RU2790346C1 - A method for producing a biocompatible coating on products made of monolithic titanium nickelide - Google Patents

Abstract

FIELD: protective coatings.

SUBSTANCE: The invention relates to protective coatings for medical implants made of titanium nickelide and can be used to reduce the survival time of implants. A method for obtaining a biocompatible coating on products made of monolithic titanium nickelide involves the sequential application of three alternating layers of titanium-nickel-titanium in an atmosphere containing argon, and heating the products to a temperature sufficient for spontaneous initiation of a self-propagating high-temperature synthesis reaction, followed by cooling under the same conditions for 60 minutes to room temperature, while the thickness of the specified layers are chosen equal to 40 ±5 nm, and the products are heated to a temperature of 1000 ±10 °C for 60 ±5 C in a gas medium composed of 80% N and 20% Ar.

EFFECT: The present invention enables to increase the cytocompatibility of the coating by achieving a mixed phase composition of titanium oxides and nitrides with optimal roughness and hydrophilicity characteristics.

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Description

SUBSTANCE: invention relates to metallurgy, specifically to protective coatings for medical implants made of titanium nickelide and can be used in medicine to reduce the survival time of implants.

TiNi alloys are widely used in medicine due to their high biomechanical compatibility, fatigue strength, which is achieved due to the superelastic functional properties of the alloy [Günter V.E. Titanium nickelide. Medical material of a new generation / V.E. Gunther, V.N. Khodorenko, Yu.F. Yasenchuk and others - Tomsk: Izd-vo MITS. - 2006. - 296 p.]. When used in the human body under aggressive corrosion-dynamic conditions, implants made of monolithic TiNi alloys with natural oxide layers on the surface are prone to cracking and adhesive wear. This leads to electrochemical corrosion, as a result of which the biotoxic degradation products of the TiNi compound dissolve and accumulate in adjacent tissues, causing malignant reactions and rejection of implants [Ryhanen, J. Biocompatibility of nickel titanium shape memory metal and its corrosion behavior in human cell cultures / J. Ryhanen, et al. // Journal of Biomedical Materials Research. - 1997. - Vol. 6. - P. 451 - 457]. When implanting metal materials into the body, the reaction of cells to the implant is important, which is determined by the state of the surface and affects the survival time. With a biochemically incompatible surface, a fibrous capsule appears around the implant, which prevents cell adhesion and proliferation, leading to failure and further rejection of the implant. The low biochemical compatibility of the surface can also manifest itself at later stages during the long-term operation of implants from a monolithic TiNi alloy, which affects its biological safety and is a serious problem.

Thus, surface modification and protective coatings for biomaterials based on the TiNi alloy are promising ways to increase their biochemical compatibility. In recent years, much attention has been paid to the biochemical improvement of the surface of titanium alloys. Thus, the corrosion resistance of implants made of nickel-titanium alloys is increased by creating oxide, nitride, oxynitride and intermetallic gradient coatings.

The deposition of thin films of titanium nitride has become a promising way to modify the surface of metal implants due to its chemical stability and corrosion resistance. The hydrophilic nature of nitride coatings allows protein to be adsorbed. In vitro biocompatibility studies conducted using the mouse embryonic fibroblast (NIH3T3) cell line demonstrated that the coatings are non-toxic and show excellent interactions between cells and materials [Aissani L. et al. Relationship between structure, surface topography and tribo-mechanical behavior of Ti-N thin films elaborated at different N2 flow rates // Thin Solid Films. - 2021. - V. 724. - P. 138598], However, titanium nitride coatings also have a number of disadvantages, such as high internal stresses and low bond strength with the substrate.

Due to good chemical stability, high hardness and excellent biocompatibility, TiN single-phase monocoatings are created, but when deformed, they experience chipping and peeling [Vaz F. et al. Influence of nitrogen content on the structural, mechanical and electrical properties of TiN thin films // Surface and Coatings Technology. - 2005. - V. 191. - No. 2-3. - P. 317-323.]. Oxide layers based on TiO2 have a developed morphology that is favorable for cell biointegration, but they are prone to cracking and do not prevent the release of metal ions to the surface [Xi X., et al. Surface burn behavior in creep-feed deep grinding of gamma titanium aluminide intermetallics: characterization, mechanism, and effects// The International Journal of Advanced Manufacturing Technology. - 2021. - V. 113. - no. 3. - P. 985-996].

Therefore, to improve the characteristics of single-layer coatings for TiNi alloys, multilayer coatings based on TiN/Ti ₂ N, SiO ₂ , TiO ₂ /TiC, ZrO ₂ , ZrN/Zr, TiN/Ti ₃ O ₅ have been proposed. However, all presented multilayer coatings do not fully meet the requirements for functional biocompatible coatings on superelastic TiNi alloys. Coatings should be solid, thin, dense, resistant to deformation by bending, have high adhesion to the substrate, resist delamination, and have a rough cytocompatible surface.

Titanium oxynitrides with various oxygen content (TiNOX) have properties superior to titanium nitrides and titanium oxides. There are positive results from a clinical study of TiNOX-based coatings for stainless steel stents. The compatibility of the titanium oxide coating with blood in terms of platelet adhesion and fibrinogen adsorption can be improved by adding nitrogen to it [Tsyganov I. A. et al. Hemocompatibility of titanium-based coatings prepared by metal plasma immersion ion implantation and deposition // Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, - 2007. - V. 257. - no. 1-2. - P. 122-127].

These difficulties in forming a protective coating can be largely overcome in the method formulated in the patent [RU 2281122 C1, IPC A61L 27/02, A61R 6/02, publ. 10.08.2006]. In a known method, the coating is obtained by introducing additional elements into the base of titanium carbonitride. The technological cycle for obtaining a coating consists of two main stages: obtaining a composite target by the method of self-propagating high-temperature synthesis and its subsequent magnetron sputtering.

The disadvantages of the known method are due to the use of a large set of additional elements, namely Ag, Ca, Zr, Si, O, P, K, Mn to achieve optimal biocompatibility and mechanical properties of the coating. Also, the target sputtering process is sensitive to changes in technological parameters, and when they deviate, the target sputtering rate changes, as a result of which the coating can have a unique composition and difference in the required properties.

Closest to the claimed method of obtaining a biocompatible coating on products made of monolithic titanium nickelide [RU 2751704, IPC C23C 14/35, B82Y 30/00, publ. July 15, 2021], which includes sequential deposition of three alternating layers of titanium-nickel-titanium in an argon atmosphere and heating of products to a temperature sufficient for the spontaneous start of the self-propagating high-temperature synthesis reaction. The application of these layers with a thickness in the range of 40-60 μm is carried out by magnetron sputtering at an argon pressure of 1 Pa. Products are heated to 800-900°C for (60±5) s in an argon atmosphere at a pressure of 10 Pa, after which they are cooled in an argon atmosphere with a pressure of 10 Pa for 60 min to room temperature.

The disadvantage of this method is the low biocompatibility, determined by the texture of the surface, namely, roughness parameters that do not correspond to physiology, which prevents the surface from being populated by cell cultures.

This is due to the following factors.

Surface topography affects the adhesion and spreading of cells of various types, proliferation both in vitro and in vivo, determines their motor activity, morphology, and orientation. Depending on the conditions of use, the implant must have a certain degree of surface roughness: it can be smooth or more rough. Ensuring the scale of roughness in the nanoscale region gives the coating a large surface energy, wettability, which is one of the important properties that affect the interactions between the cell and the material. For the deposition, adhesion and proliferation of cells and the formation of a monolayer of cells on the surface, the most favorable is the presence of a uniform nanoroughness. A smooth surface or a surface with low roughness reduces the ability of biological cells to attach to the implant surface.

In the prototype, the surface of the coating has a non-uniform roughness, dominated by relatively large grains with sizes up to 1 μm, which coagulate into islands.

The problem solved by the claimed invention is to create a biocompatible multilayer coating of small thickness with phases of titanium oxides and nitrides, which are barriers for nickel diffusion from the substrate to the surface.

The technical result of the claimed invention consists in increasing the cytocompatibility of the coating due to the formation of a surface layer with a mixed phase composition of titanium oxides and nitrides with improved roughness and hydrophilicity.

The claimed technical result is achieved by the fact that when implementing a method for obtaining a biocompatible coating on products from monolithic titanium nickelide, including the successive deposition of three alternating layers of titanium-nickel-titanium in an atmosphere containing argon, and heating the products to a temperature sufficient to spontaneously start the reaction of self-propagating high-temperature synthesis, followed by cooling under the same conditions for 60 min to room temperature, the difference is that the thickness of these layers is chosen equal to (40 ± 5) nm, and the products are heated to a temperature of (1000 ± 10) ° C for ( 60±5) s in a gaseous medium consisting of 80% N and 20% Ar.

The connection of the technical result with the distinctive features is due to the following.

1. Reducing the average thickness of the applied layers of titanium and nickel by magnetron sputtering from 50 nm to 40 nm provides a more dense and uniform coating. Limiting the thickness to about 40 nm for each deposited layer makes it possible to reduce the total thickness of the deposited laminate and the synthesized coating while maintaining strength. The tolerance of ±5 nm is determined by the technological spread. The thickness of the deposited layers should not be more than 50 nm, since a thick coating is prone to cracking during intense deformation of products made of titanium nickelide. When the thickness of the deposited layers is less than 30 nm, the resulting coating loses its continuity. The indicated boundaries of the layer thickness are optimized due to the change in the composition of the gas atmosphere in which the coating is synthesized.

2. The composition of the gaseous medium with a relatively high content of nitrogen (80% N + 20% Ar) ensures the active dissolution of nitrogen in titanium and the formation of a multilayer coating in the form of a combination of various nitride compounds.

3. The product heating temperature (1000±10)°C is determined as optimal for the selected nitrogen-argon medium from the point of view of nitrogen dissolution in titanium. Below this temperature, titanium interacts more actively with oxygen, which is naturally present as residual impurities in argon. To increase the cytocompatibility of the coating, it is favorable to have a higher content of titanium nitrides than titanium oxides. Tolerance ±10°C is determined by technological variation.

3. The developed technique for synthesizing a gradient coating in the presence of nitrogen makes it possible to obtain stable phases of titanium nitride and intermetallic oxynitrides, which serve as a reliable barrier to nickel diffusion from the substrate to the surface. It has been established that a multiphase two-layer diffusion zone is formed during the synthesis, which makes it possible to assert the reliability of the bond between the coating and the substrate. No nickel was found on the surface of the synthesized coatings, which proves the reliability of the barriers from the TiN and Ti4Ni2(N,O) phases on the way of nickel diffusion from the substrate to the surface.

4. The synthesized coating has an optimal roughness value of about 40 nm. It differs in comparison with the prototype more homogeneous structure with small regular grains.

At roughness values approaching 1 µm, cell proliferation becomes difficult.

5. The results of measuring the contact angle of wettability showed that the synthesized coating has a moderate hydrophilic ability. This is also a positive factor, since it is known that cell adhesion and proliferation are better manifested precisely on surfaces with moderate hydrophilicity than on more hydrophobic or hydrophilic ones [S. Devgan, S, Singh Sidhu, Evolution of surface modification trends in bone related biomaterials: A review, Mater. Chem. Phys. 233 (2019) 68-78].

6. The high biocompatibility of the resulting coating was confirmed by a comparative study of the cytocompatibility of the substrate and the coating synthesized by the claimed method: after 72 hours of cultivation, the largest number of living cells was found on the surface of the claimed synthesized coating. A positive effect on the cytocompatibility of the coating was exerted by: a mixed phase composition of titanium nitrides and oxides, increased surface energy, moderate roughness and hydrophilicity.

The invention is illustrated in FIG. 1-6.

In FIG. 1, 2 shows the stages of implementation of the proposed method. The thickness of the titanium and nickel layers deposited by magnetron sputtering is approximately 40 nm (Fig. 1). The thickness of the synthesized coating is about 250 nm and has a diffusion zone of about 230 nm (Fig. 2). The coating has a gradient crystalline structure. As a result of the introduction of nitrogen, oxygen, and carbon impurities, the layers swelled from an initial total thickness of 120 nm to a thickness of 250 nm, or approximately more than 2 times.

In FIG. Figure 3 shows images of samples obtained by atomic force microscopy on scanning surface areas of 5 μm × 5 μm for the original substrate (a) and for coatings obtained: 6 - in argon (prototype) and c - in a mixture of nitrogen with argon. The roughness value for the substrate was on average Ra=12 nm. The surfaces of the synthesized coatings in argon and nitrogen have a more pronounced roughness. The roughness values determined within the scanned area showed close values, namely: Ra=33 nm for the coating synthesized in argon; Ra=40 nm for a coating synthesized in a nitrogen-argon mixture. The difference is that on the surface of the coating synthesized according to the claimed method, small regular grains predominate, while the surface of the coating synthesized in argon is more heterogeneous, there are more large grains that coagulate, forming islands. Thus, the coating according to the claimed method demonstrates increased cell adhesion due to a more uniform surface nanoroughness.

In FIG. Figure 4 shows the surface profiles of the initial substrates (a) and the surfaces obtained by two methods (b).

In FIG. Fig. 5 conditionally shows the results of the study of the contact angle of wettability and surface free energy of the synthesized coating and the titanium nickelide substrate.

The results of measuring the contact angle of wetting showed that both synthesized coatings have a moderate hydrophilic surface. The contact angle 9 for the coating synthesized in argon is (53.1±0.44)°, and for the coating synthesized in a nitrogen-argon mixture - (59.6±0.42)°. The surface of the original TiNi substrate has a contact angle of (92.9±1.33)°, i.e. it is hydrophobic. It is known that cell adhesion and proliferation is best manifested on surfaces with moderate hydrophilicity, characterized by a contact angle of water 9 of the order of 60°, and is less pronounced on more hydrophobic or hydrophilic surfaces. The coating obtained by the claimed method is closest to the optimum in this parameter.

The surface free energy is about 30 mJ/ ^m2 in the titanium nickelide substrate and about 72 mJ/ ^m2 in the synthesized coating. It can be seen that there is a significant difference between the samples in the values of the total free energy, which is due to the dispersion and polar components.

The conducted studies on cytocompatibility confirm the presence of a correlation between the contact angle and cell density. The highest cell adhesion density is observed on hydrophilic surfaces. Cells cultured on the hydrophobic surface of the TiNi substrate do not form a homogeneous layer, but are grouped in separate places.

In FIG. 6 shows the results of the study of cytocompatibility of the sample without coating and with the synthesized coating. The largest number of MCF-7 cells after 72 hours of cultivation was found on the surface of the synthesized coating. The cell mass covers with a monolayer almost the entire surface of the sample with characteristic focal seals, which indicates the best cytocompatibility.

The method for obtaining a biocompatible coating on products from monolithic titanium nickelide includes a two-stage process.

Stage 1. Deposition of amorphous Ti/Ni/Ti nanolaminate.

Alternating amorphous layers of titanium, nickel, titanium with a thickness of 40/40/40 nm are deposited on TiNi substrates. Amorphous Ti/Ni/Ti layers are deposited alternately in a high-purity argon medium by magnetron sputtering, using Ti and Ni targets 80 mm in diameter with a direct current source of 1 kV, 5 A. Modes of deposition of Ti-Ni-Ti layers on a TiNi substrate, selected experimentally: working pressure Ar - 1 Pa; deposition time of Ti layers - 60 sec, Ni - 25 sec, discharge voltage - Ti (350 V), Ni (420 V), magnetron current - 1 A (Ni) and 2 A (Ti), substrate temperature - room temperature, argon flow φAr - 35 standard cubic centimeters per minute, substrate bias - floating potential (≈25 V). The distance from the substrate to the targets was 100 mm.

Stage 2. Synthesis of a protective gradient crystalline coating.

After deposition of the Ti/Ni/Ti nanolaminate, argon is pumped out of the chamber without removing the samples to a base pressure of 8 × 10-4 Pa and a gas mixture of 80% N + 20% Ar is started at an operating pressure of 8 Pa. Then the samples are heated using a heated graphite substrate holder to a temperature of (1000±10)°C with exposure at this temperature for 60 seconds. After heating, the samples are cooled together with the chamber for 60 min to room temperature.

The claimed features and the effect achieved through them in their totality are new, experimentally substantiated and do not follow from known solutions.

Implementation example.

When implementing the proposed method, an anti-corrosion coating was applied to a substrate of monolithic titanium nickelide.

Before sputtering, the substrate surface was prepared using an Ar+ ion source with a current of 70 mA and an accelerating voltage of 3.5 kV for 10 minutes. Then the Ti/Ni/Ti layers were sequentially deposited in high purity argon in a magnetron sputtering setup equipped with Ti and Ni targets 80 mm in diameter. The layers were deposited at the following parameters: operating pressure Ar - 1 Pa, discharge characteristics: for titanium 350 V, 1A, for nickel 420 V, 2A, substrate temperature - room temperature, argon flow 35 standard cubic centimeters per minute, substrate displacement - floating potential ≈25 V. The distance from the substrate to the targets was 100 mm. Under these conditions, the operating deposition rates were 40 nm/min for titanium and 100 nm/min for nickel. The structure of the deposited layers is shown in Fig. 1.

After applying the Ti-Ni-Ti laminate without removal from the chamber, the samples were heated in an 80% N + 20% Ar medium with a working pressure of 8 Pa using a heated graphite substrate holder to a temperature of (1000 ± 10)°C with holding at the working temperature for 60 sec. After heating, the samples were cooled under the same conditions for 60 min to room temperature.

The synthesized gradient coating has three crystalline layers: 1 (TiN+TiO ₂ ), II (Ti ₄ Ni ₂ (O,N)+Ti ₃ Ni ₄ ), III (TiN) with a total thickness of 250 nm (Fig. 2). Due to the small thickness, the coating can deform self-consistently with the substrate without destruction. A diffusion zone has formed in the substrate, which firmly binds the substrate to the coating. In the diffusion zone with a thickness of about 230 nm, two components of the DZA(TiNiO ₃ ) and DZB(TiNi ₃ ) zones are visually distinguished, which differ in contrast, brightness, grain size, and nickel concentration. The crystalline coating of nitrides, oxides and oxynitrides performs a barrier function, preventing the release of nickel ions to the surface. Thanks to titanium nitrides and titanium oxides on the surface layer, optimal roughness, hydrophilicity and maximum total free energy, the coating has high cytocompatibility. Thus, the resulting coating can successfully function and deform due to its small thickness, and the diffusion zone forms a strong bond with the substrate.

Claims (1)

A method for producing a biocompatible coating on products from monolithic titanium nickelide, which includes sequential deposition of three alternating layers of titanium-nickel-titanium in an atmosphere containing argon, and heating the products to a temperature sufficient for the spontaneous start of the self-propagating high-temperature synthesis reaction, followed by cooling under the same conditions within 60 min to room temperature, characterized in that the thickness of these layers is chosen equal to 40 ± 5 nm, and the products are heated to a temperature of 1000 ± 10 ° C for 60 ± 5 s in a gaseous medium consisting of 80% N and 20 %Ar.

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