Medical grade polyether ether ketone composite material, method of making and human bone implant

Abstract

This invention relates to medical-grade polyetheretherketone (PEEK) composite materials, their preparation method, and human bone implants, belonging to the field of medical materials technology. It addresses the limitations of existing human bone implants in promoting bone tissue regeneration and repair, as well as their poor antibacterial properties. The composite material comprises 1000 parts PEEK powder, 100-500 parts of HAP-modified ZIF-8 composite material after sizing, 1-3 parts of silane coupling agent, and 2-5 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; wherein HAP comprises 3-21 parts, methylimidazole 100-350 parts, and anhydrous zinc nitrate 120-380 parts. This invention can be used in human bone implants, possessing antibacterial properties, strong binding ability to bone cells and tissues, and the ability to promote the regeneration and repair of bone cells and tissues, showing broad application prospects in the medical field.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, specifically to a medical-grade polyetheretherketone composite material, its preparation method, and human bone implants. Background Technology

[0002] Polyetheretherketone (PEEK) is widely used in human bone implants due to its good biocompatibility and elastic modulus similar to that of bone. Compared with traditional metals, PEEK materials do not interfere with medical tests such as X-rays and MRI, and are also lightweight and high-strength, making them a substitute for traditional metal materials.

[0003] Existing PEEK material bone implants also have several drawbacks in application: Firstly, their surface is relatively inert, resulting in weak adhesion to bone cells and a relatively slow rate of bone integration, which is not conducive to the rapid growth and stable attachment of new bone. Secondly, they cannot actively induce the growth and differentiation of bone cells, thus having limited effect on promoting bone tissue regeneration and repair. Furthermore, PEEK has insufficient antibacterial properties, making them susceptible to bacterial infection and leading to complications such as inflammation at the implantation site. Summary of the Invention

[0004] To address the aforementioned problems in the application of existing PEEK materials as bone implants, this invention proposes a medical-grade polyetheretherketone composite material, its preparation method, and a human bone implant.

[0005] The technical solution of the present invention is as follows:

[0006] A medical-grade polyetheretherketone composite material comprising the following components in parts by weight:

[0007] 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;

[0008] The HAP-modified ZIF-8 composite material after sizing was obtained by reacting HAP, methylimidazolium and anhydrous zinc nitrate in a DMF solution of polyetherimide;

[0009] The mass fractions of HAP, methylimidazole and anhydrous zinc nitrate are as follows: HAP 3 to 21 parts, methylimidazole 100 to 350 parts, and anhydrous zinc nitrate 120 to 380 parts.

[0010] Preferably, the silane coupling agent is A-174.

[0011] Preferably, the concentration of the DMF solution of the polyetherimide is 3%.

[0012] Preferably, the reaction process of the HAP@ZIF-8 composite material after sizing is as follows:

[0013] 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 a solvothermal reaction, and finally washed with anhydrous ethanol and dried.

[0014] Preferably, the stirring time is 6h~10h; the reaction temperature of the solvothermal reaction is 100℃~180℃, and the reaction time is 12h~24h.

[0015] Preferably, the high-pressure reactor is a polytetrafluoroethylene stainless steel high-pressure reactor.

[0016] The optimal reaction temperature for the solvothermal reaction is 160°C, and the optimal reaction time is 24 h. Under these conditions, the ZIF-8 obtained in the reaction exhibits the optimal crystallinity.

[0017] The present invention also provides a method for preparing the above-mentioned medical-grade polyetheretherketone composite material, comprising the following steps:

[0018] S1. Dry PEEK powder, sizing HAP-modified ZIF-8 composite material, silane coupling agent and calcium stearate are put into a mixer for mixing to obtain a premix.

[0019] The dried PEEK powder is prepared by placing the PEEK powder in a vacuum drying oven and drying it at 120℃~180℃ for 4h~6h; most preferably, the drying temperature of the vacuum drying oven is 140℃ and the drying time is 4h.

[0020] S2. The premixed material is fed into a melt spinning machine for spinning to obtain a PEEK composite material.

[0021] Preferably, the mixing time is 20 minutes.

[0022] Preferably, the spinning temperature is 340℃~375℃.

[0023] The present invention also provides a human bone implant, which is prepared by a 3D printer from the above-mentioned medical-grade polyetheretherketone composite material.

[0024] Preferably, the nozzle temperature of the 3D printer is 400℃~450℃, and the chamber temperature is 250℃~400℃.

[0025] Most preferably, the nozzle temperature of the 3D printer is 400°C and the chamber temperature is 300°C. Human bone samples printed under these temperature conditions have the best crystallinity and uniform color.

[0026] Compared with the prior art, the specific beneficial effects of the present invention are as follows:

[0027] This invention uses polyetherimide as a sizing agent to prepare HAP@ZIF-8 nanocomposite material after sizing via a solvothermal method. The resulting ZIF-8 possesses unique structural characteristics such as tunable pore size, high specific surface area, high thermal stability, biodegradability, biocompatibility, and antibacterial properties, significantly enhancing the biocompatibility and antibacterial properties of PEEK. This promotes osteoblast adhesion, proliferation, and differentiation, provides a good channel for inorganic mineral deposition in the organic matrix, promotes bone formation, and facilitates osteoblast regeneration. The chemical composition and crystal structure of HAP are similar to the inorganic components in human bone, exhibiting good biocompatibility and osteoconductivity, thus enabling PEEK to promote bone tissue repair and anti-infection functions. Through the synergistic effect of ZIF-8 and HAP, the human bone implant provided by this invention simultaneously possesses antibacterial activity, strong binding ability with osteoblast tissue, and the ability to promote osteoblast regeneration and bone tissue regeneration and repair, showing broad application prospects in the medical field.

[0028] Experimental results showed that the HAP@ZIF-8 / PEEK composite material significantly inhibited the survival rate of Staphylococcus aureus, demonstrating excellent antibacterial activity. Furthermore, it greatly improved the survival rate of pre-osteoblasts, exhibiting a good effect in promoting osteoblast regeneration. Attached Figure Description

[0029] Figure 1 This is a schematic diagram showing the survival rate test results of Staphylococcus aureus in the material samples prepared in each embodiment and comparative example.

[0030] Figure 2 This diagram illustrates the percentage of pre-osteoblast activity in the material samples prepared for each embodiment and comparative example. Detailed Implementation

[0031] To make the technical solutions of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. It should be noted that the following embodiments are only used to better understand the technical solutions of the present invention and should not be construed as limiting the present invention.

[0032] Example 1.

[0033] First, place the polyetheretherketone powder in a vacuum drying oven and dry it at 140°C for 4 hours.

[0034] Then, 9g of HAP, 216.47g of methylimidazole and 249.14g of anhydrous zinc nitrate were added to a 3% polyetherimide DMF solution and stirred at room temperature for 8 hours. The resulting mixed solution was then transferred to a polytetrafluoroethylene stainless steel high-pressure reactor and reacted at 160°C for 24 hours. The mixture was washed and dried with anhydrous ethanol to obtain the sizing HAP@ZIF-8 composite material.

[0035] 1000g of dried polyetheretherketone powder, 300g of sizing HAP-modified ZIF-8 composite material, 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.

[0036] The premixed material was fed into a high-temperature melt spinning machine and PEEK composite filaments were prepared at 370°C.

[0037] Finally, the obtained PEEK composite filament was placed in a 3D printer with a nozzle temperature of 400℃ and a chamber temperature of 300℃ to print a human skeleton sample. The sample was designated HAP@ZIF-8 / PEEK-30.

[0038] Example 2.

[0039] The preparation method in this embodiment is the same as in Example 1, except that 4.5g HAP, 108.24g methylimidazole and 124.57g anhydrous zinc nitrate are placed in a 3% polyetherimide DMF solution and stirred at room temperature for 8 hours.

[0040] The sample prepared in this embodiment is denoted as HAP@ZIF-8 / PEEK-15.

[0041] Example 3.

[0042] The preparation method of this embodiment is the same as that of Example 1, except that 13.5g HAP, 324.71g methylimidazole and 373.71g anhydrous zinc nitrate are placed in a 3% polyetherimide DMF solution and stirred at room temperature for 8 hours.

[0043] The sample prepared in this embodiment is denoted as HAP@ZIF-8 / PEEK-45.

[0044] Comparative Example 1.

[0045] First, place the polyetheretherketone powder in a vacuum drying oven and dry it at 140°C for 4 hours.

[0046] 1000g of dried polyetheretherketone (PEEK) 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. The premix was then fed into a high-temperature melt spinning machine and PEEK filaments were prepared at 370℃. The obtained PEEK filaments were then placed in a 3D printer, and a human bone sample was printed at a nozzle temperature of 400℃ and a chamber temperature of 300℃. The sample was designated C-PEEK.

[0047] Comparative Example 2.

[0048] First, place the polyetheretherketone powder in a vacuum drying oven and dry it at 140°C for 4 hours.

[0049] 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. The premix was then fed into a high-temperature melt spinning machine and PEEK filaments were prepared at 370℃. The obtained PEEK filaments were then placed in a 3D printer, and human bone samples were printed at a nozzle temperature of 400℃ and a chamber temperature of 300℃. The samples were denoted as HAP@PEEK.

[0050] Example of an effect 1.

[0051] The survival rate of Staphylococcus aureus in the material samples prepared in each example and comparative example was determined using the plate count method.

[0052] Staphylococcus aureus (purchased from Shanghai Yuchun Biotechnology Co., Ltd., batch number SHBCC D12341) was diluted with phosphate buffer and inoculated onto culture medium. The material samples prepared in each example and comparative example were placed in the culture medium and, after 2 hours, the number of viable Staphylococcus aureus bacteria was determined using the plate count method, and the survival rate was calculated. The results are as follows: Figure 1 As shown.

[0053] The test results show that the survival rates of Staphylococcus aureus reached 97.35% and 94.5% in the presence of pure PEEK material (Comparative Example 1) and HAP / PEEK (Comparative Example 2), respectively. This indicates that the antibacterial properties of pure PEEK material and HAP-doped PEEK material are poor. After adding HAP to modify the ZIF-8 composite material, the prepared composite material exhibited excellent antibacterial properties. The HAP@ZIF-8 / PEEK-30 composite material (Example 1) had a significant inhibitory effect on the survival of Staphylococcus aureus, with a bacterial survival rate of 42.75%.

[0054] Example of effect 2.

[0055] The effect of the material samples prepared in each example and comparative example on the activity of pre-osteoblasts was determined using the MTT assay.

[0056] First, pre-osteoblasts were revived by placing them in 10% α-MEM culture medium. Then, the revived pre-osteoblasts were prepared into single-cell suspensions at a density of 2000 / 200 μL and seeded into 96-well plates. The composite materials prepared in Examples 1-3 and Comparative Examples 1-2 were added, and the plates were cultured for 3 days. After culture, a certain amount of 5 mg / mL MTT solution was added to each well, and incubation was continued for 3 hours. Finally, the pellet from each well was centrifuged, and 150 μL of dimethyl sulfoxide was added, followed by shaking to dissolve. The absorbance of each group was measured at 480 nm using a microplate reader. The results are as follows: Figure 2 As shown.

[0057] The test results show that the presence of HAP@ZIF-8 / PEEK-30 greatly improves the survival rate of pre-osteoblasts. Compared with the control group without the addition of composite materials, the survival rate of pre-osteoblasts in the culture medium with the addition of HAP@ZIF-8 / PEEK-30 increased from 34.57% to 86.46%.

[0058] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A medical-grade polyetheretherketone composite material, characterized in that, The components comprise the following parts 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 HAP@ZIF-8 composite material after sizing was obtained by stirring HAP, methylimidazole, and anhydrous zinc nitrate in a DMF solution of polyetherimide at room temperature, then transferring the mixture to a high-pressure reactor for a solvothermal reaction, and finally washing and drying with anhydrous ethanol; the stirring time was 6h~10h; the reaction temperature of the solvothermal reaction was 100℃~180℃, and the reaction time was 12h~24h; The mass parts of HAP, methylimidazole and anhydrous zinc nitrate are: HAP 3 to 21 parts, methylimidazole 100 to 350 parts, and anhydrous zinc nitrate 120 to 380 parts. The silane coupling agent is A-174; The concentration of the DMF solution of the polyetherimide is 3%.

2. A method for preparing a medical-grade polyetheretherketone composite material as described in claim 1, characterized in that, Includes the following steps: S1. Dry PEEK powder, sizing HAP@ZIF-8 composite material, silane coupling agent and calcium stearate are put into a mixer for mixing to obtain a premix. S2. The premixed material is fed into a melt spinning machine for spinning to obtain HAP@ZIF-8 / PEEK composite material.

3. The method for preparing medical-grade polyetheretherketone composite material according to claim 2, characterized in that, The mixing time is 20 minutes.

4. The method for preparing medical-grade polyetheretherketone composite material according to claim 2, characterized in that, The spinning temperature is 340℃~375℃.

5. A human bone implant, characterized in that, The human bone implant is prepared by a 3D printer using the medical-grade polyetheretherketone composite material described in claim 1.

6. The human bone implant according to claim 5, characterized in that, The nozzle temperature of the 3D printer is 400℃~450℃, and the chamber temperature is 250℃~400℃.

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