CN100496622C - Strontium containing hydroxyapatite biologically active film and preparation method thereof - Google Patents

Abstract

The invention relates to a method for preparing a bioactive film layer on the surface of a medical metal, in particular to a titanium-based porous nanometer strontium-containing hydroxyapatite bioactive film layer and a preparation method thereof. The method uses micro-arc oxidation technology to directly form a film layer on the surface of titanium and titanium alloys in situ, including providing an electrolyte solution containing phosphate ions, calcium ions, and strontium ions; and using titanium or titanium in this specific electrolyte. Titanium alloy is used as anode, stainless steel or titanium is used as cathode, micro-arc oxidation of titanium or titanium alloy is carried out by using DC power supply or DC pulse power supply; the oxidation deposition time is 3-60min; the temperature of electrolyte during electrolysis is not higher than 50°C. The strontium-containing porous hydroxyapatite membrane layer prepared by the invention has no interface with the matrix, has a modulus of elasticity close to that of bone, has good biological activity, and can be used as a substitute for parts that bear heavy loads such as femurs, hip joints, and tooth roots. Material. The preparation process is simple, the operation is convenient and the content ratio of strontium/calcium is controllable in the range of 0.5-80%, and it is easy to popularize and apply.

Description

Strontium-containing hydroxyapatite bioactive film layer and preparation method thereof

technical field

The invention relates to a method for preparing a biologically active film layer on the surface of a medical metal material, in particular to a titanium-based porous nanometer-containing strontium-containing hydroxyapatite bioactive film layer and a preparation method thereof.

Background technique

In recent years, the development and application of various biomedical materials have developed rapidly, among which metal materials were the first to be used. Metal biomaterials generally have high strength and toughness, and are suitable for hard tissue repair and fixation. Commonly used metallic biomaterials include cobalt injection. However, due to the surface hardness of titanium and titanium alloys, low-base alloys, tantalum, titanium and titanium alloys, etc., among them, titanium and its alloys have excellent corrosion resistance, high specific strength, good biocompatibility and are suitable for implantation. It has attracted wide attention due to its characteristics, but its application is limited due to its poor wear resistance. In addition, titanium and its alloys are biologically inert materials, which can only produce mechanical bonding with growing bone but not chemical bonding. Therefore, it is necessary to bioactivate titanium and its alloys. The preparation of bioactive ceramic films on the surface of metal substrates by surface modification technology has become a research hotspot and development trend in recent years.

Chinese patent ZL97119791.1 A method for preparing an artificial joint with a bioactive gradient coating discloses a method for preparing a hydroxyapatite (Hydroxyapatite, HA) coating on a metal surface. Since HA is the main mineral component of bone and has good biocompatibility, it is not only safe and non-toxic to implant into the human body, but also can conduct bone growth, so that new bone can move along the surface and internal pores from the joint between the HA implant and the original bone. Climbing and growing, so the invention makes the material not only have the bonding strength of metal materials, but also has good biological activity, and induces new bone to directly form a firm bone bond with the surface of the implant material. However, the patent adopts the method of plasma spraying, and the prepared film layer is deficient in surface porosity control, which affects the speed of postoperative bone tissue growth. Moreover, the single hydroxyapatite component in the surface layer of the membrane affects the postoperative healing speed.

Studies have found that strontium is a trace element that exists in the human body, and its content in bone accounts for about 0.01% of its weight, while more than 99% of strontium (Sr) and calcium (Ca) contained in the human body are accumulated in the bone middle. Both Sr and Ca are alkaline earth metals and have many similar properties. Sr ²⁺ in the form of ions shares the same physiological route as Ca ²⁺ , and is finally deposited in the mineralized structure of bone. Studies have shown that strontium has special pharmacological effects in the following aspects: First, in terms of mineralization and reconstruction of bone diseased areas, low doses of strontium can help increase bone mass and volume, and it has not been found that it has any effect on mineralization morphology. Secondly, in terms of bone metabolism, under the condition of continuous external supply, the content of strontium in bone varies with the anatomical position in the body, and it is found that strontium can interact with the surface of apatite crystals in bone Third, in terms of bone conduction, after comparing glass ionomer cements with different strontium content, it was found that LG125, the group with the highest strontium content, had the best bone conduction; fourth, in the treatment of bone Strontium also has a significant effect on porosity. The strontium-containing hydroxyapatite obtained by replacing part of the calcium in the apatite with Sr not only has better histocompatibility, osteoconductivity, and even a certain degree of osteoinductive ability than pure hydroxyapatite, but also changes Improved its dissolution kinetics and improved biodegradability. Therefore, if strontium can be mixed into the hydroxyapatite film layer to obtain a strontium-containing hydroxyapatite film layer, many advantages of the original film layer can be maintained, and strontium or strontium-containing apatite can be fully utilized. The above-mentioned good pharmacological properties and biological properties. However, since the diameter of strontium ions is larger than that of calcium ions, it is difficult to introduce strontium atoms into the apatite film by conventional techniques, and the ratio of strontium/calcium elements in the film is not easy to control. The preparation of strontium-containing porous hydroxyapatite film on the surface of the alloy is still blank.

At present, the main methods of preparing hydroxyapatite film on the metal surface are plasma spraying method, ion beam sputtering method, sol-gel method and micro-arc oxidation composite process method (micro-arc oxidation-hydrothermal treatment, micro-arc oxidation-electrophoresis deposition composite process, micro-arc oxidation-mineralization deposition composite process, etc.). Among them, the plasma spraying method uses hydroxyapatite powder, which is melted by high-temperature plasma to make the particles adhere to the substrate. Since the particles are easily volatilized after high-temperature heating, the composition of the formed film is difficult to control. The ion beam sputtering method is to prepare hydroxyapatite by ion beam sputtering, and the overall content of the film is difficult to control. Although the sol-gel method is easy to control the chemical composition and microstructure of the film, it requires post-treatment of high temperature annealing, which affects the properties of the matrix material. The micro-arc oxidation composite process generally has unfavorable factors such as increasing the complexity of the process and weakening the adhesion of the film layer; for example, micro-arc oxidation combined with hydrothermal treatment can transform and precipitate HA, but the bonding strength of the film layer is reduced by 40%; electrophoretic deposition uses electric field The effect makes HA deposit on the metal surface, but due to the loose combination, subsequent sintering treatment is required, which not only reduces the adhesion of the film layer, but also weakens the biological activity of the material during the sintering process. If the above-mentioned methods can be used to complement each other, it is expected to better solve the problems of bonding strength, stability and biological activity of the film layer.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies of the prior art, and to provide a strontium-containing hydroxyapatite biologically active material with high bonding strength, good stability, good biological activity and no toxic side effects on the surface of medical titanium-based metal materials. Film layer and its preparation method.

The above object of the present invention is achieved by the following measures.

A method for preparing a strontium-containing hydroxyapatite bioactive film layer, characterized in that: micro-arc oxidation technology is used to directly form a strontium-containing porous hydroxyapatite bioactive film layer on the surface of titanium and titanium alloys in situ, including the following Steps and their process conditions:

a, provide a kind of electrolytic solution that contains phosphate ion and calcium ion, strontium ion;

b. Using titanium or titanium alloy as anode and stainless steel or titanium as cathode in the above-mentioned specific electrolyte, micro-arc oxidation of titanium or titanium alloy is carried out by using DC power supply or DC pulse power supply;

c. Oxidation deposition time is 3 to 60 minutes;

d. The temperature of the electrolyte during electrolysis is not higher than 50°C.

The optimal content range of phosphate ions in the electrolyte is 0.01-0.2 mol/L, the optimal content range of calcium ions is 0.01-0.5 mol/L, and the optimal content range of strontium ions is 0.01-0.5 mol/L ;

The electrolyte that provides phosphate ion is preferably selected from at least one of sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium β-glycerophosphate or sodium hexametaphosphate; the electrolyte that provides calcium ion is preferably selected from calcium acetate, calcium nitrate, oxalic acid At least one of calcium or calcium chloride; the electrolyte providing strontium ions is preferably at least one of strontium acetate, strontium nitrate, strontium oxalate or strontium chloride.

When a DC power supply is used, the voltage is 200-500V; when a DC pulse power supply is used, the voltage is 200-700V, the frequency is 50-5000Hz, and the duty cycle is 5-60%.

The biologically active membrane layer prepared by the above method has no interface with the substrate and is in the form of a porous nanocrystalline structure. The membrane layer is mainly composed of hydroxyapatite (HA) and strontium-containing hydroxyapatite (Sr-HA) phases, wherein The chemical expression of strontium-containing hydroxyapatite is Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ , where 0<X≤10, by adjusting the ratio of phosphate ion, calcium ion and strontium ion in the electrolyte The concentration and process conditions are controlled to make the strontium/calcium content ratio in the film layer controllable in the range of 0.5-80%. That is, when the concentration of strontium/calcium ions in the electrolyte is increased, the ratio of strontium/calcium elements in the film layer increases correspondingly.

Compared with the prior art, the present invention has the following outstanding advantages:

1. The porous hydroxyapatite film layer containing strontium elements with special pharmacological effects prepared by the present invention has no interface with the matrix, has a modulus of elasticity close to that of bone, has high bonding strength, stable chemical properties, and has good biological activity and certain pharmacological effects. As the film layer of titanium-based medical implants, it not only has no toxic and side effects, but also firmly combines with the original bone. The bone substitute material and bone tissue are bone-bonded, forming a continuous and gradient interface bond between the implant and the bone. ; Solve the problems of weak binding force, low surface activity and poor biocompatibility of the existing biofilm layer, so that the material can be effectively used as a substitute material for femurs, hip joints and tooth roots that bear heavy loads.

2. Because the present invention directly generates strontium-containing hydroxyapatite bioactive film layers on the surface of titanium metal in situ, by adjusting the concentrations of phosphate ions, calcium ions, and strontium ions in the electrolyte, the strontium/calcium ions in the film layer The ratio of elements is controllable in the range of 0.5-80%.

3. The preparation process of the present invention is simple and fast, easy to operate and easy to popularize and apply.

Detailed ways

Example 1

Use distilled water to prepare a solution containing 0.01 mol/L of sodium hexametaphosphate, 0.01 mol/L of sodium β-glycerophosphate, 0.45 mol/L of calcium acetate, and 0.01 mol/L of strontium chloride. With titanium as the anode and stainless steel or titanium as the cathode, DC power is used for micro-arc oxidation. The voltage is 300-500V; keep the electrolyte temperature not higher than 50°C. The micro-arc oxidation is 5min, and a porous layer with a thickness of about 20 μm is formed on the titanium surface; X-ray diffraction analysis shows that the film layer is mainly composed of hydroxyapatite and strontium-containing hydroxyapatite (the chemical formula of strontium-containing hydroxyapatite is Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ , where 0<X≤3), EDS shows that the proportion of strontium/calcium in the film layer is 0.6%, and the bonding strength of the film layer is 43MPa, which has good biological active.

Example 2

Use distilled water to prepare a solution containing 0.15 mol/L of sodium β-glycerophosphate, 0.2 mol/L of calcium chloride, and 0.05 mol/L of strontium acetate. Use titanium alloy sheet as anode, stainless steel or titanium as cathode, and use DC power supply for micro-arc oxidation. The voltage is 200-400V; keep the electrolyte temperature not higher than 50°C. The micro-arc oxidation time was 30 min, and a porous layer with a thickness of about 33 μm was formed on the titanium surface; X-ray diffraction analysis showed that the film layer was mainly composed of hydroxyapatite and strontium-containing hydroxyapatite Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ (where X is between 4 and 6), EDS shows that the ratio of strontium/calcium elements in the film layer is 9.6%, the bonding strength is 37MPa, and has good biological activity.

Example 3

Use distilled water to prepare a solution containing 0.02 mol/L of sodium dihydrogen phosphate, 0.2 mol/L of calcium nitrate, 0.05 mol/L of strontium acetate, and 0.05 mol/L of strontium oxalate. The titanium alloy sheet is used as the anode, and the stainless steel or titanium is used as the cathode, and a DC pulse power supply is used for micro-arc oxidation. The voltage is 250-450V, the frequency is 300Hz, and the duty ratio is 55%; the electrolyte temperature is kept at 30-50°C. The oxidation deposition time is 60 min; a porous layer with a thickness of about 28 μm is formed on the titanium surface; X-ray diffraction analysis shows that the film layer is mainly composed of hydroxyapatite and strontium-containing hydroxyapatite Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ (wherein X is between 4 and 6), EDS shows that the ratio of strontium/calcium element in the film layer is 26.3%, the bonding strength of the film layer is 33MPa, and has good biological activity.

Example 4

Use distilled water to prepare a solution containing 0.01 mol/L of sodium hexametaphosphate, 0.05 mol/L of calcium oxalate, and 0.05 mol/L of strontium nitrate. With titanium as the anode and stainless steel or titanium as the cathode, DC pulse power is used for micro-arc oxidation. The voltage is 450-550V, the frequency is 50Hz, and the duty cycle is 25%; the electrolyte temperature is kept at 30-50°C, and the oxidation deposition time is 20min; a porous layer with a thickness of about 27μm is formed on the titanium surface; X-ray diffraction analysis shows that The film layer is mainly composed of hydroxyapatite and strontium-containing hydroxyapatite Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ (where X is between 6 and 8). EDS shows that strontium in the film layer The calcium/calcium element ratio is 43.7%, the film layer binding strength is 35MPa, and has good biological activity.

Example 5

Use distilled water to prepare a solution containing 0.05 mol/L of sodium hydrogen phosphate, 0.05 mol/L of calcium acetate, and 0.1 mol/L of strontium oxalate. With titanium as the anode and stainless steel or titanium as the cathode, DC pulse power is used for micro-arc oxidation. The voltage is 550-700V, the frequency is 4000Hz, and the duty cycle is 5%; the electrolyte temperature is kept at 30-50°C, and the oxidation deposition time is 3min; a porous layer with a thickness of about 39μm is formed on the titanium surface; X-ray diffraction analysis shows that The film layer is mainly composed of hydroxyapatite and strontium-containing hydroxyapatite Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ (where X is between 6 and 8). EDS shows that strontium in the film layer The calcium/calcium element ratio is 68.6%, the bonding strength of the film layer is 26MPa, and has good biological activity.

Example 6

Use distilled water to prepare a solution containing 0.2 mol/L sodium β-glycerophosphate, 0.1 mol/L calcium acetate, 0.1 mol/L calcium nitrate, and 0.5 mol/L strontium oxalate. Titanium alloy is used as anode, stainless steel or titanium is used as cathode, and DC pulse power is used for micro-arc oxidation. The voltage is 350-450V, the frequency is 500Hz, and the duty cycle is 30%; the electrolyte temperature is kept at 30-50°C, and the oxidation deposition time is 15min; a porous layer with a thickness of about 32μm is formed on the titanium surface; X-ray diffraction analysis shows that The film layer is mainly composed of hydroxyapatite and strontium-containing hydroxyapatite Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ (where X is between 7 and 10). EDS shows that strontium in the film layer The calcium/calcium element ratio is 79.4%, the bonding strength of the film layer is 21MPa, and has good biological activity.

Claims (3)

1. A method for preparing a strontium-containing hydroxyapatite bioactive film layer, characterized in that: micro-arc oxidation technology is used to directly generate a strontium-containing porous hydroxyapatite bioactive film layer on the surface of titanium and titanium alloys in situ, Including the following steps and process conditions thereof: a, provide a kind of electrolytic solution that contains phosphate ion and calcium ion, strontium ion; b. Using titanium or titanium alloy as anode and stainless steel or titanium as cathode in the above electrolytic solution, micro-arc oxidation of titanium or titanium alloy is carried out by using DC power supply or DC pulse power supply; c. Oxidation deposition time is 3 to 60 minutes; d. The temperature of the electrolyte solution during the electrolysis process is not higher than 50°C; The content of phosphate ions in the electrolyte solution ranges from 0.01 to 0.2 mol/L, the content of calcium ions ranges from 0.01 to 0.5 mol/L, and the content of strontium ions ranges from 0.01 to 0.5 mol/L; The DC power supply voltage is 200-500V; the DC pulse current voltage is 200-700V, the frequency is 50-5000Hz, and the duty cycle is 5-60%. 2. A method for preparing a strontium-containing hydroxyapatite bioactive membrane according to claim 1, wherein the electrolyte providing phosphate ions in the electrolyte solution is selected from sodium phosphate, sodium hydrogen phosphate, phosphoric acid At least one of sodium dihydrogen, sodium β-glycerophosphate or sodium hexametaphosphate; the electrolyte providing calcium ions is selected from at least one of calcium acetate, calcium nitrate, calcium oxalate or calcium chloride; the electrolyte providing strontium ions At least one selected from strontium acetate, strontium nitrate, strontium oxalate or strontium chloride. 3. A strontium-containing hydroxyapatite bioactive film prepared by the preparation method according to claim 1, characterized in that: there is no interface between the bioactive film and the substrate, and it is in the form of a porous nanocrystalline structure. It is mainly composed of hydroxyapatite and strontium-containing hydroxyapatite, and the chemical expression of strontium-containing hydroxyapatite is Ca _10-X Sr _X (PO ₄ ) ₆ (OH) ₂ , where 0<X <10, by adjusting the concentrations of phosphate ions, calcium ions, and strontium ions in the electrolyte solution and controlling the process conditions, the strontium/calcium content ratio in the film layer can be controlled within the range of 0.5 to 80%, that is, when the strontium/calcium in the electrolyte solution As the concentration of calcium ions increases, the ratio of strontium/calcium elements in the film layer increases accordingly.