PEEK-based antibacterial orthopedic internal implant medical device product and preparation method thereof

Abstract

The application discloses a PEEK-based antibacterial orthopedic internal implant medical device product and a preparation method thereof. The method comprises the following steps: 1) pre-treating the surface of a PEEK base; 2) after plasma cleaning, roughening the surface by low-pressure plasma activation etching, and then implanting titanium ions into the PEEK base; 3) introducing a titanium film on the surface of the base by magnetron sputtering, and combining an anodic oxidation process to controllably construct a TiO2 nanotube structure on the titanium film; and 4) loading an AgNO3 / carboxymethyl chitosan mixed solution into the pore channel of the TiO2 nanotube by ultrasonic, and obtaining a carboxymethyl chitosan / silver complex by in-situ ultraviolet light reduction. The application enhances the bonding strength between the titanium coating and the PEEK material by ion implantation combined with magnetron sputtering technology, constructs a coating containing Ag-TiO2 on the surface of the PEEK, and the coating has long-acting broad-spectrum antibacterial property, high biocompatibility and osteogenesis promotion performance, and can be used for solving the serious postoperative infection problem in orthopedics.

Description

Technical Field

[0001] This invention relates to the field of medical devices, specifically to a PEEK-based antibacterial orthopedic implantable medical device product and its preparation method. Background Technology

[0002] Polyetheretherketone (PEEK) is a high-performance engineering thermoplastic that has shown great promise in the medical field due to its high strength, biocompatibility, and wear resistance. Compared with traditional bioceramic materials, PEEK has an elastic modulus closer to that of cortical bone and a low coefficient of friction, so it has already been used clinically in the form of artificial hip joints and femoral prostheses, attracting the interest of doctors and researchers. However, as an inert polymer material, PEEK's surface inertness leads to poor cell-bone integration and it lacks antibacterial properties, which seriously hinders its further application in orthopedics.

[0003] Surface modification of materials is a highly effective technique for solving the aforementioned problems. It can improve the osteointegration ability between the material and bone tissue without altering the material's inherent superior properties, facilitating osteoblast adhesion, proliferation, and differentiation. Simultaneously, it can introduce antibacterial active components to combat infection. However, the insufficient bonding strength of PEEK after direct surface modification remains a critical challenge for orthopedic applications.

[0004] The "Guiding Opinions on Promoting the Healthy Development of the Pharmaceutical Industry" explicitly encourages domestic medical device companies to strengthen technological innovation and improve their core competitiveness; it also clearly proposes to achieve import substitution and accelerate the transformation and upgrading of medical devices. Therefore, this invention innovatively designs a PEEK-based antibacterial orthopedic implantable medical device. Ion implantation technology combined with magnetron sputtering titanium plating enhances the bonding strength between the coating and the PEEK material, preventing coating detachment. Simultaneously, the Ag-TiO2 coating constructed on the titanium film on the PEEK surface exhibits excellent long-lasting broad-spectrum antibacterial activity, high biocompatibility, and bone-growth promoting properties, which can be used to solve the severe infection problems after orthopedic surgery. Summary of the Invention

[0005] The purpose of this invention is to address the problems of PEEK lacking bone-promoting and anti-infection functions, as well as weak coating adhesion after surface modification. This invention provides a PEEK-based antibacterial orthopedic implantable medical device product and its preparation method. By combining a composite process, a PEEK-based antibacterial orthopedic implantable medical device product with excellent coating adhesion strength and excellent long-lasting antibacterial, biocompatibility and bone-promoting properties is obtained, thereby effectively solving the above-mentioned problems.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A PEEK-based antibacterial orthopedic implantable medical device product is made from PEEK, titanium, silver nitrate, and carboxylated chitosan as the main raw materials. It is manufactured using a combination of processes including plasma glow discharge cleaning, low-pressure plasma etching, ion implantation, magnetron sputtering, anodizing, ultrasound-assisted implantation, and in-situ ultraviolet reduction. Titanium ions are sequentially implanted into the PEEK matrix to form a titanium thin film layer, and then a TiO2 nanotube layer with a carboxylated chitosan / silver complex is formed.

[0008] Its preparation method specifically includes the following steps:

[0009] 1) The PEEK substrate surface is subjected to pretreatment in sequence, including degreasing, cleaning, and drying;

[0010] 2) After the pretreated PEEK is transferred into a vacuum furnace and vacuumed, the substrate surface is thoroughly cleaned using plasma glow discharge cleaning process, and then low-pressure plasma activation etching is combined to increase the surface roughness of the substrate; then, titanium ions are implanted into the PEEK substrate using a medium-current ion implanter.

[0011] 3) Start the titanium target power supply and deposit a titanium film on the substrate surface after 2) through magnetron sputtering; then use an organic electrolyte for anodic oxidation to form TiO2 nanotube structure on the titanium film;

[0012] 4) The previous material was immersed in an AgNO3 / carboxylated chitosan mixed solution and subjected to in-situ loading using ultrasound. Then, an in-situ ultraviolet light reduction process was used to form a carboxylated chitosan / silver complex in the TiO2 nanotube channels. Finally, after cleaning, sterilization and vacuum packaging, a PEEK-based antibacterial orthopedic implantable medical device product was obtained.

[0013] Furthermore, in step 1), the degreasing agent used in the degreasing process is an aqueous solution containing 60-80 g / L NaOH, 20-40 g / L Na2CO3, and 1-3 g / L OP; the cleaning process involves sequentially washing with room temperature deionized water, 60°C deionized water, and room temperature deionized water, with each cleaning session lasting 15-30 minutes, to thoroughly remove any degreasing agent residue.

[0014] In step 2), the substrate surface is cleaned using plasma glow discharge for 2-15 minutes to activate it and increase the contact angle. The gas used is one of argon, hydrogen, oxygen, or a fluorine-containing gas. In low-pressure plasma activation etching, the plasma sputtering pressure is 1-8 Pa, the plasma sputtering time is 100-1000 s, and the plasma sputtering voltage is 20-70 V. This treatment enhances the surface energy of the PEEK substrate, making surface activation and etching more conducive to ion implantation.

[0015] In step 2), titanium ions are implanted into the PEEK substrate using a medium-current ion implanter, with an implantation vacuum of 1-5 × 10⁻⁵. -3 The implantation energy was 10-70 keV, the beam current was 1-6 Ma, and the implantation time was 20-90 min. By adjusting the above parameters, a titanium ion implantation dose of 10 Pa was achieved on the PEEK substrate. 13 -10 17 ion / cm 2 .

[0016] In step 3), a titanium film with a thickness of 1-5 μm is deposited by magnetron sputtering, preferably with a thickness of 3-5 μm.

[0017] First, control the vacuum level of the cavity to less than 0.02 Pa, then introduce argon gas at a pressure of 50-200 sccm to maintain a vacuum level of 0.25-0.85 Pa, preferably 0.45-0.65 Pa; the current intensity is 0.5-5 A, preferably 2-3 A; the direction and speed of the rotating frame are switched between forward and reverse, with a rotation speed of 5.0-20.0 Hz; the time is 20-150 minutes, preferably 60-70 minutes.

[0018] The anodizing of the organic electrolyte in step 3) is specifically as follows: the titanium-plated PEEK thin film sample is placed in a titanium alloy fixture as the anode, and the cathode is a graphite electrode with a distance of 10-20 cm between the two electrodes; the oxidation voltage is 10-60V, preferably 40-50V; the oxidation time is 30-120 minutes, preferably 100-120 minutes; the reaction temperature is 20-30℃; the electrolyte formula is: ethylene glycol / glycerol mixed solution, ammonium fluoride, and the remainder is deionized water, and the concentration of the ethylene glycol / glycerol mixed solution is 50wt%, wherein the mass ratio of ethylene glycol and glycerol is one of 3:1, 2:1, 1:1, 1:2, 1:3, and the concentration of ammonium fluoride is 0.2-1.0wt%; the anodized sample is then ultrasonically cleaned with deionized water, cleaned with anhydrous ethanol, and dried. The resulting titanium thin film surface is oxidized to form an ordered TiO2 nanotube structure with a nanotube diameter of 50-120 nm.

[0019] In step 4), the concentration of AgNO3 in the AgNO3 / carboxylated chitosan mixed solution is 1.5-3 wt%, the number average molecular weight of carboxylated chitosan is 300,000-700,000, the degree of carboxylation is 70-90%, and the concentration is 0.1-0.5 wt%; the ultrasonic power is 80-120 W, the ultrasonic time is 1-2 h, and the ultraviolet light intensity is 80-150 mW / cm². 2 The irradiation time is 2-6 hours.

[0020] Compared with the prior art, the beneficial effects / innovations of the present invention are as follows:

[0021] 1) The PEEK-based antibacterial orthopedic implantable medical device product uses PEEK, titanium, silver nitrate, carboxylated chitosan, etc. as raw materials, and is manufactured using a combination of processes such as plasma glow discharge cleaning, low-pressure plasma etching, ion implantation, magnetron sputtering, anodizing, ultrasound-assisted implantation, and in-situ ultraviolet reduction. The selection and design of the above raw materials and processes together achieve excellent coating bonding strength and comprehensive performance of excellent long-lasting antibacterial, biocompatibility and osteopromoting properties.

[0022] 2) This invention innovatively uses a polymer as a substrate, introduces a high-bonding-strength metal coating on its surface (first-level modification stage), and further modifies the metal coating through multiple modifications (second-level modification stage). This successfully introduces a metal composite coating material with antibacterial and osteogenic activities onto the surface of an inert polymer, and effectively achieves successful fusion of the organic-inorganic interface. The coating bonding strength is greater than 25 MPa, overcoming the problems of PEEK's lack of biological activity and weak coating bonding strength after surface modification, thus extending and expanding the application of PEEK materials in the field of orthopedics.

[0023] 3) The PEEK-based antibacterial orthopedic implantable medical device product prepared by this invention simultaneously possesses high biocompatibility, osteopromoting properties, and anti-infection capabilities. These functions stem from the synergistic effect of various raw materials and processes employed in this invention: the synergistic use of four processes—plasma glow discharge cleaning, low-pressure plasma etching, ion implantation, and magnetron sputtering. First, plasma glow discharge cleaning cleans the substrate. Second, low-pressure plasma etching forms a micro-nano rough structure on the substrate surface. Ion implantation allows titanium ions to penetrate the PEEK matrix. Further, magnetron sputtering deposits a titanium film with high bonding strength. The second stage involves anodic oxidation to form osteopromoting titanium nanotubes. Finally, in-situ ultraviolet reduction is used to form carboxylated chitosan / silver complexes within the titanium nanotubes, introducing antibacterial functionality.

[0024] 4) This invention fully utilizes a multi-fusion design approach. First, titanium ions are fused into the PEEK matrix through ion implantation. Second, the micro-nano rough surface formed by low-pressure plasma etching facilitates the fusion of the titanium film and the PEEK surface, and their mechanical interlocking effect can greatly enhance the degree of fusion. Moreover, the TiO2 nanotubes are directly formed on the titanium film, and the two are an integral whole. Fourth, the ultrasonic process promotes the fusion of silver nitrate / carboxylated chitosan solution into the TiO2 nanotubes, and after in-situ ultraviolet light reduction, a complex of silver and carboxylated chitosan is formed. The carboxyl groups of carboxylated chitosan can chelate with metal ions, which is beneficial for the slow release of silver after reduction and long-lasting antibacterial effect. Attached Figure Description

[0025] Figure 1SEM image of the anodizing stage during the manufacturing process of PEEK-based antibacterial orthopedic implantable medical devices;

[0026] Figure 2 SEM image of carboxylated chitosan / silver complex formed on the surface after the in-situ ultraviolet reduction stage during the preparation of PEEK-based antibacterial orthopedic implantable medical device products. Detailed Implementation

[0027] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0028] Example 1:

[0029] 1) First, the PEEK surface is degreased using a degreasing agent (an aqueous solution containing 60g / L NaOH, 40g / L Na2CO3, and 3g / L OP); then it is rinsed with deionized water at room temperature, then with deionized water at 60℃, and then with deionized water at room temperature, each rinse lasting 30 minutes to thoroughly remove any degreasing agent residue; finally, the sample is dried in a 60℃ oven for 2 hours.

[0030] 2) After the pretreated PEEK is transferred into a vacuum furnace and evacuated, the substrate surface is thoroughly cleaned for 15 minutes using plasma glow discharge cleaning with argon gas. Then, low-pressure plasma activation etching is used to increase the surface roughness of the substrate. The plasma sputtering pressure is 1 Pa, the plasma sputtering time is 500 s, and the plasma sputtering voltage is 50 V. Finally, titanium ions are implanted into the PEEK substrate using a medium-current ion implanter with an implantation vacuum of 10... -3 The implantation parameters were set as follows: Pa, implantation energy 70 keV, beam current 3 Ma, and implantation time 30 min. By adjusting these parameters, a titanium ion implantation dose of 10-1 was achieved on the PEEK substrate. 15 ion / cm 2 ;

[0031] 3) Start the titanium target power supply and deposit a titanium film with a thickness of 3 μm on the substrate surface by magnetron sputtering. The specific operating parameters for this process are as follows: first, control the vacuum degree of the cavity to less than 0.02 Pa, then introduce argon gas at a pressure of 100 sccm to maintain a vacuum degree of 0.5 Pa, and a current intensity of 2 A; the rotating frame is in the positive direction, the rotation speed is 10.0 Hz, and the time is 60 minutes. Then, anodizing was performed using an organic electrolyte (specific parameters for anodizing were: titanium alloy clamp as anode, graphite electrode as cathode, electrode spacing of 20 cm, oxidation voltage of 15 V, oxidation time of 120 minutes, and reaction temperature of 25 °C; the electrolyte formulation was: 50 wt% ethylene glycol / glycerol mixed solution, 1.0 wt% ammonium fluoride, and the remainder being deionized water, with the ratio of ethylene glycol to glycerol in the ethylene glycol / glycerol mixed solution being 1:1), to oxidize the titanium film to form TiO2 nanotube structures. The sample was then sequentially cleaned with deionized ultrasonic cleaning, anhydrous ethanol cleaning, and dried. The final pore size of the nanotubes was approximately 50 nm.

[0032] 4) The previous material was immersed in an AgNO3 / carboxylated chitosan mixed solution (AgNO3 concentration 1.5wt%, carboxylated chitosan number-average molecular weight 700,000, degree of carboxylation 90%, concentration 0.2wt%), and in-situ loading was performed using ultrasound (ultrasound power 120W, ultrasound time 1h), followed by in-situ ultraviolet reduction (UV light intensity 100mW / cm²). 2 (Irradiation time of 4 hours) forms carboxylated chitosan / silver complex in the pores of TiO2 nanotubes. Finally, after cleaning, sterilization and vacuum packaging, PEEK-based antibacterial orthopedic implantable medical device products are obtained.

[0033] The PEEK-based antibacterial orthopedic implantable medical device product prepared by the above process exhibits high hydrophilicity (contact angle 18.4°), the bonding strength between the titanium composite coating and the PEEK substrate reaches 28.4 MPa, CCK-8 results show that the material has good biocompatibility (compared to the group cultured in the well plate, the cell survival rate reaches 92.6%), and has good antibacterial properties, with a bacteriostatic rate of 94.3%.

[0034] Example 2:

[0035] 1) First, the PEEK surface is degreased using a degreasing agent (an aqueous solution containing 60g / L NaOH, 40g / L Na2CO3, and 3g / L OP); then it is rinsed with deionized water at room temperature, then with deionized water at 60℃, and then with deionized water at room temperature, each rinse lasting 30 minutes to thoroughly remove any degreasing agent residue; finally, the sample is dried in a 60℃ oven for 2 hours.

[0036] 2) After the pretreated PEEK is transferred into a vacuum furnace and evacuated, the substrate surface is thoroughly cleaned for 15 minutes using plasma glow discharge cleaning with argon gas. Then, low-pressure plasma activation etching is used to increase the surface roughness of the substrate. The plasma sputtering pressure is 1 Pa, the plasma sputtering time is 500 s, and the plasma sputtering voltage is 50 V. Finally, titanium ions are implanted into the PEEK substrate using a medium-current ion implanter with an implantation vacuum of 10... -3 The implantation parameters were set as follows: Pa, implantation energy 70 keV, beam current 3 Ma, and implantation time 30 min. By adjusting these parameters, a titanium ion implantation dose of 10-1 was achieved on the PEEK substrate. 15 ion / cm 2 ;

[0037] 3) Start the titanium target power supply and deposit a titanium film with a thickness of 3 μm on the substrate surface by magnetron sputtering. The specific operating parameters for this process are as follows: first, control the vacuum degree of the cavity to less than 0.02 Pa, then introduce argon gas at a pressure of 100 sccm to maintain a vacuum degree of 0.5 Pa, and a current intensity of 2 A; the rotating frame is in the positive direction, the rotation speed is 10.0 Hz, and the time is 60 minutes. Then, anodizing was performed using an organic electrolyte (specific parameters for anodizing were: titanium alloy clamp as anode, graphite electrode as cathode, electrode spacing of 20 cm, oxidation voltage of 15 V, oxidation time of 120 minutes, and reaction temperature of 25 °C; the electrolyte formulation was: 50 wt% ethylene glycol / glycerol mixed solution, 1.0 wt% ammonium fluoride, and the remainder being deionized water, with the ratio of ethylene glycol to glycerol in the ethylene glycol / glycerol mixed solution being 1:1), to oxidize the titanium film to form TiO2 nanotube structures. The sample was then sequentially cleaned with deionized ultrasonic cleaning, anhydrous ethanol cleaning, and dried. The final pore size of the nanotubes was approximately 50 nm.

[0038] 4) The previous material was immersed in an AgNO3 / carboxylated chitosan mixed solution (AgNO3 concentration 3wt%, carboxylated chitosan number-average molecular weight 700,000, degree of carboxylation 90%, concentration 0.5wt%), and in-situ loading was performed using ultrasound (ultrasound power 120W, ultrasound time 1h), followed by in-situ ultraviolet reduction (UV light intensity 150mW / cm²). 2 (Irradiation time of 6 hours) forms carboxylated chitosan / silver complex in the pores of TiO2 nanotubes. Finally, after cleaning, sterilization and vacuum packaging, PEEK-based antibacterial orthopedic implantable medical device products are obtained.

[0039] Compared to Example 1, the concentration of AgNO3 / carboxylated chitosan and the reduction time were increased. The PEEK-based antibacterial orthopedic implantable medical device product prepared by the above process exhibited high hydrophilicity (contact angle 17.6°), the bonding strength between the titanium composite coating and the PEEK substrate reached 27.8 MPa, and the CCK-8 results showed that the material had good biocompatibility (the cell survival rate reached 90.4% compared to the group cultured in the well plate), and the antibacterial performance was slightly improved, with an inhibition rate of 98.3%.

[0040] Example 3:

[0041] 1) First, the PEEK surface is degreased using a degreasing agent (an aqueous solution containing 60g / L NaOH, 40g / L Na2CO3, and 3g / L OP); then it is rinsed with deionized water at room temperature, then with deionized water at 60℃, and then with deionized water at room temperature, each rinse lasting 30 minutes to thoroughly remove any degreasing agent residue; finally, the sample is dried in a 60℃ oven for 2 hours.

[0042] 2) After the pretreated PEEK is transferred into a vacuum furnace and evacuated, the substrate surface is thoroughly cleaned for 15 minutes using plasma glow discharge cleaning with argon gas. Then, low-pressure plasma activation etching is used to increase the surface roughness of the substrate. The plasma sputtering pressure is 8 Pa, the plasma sputtering time is 1000 s, and the plasma sputtering voltage is 70 V. Finally, titanium ions are implanted into the PEEK substrate using a medium-current ion implanter with an implantation vacuum of 10... -3 The implantation parameters were set as follows: Pa, implantation energy 70 keV, beam current 3 Ma, and implantation time 30 min. By adjusting these parameters, a titanium ion implantation dose of 10-1 was achieved on the PEEK substrate. 15 ion / cm 2 ;

[0043] 3) Start the titanium target power supply and deposit a titanium film with a thickness of 3 μm on the substrate surface by magnetron sputtering. The specific operating parameters for this process are as follows: first, control the vacuum degree of the cavity to less than 0.02 Pa, then introduce argon gas at a pressure of 100 sccm to maintain a vacuum degree of 0.5 Pa, and a current intensity of 2 A; the rotating frame is in the positive direction, the rotation speed is 10.0 Hz, and the time is 60 minutes. Then, anodizing was performed using an organic electrolyte (specific parameters for anodizing were: titanium alloy clamp as anode, graphite electrode as cathode, electrode spacing of 20 cm, oxidation voltage of 15 V, oxidation time of 120 minutes, and reaction temperature of 25 °C; the electrolyte formulation was: 50 wt% ethylene glycol / glycerol mixed solution, 1.0 wt% ammonium fluoride, and the remainder being deionized water, with the ratio of ethylene glycol to glycerol in the ethylene glycol / glycerol mixed solution being 1:1), to oxidize the titanium film to form TiO2 nanotube structures. The sample was then sequentially cleaned with deionized ultrasonic cleaning, anhydrous ethanol cleaning, and dried. The final pore size of the nanotubes was approximately 50 nm.

[0044] 4) The previous material was immersed in an AgNO3 / carboxylated chitosan mixed solution (AgNO3 concentration 1.5wt%, carboxylated chitosan number-average molecular weight 700,000, degree of carboxylation 90%, concentration 0.2wt%), and in-situ loading was performed using ultrasound (ultrasound power 120W, ultrasound time 1h), followed by in-situ ultraviolet reduction (UV light intensity 100mW / cm²). 2 (Irradiation time of 4 hours) forms carboxylated chitosan / silver complex in the pores of TiO2 nanotubes. Finally, after cleaning, sterilization and vacuum packaging, PEEK-based antibacterial orthopedic implantable medical device products are obtained.

[0045] Compared to Example 1, the gas pressure, time, and voltage of plasma sputtering were all increased. The PEEK-based antibacterial orthopedic implantable medical device product prepared by the above process exhibited high hydrophilicity (contact angle 17.8°), and the bonding strength between the titanium composite coating and the PEEK substrate was significantly improved, reaching 34.1 MPa. CCK-8 results showed that the material had good biocompatibility (cell survival rate reached 93.7% compared to the group cultured in the well plate) and good antibacterial properties, with a bacteriostatic rate of 92.6%.

[0046] Example 4:

[0047] 1) First, the PEEK surface is degreased using a degreasing agent (an aqueous solution containing 60g / L NaOH, 40g / L Na2CO3, and 3g / L OP); then it is rinsed with deionized water at room temperature, then with deionized water at 60℃, and then with deionized water at room temperature, each rinse lasting 30 minutes to thoroughly remove any degreasing agent residue; finally, the sample is dried in a 60℃ oven for 2 hours.

[0048] 2) After the pretreated PEEK is transferred into a vacuum furnace and evacuated, the substrate surface is thoroughly cleaned for 15 minutes using plasma glow discharge cleaning with argon gas. Then, low-pressure plasma activation etching is used to increase the surface roughness of the substrate. The plasma sputtering pressure is 1 Pa, the plasma sputtering time is 500 s, and the plasma sputtering voltage is 50 V. Finally, titanium ions are implanted into the PEEK substrate using a medium-current ion implanter with an implantation vacuum of 10... -3 The implantation parameters were set at Pa, 70 keV energy, 6 Ma beam current, and 90 min, and the titanium ion implantation dose of the PEEK substrate was achieved to be 10 Pa by adjusting the above parameters. 16 ion / cm 2 ;

[0049] 3) Start the titanium target power supply and deposit a titanium film with a thickness of 3 μm on the substrate surface by magnetron sputtering. The specific operating parameters for this process are as follows: first, control the vacuum degree of the cavity to less than 0.02 Pa, then introduce argon gas at a pressure of 100 sccm to maintain a vacuum degree of 0.5 Pa, and a current intensity of 2 A; the rotating frame is in the positive direction, the rotation speed is 10.0 Hz, and the time is 60 minutes. Then, anodizing was performed using an organic electrolyte (specific parameters for anodizing were: titanium alloy clamp as anode, graphite electrode as cathode, electrode spacing of 20 cm, oxidation voltage of 15 V, oxidation time of 120 minutes, and reaction temperature of 25 °C; the electrolyte formulation was: 50 wt% ethylene glycol / glycerol mixed solution, 1.0 wt% ammonium fluoride, and the remainder being deionized water, with the ratio of ethylene glycol to glycerol in the ethylene glycol / glycerol mixed solution being 1:1), to oxidize the titanium film to form TiO2 nanotube structures. The sample was then sequentially cleaned with deionized ultrasonic cleaning, anhydrous ethanol cleaning, and dried. The final pore size of the nanotubes was approximately 50 nm.

[0050] 4) The previous material was immersed in an AgNO3 / carboxylated chitosan mixed solution (AgNO3 concentration 1.5wt%, carboxylated chitosan number-average molecular weight 700,000, degree of carboxylation 90%, concentration 0.2wt%), and in-situ loading was performed using ultrasound (ultrasound power 120W, ultrasound time 1h), followed by in-situ ultraviolet reduction (UV light intensity 100mW / cm²). 2 (Irradiation time of 4 hours) forms carboxylated chitosan / silver complex in the pores of TiO2 nanotubes. Finally, after cleaning, sterilization and vacuum packaging, PEEK-based antibacterial orthopedic implantable medical device products are obtained.

[0051] Compared to Example 1, the ion implantation beam current and implantation time were increased. The PEEK-based antibacterial orthopedic implantable medical device product prepared by the above process exhibited high hydrophilicity (contact angle 19.5°). The bonding strength between the titanium composite coating and the PEEK substrate was slightly improved, reaching 30.7 MPa. CCK-8 results showed that the material had good biocompatibility (cell survival rate reached 91.9% compared to the group cultured in the well plate) and good antibacterial properties, with a bacteriostatic rate of 90.2%.

[0052] Example 5:

[0053] 1) First, the PEEK surface is degreased using a degreasing agent (an aqueous solution containing 60g / L NaOH, 40g / L Na2CO3, and 3g / L OP); then it is rinsed with deionized water at room temperature, then with deionized water at 60℃, and then with deionized water at room temperature, each rinse lasting 30 minutes to thoroughly remove any degreasing agent residue; finally, the sample is dried in a 60℃ oven for 2 hours.

[0054] 2) After the pretreated PEEK is transferred into a vacuum furnace and evacuated, the substrate surface is thoroughly cleaned for 15 minutes using a plasma glow discharge cleaning process with argon gas. Then, titanium ions are implanted into the PEEK substrate using a medium-current ion implanter with an implantation vacuum of 10. -3 The implantation parameters were set as follows: Pa, implantation energy 70 keV, beam current 3 Ma, and implantation time 30 min. By adjusting these parameters, a titanium ion implantation dose of 10-1 was achieved on the PEEK substrate. 15 ion / cm 2 ;

[0055] 3) Start the titanium target power supply and deposit a titanium film with a thickness of 3 μm on the substrate surface by magnetron sputtering. The specific operating parameters for this process are as follows: first, control the vacuum degree of the cavity to less than 0.02 Pa, then introduce argon gas at a pressure of 100 sccm to maintain a vacuum degree of 0.5 Pa, and a current intensity of 2 A; the rotating frame is in the positive direction, the rotation speed is 10.0 Hz, and the time is 60 minutes. Then, anodizing was performed using an organic electrolyte (specific parameters for anodizing were: titanium alloy clamp as anode, graphite electrode as cathode, electrode spacing of 20 cm, oxidation voltage of 15 V, oxidation time of 120 minutes, and reaction temperature of 25 °C; the electrolyte formulation was: 50 wt% ethylene glycol / glycerol mixed solution, 1.0 wt% ammonium fluoride, and the remainder being deionized water, with the ratio of ethylene glycol to glycerol in the ethylene glycol / glycerol mixed solution being 1:1), to oxidize the titanium film to form TiO2 nanotube structures. The sample was then sequentially cleaned with deionized ultrasonic cleaning, anhydrous ethanol cleaning, and dried. The final pore size of the nanotubes was approximately 50 nm.

[0056] 4) The previous material was immersed in an AgNO3 / carboxylated chitosan mixed solution (AgNO3 concentration 1.5wt%, carboxylated chitosan number-average molecular weight 700,000, degree of carboxylation 90%, concentration 0.2wt%), and in-situ loading was performed using ultrasound (ultrasound power 120W, ultrasound time 1h), followed by in-situ ultraviolet reduction (UV light intensity 100mW / cm²). 2 (Irradiation time of 4 hours) forms carboxylated chitosan / silver complex in the pores of TiO2 nanotubes. Finally, after cleaning, sterilization and vacuum packaging, PEEK-based antibacterial orthopedic implantable medical device products are obtained.

[0057] Compared to Example 1, the surface of the medical device product also exhibits high hydrophilicity, but due to the lack of low-pressure plasma etching treatment in the process, the bonding strength between the titanium composite coating and the PEEK substrate is reduced to 16.6 MPa.

Claims

1. A method for preparing a PEEK-based antibacterial orthopedic implantable medical device, characterized in that: The medical device product is made from PEEK, titanium, silver nitrate, and carboxylated chitosan as main raw materials, using a combination of processes including plasma glow discharge cleaning, low-pressure plasma etching, ion implantation, magnetron sputtering, anodizing, ultrasound-assisted implantation, and in-situ ultraviolet reduction; specifically, it includes the following steps: 1) The PEEK substrate surface is subjected to pretreatment in sequence, including degreasing, cleaning, and drying; 2) After the pretreated PEEK is transferred into a vacuum furnace and evacuated, the substrate surface is thoroughly cleaned using a plasma glow discharge cleaning process, followed by low-pressure plasma activation etching to increase the surface roughness of the substrate; then, a medium-current ion implanter is used to implant titanium ions into the PEEK substrate. 3) Start the titanium target power supply and deposit a titanium thin film on the substrate surface through magnetron sputtering; then use an organic electrolyte for anodic oxidation to oxidize the titanium thin film and form a TiO2 nanotube structure; 4) The previous material was immersed in an AgNO3 / carboxylated chitosan mixed solution and subjected to in-situ loading using ultrasound. Then, an in-situ ultraviolet light reduction process was used to form a carboxylated chitosan / silver complex in the TiO2 nanotube channels. Finally, after cleaning, sterilization and vacuum packaging, a PEEK-based antibacterial orthopedic implantable medical device product was obtained.

2. The method for preparing the PEEK-based antibacterial orthopedic implantable medical device product according to claim 1, characterized in that: In step 1), the degreasing agent used in the degreasing process is an aqueous solution containing 60-80 g / L NaOH, 20-40 g / L Na2CO3, and 1-3 g / L OP. The cleaning process involves sequentially washing with room temperature deionized water, 60°C deionized water, and room temperature deionized water, with each washing session lasting 15-30 minutes to thoroughly remove any degreasing agent residue.

3. The method for preparing the PEEK-based antibacterial orthopedic implantable medical device product according to claim 1, characterized in that: In step 2), the substrate surface is cleaned with plasma glow discharge for 2-15 minutes to activate it and increase the contact angle. The gas used is argon, hydrogen, oxygen or a fluorine-containing gas. In low-pressure plasma activation etching, the plasma sputtering pressure is 1-8 Pa, the plasma sputtering time is 100-1000 s, and the plasma sputtering voltage is 20-70 V.

4. The method for preparing the PEEK-based antibacterial orthopedic implantable medical device product according to claim 1, characterized in that: In step 2), titanium ions are implanted into the PEEK substrate using a medium-current ion implanter, with an implantation vacuum of 1-5 × 10⁻⁵. - 3 The implantation energy was 10-70 keV, the beam current was 1-6 Ma, and the implantation time was 20-90 min. By adjusting the above parameters, a titanium ion implantation dose of 10 Pa was achieved on the PEEK substrate. 13 -10 17 ion / cm 2 .

5. The method for preparing the PEEK-based antibacterial orthopedic implantable medical device product according to claim 1, characterized in that: In step 3), a titanium thin film with a thickness of 1-5 μm is deposited by magnetron sputtering; the vacuum degree of the cavity is first controlled to be less than 0.02 Pa, and then argon gas is introduced at a pressure of 50-200 sccm to maintain a vacuum degree of 0.25-0.85 Pa; the current intensity is 0.5-5 A; the direction and speed of the rotating frame are switched between forward and reverse, and the rotation speed is 5.0-20.0 Hz; the time is 20-150 minutes.

6. The method for preparing the PEEK-based antibacterial orthopedic implantable medical device product according to claim 1, characterized in that: The anodizing with organic electrolyte described in step 3) is specifically as follows: the titanium-plated PEEK thin film sample is placed in a titanium alloy fixture as the anode, and the cathode is a graphite electrode with a distance of 10-20 cm between the two electrodes; the oxidation voltage is 10-60V; the oxidation time is 30-120 minutes; the reaction temperature is 20-30℃; the electrolyte formula is: ethylene glycol / glycerol mixed solution, ammonium fluoride, and the remainder is deionized water, and the concentration of ethylene glycol / glycerol mixed solution in the electrolyte is 50wt%, wherein the mass ratio of ethylene glycol and glycerol is 3:1~1:3, and the concentration of ammonium fluoride is 0.2-1.0wt%; the sample after anodizing is sequentially ultrasonically cleaned with deionized water, cleaned with anhydrous ethanol, and then dried, and the surface of the obtained titanium thin film is oxidized to form an ordered TiO2 nanotube structure with a nanotube diameter of 50-120nm.

7. The method for preparing the PEEK-based antibacterial orthopedic implantable medical device product according to claim 1, characterized in that: In step 4), the concentration of AgNO3 in the AgNO3 / carboxylated chitosan mixed solution is 1.5-3 wt%, the number average molecular weight of carboxylated chitosan is 300,000-700,000, the degree of carboxylation is 70-90%, and the concentration is 0.1-0.5 wt%; the ultrasonic power is 80-120 W, the ultrasonic time is 1-2 h, and the ultraviolet light intensity is 80-150 mW / cm². 2 The irradiation time is 2-6 hours.

8. The PEEK-based antibacterial orthopedic implantable medical device product prepared by the method according to any one of claims 1-7 has a bonding strength between the surface metal composite coating and the PEEK substrate greater than 25 MPa.

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