BACTERICIDAL SURFACE COATING PROCESS ON TITANIUM IMPLANTS

Description

1 / 23 BACTERICIDAL SURFACE COATING PROCESS ON TITANIUM IMPLANTS FIELD OF THE INVENTION [1] The present invention falls within the field of Engineering, more precisely in the area of ​​Materials Engineering and Surface Engineering, and relates to a bactericidal surface coating process on titanium implants and their copper alloys. FUNDAMENTALS OF THE INVENTION [2] Bacterial contamination is a serious problem that can affect numerous applications, from domestic and everyday life, to food handling and storage, medical implants, clinical environments, biosensors and even space missions. [3] The case of medical implants is particularly critical, as an infection can develop in a patient with compromised health and immune systems. Furthermore, implant materials are preferential sites for bacterial adhesion. The development of a prosthetic infection actually involves about 1% of all total joint replacements, but this percentage increases dramatically in the case of revision surgery. For example, in the dental field, peri-implantitis has been observed in up to 14.4% of implants in the first 5 years, but a higher incidence has been documented for longer follow-ups and after a first septic failure. This complication leads to the need for prolonged antibiotic therapy (which Petition 870210108062, dated 11 / 22 / 2021, page 5 / 40 2 / 23 can last for years) and eventually lead to implant removal. The consequence of these postoperative complications, and the lack of effective treatments, is a significant increase in hospitalization times and costs, coupled with a stressful, painful, and critical situation for the patient. Furthermore, it should be remembered that a significant increase in antibiotic-resistant bacterial strains has been observed, leading to the need for innovative prevention and treatment strategies. [4] Bacterial infections are generally treated and prevented by the local and systemic application of antibiotics. The main problems related to antibiotic therapies are the increasing development of antibiotic-resistant bacterial strains (e.g., methicillin-resistant Staphylococcus aureus - MRSA) and their narrow spectrum of activity, resulting in difficulty in treating infections caused by multiple bacteria. The development of antibiotic-resistant bacterial strains has recently been defined as a “global threat” to human health that needs to be addressed. [5] In this context, a growing interest in alternative antibacterial agents has been witnessed. In particular, inorganic antibacterial agents may represent a challenging strategy in combating bacterial infections without the use of antibiotics. [6] It should be highlighted that most of the reported studies were conducted with planktonic cells and they do not Petition 870210108062, dated 11 / 22 / 2021, page 6 / 40 3 / 23 investigate biofilm formation and growth: this is a significant limitation when clinical implications must be deduced from laboratory data. This is consistent with the usual procedure for preliminary work: a general standard procedure for evaluating the antibacterial activity of biomaterials has not yet been defined. [7] Metal ions, salts and nanoparticles are part of one of the most important classes of inorganic antibacterial agents. Among these agents, silver has long been known and used as an antibacterial agent. In addition, an effective antibacterial effect has also been noted for other metal ions, such as copper and zinc. [8] The mechanisms of action of metals against bacteria have recently been reviewed. [9] For example, silver ions, Ag ions, can effectively bind to thiol groups, a feature of many proteins, and play a structural and functional role in bacterial cells, causing the death of microorganisms. Ag ions can alter the function and structure of bacterial cell wall proteins and lead to their subsequent rupture. In addition, they can bind to and alter various enzymes, which are crucial for respiration and cellular metabolism. Finally, they can interfere with DNA through cell division and replication. The multiple actions of silver ions explain the reduced development of resistance, compared to Petition 870210108062, dated 11 / 22 / 2021, page 7 / 40 4 / 23 antibiotics, and also their broad spectrum of activity, which includes many bacteria, as well as fungi and yeasts. An analogous mechanism of action has been described for other metal ions (e.g., Cu, Zn).

[10] The growing interest in silver nanoparticles as antibacterial agents has been demonstrated. Ag nanoparticles have a large surface area, which allows for a high release of silver ions. In addition, they can bind directly to the bacterial cell membrane and are also able to penetrate the cell. The antibacterial activity of silver nanoparticles depends mainly on their size and shape. On the other hand, the toxicity of these nanoparticles is currently under investigation; it should be noted that few systematic studies focus on Ag nanoparticles, despite their wide application. Surface modifications that can be introduced to obtain antibacterial metal surfaces.

[11] Several techniques have been explored in the scientific literature and in industrial and clinical applications for obtaining titanium surfaces enriched with antibacterial agents. In particular, three main categories of surface modifications can be considered for inorganic antibacterial agents: 1) enrichment of the surface of inorganic antibacterial agents without the introduction of a coating; Petition 870210108062, dated 11 / 22 / 2021, page 8 / 40 5 / 23 2) growth of a surface layer of dioxide (T1O2) and its doping with the antibacterial agent (in the same pass or in a second step); and 3) deposition of a coating (TiO2 or tin, for example, hydroxyapatite - HAp) and its doping with the antibacterial agent (in the same pass or in a second step). Introduction of copper into titanium surfaces and its alloys

[12] Although there is extensive literature on enriching titanium surfaces and its alloys with silver, very few research papers have considered the application of copper to titanium as an inorganic antibacterial agent. This is unexpected because lower cytotoxicity is reported for copper than for silver, making copper a very interesting antibacterial agent. Research papers report several techniques (ion implantation, alloys, spraying, sol-gel and chemical vapor deposition) that are used to introduce copper into titanium substrates and its alloys, in metallic or oxide form. Ion implantation

[13] As mentioned before, ion implantation has been employed to introduce different antibacterial ions (Silver (Ag), Copper (Cu)) into metallic substrates. With regard to copper, an increase in antibacterial activity against S. aureus was observed as the Petition 870210108062, dated 11 / 22 / 2021, p. 9 / 40 6 / 23 Copper content on the surface increased (0.5–4 x 1017 ions / cm2, concentrations comparable to those previously described for silver). Cu ion implantation induced a slight improvement in the wear resistance of the metallic substrate. On the other hand, a reduction in corrosion resistance was recorded for samples enriched with copper (Cu). Titanium-Copper Alloys - Ti-Cu

[14] Ti-Cu alloys with different copper contents, 1%, 5% and 10% by weight, were prepared. Ti2Cu and Cu-rich phases were detected in the 10% Ti-Cu alloy. A significant increase in hardness, yield strength and compressive strength was observed, as well as a reduction in ductility, for the Ti-Cu alloy, compared to pure Ti. Contrary to what has been reported for surfaces implanted with Cu ions, an increase in corrosion resistance was observed. No inhibition halo was observed for the 10% Ti-Cu alloy, but a significant reduction in bacteria adhering to the surface was observed for both the 10% by weight Ti-Cu alloy and the 1% and 5% alloys. A low release of Cu (0.05 mg / l after 72 h in a physiological solution) indicates that the bacteria can only be killed when they are in direct contact with the surface. Furthermore, it is known that the antibacterial behavior against S. aureus and E.E. coli activity increases with increasing copper content in the alloy, as does the cytotoxic effect on fibroblast cells; a 1% Cu content proved to be the most promising. Petition 870210108062, dated 11 / 22 / 2021, page 10 / 40 7 / 23 limit bacterial infection and ensure tissue integration. Sputtering

[15] Magnetron sputtering has been employed for the deposition of a copper-containing film on Ti6Al4V and steel substrates. In the first case, different techniques were considered (direct current magnetron sputtering, double magnetron sputtering and high-power double magnetron sputtering), and different chemical compositions were obtained for the deposited films. Generally, these films are composed of metallic Ti and Cu, but their oxides have also been detected. Cu release was occasionally verified in DMEM culture medium (up to 6 mmol / l in 24 h), depending on the chemical characteristics of the sample. The increase in antibacterial behavior (up to complete reduction of planktonic bacteria and biofilm), as well as cytotoxicity, was evidenced with the increase in the amount of copper released. In the last case, TiN and Cu were deposited.A reduction in the coefficient of friction was observed for the coated samples. Contrary to what was reported for ion-implanted copper, and in accordance with the results reported for Ti-Cu alloys, an improvement in corrosion resistance was observed for these materials, probably due to the deposition of a TiN layer on top of the surface. The antibacterial activity was... Petition 870210108062, dated 11 / 22 / 2021, page 11 / 40 8 / 23 demonstrated against E. coli (80-90% bacterial reduction after 24 h, depending on coating characteristics).

[16] A plasma surface alloying technique was also employed to obtain a Cu-Ni layer on commercially pure titanium. Compositional analyses showed a greater enrichment of the surface in Ni than in Cu, despite the known cytotoxicity of Ni. The 10 pm coating conferred antibacterial properties (near-complete reduction of bacterial viability by direct counting of colonies on the sample surface) against E. coli and S. aureus. The antibacterial activity was attributed to the release of copper. Improved wear resistance was observed on the coated surfaces compared to pure titanium. Sol-Gel

[17] Mono- and multilayer coatings of copper-doped TiO2 on TieAUV substrates and CuO / TiO2 composite nanofibers were obtained using the sol-gel technique. Titanium isopropoxide and tetrabutoxytitanate were used as TiO2 precursors, while copper acetate, copper nitrate, or copper nanoparticles were used as Cu. Regarding the coatings, the immersion coating technique has been used to deposit copper on substrates, and it was observed that the antibacterial action against S. aureus increased with the number of Cu-containing layers (up to 6log10 for 4 layers), but some signs of cell distress were observed when the number of layers was increased. Regarding the fibers, the Petition 870210108062, dated 11 / 22 / 2021, page 12 / 40 9 / 23

[18] Electrospinning was employed and a deleterious effect on the fiber structure was observed for copper acetate, while good results were obtained with Cu nanoparticles and copper nitrate. TiO2 fibers were characterized by anatase, while a rutile signal appeared for those doped with Cu. A CuO signal appeared clearly for fibers obtained using Cu nanoparticles, while it was not present for those obtained using copper nitrate. In the latter formulation, Cu-rich particles were observed by FESEM and microanalysis techniques. Antibacterial activity was tested against Klebsiella pneumoniae for fibers obtained using Cu nanoparticles, and against S. aureus and E. coli for fibers obtained using Cu nitrate. An increase in antibacterial action was observed in the first case when the copper content was increased, along with photocatalytic behavior.Cell wall damage and condensed DNA deposits were visible in bacteria treated with Cu-enriched fibers and with Cu nitrate, which can be explained by considering the mechanism of copper against microorganisms.

[19] Furthermore, TiO2-Cu composite nanoparticles (10 nm) were obtained by UV photocatalytic reduction of copper chloride containing TiO2 sol. Anatase, ionic and metallic copper were identified as the constituents of the particles. Significant antibacterial activity, in the absence of light, against E. coli (complete inhibition with Petition 870210108062, dated 11 / 22 / 2021, page 13 / 40 Inhibition of 10 / 23 nanoparticles of 21.4 μg / ml) and S. aureus (complete inhibition with nanoparticles of 14.3 μg / ml) was observed for the composite particles. The indicated values ​​are lower than those reported in the literature for pure titanium and copper / copper oxide nanoparticles. It has been suggested that negatively charged TiO2 particles could attract Cu ions and act as carriers, but no release tests have been reported. Chemical vapor deposition

[20] Copper coatings containing TiO2 were prepared on steel, silicon, and glass by pulsed liquid direct injection chemical vapor deposition (DLICVD) using copper bis(2,2,6,6-tetramethyl-3,5-heptadionate) and titanium tetraisopropoxide as Cu and TiO2 precursors. Anatase and metallic copper were identified as the main constituents of the coating; early rutile crystallization was also detected for the higher Cu content, suggesting the ability of copper to favor rutile crystallization and confirming other results already reported for silver-containing titanium oxide films and discussed previously. A decrease in film growth rate and average crystal size was observed, while a decrease in grain growth was also observed for silver-containing titanium oxide. Finally, the antibacterial behavior of the Cu-containing coatings was demonstrated against S.aureus (100% bacterial reduction for a Cu content greater than 1.5 mol%), thus. Petition 870210108062, dated 11 / 22 / 2021, page 14 / 40 11 / 23 as maintaining the coating properties for up to 5 months of storage under ambient conditions with a 30% reduction for longer periods.

[21] The chemical vapor deposition technique has also been employed for the deposition of multilayer titanium and copper oxide coatings. Significant antibacterial activity against E. coli was observed under UV irradiation (N5log bacterial reduction after 20-40 min), and a significant effect of surface roughness on antibacterial behavior was observed. In particular, the effect of nanostructures on improving surface area and Cu release was highlighted. Cu release in distilled water was measured in the range of 3.3-5.5 ppm after 80 min of immersion, depending on the coating type. Furthermore, the ability of these coatings to self-regenerate under UV irradiation has been reported.

[22] With regard to copper-enriched surfaces, antibacterial activity, analogously to silver-enriched surfaces, is often attributed to the release of Cu2+ ions, except for TiCu alloys for which extremely low release has been recorded and the antibacterial action attributed to contact killing. In comparison with silver, little data on copper release is reported.

[23] Furthermore, no bioactivity data has been reported for surfaces enriched with Cu. STATE OF THE ART Petition 870210108062, dated 11 / 22 / 2021, page 15 / 40 12 / 23

[24] Some work is related to coating medical product surfaces with antibacterial agents, for example:

[25] The document in the name of Zhang et al. entitled “Antibacterial metals and alloys for potential biomedical implants” refers to a review article on bactericidal materials and the mechanisms by which they act on cells. In this document, the authors provide a general overview of elements and materials that potentially have bactericidal properties and, for some of them, present the mechanisms of action against various types of bacteria. However, it does not present processing routes for obtaining bactericidal implants. Additionally, the document categorically refers to them as “antibacterial alloying elements,” meaning that these would be added as alloying elements mainly in the initial stages of melting the raw material.

[26] On the other hand, the present invention establishes a well-established processing route (initial copper layer thickness, temperature, time and atmosphere of heat treatment, residual copper content on the surface, etc.) that can be employed in the functionalization of surfaces of metallic implants with simple or complex geometries, such as those porous structures obtained by additive manufacturing processes, in the final processing stage, i.e., after machining and polishing, for example. It is noted that while the aforementioned document Petition 870210108062, dated 11 / 22 / 2021, page 16 / 40 Figure 13 / 23 presents some mechanisms by which bactericidal materials can kill cells; the present invention establishes a process that can be integrated into the manufacturing line of metallic implants.

[27] The document in the name of Dzogbewu & du Preez entitled “Additive Manufacturing of Titanium-Based Implants with Metal-Based Antimicrobial Agents” refers to a review article that focuses on additive manufacturing and outlines alternatives for the production of bactericidal implants. Furthermore, the document includes a section on methods used for coating biomedical objects, but makes no mention of the electrodeposition process followed by heat treatment as proposed in the present invention, much less defines processing conditions, layer thickness, etc.

[28] The focus on additive manufacturing assumes that the process of obtaining implants would be metallurgical, where the material is melted. In contrast, the present invention introduces a new combined process (electrodeposition + heat treatment in a specific atmosphere, temperature and time) in the implant manufacturing line at an advanced stage of production.

[29] The document in the name of Luís Carlos Gomes da Cunha entitled “Solid-state diffusion bonding of titanium alloys with Ti / Ni multilayers” uses the magnetron sputtering process to produce nanometric titanium and nickel (Ti / Ni) films on substrates of Petition 870210108062, dated 11 / 22 / 2021, p. 17 / 40 14 / 23 Ti6Al4V and TiNi. Sputtering is one of the PVD (physical vapor deposition) techniques, which involves the condensation of compounds in the gas phase to form materials in the solid state, usually in the form of a thin film deposited on a substrate. The idea was to produce a kind of wafer between the substrates with multilayer variations of Ti / Ni. After the deposition process, the wafers were heated under mechanical pressure to weld the parts together.

[30] However, the process proposed in the aforementioned document is in no way similar to the present invention, since it employs a PVD process, uses mechanical tension, and does not aim to produce a coating film for parts. It is observed that normally deposition processes create layers of a few nanometers to a few micrometers. These layers usually contain 100% of the deposited element. In the case of copper, this element can be cytotoxic in excessive quantities.

[31] The process of the present invention, given the definition of suitable parameters, allows the control of copper content to values ​​acceptable for cell viability, but still bactericidal. Furthermore, the deposition is done by copper electrodeposition which is much cheaper, faster (> 5 min), and allows deposition on complex surfaces of virtually any dimension. Moreover, the proposed process does not use mechanical stress, and would be easily integrated into the manufacture of implants. Petition 870210108062, dated 11 / 22 / 2021, page 18 / 40 15 / 23

[32] The document in the name of Zhang et al. entitled “A new antibacterial titanium-copper sintered alloy: Preparation and antibacterial property” presents a proposal for creating a metallic alloy by powder metallurgy. This process basically involves selecting the powders of interest, in this case Ti and Cu, followed by pressing in a closed die heated to high temperature, so that partial fusion of the powders and coalescence of the particles occurs. This is a process at the interface between mechanical and metallurgical engineering, which in no way resembles the process proposed in the present invention, which aims only to confer bactericidal character to semi-finished implants, without the need to use metallic powders, which are extremely expensive, mechanical stress and the like.

[33] Therefore, unlike the prior art, the present invention proposes a bactericidal surface coating process for titanium implants by electrodeposition of a thin film of metallic copper on the surface of the titanium implant or its alloys, followed by heat treatment for atomic diffusion. It is noted that the present invention has the advantage of functionalizing the implant surface in the final stages of manufacturing, i.e., the addition of the copper surface occurs on pre-finished implants (machined and polished) and not on the raw material.

[34] Additionally, the copper surface addition process is carried out at room temperature and does not compromise Petition 870210108062, dated 11 / 22 / 2021, page 19 / 40 16 / 23 the implant structure, and its content is controlled by heat treatment under specific processing conditions, which ensures perfect adhesion with a chemical composition gradient, so that there is no delamination of the implant surface layers. Nevertheless, the copper films are continuous and can be applied to complex surfaces such as threads, holes, etc. SUMMARY OF THE INVENTION

[35] The present invention aims to propose a bactericidal surface coating process for titanium implants and their alloys by electrodeposition of metallic films of a thin film of metallic copper on the surface of the titanium implant, followed by heat treatment for atomic diffusion, integrating the film material into the implant, forming titanium-copper intermetallic compounds. BRIEF DESCRIPTION OF THE FIGURES

[36] Figure 1 shows the sanded test specimen.

[37] Figure 2 shows an example of an electrodeposition cell.

[38] Figure 3 shows the test specimen before (left) and after (right) electrodeposition.

[39] Figure 4 shows the test specimen encapsulated in quartz for heat treatment.

[40] Figure 5 shows the test specimen after atomic diffusion. Petition 870210108062, dated 11 / 22 / 2021, page 20 / 40 17 / 23

[41] Figure 6 shows a micrograph (200X etch) Kroll) of grade 2 titanium (5% Cu) at 860 °C for 500 minutes.

[42] Figure 7 shows a micrograph (200X etch) Kroll) of Ti-6Al-4V (5% Cu) at 860 °C for 2000 minutes. DETAILED DESCRIPTION OF THE INVENTION

[43] The present invention relates to a bactericidal surface coating process for titanium implants and their alloys by electrodeposition of a thin film of metallic copper on the surface of the titanium implant, followed by heat treatment for atomic diffusion, integrating the film material into the implant, forming titanium-copper intermetallic compounds comprising the following steps: - Pre-treatment of titanium parts; - Ultrasonic bath with detergent solution; - copper electroplating; and - heat treatment for atomic diffusion.

[44] Initially, the surface of the titanium parts that will receive the coating is subjected to sanding or blasting, or even surface finishing from machining and active manufacturing processes, due to the need for minimum surface roughness for better adhesion of the film to the part. In implants produced by additive manufacturing, casting and the like, this roughness can be obtained during the manufacturing process. In implants obtained by other conventional processes, a blasting step before the coating allows obtaining the desired finish. Petition 870210108062, dated 11 / 22 / 2021, page 21 / 40 18 / 23

[45] In this case, the parts were sanded down to 600 grit sandpaper. Finer grit sandpaper, such as 1500, caused the surface layer to detach before heat treatment. Coarser grit sandpaper, such as 400 and below, left the coating looking poor. The goal is to achieve an average roughness between 25 ~ 1.6 μm for adhesion of the deposited film.

[46] Additionally, the sanded / blasted parts (Figure 1) are subjected to an ultrasonic bath with a detergent solution for between 1 and 10 minutes at room temperature to degrease the parts, followed by washing with water. In this procedure, the parts are placed in equipment that emits sonic pulses for 180 seconds. The amount of solution used must be sufficient to cover all the parts and, if after washing any residue is still visually detected on the part, the procedure is repeated. It should be noted that the time and temperature in the ultrasonic bath will depend on the dimensions and geometry of the parts. Heating the solution to 50 °C can accelerate the process. Copper Electrodeposition

[47] An example of an electrodeposition cell is shown in Figure 2, where the formation of the layer occurs when metal is removed from the positive electrode (cathode) and deposited on the surface of the negative electrode (anode), when immersed in an electrolyte and subjected to an electric current. The resulting coating has a purely mechanical bond on the surface of the material. Petition 870210108062, dated 11 / 22 / 2021, page 22 / 40 19 / 23

[48] Normally, in copper electrodeposition, acid bath solutions use 200 to 250 g / l of copper sulfate and 45 to 90 g / l of sulfuric acid. In this case, the solution for electrolytic deposition used contains 220 g / l of copper sulfate, 60 g / l of sulfuric acid and distilled water (qsp). However, other water-based solutions with acid can be used, for example, with 10 g / L of hydrochloric acid.

[49] During electrodeposition, the bath was kept under constant agitation, with a rotation of approximately 100 RPM, in order to avoid the accumulation of bubbles on the surface of the sample. These bubbles are the result of gas formation during the process and interfere with the coating, causing deposition defects on the surface. The agitation of the bath must be sufficient to remove the bubbles from the surface of the piece. It also allows the use of higher current densities without burning the film (excessive polarization).

[50] The current used in both materials (commercially pure Ti and Ti6Al4V), due to the similar size of the samples, was 200 mA, corresponding to a current density of 7.8 A / dm2. Using lower current densities, the process required a long time for material deposition, while higher densities tend to burn both the coating and the sample due to short-circuit formation during electrodeposition. It is known that in stirred baths it is possible to use current densities of up to Petition 870210108062, dated 11 / 22 / 2021, p. 23 / 40 20 / 23 However, from 5 A / dm2 onwards, excessive polarization can occur, consequently leading to burning. In this case, the current density and agitation must be balanced in order to obtain deposits with the desired properties.

[51] As a sacrificial electrode (cathode), a rectangular electrolytic copper bar was used, with dimensions, for example, of 20 x 30 x 5 mm. The test specimens were connected to the anode, being electrically insulated so as to allow the deposition of the material on only one of the faces. The deposition time was controlled in order to produce a film with a thickness of 5 µm ± 1. For the area in question, the deposition time lasted about 3 minutes, however this time will vary according to the area of ​​the part to be coated. Figure 3 shows two test specimens, highlighting the difference in their surface after electrodeposition (right). Quartz Encapsulation

[52] In order to allow heat treatment in a conventional furnace, due to the fact that titanium is extremely reactive to atmospheric oxygen when heated, the samples were encapsulated in quartz. To remove oxygen from inside the capsule, the purging procedure followed these parameters: Vacuum to -1 Bar for 10 minutes, followed by argon injection to -0.4 Bar for 2 minutes, this sequence being repeated three times and in the final step vacuum of -1 Bar for 2 minutes and argon injection to -0.7 Bar for 1 minute, followed by Petition 870210108062, dated 11 / 22 / 2021, page 24 / 40 21 / 23 Sealing the quartz tube by melting the purge connection. After 30 minutes, the tube can be filled with argon gas and sealed with a full atmosphere (atmospheric pressure) or partial atmosphere (below atmospheric pressure). It can also be sealed under vacuum. Figure 4 shows the test specimen encapsulated in quartz for heat treatment. If a vacuum furnace is used instead of conventional furnaces, this procedure is not necessary. Heat treatment

[53] Although several works in the literature demonstrate the bactericidal action of intermetallic compounds formed in the titanium / copper system, heat treatment for diffusion is necessary not only to allow the formation of such intermetallics, but also to integrate the film to the implant and adjust the chemical composition of the coating, in addition to controlling / reducing the copper content on the surface and preventing delamination of the same.

[54] Thus, for the formation of intermetallic compounds, two critical temperatures of the Ti-Cu binary system must be taken into consideration. The first is the eutectoid temperature at 790 °C, that is, the lowest temperature at which the formation of the intermetallic compound occurs in the solid state, and the second is the eutectic temperature at 875 °C, which is the lowest temperature at which the material melts. Therefore, the working range of the atomic diffusion treatment studied was between 790 and 875 °C. Petition 870210108062, dated 11 / 22 / 2021, p. 25 / 40 22 / 23

[55] To optimize the process, it should be taken into account that the lower the temperature, the longer the treatment time, but exceeding or getting too close to the upper limit can liquefy the film, causing it to run off to unwanted points. Another factor to consider is the other elements present in titanium alloys that will hinder copper diffusion. In the present invention, the temperature used in the diffusion treatment was set at 860 °C, 15 °C below the maximum (eutectic) temperature.

[56] The treatment time depends on the desired chemical composition. In the case of Ti-Cu intermetallic compounds, studies indicate bactericidal properties from 1% copper by weight, however, contents above 10% showed problems in cytotoxicity tests. Thus, three ranges of chemical composition to be worked with were determined, comprising 5%, 7.5% and 10% with a variation of ± 1%.

[57] Tables 1 and 2 below show the chemical composition of the surfaces of the test specimens, Grade 2 Titanium and TeAl4V, respectively, after diffusion heat treatment at 860 °C (Figure 5). These results were obtained using the X-ray fluorescence technique, with air as the atmosphere and the collimator of the equipment set to 010 mm. Table 1: Grade 2 Titanium - Results of Diffusion Heat Treatment at 860 °C. Petition 870210108062, dated 11 / 22 / 2021, page 26 / 40 23 / 23 Time (minutes) Sample 1 (% Cu) Sample 2 (% Cu) Sample 3 (% Cu) 150 9.485 10.262 9.631 250 6.774 7.945 6.775 500 5.731 5.651 5.062 Table 2: T6AI4V - Heat Treatment Results of Diffusion 860 °C. Time (minutes) Sample 1 (% Cu) Sample 2 (% Cu) Sample 3 (% Cu) 400 10.761 9.713 9.276 1000 6.826 7.345 7.468 2000 5.209 5.849 5.569

[58] After several attempts, the optimized treatment time for each alloy was established, with acceptable reproducibility, within the expected chemical composition range, preferably 5; 7.5 and 10% Cu.

[59] In the micrographs, represented by Figures 6 and 7, the Ti-Cu intermetallic layer integrated into the titanium substrate can be observed, confirming the diffusion process of the previously deposited copper layer. Petition 870210108062, dated 11 / 22 / 2021, page 27 / 40

Claims

1 / 1 CLAIM 1. Bactericidal surface coating process for titanium implants and their alloys, characterized by comprising the following steps: (a) pre-treatment of titanium parts and their alloys by sanding with 400 to 1500 grit sandpaper, preferably 600 grit, providing a roughness between 25 and 1.6 μm; (b) ultrasonic bath with water and detergent solution for between 1 and 10 minutes, at room temperature; (c) electrodeposition of copper in a solution of 200 to 250 g / l of copper sulfate, preferably 220 g / l, and 45 to 90 g / l of sulfuric acid, preferably 60 g / l, maintained under constant stirring at 100 RPM, current of 200 mA, current density of 7.8 A / dm2; (d) heat treatment for atomic diffusion to be carried out between 790 and 875 °C, preferably 860 °C, for a duration between 150 and 2000 minutes; and (e) obtaining an implant coated with a film with a thickness of 5 µm ± 1 and a copper concentration ranging from 5 to 10%. Petition 870210108062, dated 11 / 22 / 2021, page 28 / 40

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