Method of surface treatment of a material based on magnesium alloys

Abstract

The invention relates to a process of etching the surface of biodegradable materials based on magnesium and its alloys during the production process to ensure the best possible mechanical and corrosion properties. Nitric acid and etchants derived from it are used to remove defects related to the technology of production Mg-based medical devices and prevent cumulative contamination of products with impurities from the production process. Clearly defined etching conditions, including the incorporation of etching steps into the production process, will ensure repeatable properties of resorbable implants. Using this procedure, it is possible to obtain sufficient properties also for low-alloyed Mg alloys, which are not yet commercially used. The above procedure is applicable to a wide range of Mg products such as wires, plates, spikes, stents and screws, including those already in use.

Description

[0001] Method of surface treatment of a material based on magnesium alloys

[0002] Technical field

[0003] The invention relates to a surface treatment of a material during production of magnesium alloys and production of medical devices and implants by chemical etching of the surface layer of the material with an etchant based on nitric acid. Materials treated in this way can be used for biodegradable, resorbable and absorbable implants, cerclages, sutures, suture materials and implants for bone fixation and others.

[0004] State of the art

[0005] The production of thin-walled segments, wires, plates, screws, stents and other implants from Mg and its alloys and their parts for biomedical applications is already common practice [1], However, there are still unsolved issues regarding the micromechanisms of corrosion disruption of implants, especially in the dynamic environment of the human body. Production processes of biodegradable implants made of Mg and its alloys often use technologies that affect or directly damage the surface layers of the implant, which can result in deterioration of corrosion and mechanical properties. These are primarily surface roughness, the presence of lubricant residues and other external contaminants, the formation of microcracks, surface residual stresses and surface changes in chemical composition [2], [3], [4], Currently, a variety of methods are used to limit the localization of corrosion of Mg and its alloys, including coating implants with biodegradable polymers, surface treatment by etching, creating inorganic protective layers on the surface of implants, and interweaving or combining multiple functional elements to increase safety [5], [6], [7]. In particular, however, for implants with small dimensions in at least one direction (wires, plates), ideal surface properties may not be achieved before further treatment, which results in reduced utility properties and subsequent use of alloys with an unreasonably high amount of alloying elements or the content of elements the longterm safety of which for the human body has not yet been satisfactorily verified [8].

[0006] Direct extrusion is one of the promising forming methods for the production of thin wires from Mg and its alloys, which allows to achieve favorable microstructural, textural and mechanical parameters, and thus can compete with the more commonly used wire drawing [9]. The problem, however, is how to adequately clean the wire after extrusion in order to achieve the best possible properties. Currently, the literature does not offer sufficient solutions on how to generally modify the surface after the forming operations of Mg and its alloys. Although there are records in the patent literature using etching, it is always a means to modify the shape of the implant or its segment or to functionalize the surface of the medical device, for example to modify wettability. There is no known case where significant etching has been used to remove a surface layer of metal that has high roughness or contains impurities from the production process or contains microcracks or has residual stresses or has a different chemical composition as a result of the production process.

[0007] The solution to be compared are thin wires produced for fixation of the sternum after invasive heart operations. There is a solution under development that is currently promising. These are thin wires the production process and subsequent testing of which are described in detail in

[0010] , For the production of the wires, the manufacturer chose the LZ21 alloy, which, according to the article, is currently patented for this use

[0011] . The approximate strength characteristics of this alloy can be obtained by subtracting from the given graph such as the yield strength Rp= 207 MPa and ultimate strength Rm= 251 MPa, which does not reach the properties of thin wires prepared by direct extrusion from the alloy Mg-0.4Zn, (Rp= 216±l MPa and ultimate strength Rm= 263±2 MPa, at comparable ductility)

[0012] , Indeed, one of the stated advantages is the absence of rare-earth elements (RE) in the alloy, which can be problematic for biomedical applications [8]. However, the content of lithium in the alloy is highly problematic from the point of view of a fully biodegradable implant, as lithium is commonly used for the treatment of mental disorders and the effects of its action on a mentally healthy population are not sufficiently investigated

[0013] . Therefore, alloys containing only Mg and Zn, or Mg, Zn and Mn, are preferable

[0012] . In general, surface treatment after forming is not reported in related sources

[0014] ,

[0015] , It is also mentioned in work

[0010] that it is problematic to achieve uniformity of results. This may be due to insufficient surface quality treatment after wire production, both after drawing and annealing.

[0008] Summary of the invention

[0009] The invention relates to a method of surface treatment of Mg alloys within the production of the product, realized by means of chemical etching of the surface layer of the metal in such a way that residues of lubricants and other unwanted external contaminants from previous production processes, microcracks and surface residual stress are completely removed and changes in the chemical composition of the metal surface layer and in surface roughness are significantly limited.

[0010] The principle of the invention is the observed fact that the chemical removal of the surface layer of the metal before and after individual production steps, e.g., after machining, forming, forging, heat treatment, etc., significantly limits the localization of corrosion on Mg and Mg alloys, and thus increases utility properties such as yield strength, ultimate strength and ductility, especially during degradation in the body environment. If there is a time delay (e.g., storage of the product) between the etching and the following production step, e.g., before machining, forming, forging, heat treatment, further functionalization of the surface and / or final packaging of the medical device, etc., it is preferable to carry out the etching step just immediately before the said following production step.

[0011] This chemical removal is realized with an inorganic acid of an adequate concentration, which is able to remove the material from the entire surface. For Mg and its alloys, these are mainly aqueous solutions of nitric acid in a concentration of up to 20% and of Nital in all commonly used variants, i.e., a mixture of nitric acid with ethanol in the ranges from a 1 % solution of nitric acid in ethanol or methanol to a 15% solution of nitric acid in ethanol or methanol (volume percentages are meant, unless otherwise indicated). If necessary, it is also possible to use denatured alcohol, any combination of ethanol, methanol and water as a solvent for nitric acid. It is necessary to observe safety principles when mixing substances that can react strongly exothermically, especially using ethanol and methanol. A 10% aqueous solution of nitric acid appears to be most suitable, if necessary, followed by a short etching in Nital to remove moisture from the surface. For very small parts, it is sufficient to use Nital, e.g., 7%, or a 3% aqueous solution of nitric acid. Commonly used alkaline cleaners and degreasers have not proven effective, nor phosphoric acid solutions, which can result in the formation of undesirable corrosion products on Mg and its alloys. Other inorganic acids such as hydrochloric acid and hydrofluoric acid are not suitable for etching due to the content of undesirable ions. If necessary, it is possible to use them, however, an additional final etching in Nital or an aqueous solution of nitric acid must subsequently take place.

[0012] Etching is realized by immersing the product in an etching bath without direct mechanical action on the sample surface (polishing, wiping). If possible, it is preferable to move the product throughout the etching process at regular intervals to separate bubbles of hydrogen and other- gases that may locally limit the etching process. Analogously to this, sufficient etchant flow can be ensured during static immersion of the product, so that bubbles of hydrogen and other- gases are carried away from the surface by the etchant flow, or a combination of these procedures can be used. In the case of wires, sheets and similar products, the etching bath can be included in continuous production so that the product on the production line is guided below the level of the etching solution for a certain period of time. Immediately after etching, within 1 minute at the latest, the product must be immersed or guided in a bath containing pure ethanol, methanol, denatured alcohol, acetone or a combination thereof. Subsequently, it is preferable if the product is dried, e.g., statically in the air or by controlled air flow. Concerning the final etching and drying of a product intended for the production of medical devices, it is advantageous to use ethanol for drying or to guarantee the safe removal of all potentially dangerous residues of the drying medium before functionalization or packaging of the product.

[0013] It is advisable to carry out etching before actual forming (e.g., extrusion, rolling, forging) on the ingot or input material for the production process, as surface impurities and oxides (especially MgO from the melting and surface contamination from machining - Fe, Cu) can be processed deep into the final product, where they effectively deteriorate the utility properties.

[0014] Etching must be carried out after actual forming, forging or heat treatment, or any sequence of these processes, on the final product in such a way that the aforementioned conditions for removing surface defects are met. For most applications, this is a layer with a thickness of at least 10 pm from all points of the original surface. If it is necessary to store the material between production steps, it is preferable if the surface is etched just before the next step of the production process (e.g., applying a functional layer to the surface of the medical device, sterilization, or vacuum packaging).

[0015] If the forming is too rough and the impurities are embedded too deeply, or if the impurities are not soluble and are too compact, it is more preferred to first machine, grind, or polish these impurities, and only then etch them using the above procedure.

[0016] The fact that the product has been etched is often visible even at a glance: the product has a typical morphology of the surface after etching: visible (with the naked eye - ingots, possibly with a microscope) or partially visible grain boundaries, or their segments, or topographically highlighted crystallographically differently oriented parts of the microstructure (grains).

[0017] The general procedure for the production of a medical device will therefore take place in the sequence shown in Fig. 1, which ensures the removal of the main undesirable surface phenomena that limit the properties of the final product, especially for biomedical applications.

[0018] The requirement for the etching process can be summarized in the following statement:

[0019] The etchant used and the surface etching time must be adapted for each alloy and product in such a way that the following conditions are met simultaneously (3): a) Selection of an etchant and etching time is such that they do not create new localized corrosion products on the surface, or these products can be completely removed by additional etching in nital or in an aqueous solution of nitric acid. b) A state is reached when, after etching and drying, there are no visible corrosion products on the surface under microscopic observation and there has clearly been a reduction in surface roughness, or the new surface roughness is caused exclusively by the microstructure of the material (visible grains or phases). c) At least 10 pm is removed from each point on the original surface of the product.

[0020] The advantage of this procedure compared to the existing cleaning procedures is the guaranteed removal of surface defects and contamination at all important points of the production process. Etching can also be carried out with etchants known from the state of the art, however, after that, an aqueous solution of nitric acid or Nital must be used as the final step of each etching, which guarantees safety from the point of view of medical devices and the cleanliness of the surface, because in addition to the gaseous products of etching, upon contact with Mg, magnesium nitrate is formed, which is, however, highly soluble in water and ethanol and is not detectable on the surface of the implant after suitable etching and drying. Although the presence of these salts after etching is not expected, they are safe from the point of view of biocompatibility and possible further corrosion of Mg and its alloys, which cannot be said about alternative etchants using HC1, other acids or alkaline cleaners, which often contain substances that are unsuitable from the point of view of biocompatibility or corrosion resistance of Mg and its alloys.

[0021] A product based on Mg alloys means a product that is entirely made of magnesium alloy, as well as a composite product that contains magnesium alloy only on the surface of the product. The term "based on magnesium alloys" means that the product contains at least 85% of magnesium. The term "magnesium alloy" is not only bound to the content of the elements Zn, Ca, Mn, Y, Sc and their combinations mentioned in this application, but may also contain other elements that are usually present in products for biomedical applications (e.g., Zr, Li , Gd, Dy, Sr, La, Si, Cu, Ag, etc.).

[0022] Surface functionalization of medical devices based on Mg or its alloys is known in the art. Both natural polymers and synthetic polymers or copolymers can be used, e.g., chitosan, collagen, polylactic acid (PLA), polycaprolactone (PCL) and others, as well as combinations thereof.

[0023] The invention therefore relates to a method of surface treatment of a product based on a magnesium alloy containing at least 85 wt.% magnesium, which comprises the steps of etching at least 10 pm from each point of the product surface by immersing the product in a bath containing 3 to 20%vol. HNO3 in water or 1 to 15%vol. HNO3 in alcohol or in a mixture of alcohol and water, where the alcohol is ethanol, methanol, denatured alcohol or a mixture thereof, and washing the product in a bath containing ethanol, methanol, denatured alcohol, acetone or combination thereof, wherein the delay between the etching step and the washing step is 1 minute at most. In the etching step, the product and / or the bath is preferably non- stationary. The washing step is preferably followed by a drying step.

[0024] The etching and washing steps can already be carried out during the production of the product based on magnesium or its alloys, wherein the production of the product comprises one or more production steps selected from the group comprising machining the product, forming the product, forging the product, heat treatment of the product, homogenization, and wherein the product etching and washing steps are performed before each of the production steps.

[0025] It is preferred that the etching and washing steps are performed after each of the production steps of machining the product, forming the product, forging the product, heat treatment of the product, wherein if there is a product storage step at any time during the product production process, the etching and washing step is performed ideally after the product storage step.

[0026] In a preferred embodiment, the etching step is carried out by immersing the product in a bath containing 6 to 12%vol. HNO3 in water, ethanol, methanol, denatured alcohol, or mixture thereof, preferably in a bath containing 10%vol. HNO3 in water. Alternatively, if a precise thickness of the surface layer needs to be etched, it is preferable to use 3% HNO3 in water. At this concentration of HNO3, the etching process is slower, but it allows more precise control of the thickness of the etched layer.

[0027] The product is a product for biomedical application, which contains at least 85 wt.% magnesium. In the case of a magnesium alloy, the product may also contain, for example, Zn, Ca, Mn, Y, Sc, or their combination, in a total amount of up to 15 wt.%. In a preferred embodiment of the invention the product contains from 90 wt.% to 100 wt.% magnesium and 0 - 7 wt.% Zn, 0 - 1 wt.% Ca, 0 - 0.5 wt.% Mn, 0 - 1 wt.% Y, 0 - 0.5 wt.% Sc.

[0028] In another preferred embodiment the product is a product for biomedical application, which contains 93 wt.% to 99.95 wt.% magnesium and 0.05 - 7 wt.% Zn.

[0029] The product is preferably a medical device or a semi-finished product for the production of a medical device.

[0030] In another preferred embodiment of the invention, the washing step is followed by a drying step, and the drying step is followed by a step of product surface functionalization and / or product sterilization and / or product packaging. Description of the drawings

[0031] Fig. 1 Scheme of inclusion of etching, washing and drying to the general production process according to one exemplary embodiment of the method. In the scheme, the arrows represent time-consecutive production processes that follow each other immediately within the framework of technological possibilities. In the scheme only movement in the direction of the arrows is possible.

[0032] Fig. 2 Scheme of inclusion of etching, washing and drying in the general production process according to another exemplary embodiment of the method. Dashed arrows show the possibility to repeat some steps of the production process as needed.

[0033] Fig. 3 Photographs of alloy wires Mg-0.4Zn (= Mg + 0,4 wt.% Zn): a) untreated, (b) alkaline cleaning 2 min. in 25% solution Star® TN, (c) alkaline cleaning 2 min. in 5% solution Star® Forte, (d) etching 20 s in 4% solution H3PO4, (e) etching 20 s in 7% solution HNO3 + alkaline cleaning 2 min. in 100% solution Star® TN, (I) ) etching 20 s in 7% solution HNO3 + alkaline cleaning 2 min. in 100% solution Star® Forte.

[0034] Fig. 4 Photographs of Mg-0.4Zn alloy wires etched in HNO3 solution in ethanol: (a) 10 s in 3% solution, (b) 20 s in 3% solution, (c) 10 s in 7% solution, (d) 30 s in 7% solution.

[0035] Fig. 5 SEM photographs of ultra-pure Mg wires after etching (left) and without etching (right) after 1 hour, 4 hours and 2 months in MEM.

[0036] Fig. 6 Graph showing the dependence of the change in product weight on the immersion time of the product in MEM (top), graph showing the dependence of pH on the immersion time of the product in MEM (bottom).

[0037] Fig. 7 Photographs of a cable (taken with a 3D light microscope) produced according to Example 6, before immersion in DMEM, 4 days, 2 weeks and 1 month after immersion in DMEM.

[0038] Fig. 8 Graph showing the dependence of the maximum transmitted force on the immersion time of the cable in MEM compared to a cable whose surface was not etched but was only polished with polyurethane foam impregnated with 6% nitric acid.

[0039] Fig. 9 Graph showing measured etching depths from the surface of plates from various alloys etched in 3% aqueous HNO3 solution as a function of time.

[0040] Fig. 10 Typical examples of the new surface morphology after etching using the mentioned procedure: a) a ground piece of commercially pure Mg ingot with dimensions of approx. 6x15x1 mm3, without etching, b) the same piece of ingot after etching in a 10% nitric acid solution, c) surface morphology of the grains, visible on the wire from ultra-pure Mg, etched in 7% nitric acid solution.

[0041] Examples of embodiments

[0042] The following examples are only illustrative and the indicated etching times refer to the specific alloy used, to the specific lubricants and other substances used during the production process, and to the specific etchant, the etching ability of which depends, among others, on its freshness. In the examples fresh etchant was always used. A person skilled in the art is able to easily determine the specific etching conditions and times experimentally, for example as described in Example 1 or 2. Typical etching times range from 1 s to 20 minutes, depending on the above factors that affect etching effect, and depending on the requirements for the final product.

[0043] Example 1 (outside the scope of the invention)

[0044] Cylindrical samples of 20 mm height and 6 mm diameter of ultra-pure Mg are cut from the ingot by electro-erosion machining (EDM) using brass wire. In a beaker, 10 mL of 65% nitric acid with 90 mL of distilled water is mixed. The samples are placed in a beaker with etchant in the fume hood and left in the bath with constant stirring. After 10 s and 20 s, the diameter of the samples is measured with a digital caliper. Plastic tweezers are used to handle the samples to avoid contamination of the solution with iron when using steel tweezers. From the determined loss, the approximate time when the required material thickness is removed is linearly extrapolated (here 50 pm to compensate the thermal expansion of the sample in the inlet extrusion channel of the extrusion mold, in this case it was about 30 seconds). After a given time, the diameter of the samples is detected and the estimated time is iteratively adjusted until the desired diameter of the samples is reached, taking into account the possible need to replace the etchant with a new one. The samples are then moved as quickly as possible from the etchant beaker to the beaker with denatured alcohol. After moving all the samples, the denatured alcohol is mixed with the samples and then the samples are taken out and dried with a stream of hot air. Immediately after this procedure, the samples are transported to the extrusion mold, coated one by one on the entire surface with GLEIT - p® HP 505 lubricant and extruded in the extrusion mold at 300°C with a reduction ratio of 1 :576. The resulting 250 pm wires are wound on coils and stored in a dry environment. On the day of using the wires to investigate the properties of this material in a simulated body environment, the wires are cut into 5 cm segments. Their diameter is measured using a micrometer. In Petri dishes with a diameter of 10 cm 7% Nital from pure ethanol, and pure ethanol are prepared. One of the wire segments is cut into 1 cm sections, which are gradually etched to determine the time required to etch 10 pm from the surface of the wire, which is measured with a micrometer. On the final segment, the quality of the surface is checked using a stereo magnifier. The resulting etching time is recorded for further use on the same batch of material. The remaining wires are clamped in plastic tweezers at the very end of the wire, etched according to the determined time by immersion in the etchant while simultaneously moving the wire under the surface during etching. After the required time has elapsed, the wires are immediately immersed in a Petri dish with pure ethanol for at least 5 seconds while simultaneously moving the wire. Subsequently, the wires are dried by moving the tweezers with the wire in the air, the end of the wire clamped in the tweezers is cut off, and the resulting wires are prepared for experiments in a simulated body environment.

[0045] Example 2

[0046] From the delivered ingots of commercially pure Mg and Zn, segments are cut by a band saw in such a way so that they can be placed in a graphite cup with an internal diameter of 60 mm. These segments are etched in a 10% aqueous solution of 65% HNO3 with occasional stirring so that at least 10 pm are removed from each side. This material is subsequently remelted in an Ar atmosphere into a Mg-0.4Zn alloy (wt.%) and cast into a cylindrical steel mold with a diameter of 8 mm. This semi-finished product is subsequently machined on a lathe to a diameter of 5.9 mm, suitable for a mold for direct hot extrusion. The resulting machined bar is cut into 20 mm segments with a band saw. These are subsequently etched in a 10% aqueous solution of 65% HNO3 for such a time that at least 10 pm are removed from each side, which is determined by a caliper. These segments are coated on the entire surface with GLEIT - p® EIP 505 lubricant and extruded in the extrusion mold at 300 °C with a reduction ratio of 1 :400. The resulting 300 pm Mg-0.4Zn wires are wound on coils with a diameter of 10 cm and stored in a dry environment. A piece of wire is cut into 1 cm segments, which are gradually etched in a 10% aqueous solution of 65% HNO3 to determine the time required to etch 10 pm from the surface of the wire, which is measured with a micrometer. On the final segment, the quality of the surface is checked using a stereo magnifier. The resulting etching time is recorded for further use on the same batch of material. In this case, the etching time was about 30 seconds. The 2 - meter-long wire segments are coiled and immersed in a large container of etchant so that the wire does not bend more than when stored on the coil. Using the movement of the container, the etchant flows with respect to the wire. After the time defined by the test piece of wire has elapsed, the wires are transferred to a container of pure ethanol, washed by moving the container, and then air dried. These wires are subsequently coated with a biodegradable polymer, braided into cables of 7 wires each, sterilized and vacuum packed.

[0047] Example 3

[0048] From the Mg-0.4Zn alloy with a diameter of 300 pm wires were prepared according to Example 2 up until the wire extrusion step. Subsequently, after storage, the wire was divided into six 6 cm segments. Three of the segments were etched, washed and dried according to the procedure of Example 2 (etching 10 pm) and then immediately immersed in a tube with 45 m of minimal essential medium (DMEM modification). The other three wires were immersed in another test tube, but without etching the wires. Immediately after immersion, it was possible to observe the generation of hydrogen on both triplets of wires, but only the unetched wires generated so many hydrogen bubbles that they floated to the surface of the solution. Qualitatively, a significant reduction in hydrogen generation can be observed due to the wire etching process.

[0049] Both tubes were left open at a constant temperature of 37°C for 24 h. All 3 etched wires remained intact after 24 h. All 3 unetched wires were broken into at least 2 segments. At the bottom of the tube with unetched wires, the residues of corrosion products were visible, which gradually separated from the places where the wire breaking occurred.

[0050] Subsequently, a uniaxial tensile test was performed on these wires and on the initial wires. The original unetched wires were able to transmit a maximum of 17.1 ±0.5 N, which corresponds to 14.9±0.4N ifwe include a diameterreductionof20 pm after etching. The etched wires were able to transmit a maximum of 14.2±0.1 N after 24 h in DMEM, which is a reduction to 95% of the original value. The remaining (shorter) segments of unetched wires after 24 h in DMEM were able to transmit 15.9±1.3 N, which is a reduction to 93% of the original value. After such a short degradation, there is still no significant decrease in properties on the residues of unetched wires, however, a clearly higher dispersion of these values is evident. This variance is inappropriate for predicting the properties of wires for implant purposes. Above all, however, the fact that the wires were already segmented after 24 hours clearly precludes the possibility of using unetched wires for medical purposes.

[0051] To further verify the effectiveness of the etching process, 3 triplets of wires were prepared, which were etched in the described manner and left in the mentioned medium for 168 h. None of the wires was broken during visual inspection after this time interval. Example 4

[0052] As a part of the testing, etching tests were performed for the presence of undesirable corrosion products on thin wires made of the Mg-0.4Zn alloy, which is promising for further biomedical applications. A 10% aqueous solution of HNO3, 3% and 7% ethanol-based Nital, 4% solution of phosphoric acid in ethanol, and two commercially available alkaline cleaners without hydroxides, recommended by the manufacturer for application to Mg, were used. Fig. 3 shows the etching results in SEM photographs: a) untreated wire (without etching), (b) alkaline cleaning 2 min. in 25% solution Star® TN, (c) alkaline cleaning 2 min. in 5% solution Star® Forte, (d) etching 20 s in 4% solution H3PO4, (e) etching 20 s in 7% solution HNO3 + alkaline cleaning 2 min. in 100% solution Star® TN, (f) ) etching 20 s in 7% solution HNO3 + alkaline cleaning 2 min. in 100% solution Star® Forte. Fig. 4 shows in SEM photographs the results of etching using HNO3 solution in ethanol for different etching times and different concentrations of HNO3, specifically (a) 10 s in 3% solution, (b) 20 s in 3% solution, (c) 10 s in 7% solution, (d) 30 s in 7% solution. Scanning electron microscopy revealed insufficient etching of 250 pm wires or nucleation of undesirable corrosion products for all etchants not containing nitric acid. Alkaline cleaning with a 25% Star® TN solution or a 5% Star® Forte solution (concentration recommended by the manufacturer), with an immersion time in the solution of approx. 2 min, had no effect on the removal of the corrosion layer (Fig. 3 (b) and 3 (c)). When etching with a 4% H3PO4 solution for 20 s, the impurities were also not removed, in addition, new phases nucleated on the surface (Fig. 3 (d)). When testing the combination of alkaline cleaning and etching with HNO3 solution (in different orders), new undesirable phases also occurred (Fig. 3 (e) and 3 (1)). Considering these results, the cleaning of Mg wires with a solution of HNO3 in ethanol was evaluated as the best of these options. In the case of 3% Nital, the time needed to meet the required conditions was inadequately long (more than 10 minutes). For such thin wires, 7% Nital based on ethanol seems ideal, which is able to effectively etch the surface and ensure that the required conditions are met, i.e., it does not create new localized corrosion products, and the etching of a surface layer with a thickness of 10 pm is achieved, preferably with the necessary time within tens of seconds (~30 s).

[0053] Example 5 (outside the scope of the invention)

[0054] Furthermore, tests of this procedure were carried out on 250 pm wires made of ultra-pure Mg and commercially pure Mg prepared by direct hot extrusion using GLEIT - p® HP 505 lubricant. Minimum essential medium (MEM) was used to simulate the body environment. Wires were used in the form of commercially pure Mg without etching, ultra-pure Mg without etching, and ultra-pure Mg after etching in 10% aqueous HNO3 solution and drying in alcohol. Wires were immersed for up to 15 days in MEM in an incubator at 37°C. The change in the weight of the wires, possible segmentation of the wires and the change in the pff of the medium were monitored. The Fe content in commercially pure Mg led to segmentation of the wires after only 2 hours (can be solved by Zn or Mn alloying). The ultra-pure Mg wires remained intact for full 15 days (see Fig. 6 above). When the proposed etching procedure was not carried out and the ultra-pure Mg wires were only degreased in acetone and then washed in ethanol and dried, segmentation of these wires occurred after only 4 hours. On the surface of unetched wires, there was a very pronounced and localized nucleation of corrosion products, which, due to redeposition, accelerated the local degradation of the wire cross-section. The proposed etching procedure reduced this phenomenon very significantly.

[0055] In Fig. 5 SEM photographs of ultra-pure Mg wires after etching (left) and without etching (right) after 1 hour, 4 hours and 2 months in MEM are shown. It can be seen from the photos that if etching is not earned out, surface damage and lubricant residues lead to increased localization of corrosion, which results in worse mechanical properties and faster degradation of the product.

[0056] In Fig. 6 in the upper part there is a graph showing the dependence of the change in product weight on the immersion time of the product in MEM for commercially pure Mg wire, ultra- pure Mg wire and ultra-pure Mg wire after etching. A dashed line means that the wire has already broken. The increase in weight after the breakdown of the wire is caused by the fact that its surface increases and nucleation of corrosion products occur, e.g., phosphate, calcium, etc. From Fig. 6 above, it is clear that a wire made of commercially pure Mg will break down, due to the content of impurities, especially the ones on the surface. Impurities begin to dissolve, redeposition of material occurs in the surroundings, which accelerates local corrosion and the wire breaks down in most cases. If Mg is used after extrusion (unetched), it initially resists the degradation, but then localized corrosion due to impurities from the production step of extrusion and cracks on the surface, etc. begins to accelerate the degradation processes and the wire disintegrates very quickly (within 4 hours). If etched ultra-pure Mg is used, corrosion products increase and Mg decreases at the same time (these processes are approximately in balance).

[0057] Fig. 6 below shows the dependence of pH on the immersion time of the product in MEM. The change in pH is related to how Mg dissolves (= increases pH), which only indicates how much Mg has dissolved, but the goal is to make this process slower. The rate of the Mg dissolution process can be reduced either by using ultra-pure Mg or by adding Zn to the commercially pure Mg. The graph shows that the pH of both ultra-pure Mg increases similarly until the unetched ultra-pure Mg (i.e., with impurities from the production process) breaks down. Then it has a larger surface and Mg starts to dissolve faster. The pH graph proves that it really depends on the surface, not on the purity of the Mg itself, because even ultra-pure Mg breaks down, although it initially dissolves into the surrounding medium just as slowly as ultra- pure etched Mg, precisely due to the formation of corrosion products.

[0058] Example 6

[0059] Using the known methods, an ingot of Mg-6Zn alloy is prepared in an induction vacuum furnace and then etched for 20 s in a 10% aqueous solution of nitric acid (material removal approx. 30 pm), washed with denatured alcohol and air-dried. Subsequently, the ingot is homogenized for 24 hours at a temperature of 300°C in a protective atmosphere and etched using the same procedure, i.e., again approx. 30 pm. The ingot is machined using splinter machining into a rod with a square cross-section of 10x10 mm and then etched for 7 seconds in a 10% aqueous solution of nitric acid (material removal approx. 15 pm), washed with denatured alcohol and air-dried. Subsequently, this ingot is formed at 280°C with four passes through path "Be" by the angle channel extrusion method with the same cross-section. After each of the forming steps, the output material is machined back to a 10x10 mm cross-section and subsequently etched, washed and dried in the same procedure. From the resulting semi-finished product, screws for bone fixation with different dimensions are made by splinter machining on CNC machines. Before further processing, these screws are etched for about 20 seconds in a 10% aqueous solution of nitric acid so that at least 10 pm is removed from their surface. Subsequently, these screws are immersed in 7% nital for 120 seconds to achieve higher surface cleanliness (etched approx. 3 pm), immediately moved to pure alcohol for at least 5 seconds and then dried with a stream of hot air. These screws are then immediately sorted and vacuum packed with an emphasis on protecting their surface from contamination. The packaged screws are then sterilized by gamma radiation.

[0060] Example 7

[0061] Analogous to Example 6, homogenized ingots of the Mg-6Zn alloy are prepared and etched. These ingots are formed by direct extrusion with a large reduction ratio (> 1 TOO) at different temperatures, resulting in extruded strips several meters long with a cross-section of 1x10 mm2. These strips are then etched by immersion in a container with a 10% aqueous solution of nitric acid for 20 s to remove lubricant residues and achieve a clean surface (etched approx. 30 pm). The movement of the etching bath relative to the strips is achieved by a stirring device made of chemically resistant plastic. Plates of various sizes for bone fixation are subsequently made from the etched strips by CNC splinter etching. These plates are etched for 10 minutes in 7% nital based on denatured alcohol (material removal approx. 10 pm), washed in methanol for 10 s, dried in a well-ventilated hot air hood, vacuum packed and sterilized by gamma radiation.

[0062] Example 8

[0063] Analogously to Example 7, strips with a cross-section of 3x10 mm2are prepared from the Mg-3.3Zn-0.6Mn alloy, which are subsequently etched by immersion in a container with a 7% aqueous solution of nitric acid for 40 s to remove lubricant residues and achieve a clean surface (etched approx. 17 pm). These etched strips are subsequently hot-rolled in one step, when the strip thickness is reduced to 1.5 mm. These strips are subsequently etched by immersion in a container with a 7% aqueous solution of nitric acid for 30 s to remove lubricant residues and achieve a clean surface (etched approx. 10 pm). The movement of the etching bath relative to the strips is achieved by the movement of the strips in the etchant. Plates of various sizes for bone fixation are subsequently made from the etched rolled strips by CNC splinter etching. These plates are etched for 12 min in 7% ethanol-based nital (material removal approx. 10 pm), washed in ethanol for 10 s, dried with hot air, vacuum packed, and sterilized by gamma radiation.

[0064] Example 9

[0065] A very significant benefit of this procedure was documented in the production of a prototype of a biodegradable sternum fixation for pediatric patients. The resulting product is a braided cable of 7 wires made of Mg-0.4Zn alloy according to Example 2, where the individual wires are covered with an approximately 20 pm layer of biodegradable L-lactide / caprolactone copolymer in a molar ratio of 70 / 30. For the experiment, wires from the same production batch, made from an intermediate product that was etched after machining according to the established procedure, the same polymer and the same test medium were used. The resulting cables were soaked in MEM in an incubator for a defined time and then a uniaxial tensile test was performed on these wires to determine the loss of mechanical properties in vitro. Two groups were created where the only different parameter was the etching of the wires after extrusion, i.e., the etching step (+ washing and drying) in the diagram in Fig. 1. The first group was etched according to the required procedure. The second group was hand polished using polyurethane foam impregnated with the same etchant (10% aqueous solution of 65% HNO3) that was used to etch the first group. In the case of the second group, polishing was stopped as soon as a visually shiny surface was achieved. The unexposed (unetched) cable prototype, regardless of the cleaning process, was able to transmit a maximum of 64±3 N during a uniaxial test. After 4 weeks in MEM, the cables, prepared according to the procedure described above according to Fig. 1, were capable of transmitting 34±4 N, and cables, polished with acid-impregnated polyurethane foam, failing to meet the required procedures, only 13±3 N.

[0066] In Fig. 7 there are photographs of a cable produced according to Example 6, before immersion in DMEM, 4 days, 2 weeks and 1 month after immersion in DMEM. From the Fig. the stability of the cable produced using the process according to the invention can be seen.

[0067] Fig. 8 shows the dependence of the maximum transmitted tensile force on the immersion time of the cable in MEM, compared to a cable the surface of which was not etched, but was only polished with polyurethane foam impregnated with nitric acid. Fig. 8 shows, that the process according to the invention improves the mechanical properties of products based on magnesium and its alloys compared to products that did not undergo the process according to the invention.

[0068] Due to the fact that the system with mechanical polishing of the wire using acid-impregnated polyurethane foam was in the first version an attempt to make the etching process more efficient, and only later it turned out to be a highly unsuitable process, it is possible that there are products on the market that are cleaned inadequately. The chemical etching procedure defined here defines easily verifiable conditions that must be met to ensure the best possible properties of biodegradable implants. It is very difficult to reveal the shortcomings of conventional mechanical polishing or other forms of currently used cleaning and surface treatment of biodegradable implants based on Mg, even with the use of the most modern scientific infrastructure, which is often not available to industrial enterprises. That is why the conditions proposed here are important.

[0069] The proposed method according to the invention is therefore critical for ensuring the maximum properties of biodegradable Mg-based implants, especially those implants that have small dimensions in at least one direction (wires, plates, small screws, stents), where localized corrosion can easily lead to failure or limitation of the properties of the entire implant.

[0070] Example 10

[0071] For various etchants and alloys, approximate etching times were determined for etching of 10 pm (tio) from all locations on the product surface by linear interpolation between the two nearest measured etching times. Depending on the microstructure (history of thermomechanical processing), the etching time can vary significantly. For very dirty or deformed surfaces (e.g., thin extruded wire) the initial speed of etching can be significantly higher. The symbol ~ indicates a large data dispersion and difficult repeatability of etching, when the freshness of the etchant must also be considered. For the investigated alloys, the etching times of nital with concentrations less than 7% were inadequately long (>1000 s). The results are shown in Table 1 below.

[0072] Table 1

[0073] Example 11

[0074] Lower concentrations of the aqueous nitric acid solution are advantageous for cases where it is necessary to precisely control the thickness of the etched layer. Fig. 9 shows the measured etching depths from the surface of approximately 1 mm thick plates from various alloys etched in a 3% aqueous solution of nitric acid. For the first minute, the etching rate is strongly dependent on contamination and damage to the surface layer of the sample. After that, the etching rate is stabilized. Each point is given by the average of at least three measurements.

[0075] Industrial applicability

[0076] The procedure will find application in all cases where it is necessary to ensure the repeatability of the production of biodegradable Mg-based devices due to the degradation properties in the body environment, especially for those devices where at least one of the overall dimensions of the medical device is smaller than 2 mm (plates, wires, stents, clamps) or where there is such a thin segment of a medical implant, critical for its proper function (screws - thread) or where there is a notch or other concentrator of mechanical stress on the surface. This procedure will ensure the greatest effect for low-alloyed Mg, or such a thermomechanical treatment of Mg alloys, where there are no large phases that can cause independent, local corrosion on the original surface. These are mainly Mg-based materials in the range of alloying elements in wt.%: (0<Zn<7); (0<Ca<l); (0<Mn<0.5); (0<¥<l); (0<Sc<0.5) with an average phase size smaller than 1 pm. In general, however, the procedure can be advantageously used on all metal-based body-absorbable materials, which are etched by nitric acid and etchants derived from it, and the corrosion products of which with these etchants are not harmful to the body and do not cause localized corrosion, or can be easily dissolved by washing in ethanol or methanol or a combination thereof.

[0077] Examples of uses include (but are not limited to): cerclage wires and soft bone wires, including fixation wires (made by extrusion and drawing), Kirschner wires and K-wires, plates, miniplates, maxillofacial plates and fixation devices (made by extrusion, machining, forging, electroerosion and any combination thereof), spikes (produced by extrusion, machining, forging, electroerosion and any combination thereof), cables and ribbons made of the above- mentioned wires, the above-mentioned products subsequently or in intermediate steps coated with biodegradable polymers, copolymers or otherwise functionalized, for example by electrospinning, application of hydroxyapatite or other calcium phosphates, including substituted ones, the above-mentioned products surface-treated by means of plasma dedusting or sputtering or micro-arc oxidation, the use of the above-mentioned products for strengthening or improving the properties of biodegradable composites, including the reinforcement of bone cements and the reinforcement of scaffolds for tissue engineering and regeneration from hydroxylapatite, collagen or any combination thereof.

[0078] Reference

[0079] [1] WANG, Jia-Li, Jian-Kun XU, Chelsea HOPKINS, Dick Ho-Kiu CHOW and Ling QIN. Biodegradable Magnesium-Based Implants in Orthopedics — A General Review and Perspectives. Advanced Science. 2020, 7(8), 1902443. ISSN 2198-3844.

[0080] [2] NGUYEN, T L, A BLANQUET, M P STAIGER, G J DIAS and T B F WOODFIELD. On the role of surface roughness in the corrosion of pure magnesium in vitro. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2012, 100B(5), 1310-1318. ISSN 1552- 4973.

[0081] [3] AHMADKHANIHA, D, M FEDEL, M HEYDARZADEH SOHI and F DEFLORIAN. Corrosion behavior of severely plastic deformed magnesium based alloys: A review. Surface Engineering and Applied Electrochemistry. 2017, 53(5), 439-448. ISSN 1934-8002.

[0082] [4] GILL, Randeep Singh, Kamal KUMAR and Uma BATRA. Surface Characteristics and Corrosion Behavior of Wire Electrical Discharge Machining Processed Mg-4Zn Alloy. Journal of Materials Engineering and Performance. 2021, 30(4), 2955-2966. ISSN 1544-1024.

[0083] [5] ALI, Murad, Mohamed ELSHERIF, Ahmed E. SALIH, Anwar UL-HAMID, M. A. HUSSEIN, Seongjun PARK, Ali K. YETISEN and Haider BUTT. Surface modification and cytotoxicity of Mg-based bio-alloys: An overview of recent advances. Journal of Alloys and Compounds. 2020, 825, 154140. ISSN 09258388.

[0084] [6] WEI, Dongsong, Jinguo WANG, Yan LIU, Dawei WANG, Shuyi LI and Huiyuan WANG. Controllable superhydrophobic surfaces with tunable adhesion on Mg alloys by a simple etching method and its corrosion inhibition performance. Chemical Engineering Journal. 2021, 404, 126444. ISSN 1385-8947. [7] SEITZ, Jan-Marten, Dennis UTERMOHLEN, Eric WULF, Christian KLOSE and Friedrich-Wilhelm BACH. The Manufacture of Resorbable Suture Material from Magnesium - Drawing and Stranding of Thin Wires. Advanced Engineering Materials. 2011, 13(12), 1087- 1095. ISSN 1438-1656.

[0085] [8] WENG, Weijie, Arne BIESIEKIERSKI, Yuncang LI, Matthew DARGUSCH and Cuie WEN. A review of the physiological impact of rare earth elements and their uses in biomedical Mg alloys. Acta Biomater ialia. 2021, 130, 80-97. ISSN 1742-7061.

[0086] [9] NIENABER, Maria, Merle BRAATZ, Noomane BEN KHALIFA and Jan BOHLEN. Property profile development during wire extrusion and wire drawing of magnesium alloys AZ31 and ZX10. Materials & Design. 2022, 224, 111355. ISSN 0264-1275.

[0087]

[0010] GRIEBEL, Adam J and Natalie ROMICK. In Vitro Degradation of Magnesium Wire in Sternal-Closure-Like Conditions. In: Steven BARELA, Aeriel LEONARD, Petra MAIER, Neale R NEELAMEGGHAM and Victoria M MILLER, ed. Magnesium Technology) 2023. Cham: Springer Nature Switzerland, 2023, s. 91-94. ISBN 978-3-031-22645-8.

[0088]

[0011] A. Griebel and J. Schaffer, “Magnesium-based absorbable alloys”.

[0089] WO Patent 2020 / 247383 Al, 3 June 2019.

[0090]

[0012] TESAR Karel, Tenke hofcikove draty pro biodegradabilni implantaty, disertacni prdce, katedra materials, FJFI CVUT v Praze, 2023.

[0091]

[0013] TONDO, Leonardo, Martin ALDA, Michael BAUER, Veerle BERGINK, Paul GROF, Tomas HAJEK, Ute LEWITKA, Rasmus W LICHT, Mirko MANCHIA, Bruno MULLER- OERLINGHAUSEN, Rene E NIELSEN, Marylou SELO, Christian SIMHANDL, Ross J BALDESSARINI a for the International Group for Studies of Lithium (IGSLI). Clinical use of lithium salts: guide for users and prescribers. International Journal of Bipolar Disorders. 2019, 7(1), 16. ISSN 2194-7511.

[0092]

[0014] https: / / patents.google.com / patent / US2016Q138148Al / en

[0093]

[0015] https: / / patents.google.com / patent / US2149436A

Claims

CLAIMS1. A method of surface treatment of a product for a biomedical application based on a magnesium alloy containing at least 85 wt.% magnesium, characterized in that it comprises the steps of etching at least 10 pm from each point of the product surface by immersing the product in a bath containing 3 to 20%vol. HNO3 in water or 1 to 15%vol. HNO3 in alcohol or in a mixture of alcohol and water, where the alcohol is ethanol, methanol, denatured alcohol or a mixture thereof, washing the product in a bath containing ethanol, methanol, denatured alcohol, acetone or a combination thereof, wherein the delay between the etching step and the washing step is 1 minute at most.

2. The method of surface treatment according to the claim 1, characterized in that in the etching step, the product and / or the bath is non- stationary.

3. The method of surface treatment according to any of claims 1 and 2, characterized in that the washing step is followed by the drying step.

4. The method of surface treatment according to any of claims 1 to 3, characterized in that the washing step is followed by the drying step and the drying step is followed by the product surface functionalization step and / or product sterilization and / or product packaging step.

5. The method of surface treatment according to any of claims 1 to 4, characterized in that the etching and washing steps are performed during the production of the magnesium alloy product, wherein the production of the product comprises one or more production steps selected from the group comprising machining the product, forming the product, forging the product, heat treatment of the product, and wherein the product etching and washing steps are performed before each of the production steps.

6. The method of surface treatment according to the claim 5, characterized in that the etching and washing steps are performed after each of the production steps of machiningthe product, forming the product, forging the product, heat treatment of the product, and wherein if there is a product storage step at any time during the product production process, the etching and washing step is performed after the product storage step.

7. The method of surface treatment according to any of claims 1 to 6, characterized in that the etching is carried out by immersing the product in a bath containing 3 to 12%vol. HNO3 in water, ethanol, methanol, denatured alcohol, or a mixture thereof.

8. The method of surface treatment according to any of claims 1 to 7, characterized in that the etching is carried out by immersing the product in a bath containing 10%vol. HNO3 in water, or the etching is carried out by immersing the product in a bath containing 3%vol. HNO3 in water, or etching is carried out by immersing the product in 7% Nital.

9. The method of surface treatment according to any of claims 1 to 8, characterized in that the product is a product for biomedical application, which contains at least 90.5 wt.% magnesium and max. 7 wt.% Zn, max. 1 wt.% Ca, max. 0.5 wt.% Mn, max. 1 wt.% Y, and max. 0.5 wt.% Sc.

10. The method of surface treatment according to any of claims 1 to 8, characterized in that the product is a product for biomedical application, which contains 93% to 99.95 wt.% magnesium and 0.05 - 7 wt.% Zn.

11. The method of surface treatment according to any of claims 1 to 10, characterized in that the product is a medical device or a semi-finished product for the production of a medical device.

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