing hardness. However, other types of annealing are possible to achieve suitable grain size.
In addition to manipulation of the many variables involved in the structure of the proposed material, such as selection of anodic and cathodic materials and their proportions, dimensions of particles, manufacturing conditions and annealing conditions, in some embodiments additional particles are present in the material to control bioresorption rates.
More specifically, the medical device manufactured, such as a stent, is bioresorbable at a predetermined rate. Rate may be defined as the rate of mass lost percentage, a corrosion rate in mm/unit of time, or in any other suitable manner. To that effect, the anodic particles, cathodic particles and predetermined ratio between the two are selected such that the stent is bioresorbable at the predetermined rate due to galvanic corrosion between the anodic and cathodic materials. To guide the selection of particles, galvanic corrosion theories that relate the current density between two dissimilar materials and their degradation rates may be used. In those theoretical descriptions, an equation for galvanic corrosion is derived based on the corrosion current density of uncoupled alloys. This allows the quantification of the corrosion rates based on potentiodynamic current measurements and permits an estimate of the mass depletion rates based on these current measurements. Examples of such theories are found in “Electrochemical Theory of Galvanic Corrosion”, John W. Oldfield, ASTM STP 978 H. P. Hack Ed American Society for Testing and Materials, Philadelphia, 1988, p. 5-22 and “A Theoretical approach to galvanic corrosion, allowing for cathode dissolution”, S. Fangteng, E. A. Charles, Corrosion Science 28(7):649-655, 1988. These two documents are hereby incorporated by reference in their entirety.
In some embodiments of the invention, the bioresorbable material further includes rate control particles made of a rate control material and dispersed in the bioresorbable material. The rate control particles affect the galvanic corrosion to change the predetermined rate in accordance with a predetermined rate change. For example, the rate control particles increase the predetermined rate by increasing electron transport between the anodic and cathodic particles. In another example, the rate control particles decrease the predetermined rate by decreasing electron transport between the anodic and cathodic particles. Specific examples of rate control particles that increase the predetermined rate include salts (such as calcium, potassium and sodium salts), acids and solid electrolytes. Specific examples of rate control particles that decrease the predetermined rate include chromium, polymer, silicon, ceramics, dielectrics and oxides.
With the cold spray materials, the corrosion rate can be adjusted (decreased or increased) using specific thermal treatments. Indeed, with certain mixtures (Fe-316L), it was observed that the corrosion can be accelerated by increasing the temperatures of the heat treatment (higher temperatures generate higher corrosion rates).”
Typically, the proposed material is substantially non-porous. For example, this is achieved by having a material that has a porosity of about 0.2% or less.
An example of a manner of manufacturing a stent is given hereinbelow with reference to
In some embodiments of the invention, step 14 also includes providing a bioresorption rate control powder including rate control particles made of the rate control material. In these embodiments, step 16 also includes mixing a rate control quantity of the bioresorption rate control powder with the anodic and cathodic powders to obtain the mixed powder.
Step 22 may be performed in many possible manners. A non-exclusive but advantageous manner of performing step 22 is to first take a slice of a predetermined thickness of the bioresorbable material, removing the substrate, and then shape the slice to form the bioresorbable stent. In some embodiments, the slice is taken parallel to the substrate, so that the slice includes only the bioresorbable material, and no part of the substrate. The slice includes substantially opposed slice first and second side edges extending between substantially opposed ends of the slice. The thickness of the slice is about the thickness of the stent after it has been manufactured. For example, taking the slice of the predetermined thickness of the bioresorbable material includes cutting the slice with an electrical discharge machine (EDM). It has been found that slices of less than 100 μm in predetermined thickness are obtainable, which allows manufacturing relatively small stents.
In a first example, shaping the slice includes folding the slice to form a cylinder so that the slice first and second side edges are substantially adjacent to each other and welding the slice first and second side edges to each other. In a second example, shaping the slice includes embossing the slice to form a half-cylinder and welding a similar half-cylinder thereto to form a complete cylinder.
Typically, shaping the slice to form the stent includes forming a substantially cylindrical stent blank and cutting out portions of the stent blank to define stent struts. Typically, cutting out portions of the stent blank includes laser cutting the portions of the stent blank under conditions maintaining the stent blank under an annealing temperature of the anodic and cathodic materials, for example using a so-called “cold” laser, or femtosecond laser. However, in alternative embodiments, the portions of the flat material are first cut out and the resulting flattened stent is then folded in a cylindrical shape.
In another variant, step 22 is performed using a relatively thicker bioresorbable material and processing the bioresorbable material to form the bioresorbable stent includes cutting a cylinder in the bioresorbable material and emptying the cylinder to form the stent blank. This variant advantageously removes the need for welding.
A specific example of this variant is illustrated in greater details in
Also, in some embodiments, the EDM method is set-up to use oil-based dielectric fluids (since aqueous-based would try to corrode the amalgamate prematurely). These oil-based dielectric fluids are typically at high speed or pressure to promote high convection rates since the amalgamated material is sensitive to heat. EDM does create heat, but it quickly dissipates if we used forced convection from a high speed dielectric fluid flow.
Since EDM is a contactless method of cutting stent blanks, EDM will only minimally, if at all, mechanically affect the microstructure of the amalgamated material due to some mechanical deformation as it would occur with machining or with rolling methods. So, from this perspective EDM advantageous to preserve as much as possible the metallic microstructure of the different metallic phases, or preserve the grain sizes after a certain heat treatment due to its contactless nature.
More specifically, in this proposed variant, a mixed powder including anodic particles made of a metallic anodic material and cathodic particles made of a metallic cathodic material are provided, the anodic and cathodic materials forming a galvanic couple. The cathodic and anodic particles are as described above. As seen in
Then, as seen in
In some embodiments, as seen in
In a specific example, the amalgamated material 102 is annealed under conditions resulting in grains of the anodic and cathodic materials in the anodic and cathodic particles to remain below about 1 μm, 4 μm or 10 μm in average size. Typically, the amalgamated material is annealed at a temperature below a sintering temperature of the amalgamated material 102. For example, the amalgamated material 102 is annealed at a temperature between 70% and 90% of a melting temperature of a lowest melting temperature material selected from the anodic and cathodic materials.
For example, if the cathodic material is stainless steel and the anodic material is iron, the amalgamated material 102 may be annealed at an annealing temperature of between 800° C. and 1400° C. for an annealing duration of 30 minutes to 4 hours. In a more specific example, the annealing temperature is between 1100° C. and 1300° C. and the annealing duration is between 1 and 3 hours. The amalgamated material may be brought from room temperature to the annealing temperature at a predetermined heating rate. For example, the predetermined heating rate is between about 100° C./hr and about 400° C./hr. In a very specific example, the predetermined heating rate is about 250° C./hr. Also, the amalgamated material may be brought from the annealing temperature to the room temperature at a predetermined cooling rate, for example between about 100 and about 400° C./hr. In a very specific example, the predetermined cooling rate is about 250° C./hr.
Afterwards, a substantially tubular stent blank 104, seen in
The stent blank 104 defines a longitudinally extending stent blank passageway 106. In some embodiments, the stent blank passageway 106 is formed in the amalgamated material before a peripheral surface 108 of the stent blank is machined.
As seen in the sequence of
After the above steps, conventional stent manufacturing steps are performed, such as crimping the stent on a balloon for implantation. It should be noted that any other type of medical device that needs to be resorbed or degraded once implanted may also be machined using EDM from the amalgamated material.
To use the stent in a patient, first, a desired resorption rate of the bioresorbable stent is determined by a clinician. This determination depends on clinical and biological criteria. Then, the method of use includes selecting a patient stent from a set of predetermined stents, the patient stent having the desired resorption rate when implanted in the patient. Afterward, the patient stent is implanted in the patient. The proposed stent has been found to be advantageous for use in coronary and pulmonary blood vessels, but other uses are possible. For example, the proposed stent can be used in hepatic, biliary, and peripheral vessels. Also, the proposed stent can be used in non-blood carrying vessels. Finally, the method further comprises resorbing the stent in the patient at the desired resorption rate.
The ductility of the cold sprayed bioresorbable material typically needs to be improved with thermal treatment. Various treatments are possible to optimize the final desired mechanical properties. After cold spraying, the bioresorbable material is in a highly work-hardened state. Annealing is usually performed to restore the structure to a re-crystalized state, which is often preferable for various mechanical properties. Furthermore, control of annealing parameters enables control of the mechanical properties of the material. Annealing can be performed isothermally by heating the material, for example in an electric resistance furnace in air followed by air cooling. However, one has to ensure that the thermal treatment preserves the micro and the nano structures of the sprayed materials.
In other embodiments, wires, sheets, plates, cylinders or tubular forms of dissimilar materials are used to manufacture other bioresorbable medical devices, such as stents or scaffolds. For simplicity, reference is made hereinbelow to a stent, which includes as mentioned hereinabove scaffolds, but other types of medical devices may also be manufactured using similar structures and methods.
In a first variant, the stent includes an anodic material in filament form and a cathodic material in filament form. The stent may be made with long filaments that are for example braided together, of with shorter filament segments that form a fabric, among other possibilities. For example, the filaments have about between 1 and 10 μm in diameter, and are braided to make wires of between 50 and 200 μm in diameter. In other embodiments, the filaments and/or wires may have larger or smaller diameters. The stent is therefore made biodegradable, or bioresorbable, by braiding different filaments, for example micro-wires, of dissimilar metals. As a result, the wire (which for example defines stent struts) exhibits a micro-galvanic corrosion and thus biodegrades in presence of an electrolyte (such as, non-limitingly, blood plasma).
The resulting braided wire (with predetermined arrangements and predetermined ratios of anodic and cathodic wires) exhibits galvanic degradation at the contact areas between the two dissimilar metals. By using two metals that fully degrade (like mild steels, for example, but of different compositions) this results in a fully degradable wire. However, stents that do not fully degrade, or in other words that are only partially resorbed, are also within the scope of the invention. The wire can then be shaped in any predetermined configuration (and possibly micro-welded) to achieve a desired stent design and dimensions. It is also possible to perform heat treatments to improve the bioresorption properties of the wires and improve bonding.
The anodic and cathodic materials are typically metallic and form a galvanic couple. The anodic and cathodic materials are distributed in the stent so that the anodic and cathodic materials contact each other at a plurality of junctions. The cathodic and anodic materials usable in this variant are the same that are usable in the cold-sprayed material described above. Mild steel is also usable both in the presently described variants and in the cold-sprayed material. Bioresorption of the stent is promoted by galvanic corrosion between the anodic and cathodic materials at the junctions.
More specifically, in a specific embodiment, at least one anodic filament made of the anodic material and at least one cathodic filament made of the cathodic material are braided together in a wire, the wire including at least some of the plurality of junctions. The wire can then be folded in a conventional manner to form a wire or coil stent, or a few similar wires can be used to form the stent. Wire, or coil, stent are known in the art. For example, and non-limitingly, such stent are similar to the stent illustrates in U.S. Design Pat. No. 553,747 issued Oct. 23, 2007, to Cornova Inc., the contents of which is hereby incorporated by reference in its entirety.Typically, most of the junctions may be formed within the wire, with only a small number of them formed where the wire intersects itself. Micro-welding may be used an locations where the wire intersects itself if needed.
In some embodiments, the anodic and cathodic filaments are also braided with a carrier filament. The carrier filament may be metallic or not and made of the anodic material, cathodic material or of a material that differs from the anodic and cathodic materials. For example, the carrier filament is made of a bioresorbable polymer or of a suitable metal. The carrier filament may be of a larger diameter than any of the anodic and cathodic filaments. Larger filaments allow more contact between the filaments as more turns of the smaller filaments around the larger filament can be made. For example ratios of the diameters of the anodic, cathodic and carrier filaments may vary from about 0.1 to about 10. In some embodiments, the anodic and cathodic filaments have different pitches relative to the wire. This varies the amount of contact between dissimilar materials and also allows varying the relative quantity of the anodic and cathodic materials, which all affect the bioresorption rate of the stent.
Manufacturing of a wire as described above is schematically illustrated in
In other variants, tubular stent blanks, similar to the stent blank 104 are first manufactured as described below, and the stent is then crated by removing portions of the stent blank to create stent struts and other stent structures, for example using laser systems. The tubular stent blank can be manufactured from one or more sheets of material 400, as seen in
The sheet 400 may be manufactured using many different techniques. In a first example, illustrated in
In yet other embodiments, as seen for example in
The cathodic and anodic materials may be in the form of filaments having a substantially constant diameter therealong, as illustrated in
In the sheets described hereinabove, the cathodic and anodic materials may be sintered or otherwise thermally adhered to each other. In other embodiments, only mechanical forces, that is tension, friction and normal forces, hold the sheet together so that no welding, sintering or other treatment is required to manufacture the sheet. In such embodiments, the cathodic and anodic filaments are under tension and the junctions are created due to normal forces between the filaments at locations where the filaments intersect. The cathodic and anodic materials may have different or similar diameters, similarly to the braided variant described above. Also, a total length of the anodic material in the stent, that is a total sum of the length of all filament or filament segments of the anodic material, may be similar or may differs from a total length of the cathodic material in the stent.
In yet another variant, the sheet 400 is manufactured by laminating the anodic and cathodic materials on top of each other. For example, as seen in
In this approach, the micro-galvanic reaction is induced by layering micro-foils of dissimilar metals in alternate manners. After the lamination, the structure is for example heat treated to ensure proper bonding, for example at between 500° C. and 800° C. Following the heat treatment, the laminated structures is folded to expose the dissimilar sides to each other (in order to induce the galvanic couple). Different folding can be considered, some of which are illustrated in
Other suitable manners of manufacturing a layered structure as defines above are also within the scope of the invention, such as, for example, depositing multiple alternating layers of anodic and cathodic materials using plasma deposition, among others.
All the above structures allow to manufacture macro scale medical devices that present complete bioresorption by having galvanic couples at the micro scale (for example 1 to 10 μm order). The micro scale may be 0-dimensional (as in the particulate material), 1-dimensional (using wires) or 2-dimensional (using folded sheets). Using proper materials, dimensions and heat treatments allows for providing a predetermined, controlled, degradation rate.
Although the present invention has been described hereinabove by way of preferred embodiments thereof, it can be modified, without departing from the spirit and nature of the subject invention as defined in the appended claims.
The present application is a continuation-in-part of U.S. patent application Ser. No. 16/015,461 filed Jun. 22, 2018, which is a continuation-in-part of U.S. patent application Ser. No. 14/398,521 filed Mar. 11, 2014, now issued as U.S. Pat. No. 10,028,847, which is a national phase entry of PCT application PCT/CA2013/000445, filed May 2, 2013, which claimed priority from U.S. provisional patent application Ser. No. 61/641,398 filed May 2, 2012. The contents of all these patent applications is hereby incorporated by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2019/055272 | 6/21/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62688712 | Jun 2018 | US | |
| 61641398 | May 2012 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16015461 | Jun 2018 | US |
| Child | 17253521 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 14398521 | Nov 2014 | US |
| Child | 16015461 | US |
