METHOD FOR TREATING SURFACES OF METALLIC BIOCOMPATIBLE MATERIALS AND IMPLANT TREATED THEREWITH

Description

FIELD OF THE INVENTION

[0001] The present invention relates to the field of biocompatible materials, and more particularly the field of implants, in particular dental or spinal implants.

[0002] It relates in particular to a process for the preparation and treatment of the surface of such a material. PREVIOUS ART

[0003] Currently, dental implants, devices designed to be partially inserted into a patient's jawbone to replace a tooth, are generally made from metal alloys. These alloys most often contain titanium for strength reasons. The same is true for spinal implants.

[0004] In order to promote the osseointegration of an implant, either the application of coatings comprising calcium phosphate (for example in the form of hydroxyapatite, of a chemical nature close to that of bone) or surface treatments have been proposed to increase both their surface roughness and their hydrophilic character.

[0005] Current surface treatments most often include sandblasting the surface using alumina grains, and / or treatment with an acid solution (inorganic acids such as hydrofluoric, hydrochloric, sulfuric, phosphoric, nitric acids, etc. or a mixture of several of these acids).

[0006] An alloy based on titanium, aluminum and vanadium, for medical use, has recently been put on the market: it is TA6V ELI (Extra Low Interstitial).

[0007] However, current surface treatments of this TA6V ELl alloy, intended to create macroporosity and microporosity on the surface, are not satisfactory for the following reasons: To create surface macroporosity, sandblasting treatments with alumina particles (cheap and very hard particles) leave alumina microbeads embedded on the surface of the material. A subsequent treatment with hydrofluoric acid can remove them, but weakens the material and degrades its mechanical properties. To create microporosity, acid attacks are then used using hydrochloric acid solutions, and / or solutions combining hydrofluoric acid and nitric acid, which attack the surface of the material, leaving protruding or dislodging Vanadium atoms.

[0008] Neither the presence of alumina impurities nor vanadium atoms on the surface are desirable for practitioners. Indeed, in the dental field, any impurity can be a cause of failure of osseointegration of an implant.

[0009] Thus, the disadvantage of the TA6V ELl alloy is the presence of vanadium (4% by weight) and aluminum (6% by weight) in its composition. These two elements, which are not biocompatible, can alter the biological properties of implants made from this material.

[0010] WO2013 / 124693 describes a method for manufacturing superhydrophilic implants. US2011 / 233169 describes a dental implant having a nanoscale surface topography and a method for manufacturing such a dental implant. CN104451684 describes a method for manufacturing a multifunctional surface of a titanium-based bionic implant. EP1847278 describes a dental implant, a packaging for this dental implant and a method for treating this dental implant, which prevent the biologically active surface of the implant from being altered by contaminants. EP2476443 describes a ceramic-based dental implant having a hydrophilic surface for at least partial insertion into a bone. AIMS OF THE INVENTION

[0011] A first aim of the present invention is therefore to overcome the drawbacks of the above methods and to propose a method for surface treatment of a biocompatible metallic material, such as an implant, which increases the surface roughness without leaving residues which could hinder the osteointegration of said material.

[0012] Another aim of the invention is to propose a surface treatment method which is adaptable to the titanium, aluminium and vanadium based alloy, for medical use TA6V ELI.

[0013] Another aim of the invention is also to propose a method for treating the surface of a biocompatible material, such as an implant, which increases the hydrophilic character of its surface. DETAILED DESCRIPTION

[0014] For this purpose, the present invention relates to a method for surface treatment of a biocompatible metallic material, such as an implant, according to claim 1.

[0015] The main advantage of this process is that the so-called "sandblasting" step, i.e. the abrasive mechanical treatment step, uses grains made of hydroxyapatite and tricalcium phosphate, which are constituent materials of the bone structure. If residues remain on the surface, these do not constitute impurities, but can instead participate in the osseointegration of the material.

[0016] Until now, such mechanical treatment using hydroxyapatite and tricalcium phosphate grains had only been carried out for surfaces made of polymer material (FR 2.906.147). However, surprisingly, abrasive mechanical treatment using calcium phosphate grains, such as a mixture of hydroxyapatite and tricalcium phosphate grains, carried out by high-pressure projection of said abrasive grains, makes it possible to create, on the surface of a metallic material, such as a titanium alloy material, macroporosities on the surface of said material in the form of alveoli with dimensions of the order of 50 µm to 250 µm.

[0017] Hot treatments, at a temperature above 40°C, in acid and sodium environments respectively, then allow the creation of microporosity (pores of the order of 1 to 50 µm) as well as nanoporosity (pores smaller than a micrometer) in the said first cells, in a homogeneous manner over the entire treated surface.

[0018] The first anchoring of the implant is carried out thanks to the surface macroporosity of the material; the microporosity helps to promote the creation of bridges or secondary anchoring tentacles, and finally the nano-porosity produces a suction effect (capillarity) increasing the vascularization of this graft, and therefore its osseointegration.

[0019] Preferably, the biocompatible material is a titanium alloy, more particularly an alloy based on titanium, aluminum and vanadium, such as the alloy called TA6V ELI (according to standard ASTM F136).

[0020] It has indeed been found, surprisingly, that the combination of the steps of the surface treatment process, according to the present invention, applied to the TA6V ELI alloy makes it possible to create a very rough and hydrophilic surface without causing detachable vanadium crystals to appear or leaving residues of undesirable abrasive materials on the surface of the implants.

[0021] According to advantageous characteristics of the invention: The mixture of hydroxyapatite and tricalcium phosphate grains comprises 80 to 90% hydroxyapatite and 10 to 20% tricalcium phosphate.

[0022] The hardness of these grains is preferably greater than 350 Hv (Vickers hardness)

[0023] The abrasive grains of calcium phosphate, in particular hydroxyapatite and tricalcium phosphate, have a particle size of between 160 and 400 micrometers, preferably between 200 and 360 micrometers.

[0024] The acid bath consists of 45 to 55% by volume of 95% sulfuric acid and 45 to 55% by volume of 37% hydrochloric acid.

[0025] The acid treatment is carried out by soaking said material in a bath at a temperature between 60 and 70°C for a period of 18 to 30 minutes, preferably 20 to 25 minutes.

[0026] The sodium treatment is carried out by soaking the said material in soda at a concentration of 4 to 6 molar and at a bath temperature of between 60 and 70°C for a period of between 18 and 30 minutes, preferably between 20 and 25 minutes.

[0027] The treatments in the acid and sodium baths are advantageously carried out with stirring, and carried out immediately after each other in the order indicated above.

[0028] The present invention also relates to an implant according to claim 8.

[0029] The implant according to the invention having undergone a surface treatment by means of the method described above is also characterized in that the contact angle of the treated surface is less than or equal to 10° in the presence of distilled water or ethylene glycol as a wetting agent. This hydrophilic character of the surface thus increases the capillarity in the pores of the surface of the material, in particular for physiological liquids.

[0030] The implant according to the invention may also be an implant made of an alloy of titanium, aluminium and vanadium, such as the alloy called TA6V ELI, characterized in that it has undergone a surface treatment using the method described above, its treated surface having reduced aluminium and vanadium contents of at least 30% compared to the starting alloy, measured by EDS (Energy Dispersive Spectroscopy) analysis.

[0031] The surface treatment according to the invention is suitable for implants having a threaded outer surface. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The invention will be better understood upon reading the following description of an exemplary embodiment, with reference to the appended drawings, in which: there Figure 1 is a scanning electron microscopy image, with a magnification of 500, of the surface of an implant treated according to the method of the present invention; Figure 2 is an image of the implant surface Figure 1 with a magnification of 2,000; the Figure 3 is an image of the implant surface Figure 1 with a magnification of 5,000; the Figure 4 is an image of the implant surface Figure 1 with a magnification of 10,000; the Figure 5 is an image of the implant surface Figure 1 with a magnification of 30,000; the Figure 6is a diagram comparing the contact angles of the implant surfaces of Examples 1 and 2 measured with different wetting agents. EXAMPLES Example 1 according to the invention

[0033] The surface treatment of an implant made of TA6V ELI alloy (according to ASTM F136 standard titanium-based alloy, containing 6% by mass of aluminium and 4% by mass of vanadium: see table 1) is carried out using a treatment called “Nano-etching” in three consecutive stages, detailed below. Table 1 Fe% max. 0% max. N% max. C% max. H% max. Al % V % 0,25 0,13 0,05 0,08 0,012 5,50 - 6,50 3,50 - 4,50 Step 1 : Mechanical treatment

[0034] The implants are sandblasted with an abrasive composed of hydroxyaptite (85 ± 5%) and tricalcium phosphate (15 ± 5%) with a Vickers hardness of 532 Hv, with a powder grain diameter between 160 and 400 µm, with a predominance of grains between 200 and 360 µm in diameter.

[0035] This step involves creating porosities up to 250 µm in diameter. The abrasive grains are projected using a nozzle placed approximately 10 to 20 cm from the implant surface under a pressure of 5 to 7 bar for 60 ± 10 seconds. Step 2 : Acid treatment

[0036] This step consists of creating porosities of a few tens of microns in diameter and depth in a homogeneous manner over the entire treated surface.

[0037] The treatment is carried out in a mixture composed of two acids. The acid composition and treatment parameters are described below: Bath composition: 50% ± 5% by volume of 95% sulfuric acid and 50% ± 5% by volume of 37% hydrochloric acid. Treatment temperature: 67 ± 2.5 °C, Treatment duration: 22 ± 1 min, Bath stirring required.

[0038] Longer processing time or temperature above the indicated range leads to attack of the macro-roughness created in step 1. Step 3 : Sodium treatment

[0039] This treatment aims to create a nanometric porosity tissue on the surface of the implant.

[0040] This step is carried out in a sodium hydroxide bath, as follows: Bath composition: sodium hydroxide at 5 ± 0.5 M (5 ± 0.5 mol / L) Bath temperature: 67 ± 2.5 °C, Treatment duration: 22 ± 1 min, Bath agitation.

[0041] Insufficient sodium treatment (insufficient NaOH concentration, pores below 4 mol / L, lower temperature or shorter treatment time) leads to less hydrophilic surfaces with contact angles in the presence of distilled water, ethylene glycol or diiodomethane above 50°, or even above 70°, as well as insufficient nanoporosity. Results of SEM observations :

[0042] The images obtained under scanning electron microscope observation, presented on the figures 1 to 5 under different magnifications (respectively 500, 2000, 5000, 10,000, and 30,000), show a very uneven and very rough surface.

[0043] The surface, in fact, has an appearance with porosities of a few tens of microns in diameter which themselves include porosities of a few microns in diameter and depth. These same microporosities also include porosities of diameter and depth less than a micron, namely a few hundred nanometers. The presence of this triple level of porosity on the surface of the material constitutes a significant advantage for the osseointegration of the implant.

[0044] We can even observe on the SEM image with a magnification of 30,000 a fabric of very fine fibers which covers the entire treated surface.

[0045] EDS (Energy Dispersive Spectroscopy, carried out under vacuum with a FEl QUANTA 200 device) analyses of this surface show a strong presence of titanium and oxygen (therefore probably titanium oxide), as presented in Table 2 below which compares the chemical composition of the treated surface and that of the raw alloy before treatment. Table 2 Elements Mass composition (%) Surface-treated alloy Raw alloy Titanium 66,15 86,95 - 89,20 Oxygen 26,11 0,5 Aluminum 3,50 5,5 - 6,75 Vanadium 1,92 3,5 - 4,5 Carbon 1,44 0,08 Sodium 0,11 - Iron - 0,4 Hydrogen - 0,015

[0046] The surface of the alloy treated according to the invention has lower aluminum and vanadium contents than those present on the surface of a raw grade 23 titanium alloy (TA6V ELI). These analyses also highlight the high presence of oxygen on the surface of the treated implant, which means that a layer of titanium oxide is formed. Comparative example 2

[0047] A surface treatment of a Straumann SLA ® titanium-based alloy implant is carried out in the same three steps and under identical conditions as in Example 1 above. Roughness measurements :

[0048] The results of the roughness measurements Ra and Rz (carried out using a MITOTOYO device, reference SJ400) comparing the surfaces of the implants treated according to example 1 and comparative example 2 are presented in table 3 below.

[0049] The meanings of Ra and Rz are as follows: "Ra": average deviation. This is the arithmetic mean of the absolute values ​​of the deviations between peaks and troughs. "Ra" measures the distance between this average and the "central line". "Rz": regularity. This is the average of the greatest difference in altitude between the highest peak of a peak and the lowest bottom of a trough, observed over 5 lengths. Table 3 Tested surfaces Ra Rz Comments Example 1 1,90 µm 10,46 µm The surface of the implant in Example 1 is rougher than that of the implant in Example 2. Example 2 (Comp.) 1,83 µm 10,03 µm Contact angle measurements :

[0050] Contact angle measurements were performed with three different liquids (distilled water, ethylene glycol and diiodomethane) for the implants of examples 1 and 2. The results, presented on the Figure 6 , show significant differences when the wetting agent is either distilled water or ethylene glycol, proving a much superior hydrophilic character for the surface treated according to the method of the present invention.

Claims

1. Process for the surface treatment of a titanium alloy biocompatible metallic material, such as an implant, comprising the following consecutive steps: i) abrasive mechanical treatment of the surface of said material by means of abrasive grains based on a mixture of hydroxyapatite and tricalcium phosphate; ii) acid treatment by soaking said material, at a temperature above 40°C, in a bath comprising sulfuric acid and hydrochloric acid, followed by at least one rinse, preferably two rinses, with demineralized water; iii) sodium treatment by soaking said material, at a temperature above 40°C, in a sodium hydroxide-based bath followed by at least one rinse, preferably two rinses, with demineralized water and by hot air drying, said steps making it possible to create, on the surface of said biocompatible metallic material, a macroporosity in the form of cells with a diameter of the order of 50 µm to 250 µm, said cells comprising pores with a diameter and depth of 1 µm to 50 µm, and pores with a diameter and depth of less than one micrometre, homogeneously over the entire surface treated, said treated surface having a surface roughness Ra of greater than or equal to 1.90 µm.

2. Process according to Claim 1, characterized in that the biocompatible metallic material is an alloy of titanium, aluminium and vanadium, preferably the titanium alloy containing from 5.50% to 6.50% by weight of aluminium, from 3.50% to 4.50% by weight of vanadium, 0.25% max. of iron, 0.13% max. of oxygen, 0.05% max. of nitrogen, 0.08% max. of carbon and 0.012% max. of hydrogen.

3. Process according to either one of the preceding claims, characterized in that the mixture of hydroxyapatite and tricalcium phosphate grains comprises from 80% to 90% of hydroxyapatite and from 10% to 20% of tricalcium phosphate.

4. Process according to Claim 3, characterized in that the abrasive grains of hydroxyapatite and tricalcium phosphate have a particle size of between 160 and 400 micrometres, preferably between 200 and 360 micrometres.

5. Process according to any one of the preceding claims, characterized in that the acid bath comprises from 45% to 55% by volume of 95% sulfuric acid and from 45% to 55% by volume of 37% hydrochloric acid.

6. Process according to Claim 5, characterized in that the acid treatment is carried out by soaking said material in a bath at a temperature between 60°C and 70°C for a duration of from 18 to 30 minutes, preferably from 20 to 25 minutes.

7. Process according to any one of the preceding claims, characterized in that the sodium treatment is carried out by soaking said material in sodium hydroxide at a molar concentration of 4 to 6 M and at a bath temperature of between 60°C and 70°C for a duration of between 18 and 30 minutes, preferably between 20 and 25 minutes.

8. Implant made of titanium alloy biocompatible metallic material that has undergone a surface treatment by means of the process according to any one of the preceding claims, characterized in that its surface has a macroporosity in the form of cells with a diameter of the order of 50 µm to 250 µm, said cells comprising pores with a diameter and depth of 1 µm to 50 µm, and pores with a diameter and depth of less than one micrometre, homogeneously over the entire surface treated, said treated surface having a surface roughness Ra of greater than or equal to 1.90 µm.

9. Implant according to Claim 8, characterized in that the contact angle of the treated surface is less than or equal to 10° in the presence of distilled water or ethylene glycol as wetting agent.

10. Implant according to Claim 8 or 9, made of an alloy of titanium, aluminium and vanadium, characterized in that it has undergone a surface treatment by means of the process according to one of Claims 2 to 7, its treated surface having contents of aluminium and vanadium that are reduced by at least 30% relative to the initial alloy, measured by EDS analysis carried out under vacuum, and the presence of titanium oxide.

11. Implant according to Claim 10, characterized in that it is made of titanium alloy containing from 5.50% to 6.50% by weight of aluminium, from 3.50% to 4.50% by weight of vanadium, 0.25% max. of iron, 0.13% max. of oxygen, 0.05% max. of nitrogen, 0.08% max. of carbon and 0.012% max. of hydrogen.