Method of making a medical device or medical component

Abstract

The present invention relates to a method of preparing a medical device or a medical component comprising a material body containing an amorphous alloy. The method comprises the steps of: (a) providing a starting material body comprising an amorphous alloy, the amorphous alloy comprising: i. a primary alloying component selected from the group consisting of titanium copper (TiCu) and zirconium copper (ZrCu), and ii. one or more secondary alloying components comprising at least one noble metal selected from the group consisting of ruthenium (Ru), rhodium (Rh), palladium (Pd), silver (Ag), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), and combinations thereof, and (b) subjecting the starting material body to an etching treatment using an etching solution that dissolves at least one alloying element of the primary alloying component i) at a higher dissolution rate than at least one noble metal of the secondary alloying components ii).

Description

[0001] The present invention relates to a method for preparing a medical device or medical component as described in the preamble of claim 1, and to a medical device or medical component prepared by the method.

[0002] Medical devices or medical components, such as surgical devices or implants, are typically made of biocompatible materials that exhibit mechanical properties that meet the stringent requirements of the device or component.

[0003] For example, dental implants are typically made of pure titanium or ceramic materials, particularly zirconia-based ceramics. Furthermore, dental implants made of titanium alloys (such as titanium-zirconium alloys or Ti-6Al-4V alloys) have been successfully introduced to the market due to the material's excellent combination of high strength, high corrosion resistance, and sufficient biocompatibility.

[0004] Despite the excellent mechanical properties of titanium alloys currently in use, further reduction in the size of dental implants and other medical devices or components is limited due to the associated decrease in stability.

[0005] To meet the needs of modern surgery for further miniaturization of medical devices or components without unacceptably reducing their mechanical properties, amorphous metals, especially amorphous alloys such as bulk metallic glass, have recently gained increasing attention.

[0006] For example, CN110464497A relates to a dental implant made of titanium-based amorphous metal, characterized by comprising: 30-75 parts titanium, 0-25 parts zirconium, 0-45 parts copper, 0-20 parts silicon, 0-10 parts iron, 0-10 parts zinc, 0-5 parts silver and 0-15 parts palladium.

[0007] Similarly, CN110464498A relates to a zirconium-based amorphous metal dental implant, characterized by comprising: 30-65 parts zirconium, 0-25 parts titanium, 0-45 parts copper, 0-20 parts aluminum, 0-20 parts silicon, 0-10 parts iron, 0-10 parts zinc and 0-5 parts palladium.

[0008] The amorphous metal compositions disclosed in CN110464497A have been found to possess the potential to exhibit significantly higher compressive yield strength and fatigue resistance than Ti-6Al-4V. Furthermore, these materials have been found to have high biocompatibility. Therefore, this material is an attractive candidate for applications aiming to reduce device size but where degradation of mechanical properties must be avoided or at least kept to a low level.

[0009] Specifically, Ti 40 Zr 10 Cu 36 Pd14 Bulk metallic glasses (BMGs) have been reported as promising candidates for future biomedical applications due to their high glass-forming ability, absence of toxic elements, and favorable mechanical properties (see A. Liens et al., “On the Potential of Bulk Metallic Glasses for Dental Implantology: Case Study on Ti...). 40 Zr 10 Cu 36 Pd 14 (Materials 2018, 11, 249). The article by A. Liens et al. also reported that each BMG has a higher corrosion potential than the Ti-6Al-4V alloy, indicating that BMG requires more energy to initiate the corrosion reaction.

[0010] However, the article also reports pitting corrosion in titanium-based glassy (amorphous) alloys. In the article cited above, this undesirable effect is explained by the presence of copper oxide on the surface of the passivation layer of BMG, and copper is found to significantly reduce the corrosion resistance of both the metallic alloy and the metallic glass.

[0011] Although the harmful effects of pitting corrosion on materials are not yet fully understood, given that the materials are intended for use in medical devices or components, it is desirable to reduce or even eliminate such effects while maintaining the desired properties of mechanical stability and biocompatibility.

[0012] In view of the above-mentioned drawbacks, the object of the present invention is to provide a method for manufacturing a medical device or component having amorphous alloy (particularly Ti-based BMG, such as Ti) in terms of mechanical properties and biocompatibility. 40 Zr 10 Cu 36 Pd 14 It exhibits the beneficial properties of ) but at the same time shows a reduced tendency to pitting corrosion.

[0013] This objective is achieved by the subject matter of claim 1. Preferred embodiments of the invention are defined in the dependent claims.

[0014] Therefore, as claimed in claim 1, the present invention relates to a method for preparing a medical device or medical component comprising a body of material containing an amorphous alloy.

[0015] The method includes the following steps:

[0016] (a) Providing a starting material bulk comprising an amorphous alloy, the amorphous alloy comprising:

[0017] i. Select the main alloying components from the group consisting of titanium copper (TiCu) and zirconium copper (ZrCu), and

[0018] ii. One or more secondary alloying components comprising at least one noble metal selected from the group consisting of ruthenium (Ru), rhodium (Rh), palladium (Pd), silver (Ag), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), and combinations thereof, and

[0019] (b) The starting material body is etched using an etching solution that dissolves at least one alloying element of the primary alloying component of (i) at a higher dissolution rate than at least one noble metal of the secondary alloying component of (ii).

[0020] Therefore, the etching solution enables the alloying elements (i.e., titanium or zirconium, or copper, depending on the case) in the primary alloying component of i) to be preferentially dissolved compared to one or more noble metals in the secondary alloying component of ii).

[0021] According to a preferred embodiment, the etching solution dissolves the at least one noble metal in ii) at a lower dissolution rate than all the other alloy components. Specifically, the at least one noble metal in ii) is either completely undissolved or only dissolved to a negligible degree.

[0022] According to a specific embodiment of the present invention, wherein one or more secondary alloying components of ii) comprise palladium (Pd) and at least one noble metal selected from the group consisting of ruthenium (Ru), rhodium (Rh), silver (Ag), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), and combinations thereof, and the etching solution primarily dissolves titanium and / or zirconium, which are alloying elements of the main alloying component i).

[0023] According to another specific embodiment, wherein one or more secondary alloying components of ii) do not contain palladium and at least one noble metal selected from the group consisting of ruthenium (Ru), rhodium (Rh), silver (Ag), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), and combinations thereof, and the etching solution primarily dissolves copper, which is an alloying element of the primary alloying component i). In other words, if the amorphous alloy does not contain palladium, the dissolution of copper takes precedence over other alloying elements of the primary alloying component i) (i.e., titanium and / or zirconium) and other noble metals of the secondary alloying component ii).

[0024] In the course of this invention, it has been found that a surface region obtained through the specific etching process of this invention contains a higher proportion of the noble metal component of the secondary alloying component (ii) compared to the material of the rest of the material body. This surface region (at least its outermost region) has been found to be crystalline.

[0025] Regarding corrosion resistance, the modified surface areas have been found to exhibit properties similar to passivation layers (or pseudo-passivation layers), thus significantly reducing the tendency for devices or components to suffer pitting corrosion. (In this respect, pseudo-passivation is characterized by a moderate increase in current density when the potential is increased.)

[0026] Ultimately, the method of the present invention thus allows for the production of medical devices or components that exhibit excellent mechanical properties and remain stable even when kept in corrosive environments. This, in turn, makes it possible to further reduce the size of existing medical devices or components while still exhibiting sufficient mechanical properties and stability over time despite the reduction in size.

[0027] In addition to the above findings, it was also found that the high biocompatibility of the amorphous alloy is not negatively affected by the etching treatment in step (b). Specifically, for the medical device or component of the present invention, very low percentages of hemolysis of red blood cells and whole blood were measured, highlighting its suitability for invasive procedures that come into contact with blood and body tissues. According to this finding, fibroblast activity was found to be unaffected by or even slightly improved by the treatment according to the present invention, and the treatment does not increase the low cytotoxicity of the amorphous alloy.

[0028] Furthermore, the medical device or component has been found to exhibit antibacterial activity, as confirmed by increased OH radical release and reduced biofilm formation in relevant biofilm studies. This further underscores the material's suitability for use in medical devices or components that come into direct contact with the human body.

[0029] Furthermore, in the context of this invention, it has been found that etching processes result in roughening of the surface of the device or component, particularly of porous surface areas. This is especially important for the potential use of the device or component in dental implant systems (more particularly as a dental implant or dental implant abutment), as there is evidence that more significant roughness is associated with improved surface-to-surrounding tissue interaction. Therefore, components of dental implant systems exhibiting improved osseointegration properties and / or improved soft tissue interaction capabilities can be obtained.

[0030] In addition to increased corrosion resistance and improved bone-soft tissue interaction, the method of the present invention also causes a color change in the starting material, particularly a golden hue. This can be advantageous in some applications, especially considering the enhanced aesthetic appearance of the device or component. In particular, the golden color is of particular interest for the transmucosal region (implant-soft tissue interface) of dental implant systems, such as abutments for dental implant systems. Furthermore, the resulting golden color can also be advantageously used to facilitate intraoral scanning due to the associated brightness and reflectivity; therefore, the devices or components of the present invention are particularly suited for such applications.

[0031] According to a particularly preferred embodiment of the invention, the material body containing the amorphous alloy used is in the form of bulk metallic glass (or BMG), amorphous alloy ribbon, or amorphous alloy film. In the context of this invention, the terms "bulk metallic glass" or "BMG" refer to amorphous alloys in bulk form (synonymous with metallic glass). Specifically, the term "bulk form" in this respect means that the amorphous alloy can be produced in the form of a fully dense amorphous rod having a diameter or thickness of at least 100 μm, preferably at least 1 mm. In contrast, amorphous alloy ribbons involve a bulk with a smaller thickness (typically in the range of 10 μm to 100 μm), while amorphous alloy films have a thickness smaller than that of amorphous alloy ribbons and typically less than 10 μm. Thin films (e.g., films deposited on the surface of a substrate or core) typically have a thickness of up to 500 nm.

[0032] For the purposes of this invention, amorphous alloys containing titanium and copper as primary alloying components are particularly preferred because they offer excellent specific strength, high corrosion resistance, high hardness, low Young's modulus, and ductility and machinability, which are particularly advantageous for medical devices and components. Further preferred in this respect is that the titanium-copper based amorphous alloy optionally also contains palladium (Pd) and zirconium (Zr) as secondary alloying components, as this material has been found to be particularly suitable for biomedical applications, primarily due to the absence of toxic elements such as nickel (Ni) or beryllium (Be). Furthermore, the amorphous alloys of this system have been found to exhibit sufficiently high glass-forming ability to cast fully amorphous phases, such as dental implants and dental instruments for oral implantation, without impairing their mechanical properties.

[0033] Regarding the titanium-copper-based amorphous alloy that optionally contains Pd and Zr as secondary alloying components, it is further preferred that the amorphous alloy also contains at least one third alloying component selected from the group consisting of iron (Fe), gallium (Ga), tin (Sn), silicon (Si), yttrium (Y), silver (Ag), scandium (Sc), sulfur (S), niobium (Nb), hafnium (Hf), zinc (Zn), tantalum (Ta), and mixtures thereof.

[0034] More specifically, based on a total amount of 100% by weight of amorphous alloy, the amorphous alloy comprises 15-55% by weight of titanium, 1-45% by weight of copper, 0-30% by weight of palladium, 0-30% by weight of zirconium, 0-10% by weight of silicon, 0-20% by weight of iron, 0-10% by weight of zinc and 0-20% by weight of silver.

[0035] In this regard, it is further preferred that, based on a total amount of 100% by weight of the amorphous alloy, the amorphous alloy comprises:

[0036] 20-45% by weight, preferably 25-35% by weight, of titanium.

[0037] 15-45% by weight, preferably 30-45% by weight of copper.

[0038] 5-30% by weight, preferably 10-20% by weight, of zirconium.

[0039] Palladium of 0-30% by weight, preferably 0-25% by weight,

[0040] 0-15% by weight, preferably 0-10% by weight of tin.

[0041] 0-2% by weight, preferably 0-1% by weight, of silicon.

[0042] 0-10% by weight, preferably 0-5% by weight of iron,

[0043] And 0-15% by weight, preferably 0-10% by weight, of silver.

[0044] Most preferably, the amorphous alloy has a composition of Ti. 40 Cu 36 Zr 10 Pd 14 (or Ti) 40 Zr 10 Cu 36 Pd 14 The subscripts refer to the atomic percentages of each component. This material has been found to exhibit exceptionally good mechanical properties compared to currently used Ti-6Al-4V alloys, particularly much higher strength and a much lower Young's modulus. The specific suitability of this material for the purposes of this invention will be discussed in detail in the context of the working examples below.

[0045] Alternatively, amorphous alloys can have Ti 40 Cu 40 Zr 11 The composition of Fe3Sn3Ag3, where the subscripts refer to the atomic percentage of each component. This material and its specific suitability for the purposes of this invention are also the subject of the working examples discussed below.

[0046] Regarding step (b) of the method of the present invention, it has been found that a very efficient etching process is achieved when using an etching solution containing NH4 and H2O2, which therefore relates to a particularly preferred embodiment of the present invention. If desired, the preferred etching solution may also contain H2O to reduce reaction kinetics. Regarding the percentages and proportions of the components, it is preferred that the volume percentages of NH4 and H2O2 in the etching solution are each from 25 vol% to 75 vol%. According to a particularly preferred embodiment, the etching solution is a mixture containing NH4 and H2O2 in a volume ratio of about 1:1. If water is added, the etching solution can particularly be a mixture of NH4, H2O2, and H2O in a volume ratio of about 5:1:4 to about 5:4:1, for example, volume ratios of 5:1:1, 5:2:1, 5:3:1, 5:4:1, 5:1:2, 5:1:3, and 5:1:4. In one embodiment, the volume ratio is preferably 5:4:1. In another embodiment, the volume ratio is preferably 5:1:4.

[0047] By appropriately setting the processing temperature, the reaction kinetics can be further adjusted to suit specific needs. According to a straightforward and safe implementation of the method, the etching process is performed at room temperature.

[0048] The duration of etching depends on the selected temperature and the target size of the modified surface region. In the context of this invention, it has been found that surface region modification occurs within the first few minutes of the etching process due to the different dissolution rates of the alloying elements. According to a preferred embodiment, the etching process is therefore carried out at room temperature for at least 5 minutes, preferably at least 15 minutes, and more preferably at least 30 minutes. According to another preferred embodiment, the etching process can continue for several hours.

[0049] In addition to the methods described above, according to another aspect, the present invention relates to medical devices or medical components prepared by such methods. Therefore, devices or components according to this aspect of the invention comprise a material body containing an amorphous alloy, said amorphous alloy comprising:

[0050] I. Select the main alloying components from the group consisting of titanium copper (TiCu) and zirconium copper (ZrCu), and

[0051] II. One or more secondary alloying components, comprising at least one noble metal selected from the group consisting of ruthenium (Ru), rhodium (Rh), palladium (Pd), silver (Ag), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), and combinations thereof.

[0052] According to the present invention, the material body includes a surface region having at least one noble metal of a secondary alloy component in an increased proportion compared to the rest of the material body.

[0053] Referring to the method of the present invention disclosed above, depending on whether the secondary alloying component contains palladium (depending on ii), the surface region is obtained by selective or preferential dissolution of titanium, zirconium, or copper. Therefore, the term "remaining portion of the material body" refers to a portion of the material body extending from its depth in a direction away from its surface. More specifically, in this respect, depth refers to a region of the material body that the etching solution cannot reach.

[0054] According to one specific embodiment, the device or component of the present invention comprises a core or substrate and a surface region at least partially surrounding said core or substrate. Thus, the core or substrate can be made of an amorphous alloy, and specifically relates to the amorphous alloy state of the starting material bulk prior to processing. Alternatively, it is also contemplated that the core or substrate is made of a crystalline material, such as a metal, such as titanium or a titanium alloy (e.g., Ti6Al4V), on which the aforementioned surface region is coated. Considering the coating of the core or substrate (e.g., by deposition of an amorphous alloy), it is also contemplated that the surface of the core or substrate be modified by roughening treatments (e.g., by sandblasting, laser processing, or machining) to improve coating adhesion.

[0055] As described above, the medical device or component of the present invention exhibits a significantly reduced tendency to pitting corrosion. Due to the improved corrosion resistance (having properties similar to a passivation layer), the device or component has the advantage of maintaining corrosion resistance even after prolonged exposure to humid and warm environments.

[0056] As described above, the etching process of the above method results in surface roughening. Specifically, pores are formed by selectively dissolving alloy components other than noble metals contained in the amorphous alloy.

[0057] More specifically, the surface region of the device or component preferably contains holes and / or pores with an average size of 5-30 nm. These holes or pores are particularly important for devices or components intended to interact with surrounding tissues at the point of use. This is especially true when the device or component is used as a dental implant or dental implant abutment, where improved osseointegration and / or improved soft tissue interaction capabilities can be achieved due to the aforementioned surface morphology.

[0058] According to one specific embodiment, the surface has a diameter of 2-3 m. 2 / g, especially 2.17 m 2 The morphology defined by the BET surface area / g (+ / -0.09). The measurement of BET surface area (according to the Brunauer-emmett-teller (BET) theory) is known to those skilled in the art and involves the physical adsorption of gas molecules on a solid surface, thus reflecting the specific surface area of ​​the corresponding surface portion of the device or component.

[0059] The device or component is further preferred for use as a dental implant or dental implant abutment from the perspective that, due to the high stability of the amorphous alloy used according to the invention, a smaller implant or abutment size than conventional metals can be achieved. However, in addition to the dental implants and dental implant abutments described above, the invention covers any type of medical device or component, particularly any surgical and dental device and its components.

[0060] Therefore, the medical device or medical component is preferably a surgical device or dental implant, prosthesis, or abutment, preferably a prosthesis or abutment supporting a dental implant, and more preferably a screw for supporting a prosthesis or abutment of a dental implant. However, the medical device or component may also be a surgical or dental instrument, preferably a dental instrument, more preferably a dental drive tool, or a handheld device for surgical or dental procedures, particularly a handheld device for dental procedures, or a motor for surgical or dental procedures, particularly a motor for dental procedures.

[0061] Example

[0062] The present disclosure is further illustrated by the following examples, which should not be construed as limiting the scope or spirit of the disclosure, but rather as illustrating certain implementation methods. Unless otherwise specified, reagents and solvents are used as is, from commercial suppliers.

[0063] In the context of these embodiments, reference is made particularly to the accompanying drawings, in which:

[0064] Figure 1 The method of the present invention shows the Ti obtained after treating the sample with a mixture containing NH4 and H2O2 (volume ratio 1:1) for 1 hour at room temperature. 40 Zr 10 Cu 36 Pd 14 SEM images of the morphology of BMG components;

[0065] Figure 2 shows the etching solution used as the first sample. Figure 2B The second sample's etching solution consisted of a mixture of NH4 and H2O2 (volume ratio 1:1), which was treated at room temperature for 1 hour on Ti. 40 Zr 10 Cu 36 Pd 14 XPS spectra measured on an amorphous alloy (BMG) disk, compared with those of an untreated control sample. Figure 2A ) for comparison;

[0066] Figure 3 It shows a composition of Ti 40 Zr10 Cu 36 Pd 14 Anodic and cathodic polarization curves of a body made of amorphous alloy and treated according to the present invention (“CS”, treated with a 1:1 NH4 / H2O2 etching solution for 1 hour), wherein polarization was performed in a 0.9% w / v NaCl solution at pH 7.4 and 37°C, were compared with polarization curves measured on an untreated body.

[0067] Figure 4 As shown above, for Figure 3 The anodic and cathodic polarization curves of the defined composition and treated bulk, wherein polarization was performed at pH 2.3 and 37 °C in 0.9 % w / v NaCl solution (also containing 1 % w / v lactic acid), were compared with the polarization curves measured for the untreated bulk.

[0068] Figure 5 illustrates the method according to the invention (based on Ti) using a concentrated etch solution (CS) as defined above. 40 Zr 10 Cu 36 Pd 14 Whole blood on the sample obtained ( Figure 5A ) and red blood cells ( Figure 5B The percentage of hemolysis was plotted against untreated samples and control samples made of SiO2, Mg alloy and commercially pure titanium (Cp-Ti).

[0069] Figure 6 The figure shows the adhesion to the surface treated according to the present invention (based on Ti mentioned in Figure 2), as determined by nucleocounting. 40 Zr 10 Cu 36 Pd 14 A diagram illustrating the average number of HGF-1 cells (human gingival fibroblasts) in the BMG disc, compared with the average number of cells attached to an untreated control sample;

[0070] Figure 7 A diagram illustrating the average lactate dehydrogenase (LDH) activity of HGF-1 cells after contact with a surface treated according to the present invention is shown, compared with an untreated control sample.

[0071] Figure 8 The results show the effects on Ti after treatment for 1 hour and 6 hours without stirring using a mixture of NH4, H2O2, and H2O (“DS”; volume ratio 5:1:4) as the etching solution, as well as after treatment for 1 hour with the same etching solution under stirring. 40 Cu 40 Zr11 XPS spectra measured on an amorphous alloy strip of Fe3Sn3Ag3, compared with an untreated reference sample;

[0072] Figure 9 The diagram illustrates the advancing contact angles measured for a first sample treated with an etching solution of NH4 and H2O2 (volume ratio 1:1), a second sample treated with an etching solution of NH4, H2O2 and H2O (volume ratio 5:1:4), and an untreated control sample when in contact with deionized water (for the first wettability measurement) and diiodomethane (for the second wettability measurement).

[0073] Figure 10 This involves Ti treated with etching solution for three different processing times. 40 Cu 40 Zr 11 The image shows the release of OH radicals on the Fe3Sn3Ag3 amorphous alloy strip as determined by EPR (electron paramagnetic resonance) spectroscopy, compared with the untreated strip and the blank control. The first sample was treated with an etching solution of NH4 and H2O2 (volume ratio 1:1), and the second sample was treated with an etching solution of NH4, H2O2 and H2O (volume ratio 5:1:4).

[0074] Figure 11 Involving in Figure 10 The bacterial biofilm formation on the sample mentioned in the article (Pseudomonas aeruginosa) pseudomonas aeruginosa The diagram illustrates the extent of the effect, which is further compared with the corresponding data obtained for Cu and Cp-Ti samples;

[0075] Figure 12 involves Figure 10 Hemolysis of the sheep defibrinated whole blood sample shown ( Figure 12A ) and hemolysis of purified red blood cells obtained from them ( Figure 12B The figure is illustrated and further compared with the corresponding hemolysis values ​​measured for quartz particles, Mg alloys and Cp-Ti.

[0076] Experimental details

[0077] Sample preparation

[0078] Ti was prepared by arc melting (Edmund Buhler AM-200) of pure elements (purity >99.5%) under an argon atmosphere protected by a Ti absorber. 40 Zr 10 Cu 36 Pd 14(atomic %) or Ti 29 Zr 14 Cu 35 Pd 23 (wt%) and Ti 40 Cu 40 Zr 11 Fe3Sn3Ag3 (atomic %) or Ti 30 Cu 40 Zr 16 Fe3Sn6Ag5 (wt%) master alloy ingot. The master alloy is arc-melted at least 3 times to ensure chemical homogeneity.

[0079] Ti 40 Zr 10 Cu 36 Pd 14 The alloy was melted by induction heating and then cast into a water-cooled mold to form bars with a diameter of 3.4 mm and dimensions of 25×15×2 mm. 2 The plate. The rod and plate are further cut into 0.1 mm thick discs and 15×10×2 mm discs. 3 The plates were polished to 1 μm using #1200 and #2500 mesh silicon carbide paper and a micron-sized (3-1 μm) diamond suspension.

[0080] Ti was processed using a boron nitride (BN) crucible. 40 Cu 40 Zr 11 Fe3Sn3Ag3 alloy was melt-spun (using a melt-spinning machine SC) to produce an amorphous alloy strip. The alloy was melted using induction heating; in an argon atmosphere of 1 bar, the molten liquid at 1100°C was sprayed onto a rotating copper wheel at an overpressure Δp of 0.3 bar at a speed of 30 m / s. The quenched strip was 4 mm wide and 50 μm thick.

[0081] Prior to etching, the sample was cleaned in an ultrasonic bath of acetone and ethanol. The sample was then immersed in an etching solution containing NH4 and H2O2, with H2O added finally. After treatment, the sample was dried in ambient air.

[0082] SEM

[0083] The surface of the treated sample was observed using a Zeiss FEG-SEM Supra 55 VP in secondary electron mode with an accelerating voltage of 5 kV and a working distance of 5 mm.

[0084] XPS

[0085] For Ti 40 Zr 10 Cu36 Pd 14 Samples were measured using a PHI5000 Versaprobe II (ULVAC Inc.) instrument equipped with a monochromatic AlKα excitation (1486.6 eV) over a 200 μm diameter region by XPS. Full spectra were recorded from 1100 eV to 0 eV and post-processed using CasaXPS software. For Ti... 40 Cu 40 Zr 11 The Fe3Sn3Ag3 sample was subjected to XPS measurements using an argon ion (SPECS ion gun) with a 100 mm hemispherical analyzer. A non-monochromatic Mg-Kα X-ray source was used at 400 W and 15 kV. All measurements were subjected to satellite peak subtraction and charge calibration at 284.8 eV for carbon.

[0086] Measurement of corrosion resistance

[0087] The corrosion properties of the sample bulk were investigated using an electrochemical measurement in a three-electrode glass cell, employing a Gamry 600+ potentiostat (GAMRY Instruments). A graphite rod served as the counter electrode, and a saturated calomel electrode (SCE) served as the control electrode (ESCE = 268 mV relative to the standard hydrogen electrode potential at 25 °C). The working electrode consisted of the sample bulk, with one circular facet connected to a copper wire. Only one treated circular facet of the sample bulk was in contact with the electrolyte solution; the rest of the sample bulk was insulated by a waterproof sheath.

[0088] Electrochemical tests were conducted in two different electrolyte solutions maintained at 37°C by a water circulation temperature control unit: 1) in an aerated neutral saline solution (pH=7.4) consisting of 0.9 w / v% sodium chloride (NaCl), as recommended in ISO 10271; and 2) in an aerated acidic saline solution (pH=2.3) consisting of 0.9 w / v% NaCl + 1 w / v% lactic acid.

[0089] Electrochemical testing consisted of open-circuit potential (OCP) measurements over 6 hours to reach steady state, followed by potentiodynamic polarization measurements. Polarization curve parameters were set at a scan rate of 0.17 mV / s, ranging from -0.2 V to +1 V relative to the SCE.

[0090] Hemolysis assessment

[0091] Hemolysis was studied using defibrinated sheep blood (whole blood, Microbiol Diagnostic) and purified red blood cells (RBCs) from sheep blood, separated in Alsever's solution (Thermo Fisher). Each medium (i.e., whole blood and RBCs) was diluted in phosphate-buffered saline (PBS) at a volume ratio of 4:5 (blood:PBS). The absorbance (Abs) was adjusted to 0.9–1.0 by adding either PBS or blood. A positive control was prepared using 10 mL of ultrapure water (Merck-Millipore) and 0.2 mL of diluted medium (total volume = 10.2 mL). Similarly, a negative control was prepared using PBS and diluted medium.

[0092] Samples were sterilized with 70% ethanol and then washed with ultrapure water and PBS. Samples were then immersed in glass vials containing 10.2 mL of whole blood and 10.2 mL of RBC media, respectively, and incubated at 37°C for 60 minutes in a horizontally controlled shaker. For comparison, quartz particles (SiO2, Min-U-Sil 5, US Silica, 200 cm⁻¹) were used. 2 / ml, specific surface area: 5m³ 2 / g) and magnesium alloy (WE43B, Goodfellow) were used as positive control materials (i.e., materials that induce hemolysis), while commercially pure titanium (Cp-Ti) was used as negative control material (i.e., materials that have no effect on hemolysis).

[0093] After immersion, the supernatant containing potentially released hemoglobin was separated by centrifugation at 500 G (Centrifuge Rotina 380R) for 5 minutes, and the absorbance was measured at a wavelength of 540 nm using a UVS 900 Lite spectrophotometer. Each sample was measured three times. The percentage of hemolysis in the test samples was calculated as follows:

[0094] (Equation 1)

[0095] Assessment of fibroblast activity

[0096] HGF-1 (human gingival fibroblast) cell line (ATCC CRL-2014, Manassas, USA) was cultured in DMEM (Dulbecco's Modified Eagle's Medium) supplemented with 10% fetal bovine serum and 1% penicillin / streptomycin solution (Gibco Life Technologies, Carlsbad, California, USA). Cells were cultured at 75 cm⁻¹. 2Cells were grown in culture flasks (Sarstedt, Nümbrecht, Germany) at 37°C in a humidified incubator with 5% CO2. Prior to cell seeding, cells derived from Ti... 40 Zr 10 Cu 36 Pd 14 The BMG discs were sterilized by immersing the disc-shaped material in 70% ethanol for 20 minutes, followed by rinsing three times with sterile water and air-drying. After incubation on the samples for 24 hours, HGF-1 cells were isolated using trypsin (Gibco Life Technologies, Waltham, USA), and the number of surviving attached cells on the surface was quantified using the NucleoCounter® NC-200™ system (ChemoMetec A / S, Lillerød, Denmark) according to the manufacturer's instructions. Additionally, LDH (lactate dehydrogenase) activity was measured from the supernatant using the CyQUANT™ LDH cytotoxicity assay (Thermo Fisher Scientific, Roskilde, Denmark) according to the manufacturer's operating procedures. Absorbance at 490 nm was measured per minute for 30 minutes using a FLUOstar Omega microplate reader (BMG LABTECH, Ortenberg, Germany).

[0097] Wettability study; contact angle measurement

[0098] Wetting properties were studied in fixed droplets using a Theta lite optical tensiometer (Biolin Scientific). Polar and non-polar solvents were used to understand the wettability and surface free energy (SFE) of the sample surfaces. Contact angles were measured using oneAttension software 1 second after placing droplets of 3 μL volume deionized water (polar) and diiodomethane (non-polar). The SFE of pseudo-dealloyed samples was calculated using Young's equation and the Owen, Wendt, Rabel, and Fowkes (OWRK) method. For each group (n=9), measurements were recorded for at least three droplets on three samples.

[0099] Biofilm assay

[0100] To study biofilm formation, Gram-negative *Pseudomonas aeruginosa* (PAO1) was used. Bacterial inoculum was grown in a lysogenic broth (Sigma-Aldrich, LB medium: 1% tryptone, 0.5% yeast extract, 0.5% NaCl) in deionized water (DI H2O). Samples (0.4 × 2 cm) were sterilized by immersion in 70% ethanol prior to inoculation. Three biological replicas and two technical replicas were used in each study.

[0101] Overnight cultures of *Pseudomonas aeruginosa* were grown in 15 mL of LB (lysogenic broth) medium at 37°C. Bacterial counts were quantified by diluting fresh medium into aliquots at a 1:10 ratio, and the optical density (OD) was measured at 600 nm using a spectrophotometer (Spectramax m384). The cultures were then adjusted to 0.1 OD600 cultures (10... 7 The samples were then prepared for inoculation with CFU (colony-forming units) / mL. The samples were then incubated in 1 mL of adjusted bacterial culture in a sterile 24-well flat-bottomed tissue culture plate at 37°C for 24 hours without shaking.

[0102] After the incubation period, samples were transferred to new wells containing phosphate-buffered saline (PBS) solution and gently rinsed three times with PBS to remove any unattached airborne bacteria. The samples were then dried at 37°C for 30 minutes. 1 mL of 1% crystal violet (CV) solution was added to each well and incubated at room temperature for 15 minutes. After staining, the bands were transferred to new wells, rinsed three times with PBS, and dried at 37°C for 30 minutes. Then, 1 mL of elution buffer (80% ethanol and 20% acetone) was added to each well and incubated at room temperature for 15 minutes. 1 mL of this elution buffer was then transferred to an optically clear plastic cuvette, and the OD of the solution was measured at 595 nm using the elution buffer as a blank control, thus providing a quantitative measurement of biofilm biomass.

[0103] EPR Spectroscopy

[0104] EPR spectroscopy for determining the extent of OH radical release was performed using a spin trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy. Clean metal samples measuring 0.4 × 1 cm were immersed in 1 mL of phosphate buffer (PB, 0.5 M, pH 7.4, Sigma-Aldrich, Milan, Italy) containing 0.04 M DMPO (5,5-dimethyl-1-pyrrolino-1-oxide, Cayman Chemical Company, Ann Arbor, Michigan) as the spin trapping molecule and freshly prepared 0.2 M H₂O₂ as the target molecule. The samples were incubated in solution at 37 °C with continuous stirring in the dark using a thermostatic shaker. After 10, 30, and 60 minutes, 50 μL of supernatant was collected in capillaries, and electron paramagnetic resonance (EPR) spectra were recorded using a Miniscope MS100 spectrometer (Magnetech, Berlin, Germany) at a microwave power level of 10 mW, modulation of 1 Gauss (G), a scan range of 120 G, and a central field of 3355 G. A blank control without the sample was prepared. The amount of free radicals released was proportional to the intensity of the EPR signal. To compare the amount of hydroxyl radicals generated from the sample, the signal was double-integrated using Origin 2023 software, and the results were reported in arbitrary units. Measurements were repeated twice.

[0105] result

[0106] like Figure 1 As shown in the SEM images, the treatment according to step b) of the invention results in the formation of nanoscale features, particularly nanoscale pores and holes, thus providing clear evidence of selective / preferred etching.

[0107] The modification of the surface region obtained by the treatment is further revealed by Figure 2, which shows that, compared with the untreated sample, the treatment of the sample according to the invention exhibits a significant reduction in Ti and O and an increase in Pd (i.e., the noble metal of the minor alloying component of II) in the surface region of the sample.

[0108] Analysis shows that, through the etching process of the present invention, the noble metal palladium contained in the amorphous alloy dissolves at a lower dissolution rate than the other alloy components, thereby producing a surface region containing a higher proportion of palladium compared to the untreated sample. Since the etching process according to the present invention is limited to the surface region of the starting material bulk that the etching solution "can reach," an amorphous alloy bulk is obtained whose surface region has an increased proportion of palladium compared to the rest of the material bulk.

[0109] like Figure 3As shown in the corrosion resistance measurements at physiological pH, increasing the potential resulted in a larger pseudo-passivation region in the sample of this invention, with a moderate increase in current density. In contrast, the untreated sample showed a sudden increase in current density at a potential of 0.48 V / SCE, which is characteristic of pitting corrosion.

[0110] Similar results showing reduced pitting susceptibility in the samples of this invention are illustrated in Figure 4 (Involves corrosion resistance measurements in acidic environments). According to... Figure 4 For the samples of the present invention, a high / large passivation plateau without pitting events was observed, indicating that the resulting surface area (which acts as a passivation layer) is also protective in environments containing both chlorine and acid.

[0111] These two results ( Figure 3 and Figure 4 All of these studies indicate that, compared with the comparative samples, the samples according to the present invention have higher corrosion resistance and lower pitting sensitivity.

[0112] The samples treated according to the present invention further exhibited good blood compatibility, as shown in Figure 5. Specifically, the percentage of hemolysis in whole blood measured according to the present invention was comparable to that obtained with commercially available pure titanium (Cp-Ti), known for its high biocompatibility, and significantly lower than that measured with SiO2 and Mg alloys. Similarly, the percentage of erythrocyte (RBC) hemolysis in the samples of the present invention was also significantly lower than that measured with SiO2 and Mg alloys. Since the percentages of hemolysis in whole blood and RBCs measured with the samples of the present invention were comparable to (or even slightly lower than) those in untreated samples, this data indicates that the treatment of the present invention did not negatively affect the biocompatibility of the amorphous alloys.

[0113] Figure 6 This further illustrates the suitability of the samples according to the present invention for invasive procedures. Figure 6 The number of cells attached to surfaces treated by the method of the present invention is shown compared to untreated samples. Specifically, the cell nucleus count shows that the average number of cells attached to the samples of the present invention is slightly higher than that of the untreated samples, indicating that the treated samples have similar or even higher fibroblast activity.

[0114] like Figure 7 As shown, the LDH activity of cells after contact with the surface treated according to the present invention is similar to that measured for cells in contact with untreated samples, indicating that the samples of the present invention exhibit similar (low) cytotoxicity to the untreated samples.

[0115] The findings discussed above in the context of Figure 2, namely the treatment of the present invention, result in the surface region containing a higher proportion of the secondary alloying component ii) of noble metals compared to the untreated sample, through Figure 8 XPS spectra confirmed that it involved different amorphous alloys, namely Ti 40 Cu 40 Zr 11 Fe3Sn3Ag3. Figure 8 The XPS spectra were further shown to change over time (particularly after 1 hour and 6 hours), indicating a significant decrease in the proportion of copper in the surface region after 6 hours of etching. The spectra also showed an increase in the content of titanium (Ti) and oxygen (O) over time, indicating the formation of titanium oxide in the surface region through the extended etching process.

[0116] For the materials of the present invention (in) Figure 8 (As mentioned in the context), further studies using deionized water and diiodomethane as contact media revealed increased hydrophilicity. This was reflected in the corresponding contact angles measured on the two samples of the present invention (obtained by etching with 1:1 NH4 / H2O2, referred to as CS; and obtained by etching with 5:1:4 NH4 / H2O2 / H2O, referred to as DS) and an untreated control sample, the results of which are shown in... Figure 9 The data obtained from these studies involve surface free energy (SFE; in mN / m), where the DS sample has 50.17 mN / m and the CS sample has 46.85 mN / m, compared to 40.85 mN / m for the untreated sample.

[0117] like Figure 10 As shown, it was found that the release of OH radicals in the samples according to the present invention was significantly increased, and this increase was more pronounced with prolonged treatment duration, particularly for samples obtained by treatment with a diluted etching solution (5:1:4 NH4 / H2O2 / H2O) than for samples obtained by treatment with a concentrated etching solution (1:1 NH4 / H2O2). Therefore, the samples of the present invention can promote the generation of reactive oxygen species in a cell-free system simulating inflammatory conditions, which can exhibit antibacterial activity.

[0118] The results of biofilm studies using crystal violet (CV1%) measurements further confirm that the samples of the present invention exhibit enhanced antibacterial properties, as demonstrated by the results in... Figure 11 According to this study, a significant reduction in optical density was determined, and therefore a significant reduction in biofilm formation (Pseudomonas aeruginosa), further demonstrating that the sample according to the invention has antibacterial activity and can therefore prevent bacterial attachment and biofilm formation.

[0119] As shown in Figure 12, the samples obtained by the method of the present invention have shown to be blood-compatible. In other words, it has been found that the high blood compatibility of the untreated material is unaffected by the treatment of the present invention, as described above in the context of Figure 5 for Ti.40 Zr 10 Cu 36 Pd 14 The subject of discussion.

Claims

1. A method for manufacturing a medical device or medical component, said medical device or medical component comprising a material body containing an amorphous alloy, said method comprising the following steps: (a) Providing a starting material bulk comprising an amorphous alloy, the amorphous alloy comprising: i. Select the main alloying components from the group consisting of titanium copper (TiCu) and zirconium copper (ZrCu), and ii. One or more secondary alloying components comprising at least one noble metal selected from the group consisting of ruthenium (Ru), rhodium (Rh), palladium (Pd), silver (Ag), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), and combinations thereof, and (b) The starting material body is etched using an etching solution that dissolves at least one alloying element of the primary alloying component of (i) at a higher dissolution rate than at least one noble metal of the secondary alloying component of (ii).

2. The method as described in claim 1, wherein, The etching solution dissolves at least one noble metal (ii) at a lower dissolution rate than all the other alloy components.

3. The method as described in any of the preceding claims, wherein, The material containing amorphous alloy is in the form of bulk metallic glass, amorphous alloy strip, or amorphous alloy film.

4. The method as described in any of the preceding claims, wherein, The amorphous alloy comprises titanium and copper as primary alloying components, and optionally also comprises palladium (Pd) and zirconium (Zr) as secondary alloying components.

5. The method according to any one of claims 1 to 4, wherein, The amorphous alloy further comprises at least one third alloying component selected from the group consisting of iron (Fe), gallium (Ga), tin (Sn), silicon (Si), yttrium (Y), silver (Ag), scandium (Sc), sulfur (S), niobium (Nb), hafnium (Hf), zinc (Zn), tantalum (Ta), and mixtures thereof.

6. The method of claim 5, wherein, Based on a total amount of 100% by weight of the amorphous alloy, the amorphous alloy comprises 15-55% by weight of titanium, 1-45% by weight of copper, 0-30% by weight of palladium, 0-30% by weight of zirconium, 0-10% by weight of silicon, 0-20% by weight of iron, 0-10% by weight of zinc and 0-20% by weight of silver.

7. The method of claim 6, wherein, Based on a total amount of 100% by weight of the amorphous alloy, the amorphous alloy comprises: 20-45% by weight, preferably 25-35% by weight, of titanium. 15-45% by weight, preferably 30-45% by weight of copper. 5-30% by weight, preferably 10-20% by weight, of zirconium. Palladium of 0-30% by weight, preferably 0-25% by weight, 0-15% by weight, preferably 0-10% by weight of tin. 0-2% by weight, preferably 0-1% by weight, of silicon. 0-10% by weight, preferably 0-5% by weight of iron, And 0-15% by weight, preferably 0-10% by weight, of silver.

8. The method according to any one of claims 1 to 7, wherein, The amorphous alloy has a composition of Ti. 40 Zr 10 Cu 36 Pd 14 The subscripts indicate the atomic percentage of each component.

9. The method as described in any of the preceding claims, wherein, The etching solution contains NH4 and H2O2.

10. The method of claim 9, wherein, In the etching solution, the volume percentages of NH4 and H2O2 are each from 25% to 75% by volume, and preferably, the etching solution is a mixture of NH4 and H2O2 in a volume ratio of about 1:

1.

11. The method as described in any of the preceding claims, wherein, The etching process is performed at room temperature for at least 5 minutes, preferably at least 15 minutes, and more preferably at least 30 minutes.

12. A medical device or medical component prepared by the method of any one of the preceding claims, the device or component comprising a material body containing an amorphous alloy, the amorphous alloy comprising: I. Select the main alloying components from the group consisting of titanium copper (TiCu) and zirconium copper (ZrCu), and II. One or more secondary alloying components comprising at least one noble metal selected from the group consisting of ruthenium (Ru), rhodium (Rh), palladium (Pd), silver (Ag), osmium (Os), iridium (Ir), platinum (Pt), gold (Au), and combinations thereof, and in, The material body includes a surface region having at least one noble metal of the secondary alloy component (II) in an increased proportion compared to the rest of the material body.

13. The medical device or medical component as claimed in claim 12, wherein, The surface region contains holes and / or pores with an average size of 5 nm to 30 nm.

14. The medical device or medical component as claimed in claim 12 or 13, wherein, The medical device or medical component is part of a dental implant system, particularly a dental implant or dental implant abutment.

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