CN101766841A - Artificial joint having slow-release function of rare earth element cerium and preparation method thereof - Google Patents

Abstract

The invention relates to an artificial joint with slow-release function of rare earth element cerium and a preparation method thereof. The artificial joint is composed of pure titanium or titanium alloy artificial joint matrix and micropores loaded with rare earth element cerium and bone morphogenetic protein (BMP). Sodium titanate bioactive layer composition. The aforementioned bioactive layer of sodium titanate layer with a microporous structure is combined with the surface of the metal substrate, and the microporous structure of sodium titanate formed by the hydrothermal reaction of the surface of the titanium or titanium alloy substrate and the sodium hydroxide solution is stacked alternately. , Cerium and sodium are cation-exchanged and incorporated into the coating, and BMP is compounded in the microporous structure through centrifugal force and capillary action. The preparation method is as follows: first select pure titanium or titanium alloy to process the artificial joint; then use lye hydrothermal synthesis technology to obtain a sodium titanate layer with a microporous structure on the surface of the artificial joint; then impregnate the ion exchange on the microporous titanium The rare earth element cerium was mixed into the sodium titanate layer; finally, the bone morphogenetic protein was loaded in the microporous sodium titanate layer doped with cerium by centrifugal loading technology.

Description

Rare earth element cerium sustained-release functional artificial joint and preparation method thereof

technical field

The present invention relates to an artificial joint with slow-release function of rare earth element cerium and its preparation method, in particular to a microporous sodium titanate bioactive coating obtained by selecting pure titanium or titanium alloy as a substrate and adopting lye hydrothermal synthesis technology The invention relates to an artificial joint loaded with bone morphogenetic protein through solution impregnation ion exchange doped with cerium and using a centrifugal loading technique and a preparation method thereof, belonging to the technical field of artificial joint materials.

Background technique

At present, the number of cases of artificial joint implanted into the human body can reach 1.2 million cases per year, and it is one of the implant materials with the largest demand in orthopedics at home and abroad. The commonly used artificial joints are metal materials. Because they are biologically inert materials, they cannot form a firm physiological bond with human bone tissue. After several years of implantation, they often loosen and sink, resulting in failure of artificial joint replacement. Second surgery is inevitable. Using surface modification technology to prepare biological coatings (films) on the surface of artificial joint metal substrates can reduce the dissolution of harmful metal ions in the human environment, improve their biocompatibility and biological activity, and make the artificial joints and human bone tissue form Strong physical bond.

The rare earth element cerium has good physical and chemical stability, and can be sterilized by high temperature, high pressure and filtration. Cerium has a variety of biological effects: high concentrations of cerium separate it by softening the cell wall, and gradually cause the protoplasm to overflow, thereby achieving the purpose of inhibiting bacterial growth; it may also fix the lipoprotein mixture produced during burns and prevent it from entering In vivo, so as to reduce the inflammatory reaction and prevent the immunosuppressive phenomenon after burns, so that the damage to the tissue will not be further aggravated; it can achieve anti-mutation by promoting the correct DNA repair and blocking the normal DNA damage caused by the mutagen effect.

Bone morphogenetic protein (BMP) is a low-molecular-weight glycoprotein polypeptide widely present in the bone matrix, which can act on the surface receptors of mesenchymal cells and induce the transformation of undifferentiated mesenchymal cells around blood vessels and bone marrow stromal cells into Cartilage and bone cells with biological properties that induce bone formation. Loading bone morphogenetic protein (BMP) on the surface of the artificial joint can significantly improve the ability of the surface of the artificial joint to induce osteogenesis at the initial stage of implantation. However, BMP is easily absorbed and degraded quickly, and a suitable carrier must be provided to improve its release cycle.

The main inorganic substance of human hard tissue is calcium-phosphorus phase, and sodium titanate can be converted into hydrated titanium dioxide in body fluids, so that many Ti-OH groups are formed on the metal surface in situ, thereby inducing the deposition of calcium and phosphorus in body fluids, forming Apatite layers (Ceramics International, 1996, 79(24): 1127-1129). In addition, due to the special structure of sodium titanate crystals, sodium ions have a strong exchange capacity, which can be replaced with a variety of cations, so as to perform ion release and strengthen the functionality of the sodium titanate structural layer. At the same time, the special morphology of the micropores on the surface increases the specific surface area, which greatly enhances the loading capacity of the sodium titanate structure layer.

A common method for preparing biologically active sodium titanate structures is lye hydrothermal synthesis technology. Chinese patent ZL02117866.6 "A process for preparing hydrated sodium titanate and a series of titanate nanotubes" discloses a method for preparing sodium titanate nanostructures based on lye hydrothermal synthesis technology, that is, in a closed container Titanium dioxide powder or metatitanic acid powder is used for hydrothermal reaction with sodium hydroxide solution to finally prepare dispersed sodium titanate salt with tubular structure. However, this preparation method can only prepare dispersed titanate structures, and does not involve the preparation of the surface of the metal substrate. As a biomedical material with great potential, sodium titanate is rarely used in the technical field of artificial joint materials. Therefore, looking for a suitable process to prepare a sodium titanate bioactive coating with a special structure on the surface of the artificial joint metal substrate, and to enhance its functionality and load capacity will be more and more valued by the technical field of artificial joint materials.

Contents of the invention

Technical problem: The purpose of the present invention is to address the above-mentioned shortcomings of artificial joint materials, and propose an artificial joint with a slow-release function of rare earth element cerium, and can significantly improve the ability of the artificial joint surface to induce osteogenesis at the initial stage of implantation and its preparation method.

Technical solution: The artificial joint with rare earth element cerium slow-release function has a layer of sodium titanate bioactive layer with microporous structure prepared by lye hydrothermal synthesis technology on the surface of the metal substrate, and its surface is treated by ion exchange by solution impregnation. Doped with cerium and complexed with bone morphogenetic protein (BMP) using centrifugal loading technology. The sodium titanate bioactive layer with a microporous structure has high bonding strength to the metal substrate. Since the microporous structure of sodium titanate alternately stacks and grows on the surface of the substrate, it has good biological activity and can promote the deposition and growth of the apatite layer; cerium After the elements are incorporated, they are released slowly on the surface of the artificial joint, which has a variety of biological effects, and can produce beneficial effects such as inhibiting the growth of bacteria and reducing inflammatory reactions. At the same time, the microporous structure is also an ideal carrier for BMP. Artificial joints and BMP composites usually use centrifugal loading technology. BMP can penetrate deeply into the microporous sodium titanate coating through the dual effects of centrifugal effect and capillary effect, which greatly increases the carrying capacity of BMP on the surface of artificial joints. After the artificial joint is implanted in the human body, the release cycle of BMP on its surface is prolonged, which is conducive to the full play of BMP-induced osteogenesis.

The present invention is realized through the following technical solutions:

There is a layer of sodium titanate bioactive coating with a microporous structure on the surface of the artificial joint metal substrate with slow-release function of rare earth element cerium. The microporous coating is further doped with cerium and compounded with bone morphogenetic protein (BMP). .

The microporous structure of the sodium titanate bioactive coating is combined with the surface of the metal substrate, and the sodium titanate microporous structure formed by the hydrothermal reaction between the surface of the titanium or titanium alloy substrate and the sodium hydroxide solution is stacked alternately. The mentioned cerium element is cation-exchanged with the sodium ion of sodium titanate through solution impregnation; the mentioned BMP is compounded in the microporous structure coating by centrifugal loading technology.

Its preparation steps are as follows:

1) First choose pure titanium or titanium alloy to process the artificial joint;

2) Grinding and polishing the surface of the artificial joint, and then using lye hydrothermal synthesis technology to obtain a sodium titanate bioactive coating with a microporous structure on the surface;

3) doping the rare earth element cerium in the microporous sodium titanate layer through solution impregnation ion exchange;

4) Finally, the bone morphogenetic protein is loaded in the microporous sodium titanate layer doped with cerium by centrifugal loading technology.

The lye hydrothermal synthesis technology mentioned above uses NaOH aqueous solution with a concentration of 5-15 mol/L, the treatment time is 4-200 hours, and the treatment temperature is 60-180 degrees Celsius.

The above-mentioned solution is impregnated with ion exchange, using a soluble cerium salt solution with a concentration of 0.05-5.0mol L ^-1 , the liquid surface of the soluble cerium salt solution should be submerged over the artificial joint, the immersion time is not less than 24 hours, and then deionized water Wash several times to eliminate remaining soluble ions, and dry the sample at 60-100°C under vacuum for no less than 6 hours; the soluble cerium salt solution uses one or both of cerium nitrate, cerium nitrate ammonium or cerium chloride A soluble cerium salt preparation.

The specific operation of the centrifugal loading technology mentioned is as follows: the artificial joint with the bioactive coating of cerium-doped microporous sodium titanate on the surface is placed in a centrifuge, and the concentration of 0.1-50 mg/L bone morphogenetic protein and 0.1 mol/L phosphate-buffered saline solution, and submerged to more than twice the height, and worked at a centrifugal speed of 2000-80000rpm for 5-30min, during which the working temperature was kept at 4-40°C.

Beneficial effect:

(1) The cerium element has various biological effects. Doping cerium into the microporous sodium titanate bioactive layer on the surface of the artificial joint can produce beneficial effects such as inhibiting the growth of bacteria and reducing inflammatory reactions. The artificial joint material has good biological activity, bactericidal effect and osteogenic effect, and can safely form a firm physiological combination with bone tissue in a short period of time.

(2) The sodium titanate bioactive coating on the surface of the artificial joint has high bonding strength with the metal matrix, and has an ideal microporous structure, which can be used as a "crystal nucleus base" to promote the deposition and growth of the apatite layer. In the sodium titanate structure The high sodium cations are easy to be ion-exchanged and incorporated into various elements, and the micropores are also ideal carriers for BMP, which is conducive to the full play of BMP-induced osteogenesis.

Description of drawings

Fig. 1 is the scanning electron microscope (SEM) photo of the sodium titanate surface layer morphology that artificial joint surface of the present invention has microporous structure;

Fig. 2 is the X-ray diffraction (XRD) spectrum of the sodium titanate surface layer with microporous structure on the artificial joint surface of the present invention;

Detailed ways

Example 1

(1) First choose pure titanium to process the artificial joint;

(2) Hydrothermal treatment of the artificial joint surface: the artificial joint is ground and polished, then ultrasonically cleaned with acetone, 70% alcohol, and distilled water, and the hydrothermal reaction is carried out with a sodium hydroxide aqueous solution with a concentration of 10mol/L, and the working temperature is 120 degrees Celsius. The time is 6 hours, and a sodium titanate bioactive coating with a microporous structure is obtained on the surface of the artificial joint.

(3) Cerium doping treatment by dipping method: the artificial joint covered with microporous sodium titanate bioactive layer prepared above is immersed in soluble cerium salt (NH ₄ ) ₂ Ce(NO ₃ ) ₆ aqueous solution and doped with rare earth through ion exchange The element cerium, (NH ₄ ) ₂ Ce(NO ₃ ) ₆ aqueous solution concentration is 0.05mol·L ^-1 , the liquid surface of the solution should submerge the artificial joint, the immersion time is not less than 24 hours, and then washed several times with deionized water, In order to eliminate the remaining soluble ions (NH ₄ ⁺ , Ce ⁴⁺ , NO ₃ ^- ), the sample was dried under vacuum at 60-100°C for no less than 6 hours to obtain the biological activity of cerium-doped sodium titanate on the artificial joint surface layer;

(4) Centrifugal load treatment of BMP: fix the artificial joint with cerium-doped sodium titanate bioactive coating with microporous structure on the surface in the centrifuge cylinder, pour 0.1-50mg/L bone morphogenetic protein and 0.1mol/ A mixed solution composed of 1 L of phosphate buffered saline solution, and submerged to more than twice the height, worked at a centrifugal speed of 6000rpm for 5-30min, and kept at a working temperature of 4-40°C, then took it out;

(5) After taking out the above-mentioned artificial joint and rinsing it with alcohol, vacuum-dry it, store it aseptically after disinfection, and keep it for later use, the artificial joint with slow-release function of rare earth element cerium of the present invention can be obtained.

Example 2

(1) First choose Ti6Al4V alloy to process the artificial joint;

(2) Hydrothermal treatment of the artificial joint surface: the artificial joint is ground and polished, then ultrasonically cleaned with acetone, 70% alcohol, and distilled water, and the hydrothermal reaction is carried out with a sodium hydroxide aqueous solution with a concentration of 10mol/L, and the working temperature is 120 degrees Celsius. The time is 6 hours, and a sodium titanate bioactive coating with a microporous structure is obtained on the surface of the artificial joint.

(3) Cerium doping treatment by dipping method: the artificial joint prepared above covered with the microporous sodium titanate bioactive layer was immersed in the soluble cerium salt Ce(NO ₃ ) ₄ aqueous solution, and the rare earth element cerium, Ce( The concentration of the NO ₃ ) ₄ aqueous solution is 0.05mol·L ^-1 , the liquid surface of the solution should be submerged over the artificial joint, the soaking time should not be less than 24 hours, and then washed several times with deionized water to eliminate the remaining soluble ions (Ce ⁴⁺ , NO ₃ ^- ), the sample was dried under vacuum at 60-100°C for no less than 6 hours to obtain a bioactive layer of cerium-doped sodium titanate on the artificial joint surface;

(4) Centrifugal load treatment of BMP: fix the artificial joint with cerium-doped sodium titanate bioactive coating with microporous structure on the surface in the centrifuge cylinder, pour 0.1-50mg/L bone morphogenetic protein and 0.1mol/ A mixed solution composed of 1 L of phosphate buffered saline solution, and submerged to more than twice the height, worked at a centrifugal speed of 8000rpm for 5-30min, and kept the working temperature at 4-40°C, and took it out;

(5) After taking out the above-mentioned artificial joint and rinsing it with alcohol, vacuum-dry it, store it aseptically after disinfection, and keep it for later use, the artificial joint with slow-release function of rare earth element cerium of the present invention can be obtained.

Example 3

(1) First choose pure titanium to process the artificial joint;

(2) Hydrothermal treatment of the artificial joint surface: the artificial joint is ground and polished, then ultrasonically cleaned with acetone, 70% alcohol, and distilled water, and the hydrothermal reaction is carried out with a sodium hydroxide aqueous solution with a concentration of 10mol/L, and the working temperature is 150 degrees Celsius. After 72 hours, a sodium titanate bioactive coating with a microporous structure was obtained on the surface of the artificial joint, and its SEM photo and XRD spectrum are shown in Figure 1 and Figure 2, respectively.

(3) Cerium doping treatment by dipping method: the artificial joint covered with microporous sodium titanate bioactive layer prepared above is immersed in soluble cerium salt (NH ₄ ) ₂ Ce(NO ₃ ) ₆ aqueous solution and doped with rare earth through ion exchange The element cerium, (NH ₄ ) ₂ Ce(NO ₃ ) ₆ aqueous solution concentration is 0.05mol·L ^-1 , the liquid surface of the solution should submerge the artificial joint, the immersion time is not less than 24 hours, and then washed several times with deionized water, In order to eliminate the remaining soluble ions (NH ₄ ⁺ , Ce ⁴⁺ , NO ₃ ^- ), the sample was dried under vacuum at 60-100°C for no less than 6 hours to obtain the biological activity of cerium-doped sodium titanate on the artificial joint surface layer;

(4) Centrifugal load treatment of BMP: fix the artificial joint with cerium-doped sodium titanate bioactive coating with microporous structure on the surface in the centrifuge cylinder, pour 0.1-50mg/L bone morphogenetic protein and 0.1mol/ A mixed solution composed of 1 L of phosphate buffered saline solution, and submerged to more than twice the height, worked at a centrifugal speed of 6000rpm for 5-30min, and kept at a working temperature of 4-40°C, then took it out;

(5) After taking out the above-mentioned artificial joint and rinsing it with alcohol, vacuum-dry it, store it aseptically after disinfection, and keep it for later use, the artificial joint with slow-release function of rare earth element cerium of the present invention can be obtained.

Example 4

(1) First choose Ti6Al4V alloy to process the artificial joint;

(2) Hydrothermal treatment of the artificial joint surface: the artificial joint is ground and polished, then ultrasonically cleaned with acetone, 70% alcohol, and distilled water, and the hydrothermal reaction is carried out with a sodium hydroxide aqueous solution with a concentration of 10mol/L, and the working temperature is 150 degrees Celsius. The time is 72 hours.

(3) Cerium doping treatment by dipping method: the artificial joint prepared above covered with microporous sodium titanate bioactive layer is immersed in soluble cerium salt CeCl ₄ aqueous solution and doped with rare earth element cerium by ion exchange, the concentration of CeCl ₄ aqueous solution is 0.05 mol·L ^-1 , the liquid level of the solution should cover the artificial joint, the soaking time should not be less than 24 hours, and then wash several times with deionized water to eliminate the remaining soluble ions (Ce ⁴⁺ , Cl ^- ), the sample is vacuum Dry at 60-100°C for no less than 6 hours to obtain a bioactive layer of cerium-doped sodium titanate on the surface of the artificial joint;

(4) Centrifugal load treatment of BMP: fix the artificial joint with cerium-doped sodium titanate bioactive coating with microporous structure on the surface in the centrifuge cylinder, pour 0.1-50mg/L bone morphogenetic protein and 0.1mol/ A mixed solution composed of 1 L of phosphate buffered saline solution, and submerged to more than twice the height, worked at a centrifugal speed of 80,000rpm for 5-30min, and kept at a working temperature of 4-40°C, then took it out;

(5) After taking out the above-mentioned artificial joint and rinsing it with alcohol, vacuum-dry it, store it aseptically after disinfection, and keep it for later use, the artificial joint with slow-release function of rare earth element cerium of the present invention can be obtained.

Apparently, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limiting the implementation of the present invention. For those of ordinary skill in the art, other different forms of changes or changes can also be made on the basis of the above description, and it is not necessary and impossible to exhaustively enumerate all the implementation modes here, and these are derived from the spirit of the present invention. Obvious changes or modifications are still within the protection scope of the present invention.

Claims (4)

1. A rare earth element cerium slow-release functional artificial joint and a preparation method thereof, characterized in that: the rare earth element cerium slow-release functional artificial joint is made of pure titanium or titanium alloy artificial joint matrix and loaded with rare earth The sodium titanate bioactive layer with a microporous structure is composed of element cerium and bone morphogenetic protein (BMP), and the sodium titanate bioactive layer with a microporous structure is combined with the surface of a metal substrate, and is made of titanium or titanium alloy The sodium titanate microporous structure formed by the hydrothermal reaction between the surface of the substrate and the sodium hydroxide solution is stacked alternately, and then the rare earth element cerium is doped in the microporous sodium titanate layer through solution impregnation and ion exchange, and finally the centrifugal loading technology is used in the Bone morphogenetic protein (BMP) was loaded in the microporous sodium titanate layer doped with cerium. The preparation method of the artificial joint with the slow-release function of the rare earth element cerium is carried out as follows: 1) First choose pure titanium or titanium alloy to process the artificial joint; 2) Grinding and polishing the surface of the artificial joint, and then using lye hydrothermal synthesis technology to obtain a sodium titanate bioactive coating with a microporous structure on the surface; 3) doping the rare earth element cerium in the microporous sodium titanate layer through solution impregnation ion exchange; 4) Finally, the bone morphogenetic protein is loaded in the microporous sodium titanate layer doped with cerium by centrifugal loading technology. 2. the preparation method of the artificial joint of rare earth element cerium sustained-release functionality according to claim 1, is characterized in that described and lye hydrothermal synthesis technology, adopts the NaOH aqueous solution that concentration is 5～15mol/L, processes The time is 4 to 200 hours, and the treatment temperature is 60 to 180 degrees Celsius. 3. the preparation method of the artificial joint of rare earth element cerium sustained-release functionality according to claim 1, is characterized in that described and solution impregnation ion exchange, adopting concentration is 0.05-5.0 mol L-1 soluble cerium salt solution , the surface of the soluble cerium salt solution should submerge the artificial joint, the soaking time is not less than 24 hours, and then washed several times with deionized water to eliminate the remaining soluble ions, and the sample is dried under vacuum at 60-100°C for not less than 6 hours; the soluble cerium salt solution is prepared by using one or two soluble cerium salts in cerium nitrate, ammonium cerium nitrate or cerium chloride. 4. The preparation method of the artificial joint of rare earth element cerium sustained-release functionality according to claim 1, characterized in that the centrifugal loading technology mentioned above, the specific operation is: the surface has the biological activity of cerium-doped microporous sodium titanate The coated artificial joint is placed in a centrifuge, poured into a mixed solution consisting of 0.1-50 mg/L bone morphogenetic protein and 0.1 mol/L phosphate buffered saline solution, and submerged to more than twice the height. Work at a centrifugal speed of ~80000rpm for 5-30 minutes, during which the working temperature is kept at 4-40°C.

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