A composite coating on the tooth surface of an atlantoaxial PEEK interbody fusion device

Abstract

This invention discloses a composite coating for the tooth surface of an atlantoaxial PEEK interbody fusion cage, relating to the field of medical materials technology. The composite coating for the atlantoaxial PEEK interbody fusion cage comprises a transition layer covering the tooth surface of the atlantoaxial PEEK interbody fusion cage and a hydroxyapatite coating on the surface of the transition layer; the transition layer is obtained by mixing modified nano-hydroxyapatite and modified PEEK; the hydroxyapatite coating is obtained by plasma spraying of nano-hydroxyapatite. This application sets a transition layer between the PEEK and the hydroxyapatite coating, effectively addressing the problem of easy coating detachment due to the difference in physicochemical properties between the PEEK and hydroxyapatite coatings. The composite coating prepared in this application improves the bonding strength between the coating and the substrate, and the prepared material can be used in biological organisms for a long time.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, specifically to a composite coating on the tooth surface of an atlantoaxial PEEK interbody fusion device. Background Technology

[0002] Degenerative lumbar spine diseases are very common in orthopedic clinics, including lumbar disc herniation and lumbar spondylolisthesis, which can cause low back pain and nerve compression symptoms, seriously affecting patients' quality of life. Atlantoaxial diseases often result in atlantoaxial instability, leading to spinal cord compression and nerve damage, frequently requiring surgery to completely relieve the compression and restore the physiological curvature of the lumbar spine. Currently, atlantoaxial fusion surgery in clinical practice still uses simple bone grafting and fusion devices for fixation, with autologous iliac bone as the primary bone graft material. This simple bone grafting fixation method lacks stress load at the fusion site, making it prone to complications such as collapse and pseudoarthrosis. Combining the conventional application of PEEK fusion devices in spinal fusion, and based on years of clinical experience, our company has designed a surface-coated modified PEEK interbody fusion device for the atlantoaxial joint.

[0003] Polyetheretherketone (PEEK) resin is a synthetic semi-crystalline polymer with an elastic modulus similar to that of cortical bone. It also possesses advantages such as good biocompatibility, radiopermeability, and the absence of artifacts in magnetic resonance imaging (MRI), making it highly valued in the medical device industry, particularly in implantable devices. However, as PEEK is a hydrophobic, bioinert material, its low surface energy limits cell adhesion, resulting in limited osteoconduction and osseointegration capabilities. This prevents the implant from promoting osteoblast attachment and proliferation. To obtain PEEK implants with good osseointegration performance, surface modification is necessary. Common modification methods to improve osseointegration performance include surface coating and surface treatment techniques. Surface coating is a commonly used material surface modification technique that can improve the biological properties of PEEK while preserving its original mechanical properties. Bioactive materials such as titanium (Ti) and hydroxyapatite (HA) are used to coat the PEEK surface to enhance its osseointegration performance. Titanium possesses excellent mechanical and biocompatibility, promoting bone growth. Cell growth and diffusion are more active on the surface of titanium-coated PEEK. However, titanium coatings can cause artifacts in medical imaging, affecting the visualization of the bone-implant interface. Hydroxyapatite, a major component of human bone, is superior to titanium in terms of biocompatibility. However, the significant differences in chemical and physical properties between the inorganic material hydroxyapatite and the polymeric material PEEK result in low bonding strength and a tendency for coating peeling. Summary of the Invention

[0004] The purpose of this invention is to provide a composite coating for the tooth surface of an atlantoaxial PEEK interbody fusion device, thereby solving the following technical problems:

[0005] The significant differences in chemical and physical properties between the inorganic material hydroxyapatite and the polymeric material PEEK result in low bonding strength between the two.

[0006] The objective of this invention can be achieved through the following technical solutions:

[0007] A composite coating for the tooth surface of an atlantoaxial PEEK interbody fusion device includes a transition layer covering the tooth surface of the atlantoaxial PEEK interbody fusion device and a hydroxyapatite coating on the surface of the transition layer.

[0008] The method for preparing the transition layer includes the following steps:

[0009] S1: Add epoxidized hydroxyapatite and sulfolane to a reaction vessel and disperse them evenly. Control the temperature at 210-220℃ to obtain solution A.

[0010] S2: Add phosphorylated PEEK and sulfolane to a reaction vessel, heat and stir to dissolve, and add solution A under heat preservation conditions to disperse evenly, thus obtaining a transition layer slurry;

[0011] S3: The transition layer slurry is coated on the tooth surface of the atlantoaxial PEEK intervertebral fusion device, sintered at high temperature and heat-treated to obtain the transition layer;

[0012] The preparation method of epoxidized hydroxyapatite includes the following steps:

[0013] Anhydrous ethanol and deionized water were added to the reaction vessel and dispersed evenly. The pH was adjusted to 4-5. γ-glycidyl etheroxypropyltriethoxysilane was added and stirred at room temperature for 0.5-1 h. Nano-hydroxyapatite was added, and the temperature was controlled at 60-65℃. The mixture was kept warm and stirred for 2-4 h. After filtration, washing with water, and drying, epoxidized hydroxyapatite was obtained.

[0014] The preparation method of the phosphorylated PEEK includes the following steps:

[0015] A1: Add polyetheretherketone and concentrated sulfuric acid to a reaction vessel, control the temperature at 0-5℃, disperse until the solution becomes transparent, add chloromethyl octyl ether, keep warm and stir for 1-3 hours, add ice water to stop the reaction, filter, wash with water until neutral, wash with ethanol and dry to obtain component one;

[0016] A2: Add component 1 and N-methylpyrrolidone to the reaction vessel and disperse evenly. Add triethyl phosphite, control the temperature at 110-120℃, and keep the reaction at this temperature for 12-18 hours. Remove triethyl phosphite by vacuum distillation, wash with water, dry, add concentrated hydrochloric acid, heat under reflux for 9-15 hours, filter, wash with water, and dry to obtain phosphorylated PEEK.

[0017] As a further embodiment of the present invention, the preparation method of the nano-hydroxyapatite includes the following steps: using 0.5-2.5 mol / L calcium nitrate tetrahydrate [Ca(NO3)2·4H2O] aqueous solution, 0.5-3 mol / L diammonium hydrogen phosphate [(NH4)2HPO4] aqueous solution, and ammonium fluoride as raw materials, and preparing them according to the Ca:P:F molar ratio of 16.7:10:1, adjusting the pH to 9-10 with 10-30 wt% ammonia water, controlling the temperature at 60-90℃, maintaining the temperature for reaction, filtering, aging for 24-48 h, and dialysis with deionized water to remove ammonia and salt, thereby obtaining nano-hydroxyapatite.

[0018] As a further aspect of the present invention: the epoxidized hydroxyapatite accounts for 30-50% of the total mass of the transition layer.

[0019] As a further aspect of the present invention, the thickness of the transition layer is 15-125 μm.

[0020] As a further embodiment of the present invention: the addition ratio of anhydrous ethanol, deionized water, γ-glycidyl etheroxypropyltriethoxysilane, and nano-hydroxyapatite is 45-90 mL: 5-10 mL: 2.5-5 mL: 1 g.

[0021] As a further aspect of the present invention: the addition ratio of polyether ether ketone, concentrated sulfuric acid, and chloromethyl octyl ether in A1 is 1g: 50-75mL: 8-15mL.

[0022] As a further aspect of the present invention: the addition ratio of component one, N-methylpyrrolidone, and triethyl phosphite in A2 is 1g: 20-40mL: 2-4mL. As a further aspect of the present invention: the hydroxyapatite coating is prepared by using nano-hydroxyapatite as a raw material to form a suspension, which is then obtained through plasma spraying technology.

[0023] As a further aspect of the present invention, the plasma spraying technology specifically includes the following steps:

[0024] B1: A suspension is obtained by blending nano-hydroxyapatite and distilled water, wherein the solid content of the suspension is 5-15%;

[0025] B2: The suspension is sprayed using plasma spraying technology to obtain a hydroxyapatite coating.

[0026] As a further aspect of the present invention, the specific spraying parameters during plasma spraying are: gas flow rate 150-180L / min, arc current 180-230A, and spraying distance 50-80mm.

[0027] As a further aspect of the present invention, the thickness of the hydroxyapatite coating is 45-75 μm.

[0028] As a further aspect of the present invention: the transition layer is applied to the surface of the PEEK component of the atlantoaxial PEEK interbody fusion device; the PEEK component is obtained by surface sulfonation treatment of PEEK resin.

[0029] As a further aspect of the present invention, the specific steps of the sulfonation treatment are as follows: immersing the PEEK component in concentrated sulfuric acid, controlling the temperature at 50-70°C, maintaining the reaction temperature for 6-9 hours under stirring, washing with ice water, and drying.

[0030] As a further aspect of the present invention: the concentrated sulfuric acid in the sulfonation treatment is an 85-98wt% sulfuric acid aqueous solution, and the addition ratio of PEEK to concentrated sulfuric acid is 1g:8-12mL.

[0031] As a further aspect of the present invention: the atlantoaxial PEEK interbody fusion cage includes a fusion cage body, a radiopaque screw for intraoperative imaging and positioning, and a composite coating; the fusion cage body is made of PEEK resin, and the contact surface between the fusion cage body and the vertebral body is designed with a toothed structure for product anti-retraction; the composite coating covers the surface of the toothed structure.

[0032] As a further aspect of the present invention: the imaging pin is made of titanium alloy or pure tantalum material, and the imaging pin is used for intraoperative and postoperative imaging.

[0033] As a further aspect of the present invention: the middle part of the atlantoaxial PEEK interbody fusion device is reserved with a bone graft window for filling with bone graft material, and a circumferential protruding ring structure is designed in the middle of the bone graft window to facilitate the fixation of the bone graft material; and an instrument clamping groove is designed at the tail of the product to facilitate the adjustment of the position of the fusion device during the operation.

[0034] The beneficial effects of this invention are:

[0035] (1) This application uses nano-hydroxyapatite as a base and modifies it with an epoxy silane coupling agent to prepare epoxidized hydroxyapatite. This application uses concentrated sulfuric acid as a solvent to perform a chloromethylation reaction on polyether ether ketone using chloromethyl octyl ether to obtain chloromethylated polyether ether ketone, i.e., component one; and uses component one and triethyl phosphite as raw materials, and through the Michaels-Arbuzov reaction, uses the phosphate ester group of triethyl phosphite to replace the chloride ion on the molecular chain of component one, and finally performs hydrolysis to obtain phosphorylated PEEK; this application mixes epoxidized hydroxyapatite and phosphorylated PEEK with sulfolane respectively, and blends them under high temperature conditions. The epoxy group of epoxidized hydroxyapatite and the phosphate group of phosphorylated PEEK undergo a ring-opening reaction, and hydroxyapatite is grafted onto the PEEK molecular chain through chemical bonds to prepare a transition layer slurry. The transition layer slurry is coated on the surface of the sulfonated PEEK component, and heat treatment is set to remove the sulfolane in the transition layer slurry. Moreover, the heat treatment effectively improves the mechanical properties of the coating.

[0036] This application utilizes epoxidized hydroxyapatite and phosphorylated PEEK as raw materials to prepare a transition layer, effectively addressing the problem of residual stress between the coating material and the substrate due to the large difference in thermal expansion coefficients and elastic moduli between the hydroxyapatite coating and the PEEK component, which leads to low bonding strength. This application introduces a transition layer between the coating and the substrate, controlling its thermal expansion coefficient and elastic modulus to fall between those of the substrate and the coating. This achieves a gradient change in the thermal expansion coefficient and elastic modulus of the material, reducing residual stress between the substrate and the coating, improving the bonding strength between the coating and the substrate, and allowing the prepared material to be used long-term in biological organisms.

[0037] (2) This application uses concentrated sulfuric acid to corrode the PEEK component, forming a three-dimensional porous structure on the surface of the PEEK component. Sulfonic acid groups are also generated on the surface and in the pores of the PEEK. The sulfonation treatment of PEEK in this application not only increases the surface roughness of PEEK, improves hydrophilicity, and enhances the osseointegration performance of the PEEK implant, but also improves cell adhesion and promotes the growth of soft and hard tissues into the implant material, generating more bio-anchoring to improve its stability. Moreover, this application coats the prepared transition layer slurry onto the surface of the sulfonated PEEK component, improving the bonding strength between the transition layer and PEEK.

[0038] (3) This application uses calcium nitrate tetrahydrate [Ca(NO3)2·4H2O] aqueous solution, diammonium hydrogen phosphate [(NH4)2HPO4] aqueous solution and ammonium fluoride as raw materials to prepare nano-hydroxyapatite. The nano-hydroxyapatite prepared in this application is doped with fluoride ions. Fluoride ions not only have antibacterial effects, but also have a smaller radius than hydroxyl ions. The incorporation of fluoride ions reduces the crystal constant of hydroxyapatite, improves crystal stability, and reduces the solubility of the coating in the human body.

[0039] (4) This application utilizes suspension plasma spraying technology to prepare a suspension by mixing the prepared hydroxyapatite with distilled water. A hydroxyapatite coating is then sprayed onto the surface of a PEEK substrate with an attached transition layer. Distilled water is used as a pore-forming agent, resulting in a hydroxyapatite coating with a good porous structure, which is beneficial for cell adhesion. Furthermore, the porous structure with a fully interconnected network is conducive to the inward growth of osteoblasts. In addition to mechanical bonding, the bonding between the coating and the transition layer, as well as between coating particles, can also produce micro-regional metallurgical bonding and chemical bonding, exhibiting high bonding strength. This application uses suspension plasma spraying technology to prepare the hydroxyapatite coating, which does not require a special vacuum or atmosphere, has high deposition efficiency, low preparation cost, and can effectively reduce material waste.

[0040] (5) The composite coating prepared in this application coats the PEEK resin surface of the atlantoaxial PEEK interbody fusion device, which has initial stability and long-term mechanical stability. At the same time, the coating modification on the product surface can provide better fusion device fixation. The coating can guide the growth of new bone, provide a physiological scaffold for the formation of new bone, and be closely combined with bone tissue, which greatly improves the bioactivity and biocompatibility of the PEEK surface. Attached Figure Description

[0041] The invention will now be further described with reference to the accompanying drawings.

[0042] Figure 1 This is a schematic diagram of the composite coating applied to the tooth surface of the atlantoaxial PEEK interbody fusion device.

[0043] Reference numerals: 1. Fusion unit body; 2. Development pin; 3. Composite coating. Detailed Implementation

[0044] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example 1

[0045] The preparation method of nano-hydroxyapatite includes the following steps:

[0046] Using 2.5 mol / L calcium nitrate tetrahydrate [Ca(NO3)2·4H2O] aqueous solution, 1.5 mol / L diammonium hydrogen phosphate [(NH4)2HPO4] aqueous solution, and ammonium fluoride as raw materials, a mixture was prepared according to a Ca:P:F molar ratio of 16.7:10:1. The pH was adjusted to 10 with 30 wt% ammonia water, and the temperature was controlled at 70℃. The reaction was maintained at this temperature, filtered, aged for 36 h, and dialyzed with deionized water to remove ammonia and salt, yielding nano-hydroxyapatite. Example 2

[0047] The preparation method of epoxidized hydroxyapatite includes the following steps:

[0048] 450 mL of anhydrous ethanol and 50 mL of deionized water were added to the reaction vessel and dispersed evenly. Acetic acid buffer was added to adjust the pH to 4. 25 mL of γ-glycidoxypropyltriethoxysilane was added and stirred at room temperature for 0.5 h. 10 g of nano-hydroxyapatite prepared in Example 1 was added and dispersed evenly. The temperature was controlled at 60 °C and stirred for 2 h. After filtration, washing with water and drying, epoxidized hydroxyapatite was obtained.

[0049] The preparation method of phosphorylated PEEK includes the following steps:

[0050] A1: Add 10g of polyetheretherketone (PEEK 450PF powder produced by Victrex, UK) and 500mL of 85wt% concentrated sulfuric acid to a reaction vessel, control the temperature at 0℃, disperse until the solution becomes transparent, add 80mL of chloromethyl octyl ether, keep warm and stir for 1h, add ice water to stop the reaction, filter, wash with water until neutral, wash with ethanol and dry to obtain component one;

[0051] A2: Add 10g of component one and 200mL of N-methylpyrrolidone to a reaction vessel and disperse evenly. Add 20mL of triethyl phosphite, control the temperature at 110℃, and keep the reaction at this temperature for 12h. Remove the triethyl phosphite by vacuum distillation, wash with water, dry, add 36wt% concentrated hydrochloric acid, heat under reflux for 9h, filter, wash with water, and dry to obtain phosphorylated PEEK. Example 3

[0052] The preparation method of epoxidized hydroxyapatite includes the following steps:

[0053] 630 mL of anhydrous ethanol and 70 mL of deionized water were added to the reaction vessel and dispersed evenly. Acetic acid buffer was added to adjust the pH to 4. 35 mL of γ-glycidyl etheroxypropyltriethoxysilane was added and stirred at room temperature for 0.5 h. 10 g of nano-hydroxyapatite prepared in Example 1 was added and dispersed evenly. The temperature was controlled at 65 °C and stirred for 2 h. After filtration, washing with water and drying, epoxidized hydroxyapatite was obtained.

[0054] The preparation method of phosphorylated PEEK includes the following steps:

[0055] A1: Add 10g of polyetheretherketone (PEEK 450PF powder produced by Victrex, UK) and 650mL of 85wt% concentrated sulfuric acid to a reaction vessel, control the temperature at 0℃, disperse until the solution becomes transparent, add 120mL of chloromethyl octyl ether, keep warm and stir for 1h, add ice water to stop the reaction, filter, wash with water until neutral, wash with ethanol and dry to obtain component one;

[0056] A2: Add 10g of component one and 300mL of N-methylpyrrolidone to a reaction vessel and disperse evenly. Add 30mL of triethyl phosphite, control the temperature at 110℃, and keep the reaction at this temperature for 18h. Remove the triethyl phosphite by vacuum distillation, wash with water, dry, add 36wt% concentrated hydrochloric acid, heat under reflux for 12h, filter, wash with water, and dry to obtain phosphorylated PEEK. Example 4

[0057] The preparation method of epoxidized hydroxyapatite includes the following steps:

[0058] 900 mL of anhydrous ethanol and 100 mL of deionized water were added to the reaction vessel and dispersed evenly. Acetic acid buffer was added to adjust the pH to 4. 50 mL of γ-glycidoxypropyltriethoxysilane was added and stirred at room temperature for 1 h. 10 g of nano-hydroxyapatite prepared in Example 1 was added and dispersed evenly. The temperature was controlled at 65 °C and stirred for 4 h. After filtration, washing with water and drying, epoxidized hydroxyapatite was obtained.

[0059] The preparation method of phosphorylated PEEK includes the following steps:

[0060] A1: Add 10g of polyetheretherketone (PEEK 450PF powder produced by Victrex, UK) and 750mL of 85wt% concentrated sulfuric acid to a reaction vessel, control the temperature at 0℃, disperse until the solution becomes transparent, add 150mL of chloromethyl octyl ether, keep warm and stir for 3h, add ice water to stop the reaction, filter, wash with water until neutral, wash with ethanol and dry to obtain component one;

[0061] A2: Add 10g of component one and 400mL of N-methylpyrrolidone to a reaction vessel and disperse evenly. Add 40mL of triethyl phosphite, control the temperature at 120℃, and keep the reaction at this temperature for 18h. Remove the triethyl phosphite by vacuum distillation, wash with water, dry, add 36wt% concentrated hydrochloric acid, heat under reflux for 15h, filter, wash with water, and dry to obtain phosphorylated PEEK. Example 5

[0062] Please see Figure 1 The atlantoaxial PEEK interbody fusion cage includes a fusion cage body 1, a radiopaque pin 2 for intraoperative imaging and positioning, and a composite coating 3. The fusion cage body is made of PEEK resin (PEEK 450PF powder produced by Victrex, UK). The contact surface between the fusion cage body and the vertebral body is designed with a toothed structure for product anti-retraction. The composite coating covers the surface of the toothed structure.

[0063] The composite coating is a composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device, which includes a transition layer covering the tooth surface of the pretreated atlantoaxial PEEK interbody fusion device and a hydroxyapatite coating on the surface of the transition layer.

[0064] The preparation method for the pre-treated atlantoaxial PEEK interbody fusion cage tooth surface includes the following steps:

[0065] The fusion device body 1 was immersed in 85wt% concentrated sulfuric acid at a solid-liquid ratio of 1g:10mL, and the temperature was controlled at 60℃. The reaction was carried out under stirring conditions for 6h. After washing with ice water and drying, the pretreated atlantoaxial PEEK interbody fusion device was obtained.

[0066] The method for preparing the transition layer includes the following steps:

[0067] S11: Add the epoxidized hydroxyapatite and sulfolane prepared in Example 2 into the reaction vessel and disperse them evenly. Control the temperature at 210°C to obtain solution A;

[0068] S12: Add the phosphorylated PEEK and sulfolane prepared in Example 2 into a reaction vessel and heat to 250°C. Stir to dissolve and then add solution A under heat preservation conditions to disperse evenly, thus obtaining a transition layer slurry.

[0069] S13: The transition layer slurry was coated onto the tooth surface of the atlantoaxial PEEK interbody fusion device. High-temperature sintering was performed at a controlled temperature of 270℃ for 15 minutes, followed by a controlled temperature of 170℃ and a heat treatment for 12 hours to obtain a transition layer with a thickness of 125 μm. The transition layer contained 30 wt% epoxidized hydroxyapatite.

[0070] The preparation method of hydroxyapatite coating includes the following steps:

[0071] S21: The nano-hydroxyapatite prepared in Example 1 was mixed with distilled water to obtain a suspension with a solid content of 15%.

[0072] S22: The suspension was sprayed using plasma spraying technology (gas flow rate 180L / min, arc current 180A, spraying distance 80mm) to obtain a hydroxyapatite coating with a thickness of 75um. Example 6

[0073] Please see Figure 1 The atlantoaxial PEEK interbody fusion cage includes a fusion cage body 1, a radiopaque pin 2 for intraoperative imaging and positioning, and a composite coating 3. The fusion cage body is made of PEEK resin (PEEK 450PF powder produced by Victrex, UK). The contact surface between the fusion cage body and the vertebral body is designed with a toothed structure for product anti-retraction. The composite coating covers the surface of the toothed structure.

[0074] The composite coating is a composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device, which includes a transition layer covering the tooth surface of the pretreated atlantoaxial PEEK interbody fusion device and a hydroxyapatite coating on the surface of the transition layer.

[0075] The preparation method for the pre-treated atlantoaxial PEEK interbody fusion cage tooth surface includes the following steps:

[0076] The fusion device body 1 was immersed in 85wt% concentrated sulfuric acid at a solid-liquid ratio of 1g:10mL, and the temperature was controlled at 60℃. The reaction was carried out under stirring conditions for 6h. After washing with ice water and drying, the pretreated atlantoaxial PEEK interbody fusion device was obtained.

[0077] The method for preparing the transition layer includes the following steps:

[0078] S11: Add the epoxidized hydroxyapatite and sulfolane prepared in Example 3 into the reaction vessel and disperse them evenly. Control the temperature at 210°C to obtain solution A;

[0079] S12: Add the phosphorylated PEEK and sulfolane prepared in Example 3 into the reaction vessel and heat to 250°C. Stir to dissolve and then add solution A under the heat preservation condition to disperse evenly to obtain the transition layer slurry.

[0080] S13: The transition layer slurry was coated onto the tooth surface of the atlantoaxial PEEK interbody fusion device. High-temperature sintering was performed at a controlled temperature of 270℃ for 15 minutes, followed by a controlled temperature of 170℃ and a heat treatment for 12 hours to obtain a transition layer with a thickness of 125 μm. The transition layer contained 30 wt% epoxidized hydroxyapatite.

[0081] The preparation method of hydroxyapatite coating includes the following steps:

[0082] S21: The nano-hydroxyapatite prepared in Example 1 was mixed with distilled water to obtain a suspension with a solid content of 15%.

[0083] S22: The suspension was sprayed using plasma spraying technology (gas flow rate 180L / min, arc current 180A, spraying distance 80mm) to obtain a hydroxyapatite coating with a thickness of 75um. Example 7

[0084] Please see Figure 1 The atlantoaxial PEEK interbody fusion cage includes a fusion cage body 1, a radiopaque pin 2 for intraoperative imaging and positioning, and a composite coating 3. The fusion cage body is made of PEEK resin (PEEK 450PF powder produced by Victrex, UK). The contact surface between the fusion cage body and the vertebral body is designed with a toothed structure for product anti-retraction. The composite coating covers the surface of the toothed structure.

[0085] The composite coating is a composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device, which includes a transition layer covering the tooth surface of the pretreated atlantoaxial PEEK interbody fusion device and a hydroxyapatite coating on the surface of the transition layer.

[0086] The preparation method for the pre-treated atlantoaxial PEEK interbody fusion cage tooth surface includes the following steps:

[0087] The fusion device body 1 was immersed in 85wt% concentrated sulfuric acid at a solid-liquid ratio of 1g:10mL, and the temperature was controlled at 60℃. The reaction was carried out under stirring conditions for 6h. After washing with ice water and drying, the pretreated atlantoaxial PEEK interbody fusion device was obtained.

[0088] The method for preparing the transition layer includes the following steps:

[0089] S11: Add the epoxidized hydroxyapatite and sulfolane prepared in Example 4 into the reaction vessel and disperse them evenly. Control the temperature at 210°C to obtain solution A.

[0090] S12: Add the phosphorylated PEEK and sulfolane prepared in Example 4 to the reaction vessel and heat to 250°C. Stir to dissolve and then add solution A under the heat preservation condition to disperse evenly to obtain the transition layer slurry.

[0091] S13: The transition layer slurry was coated onto the tooth surface of the atlantoaxial PEEK interbody fusion device. High-temperature sintering was performed at a controlled temperature of 270℃ for 15 minutes, followed by a controlled temperature of 170℃ and a heat treatment for 12 hours to obtain a transition layer with a thickness of 125 μm. The transition layer contained 30 wt% epoxidized hydroxyapatite.

[0092] The preparation method of hydroxyapatite coating includes the following steps:

[0093] S21: The nano-hydroxyapatite prepared in Example 1 was mixed with distilled water to obtain a suspension with a solid content of 15%.

[0094] S22: The suspension was sprayed using plasma spraying technology (gas flow rate 180L / min, arc current 180A, spraying distance 80mm) to obtain a hydroxyapatite coating with a thickness of 75um.

[0095] Comparative Example 1

[0096] The preparation method of nano-hydroxyapatite includes the following steps:

[0097] Using 2.5 mol / L calcium nitrate tetrahydrate [Ca(NO3)2·4H2O] aqueous solution and 1.5 mol / L diammonium hydrogen phosphate [(NH4)2HPO4] aqueous solution as raw materials, a Ca:P molar ratio of 16.7:10 was prepared. The pH was adjusted to 10 with 30 wt% ammonia water, and the temperature was controlled at 70℃. The reaction was kept at this temperature, filtered, aged for 36 h, and dialyzed with deionized water to remove ammonia and salt, thus obtaining nano-hydroxyapatite.

[0098] Comparative Example 2

[0099] The preparation method of epoxidized hydroxyapatite includes the following steps:

[0100] 630 mL of anhydrous ethanol and 70 mL of deionized water were added to the reaction vessel and dispersed evenly. Acetic acid buffer was added to adjust the pH to 4. 35 mL of γ-glycidyl etheroxypropyltriethoxysilane was added and stirred at room temperature for 0.5 h. 10 g of nano-hydroxyapatite prepared in Comparative Example 1 was added and dispersed evenly. The temperature was controlled at 65 °C and stirred for 2 h. After filtration, washing with water and drying, epoxidized hydroxyapatite was obtained.

[0101] The preparation method of phosphorylated PEEK includes the following steps:

[0102] A1: Add 10g of polyetheretherketone (PEEK 450PF powder produced by Victrex, UK) and 650mL of 85wt% concentrated sulfuric acid to a reaction vessel, control the temperature at 0℃, disperse until the solution becomes transparent, add 120mL of chloromethyl octyl ether, keep warm and stir for 1h, add ice water to stop the reaction, filter, wash with water until neutral, wash with ethanol and dry to obtain component one;

[0103] A2: Add 10g of component one and 300mL of N-methylpyrrolidone to a reaction vessel and disperse evenly. Add 30mL of triethyl phosphite, control the temperature at 110℃, and keep the reaction at this temperature for 18h. Remove the triethyl phosphite by vacuum distillation, wash with water, dry, add 36wt% concentrated hydrochloric acid, heat under reflux for 12h, filter, wash with water, and dry to obtain phosphorylated PEEK.

[0104] Comparative Example 3

[0105] Please see Figure 1 The atlantoaxial PEEK interbody fusion cage includes a fusion cage body 1, a radiopaque pin 2 for intraoperative imaging and positioning, and a composite coating 3. The fusion cage body is made of PEEK resin (PEEK 450PF powder produced by Victrex, UK). The contact surface between the fusion cage body and the vertebral body is designed with a toothed structure for product anti-retraction. The composite coating covers the surface of the toothed structure.

[0106] The composite coating is a composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device, which includes a transition layer covering the tooth surface of the pretreated atlantoaxial PEEK interbody fusion device and a hydroxyapatite coating on the surface of the transition layer.

[0107] The preparation method for the pre-treated atlantoaxial PEEK interbody fusion cage tooth surface includes the following steps:

[0108] The fusion device body 1 was immersed in 85wt% concentrated sulfuric acid at a solid-liquid ratio of 1g:10mL, and the temperature was controlled at 60℃. The reaction was carried out under stirring conditions for 6h. After washing with ice water and drying, the pretreated atlantoaxial PEEK interbody fusion device was obtained.

[0109] The method for preparing the transition layer includes the following steps:

[0110] S11: Add the epoxidized hydroxyapatite and sulfolane prepared in Comparative Example 2 into the reaction vessel and disperse them evenly. Control the temperature at 210℃ to obtain solution A.

[0111] S12: Add the phosphorylated PEEK and sulfolane prepared in Comparative Example 2 into the reactor and heat to 250°C. Stir to dissolve and then add solution A under the heat preservation condition to disperse evenly, thus obtaining the transition layer slurry.

[0112] S13: The transition layer slurry was coated onto the tooth surface of the atlantoaxial PEEK interbody fusion device. High-temperature sintering was performed at a controlled temperature of 270℃ for 15 minutes, followed by a controlled temperature of 170℃ and a heat treatment for 12 hours to obtain a transition layer with a thickness of 125 μm. The transition layer contained 30 wt% epoxidized hydroxyapatite.

[0113] The preparation method of hydroxyapatite coating includes the following steps:

[0114] S21: The nano-hydroxyapatite prepared in Comparative Example 1 was mixed with distilled water to obtain a suspension with a solid content of 15%.

[0115] S22: The suspension was sprayed using plasma spraying technology (gas flow rate 180L / min, arc current 180A, spraying distance 80mm) to obtain a hydroxyapatite coating with a thickness of 75um.

[0116] Comparative Example 4

[0117] Compared with Example 6, Comparative Example 4 only replaced the epoxidized hydroxyapatite prepared in Example 3 used in Example 6 to prepare the transition layer with an equal amount of the hydroxyapatite prepared in Example 1. The remaining components and preparation methods in Comparative Example 4 are completely the same as those in Example 6.

[0118] Comparative Example 5

[0119] Compared with Example 6, Comparative Example 5 only replaced the phosphorylated PEEK prepared in Example 3 in Example 6 with an equal amount of PEEK resin (PEEK 450PF powder produced by Victrex, UK) in the preparation of the transition layer. The remaining components and preparation methods in Comparative Example 5 were completely the same as those in Example 6.

[0120] Comparative Example 6

[0121] Please see Figure 1 The atlantoaxial PEEK interbody fusion cage includes a fusion cage body 1, a radiopaque screw 2 for intraoperative imaging and positioning, and a composite coating 3. The fusion cage body is made of PEEK resin (PEEK 450PF powder produced by Victrex, UK). The contact surface between the fusion cage body and the vertebral body is designed with a toothed structure for preventing product slippage. The composite coating covers the surface of the toothed structure. The composite coating is a hydroxyapatite coating.

[0122] The composite coating is a composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device, including a hydroxyapatite coating covering the tooth surface of the pretreated atlantoaxial PEEK interbody fusion device.

[0123] The preparation method for the pre-treated atlantoaxial PEEK interbody fusion cage tooth surface includes the following steps:

[0124] The fusion device body 1 was immersed in 85wt% concentrated sulfuric acid at a solid-liquid ratio of 1g:10mL, and the temperature was controlled at 60℃. The reaction was carried out under stirring conditions for 6h. After washing with ice water and drying, the pretreated atlantoaxial PEEK interbody fusion device was obtained.

[0125] The preparation method of hydroxyapatite coating includes the following steps:

[0126] S21: The nano-hydroxyapatite prepared in Example 1 was mixed with distilled water to obtain a suspension with a solid content of 15%.

[0127] S22: The suspension was sprayed using plasma spraying technology (gas flow rate 180L / min, arc current 180A, spraying distance 80mm) to obtain a hydroxyapatite coating with a thickness of 200um.

[0128] Comparative Example 7

[0129] Please see Figure 1 The atlantoaxial PEEK interbody fusion cage includes a fusion cage body 1, a radiopaque pin 2 for intraoperative imaging and positioning, and a composite coating 3. The fusion cage body is made of PEEK resin (PEEK 450PF powder produced by Victrex, UK). The contact surface between the fusion cage body and the vertebral body is designed with a toothed structure for product anti-retraction. The composite coating covers the surface of the toothed structure.

[0130] The composite coating is a composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device, including a transition layer covering the tooth surface of the atlantoaxial PEEK interbody fusion device and a hydroxyapatite coating on the surface of the transition layer.

[0131] The method for preparing the transition layer includes the following steps:

[0132] S11: Add the epoxidized hydroxyapatite and sulfolane prepared in Example 3 into the reaction vessel and disperse them evenly. Control the temperature at 210°C to obtain solution A;

[0133] S12: Add the phosphorylated PEEK and sulfolane prepared in Example 3 into the reaction vessel and heat to 250°C. Stir to dissolve and then add solution A under the heat preservation condition to disperse evenly to obtain the transition layer slurry.

[0134] S13: The transition layer slurry was coated onto the tooth surface of the atlantoaxial PEEK interbody fusion device. High-temperature sintering was performed at a controlled temperature of 270℃ for 15 minutes, followed by a controlled temperature of 170℃ and a heat treatment for 12 hours to obtain a transition layer with a thickness of 125 μm. The transition layer contained 30 wt% epoxidized hydroxyapatite.

[0135] The preparation method of hydroxyapatite coating includes the following steps:

[0136] S21: The nano-hydroxyapatite prepared in Example 1 was mixed with distilled water to obtain a suspension with a solid content of 15%.

[0137] S22: The suspension was sprayed using plasma spraying technology (gas flow rate 180L / min, arc current 180A, spraying distance 80mm) to obtain a hydroxyapatite coating with a thickness of 75um.

[0138] Performance testing

[0139] (1) Contact angle: The SL2008 water contact meter was used to test the water contact angle. A droplet of 2 μL of deionized water was dropped freely from the needle (OD=1 mm, ID=0.82 mm) onto the surface of the composite coating. The angle between the solid and liquid interfaces when the droplet stabilized on the surface of the auxiliary material was measured as the water contact angle. The test results are shown in Table 1.

[0140] (2) Bonding strength: The bonding strength of the coating was tested using a WS-2005 automatic coating adhesion scratch tester. The critical load was determined based on the acoustic emission signal captured in the scratch test. The indenter was slid across the coating surface, and the load was continuously increased during the process. When the critical value Lc (critical load) was reached, the coating began to peel off from the substrate. At this time, the critical load was the coating bonding strength. The test results are shown in Table 1.

[0141] (3) Solubility: Record the weight W of the sample when it is dried. 干 The samples were immersed in centrifuge tubes filled with 50 mL of phosphate-buffered saline (PBS) for 21 days, then removed and dried. The mass loss of the coating was calculated, and the results are shown in Table 1.

[0142] Prepare phosphate buffer: Dissolve 8.0g NaCl, 0.2g KCl, 1.4g Na2HPO4 and 0.2g KH2PO4 in 1000mL of distilled water, adjust the pH to 4 with 1mol / L citric acid, dispense into autoclaves and store at 4℃.

[0143] Table 1: Statistical Table of Mechanical Property Test Data for Examples 5-7 and Comparative Examples 3-7

[0144]

[0145] As shown in Table 1, the hydroxyapatite prepared in this application, used as a raw material for the hydroxyapatite coating, effectively regulates the hydrophilicity of the coating by doping with fluorine ions. The contact angle of the coatings prepared in Examples 5-7 of this application is close to 70°, which is the most suitable angle for cell adhesion and can accelerate cell migration. This application effectively addresses the problem of easy coating detachment caused by the difference in mechanical properties between hydroxyapatite and PEEK by setting a transition layer between the hydroxyapatite coating and the PEEK substrate. The prepared material can be used in biological organisms for a long time. In addition, the water absorption rate and swelling rate of the material prepared in this application are 0% after soaking in PBS for 16 days, and there is no change in mass and volume. That is, in the body fluid environment, the structure and function of the material prepared in this application are stable, ensuring support and reconstruction of surrounding bone tissue.

[0146] (4) Biocompatibility

[0147] Cell culture: MC3T3-E1 cells (mouse embryonic osteoblast precursor cells purchased from Wuhan Pronosai Company) were selected and cultured in serum cell culture medium (DMEM) containing 89% DMEM+F12, 10% fetal bovine serum (FBS), 1% penicillin and streptomycin in a sterile incubator at 37°C, 5% CO2 concentration and 95% humidity.

[0148] ① Cell proliferation detection

[0149] The materials prepared in Examples 5-7 and Comparative Examples 3-7 were placed in 24-well plates, and MC3T3-E1 cells were introduced at a density of 5 × 10⁻⁶ cells / well. 3 Cells were seeded at a density of 1 mL / well on the material, with 1 mL of liquid per well. The plates were gently washed with PBS on days 1, 3, and 7, and cell proliferation was then measured using a CCK-8 assay kit. Details are as follows: CCK-8 stock solution was mixed with ordinary culture medium at a ratio of 1:10 to prepare a working solution (premixed). 100 μL of the working solution was added to each well of the sample plate. A blank plate was also prepared with 100 μL added to each well as a control. The plates were incubated at 37°C for 2.5 h. Finally, the incubated liquid was transferred to a 96-well plate and the absorbance was measured at 450 nm using an ELx800 microplate reader. The absorbance of the sample plate minus the absorbance of the blank plate reflects the cell proliferation status; the results are shown in Table 3.

[0150] ②Cytotoxicity detection

[0151] The materials prepared in Examples 5-7 and Comparative Examples 3-7 were placed in 24-well plates, and MC3T3-E1 cells were introduced at a concentration of 1×10⁻⁶. 4Seeds were placed on the material at a density of / ml / well, with 1mL of liquid per well. After 24 hours, the plates were gently washed with PBS, and then cytotoxicity was detected using a Calcein-AM / PI double staining kit. Details are as follows: Following the manufacturer's instructions, Calcein-AM and PI were added to PBS to prepare working solutions with final concentrations of 2μM and 4.5μM, respectively. The liquid volume per well was sufficient to cover the slide. Staining was performed at room temperature for 15 minutes, avoiding light throughout the process. Finally, observation was conducted using a fluorescence microscope. Cytotoxicity was reflected by relative growth rate (RGR). The cytotoxicity criteria for RGR determination are shown in Table 2, and the detection results are shown in Table 3.

[0152] Table 2: Cytotoxicity Criteria for RGR Assay

[0153]

[0154] Table 3: Statistical table of biocompatibility test data for Examples 5-7 and Comparative Examples 3-7

[0155]

[0156] As shown in Table 3, when MC3T3-E1 cells were cultured on the coatings prepared in Examples 5-7 and Comparative Examples 3-7 of this application, it can be seen that the coatings prepared in this application provide an environment conducive to osteoblast attachment and have the best cell proliferation activity. This can promote the initial adhesion and spread of osteoblasts on the material surface, which is beneficial to the further growth of osteoblasts and the rapid formation of early bone tissue.

[0157] The foregoing has provided a detailed description of one embodiment of the present invention, but this description is merely a preferred embodiment and should not be construed as limiting the scope of the invention. All equivalent variations and modifications made within the scope of the claims of this invention should still fall within the patent coverage of this invention.

Claims

1. A composite coating on the tooth surface of an atlantoaxial PEEK interbody fusion device, characterized in that, This includes a transition layer covering the tooth surface of the atlantoaxial PEEK interbody fusion cage and a hydroxyapatite coating on the surface of the transition layer. The method for preparing the transition layer includes the following steps: S1: Add epoxidized hydroxyapatite and sulfolane to a reaction vessel and disperse them evenly. Control the temperature at 210-220℃ to obtain solution A. S2: Add phosphorylated PEEK and sulfolane to a reaction vessel, heat and stir to dissolve, and add solution A under heat preservation conditions to disperse evenly, thus obtaining a transition layer slurry; S3: The transition layer slurry is coated on the tooth surface of the atlantoaxial PEEK intervertebral fusion device, sintered at high temperature and heat-treated to obtain the transition layer; The preparation method of the epoxidized hydroxyapatite includes the following steps: Anhydrous ethanol and deionized water were added to the reaction vessel and dispersed evenly. The pH was adjusted to 4-5. γ-glycidyl etheroxypropyltriethoxysilane was added and stirred at room temperature for 0.5-1 h. Nano-hydroxyapatite was added, and the temperature was controlled at 60-65℃. The mixture was kept warm and stirred for 2-4 h. After filtration, washing with water, and drying, epoxidized hydroxyapatite was obtained. The preparation method of the hydroxyapatite includes the following steps: 0.5-2.5 mol / L calcium nitrate tetrahydrate aqueous solution, 0.5-3 mol / L diammonium hydrogen phosphate aqueous solution, and ammonium fluoride are mixed and the pH is adjusted to 9-10. The temperature is controlled at 60-90℃, the reaction is kept at the temperature, filtered, aged for 24-48 hours, and dialyzed with deionized water to remove ammonia and salt, so as to obtain nano-hydroxyapatite. The preparation method of the phosphorylated PEEK includes the following steps: A1: Add polyetheretherketone and concentrated sulfuric acid to a reaction vessel, control the temperature at 0-5℃, disperse until the solution becomes transparent, add chloromethyl octyl ether, keep warm and stir for 1-3 hours, add ice water to stop the reaction, filter, wash with water until neutral, wash with ethanol and dry to obtain component one; A2: Add component 1 and N-methylpyrrolidone to the reaction vessel and disperse evenly. Add triethyl phosphite, control the temperature at 110-120℃, and keep the reaction at this temperature for 12-18 hours. Remove triethyl phosphite by vacuum distillation, wash with water, dry, add concentrated hydrochloric acid, heat under reflux for 9-15 hours, filter, wash with water, and dry to obtain phosphorylated PEEK.

2. The composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device according to claim 1, characterized in that, The epoxidized hydroxyapatite accounts for 30-50% of the total mass of the transition layer.

3. The composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device according to claim 1, characterized in that, The thickness of the transition layer is 15-125 μm.

4. The composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device according to claim 1, characterized in that, The addition ratio of anhydrous ethanol, deionized water, γ-glycidyl etheroxypropyltriethoxysilane, and nano-hydroxyapatite is 45-90 mL: 5-10 mL: 2.5-5 mL: 1 g.

5. The composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device according to claim 1, characterized in that, The addition ratio of polyether ether ketone, concentrated sulfuric acid, and chloromethyl octyl ether in A1 is 1g: 50-75mL: 8-15mL.

6. The composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device according to claim 1, characterized in that, The addition ratio of component A2, N-methylpyrrolidone, and triethyl phosphite is 1g: 20-40mL: 2-4mL.

7. The composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device according to claim 1, characterized in that, The hydroxyapatite coating is made by preparing a suspension from nano-hydroxyapatite, which is then obtained through plasma spraying technology. The thickness of the hydroxyapatite coating is 45-75 μm.

8. The composite coating on the tooth surface of the atlantoaxial PEEK interbody fusion device according to claim 1, characterized in that, The calcium nitrate tetrahydrate aqueous solution, diammonium hydrogen phosphate aqueous solution, and ammonium fluoride were prepared in a Ca:P:F molar ratio of 16.7:10:

1.

9. A composite coating on the tooth surface of an atlantoaxial PEEK interbody fusion device according to any one of claims 1-8, characterized in that, The transition layer is applied to the surface of the PEEK component of the atlantoaxial PEEK interbody fusion device; the PEEK component is obtained by surface sulfonation treatment of PEEK resin.

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