Bioactive and photocatalytic coating on metal orthopaedic and dental implants and procedure of preparation

Bioactive and photocatalytic coating on metal orthopedic and dental implants and preparation process

The subject of the invention is a bioactive and photocatalytic coating on metal orthopedic and dental implants and a process for preparing the coating. Titanium oxide coating applied by hydrothermal synthesis to a smooth, rough or macroporous surface of metal orthopedic or dental implants for permanent or temporary skeletal support, or as a substitute for the missing skeleton, is biocompatible, bioactive, hydrophilic and photophilic does not combine any known implant coatings.

Known state

Most dental and orthopedic implants that serve as a permanent or temporary support to the skeleton, or that replace part of the bone, are metal, since metals are significantly more resistant to fractures than other materials. In dental and orthopedic reconstruction, titanium and its alloys quickly gained a great advantage over other metals and alloys, because of their relatively good corrosion resistance and biocompatibility, according to clinical research, they are better tolerated by the body than other metals and alloys. Typically, metals and implants for implants, e.g. various steels, Co-Cr alloys and titanium alloys also contain elements that are cytotoxic or neurotoxic to increase mechanical strength. Recently, the implant material has been dominated by Ti6A14V alloy, which is less expensive and more mechanically resistant than pure titanium, but its disadvantage is the presence of aluminum and vanadium, which are toxic to the body.

The disadvantage of metals is that they corrode in contact with body fluid, that metal atoms diffuse into the environment and cause various negative reactions of the organism and that the surrounding tissue grows relatively poorly at the implant. There are also frequent inflammations that are largely due to the presence of bacteria during surgery, which can in turn lead to implant malfunction, which requires replacement of the implant, ie reoperation. Allergic reactions to elements in the metal that diffuse into the surrounding tissue are also possible, causing various health issues, sometimes requiring even removal of the implant.

Because osteointegration, ie bone healing and metal implantation, is worse than in other materials, e.g. for hydroxyapatite and bioactive glass, many modification techniques have been developed

-2 Surfaces of metal for bone implants. In order to improve osteointegration, implants have been developed, e.g. hip joints with a rough surface, e.g. with furrows, metal beads or porous metal coating, sandblasting, etc. The disadvantage of such coatings is that in addition to the diffusion of metal atoms into the body, they are relatively poorly absorbed by the blood plasma, which reduces the rate of adsorption of intercellular proteins to the implant. For fast, firm and permanent osteointegration of the bone implant, it is important to quickly bind proteins, e.g. fibronectin as soon as the implant contacts the intracellular.

Bone implants are also referred to as non-metallic coatings, e.g. SiC, diamond-like "DLC" coatings, TiN, AI2O3, isotropic pyrolytic graphite and other non-metallic coatings. The disadvantage of these coatings is that they are either not bioactive, poorly dipped in blood plasma, e.g. DLCs ​​contain cytotoxic or neurotoxic elements, e.g. A12O3, or are not firmly attached to and exfoliate from the substrate, e.g. some types of titanium oxide coatings.

Partial improvement of osteointegration was achieved by applying biocompatible and bioactive coatings based on hydroxyapatite, which is similar in composition to the mineral part of the bone and is therefore highly bioactive, which greatly accelerates the process of mineral tissue formation upon contact with the implant. However, due to the biodegradability of hydroxyapatite, the improvement is only temporary and the negative effects of the release and propagation of metal ions into the body are only temporary.

Also known is a composite bioactive coating of titanium oxide and hydroxyapatite, which is prepared by a combined process, first applying hydroxyapatite, followed by the procedure "micro are anodisation" or. MAO. The purpose is to dop titanium oxide with calcium and phosphorus to improve osteointegration and cellular activity. The disadvantage of this coating is that due to the resorption of hydroxyapatite, the release of titanium oxide particles is high.

Somewhat similar to the proposed solution is a calcium titanate coating that was prepared by a hydrothermal process in CaO solution and is described in an article by Kenichi Hamada, Masayuki Kon, Takao Hanawa, Kenichi Yokoyama, Youji Miyamoto, Kenzo Asaoka, Hydrothermal modification of titanium surface in calcium Solutions, Biomaterials 23 (2002) 2265-2272 and Patent W0 / 2007/040298. It is prepared by a similar process to the solution of the invention Bioactive and photocatalytic coating on metal implants and the preparation process, except that different ingredients are used and therefore the composition of the coating is different. Cover from

Calcium titanate is said to be bioactive, as apatite grows on it within 30 days, is firmly bound to the substrate, but is not hydrophilic and photocatalytic.

Also known are titanium oxide based coatings which are applied to the surface of metal implants by the procedures described below.

Most of the known processes for the preparation of titanium oxide coatings involve heating to temperatures at which usually the most stable but less suitable form of titanium oxide, rutile, is produced for biomedical use. Anatase, which is one of the three crystalline forms of titanium oxide - rutile, anatase, brokite, is known for its special properties, among which biocompatibility, bioactivity, photoactivity and superhydrophilicity are reported separately in the literature. The proposed process for the application of a titanium oxide coating by hydrothermal treatment of metal implants is carried out at temperatures where no transition occurs, so the coating is predominantly in the form of anatases. Anatase typically forms spike-shaped crystals, which adversely affect osteointegration due to the unfavorable cellular response.

One of the characteristic properties of nanocrystalline titanium oxide in the form of anatases is the photocatalyticity utilized in various fields, e.g. for self-cleaning coatings, additives in cosmetics and elsewhere. Photocatalyticity can be used, inter alia, for the biological decontamination of surfaces (eg organic impurities, microorganisms such as viruses, bacteria, mold spores and fungi). The sterilizing effect of a titanium oxide coating prepared by the sol-gel process on aluminum fibers is described in an article by L. Luo, L. Miao, S. Tanemura, M. Tanemura, Photocatalytic sterilization of TiO₂ films coated on Al fiber, Materials Science and Engineering: B, 148 (2008) 183-186.

The bioactivity of the plasma titanium oxide coating after irradiation with UV light is also reported, which is not typical for unshaded titanium dioxide.

The articles also report superhydrophilicity attributed to the photocatalytic activity of titanium oxide. The effect diminishes over time in the absence of UV light, but can be prolonged by the addition of silica. In an article by S. Permpoon, M. Houmard, D. Riassetto, L. Rapenne, G. Berthome, B. Baroux, J. C. Joud, M. Langlet, Natural and persistent superhydrophilicity of SiO2 / TiO2 and TiO2 / SiO2 bi-layer films, Thin Solid Films 516 (2008) 957-966, is described • ·

-4 Two-layer titanium and silica coating prepared by sol-gel process where the presence of silicon oxide is expected to contribute to a more lasting photocatalytic effect. Such bone replacement coatings have not yet been described.

Depending on the composition, titanium oxide based coatings are known, typically pure titanium oxide or a titanium oxide composite with silica or hydroxyapatite. None of the titanium oxide coatings contain essential elements that significantly affect osteointegration, namely calcium, silicon, phosphorus, strontium and zinc, which play the following role: Silicon reduces the absorption of aluminum and plays a key role in bone and connective tissue formation, strontium stimulates osteoblast growth, increases bone production and inhibits bone-degrading osteoclasts, zinc promotes collagen synthesis, which is a key component of bone, calcium and phosphorus being the main components the mineral part of the bone and therefore the most important element in the composition of the bone.

As described above, a number of different coatings are known, but they have disadvantages that are also partly related to the coating preparation process. The following procedures are known for preparing a titanium oxide coating on metal implants:

Titanium oxide is formed on the titanium spontaneously by oxidation under normal conditions, but the oxide layer formed is too thin to serve as a protective or protective agent. barrier to diffusion of metal atoms, nor is the naturally oxidized surface of titanium bioactive, photocatalytic and hydrophilic.

A thicker layer results from thermal treatment in an oxygen atmosphere - the layer is usually relatively poorly adhered to the substrate, so it is not suitable for implants.

- Electrochemical oxidation (anodization) in solution is also known. The coatings thus prepared do not have the coating properties of the present invention.

- Sputter deposition is also used to apply titanium oxide coatings, which is quite expensive. Coatings are not bioactive and photocatalytic.

- A process for applying titanium oxide coatings to various sol-gel synthesis substrates is also known, using titanium (IV) propoxide and Ti (IV) butoxide as precursors, but may also be an inorganic precursor. After hydrolysis, condensation and polymerization, a thermal treatment is required which results in the crystallization of the resulting gel. The process is not suitable for

-5 Substrates which for any reason should not be heated to the temperature required for crystallization but the coatings do not have all the desired properties.

- The process of chemical vapor deposition (CVD) is also known, in which the organic precursor decomposes upon contact with the substrate and forms an oxide layer. Covers do not have all the target properties.

- The "Ion-beam-assisted sputter deposition (IBASD)" procedure is also known. The coatings thus prepared do not have the coating properties of the present invention.

The process, which is partially similar to the one proposed and described in the article by K. Hmada et al., Biomaterials 23 (2002) 2265-2272, is hydrothermal treatment of the metal in the presence of Ca (OH) 2 followed by heating to increase the crystallinity of the coating at 600 ° C under vacuum. The coating thus prepared consists of calcium titanate, which is bioactive but does not have the other properties of the proposed titanium oxide based coating.

A problem that is not satisfactorily resolved

Although described, several types of coatings with different chemical composition, including titanium oxide, are known, but none combines all the desired properties, i.e. reduction of diffusion of metal atoms into the body, biocompatibility, bioactivity, hydrophilicity and photocatalytic. The most similar process to the proposed method is the hydrothermal treatment of metal implants in CaO solution, the product of which is not titanium oxide but CaTiO3, which has no titanium oxide properties. None of the titanium oxide coatings contain elements that significantly affect osteointegration, namely calcium, silicon, strontium, zinc, magnesium and phosphorus.

The aim of the invention is to improve metal implants by applying a thin biocompatible, bioactive, hydrophilic and photocatalytic coating based on titanium oxide in the predominant modification of anatases with pinakoid grain form with the addition of essential elements and with features that contribute to improving the adhesion of the implant with bone and reducing the negative effects of diffusion of metal ions in the body.

Proposed solution

According to the invention, a titanium oxide coating in the form of anatase with pinakoid grains is applied to a metal base made of titanium, titanium alloy or other metal substrate and embedded therein

-6elements for enhancing osteointegration of Ca, Si, P, Mg, Sr and / or Zn. Such coating prevents direct contact with body-harmful metal ions and reduces the diffusion of metal ions into the body and, in addition, is prepared by the proposed process, ie hydrothermal synthesis under the conditions described below, bioactive, hydrophilic and photocatalytic. Compared to the known titanium oxide coating methods, the proposed process is simple and inexpensive, and the coating thus prepared combines properties not achieved by any known metal implant coating.

Procedure description

The process of preparing a biocompatible, bioactive and photocatalytic TiO2-based coating on the surface of metal implants intended to permanently or temporarily support the skeleton or to replace the missing part of the skeleton and its properties is described in more detail below:

- Prepare a saturated aqueous solution of titanium ions. To the solution is added an inorganic or organic base, namely NaOH, KOH, Ca (0H) 2, NH40H or tetraalkyl ammonium hydroxide, citric and phosphoric acid to adjust the pH to a value in the range 3 to 12. In addition, 0.05 to 1 is added. by weight of CaF2 or SrF2 or MgF2 or ZnO or other divalent salt and 0.001 to 0.1% SiO2 by weight of water. The mixture is prepared in a container or poured into a container with an inner lining of titanium or teflon or other thermally stable and chemically inert polymer. The metal implant is immersed in the prepared mixture.

- Close the container tightly and heat to 100 to 300 ° C at a speed of 2 to 10 ° C / min. It is kept at this temperature for 6 to 96 hours, then automatically cooled to room temperature.

- The container is opened and the metal implant coated with the mixture is opened and the implant is then thoroughly rinsed under running water or in an ultrasonic bath and in acetone or alcohol to remove unused reagents. The cleaned implants are automatically dried at room temperature or up to 150 ° C.

- The implant can be further cleaned and sterilized by irradiation in the UV light of a wavelength of 300-400 nm.

The process of preparing bioactive and photocatalytic coatings on metal implants is characterized in that the implants are immersed in a saturated solution containing Ti, Ca, Mg, P, Si, Zn and / or Sr ions having a pH of 3 to 12, 6 to 96 for hours they are heated in a tightly closed autoclave at 100-300 ° C and then taken out of the autoclave and cooled to room temperature, washed and dried, • ·

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-It can also be irradiated in UV light. The process allows the coating of various materials and implants with a smooth or very rough surface.

The coating according to the invention and made according to the described procedure consists of up to 5 micrometers of a thick layer of titanium oxide in a predominantly pinakoidal anatase form with the addition of essential elements and is firmly attached to the substrate. The coating is hydrophilic, preventing direct contact of blood plasma with cytotoxic and allergenic metals, e.g. with aluminum and vanadium in Ti6A14V and is bioactive - hydroxyapatite forms on the surface in 2 to 3 weeks in the simulated body fluid. The coating is photocatalytic - when irradiated with UV light of a wavelength of 300-400 nm, organic and biological impurities are degraded and the implant is sterilized.

Bioactive and photocatalytic coating on metal implants is characterized in that it has a composition and properties that promote and enhance osteointegration of each, namely it is bioactive and forms hydroxyapatite in it, photocatalytic and radicals upon irradiation in UV light. which break down organic and biological impurities, the coating is sterilized in this way, it is hydrophilic, and therefore the cell is quickly and completely enveloped by the cell to allow rapid protein adsorption.

The invention will hereinafter be described in detail based on embodiments:

Example 1:

In 100 ml of distilled water, 5 g of titanium oxide powder with a particle size of 50 nm and 0.1 g of ZnO and 0.1 g of SrF2 are added. With the addition of Ca (OH) 2, NaOH, TMAH and citric acid, the pH was adjusted to 10. The suspension was poured into a Teflon container and a metal Ti6A14V alloy implant was immersed therein. The container is sealed tightly, heated to 200 ° C and heated for 36 hours. The vessel is then automatically cooled to room temperature, opened, and the coated implant is rinsed for 1 hour under running water and 1 h in an ultrasonic bath with distilled water and 1 h in an ultrasonic bath with ethanol, ensuring the supply of fresh water or ethanol. The implant is dried for 3 hours in a stream of hot air at 150 ° C, then cooled and irradiated for 12 hours with UV light of 300-400 nm.

• ·

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Example 2:

To 100 ml of distilled water is added 1 g of titanium powder with a particle size of 500 nm and 0.5 g of CaF2 and 0.1 g of SiO2. With the addition of NaOH, TMAH, phosphoric and citric acid, the pH is adjusted to 11. The suspension is poured into a titanium vessel and a metal Ti6A14V implant is immersed therein. The container is sealed tightly, heated to 150 ° C and heated for 48 hours. The vessel is then automatically cooled to room temperature, opened, and the coated implant is rinsed for 1 hour under running water and 1 h in an ultrasonic bath with distilled water and 1 h in an ultrasonic bath with ethanol, ensuring the supply of fresh water or ethanol. The implant is dried for 3 hours in a flow of hot air at 100 ° C, then cooled and irradiated for 12 hours with UV light of 300-400 nm.

The implant according to the invention is coated with a tightly bound titanium oxide based coating, which forms a barrier between the metal implant and the intercellular, thus preventing direct contact of the metal with bone for a long time and restricting or preventing the passage of metal ions other than titanium into the body. Titanium oxide based coating also contains essential elements that promote osteointegration. The coating is also bioactive and hydroxyapatite forms on the intercellular surface, which accelerates osteointegration. The coating is photocatalytic and, when irradiated in UV light, radicals are formed on it, which break down organic and biological impurities, the coating being sterilized in this way. The coating is also hydrophilic, so it is quickly and completely enveloped by the intercellulose to allow rapid protein adsorption.

The bioactive and photocatalytic coating on metal orthopedic and dental implants according to the invention is characterized by the fact that it consists of up to 5 micrometers of a thick layer of titanium oxide in a predominantly pinakoidal anatase form with the addition of essential elements and is firmly attached to the metal substrate. The coating has a composition and properties that accelerate and enhance the osteointegration of each, namely, it is bioactive and forms hydroxyapatite in the intercellular space, photocatalytic and, when irradiated in UV light, it forms radicals that break down organic and biological impurities. it is sterilized, hydrophilic, so the cell is quickly and completely enveloped by the cell to allow rapid protein adsorption. The process of preparing a bioactive and photocatalytic coating on metal orthopedic and dental implants according to the invention is characterized in that the implants are immersed in a saturated solution containing Ti, Ca, Mg, P, Si, Zn and / or Sr ions having a pH of 3 to 12, then heated for 6 to 96 hours in a tightly closed autoclave at 100-300 ° C and then taken out of the autoclave and cooled to room temperature, washed and dried, • · · «· &lt;

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-9can also be irradiated in UV light. The bioactive and photocatalytic coating on metal orthopedic implants is made according to the method of claim 3.