One-step preparation of multi-element doped hydroxyapatite implant coating

Abstract

The present invention discloses a one-step method for preparing a multi-element doped hydroxyapatite implant coating, which comprises the following steps: Step (1), placing a phosphorus source in deionized water, stirring until the solution is clear and transparent, and then standing for hydrolysis to obtain solution A; Step (2), dissolving a calcium source in deionized water and stirring until dissolved to obtain solution B; Step (3), adding nitrates or acetates of elements to be doped into solution B, stirring and mixing until dissolved to obtain solution C; Step (4), under the condition of stirring at room temperature, dropping solution C into solution A. After the dropping of solution C is completed, continue to stir and mix for aging. After the aging is completed, a spraying solution is obtained; Step (5), spraying the spraying solution onto a pretreated substrate by solution plasma spraying to prepare a multi-element doped hydroxyapatite implant coating. The present invention can solve problems such as low purity and low crystallinity of the doped hydroxyapatite coating.

Description

Technical Field

[0001] The present invention relates to the technical field of hydroxyapatite doping. Specifically, it is a one-step method for preparing a multi-element doped hydroxyapatite implant coating. Background Art

[0002] Hydroxyapatite (Ca 10 (PO4)6(OH)2, HA) shows good bioactivity because of its chemical composition and structure similar to those of calcium phosphate salts in biological bone tissue, can form chemical bonds with human bone tissue, and induce the differentiation of bone precursor cells to form new bone.

[0003] The preparation of hydroxyapatite coatings on the surface of medical metal materials by atmospheric plasma spraying technology has been applied in the field of hard tissue repair such as artificial hip joints and dental implants. The preparation of coatings by atmospheric plasma spraying technology usually requires three steps: ① synthesizing hydroxyapatite powder (or doped hydroxyapatite powder); ② spray granulation; ③ plasma spraying process. The quality of the powder preparation and spray granulation in the early stage of this process will directly affect the performance of the final hydroxyapatite coating. Therefore, a lot of energy is often required for powder preparation and granulation, which results in the disadvantages of low production efficiency and high production cost in the preparation of hydroxyapatite coatings by this process.

[0004] As a crystal with a close-packed hexagonal structure, the structural characteristics of hydroxyapatite enable the Ca 2+ , PO4 3- and OH - groups in it to be doped or replaced by other elements. The doping and substitution of hydroxyapatite are effective means to optimize its performance. The introduction of different elemental ions can endow HA with new physical and chemical properties and achieve the purpose of improving its bioactivity. At present, there have been literature reports on doping modification of HA, such as single doping or double doping of Ag + , Zn 2+ , Cu 2+ , Mg 2+ , La 3+ , F - , Sm 3+ , Sr 2+ , Mn 3+ and CO3 2- . However, there are still problems such as unsatisfactory purity and crystallinity of the prepared doped hydroxyapatite coatings in the existing doping modification methods. Summary of the Invention

[0005] Therefore, the technical problem to be solved by the present invention is to provide a one-step method for preparing a multi-element doped hydroxyapatite implant coating to solve the problems such as low purity and low crystallinity of the doped hydroxyapatite coating.

[0006] To solve the above technical problems, the present invention provides the following technical solutions:

[0007] A one-step method for preparing a multi-element doped hydroxyapatite implant coating, comprising the following steps:

[0008] Step (1): Place the phosphorus source in deionized water, stir until the solution is clear and transparent, then let it stand for hydrolysis to obtain solution A;

[0009] Step (2): Dissolve the calcium source in deionized water and stir until dissolved to obtain solution B;

[0010] Step (3): Add the nitrate or acetate of the element to be doped to solution B, stir and mix until dissolved to obtain solution C;

[0011] Step (4): Under the condition of stirring at room temperature, drop solution C into solution A. After the addition of solution C is completed, continue to stir and mix for aging. After the aging is completed, a spraying solution is obtained;

[0012] Step (5): Spray the spraying solution onto the pretreated substrate by solution plasma spraying to prepare a multi-element doped hydroxyapatite implant coating.

[0013] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (1), the phosphorus source is one or a mixture of two or more of triethyl phosphite, triethyl phosphate, trimethyl phosphite or tributyl phosphite; triethyl phosphite has better preparation effect due to its higher hydration activity and relatively shorter hydrolysis time.

[0014] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (1), the phosphorus source is a mixture of triethyl phosphite and tributyl phosphite mixed in a molar ratio of 4:1; theoretically, trimethyl phosphite has the fastest hydrolysis rate, but in actual experiments, it is found that when the phosphorus source is a mixture of triethyl phosphite and tributyl phosphite mixed in a molar ratio of 4:1 as the phosphorus source for preparing a multi-element doped hydroxyapatite implant coating, the crystallinity and purity of the prepared coating are more ideal, and the improvement of the bioactivity of the doped elements in the coating on the hydroxyapatite implant coating is also more significant.

[0015] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (1), the standing hydrolysis time is 1 to 7 days, which can make the hydrolysis of the phosphorus source more complete; the concentration of phosphorus element in solution A is 4 to 6 mol / L. If the concentration of phosphorus element in solution A is too high, the acidity of the prepared spraying solution is too strong, which will cause serious corrosion to the equipment during the spraying process. However, if the concentration of phosphorus element in solution A is lower than 4 mol / L, it will affect the spraying efficiency and the crystallinity of the generated coating.

[0016] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (2), the calcium source is calcium nitrate and / or calcium acetate; the concentration of calcium ions in solution C is 0.8 - 1 mol / L. The concentration of the hydroxyapatite sol in the spraying solution prepared using solution C with this calcium concentration is appropriate, and a multi-element doped hydroxyapatite implant coating with high purity and good crystallinity can be formed under the spraying conditions of the present invention.

[0017] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (3), the elements to be doped are any one or a mixture of two or more of zinc, strontium, magnesium, iron, and cerium; in solution C, the ratio of the total amount of the elements to be doped to the amount of calcium ions is 1:4 - 20. At this doping ratio, the purpose of improving the bioactivity of the hydroxyapatite implant coating can be achieved, and the compatibility of the coating with human bone tissue will not be affected.

[0018] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (4), solution C is completely added dropwise to solution A within 10 - 60 minutes, so that phosphorus, calcium, and the elements to be doped can basically all participate in the reaction to form hydroxyapatite; the aging time for continuous stirring and mixing is 1 - 3 days. This aging condition can, on the one hand, ensure complete reaction, and on the other hand, enable the crystal grains to grow to an appropriate size, so that the obtained coating has good structural compactness and will not be too loose; the dropping amount of solution C is such that the ratio of the total amount of the elements to be doped and calcium elements to the amount of phosphorus elements in the spraying solution is (10 - 10.5):6.

[0019] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (5), the substrate is pure titanium, a titanium alloy, stainless steel, or a cobalt-chromium-molybdenum alloy; the pretreatment method of the substrate is: after cleaning and drying the substrate, it is sandblasted with corundum.

[0020] In the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (5), the roughness of the substrate after sandblasting is 3.5 - 4.5 μm, which can ensure an ideal bonding strength of the coating on the substrate and will not affect the surface structure of the coating.

[0021] For the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (5), the conditions of the solution plasma spraying method are as follows: spraying power is 20 - 100 kW; spraying distance is 30 - 100 mm; liquid feeding rate is 20 - 100 mL / min; atomization pressure is 0.8 - 2.0 bar; substrate preheating temperature is 150 - 400 °C, and the gun moving speed is 400 - 700 mm / s. Spraying the spraying solution prepared by the method of the present invention under these spraying conditions not only has a high spraying efficiency, but also the generated coating has an ideal chemical composition and microstructure (the generated doped hydroxyapatite coating has high purity and good crystallinity), and finally a multi-element doped hydroxyapatite implant coating with good physical and chemical properties and biological properties is obtained.

[0022] For the above one-step method for preparing a multi-element doped hydroxyapatite implant coating, in step (1), the stirring time is 4 - 10 h; in step (2), the stirring time is 1 - 2 h; in step (3), the stirring time is 1 - 2 h.

[0023] The technical solution of the present invention has achieved the following beneficial technical effects:

[0024] 1. The multi-element doped hydroxyapatite coating can be prepared on the surface of the metal substrate by only one step using the solution plasma spraying technology proposed by the present invention, avoiding the previous powder making and spray granulation processes, contributing to the saving of production costs and the improvement of production efficiency, and the prepared coating shows good biocompatibility.

[0025] 2. By selecting appropriate phosphorus sources and calcium sources, preparing a phosphorus-containing solution A and a calcium-containing solution B with reasonable concentrations, and adding a specific amount of elements to be doped in the form of nitrates or acetates to the calcium-containing solution B to prepare a solution C, and by controlling the dropping rate of the solution C into the solution A and the aging time, phosphorus, calcium, and elements to be doped in the spraying solution exist in the form of a hydroxyapatite sol with appropriate concentrations; spraying the spraying solution using the spraying process of the present invention can generate a multi-element doped hydroxyapatite implant coating with high purity and good crystallinity, and the elements doped in the coating can significantly improve the bioactivity of the hydroxyapatite implant coating without affecting the biocompatibility of the coating. Brief Description of the Drawings

[0026] Figure 1 SEM pictures and EDS energy spectrum diagrams of the coating prepared in Example 1 of the present invention;

[0027] Figure 2 XRD pattern of the coating prepared in Example 1 of the present invention;

[0028] Figure 3 SEM pictures and EDS energy spectrum diagrams of the coating prepared in Example 2 of the present invention;

[0029] Figure 4 XRD pattern of the coating prepared in Example 2 of the present invention;

[0030] Figure 5 SEM image and EDS spectrum of the coating prepared in Example 3 of the present invention;

[0031] Figure 6 XRD pattern of the coating prepared in Example 3 of the present invention;

[0032] Figure 7 SEM image and EDS spectrum of the coating prepared in Comparative Example 1 of the present invention;

[0033] Figure 8 XRD pattern of the coating prepared in Comparative Example 1 of the present invention;

[0034] Figure 9 Comparison chart of the activities of MC3T3-E1 osteoblasts tested by the MTT method for the coatings prepared in Example 3 and Comparative Example 1 of the present invention. Detailed implementation manners

[0035] Example 1

[0036] In this example, a magnesium-doped hydroxyapatite implant coating was prepared by a one-step method, including the following steps:

[0037] Step (1): Place 35.56 g of triethyl phosphite in 43 mL of deionized water, stir for 4 h until the solution is clear and transparent, and then stand for hydrolysis for 2 days to obtain solution A;

[0038] Step (2): Dissolve 113.88 g of calcium nitrate tetrahydrate in 500 mL of deionized water and stir magnetically for 2 h until dissolved to obtain solution B;

[0039] Step (3): Add 5.42 g of magnesium acetate tetrahydrate to solution B and stir to mix and dissolve to obtain solution C;

[0040] Step (4): Under stirring at room temperature, slowly dropwise add solution C to solution A, and finish dropping in 15 min; after solution C is dropped, make up the volume to 1 L, continue to stir and mix until there is no precipitate, and age for 1 day to obtain the spraying solution;

[0041] Step (5): Spray the spraying solution onto the pretreated substrate by solution plasma spraying to prepare a multi-element doped hydroxyapatite implant coating; Use the cleaned and dried Ti6Al4V alloy as the substrate, with a size of 10*10*2 mm. Perform sandblasting treatment with corundum. After sandblasting, the roughness of the substrate is about 3.8 μm. The specific process parameters during spraying are: spraying power 38.2 kW; spraying distance 50 mm; liquid feeding rate 40 mL / min; atomization pressure 1.2 bar; substrate preheating temperature 250 °C, and the gun moving speed is 500 mm / s.

[0042] The EDS energy spectrum and XRD pattern of the coating prepared in this example are shown in Figure 1 and Figure 2 ; It can be seen from Figure 1 and Figure 2 that the coating prepared in this example is successfully doped with magnesium element, and the magnesium-doped hydroxyapatite coating has a high purity (86.8%) and crystallinity (81.4%).

[0043] Example 2

[0044] In this example, a zinc-magnesium co-doped hydroxyapatite implant coating is prepared by a one-step method, which includes the following steps:

[0045] Step (1): Place 28.46 g of triethyl phosphite and 12.78 g of tributyl phosphite in 43 mL of deionized water and stir for 4 h until the solution is clear and transparent, then let it stand for hydrolysis for 2 days to obtain solution A;

[0046] Step (2): Dissolve 107.89 g of calcium nitrate tetrahydrate in 500 mL of deionized water and stir magnetically for 2 h until dissolved to obtain solution B;

[0047] Step (3): Add 5.42 g of magnesium acetate tetrahydrate and 4.59 g of zinc acetate to solution B and stir to mix and dissolve to obtain solution C;

[0048] Step (4): Under the condition of stirring at room temperature, slowly dropwise add solution C to solution A drop by drop, and finish dropping in 15 min; After solution C is dropped, make up the volume to 1 L, continue to stir and mix until there is no precipitate, and age for 1 day to obtain the spraying solution;

[0049] Step (5): Spray the spraying solution onto the pretreated substrate by solution plasma spraying method to prepare a multi-element doped hydroxyapatite implant coating; Use the cleaned and dried stainless steel as the substrate, with a size of 10*10*2 mm, perform sandblasting treatment with corundum, and the roughness of the substrate after sandblasting is about 4.3 μm; The specific process parameters during spraying are: spraying power 38.2 kW; spraying distance 50 mm; liquid feeding rate 40 mL / min; atomization pressure 1.2 bar; substrate preheating temperature 250 °C, and the gun moving speed is 500 mm / s.

[0050] The EDS energy spectrum and XRD spectrum of the coating prepared in this example are shown in Figure 3 and Figure 4 ; It can be seen from Figure 3 and Figure 4 that the coating prepared in this example is successfully doped with magnesium element and zinc element, and the magnesium-zinc double-doped hydroxyapatite coating has a high purity (92.6%) and crystallinity (84.7%).

[0051] Example 3

[0052] In this example, a zinc-magnesium-strontium triple-doped hydroxyapatite implant coating is prepared by a one-step method, including the following steps:

[0053] Step (1): Place 56.92 g of triethyl phosphite and 25.56 g of tributyl phosphite in 86.4 mL of deionized water and stir for 4 h until the solution is clear and transparent, then let it stand for hydrolysis for 2 days to obtain solution A;

[0054] Step (2): Dissolve 193.34 g of calcium nitrate tetrahydrate in 1 L of deionized water and stir magnetically for 2 h until dissolved to obtain solution B;

[0055] Step (3): Add 13.98 g of magnesium acetate tetrahydrate, 11.84 g of zinc acetate, and 13.41 g of strontium acetate to solution B and stir to mix and dissolve to obtain solution C;

[0056] Step (4): Under the condition of stirring at room temperature, slowly dropwise add solution C to solution A drop by drop, and finish dropping in 30 min; After solution C is dropped, make up the volume to 2 L, continue to stir and mix until there is no precipitate, and age for 1 day to obtain the spraying solution;

[0057] Step (5): Spray the spraying solution onto the pretreated substrate by solution plasma spraying to prepare a multi-element doped hydroxyapatite implant coating; Use the cleaned and dried stainless steel as the substrate, with dimensions of 10*10*2 mm, and perform sandblasting treatment with corundum. After sandblasting, the roughness of the substrate is about 4.3 μm; The specific process parameters during spraying are: spraying power 39.8 kW; spraying distance 45 mm; liquid feeding rate 40 mL / min; atomization pressure 1.2 bar; substrate preheating temperature 250 °C, and the gun moving speed is 500 mm / s.

[0058] The EDS energy spectrum and XRD pattern of the coating prepared in this example are shown in Figure 5 and Figure 6 ; It can be seen from Figure 5 and Figure 6 that the coating prepared in this example is successfully doped with magnesium, zinc, and strontium elements, and the magnesium-zinc-strontium triple-doped hydroxyapatite coating has a high purity (91.7%) and crystallinity (86.6%).

[0059] Comparative Example 1

[0060] The hydroxyapatite implant coating is prepared by a one-step method in this comparative example, including the following steps:

[0061] Step (1): Place 31.79 g of triethyl phosphite in 27 mL of deionized water and stir for 4 h until the solution is clear and transparent, then let it stand for hydrolysis for 2 days to obtain solution A;

[0062] Step (2): Dissolve 73.80 g of calcium nitrate tetrahydrate in 500 mL of deionized water and stir magnetically for 2 h until dissolved to obtain solution B;

[0063] Step (3): Under stirring at room temperature, slowly dropwise add solution B to solution A, and finish dropping in 10 min; After solution B is dropped, make up the volume to 1 L, continue to stir and mix until there is no precipitate, and age for 1 day to obtain the spraying solution;

[0064] Step (5): Spray the spraying solution onto the pretreated substrate by solution plasma spraying to prepare a multi-element doped hydroxyapatite implant coating; Use the cleaned and dried Ti6Al4V as the substrate, with dimensions of 10*10*2 mm, and perform sandblasting treatment with corundum. After sandblasting, the roughness of the substrate is about 3.8 μm; The specific process parameters during spraying are: spraying power 36.4 kW; spraying distance 60 mm; liquid feeding rate 40 mL / min; atomization pressure 1.2 bar; substrate preheating temperature 230 °C, and the gun moving speed is 500 mm / s.

[0065] Figure 7 and Figure 8EDS energy spectrum and XRD pattern of the coating prepared in this example. It can be seen from the figure that the coating prepared in this example is a pure hydroxyapatite implant coating; however, its purity (80.1%) and crystallinity (74.8%) are slightly worse than those in Examples 1 to 3.

[0066] Figure 9 Cell viability of osteoblast MC3T3-E1 cultured on the surface of zinc-magnesium-strontium ternary-doped hydroxyapatite coating and undoped hydroxyapatite coating for 2 days and 4 days; it can be seen from the figure that the zinc-magnesium-strontium ternary-doped hydroxyapatite coating, like the pure hydroxyapatite coating, has good cell viability, and with the increase of culture time, the cell proliferation ability gradually increases.

[0067] Obviously, the above examples are only for illustration and are not intended to limit the implementation. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementations here. And the obvious changes or modifications derived therefrom are still within the scope of protection of the claims of this patent application.

Claims

1. The one-step method for preparing a multi-element doped hydroxyapatite implant coating, characterized in that, It includes the following steps: Step (1): Place the phosphorus source in deionized water, stir until the solution is clear and transparent, then let it stand for hydrolysis to obtain solution A. The phosphorus source is a mixture of triethyl phosphite and tributyl phosphite mixed in a molar ratio of 3.35:

1. The standing hydrolysis time is 1 - 7 days. The concentration of phosphorus element in solution A is 4 - 6 mol / L. Step (2): Dissolve the calcium source in deionized water and stir until it is dissolved to obtain solution B. The calcium source is calcium nitrate and / or calcium acetate. Step (3): Add the nitrate or acetate of the element to be doped into solution B, stir and mix until dissolved to obtain solution C. The concentration of calcium ions in solution C is 0.8 - 1 mol / L. The element to be doped is any one or a mixture of two or more of zinc, strontium, magnesium, iron, and cerium. In solution C, the total molar amount of the element to be doped and the molar amount of calcium ions is in a ratio of 1:4 - 20. Step (4): Under the condition of stirring at room temperature, drip solution C into solution A. After the dripping of solution C is completed, continue to stir and mix for aging. After the aging is completed, a spraying solution is obtained. Solution C is dripped within 10 - 60 min. The continuous stirring and mixing time is 1 - 3 days. The dripping amount of solution C is such that the ratio of the total molar amount of the element to be doped and calcium element in the spraying solution to the molar amount of phosphorus element is (10 - 10.5):

6. Step (5): Spray the spraying solution onto the pretreated substrate by solution plasma spraying method to prepare a multi - element doped hydroxyapatite implant coating.

2. The one-step method for preparing a multi-element doped hydroxyapatite implant coating according to claim 1, wherein In step (5), the substrate is pure titanium, titanium alloy, stainless steel or cobalt - chromium - molybdenum alloy. The pretreatment method of the substrate is: after cleaning and drying the substrate, perform sandblasting with corundum. The roughness of the substrate after sandblasting is 3.5 - 4.5 μm.

3. The one-step method for preparing a multi-element doped hydroxyapatite implant coating according to claim 2, characterized in that, In step (5), the conditions of the solution plasma spraying method are: spraying power 20 - 100 kW; spraying distance 30 - 100 mm; liquid feeding rate 20 - 100 mL / min; atomization pressure 0.8 - 2.0 bar; substrate preheating temperature 150 - 400 °C, and the gun moving speed is 400 - 700 mm / s.

4. The one-step method for preparing a multi-element doped hydroxyapatite implant coating according to any one of claims 1-3, characterized in that, In step (1), the stirring time is 4 - 10 h; in step (2), the stirring time is 1 - 2 h; in step (3), the stirring time is 1 - 2 h.

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