Integrated ossicular prosthesis

Abstract

The application relates to the technical field of medical devices, and particularly discloses an integrated ossicle prosthesis, which comprises a total ossicle prosthesis, a partial ossicle prosthesis, an anvil prosthesis and a stapes prosthesis; the total ossicle prosthesis, the partial ossicle prosthesis, the anvil prosthesis and the stapes prosthesis are integrally formed by injection molding of PEEK material, and comprise a head and a connecting rod; the connecting rod is deformable by heating. The application solves the problems of the current clinical widely used metal ossicle prosthesis, such as long-term implantation of metal ions, release of implants, high ejection rate, difficult shaping during operation, high stress shielding risk, poor MRI compatibility and the like, by integrally forming the PEEK material by injection molding. Meanwhile, the structure of the prosthesis can be adjusted by a simple heating mode to adapt to the differences in middle ear structures of different patients. The specific PEEK material is beneficial to the climbing of human soft tissues and prevents the prosthesis from falling off.

Description

Technical Field

[0001] The present application relates to the technical field of medical devices, and more specifically, to an integrated ossicular prosthesis. Background Art

[0002] PEEK (polyetheretherketone) is a thermoplastic specialty engineering plastic characterized by high heat resistance, radiation resistance, high impact strength, good friction and fatigue resistance, flame retardancy, and excellent electrical properties. It has found widespread application in aerospace, automotive, electronics, chemical, machinery, and medical fields. In recent years, PEEK has become particularly attractive as an implant material in the biomedical field, replacing stainless steel, titanium, titanium alloys, and other metals in the preparation of orthopedic implants.

[0003] Current ossicular prostheses generally include a head and a connecting rod, which replaces the damaged ossicles in the ossicular chain. However, existing ossicular prostheses are made in different lengths to accommodate the natural differences in anatomical distances between the middle ear structures of different patients. This increases the size specifications of each prosthesis, making it more difficult for doctors to prepare during surgery. In addition, most ossicular prostheses are fixed structures, and the angle between the connecting rod and the head cannot be adjusted. The angle between the head and the connecting rod is adjusted by assembling the connecting rod and the head or connecting them together with different materials. However, ossicular prostheses made by assembly or combining different materials will also affect the sound transmission effect of the prosthesis due to the different elastic moduli and densities of different materials, thereby reducing the hearing effect.

[0004] Therefore, improving the adjustability of the connecting rod is of great significance to the development of ossicular prostheses. Summary of the Invention

[0005] In order to improve the adjustability of the connecting rod, the present application provides an integrated ossicular prosthesis.

[0006] The present application provides an integrated ossicular prosthesis, which adopts the following technical solutions:

[0007] The one-piece ossicular prosthesis is formed by injection molding of PEEK material and includes a head and a connecting rod. The connecting rod can be deformed when heated.

[0008] By adopting the above technical solution, PEEK has excellent mechanical properties, excellent biocompatibility and clinical feedback, and multiple molding methods. It is an optimal prosthesis molding material. The present application uses PEEK material injection molding to solve the problems of long-term implantation of metal ossicular prostheses (pure titanium, titanium alloy, stainless steel, etc.) that lead to implant failure, high expulsion rate, difficulty in shaping during surgery, high risk of stress shielding, and poor MRI compatibility. PEEK material can be deformed under heating conditions and made into different sizes to adapt to the natural differences in anatomical distances between the middle ear structures of different patients. At the same time, in clinical practice, different patients have different physical signs and have different requirements for the shape and design angle of the prosthesis. The angle between the connecting rod and the head can be adjusted through deformation to improve the tightness between the prosthesis and the ear canal. The deformation adjustment is achieved by heating the connecting rod, which is highly operational and takes a short time. It can save time during surgery, greatly improve surgical efficiency, and reduce patient risks.

[0009] In a specific possible implementation scheme, the integrated ossicular prosthesis is a full ossicular prosthesis, which is coaxially connected from top to bottom by a head, a connecting rod and a tail rod, wherein the head is a disc with a through hole, the connecting rod is deformable, and the tail rod is provided with a groove.

[0010] By adopting the above technical solution, the through holes on the disc can not only reduce the weight of the product, but also increase the doctor's observation field of view during surgery, and are also conducive to the growth of tympanic membrane tissue, so that the disc and tympanic membrane fit more stably, and prevent the prosthesis from falling off the tympanic membrane; the connecting rod can be bent by heating to the load deformation temperature, so that it is convenient for the doctor to adjust the angle and position of the disc according to needs; the groove on the tail rod makes it convenient for the doctor to use tweezers to clamp the prosthesis during surgery.

[0011] In a specific embodiment, the integrated ossicular prosthesis is a partial ossicular prosthesis, which is coaxially connected from top to bottom by a head, a connecting rod and a base, wherein the head is a disc and the base is a hemispherical groove.

[0012] By adopting the above technical solution, the base is a hemispherical groove, which is convenient for placement on the stapes head and more tightly combined with the stapes, and the spherical concave surface can be rotated to adjust the position to adapt to the fit between the disc and the eardrum.

[0013] In a specific embodiment, the integrated ossicular prosthesis is an incus prosthesis, which is coaxially connected from top to bottom by a head, a connecting rod and a base. The head is a cylinder, and an arc-shaped groove matching the end of the malleus is provided on the end face of the cylinder.

[0014] By adopting the above technical solution, the arc-shaped groove is provided to fit the handle of the malleus during surgery, making the connection between the incus prosthesis and the malleus more stable. The base is a hemispherical groove, which is convenient for placement on the stapes head and more tightly connected to the stapes.

[0015] In a specific embodiment, the integrated ossicular prosthesis is a stapes prosthesis, which is coaxially connected from top to bottom via a head and a connecting rod, wherein the head is a hook and a horn opening is provided at the hook.

[0016] By adopting the above technical solution, the trumpet opening facilitates the long process of the incus to better enter the hook during surgery, thereby improving the tightness of the connection between the stapes prosthesis and the long process of the incus, thereby transmitting sound vibrations from the incus to the oval window, thereby realizing sound transmission.

[0017] In a specific embodiment, the method for preparing the PEEK material comprises the following steps:

[0018] S1, surface modification of PEEK to reduce the carbonyl groups on its surface to hydroxyl groups to form hydroxylated polyetheretherketone;

[0019] S2, using amino acids as grafting agents to graft active functional groups onto the surface of the hydroxylated polyetheretherketone.

[0020] By adopting the above technical solution, hydroxylated polyetheretherketone is modified with amino acids essential to the human body. The hydroxyl groups in the hydroxylated polyetheretherketone interact with the carboxylic acid groups on the amino acids, so that active functional groups are grafted onto its surface, thereby improving the bioactivity and biocompatibility of PEEK, and making the PEEK material have good bioactivity and osteoinductivity.

[0021] In a specific embodiment, the specific preparation process of S1 is: PEEK, sodium borohydride and dimethyl sulfoxide are reacted at 115-125°C for 7-9 hours to obtain hydroxylated polyetheretherketone, and the filter cake is obtained by filtration, and the filter cake is washed with anhydrous ethanol, deionized water, hydrochloric acid, and deionized water in sequence and then dried; the mass ratio of PEEK to sodium borohydride is 4-6:1, and the mass volume ratio of PEEK to dimethyl sulfoxide is 0.03-0.05 g / ml.

[0022] By adopting the above technical solution, dimethyl sulfoxide is used as a dispersion medium to prevent sodium borohydride from decomposing easily. PEEK is modified by sodium borohydride to form a modified layer on the PEEK surface, and the carbonyl groups on the PEEK surface are reduced to hydroxyl groups, which is conducive to the subsequent grafting reaction with amino acids. This can not only improve the activity of the PEEK material and the biocompatibility of the material, but also retain the excellent mechanical properties of PEEK.

[0023] In a specific embodiment, the specific preparation process of S2 is as follows: adding hydroxylated polyetheretherketone to DMF, ultrasonically dispersing it at room temperature for 25-35 minutes to form a solution A; adding amino acid to a DMF solution containing dicyclohexylcarbodiimide and 4-lutidine, ultrasonically dispersing it at 45-55°C for 25-35 minutes to form a solution B; mixing solution A and solution B, ultrasonically dispersing them at 45-55°C for 25-35 minutes, and then maintaining the mixture under inert gas. The mixture is refluxed at 45-55° C. for 3-5 hours under protection to form a C solution, anhydrous ethanol is added to the C solution, and the mixture is stirred in a water bath at 45-55° C. for 45-55 minutes. The obtained substance is filtered to obtain a filter cake, which is washed with anhydrous ethanol and then dried. The mass volume ratio of the hydroxylated polyetheretherketone to DMF is 0.08-0.15 g / ml, and the mass ratio of the amino acid, dicyclohexylcarbodiimide and 4-lutidine is 23-28:4-7:1.

[0024] By adopting the above technical solution, amino acids are grafted onto hydroxylated polyetheretherketone, so that the two substances are connected through chemical bonds, thereby improving the activity of PEEK and increasing the biocompatibility of PEEK materials.

[0025] In a specific embodiment, the amino acid is one or more of alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, methionine, glycine, tyrosine, serine, threonine, cysteine, asparagine, glutamine, lysine, arginine, histidine, aspartic acid, and glutamic acid; preferably one or both of aspartic acid and glutamic acid.

[0026] By adopting the above technical solution, the chemical structures of aspartic acid and glutamic acid both contain two carboxyl groups, which can increase the grafting rate with hydroxylated polyetheretherketone, thereby further improving the bioactivity and biocompatibility of PEEK materials.

[0027] In summary, this application has the following beneficial effects:

[0028] 1. The present application adopts PEEK material to form the ossicular prosthesis by one-piece injection molding, which not only makes the connecting rod easy to deform when heated, but also makes ossicular prostheses of different lengths and sizes to meet the natural differences in anatomical distances between the middle ear structures of different patients; at the same time, it is convenient to adjust the angle and position of the head, improve the tightness of the combination of the ossicular prosthesis and the ear canal, and improve the hearing effect; 2. The present application adopts PEEK material to form the ossicular prosthesis by one-piece injection molding, which improves the compatibility of the ossicular prosthesis with the human body. At the same time, the one-piece molding process effectively avoids the reflection and diffraction of sound waves during the transmission of sound waves, resulting in the occurrence of disharmonious sound effects such as noise and overtones, and may also cause scattering and diffusion of sound waves, resulting in sound energy attenuation, thereby improving the hearing effect; 3. The present application modifies the surface of PEEK, reduces the carbonyl groups on its surface to hydroxyl groups, forms hydroxylated polyetheretherketone, and then uses amino acids to graft active functional groups on the surface of hydroxylated polyetheretherketone, thereby improving the bioactivity and biocompatibility of PEEK. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 and Figure 2 is a schematic diagram of the appearance of the total ossicular prosthesis of Example 1 of the present application;

[0030] Figure 3 and Figure 4 is a schematic diagram of the appearance of a portion of the ossicular prosthesis of Example 2 of the present application;

[0031] Figure 5 is a schematic diagram of the appearance of the incus prosthesis of Example 3 of the present application;

[0032] Figure 6 This is a schematic diagram of the appearance of the stapes prosthesis of Example 4 of the present application.

[0033] Description of reference numerals:

[0034] 1. Disc; 2. Connecting rod; 3. Tail rod; 4. Through hole; 5. Groove; 6. Base; 7. Cylinder; 8. Arc-shaped groove; 9. Hook; 10. Speaker opening. DETAILED DESCRIPTION

[0035] The following is combined with Figure 1-6 , Examples and Examples further illustrate the present application in detail. The raw materials involved in the present application can be obtained commercially.

[0036] Example

[0037] Example 1

[0038] This embodiment discloses an integrated ossicular prosthesis, specifically a full ossicular prosthesis.

[0039] like Figure 1 and Figure 2As shown, the one-piece, full-ossicular prosthesis, injection-molded from PEEK, consists of a disc 1, a connecting rod 2, and a tail rod 3 coaxially connected from top to bottom. The disc 1 is provided with spaced-apart holes 4 of varying sizes, reducing product weight while also enhancing the surgeon's field of view during surgery. Furthermore, the holes facilitate the growth of tympanic membrane tissue, ensuring a more stable fit between the disc 1 and the tympanic membrane and preventing the prosthesis from dislodging. The connecting rod 2 can be heated to 150°C to deform under load, allowing the surgeon to adjust the angle and position of the disc 1 as needed to enhance the tightness of the full-ossicular prosthesis to the stapes. The prosthesis can be manufactured in various lengths to accommodate the natural anatomical distances between middle ear structures in different patients. The tail rod 3 is provided with multiple grooves 5 on its surface to facilitate the surgeon's use of forceps to grasp the prosthesis during surgery.

[0040] In this embodiment, PEEK material was injected using a conventional high-temperature injection molding method using a heat-resistant mold. The dried PEEK material was then molded into a complete ossicular prosthesis that met the requirements. The injection molding machine was operated at an injection temperature of 380°C, an injection pressure of 90 MPa, a material storage pressure of 110 MPa, a mold closing pressure of 33 MPa, a mold temperature of 120°C, and a screw speed of 80 r / min. The heat-resistant mold was a self-made mold. This one-piece ossicular prosthesis, injection-molded using PEEK, effectively avoids sound wave reflection and diffraction during sound wave transmission, which can lead to dissonant sounds such as noise and overtones. It also avoids sound wave scattering and diffusion, which can attenuate sound energy, thereby improving auditory quality and compatibility with the human body.

[0041] The preparation method of the PEEK material in this embodiment is specifically carried out by the following steps:

[0042] (1) Weigh 150g of PEEK and place it in a glass dish, place the glass dish in a vacuum drying oven, and dry it at 80°C for 12h; place the dried PEEK in a grinder for crushing, and then screen the crushed PEEK with a 30-mesh sieve (pore size of 0.6mm); measure 100ml of dimethyl sulfoxide and place it in a 500ml three-necked flask, and add 4g of crushed PEEK and 1g of sodium borohydride; place the three-necked flask in an oil bath (dimethyl silicone oil), and react for 9h at an oil bath temperature of 115°C and stirring; after the reaction is completed, the temperature of the three-necked flask is cooled to room temperature, and then filtered with microporous filter paper, and washed with anhydrous ethanol, deionized water, hydrochloric acid, and deionized water in sequence; after the filtration is completed, the filtrate is discarded, the filter cake is placed in a glass dish, and then the glass dish is placed in a vacuum drying oven and dried at 80°C for 12h; the dried material is ground to obtain hydroxylated polyetheretherketone;

[0043] (2) Add 8g of hydroxylated polyetheretherketone and 100ml of DMF to a three-necked flask, and ultrasonically disperse for 25min at room temperature to form a suspension solution A; take 23g of glutamic acid and add it to a 20ml DMF solution beaker containing 4g of dicyclohexylcarbodiimide and 1g of 4-dimethylaminopyridine, place the beaker on an ultrasonic instrument, set the ultrasonic temperature to 45℃, and ultrasonically disperse for 35min to form a suspension solution B; add the suspension solution B to the three-necked flask containing the suspension solution A, continue to place the three-necked flask on the ultrasonic instrument, and ultrasonically disperse at 45℃ for 35min; move the three-necked flask to a magnetic heating and stirring device, perform fixed stirring, and heat in a water bath at a water bath temperature of 45℃. The mixture was filled with nitrogen and the nitrogen was continuously filled for 30 minutes. The reflux reaction was carried out under vacuum conditions for 3 hours to form a C suspension solution. The C suspension solution was poured into a beaker and 300 ml of anhydrous ethanol was added at the same time. The beaker was placed on a water bath stirring device and treated at 45°C for 55 minutes to fully mix DMF and anhydrous ethanol. The suspension was filtered on a Buchner funnel with microporous filter paper and rinsed with anhydrous ethanol to rinse the dicyclohexylcarbodiimide and 4-dimethylaminopyridine adsorbed on the suspension. The filtrate was then discarded and the filter cake was placed in a glass dish. The glass dish containing the filter cake was placed in a vacuum drying oven and dried at 80°C for 15 hours to obtain a PEEK material.

[0044] Example 2

[0045] This embodiment differs from the embodiment in that this embodiment discloses an integrated ossicular prosthesis, specifically a partial ossicular prosthesis.

[0046] like Figure 3 and Figure 4 As shown, the one-piece partial ossicular prosthesis, injection-molded from PEEK material, is coaxially connected from top to bottom by a disc 1, a connecting rod 2, and a base 6. The disc 1 is provided with spaced-apart holes 4 of varying sizes, which reduce the product's weight while also enhancing the surgeon's field of view during surgery. Furthermore, the holes 4 facilitate the growth of tympanic membrane tissue, ensuring a more stable fit between the disc 1 and the tympanic membrane and preventing the prosthesis from falling out. The connecting rod 2 can be heated to 150°C to deform under load, allowing the surgeon to adjust the angle and position of the disc 1 as needed to enhance the tightness of the partial ossicular prosthesis' fit with the stapes. The disc 1 can be manufactured in various lengths to accommodate the natural variations in anatomical distances between middle ear structures in different patients. The base 6 features a hemispherical groove, facilitating placement on the stapes head for a tighter fit. The spherical groove can be rotated to adjust the disc 1's fit to the tympanic membrane.

[0047] Example 3

[0048] This embodiment differs from the embodiment in that this embodiment discloses an integrated ossicular prosthesis, specifically an incus prosthesis.

[0049] like Figure 5 As shown, the one-piece incus prosthesis, injection-molded from PEEK material, is coaxially connected from top to bottom by a cylinder 7, a connecting rod 2, and a base 6. The cylinder 7 has an arcuate groove 8 on its upper end surface that matches the end of the malleus. This arcuate groove 8 facilitates contact with the handle of the malleus during surgery, ensuring a more stable connection between the incus prosthesis and the malleus. The connecting rod 2 can be heated to 150°C to deform under load, allowing the surgeon to adjust the angle and position of the cylinder 7 as needed to improve the tightness of the incus prosthesis and the malleus. The incus prosthesis can also be manufactured in various lengths to accommodate the natural anatomical distances between different patients' middle ear structures. The base 6 has a hemispherical groove, which facilitates placement on the stapes head for a tighter fit. The spherical groove can be rotated and adjusted to adjust the disc's fit to the eardrum. The diameter of the connection between the connecting rod 2 and the cylinder 7 is smaller than that of the connection between the connecting rod 2 and the base 6, facilitating adaptive adjustment of the angle between the head and the connecting rod 2 to ensure a better connection between the cylinder 7 and the base 6, respectively.

[0050] Example 4

[0051] The difference between this embodiment and the embodiment is that this embodiment discloses an integrated ossicular prosthesis, specifically a stapes prosthesis.

[0052] like Figure 6 As shown, the one-piece stapes prosthesis, injection-molded from PEEK material, is coaxially connected from top to bottom via a hook 9 and a connecting rod 2. The hook 9 is provided with a horn opening 10, which facilitates the entry of the long process of the incus into the hook 9 during surgery, thereby improving the tightness of the connection between the stapes prosthesis and the long process of the incus, thereby transmitting sound vibrations from the incus to the oval window, achieving effective sound transmission. The connecting rod 2 is cylindrical, allowing it to be rotated to adjust the position of the hook 9 and the long process of the incus after insertion into the hole in the stapes footplate. The connecting rod 2 can also be heated to 150°C to cause load deformation. The doctor can adjust the angle and position of the hook 9 as needed to improve the tightness of the stapes prosthesis and the auditory canal. The rod can also be manufactured in different lengths to accommodate the natural differences in anatomical distances between different patients' middle ear structures.

[0053] Example 5

[0054] The difference between this embodiment and embodiment 1 is that, in this embodiment, the preparation method of the PEEK material is specifically carried out by the following steps:

[0055] (1) Weigh 150g of PEEK and place it in a glass dish, place the glass dish in a vacuum drying oven, and dry it at 80°C for 12h; place the dried PEEK in a grinder for crushing, and then screen the crushed PEEK with a 30-mesh sieve (pore size of 0.6mm); measure 100ml of dimethyl sulfoxide and place it in a 500ml three-necked flask, and add 5g of the crushed PEEK and 1g of sodium borohydride; place the three-necked flask in an oil bath (dimethyl silicone oil), and react for 8h under the condition of an oil bath temperature of 120°C and stirring; after the reaction is completed, the temperature of the three-necked flask is cooled to room temperature, and then filtered with microporous filter paper, and washed with anhydrous ethanol, deionized water, hydrochloric acid, and deionized water in sequence; after the filtration is completed, the filtrate is discarded, the filter cake is placed in a glass dish, and then the glass dish is placed in a vacuum drying oven and dried at 80°C for 12h; the dried material is ground to obtain hydroxylated polyetheretherketone;

[0056] (2) Add 8g of hydroxylated polyetheretherketone and 100ml of DMF to a three-necked flask, and ultrasonically disperse for 25min at room temperature to form a suspension solution A; take 23g of glutamic acid and add it to a 20ml DMF solution beaker containing 4g of dicyclohexylcarbodiimide and 1g of 4-dimethylaminopyridine, place the beaker on an ultrasonic instrument, set the ultrasonic temperature to 45℃, and ultrasonically disperse for 35min to form a suspension solution B; add the suspension solution B to the three-necked flask containing the suspension solution A, continue to place the three-necked flask on the ultrasonic instrument, and ultrasonically disperse at 45℃ for 35min; move the three-necked flask to a magnetic heating and stirring device, perform fixed stirring, and heat in a water bath at a water bath temperature of 45℃. The mixture was filled with nitrogen and the nitrogen was continuously filled for 30 minutes. The reflux reaction was carried out under vacuum conditions for 3 hours to form a C suspension solution. The C suspension solution was poured into a beaker and 300 ml of anhydrous ethanol was added at the same time. The beaker was placed on a water bath stirring device and treated at 45°C for 55 minutes to fully mix DMF and anhydrous ethanol. The suspension was filtered on a Buchner funnel with microporous filter paper and rinsed with anhydrous ethanol to rinse the dicyclohexylcarbodiimide and 4-dimethylaminopyridine adsorbed on the suspension. The filtrate was then discarded and the filter cake was placed in a glass dish. The glass dish containing the filter cake was placed in a vacuum drying oven and dried at 80°C for 15 hours to obtain a PEEK material.

[0057] Example 6

[0058] The difference between this embodiment and embodiment 1 is that, in this embodiment, the preparation method of the PEEK material is specifically carried out by the following steps:

[0059] (1) Weigh 150g of PEEK and place it in a glass dish, place the glass dish in a vacuum drying oven, and dry it at 80°C for 12h; place the dried PEEK in a grinder for crushing, and then screen the crushed PEEK with a 30-mesh sieve (pore size of 0.6mm); measure 100ml of dimethyl sulfoxide and place it in a 500ml three-necked flask, and add 6g of crushed PEEK and 1g of sodium borohydride; place the three-necked flask in an oil bath (dimethyl silicone oil), and react for 7h at an oil bath temperature of 125°C and stirring; after the reaction is completed, the temperature of the three-necked flask is cooled to room temperature, and then filtered with microporous filter paper, and washed with anhydrous ethanol, deionized water, hydrochloric acid, and deionized water in sequence; after the filtration is completed, the filtrate is discarded, the filter cake is placed in a glass dish, and then the glass dish is placed in a vacuum drying oven and dried at 80°C for 12h; the dried material is ground to obtain hydroxylated polyetheretherketone;

[0060] (2) Add 8g of hydroxylated polyetheretherketone and 100ml of DMF to a three-necked flask, and ultrasonically disperse for 25min at room temperature to form a suspension solution A; take 23g of glutamic acid and add it to a 20ml DMF solution beaker containing 4g of dicyclohexylcarbodiimide and 1g of 4-dimethylaminopyridine, place the beaker on an ultrasonic instrument, set the ultrasonic temperature to 45℃, and ultrasonically disperse for 35min to form a suspension solution B; add the suspension solution B to the three-necked flask containing the suspension solution A, continue to place the three-necked flask on the ultrasonic instrument, and ultrasonically disperse at 45℃ for 35min; move the three-necked flask to a magnetic heating and stirring device, perform fixed stirring, and heat in a water bath at a water bath temperature of 45℃. The mixture was filled with nitrogen and the nitrogen was continuously filled for 30 minutes. The reflux reaction was carried out under vacuum conditions for 3 hours to form a C suspension solution. The C suspension solution was poured into a beaker and 300 ml of anhydrous ethanol was added at the same time. The beaker was placed on a water bath stirring device and treated at 45°C for 55 minutes to fully mix DMF and anhydrous ethanol. The suspension was filtered on a Buchner funnel with microporous filter paper and rinsed with anhydrous ethanol to rinse the dicyclohexylcarbodiimide and 4-dimethylaminopyridine adsorbed on the suspension. The filtrate was then discarded and the filter cake was placed in a glass dish. The glass dish containing the filter cake was placed in a vacuum drying oven and dried at 80°C for 15 hours to obtain a PEEK material.

[0061] Example 7

[0062] The difference between this embodiment and embodiment 5 is that, in this embodiment, the preparation method of the PEEK material is specifically carried out by the following steps:

[0063] (1) Weigh 150g of PEEK and place it in a glass dish, place the glass dish in a vacuum drying oven, and dry it at 80°C for 12h; place the dried PEEK in a grinder for crushing, and then screen the crushed PEEK with a 30-mesh sieve (pore size of 0.6mm); measure 100ml of dimethyl sulfoxide and place it in a 500ml three-necked flask, and add 5g of the crushed PEEK and 1g of sodium borohydride; place the three-necked flask in an oil bath (dimethyl silicone oil), and react for 8h under the condition of an oil bath temperature of 120°C and stirring; after the reaction is completed, the temperature of the three-necked flask is cooled to room temperature, and then filtered with microporous filter paper, and washed with anhydrous ethanol, deionized water, hydrochloric acid, and deionized water in sequence; after the filtration is completed, the filtrate is discarded, the filter cake is placed in a glass dish, and then the glass dish is placed in a vacuum drying oven and dried at 80°C for 12h; the dried material is ground to obtain hydroxylated polyetheretherketone;

[0064] (2) Add 12g of hydroxylated polyetheretherketone and 100ml of DMF to a three-necked flask, and ultrasonically disperse for 30min at room temperature to form a suspension solution A; take 25g of glutamic acid and add it to a 20ml DMF solution beaker containing 6g of dicyclohexylcarbodiimide and 1g of 4-dimethylaminopyridine, place the beaker on an ultrasonic instrument, set the ultrasonic temperature to 50℃, and ultrasonically disperse for 30min to form a suspension solution B; add the suspension solution B to the three-necked flask containing the suspension solution A, continue to place the three-necked flask on the ultrasonic instrument, and ultrasonically disperse at 50℃ for 30min; move the three-necked flask to a magnetic heating and stirring device, perform fixed stirring, and heat in a water bath at a water bath temperature of 50℃. The mixture was filled with nitrogen and the nitrogen was continuously filled for 30 minutes. The reflux reaction was carried out under vacuum conditions for 4 hours to form a C suspension solution. The C suspension solution was poured into a beaker and 300 ml of anhydrous ethanol was added at the same time. The beaker was placed on a water bath stirring device and treated at 50°C for 50 minutes to fully mix DMF and anhydrous ethanol. The suspension was filtered on a Buchner funnel with microporous filter paper and rinsed with anhydrous ethanol to rinse the dicyclohexylcarbodiimide and 4-dimethylaminopyridine adsorbed on the suspension. The filtrate was then discarded and the filter cake was placed in a glass dish. The glass dish containing the filter cake was placed in a vacuum drying oven and dried at 80°C for 15 hours to obtain a PEEK material.

[0065] Example 8

[0066] The difference between this embodiment and embodiment 5 is that, in this embodiment, the preparation method of the PEEK material is specifically carried out by the following steps:

[0067] (1) Weigh 150g of PEEK and place it in a glass dish, place the glass dish in a vacuum drying oven, and dry it at 80°C for 12h; place the dried PEEK in a grinder for crushing, and then screen the crushed PEEK with a 30-mesh sieve (pore size of 0.6mm); measure 100ml of dimethyl sulfoxide and place it in a 500ml three-necked flask, and add 5g of the crushed PEEK and 1g of sodium borohydride; place the three-necked flask in an oil bath (dimethyl silicone oil), and react for 8h under the condition of an oil bath temperature of 120°C and stirring; after the reaction is completed, the temperature of the three-necked flask is cooled to room temperature, and then filtered with microporous filter paper, and washed with anhydrous ethanol, deionized water, hydrochloric acid, and deionized water in sequence; after the filtration is completed, the filtrate is discarded, the filter cake is placed in a glass dish, and then the glass dish is placed in a vacuum drying oven and dried at 80°C for 12h; the dried material is ground to obtain hydroxylated polyetheretherketone;

[0068] (2) Add 15g of hydroxylated polyetheretherketone and 100ml of DMF to a three-necked flask, and ultrasonically disperse for 35min at room temperature to form a suspension solution A; take 28g of glutamic acid and add it to a 20ml DMF solution beaker containing 7g of dicyclohexylcarbodiimide and 1g of 4-dimethylaminopyridine, place the beaker on an ultrasonic instrument, set the ultrasonic temperature to 55℃, and ultrasonically disperse for 25min to form a suspension solution B; add the suspension solution B to the three-necked flask containing the suspension solution A, continue to place the three-necked flask on the ultrasonic instrument, and ultrasonically disperse at 55℃ for 25min; move the three-necked flask to a magnetic heating and stirring device, perform fixed stirring, and heat in a water bath at a water bath temperature of 55℃. The mixture was filled with nitrogen and the nitrogen was continuously filled for 30 minutes. The reflux reaction was carried out under vacuum conditions for 5 hours to form a C suspension solution. The C suspension solution was poured into a beaker and 300 ml of anhydrous ethanol was added at the same time. The beaker was placed on a water bath stirring device and treated at 55°C for 45 minutes to fully mix DMF and anhydrous ethanol. The suspension was filtered on a Buchner funnel with microporous filter paper and rinsed with anhydrous ethanol to rinse the dicyclohexylcarbodiimide and 4-dimethylaminopyridine adsorbed on the suspension. The filtrate was then discarded and the filter cake was placed in a glass dish. The glass dish containing the filter cake was placed in a vacuum drying oven and dried at 80°C for 15 hours to obtain a PEEK material.

[0069] Example 9

[0070] The difference between this embodiment and embodiment 7 is that an equal amount of glutamic acid in step (2) is replaced by aspartic acid.

[0071] Example 10

[0072] The difference between this example and Example 7 is that the glutamic acid in step (2) is replaced by a mixture of 10 g of glutamic acid and 15 g of aspartic acid.

[0073] Example 11

[0074] The difference between this embodiment and embodiment 1 is that, in this embodiment, the PEEK material is the same commercially available PEEK as in the embodiment and is not modified.

[0075] In this embodiment, PEEK is subjected to conventional high-temperature injection molding method, and the mold is a high-temperature resistant mold. The dried PEEK material is made into a full ossicular prosthesis that meets the requirements, wherein the injection molding temperature of the injection molding machine is 380°C, the injection molding pressure is 90Mpa, the material storage pressure is 110Mpa, the mold closing pressure is 33Mpa, the mold temperature is 120°C, the screw speed is 80r / min, and the high-temperature resistant mold is a self-made mold of our company.

[0076] Performance testing methods

[0077] 1. Biological activity test

[0078] Cytological bioactivity assays were performed on the total ossicular prostheses prepared in Examples 1 and 5-11 using membrane-derived human osteoblast-like cell line MG-63 osteoblasts. MG-63 osteoblasts were revived in a high-glucose cell culture medium containing 10% fetal bovine serum and placed in a cell culture incubator at 37°C, 95% humidity, and 5% CO2. The culture medium was changed every other day, and the cell viability was observed under an optical microscope. MG-63 osteoblasts in the logarithmic growth phase were prepared into a cell suspension.

[0079] The standard test samples of Examples 1 and 5-11 were sterilized by gamma ray irradiation for 2 hours and placed in a 24-well plate. The prepared MG-63 cell suspension was inoculated on the surface of the sample of each example, and the cell culture was terminated after 24 hours. The number of cell adhesion and proliferation was detected by acridine orange fluorescence staining. Rinse with PBS (phosphate buffered saline, 1L PBS formula: 8g sodium chloride, 0.2g potassium chloride, 1.44g disodium hydrogen phosphate, 0.24g potassium dihydrogen phosphate) three times, fix with 95% ethanol for 5 minutes, stain with 0.05% acridine orange for 5 minutes, and rinse with PBS three times; observe and count under a fluorescence microscope. The number of cells adhering to and proliferating on the surface of the material is shown in Table 1.

[0080] 2. Tensile strength

[0081] The ossicular prostheses prepared in Examples 1 and 5-11 were subjected to tensile testing according to ASTM D638 using an Instron Model 5544 universal electronic tensile testing machine from Instron Corporation. At room temperature, the tensile speed and gauge length were 2 mm / min and 20 mm, respectively. The test results are shown in Table 1.

[0082] Table 1 Performance test data of Examples 1, 5-11

[0083]

[0084] With reference to Table 1, in combination with Examples 1, 5-10 and 11, it can be seen that the ossicular prostheses prepared in Examples 1 and 5-10 meet the tensile strength requirements of biological bone (60-140 MPa) while retaining the excellent mechanical properties of PEEK, compared with the ossicular prosthesis prepared in Example 11, so that the ossicular prosthesis has higher bioactivity and biocompatibility. The present application modifies PEEK by sodium borohydride, so that a modified layer is formed on the surface of PEEK, and the carbonyl groups on the surface of PEEK are reduced to hydroxyl groups to form hydroxylated polyetheretherketone. The hydroxylated polyetheretherketone is modified by amino acids essential to the human body. The hydroxyl groups in the hydroxylated polyetheretherketone interact with the carboxylic acid groups on the amino acids, so that active functional groups are grafted onto its surface, thereby improving the bioactivity and biocompatibility of PEEK and making the PEEK material have good bioactivity. The ossicular prosthesis prepared therefrom has higher bioactivity, which is beneficial for the attachment of human soft tissues such as blood vessels, thereby improving the bonding effect between the prosthesis and human tissue, further strengthening the fixation of the prosthesis, and preventing deformation and falling off.

[0085] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. An integrated ossicular prosthesis, characterized in that: The one-piece ossicular prosthesis is formed by injection molding of PEEK material and comprises a head and a connecting rod (2), wherein the connecting rod (2) is deformable upon heating; The preparation method of the PEEK material comprises the following steps: S1, surface modification of PEEK to reduce the carbonyl groups on its surface to hydroxyl groups to form hydroxylated polyetheretherketone; S2, using amino acids as grafting agents to graft active functional groups on the surface of the hydroxylated polyetheretherketone; The specific preparation process of S2 is as follows: adding hydroxylated polyetheretherketone to DMF, ultrasonically dispersing it at room temperature for 25-35 minutes to form solution A; adding amino acid to a DMF solution containing dicyclohexylcarbodiimide and 4-lutidine, ultrasonically dispersing it at 45-55°C for 25-35 minutes to form solution B; mixing solution A and solution B, ultrasonically dispersing them at 45-55°C for 25-35 minutes, and then refluxing them at 45-55°C for 3-5 hours under inert gas protection to form solution C, adding anhydrous ethanol to solution C, stirring the mixture in a water bath at 45-55°C for 45-55 minutes, filtering the obtained substance to obtain a filter cake, washing it with anhydrous ethanol, and then drying it; the mass volume ratio of the hydroxylated polyetheretherketone to DMF is 0.08-0.15 g / ml, and the mass ratio of the amino acid, dicyclohexylcarbodiimide, and 4-lutidine is 23-28:4-7:1; The amino acids are glutamic acid and aspartic acid; The connecting rod (2) can be heated to 150° C. to cause load deformation.

2. The integrated ossicular prosthesis according to claim 1, characterized in that: The integrated ossicular prosthesis is a full ossicular prosthesis, which is formed by coaxially connecting a head, a connecting rod (2) and a tail rod (3) from top to bottom, wherein the head is a disc (1), a through hole (4) is provided on the disc (1), the connecting rod (2) is deformable, and a groove (5) is provided on the tail rod (3).

3. The integrated ossicular prosthesis according to claim 1, characterized in that: The integrated ossicular prosthesis is a partial ossicular prosthesis, which is formed by coaxially connecting a head, a connecting rod (2) and a base (6) from top to bottom, wherein the head is a disc (1) and the base (6) is a hemispherical groove.

4. The integrated ossicular prosthesis according to claim 1, characterized in that: The integrated ossicular prosthesis is an incus prosthesis, which is coaxially connected from top to bottom via a head, a connecting rod (2) and a base (6), wherein the head is a cylinder (7), and an arc-shaped groove (8) matching the end of the malleus is provided on the end surface of the cylinder (7).

5. The integrated ossicular prosthesis according to claim 1, characterized in that: The integrated ossicular prosthesis is a stapes prosthesis, which is formed by coaxially connecting a head and a connecting rod (2) from top to bottom, wherein the head is a hook (9) and a horn opening (10) is provided at the hook (9).

6. The integrated ossicular prosthesis according to claim 1, characterized in that: The specific preparation process of S1 is: PEEK, sodium borohydride and dimethyl sulfoxide are reacted at 115-125°C for 7-9 hours to obtain hydroxylated polyetheretherketone, and the filter cake is filtered out, and washed with anhydrous ethanol, deionized water, hydrochloric acid and deionized water in sequence and then dried; the mass ratio of PEEK to sodium borohydride is 4-6:1, and the mass-to-volume ratio of PEEK to dimethyl sulfoxide is 0.03-0.05 g / ml.

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