Preparation method of polyetheretherketone auditory ossicular prosthesis and polyetheretherketone auditory ossicular prosthesis

Abstract

This application relates to a method for preparing a polyetheretherketone (PEEK) auditory ossicular prosthesis, using 3D printing technology to form the prosthesis in one piece. The raw materials used are PEEK and / or PEEK composite materials. This application utilizes the excellent chemical stability and biocompatibility of PEEK and / or PEEK composite materials. Using 3D printing technology, the PEEK composite materials are sintered onto the surface of the ossicular prosthesis to form a rough microporous structure, thereby resolving the issue of soft tissue and blood vessels having difficulty attaching to the prosthesis.

Description

Technical Field

[0001] The present application relates to the technical field of medical devices, and in particular to a preparation method of a polyetheretherketone (PEEK) auditory ossicular prosthesis and the PEEK auditory ossicular prosthesis. Background Art

[0002] The auditory ossicles, also known as the ossicles, are the smallest bones in the human body. Each ear consists of three ossicles, the malleus, the incus, and the stapes. Most of these bones are located in the epitympanic cavity and are connected by ligaments and joints to form the ossicular chain. The malleus is connected to the incus, which is in turn connected to the stapes, forming a sequential mechanical system that transmits sound waves from the eardrum to the inner ear and amplifies the sound vibrations to facilitate the perception of auditory cells. During this transmission process, the ossicular chain amplifies the sound through the principle of leverage, making it easier for auditory cells to perceive. When the ossicles are damaged due to disease or congenital reasons, surgical implantation of an ossicular prosthesis is generally required to replace the function of the ossicles.

[0003] Currently, most of the ossicular prostheses widely used in clinical practice are made of metal materials such as pure titanium, titanium alloy, and stainless steel. The release of metal ions after long-term implantation can easily lead to implant failure, high expulsion rate, high risk of stress shielding, and poor MRI compatibility. These problems have not been well resolved. In accordance with the above requirements, polyetheretherketone (PEEK) stands out due to its excellent mechanical properties, excellent biocompatibility, and elastic modulus similar to that of human bone. It is used as a bone tissue repair substitute in neurosurgery and orthopedics and is widely used in the field of medical devices. However, due to the inertness of PEEK, it is difficult for soft tissues and blood vessels in the human body to adhere to its surface, which greatly affects the postoperative stability of the product. At the same time, traditional machining and injection molding processes are difficult to solve this problem. Summary of the Invention

[0004] In order to solve the problem that soft tissue blood vessels are difficult to attach, the present application provides a preparation method of a polyetheretherketone (PEEK) ossicular prosthesis and a PEEK ossicular prosthesis.

[0005] In a first aspect, the present application provides a method for preparing a polyetheretherketone ossicular prosthesis, using the following technical solution:

[0006] The invention relates to a method for preparing a polyetheretherketone auditory ossicle prosthesis, which adopts 3D printing technology to form the prosthesis in one piece; the raw materials for the preparation are polyetheretherketone and / or polyetheretherketone composite materials.

[0007] By adopting the above technical solution, the excellent chemical stability and biocompatibility of polyetheretherketone and / or polyetheretherketone composite materials are utilized to prepare ossicular prostheses, and a rough microporous structure is sintered on the surface of the prosthesis through 3D printing technology, thereby increasing its surface area and providing more attachment points, so that the prosthesis is more firmly fixed in the position of the ossicular chain and is not prone to detachment; at the same time, these rough microporous structures can also promote the growth of surrounding tissues, effectively solving the problem that soft tissue blood vessels in the human body are difficult to attach, thereby further enhancing the postoperative stability of the prosthesis.

[0008] In a specific embodiment, the ossicular prosthesis includes at least one of a malleus prosthesis, an incus prosthesis, and a stapes prosthesis.

[0009] In a specific embodiment, the malleus prosthesis and the incus prosthesis are connected via a ball-and-socket joint.

[0010] By adopting the above technical solution, the malleus prosthesis and the incus prosthesis are connected by a ball-and-socket joint, so that the angle between the malleus prosthesis and the incus prosthesis can be adjusted conveniently and flexibly, which is suitable for buffering the shear stress of the artificial auditory ossicle on the tympanic membrane when the middle ear pressure changes. At the same time, it can solve the problem that this feature cannot be assembled due to machining and injection molding processes.

[0011] In a specific embodiment, the polyetheretherketone composite material includes the following raw materials in weight percentage: 15-37% nano-hydroxyapatite, 55-72% sulfonated polyetheretherketone, 5-8% modified carbon nanotubes, and 3-5% glass fiber.

[0012] By adopting the above technical solution, sulfonated polyetheretherketone and nanohydroxyapatite are selected as the main mixed matrix of the ossicular prosthesis, among which sulfonated polyetheretherketone, as a semi-crystalline thermoplastic polymer, has excellent mechanical properties and chemical stability; nanohydroxyapatite, as a bioactive ceramic, has a composition similar to that of living bone matrix and has excellent biocompatibility and osteoconductivity; at the same time, carbon nanotubes and glass fibers are added on their basis, among which glass fibers have good affinity with polyetheretherketone. By modifying the carbon nanotubes to improve their compatibility, the two are mixed with the main mixed matrix, thereby effectively improving the mechanical properties and bioactivity of the composite material.

[0013] In a specific embodiment, the sulfonated polyetheretherketone is prepared as follows:

[0014] Add polyetheretherketone into concentrated sulfuric acid solution and react for 60-100 minutes. After the reaction, pour the mixed solution into an ice water bath for washing. After solid precipitates, wash it with deionized water for multiple times, filter it, and dry it to obtain sulfonated polyetheretherketone.

[0015] By adopting the above technical solution, since polyetheretherketone is biologically inert, resulting in poor bone integration effect, polyetheretherketone is sulfonated and modified, so that hydrophilic sulfonate groups are introduced into the surface of the modified polyetheretherketone, thereby improving its surface reactivity and promoting apatite formation and bone tissue growth.

[0016] In a specific embodiment, the modified carbon nanotubes are grafted with sulfonated polyetheretherketone, and the specific processing steps are as follows:

[0017] (1) Carboxylation-modified carbon nanotubes: Multi-walled carbon nanotubes are added to an acid solution for reaction. After the reaction is completed, deionized water is added to dilute the solution. After multiple washings and centrifugation, the resulting precipitate is filtered, dried, and ground to obtain carboxylation-modified carbon nanotubes.

[0018] (2) Amino-modified carbon nanotubes: neutralize the carboxyl-modified carbon nanotubes and mix them with N,N-dimethylformamide to obtain a modified carbon nanotube solution; then add 1,6-hexanediamine and N,N-dicyclohexylcarbodiimide to react, filter and wash after the reaction, and finally dry to obtain amino-modified modified carbon nanotubes;

[0019] (3) Grafting sulfonated polyetheretherketone: The amino-modified modified carbon nanotubes and N,N-dimethylformamide are mixed to obtain a modified carbon nanotube solution; the sulfonated polyetheretherketone and N,N-dimethylformamide are then mixed to obtain a sulfonated polyetheretherketone solution; the modified carbon nanotube solution, N,N-dicyclohexylcarbodiimide and the sulfonated polyetheretherketone solution are mixed and reacted, and after the reaction is completed, the mixture is filtered, washed, dried and ground to obtain modified carbon nanotubes grafted with sulfonated polyetheretherketone.

[0020] By adopting the above technical solution, carbon nanotubes have excellent mechanical properties and surface activity, but when they are directly physically blended with sulfonated polyetheretherketone, they are prone to agglomeration due to poor interfacial compatibility, which is not conducive to improving the mechanical properties of the composite material; by utilizing the reaction between amino groups and sulfonate groups, sulfonated polyetheretherketone is grafted onto the modified carbon nanotubes, thereby improving the compatibility with sulfonated polyetheretherketone through their similar structures, and solving the problem of carbon nanotubes being easily agglomerated in sulfonated polyetheretherketone; first, the carbon nanotubes are subjected to carboxylation modification, and the carboxyl-modified carbon nanotubes are subjected to amino modification, thereby providing a basis for the subsequent grafting of sulfonated polyetheretherketone with amino groups on the carbon nanotubes, and at the same time it is beneficial to improve the compatibility of carbon nanotubes with sulfonated polyetheretherketone and reduce agglomeration.

[0021] Preferably, the surface of the ossicular prosthesis is treated with oxygen or argon plasma.

[0022] By adopting the above technical solution, the surface of the ossicular prosthesis is treated with oxygen and argon plasma, so that high-energy particles collide with the surface of the prosthesis to form an uneven nanoscale structure, increasing the surface area of ​​the matrix material, which is conducive to better attachment of soft tissue and blood vessels in the human body.

[0023] In a specific feasible implementation scheme, the 3D printing technology is SLS selective laser sintering technology or FDM fused deposition modeling technology; during the one-piece molding process of the SLS selective laser sintering technology, the laser temperature is 332-338°C, the temperature in the printing chamber is 310-315°C, and the printing platform temperature is 310-315°C; during the one-piece molding process of the FDM fused deposition modeling technology, the nozzle temperature is 377-383°C and the printing base plate temperature is 257-263°C.

[0024] By adopting this technical solution, the resulting ossicles are highly robust, resisting cracking due to excessive temperatures and warping due to low temperatures. Furthermore, the sintered ossicles have a uniformly roughened surface with micropores, resulting in a large surface area and numerous attachment points. This allows the resulting ossicular prosthesis to be firmly fixed within the human body, providing high stability.

[0025] In a specific embodiment, the surface of the auditory ossicular prosthesis is loaded with a polydopamine layer, which is specifically prepared as follows: dopamine is dissolved in Tris-HCl buffer to prepare a dopamine solution; the auditory ossicular prosthesis is then immersed in the dopamine solution for reaction. After the reaction is completed, the prosthesis is taken out and repeatedly rinsed with deionized water, and dried to obtain the auditory ossicular prosthesis with the surface loaded with polydopamine.

[0026] By adopting the above technical solution, due to the breakage of the polymer chains on the surface of the matrix material caused by the plasma surface treatment, new elements and functional groups are introduced on the surface by bonding with the active particles in the plasma, which is beneficial to the deposition of dopamine; at the same time, by loading a polydopamine layer on the surface of the auditory ossicles, the biological activity of polyetheretherketone and / or polyetheretherketone composite materials is further enhanced, thereby promoting the bone integration effect.

[0027] In a specific embodiment, the polydopamine layer is further loaded with a protein composite material, which is specifically prepared as follows:

[0028] The rhBMP-2 solution is prepared by dissolving rhBMP-2 in an acetic acid solution, and then the rhBMP-2 solution is adsorbed on a collagen membrane, preformed into a spherical shape, and freeze-dried to form a protein composite material;

[0029] The protein composite material is uniformly mixed in deionized water to prepare a suspension; the auditory ossicle loaded with the polydopamine layer is placed in the suspension to react for 4-6 hours, and then freeze-dried after the reaction to obtain an auditory ossicle prosthesis also loaded with the protein composite material.

[0030] By adopting the above technical solution, polydopamine is used as a secondary reaction platform, and the adhesion of polydopamine is utilized to fix the protein composite material on the surface of the prosthesis. The protein composite material is composed of type I collagen membrane and rhBMP-2, which is beneficial to promote MSCs cell proliferation and further improve the bone bonding effect.

[0031] In a second aspect, the present application provides a polyetheretherketone ossicular prosthesis, which adopts the following technical solution:

[0032] The invention relates to a polyetheretherketone auditory ossicular prosthesis, which is prepared by a preparation method of the polyetheretherketone auditory ossicular prosthesis.

[0033] In summary, this application includes at least one of the following beneficial technical effects:

[0034] 1. The present application utilizes the excellent chemical stability and biocompatibility of polyetheretherketone and / or polyetheretherketone composite materials, and uses 3D printing integrated technology to sinter the surface of the ossicular prosthesis to form a rough microporous structure, thereby increasing its surface area and making the prosthesis more firmly fixed in the position of the ossicular chain. At the same time, these rough microporous structures can also promote the growth of surrounding tissues, and effectively solve the problem that it is difficult for soft tissue blood vessels in the human body to attach, thereby further enhancing the postoperative stability of the prosthesis.

[0035] 2. When the present application adopts polyetheretherketone composite materials to prepare polyetheretherketone ossicular prosthesis, sulfonated polyetheretherketone is selected to give the ossicular prosthesis matrix excellent mechanical properties and chemical stability, and nanohydroxyapatite is selected to give the ossicular matrix excellent biocompatibility and osteoconductivity. The advantages of the two are combined, and modified carbon nanotubes and glass fibers are added to prepare a composite matrix material with high strength and high bioactivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 Schematic diagram of the structure of the polyetheretherketone ossicular prosthesis in the embodiment of the present application.

[0037] Figure 2 Schematic diagram of the structure of the polyetheretherketone ossicular prosthesis in the embodiment of the present application.

[0038] Explanation of the accompanying drawings: 1. malleus prosthesis; 2. incus prosthesis. DETAILED DESCRIPTION

[0039] The nano-hydroxyphosphate in this application was purchased from Shanghai Aladdin; the collagen membrane is specifically type I collagen membrane, purchased from Shanghai Qisheng Biology; rhBMP-2 is specifically recombinant human bone morphogenetic protein-2, purchased from Shanghai Aimejie; other raw materials can be obtained commercially.

[0040] The polyetheretherketone ossicular prosthesis of the present application includes a malleus prosthesis and an incus prosthesis, which are connected by a ball-and-socket joint and are integrally formed using 3D printing technology.

[0041] Preparation Example

[0042] Preparation Example 1

[0043] Polyetheretherketone was added to concentrated sulfuric acid solution to prepare a mixed solution with a mass ratio of 1:20, stirred at a constant temperature of 50°C and reacted for 60 minutes. After the reaction, the mixed solution was poured into an ice water bath for washing, and the stirring state was maintained during the pouring process. After solid precipitation, it was washed with deionized water several times until the pH was about 7. After filtering, it was vacuum dried at 60°C for 16 hours to obtain sulfonated polyetheretherketone.

[0044] Preparation Example 2

[0045] Polyetheretherketone was added to concentrated sulfuric acid solution to prepare a mixed solution with a mass ratio of 1:30, and the solution was stirred at a constant temperature of 70°C and reacted for 100 minutes. After the reaction, the mixed solution was poured into an ice water bath for washing, and the stirring state was maintained during the pouring process. After solid precipitation, it was washed with deionized water several times until the pH was about 7. After filtering, it was vacuum dried at 60°C for 24 hours to obtain sulfonated polyetheretherketone.

[0046] Preparation Example 3

[0047] Multi-walled carbon nanotubes were added to a concentrated sulfuric acid solution and a concentrated nitric acid solution in a mass ratio of 1:3 to react for 1 hour. After the reaction, deionized water was added to dilute the solution at room temperature for 24 hours. The purified multi-walled carbon nanotubes were washed with deionized water multiple times and centrifuged at a centrifugal speed of 10,000 rpm for 20 minutes until the pH reached about 7. The solution was then filtered and dried at 50°C for 22 hours. After drying, the solution was ground to obtain carboxyl-modified carbon nanotubes.

[0048] N, N-dimethylformamide was added to the carboxyl-modified carbon nanotubes to prepare a modified carbon nanotube solution with a mass ratio of 1:80, and ultrasonicated at 30°C for 30 minutes; after dispersion, 1,6-hexanediamine and N, N-dicyclohexylcarbodiimide with a mass ratio of 4:1 were weighed for condensation reflux, and then added to the modified carbon nanotube solution, reacted at 80°C for 22 hours, filtered after the reaction, and then washed with anhydrous ethanol. After washing, deionized water was added for secondary washing, and finally dried at 80°C for 24 hours to obtain amino-modified modified carbon nanotubes.

[0049] The amino-modified modified carbon nanotubes were ground, and then N, N-dimethylformamide was added and dispersed after ultrasonic treatment for 1 hour to prepare a modified carbon nanotube solution with a mass ratio of 1:40; the sulfonated polyetheretherketone in part of Preparation Example 1 was added to N, N-dimethylformamide and dispersed after ultrasonic treatment for 30 minutes to prepare a sulfonated polyetheretherketone solution with a mass ratio of 1:20; the modified carbon nanotube solution and N, N-dicyclohexylcarbodiimide with a mass ratio of 1:5 were condensed and refluxed, and then a sulfonated polyetheretherketone solution with a mass ratio of 5:1 to the modified carbon nanotube solution was added, and the mixture was reacted at 80°C for 28 hours. After the reaction was completed, the mixture was filtered, and then anhydrous ethanol was added for several washings, and then deionized water was added for several washings. Finally, the mixture was dried at 60°C for 24 hours, and the modified carbon nanotubes grafted with sulfonated polyetheretherketone were obtained after grinding.

[0050] Preparation Example 4

[0051] Multi-walled carbon nanotubes were added to a concentrated sulfuric acid solution and a concentrated nitric acid solution in a mass ratio of 1:3 and reacted for 3 hours. After the reaction, deionized water was added and diluted at room temperature for 24 hours. The purified multi-walled carbon nanotubes were washed with deionized water multiple times and centrifuged at a centrifugal speed of 10,000 rpm for 20 minutes until the pH reached about 7, and then filtered. After filtration, the mixture was dried at 70°C for 26 hours, and then ground to obtain carboxyl-modified carbon nanotubes.

[0052] N, N-dimethylformamide was added to the carboxyl-modified carbon nanotubes to prepare a modified carbon nanotube solution with a mass ratio of 1:120, and ultrasonicated at 30°C for 90 minutes; after dispersion, 1,6-hexanediamine and N, N-dicyclohexylcarbodiimide with a mass ratio of 6:1 were weighed and condensed and refluxed, and then the modified carbon nanotube solution was added and reacted at 100°C for 26 hours. After the reaction was completed, the solution was filtered and then washed with anhydrous ethanol. After washing, deionized water was added for a second washing, and finally dried at 80°C for 24 hours to obtain amino-modified modified carbon nanotubes.

[0053] The amino-modified modified carbon nanotubes were ground, and then N, N-dimethylformamide was added and dispersed after ultrasonic treatment for 2 hours to prepare a modified carbon nanotube solution with a mass ratio of 1:60; the sulfonated polyetheretherketone in part of Preparation Example 1 was added to N, N-dimethylformamide and dispersed after ultrasonic treatment for 1 minute to prepare a sulfonated polyetheretherketone solution with a mass ratio of 1:20; the modified carbon nanotube solution and N, N-dicyclohexylcarbodiimide with a mass ratio of 1:5 were condensed and refluxed, and then a sulfonated polyetheretherketone solution with a mass ratio of 8:1 to the modified carbon nanotube solution was added, and the mixture was reacted at 120°C for 32 hours. After the reaction was completed, the mixture was filtered, and then anhydrous ethanol was added for washing several times, and then deionized water was added for washing several times. Finally, the mixture was dried at 60°C for 24 hours, and modified carbon nanotubes grafted with sulfonated polyetheretherketone were obtained after grinding.

[0054] Example

[0055] Example 1

[0056] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The preparation raw material is a polyetheretherketone composite material, which includes the following raw materials: 15g of nanohydroxyapatite, 72g of sulfonated polyetheretherketone, 8g of modified carbon nanotubes, and 5g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0057] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0058] The composite powder was extruded through a twin-screw extruder at 300°C to obtain a 3D printing filament with a wire diameter of 1.75±0.05mm and uniform thickness; the 3D printing filament was dried at 150°C for 24 hours and then subjected to fused deposition modeling using a 3D printer with a nozzle temperature of 380°C, a printing speed of 40mm / s, a printing layer thickness of 0.2mm, a printing base temperature of 260°C, and a porosity of 70% for the scaffold material, ultimately obtaining a 3D-printed ossicular prosthesis.

[0059] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0060] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0061] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0062] The polydopamine-loaded ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0063] Example 2

[0064] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The raw material for the preparation is a polyetheretherketone composite material, which includes the following raw materials: 26g of nanohydroxyapatite, 63.5g of sulfonated polyetheretherketone, 6.5g of modified carbon nanotubes, and 4g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0065] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0066] The composite powder was extruded through a twin-screw extruder at 300°C to obtain a 3D printing filament with a wire diameter of 1.75±0.05mm and uniform thickness; the 3D printing filament was dried at 150°C for 24 hours and then subjected to fused deposition modeling using a 3D printer with a nozzle temperature of 380°C, a printing speed of 40mm / s, a printing layer thickness of 0.2mm, a printing base temperature of 260°C, and a porosity of 70% for the scaffold material, ultimately obtaining a 3D-printed ossicular prosthesis.

[0067] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0068] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0069] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0070] The polydopamine-loaded ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0071] Example 3

[0072] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The raw material for the preparation is a polyetheretherketone composite material, which includes the following raw materials: 37g of nanohydroxyapatite, 55g of sulfonated polyetheretherketone, 5g of modified carbon nanotubes, and 3g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0073] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0074] The composite powder was extruded through a twin-screw extruder at 300°C to obtain a 3D printing filament with a wire diameter of 1.75±0.05mm and uniform thickness; the 3D printing filament was dried at 150°C for 24 hours and then subjected to fused deposition modeling using a 3D printer with a nozzle temperature of 380°C, a printing speed of 40mm / s, a printing layer thickness of 0.2mm, a printing base temperature of 260°C, and a porosity of 70% for the scaffold material, ultimately obtaining a 3D-printed ossicular prosthesis.

[0075] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0076] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0077] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0078] The polydopamine-loaded ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0079] Example 4

[0080] The only difference between this embodiment and embodiment 1 is that the sulfonated polyetheretherketone is prepared by the preparation example 2.

[0081] Example 5

[0082] The only difference between this embodiment and embodiment 1 is that the modified carbon nanotubes are prepared according to preparation example 4.

[0083] Example 6

[0084] The only difference between this embodiment and embodiment 1 is that the polyetheretherketone composite material includes the following raw materials: 15 g of nano-hydroxyapatite, 72 g of sulfonated polyetheretherketone, and 13 g of modified carbon nanotubes.

[0085] Example 7

[0086] The only difference between this embodiment and embodiment 1 is that the polyetheretherketone composite material includes the following raw materials: 15 g of nano-hydroxyapatite, 72 g of sulfonated polyetheretherketone, and 13 g of glass fiber.

[0087] Example 8

[0088] The only difference between this embodiment and embodiment 1 is that the polyetheretherketone composite material includes the following raw materials: 15 g of nano-hydroxyapatite and 85 g of sulfonated polyetheretherketone.

[0089] Example 9

[0090] The only difference between this embodiment and embodiment 1 is that the polyetheretherketone composite material includes the following raw materials: 15 g of nano-hydroxyapatite, 72 g of sulfonated polyetheretherketone, 8 g of carbon nanotubes, and 5 g of glass fiber.

[0091] Example 10

[0092] The only difference between this embodiment and embodiment 1 is that the surface is treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 450 V and a pressure of 15 Pa for 15 minutes, and then ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated ossicular prosthesis.

[0093] Example 11

[0094] The only difference between this embodiment and embodiment 1 is that the surface is treated with 30% oxygen and 70% argon low-temperature plasma for 25 minutes under the conditions of 500V voltage and 20Pa pressure, and then ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated ossicular prosthesis.

[0095] Example 12

[0096] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The preparation raw material is a polyetheretherketone composite material, which includes the following raw materials: 15g of nanohydroxyapatite, 72g of sulfonated polyetheretherketone, 8g of modified carbon nanotubes, and 5g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0097] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0098] The composite powder was extruded through a twin-screw extruder at 300°C to obtain a 3D printing filament with a wire diameter of 1.75±0.05mm and uniform thickness; the 3D printing filament was dried at 150°C for 24 hours and then subjected to fused deposition modeling using a 3D printer with a nozzle temperature of 380°C, a printing speed of 40mm / s, a printing layer thickness of 0.2mm, a printing base temperature of 260°C, and a porosity of 70% for the scaffold material, ultimately obtaining a 3D-printed ossicular prosthesis.

[0099] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0100] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0101] The polydopamine-loaded ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0102] Example 13

[0103] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The preparation raw material is a polyetheretherketone composite material, which includes the following raw materials: 15g of nanohydroxyapatite, 72g of sulfonated polyetheretherketone, 8g of modified carbon nanotubes, and 5g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0104] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0105] The composite powder was extruded through a twin-screw extruder at 300°C to obtain a 3D printing filament with a wire diameter of 1.75±0.05mm and uniform thickness; the 3D printing filament was dried at 150°C for 24 hours and then subjected to fused deposition modeling using a 3D printer with a nozzle temperature of 380°C, a printing speed of 40mm / s, a printing layer thickness of 0.2mm, a printing base temperature of 260°C, and a porosity of 70% for the scaffold material, ultimately obtaining a 3D-printed ossicular prosthesis.

[0106] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0107] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0108] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0109] Dissolve rhBMP-2 in acetic acid solution to prepare a concentration of 100 μg / mL -1 The rhBMP-2 solution was then adsorbed on a 5cm×5cm×0.5cm collagen membrane to form a spherical shape with a diameter of 0.8cm, which was then freeze-dried to form a protein composite material.

[0110] The protein composite material was uniformly mixed in deionized water to form a suspension at a mass ratio of 1:100. The polydopamine-coated auditory ossicles were placed in the suspension to react for 4 hours. After the reaction, the ossicles were freeze-dried to obtain an ossicular prosthesis also loaded with the protein composite material. The ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored under vacuum until use.

[0111] Example 14

[0112] The only difference between this example and Example 13 is that the auditory ossicles loaded with the polydopamine layer are placed in the suspension for reaction for 6 hours.

[0113] Example 15

[0114] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The preparation raw material is a polyetheretherketone composite material, which includes the following raw materials: 15g of nanohydroxyapatite, 72g of sulfonated polyetheretherketone, 8g of modified carbon nanotubes, and 5g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0115] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0116] The composite powder was extruded through a twin-screw extruder at 300°C to obtain a 3D printing filament with a wire diameter of 1.75±0.05mm and uniform thickness; the 3D printing filament was dried at 150°C for 24 hours and then subjected to fused deposition modeling using a 3D printer with a nozzle temperature of 380°C, a printing speed of 40mm / s, a printing layer thickness of 0.2mm, a printing base temperature of 260°C, and a porosity of 70% for the scaffold material, ultimately obtaining a 3D-printed ossicular prosthesis.

[0117] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0118] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0119] The ossicular prosthesis was sterilized by ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0120] Example 16

[0121] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The preparation raw material is a polyetheretherketone composite material, which includes the following raw materials: 15g of nanohydroxyapatite, 72g of sulfonated polyetheretherketone, 8g of modified carbon nanotubes, and 5g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0122] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0123] The composite powder was subjected to SLS selective laser sintering molding using a 3D printer. The laser temperature was 335°C, the printing chamber temperature was 310°C, the printing base temperature was 310°C, the scanning speed was 1200mm / s, the printing layer thickness was 0.2mm, and the porosity of the scaffold material was set to 70%. Finally, a 3D printed ossicular prosthesis was obtained.

[0124] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0125] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0126] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0127] The polydopamine-loaded ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0128] Example 17

[0129] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The preparation raw material is a polyetheretherketone composite material, which includes the following raw materials: 15g of nanohydroxyapatite, 72g of sulfonated polyetheretherketone, 8g of modified carbon nanotubes, and 5g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0130] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0131] The composite powder was subjected to SLS selective laser sintering molding using a 3D printer. The laser temperature was 320°C, the printing chamber temperature was 310°C, the printing base temperature was 310°C, the scanning speed was 1200mm / s, the printing layer thickness was 0.2mm, and the porosity of the scaffold material was set to 70%. Finally, a 3D printed ossicular prosthesis was obtained.

[0132] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0133] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0134] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0135] The polydopamine-loaded ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0136] Example 18

[0137] The preparation method of the polyetheretherketone auditory ossicular prosthesis adopts 3D printing technology for one-piece molding. The preparation raw material is a polyetheretherketone composite material, which includes the following raw materials: 15g of nanohydroxyapatite, 72g of sulfonated polyetheretherketone, 8g of modified carbon nanotubes, and 5g of glass fiber; wherein the sulfonated polyetheretherketone is prepared by Preparation Example 1, and the modified carbon nanotubes are prepared by Preparation Example 3.

[0138] During the preparation, nano-hydroxyapatite, sulfonated polyetheretherketone, modified carbon nanotubes and glass fiber are added into N,N-dimethylformamide and mixed while stirring continuously for 30 minutes at a stirring rate of 8000r / min. The material is discharged into a 50% ethanol solution, boiled and washed, and dried at 150°C for 24 hours to obtain a composite powder.

[0139] The composite powder was subjected to SLS selective laser sintering molding using a 3D printer. The laser temperature was 335°C, the printing chamber temperature was 300°C, the printing base temperature was 310°C, the scanning speed was 1200mm / s, the printing layer thickness was 0.2mm, and the porosity of the scaffold material was set to 70%. Finally, a 3D printed ossicular prosthesis was obtained.

[0140] After printing, the ossicular prosthesis was ultrasonically cleaned with acetone, anhydrous ethanol, and deionized water for 10 minutes in sequence to remove surface contaminants. Finally, the ossicular prosthesis was dried at 70°C for 48 hours.

[0141] The surface was treated with 30% oxygen and 70% argon low-temperature plasma at a voltage of 400 V and a pressure of 10 Pa for 5 minutes. After treatment, the surface was ultrasonically cleaned with deionized water for 5 minutes and dried to obtain the plasma-treated auditory ossicle prosthesis.

[0142] Prepare 10mmol / L Tris-HCl buffer; dissolve dopamine in Tris-HCl buffer to prepare a dopamine solution with a pH of 8.5 and a concentration of 2g / L; then immerse the auditory ossicle prosthesis in the dopamine solution and react at 37°C with shaking for 24 hours. Then remove the prosthesis and ultrasonically rinse it with deionized water for 3 minutes to remove the unloaded dopamine on the surface. After drying, the auditory ossicle prosthesis with polydopamine loaded on the surface is obtained.

[0143] The polydopamine-loaded ossicular prosthesis was sterilized with ethylene oxide or cobalt-60 and then stored aseptically under vacuum until use.

[0144] Example 19

[0145] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 1.

[0146] Example 20

[0147] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 2.

[0148] Example 21

[0149] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 3.

[0150] Example 22

[0151] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 4.

[0152] Example 23

[0153] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 5.

[0154] Example 24

[0155] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 6.

[0156] Example 25

[0157] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 7.

[0158] Example 26

[0159] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 8.

[0160] Example 27

[0161] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 9.

[0162] Example 28

[0163] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 10.

[0164] Example 29

[0165] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 11.

[0166] Example 30

[0167] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 12.

[0168] Example 31

[0169] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 13.

[0170] Example 32

[0171] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 14.

[0172] Example 33

[0173] The polyetheretherketone auditory ossicular prosthesis was prepared by the preparation method in Example 15.

[0174] Comparative Example

[0175] Comparative Example 1

[0176] The only difference between this comparative example and Example 1 is that the raw material for preparing the polyetheretherketone auditory ossicular prosthesis is titanium material.

[0177] Performance testing

[0178] The auditory ossicular prostheses prepared in Examples 1 to 18 and Comparative Example 1 were tested.

[0179] Determination of the mechanical properties of the auditory ossicle prosthesis: The tensile and compressive properties of the auditory ossicle prosthesis were tested using a material testing machine with a tensile speed of 5 mm / min and a compression speed of 1 mm / min. The test was conducted at room temperature, and the computer automatically collected the data and calculated the results.

[0180] The hardness of the ossicular prosthesis was measured using a MTHV-1MMDT Vickers hardness tester. A 10 mm × 10 mm × 10 mm sample was selected and sanded until there was no scratch. The load F was set to 500 g. The indenter was pressed into the test surface of the sample for 10 seconds. The diagonal length d of the sample was measured and its surface area S was calculated. Find the hardness value.

[0181] Determination of the wear resistance of auditory ossicular prosthesis: A JB-5C roughness profiler is used. After friction and wear, arc-shaped grooves appear on the surface of the sample. The cross-sectional profile can be extracted by operating it. The stylus is at the end of the instrument's measuring rod. During the measurement process, the stylus is perpendicular to the measured surface and moves on the measured surface at a certain speed. The surface profile of the measured sample can be obtained, and the wear volume value of the sample can be calculated.

[0182] Table 1 Performance measurement of auditory ossicle prosthesis

[0183]

[0184] Since the composite material ossicular prosthesis will come into contact with the surface of other bones during middle ear surgery, the replaced ossicular chain will transmit vibrations in the ossicular chain system, playing a guiding, enhancing and protective role. Therefore, the ossicular prosthesis needs to match the surgical position of the ossicular chain and meet certain mechanical performance test requirements. Referring to Table 1, according to Comparative Example 1 and Examples 1-3, it can be seen that the polyetheretherketone composite material has excellent mechanical properties and chemical stability. The surface of the ossicular prosthesis is sintered to form a rough microporous structure through 3D printing integrated technology, thereby increasing its surface area and providing more attachment points, so that the prosthesis is more firmly fixed in the position of the ossicular chain and is not easy to detach. At the same time, these rough microporous structures can also promote the growth of surrounding tissues, which effectively solves the problem that soft tissue and blood vessels in the human body are difficult to attach, thereby further enhancing the postoperative stability of the prosthesis. According to the measurements of the experimenters, it was found that the effects of 3D printing integrated technology and non-integrated technology on sound conduction are different. Among them, the integrated technology has a better conduction effect. This is because when the vibration of the eardrum is transmitted to the vestibule, it can be better transmitted to the subsequent stage through the integrated structure, thereby affecting the effect of the patient's postoperative hearing recovery.

[0185] Referring to Table 1, it can be seen from Examples 1-3 and 4-8 that sulfonated polyetheretherketone and nanohydroxyapatite are selected as the main mixed matrix of the ossicular prosthesis. Nanohydroxyapatite, as an important inorganic component in the human bone tissue structure, has excellent biocompatibility and osteoconductivity, and is a highly promising hard tissue repair material; however, nanohydroxyapatite itself is difficult to directly mold and has low strength; polyetheretherketone, as a semi-crystalline thermoplastic polymer, has excellent mechanical properties and chemical stability and is non-toxic and harmless to the human body; and because polyetheretherketone is biologically inert, its bone integration effect in the body is not ideal. By sulfonating the polyetheretherketone and compounding the two at the same time, a high-strength and high-bioactivity composite material is prepared. Comparative Examples 6-8, the polyetheretherketone composite material is further added with carbon nanotubes and / or glass fibers. By adding carbon nanotubes and glass fibers to the system, the bonding between nanohydroxyapatite and sulfonated polyetheretherketone is enhanced, thereby mixing the two with the main mixed matrix, effectively improving the mechanical properties and bioactivity of the composite material.

[0186] With reference to Table 1, and in comparison with Example 9, it can be seen in combination with Example 1 and Example 5 that carbon nanotubes have excellent mechanical properties and surface activity. The elastic modulus of the carbon nanotubes is almost close to that of diamond, and the carbon nanotubes have good toughness and can be stretched. However, due to poor interfacial compatibility, agglomeration easily occurs when directly physically blended with sulfonated polyetheretherketone, which is not conducive to improving the mechanical properties of the composite material. By subjecting the carbon nanotubes to carboxylation modification, and then subjecting the carboxylated modified carbon nanotubes to secondary modification, and chemically grafting the sulfonated polyetheretherketone onto the surface of the modified carbon nanotubes, the carbon nanotubes can improve their compatibility with the sulfonated polyetheretherketone due to their identical structure, thereby solving the agglomeration problem of the carbon nanotubes in the sulfonated polyetheretherketone.

[0187] Referring to Table 1 and comparing Example 12, it can be seen from Examples 1, 10, and 11 that the surface of the ossicular prosthesis treated with oxygen and argon plasma resulted in depressions of varying sizes appearing on the surface of the ossicular prosthesis treated with oxygen and argon low-temperature plasma, making the surface rough and uneven. This increased the surface area of ​​the base material, facilitating better attachment of soft tissue and blood vessels in the human body. Furthermore, the ossicular prosthesis modified with oxygen and argon low-temperature plasma successfully developed a nanotopological structure on its surface. When argon bombarded the ossicular prosthesis, the free radicals formed on its surface rapidly reacted with oxygen, facilitating the functionalization of the free radicals. This also increased the hydrophilicity of the material surface, providing favorable conditions for the subsequent deposition of polydopamine.

[0188] Referring to Table 1, Example 1 and Examples 16-18, by setting the temperature of the molding process, the obtained auditory ossicles are denser, less prone to warping and cracking, and have better strength performance.

[0189] Biocompatibility of auditory ossicular prostheses: Mouse bone marrow mesenchymal stem cells were used to evaluate the biocompatibility of auditory ossicular prostheses. Extracts were prepared according to GB / T16886.5-2017. The ossicular prostheses were immersed in DMEM culture medium at a ratio of 0.2 g / mL and placed in an incubator at 37°C for 72 hours.

[0190] Table 2 Biocompatibility determination of ossicular prosthesis

[0191]

[0192] Referring to Table 2 and comparing Example 15 with Examples 1, 13, and 14, it can be seen that by loading the surface of the ossicular prosthesis with a polydopamine layer, the bioactivity of the polyetheretherketone composite can be further enhanced, promoting MSC cell proliferation and thus promoting osseointegration. Furthermore, after polydopamine is deposited on the surface of the ossicular prosthesis, the original uneven topography of the surface becomes less pronounced, and polydopamine particles can be observed, increasing the hydrophilicity of the material surface. Polydopamine is then used as a secondary reaction platform, leveraging its adhesive properties to secure the protein composite to the prosthesis surface. The protein composite, composed of a type I collagen membrane and rhBMP-2, promotes MSC cell proliferation and further enhances osseointegration.

[0193] The above are all preferred embodiments of the present application, and are not intended to limit the scope of protection of the present application. Therefore, any equivalent changes made based on the structure, shape, and principle of the present application should be included in the scope of protection of the present application.

Claims

1. A method for preparing a polyetheretherketone ossicular prosthesis, characterized in that: It is formed in one piece using 3D printing technology; the raw material is polyetheretherketone composite material; The ossicular prosthesis includes a malleus prosthesis and an incus prosthesis; the malleus prosthesis and the incus prosthesis are connected via a ball-and-socket joint; The polyetheretherketone composite material comprises the following raw materials in weight percentage: 15-37% nanohydroxyapatite, 55-72% sulfonated polyetheretherketone, 5-8% modified carbon nanotubes, and 3-5% glass fiber; The modified carbon nanotubes are grafted with sulfonated polyetheretherketone; The 3D printing technology is SLS selective laser sintering technology or FDM fused deposition modeling technology; during the one-piece molding process of the SLS selective laser sintering technology, the laser temperature is 332-338°C, the temperature in the printing chamber is 310-315°C, the temperature of the printing platform is 310-315°C, the scanning speed is 1200mm / s, the printing layer thickness is 0.2mm, and the porosity of the scaffold material is set to 70%; during the one-piece molding process of the FDM fused deposition modeling technology, the nozzle temperature is 377-383°C, the printing base temperature is 257-263°C, the printing speed is 40mm / s, the printing layer thickness is 0.2mm, and the porosity of the scaffold material is set to 70%; The surface of the ossicular prosthesis is treated with oxygen and argon plasma; The surface of the ossicular prosthesis is loaded with a polydopamine layer; The polydopamine layer is also loaded with a protein composite material, which is specifically prepared as follows: The rhBMP-2 solution is prepared by dissolving rhBMP-2 in an acetic acid solution, and then the rhBMP-2 solution is adsorbed on a collagen membrane, preformed into a spherical shape, and freeze-dried to form a protein composite material; The protein composite material is uniformly mixed in deionized water to prepare a suspension; the auditory ossicle loaded with the polydopamine layer is placed in the suspension to react for 4-6 hours, and then freeze-dried after the reaction to obtain an auditory ossicle prosthesis also loaded with the protein composite material.

2. The method for preparing a polyetheretherketone ossicular prosthesis according to claim 1, characterized in that: The preparation of the sulfonated polyetheretherketone is as follows: Add polyetheretherketone into concentrated sulfuric acid solution and react for 60-100 minutes. After the reaction, pour the mixed solution into an ice water bath for washing. After solid precipitates, wash it with deionized water for multiple times, filter it, and dry it to obtain sulfonated polyetheretherketone.

3. The method for preparing the polyetheretherketone ossicular prosthesis according to claim 1, characterized in that: The modified carbon nanotubes are grafted with sulfonated polyetheretherketone, and the specific processing steps are as follows: (1) Carboxylation-modified carbon nanotubes: Multi-walled carbon nanotubes are added to an acid solution for reaction. After the reaction is completed, deionized water is added to dilute the solution. After multiple washings and centrifugation, the resulting precipitate is filtered, dried, and ground to obtain carboxylation-modified carbon nanotubes. (2) Amino-modified carbon nanotubes: neutralize the carboxyl-modified carbon nanotubes and mix them with N,N-dimethylformamide to obtain a modified carbon nanotube solution; then add 1,6-hexanediamine and N,N-dicyclohexylcarbodiimide to react, filter and wash after the reaction, and finally dry to obtain amino-modified modified carbon nanotubes; (3) Grafting sulfonated polyetheretherketone: Mix the amino-modified modified carbon nanotubes and N,N-dimethylformamide to obtain a modified carbon nanotube solution; then mix the sulfonated polyetheretherketone and N,N-dimethylformamide to obtain a sulfonated polyetheretherketone solution; mix the modified carbon nanotube solution, N,N-dicyclohexylcarbodiimide and the sulfonated polyetheretherketone solution and react them. After the reaction is completed, filter and wash, and finally dry and grind to obtain modified carbon nanotubes grafted with sulfonated polyetheretherketone.

4. The method for preparing a polyetheretherketone ossicular prosthesis according to claim 1, characterized in that: The surface of the auditory ossicular prosthesis is loaded with a polydopamine layer, which is specifically prepared as follows: Dopamine was dissolved in Tris-HCl buffer to prepare a dopamine solution; the auditory ossicle prosthesis was then immersed in the dopamine solution for reaction, and after the reaction was completed, the prosthesis was taken out and repeatedly rinsed with deionized water, and dried to obtain an auditory ossicle prosthesis with polydopamine loaded on the surface.

5. Polyetheretherketone ossicular prosthesis, characterized by: The polyetheretherketone ossicular prosthesis is prepared by the preparation method of any one of claims 1 to 4.

Images