WO1995032744A1

WO1995032744A1 - Process for the surface coating of metal implants with hydroxiapatite

Info

Publication number: WO1995032744A1
Application number: PCT/ES1995/000065
Authority: WO
Inventors: Rafael Rodriguez Clemente
Original assignee: Consejo Superior Investigaciones Cientificas
Priority date: 1994-05-31
Filing date: 1995-05-31
Publication date: 1995-12-07
Also published as: ES2088767B1; ES2088767A1

Abstract

The invention relates to a new process for coating with hydroxiapatite, (Ca10(OH)2(PO4)6), well crystallized and stoichiometric, from aqueous solutions, the surfaces of metal prostheses which are in contact with living tissues of the human body, the process comprising the following steps: a) functionalisation of the surfaces to be coated; b) immersion of the surfaces into a circulating solution and c) local heating of the surface of the prosthesis to a temperature higher than 80 °C.

Description

PROCEDURE FOR SURFACE COVERING WITH METAL IMPLANTS HYDROXIAPATITO

Object of the invention

The invention consists of a new technique for coating with hydroxyapatite, (Ca ₁₀ (OH) ₂ (PO ₄ ) ₅ ), well crystallized and stoichiometric, from aqueous solutions, the surfaces of metal prostheses that will be in contact with tissues alive of the human body.

State of the art

One of the main problems of medicine is the rejection by the human body of all foreign objects. Implants, therefore, must be designed so that they can be accepted by the body in order to perform the substitute function. In the case of metal implants used for mechanical functions, such as dental, hip, plaque, etc., acceptance is achieved by calcium phosphate coatings, especially hydroxyapatite, of metal surfaces in contact with living tissues.

These calcium phosphate coatings have good biocompatibility, that is, ability to perform their functions with a good response from the subject in a specific application "(DF Williams, Biofunctionality and Biocompatibility, in" Medical and Dental Materials ", Ed. By DF Williams , VCH Verlagsgesellschaf mbH, Weinheim, RFA, 1992) This response must include non-rejection and, in some cases, the subject's bioactivity or ability to dissolve the coating locally and use the dissolution material to generate the inorganic bone tissue fraction Alternatively, good biocompatibility can be manifested by the ability of the implant to promote the creation of new bone tissue, without the need for prior dissolution of the coating (H. Solnic-Leggg and K. Legg, Ion beam and plasma technology for improved biocompatible curfaces, MRS Bull., 17 (4) (1989) 27-30), through porous surfaces that allow the development of cells in the pores (SD Cook, KA Thomas, JF Kay, M. Jarcho, Hydroxyapatite-Coated Titanium for Orthopedic Implant Applications, Clin. Orthop. 232 (1988) 225-243).

Since hydroxyapatite is the natural inorganic component of bones, most efforts have been focused on achieving coatings of this material (4). The conditions required to measure the success of each coating method are the following (WR Lacefield, Hydroxyapatite coatings, Annals of the New York Academy of Sciences, Vol. 523 (1988) 72-80): 1) The hydroxyapatite should not be altered irreversible during the deposition process.

2) The mechanical properties of the substrate should not be affected by deposition operations.

3) The adhesion between the substrate and the coating must be sufficient to ensure that there will be no interfacial failure during the life of the implant.

4) The added cost of the coating process should not significantly increase the cost of the implant.

To date, numerous techniques have been used to obtain hydroxyapatite coatings. The most commonly used is plasma spray or thermal lance "plasma or trust spray", consisting of introducing into the plasma or flame hydroxyapatite powder and projecting the semi-molten powder onto the surface to be coated (JGC Wolke, JMA of Blieck-Hogervorst, WJA Dhert, CPAT Klein and K. de Groot, Studies on the thermal spraying of apatite bioceramics, J. Thermal Spray Tech., 1 (1992) 75-82). This method has the disadvantage of transforming part of the hydroxyapatiro into oxyapatite or tricalcium phosphate, with the consequent loss of condition 1) set forth above. On the other hand, it produces surfaces with little porosity and the appearance of fissures during the cooling process (LC Lucas, WR Lacefield, JL Ong and RY whitehead, Calcium phosphate coating for medical and dental implants, Colloids and Surfaces A, 77 (1993) 141-147).

Electrophoretic deposition of hydroxyapatite particles is another of the methods tested (R. Damodaran and BM Moudgil, Electrophoretic deposition of calcium phosphate from non-aqueous media, Colloids and Surfaces A, 80 (1993) 191-195) to obtain a green "that can be further processed by conventional ceramic techniques. This method has the disadvantage of its high cost and the need for further processing. On the other hand, techniques for obtaining hydroxyapatite coatings have recently been tested using a polymeric route (T. Brendel, A. Engel and C. Rüssel, Hydroxyapatite coatings by a polymeric route, J. Mat. Sci .: Materials in Medicine, 3 (1992) 175-179), consisting of producing a precursor gel by reaction between Phenyl dichlorophosphine (C ₆ H ₅ PC1 ₂ ), hydrolyzed by water in the presence of acetone, and calcium nitrate dissolved in acetone. The prosthesis is immersed in the viscous solution and subsequently calcined at temperatures between 1200 and 1300ΩC, obtaining a very reactive hydroxyapatite as a coating.

Ion-beam sputtering hydroxyapatite deposition (LC Lucas, WR Lacefield, JL Ong and RY whitehead, Calcium phosphate coating for medical and dental implants, Colloids and Surfaces A, 77 (1993) 141-147) produces fairly uniform layers and well bonded of very soluble amorphous material. This solubility can be reduced by a sintering treatment during which crystalline phases are formed in the coating. As in the previous case, the high cost of this technique makes it not recommended yet for its industrial exploitation.

Hydroxyapatite deposition using pulsed laser (CM Cotell and KS Grabowski, Novel materials applications of pulsed laser deposition, MRS Bull., 17 (2) (1992) 44-53) is a variant of the "Sputtering" techniques that employ laser activation. As in the previous case, well-bonded and fairly homogeneous coatings are obtained, consisting of nodules of 1 to 3 microns. These coatings correspond to various phases of calcium phosphates according to experimental conditions, but for substrate temperatures between 400 and 700ΩC, it has been possible to obtain hydroxyapatite coatings, as shown by the diffraction diagrams.

As can be seen, the hydroxyapatite coating in metal prostheses has traditionally been addressed by techniques based on the projection on the metal surface of the partially molten solid material, with the consequent loss of the composition control, obtaining an adhesion based on the roughness existing in the interface The wet techniques tested usually produce precursor systems that need subsequent heat treatments.

Our technique is the first described that produces direct coatings of hydroxyapatite from aqueous solutions taking advantage of the inverse solubility of the hydroxyaptite, its relative stability against other calcium phosphates at temperatures above 70 C, and the possibility of obtaining metastable solutions, with high Induction time for precipitation, by complexing the calcium ion by a suitable ligand such as citrate anion, among others. These conditions allow us to proceed to cause the deposition of the hydroxyapatite from cold and basic pH buffered solutions of phosphate ion and complexed calcium ion, which we circulate on the hot surfaces of the implant, previously phosphated. In some ways, the phenomenon we cause is similar to the deposition of insoluble salt crusts in the solution conduit pipes. • Description of the invention

This invention describes a method of obtaining surface coating of hydroxyapatite (Ca ₁₀ (P0 ₄ ) ₆ (OH) ₂ ) (PAH) on titanium implants or Ti alloys. Titanium implants, or their alloys, are used in dentistry and traumatology, due to their excellent resistance to corrosion and good biocompatibility, meaning the absence of rejection of the natural formation of tissue on its surface, thus establishing a continuous interface . The HAP coating must completely cover the metal surface and be firmly adhered to it.

In order to ensure that the hydroxyapatite layer is anchored firmly on the metal, we have designed a procedure consisting of depositing an intermediate layer between the metal and the hydroxyapatite, which establishes the bond between both materials by true chemical bonds. Since there are no common elements between titanium and PAH, and the chemical bonds existing in both structures are different, the procedure followed consists in first phosphating the metal surface, which generates a layer of a titanium phosphate that would act as interface between the metal and the calcium phosphate layer that would be deposited next.

Our technique consists in producing direct hydroxyapatite coatings from aqueous solutions taking advantage of the inverse solubility of the hydroxyapatite, its relative stability against other calcium phosphates, in aqueous solutions, at temperatures above 70QC, and the possibility of obtaining metastable solutions, with high induction time for precipitation, by complexing the calcium ion by a suitable ligand such as the citrate anion, among others. These conditions allow us to proceed to cause the deposition of the hydroxyapatite from cold and basic pH buffered solutions of phosphate ion and complexed calcium ion, which we circulate on hot surfaces of the implant, previously phosphated. In some ways, the phenomenon we cause is similar to the deposition of insoluble salt crusts in the solution conduit pipes.

The experimental procedure comprises the following steps: a thorough cleaning treatment is carried out, at room temperature, of the surfaces of the prostheses with dilute nitric acid. Then, in a high temperature thermostated reactor, 70-80 ^Q C, and also in an acid medium, the metal surface is treated with dilute phosphoric acid and hydrogen peroxide for about three hours, in order to obtain a phosphating thereof. After the phosphating process, the surfaces are washed with distilled water. The next step is to submerge the surfaces of the prostheses to be coated, in a circulating and cooled solution formed by mixing solutions of potassium phosphate and calcium citrate, with the pH adjusted to alkaline conditions by means of an NH ₃ / NH ₄ buffer solution OH, and cause an elevated temperature, higher than 80SC, on the surface of the prosthesis by local heating. The basicity of the medium and the high temperature cause the deposition on the surface of the prosthesis, previously phosphated, of the insoluble hydroxyapatite phase in the form of well crystallized prismatic particles, and well adhered to the substrate thanks to the existence of the intermediate phosphating layer between Metal and ceramics

Detailed description of the invention.

The invention consists of a process for producing localized coatings, from aqueous solutions, of insoluble mineral salts on metal surfaces, previously treated with agents that allow incorporating at least one of the components of the insoluble salt on the surfaces. The novelty lies in preventing the precipitation of mineral salts by proceeding to the mixing of constituents dissolved, by complexing at least one of the constituents, usually the cation, and forcing local precipitation on the surfaces of the insoluble salt, by thermal excitation through the surface of the complexes present in the solution. This procedure simulates the formation of insoluble salt scale in solution conduit pipes.

Given its importance in restorative medicine, we have applied the concepts described above to obtain hydroxyapatite coatings, well crystallized and stoichiometric composition, on Ti prostheses. We have used citrate as a complexing agent for calcium.

To perform the localized deposition, we have developed a device that allows heating, by heat transmission through solids, cylindrical prostheses firmly fixed in external holes, of the same diameter, made of a stainless steel block. This block is isolated from the circulating solutions, except through the external holes, by ceramic and Teflon protections, and is heated by a resistor located in a cylindrical hole made inside. The temperature inside the block is regulated by a controller and a thermocouple located in another internal hole. In this way, most of the metal surfaces heated by the resistance and in contact with the circulating cold solutions, correspond to the prostheses, so, when the temperature on these surfaces is higher than 802C, we cause them to directly deposit the hydroxyapatite The phosphating layer created previously allows the creation of chemical bonds between the substrate and the deposited layer.

With this invention we claim a deposition technique from solutions, aqueous or other solvents, based on the creation of metastable solutions of insoluble salts, by complexing some of its constituents, and in the ocal precipitation of salts on heated surfaces that cause salt deposition.

Example of realization.

The coating technique has been used with pure Ti inserts and Ti alloy cylinders previously coated with Ti microspheres.

The realization of a coating of Ti inserts comprises the following steps:

1. Cleaning the titanium parts. 2. Phosphation of titanium parts.

3. Synthesis and deposition of hydroxyapatite.

1. Cleaning the titanium parts

Plates of pure titanium 0.5 mm thick and dimensions 18.5 x 16.5 mm are used. Prior to treatment, they are polished and cleaned using ultrasound. To clean them, they are treated with dilute nitric acid at room temperature for 1 h.

2. Phosphation of titanium parts

Once the plate is cleaned, it is immersed in a stirred bath of the following composition: 6 ml H ₃ P0 ₄ (85%) in a total volume of 600 ml. Bath conditions: T = 80 ° C pH ₀ (initial) = 1.5 time = 3 h. After this time, an oxidant, 11 ml H ₂ 0 ₂ , is added to the bath, maintaining the same temperature and proceeding for an additional hour.

3. Synthesis and deposition of hydroxyapatite The precipitation of hydroxyapatite from basic aqueous solutions takes place directly, that is to say without formation of solid precursor substances, at temperatures above 80SC. Since calcium phosphates are very insoluble materials, they would precipitate immediately when mixing the solutions containing phosphate and calcium. To avoid this, we first complex calcium with citrate or any organic ligand with carboxyl groups, obtaining a soluble complex of Ca-citrate, in the case of using citrate, which, when mixed with phosphate ion containing solutions, for example ammonium phosphates, hinders the immediate precipitation of calcium phosphates. The complexing of calcium allows us to cause an induction time for the precipitation of calcium phosphates, which we use to bring the solution into contact with the hot surfaces of the prosthesis. The high temperature of the surfaces of the prostheses, creates in that place the most favorable conditions to decompose the calcium citrate complex and cause the direct precipitation of the hydroxyapataite, without giving rise to the formation of other metastable calcium phosphates.

Reaction:

6 KH ₂ PO ₄ +10 Ca-Cit + 2 OH ^" > Ca ₁₀ (P0 ₄ ) ₆ (OH) ₂ + 6 K ^* +10 H _n -Cit

where _n indicates an undetermined number of protons bound to the citrate ion.

Preparation of hydroxyapatite generating solutions:

Distilled and deionized water is boiled to extract the

C0 ₂ dissolved. With this water, buffered solutions (NH ₃ / NH ₄ C1 buffer) at pH 11 of CaCL ₂ .2H ₂ 0 / K ₃ C ₆ H ₅ 0 ₇ .H ₂ 0 and KH are prepared under flow of N ₂ and separately ₂ P0 ₄ to obtain a final buffered solution at pH 11, with the following concentrations:

- KH ₂ P0 ₄ = 3.10 ^'4 M / l - K ₃ Cit = 10 ^"3 M / l

- Ca ₂ C1. 2H ₂ 0 = 5. 10 ^"4 M / 1

This solution is placed in a thermostated reactor that maintains it at a temperature of about 102C and from which the solution can be extracted by means of a pump, to circulate it through a closed circuit where the prostheses are located and where there is a column filled with pieces of glass , before the solution is returned to the thermostated reactor.

By way of example, the procedure in a non-restrictive device of the object of the invention is described below: The titanium prostheses are placed on a device that allows only the local heating of its outer surfaces. This device is placed within the circuit of the generating solutions, so that the circulating solutions directly affect the heated surfaces of the prostheses.

We establish a circulation regime of the solutions, and proceed to heat the prostheses in such a way that the temperature on the outer surfaces in contact with the solution is higher than 80SC.

The high surface temperature causes instantaneous precipitation on it of the hydroxyapatite, which is adhered by the formation of physical and chemical bonds with the phosphated intermediate layer. The thickness of the layer formed depends on how long we keep the prosthesis immersed in the circulating solution. Hydroxyapatite deposition takes place throughout the heated surface

Once the coating operation is performed, the prosthesis is removed from the circuit, washed repeatedly with deionized water and dried for 10 hours in an oven heated to 120SC.

Characterization of the coated samples:

-X-ray diffraction

The X-ray diffraction diagrams of the coated titanium inserts show the most important lines of the hydroxyapatite next to those of the Ti.

-Observation with electron microscope

The observation under the electron microscope of the plates is performed without prior metallization. It is observed that the surface of Ti is completely covered with prismatic microcrystals that have the theoretical morphology of the hydroxyapatite. The size of these microcrystals is quite homogeneous with a maximum dimension of 1-3 microns and width of 0.1 miera.

-Measurement of the adhesion of the layer

Adhesion measurements have been made between the Ti base and the layer deposited by the tensile method, consisting of gluing two Ti bars with the cyanoacrylic cement over the coated basal surface, and stretching until the rupture occurs. This rupture occurs at the Ti-Hydroxyapatite interface and the applied force / surface ratio gives us an adhesion value of the order of 6.7 MPa.

Claims

1. PROCEDURE FOR SURFACE COATING WITH HYDROXIAPATITE METALLIC IMPLANTS of titanium or titanium alloys, characterized by the following stages: a) functionalization of the surfaces to be coated, which includes cleaning the prostheses, phosphating and washing them. b) immersion of the surfaces in a circulating solution, cooled to a temperature below 20 ° C, formed by a mixture of solutions of potassium phosphate and calcium citrate, with the pH adjusted between 9 and 11, preferably not greater than 11, in alkaline conditions by means of a buffer solution of NH ₃ / NH ₄ OH. c) local heating of the surface of the prosthesis at a temperature above 80 ° C.

2. Method according to claim 1 characterized in that the immersion of the surfaces is carried out with a mixture of calcium phosphate and any organic ligand with carboxyl groups.

3. Method according to previous claims characterized in that the circulating solution is precipitated on the surface of the implant so that different coating thicknesses are obtained depending on the immersion time.