Medical-grade polyether-ether-ketone composite material, preparation method thereof and human skeleton implant

Abstract

The invention discloses a medical-grade polyether-ether-ketone composite material, a preparation method thereof and a human skeleton implant, relates to the technical field of medical materials, and solves the problems that an existing human skeleton implant is limited in bone tissue regeneration and repair promotion effect and poor in antibacterial property. The PEEK modified ZIF-8 composite material comprises 1000 parts of PEEK powder, 100 to 500 parts of a sized HAP modified ZIF-8 composite material, 1 to 3 parts of a silane coupling agent and 2 to 5 parts of calcium stearate. The glued HAP modified ZIF-8 composite material is obtained by reacting HAP, methylimidazole and anhydrous zinc nitrate in a DMF (Dimethyl Formamide) solution of polyetherimide; wherein the HAP accounts for 3 to 21 parts, the methylimidazole accounts for 100 to 350 parts, and the anhydrous zinc nitrate accounts for 120 to 380 parts. The material disclosed by the invention can be used for human skeleton implants, has a bacteriostatic effect, a relatively strong capability of combining with bone cell tissues and a function of promoting regeneration and repair of bone cells and bone tissues, and has a wide application prospect in the medical field.

Description

Technical Field

[0001] The invention relates to the technical field of medical materials, and in particular to a medical-grade polyetheretherketone composite material and a preparation method thereof and a human bone implant. Background Art

[0002] Polyetheretherketone (PEEK) is widely used in human bone implants due to its good biocompatibility and elastic modulus similar to that of bones. Compared with traditional metals, PEEK material will not interfere with medical tests such as X-rays and magnetic resonance imaging. It also has the characteristics of light weight and high strength, making it a substitute for traditional metal materials.

[0003] Existing PEEK human bone implants also have many disadvantages in application: on the one hand, its surface is relatively inert, its ability to bind to bone cell tissue is weak, and its bone integration speed is relatively slow, which is not conducive to the rapid growth and stable attachment of new bone. On the other hand, it cannot actively induce the growth and differentiation of bone cells, and its role in promoting the regeneration and repair of bone tissue is limited. In addition, polyetheretherketone has insufficient antibacterial properties and is susceptible to bacterial infection, leading to complications such as inflammation at the implant site. Summary of the invention

[0004] In order to solve the above problems in the application of existing PEEK materials as bone implants, the present invention provides a medical-grade polyetheretherketone composite material, a preparation method thereof, and a human bone implant.

[0005] The technical solution of the present invention is as follows: A medical-grade polyetheretherketone composite material comprising the following components in parts by weight: 1000 parts of PEEK powder, 100 to 500 parts of HAP-modified ZIF-8 composite material after sizing, 1 to 3 parts of silane coupling agent, and 2 to 5 parts of calcium stearate; The sizing-treated HAP-modified ZIF-8 composite material is obtained by reacting HAP, methylimidazole and anhydrous zinc nitrate in a DMF solution of polyetherimide; The mass proportions of HAP, methylimidazole and anhydrous zinc nitrate are: 3 to 21 parts of HAP, 100 to 350 parts of methylimidazole, and 120 to 380 parts of anhydrous zinc nitrate.

[0006] Preferably, the silane coupling agent is A-174.

[0007] Preferably, the concentration of the DMF solution of polyetherimide is 3%.

[0008] Preferably, the reaction process of the HAP@ZIF-8 composite material after sizing is specifically as follows: HAP, methylimidazole and anhydrous zinc nitrate were added to a DMF solution of polyetherimide, stirred at room temperature, then transferred to a high-pressure reactor for solvothermal reaction, and finally washed with anhydrous ethanol and dried.

[0009] Preferably, the stirring time is 6 h to 10 h; the reaction temperature of the solvothermal reaction is 100° C. to 180° C., and the reaction time is 12 h to 24 h.

[0010] Preferably, the high-pressure reactor is a polytetrafluoroethylene stainless steel high-pressure reactor.

[0011] The most preferred reaction temperature of the solvent thermal reaction is 160° C., and the most preferred reaction time is 24 h. Under this temperature and reaction time, the ZIF-8 obtained in the reaction has the best crystallinity.

[0012] The present invention also provides a method for preparing the above-mentioned medical-grade polyetheretherketone composite material, comprising the following steps: S1, putting the dried PEEK powder, the HAP-modified ZIF-8 composite material after sizing, the silane coupling agent and calcium stearate into a mixer for mixing to obtain a premix; The dried PEEK powder is placed in a vacuum drying oven and dried at 120°C to 180°C for 4h to 6h; most preferably, the drying temperature of the vacuum drying oven is 140°C and the drying time is 4h; S2, putting the premix into a melt spinning machine for spinning to obtain a PEEK composite material.

[0013] Preferably, the mixing time is 20 min.

[0014] Preferably, the spinning temperature is 340°C to 375°C.

[0015] The present invention also provides a human bone implant, which is prepared from the medical-grade polyetheretherketone composite material by a 3D printer.

[0016] Preferably, the nozzle temperature of the 3D printer is 400°C to 450°C, and the chamber temperature is 250°C to 400°C.

[0017] Most preferably, the nozzle temperature of the 3D printer is 400°C and the chamber temperature is 300°C. The human bone samples printed under this temperature condition have the best crystallinity and uniform color.

[0018] Compared with the prior art, the specific beneficial effects of the present invention are: The invention uses polyetherimide as a sizing agent and utilizes a solvothermal method to prepare a HAP@ZIF-8 nanocomposite material after sizing. Since the formed ZIF-8 has unique structural characteristics such as adjustable pore size, high specific surface area, high thermal stability, biodegradability, biocompatibility, antibacterial performance, etc., the biocompatibility and antibacterial performance of PEEK are greatly improved, the adhesion, proliferation and differentiation of bone cells are promoted, a good channel is provided for the deposition of inorganic minerals in an organic matrix, and the formation of bones and the regeneration of bone cells are promoted. The chemical composition and crystal structure of HAP are similar to those of inorganic components in human bones, and HAP has good biocompatibility and osteoconductivity, and realizes the repair and anti-infection function of PEEK in promoting bone tissue. Under the synergistic effect of ZIF-8 and HAP, the human bone implant provided by the invention has an antibacterial effect, a strong ability to combine with bone cell tissue, and a regeneration and repair effect of promoting bone cell regeneration and bone tissue, and has broad application prospects in the medical field.

[0019] The experimental results show that HAP@ZIF-8 / PEEK composite material can significantly inhibit the survival rate of Staphylococcus aureus, showing a good antibacterial effect. It also greatly improves the survival rate of pre-osteoblasts, showing a good effect in promoting osteoblast regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a schematic diagram of the test results of the survival rate of Staphylococcus aureus in the presence of the material samples prepared in each embodiment and comparative example; Figure 2 It is a schematic diagram of the test results of the activity percentage of pre-osteoblasts in the presence of material samples prepared in various embodiments and comparative examples. DETAILED DESCRIPTION In order to make the technical solution of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the specification of the present invention. It should be noted that the following embodiments are only used to better understand the technical solution of the present invention and should not be understood as a limitation to the present invention.

[0021] Example 1. First, the polyetheretherketone powder was placed in a vacuum drying oven and dried at 140° C. for 4 h.

[0022] Then, 9 g HAP, 216.47 g methylimidazole and 249.14 g anhydrous zinc nitrate were placed in a 3% polyetherimide DMF solution and stirred at room temperature for 8 h. The resulting mixed solution was transferred into a polytetrafluoroethylene stainless steel high-pressure reactor and reacted at 160 ° C for 24 h. The mixture was washed with anhydrous ethanol and dried to obtain the HAP@ZIF-8 composite material after sizing.

[0023] 1000 g of dried polyetheretherketone powder, 300 g of sized HAP-modified ZIF-8 composite material, 3 g of silane coupling agent A-174 and 3 g of calcium stearate were put into a high-speed mixer and mixed at high speed for 20 minutes to obtain a premix.

[0024] The premix was put into a high-temperature melt spinning machine to prepare PEEK composite filaments at 370°C.

[0025] Finally, the obtained PEEK composite filament was placed in a 3D printer with a nozzle temperature of 400°C and a chamber temperature of 300°C to print human bone samples. The sample was recorded as HAP@ZIF-8 / PEEK-30.

[0026] Example 2. The preparation method of this embodiment is the same as that of embodiment 1, except that 4.5 g of HAP, 108.24 g of methylimidazole and 124.57 g of anhydrous zinc nitrate are placed in a 3% polyetherimide DMF solution and stirred at room temperature for 8 h.

[0027] The sample prepared in this example is recorded as HAP@ZIF-8 / PEEK-15.

[0028] Example 3. The preparation method of this embodiment is the same as that of embodiment 1, except that 13.5 g of HAP, 324.71 g of methylimidazole and 373.71 g of anhydrous zinc nitrate are placed in a 3% polyetherimide DMF solution and stirred at room temperature for 8 h.

[0029] The sample prepared in this example is denoted as HAP@ZIF-8 / PEEK-45.

[0030] Comparative Example 1. First, the polyetheretherketone powder was placed in a vacuum drying oven and dried at 140° C. for 4 h.

[0031] 1000g of dried polyetheretherketone powder, 3g of silane coupling agent A-174 and 3g of calcium stearate were placed in a high-speed mixer and mixed at high speed for 20 minutes to obtain a premix, which was then placed in a high-temperature melt spinning machine to prepare PEEK filaments at 370°C. The obtained PEEK filaments were then placed in a 3D printer with a nozzle temperature of 400°C and a chamber temperature of 300°C to print human bone samples, which were recorded as C-PEEK.

[0032] Comparative Example 2. First, the polyetheretherketone powder was placed in a vacuum drying oven and dried at 140° C. for 4 h.

[0033] 1000g of dried polyetheretherketone powder, 3g of HAP, 3g of silane coupling agent A-174 and 3g of calcium stearate were placed in a high-speed mixer and mixed at high speed for 20 minutes to obtain a premix, which was then placed in a high-temperature melt spinning machine to prepare PEEK filaments at 370°C. The obtained PEEK filaments were then placed in a 3D printer with a nozzle temperature of 400°C and a chamber temperature of 300°C to print human bone samples, which were recorded as HAP@PEEK.

[0034] Effect example 1. The survival rate of Staphylococcus aureus in the presence of the material samples prepared in each embodiment and comparative example was determined by plate counting method.

[0035] Staphylococcus aureus (purchased from Shanghai Yuchun Biotechnology Co., Ltd., batch number SHBCC D12341) was diluted with phosphate buffer and inoculated into a culture medium. The material samples prepared in each embodiment and comparative example were placed in the culture medium. After waiting for 2 hours, the number of surviving Staphylococcus aureus was determined by plate count method, and the survival rate was calculated. The results are as follows: Figure 1 shown.

[0036] It can be seen from the test results that in the presence of pure PEEK material (Comparative Example 1) and HAP / PEEK (Comparative Example 2), the survival rates of Staphylococcus aureus reached 97.35% and 94.5%. This shows that the antibacterial properties of pure PEEK material and HAP-doped PEEK material are poor. After adding HAP-modified ZIF-8 composite material, the prepared composite material exhibits excellent antibacterial properties. The HAP@ZIF-8 / PEEK-30 composite material (Example 1) has a great inhibitory effect on the survival of Staphylococcus aureus, and its bacterial survival rate is 42.75%.

[0037] Effect example 2. The MTT method was used to determine the effects of the material samples prepared in each embodiment and comparative example on the activity of preosteoblasts.

[0038] First, the preosteoblasts were placed in a 10% α-MEM culture medium to revive the preosteoblasts. The revived preosteoblasts were then prepared into a single cell suspension with a density of 2000 / 200 μL and inoculated into a 96-well plate. The composite materials prepared in Examples 1-3 and Comparative Examples 1-2 were added respectively and cultured for 3 days. After the culture was completed, a certain amount of MTT solution with a concentration of 5 mg / mL was added to each well, and the incubation continued for 3 hours. Finally, each well was centrifuged to obtain the precipitate, 150 μL of dimethyl sulfoxide was added, and the solution was dissolved by shaking. Finally, the absorbance of each group was measured at 480 nm using an enzyme reader. The results are shown in the figure. Figure 2 shown.

[0039] The test results show that the presence of HAP@ZIF-8 / PEEK-30 greatly improves the survival rate of preosteoblasts. Compared with the control time without adding composite materials, the survival rate of preosteoblasts in the culture medium with HAP@ZIF-8 / PEEK-30 added increased from the original 34.57% to 86.46%.

[0040] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. A medical-grade polyetheretherketone composite material, characterized in that: Contains the following components by mass: 1000 parts of PEEK powder, 100 to 500 parts of HAP@ZIF-8 composite material after sizing, 1 to 3 parts of silane coupling agent, and 2 to 5 parts of calcium stearate; The sizing HAP@ZIF-8 composite material is obtained by reacting HAP, methylimidazole and anhydrous zinc nitrate in a DMF solution of polyetherimide; The mass proportions of HAP, methylimidazole and anhydrous zinc nitrate are: 3 to 21 parts of HAP, 100 to 350 parts of methylimidazole, and 120 to 380 parts of anhydrous zinc nitrate.

2. The medical-grade polyetheretherketone composite material according to claim 1, characterized in that: The silane coupling agent is A-174.

3. The medical-grade polyetheretherketone composite material according to claim 1, characterized in that: The concentration of the DMF solution of polyetherimide is 3%.

4. The medical-grade polyetheretherketone composite material according to claim 1, characterized in that: The reaction process of the HAP@ZIF-8 composite material after sizing is specifically as follows: HAP, methylimidazole and anhydrous zinc nitrate were added to a DMF solution of polyetherimide, stirred at room temperature, then transferred to a high-pressure reactor for solvothermal reaction, and finally washed with anhydrous ethanol and dried.

5. The medical-grade polyetheretherketone composite material according to claim 4, characterized in that: The stirring time is 6h~10h; the reaction temperature of the solvent thermal reaction is 100°C~180°C, and the reaction time is 12h~24h.

6. A method for preparing a medical-grade polyetheretherketone composite material according to any one of claims 1 to 5, characterized in that: The steps include: S1, putting the dried PEEK powder, the sizing HAP@ZIF-8 composite material, the silane coupling agent and the calcium stearate into a mixer for mixing to obtain a premix; S2. Putting the premix into a melt spinning machine for spinning to obtain a HAP@ZIF-8 / PEEK composite material.

7. The method for preparing the medical-grade polyetheretherketone composite material according to claim 6, characterized in that: The mixing time is 20 min.

8. The method for preparing the medical-grade polyetheretherketone composite material according to claim 6, characterized in that: The spinning temperature is 340°C to 375°C.

9. A human bone implant, characterized in that: The human bone implant is prepared by a 3D printer from the medical-grade polyetheretherketone composite material according to any one of claims 1 to 5.

10. The human bone implant according to claim 9, characterized in that: The nozzle temperature of the 3D printer is 400°C to 450°C, and the chamber temperature is 250°C to 400°C.

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