Bone implant material super-hydrophilic coating and preparation thereof

Abstract

The invention discloses a bone implant material super-hydrophilic coating and a preparation method thereof. The preparation method comprises the following steps: adding calcium hydroxide, strontium hydroxide and ethylenediamine tetraacetic acid disodium salt into water to form turbid liquid; standing the turbid liquid to obtain a layered solution; adding disodium hydrogen phosphate into the layered solution, and adjusting the pH value to obtain a mixed solution; a bone implant and the obtained mixed solution are subjected to a hydrothermal reaction, and then the super-hydrophilic coating is formed on the bone implant. Other surfactants and template molecules do not need to be added, so that no toxic substance is generated, and the method is safe and environment-friendly; the super-hydrophilic nano-hydroxyapatite reticular coating is synthesized in one step, the reaction time is short, the temperature is low, the cost is low, and the process repeatability is good; the obtained net-shaped coating is uniform in morphology and high in wrapping performance, the roughness of the surface of the implant is increased, better attachment points are provided for bone cells, and growth of bone tissue and fixation of the implant are promoted; the obtained coating has super-hydrophilicity; the biocompatibility is good.

Description

Technical Field

[0001] The present invention relates to the preparation of a hydrophilic coating, especially a super-hydrophilic coating for bone implant materials. Background Art

[0002] Hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , HAP) is the main inorganic component of human bones and teeth, and has excellent hydrophilicity, biocompatibility and biodegradability, making it a surface modification material widely used in orthopedic and dental implants. Due to the similar chemical composition of hydroxyapatite to human bone tissue, it is widely used in the surface modification of bone repair and dental implants. However, the nano-hydroxyapatite particles prepared by traditional methods usually have larger sizes and poor dispersibility, which limits their application in the biomedical field.

[0003] The preparation methods of hydroxyapatite mainly include hydrothermal synthesis method, sol-gel method, microemulsion method, solid-phase reaction method, biomimetic synthesis method and neutralization method, etc. The hydroxyapatite coatings synthesized by different methods have different morphological characteristics, crystal sizes and physical and chemical properties, and thus can have different specific applications.

[0004] The preparation method of hydroxyapatite and the regulation of its microscopic morphology are crucial for its application in the biomedical field. At present, in the preparation process of hydrothermally synthesized hydroxyapatite nanostructures, most of them need to add inorganic or organic templates or surfactants to achieve the control of the microscopic morphology of hydroxyapatite.

[0005] Guang S et al. (Guang S, Ke F, Shen Y. Controlled Preparation and Formation Mechanism of Hydroxyapatite Nanoparticles under Different Hydrothermal Conditions[J]. Journal of Materials Science & Technology, 2015, 31(08): 852-856.) added template molecules with longer hydrophobic groups, resulting in the hydrothermal synthesis of longer hydroxyapatite rod-like crystals with a larger aspect ratio. CN102730658A uses calcium nitrate tetrahydrate and diammonium hydrogen phosphate as raw materials, adds urea and sorbitol, and prepares sea urchin-like hydroxyapatite. CN104310363A prepares silicon-doped hydroxyapatite nanowires using ethylenediaminetetraacetic acid and CTAB as templates. However, the surfactants and organic and inorganic templates added in the above preparation methods need to be removed in subsequent treatments, which on the one hand increases the complexity of the process and the preparation cost, and on the other hand, these added organic substances are prone to residues, which may ultimately affect the performance of the material and cause environmental pollution.

[0006] In addition, hydrophilicity is particularly crucial for implants: Research shows that hydrophilic surface modification treatment can promote implant osseointegration. When comparing 4 weeks after implant placement with 2 weeks, the implant stability quotient (ISQ), critical unscrewing torque (CST), and bone bonding rate are all significantly increased. Hydrophilicity is very important for implants because it can significantly affect the osseointegration speed and success rate of implants. Hydrophilicity enables the implant surface to quickly attach proteins and blood, accelerating the generation of bone cells, thereby shortening the healing period, which can generally be shortened from 6-8 weeks to 3-4 weeks. Hydrophilic implants also have the ability to promote bone regeneration, can reduce bacterial invasion and bone resorption, and make dental implants more stable. For special populations with poor bone quality and slow metabolism, such as patients with hypertension, high blood sugar, and diabetes, hydrophilic implants have a wider range of indications due to their good biocompatibility with the human body, can reduce the surgical risk, and improve the success rate of dental implants. Summary of the Invention

[0007] The purpose of the present invention is to provide a preparation method for a superhydrophilic coating of a bone implant material, which can at least overcome certain or some of the defects mentioned in the above prior art.

[0008] According to one aspect of the present invention, there is provided a preparation method for a superhydrophilic coating of a bone implant material, comprising:

[0009] Adding calcium hydroxide, strontium hydroxide, and disodium ethylenediaminetetraacetate to water to form a suspension;

[0010] A layered solution is obtained after standing the suspension;

[0011] Disodium hydrogen phosphate is added to the layered solution, and the pH value is adjusted to 10 - 12. After stirring evenly, a mixed solution is obtained;

[0012] The bone implant is placed in a polytetrafluoroethylene - lined bile;

[0013] The obtained mixed solution is transferred to the polytetrafluoroethylene - lined bile, and then the polytetrafluoroethylene - lined bile is sealed;

[0014] The sealed polytetrafluoroethylene - lined bile is placed in a reaction kettle, and then the reaction kettle is also sealed; and

[0015] The sealed reaction kettle is heated to form a super - hydrophilic coating on the bone implant by hydrothermal reaction, wherein the heating temperature is 80 - 90 °C and the time is 2 - 6 h.

[0016] According to the preparation method of the present invention, the pH value is preferably adjusted by adding sodium hydroxide. The pH value is preferably about 11.

[0017] According to the preparation method of the present invention, the molar ratio of calcium hydroxide, strontium hydroxide and disodium ethylenediaminetetraacetate is preferably about 1:1:1.

[0018] According to the preparation method of the present invention, the molar ratio of sodium dihydrogen phosphate to calcium hydroxide is preferably about 1:1.

[0019] According to the preparation method of the present invention, the volume ratio of the polytetrafluoroethylene - lined bile is preferably controlled to be 70% - 80%.

[0020] According to the preparation method of the present invention, it is preferred to first add calcium hydroxide and strontium hydroxide and stir evenly, and then add disodium ethylenediaminetetraacetate.

[0021] According to the preparation method of the present invention, it may further include cooling and taking out the bone implant formed with the super - hydrophilic coating, and then cleaning and drying it.

[0022] According to the preparation method of the present invention, the bone implant is preferably made of titanium alloy and is subjected to sandblasting and acid - etching treatment.

[0023] According to another aspect of the present invention, a bone implant material is provided, on the surface of which a super - hydrophilic coating prepared by the above - mentioned method is formed.

[0024] The preparation method of the super - hydrophilic coating of the bone implant material according to the present invention has at least the following advantages.

[0025] Calcium hydroxide and strontium hydroxide are both alkaline. As the essential calcium source and strontium source for the growth of hydroxyapatite, they have a relatively small molecular weight, and calcium hydroxide and strontium hydroxide can effectively increase the alkalinity of the solution, providing an alkaline environment for the subsequent chelation reaction; disodium ethylenediaminetetraacetate, as a chelating agent, should play a complexing role after the addition of the above two, and chelate with metal calcium ions Sr 2+ 、Ca 2+ to form stable chelates CaY 2- and SrY 2- . This process is usually carried out in an alkaline environment with a relatively high pH value because the chelating ability of EDTA is the strongest under alkaline conditions.

[0026] The chemical equation of the reaction can be expressed as:

[0027] Sr 2+ +H 2 Y 2- →SrY 2- +2H +

[0028] Ca 2+ +H 2 Y 2- →CaY 2- +2H +

[0029] where H 2 Y - is the negative ion form of disodium EDTA, and SrY 2- and CaY 2- are the formed chelates.

[0030] Sodium dihydrogen phosphate is acidic and easily soluble in water, providing a phosphorus source for the growth of hydroxyapatite. When calcium hydroxide and strontium hydroxide solutions are added with disodium ethylenediaminetetraacetate first and then disodium hydrogen phosphate, the following reactions will occur:

[0031] Ca 2+ +H 2 PO 4- →CaHPO 4

[0032] Sr 2+ +H 2 PO 4- →SrHPO 4

[0033] CaHPO 4 +Ca 2+ +PO 4 3- →Ca 3 (PO 4 )2 ↓ + H 2 O

[0034] SrHPO 4 + Sr 2+ + PO 4 3- → Sr 3 (PO 4 ) 2 ↓ + H 2 O

[0035] Disodium hydrogen phosphate dissociates into H 2 PO 4 - ions in solution, which react with calcium ions Ca 2+ to form calcium phosphate Ca 3 (PO 4 ) 2 precipitate. The reaction usually takes place at a relatively high pH value because the chelating ability of EDTA is the strongest under alkaline conditions, and the solubility of calcium phosphate is the lowest under alkaline conditions, which is conducive to the formation of the precipitate.

[0036] The raw materials required are only calcium hydroxide, strontium hydroxide, disodium hydrogen phosphate, disodium ethylenediaminetetraacetate and sodium hydroxide. There is no need to add other surfactants and template molecules, and thus no toxic substances will be produced, which is safe and environmentally friendly.

[0037] There is no need to change any parameters midway, and superhydrophilic nano-hydroxyapatite reticular coatings can be synthesized in one step. The reaction time is short, the temperature is low, the cost is low, and the process repeatability is good.

[0038] The obtained nano-hydroxyapatite reticular coatings have a uniform morphology, high purity, large coverage rate and strong wrapping ability for implants, increasing the surface roughness of titanium alloy, providing better attachment points for bone cells, and promoting bone tissue growth and implant fixation.

[0039] The large-grit sandblasted and acid-etched (SLA) surface containing nano-hydroxyapatite reticular structure prepared has superhydrophilicity, and its hydrophilicity performance is still the same as the initial one after one month of continuous testing.

[0040] The proliferation experiment of rat BMSC cells shows that the prepared SLA has good biocompatibility, can reduce the inflammatory reaction after implant implantation, reduce the risk of complications, accelerate the recovery of damaged tissues after surgery, and shorten the recovery time of patients. Description of the Drawings

[0041] Figure 1a This is the scanning electron microscope picture of the product obtained in the embodiment of the present invention.

[0042] Figure 1b This is the interface wettability test chart of the product obtained in the embodiment of the present invention.

[0043] Figure 1c This is the fluorescence detection image of the product obtained in the embodiment of the present invention after 2 hours of cell adhesion.

[0044] Figure 1d This is the physical image of ALP staining after 7 days of osteogenic induction of the product obtained in the embodiment of the present invention.

[0045] Figure 1e This is the antibacterial effect diagram of the product obtained in the embodiment of the present invention.

[0046] Figure 2a This is the scanning electron microscope image of the product obtained in the comparative example.

[0047] Figure 2b This is the interfacial wettability test diagram of the product obtained in the comparative example.

[0048] Figure 2c This is the fluorescence detection image of the product obtained in the comparative example after 2 hours of cell adhesion.

[0049] Figure 2d This is the physical image of ALP staining after 7 days of osteogenic induction of the product obtained in the comparative example.

[0050] Figure 2e This is the antibacterial effect diagram of the product obtained in the comparative example. Detailed implementation mode

[0051] The present invention will be described in detail below with reference to specific embodiments and the accompanying drawings.

[0052] Embodiment

[0053] (1) 1 g of calcium hydroxide solid, 1.64 g of strontium hydroxide, and 4.5 g of disodium ethylenediaminetetraacetate were successively added to 50 ml of deionized water and stirred to form a suspension.

[0054] (2) After the suspension in step (1) was allowed to stand for 2 minutes, a flocculent layered solution was obtained. 1.72 g of disodium hydrogen phosphate solid was added, and the pH value was adjusted to 11 with sodium hydroxide solid. The mixture was stirred evenly with a magnetic stirrer for 10 minutes to obtain a milky white mixture.

[0055] (3) The titanium alloy sample sheet treated by sandblasting and acid etching (SLA) was placed in a polytetrafluoroethylene-lined inner liner. The milky white mixed solution in step (2) was transferred to the polytetrafluoroethylene-lined inner liner with a dropper. The volume ratio was controlled to be 75%, and the lid of the inner liner was tightened and then placed in a reaction kettle. The reaction kettle was tightened and placed in an 85°C water bath for 4 hours.

[0056] (4) The hydrothermal reaction kettle after the reaction in step (3) was cooled to room temperature of 25°C. The SLA sample sheet was taken out with tweezers, ultrasonically washed 3 times with deionized water, and dried in a vacuum incubator at 60°C.

[0057] Comparative example

[0058] (1) Add 1 g of calcium hydroxide solid and 4.5 g of disodium ethylenediaminetetraacetate to 50 ml of deionized water in sequence and stir the suspension.

[0059] (2) Let the suspension in step (1) stand for 2 min to obtain a flocculent stratified solution, add 1.72 g of disodium hydrogen phosphate solid, adjust the pH value to 11 with sodium hydroxide solid, and stir evenly with a magnetic stirrer for 10 min to obtain a milky white mixture.

[0060] (3) Place the titanium alloy sample treated by sandblasting and acid etching (SLA) in a polytetrafluoroethylene-lined inner container. Use a dropper to transfer the milky white mixed solution in step (2) to the polytetrafluoroethylene-lined inner container, control the volume ratio to 75%, cover the lid of the inner container tightly, then put it into a reaction kettle, tighten the reaction kettle, and place the reaction kettle in an 85°C water bath for 4 hours.

[0061] (4) Cool the hydrothermal reaction kettle after the reaction in step (3) to room temperature of 25°C, take out the SLA sample with tweezers, wash it ultrasonically with deionized water 3 times, and dry it in a vacuum incubator at 60°C.

[0062] Performance test

[0063] Figures 1a - 1e They are respectively the scanning electron microscope picture, the interfacial wettability test picture, the fluorescence detection picture of cell adhesion for 2 h, and the physical picture of ALP staining after osteogenic induction of the product obtained in the example. It can be observed that the nano-hydroxyapatite flaky coating prepared in the example has a uniform morphology, high purity, a large coverage rate of the implant, strong wrapping property, increases the surface roughness of the titanium alloy, provides better attachment points for bone cells, and promotes the growth of bone tissue and the fixation of the implant. The SLA with nano-hydroxyapatite flaky structure on the surface prepared has superhydrophilicity; the edge of cell spreading on the SLA surface is clear, the cytoskeleton develops perfectly, and the number of cells is large. In addition, positive reactions (gray-black particles or massive precipitates) can be observed in the cytoplasm of the cells, the staining intensity is significant, the degree of osteogenic differentiation and cell activity of the cells are strong, and the distribution is uniform and dense. The antibacterial rate is 77%.

[0064] Figures 2a - 2eThey are respectively the scanning electron microscope image of the product obtained in the comparative example, the interfacial wettability test chart, the fluorescence detection chart of cell adhesion for 2 h, and the ALP staining physical chart of osteogenic induction for 7 days. It can be observed that the nano-hydroxyapatite reticular coating prepared in the comparative example has a uniform morphology, high purity, a large coverage rate of the implant, strong encapsulation, increases the surface roughness of the titanium alloy, provides better attachment points for osteocytes, and promotes the growth of bone tissue and the fixation of the implant. The SLA with a nano-hydroxyapatite reticular structure on the surface prepared has hydrophilicity; the cell spreading edge on the SLA surface is clear, the cytoskeleton develops perfectly, but the number of cells is small. In addition, positive reactions (gray-black particles or massive precipitates) can be observed in the cytoplasm of the cells, the staining intensity is obvious, the degree of osteogenic differentiation and cell activity of the cells are strong, but the distribution is relatively sparse. The antibacterial rate is 58%.

[0065] In summary, the present invention does not use any templates and surface activators with groups, does not need to change any parameters midway, and synthesizes a strontium-doped hydroxyapatite superhydrophilic nano-coating in one step. Compared with other preparation methods such as plasma spraying and laser etching, it has the outstanding characteristics of mild preparation conditions, strong controllability, superhydrophilicity, excellent biocompatibility, and strong ability to promote bone regeneration. Scanning electron microscopy shows that the strontium-doped nano-hydroxyapatite coating prepared by this method is evenly distributed, has a uniform morphology, has good encapsulation of the implanted titanium alloy, also increases the surface roughness of the titanium alloy, provides better attachment points for osteocytes, and promotes the growth of bone tissue and the fixation of the implant. Liquid surface tension tests show that the SLA with a strontium-doped hydroxyapatite flake structure on the surface prepared by this method has superhydrophilicity, and its hydrophilicity performance remains the same when tested again after one month. The rat BMSC cell proliferation experiment shows that the SLA prepared under this condition has good biocompatibility, excellent cell morphology after 2 hours of cell adhesion, complete cell spreading, and many cell tail feet. The ALP staining experiment of osteogenic induction for 7 days shows that the osteogenic induction effect of strontium-doped hydroxyapatite is better. The antibacterial experiment also fully proves that the strontium-doped hydroxyapatite coating endows the implant with good antibacterial effects, can reduce the inflammatory reaction after implant implantation, reduce the risk of complications, accelerate the recovery of damaged tissues after surgery, and shorten the recovery time of patients.

Claims

1. A method for preparing a super-hydrophilic coating of a bone implant material, comprising: Adding calcium hydroxide, strontium hydroxide and disodium ethylenediaminetetraacetic acid into water to form a suspension; After the suspension is allowed to stand, a layered solution is obtained; Add disodium hydrogen phosphate to the layered solution, adjust the pH value to 10-12, and stir evenly to obtain a mixed solution; The bone implant is placed in a polytetrafluoroethylene-lined bladder; The obtained mixed solution is transferred into a polytetrafluoroethylene-lined liner and then the polytetrafluoroethylene-lined liner is sealed; Place the sealed polytetrafluoroethylene liner in the reactor and seal the reactor as well; as well as The closed reaction kettle is heated to react and form a super-hydrophilic coating on the bone implant, wherein the heating temperature is 80-90° C. and the heating time is 2-6 hours.

2. The preparation method according to claim 1, wherein the pH value is adjusted by adding sodium hydroxide.

3. The preparation method according to claim 1, wherein the molar ratio of calcium hydroxide, strontium hydroxide and disodium ethylenediaminetetraacetic acid is 1:(0.8-1.2):(0.8-1.2).

4. The preparation method according to claim 1, wherein the molar ratio of sodium dihydrogen phosphate to calcium hydroxide is (0.8-1.2):

1.

5. The preparation method according to claim 1, wherein the volume ratio of the polytetrafluoroethylene liner is controlled to be 70% to 80%.

6. The preparation method according to claim 1, wherein calcium hydroxide and strontium hydroxide are first added and stirred evenly before adding disodium ethylenediaminetetraacetic acid.

7. The preparation method according to claim 1, further comprising cooling and taking out the bone implant formed with the super-hydrophilic coating, and then cleaning and drying it.

8. The preparation method according to claim 1, wherein the bone implant is made of titanium alloy and is subjected to sandblasting and acid etching treatment.

9. A bone implant material, the surface of which is formed with a super-hydrophilic coating prepared according to any one of claims 1 to 8.

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