Method for constructing antibacterial peptide-loaded nanotube hydroxyapatite coating on surface of polyetherketoneketone

Abstract

The invention discloses a method for constructing an antibacterial peptide-loaded nanotube hydroxyapatite coating on the surface of polyetherketoneketone. The method comprises the following steps: S1, polishing and cleaning the surface of the polyetherketoneketone; s2, carrying out acid etching sulfonation treatment on the surface of the polyether ketone ketone to obtain PEKK-S; s3, preparing an HA nanotube; s4, dopamine is dissolved in the Tris-HCL buffer solution, and a dopamine solution A is formed; preparing another dopamine solution with the same concentration, and adding the HA nanotube and the antibacterial peptide to obtain a mixed solution B; pEKK-S is soaked in the dopamine solution A, and the solution A and the mixed solution B are placed in a vibrator to be vibrated for 12-24 h; pEKK-S is taken out from the dopamine solution A, cleaned, dried, completely soaked in the mixed solution B, placed in a vibrator to be vibrated for 12-24 h, cleaned and dried, polyether ketone ketone with the surface containing the antibacterial peptide-loaded nanotube hydroxyapatite coating is obtained, the antibacterial peptide can be stably and enduringly released, and therefore the antibacterial effect is improved, and bone tissue recovery is promoted.

Description

Technical Field

[0001] The present invention relates to the technical field of biochemistry, in particular to a method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of a polyetherketoneketone. Background Art

[0002] Polyetherketoneketone (PEKK), a high-performance polymer, has become a widely used implant material in orthopedics and traumatology due to its excellent biocompatibility, mechanical strength, corrosion resistance, and radiolucency. However, due to PEKK's chemical and biological inertness, it lacks stable osseointegration with the host bone after service, which can easily lead to implant loosening and even failure. Furthermore, postoperative bacterial colonization and the formation of bacterial biofilms on the implant surface can not only hinder the bactericidal effect of antimicrobial drugs but also hinder the formation of new bone, another key factor affecting the long-term success rate of orthopedic implants.

[0003] In order to improve the bioactivity of PEEK, promote bone formation and prevent bone infection, researchers have adopted surface modification strategies such as roughening, introduction of chemical groups and coatings to enhance the antibacterial properties and osteogenic activity of PEKK. Surface coating modification is an effective method to improve biological properties without affecting mechanical strength and destroying favorable volumetric properties. Hydroxyapatite (HA), as the main mineral component of animal and human bones, is often used alone as a prosthesis to fill bone defects or combined with implants in the form of a coating to enhance its surface bioactivity. A large number of biocompatibility tests have shown that artificially synthesized HA coatings are non-toxic, non-irritating and non-allergenic. Therefore, HA coatings have great application potential in promoting bone formation. However, most of the HA particles currently studied are dense bodies, such as rods, needles and spheres, which are not suitable for the efficient loading and release of active factors. Summary of the Invention

[0004] In view of the problem that the hydroxyapatite used in the surface modification of PEEK in the prior art is not suitable for the efficient loading and release of active factors, the present invention provides a method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone.

[0005] The present invention provides a method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone. Using polyetherketoneketone as the research object, the invention combines sulfonation treatment, organic amine-assisted biomimetic methods, and dopamine oxidative polymerization to construct a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone. This allows for stable and sustained release of the antimicrobial peptides, thereby enhancing the antimicrobial effect and promoting bone tissue recovery. The specific method is as follows:

[0006] S1. Polyetherketoneketone surface polishing and cleaning treatment:

[0007] The polyetherketoneketone was processed into sheets, polished with 1200 grit sandpaper, and then ultrasonically cleaned with acetone, ethanol, and ultrapure water in sequence.

[0008] S2. The surface of polyetherketoneketone is subjected to acid etching and sulfonation treatment using concentrated sulfuric acid to obtain sulfonated PEKK, referred to as PEKK-S.

[0009] The specific method is as follows: the polyetherketoneketone is immersed in concentrated sulfuric acid under stirring conditions for acid etching and sulfonation, and the sulfonation time is 2-4 minutes; the sulfonated polyetherketoneketone is rinsed with deionized water, and after the acid-etched part is fully leached, ultrasonic cleaning is performed for 15-20 minutes, and then drying is performed at 60°C to obtain sulfonated PEKK.

[0010] S3. Prepare hydroxyapatite nanotubes as follows:

[0011] S31, adding Ca(H2PO4)2 and CaCl2 into water, stirring and dissolving to obtain an aqueous solution;

[0012] S32, dissolving dodecylamine and hexadecylamine in anhydrous ethanol to obtain an organic amine solution;

[0013] S33. Preheat the aqueous solution to 80°C, then add the organic amine solution dropwise to the aqueous solution, heat to 120°C for hydrothermal reaction for 48 hours, and centrifuge to obtain a solid. The solid is first rinsed with deionized water, then ultrasonically cleaned for 5-10 minutes, and finally dried at 60°C; then disperse the solid in a methylamine chloride solution, stir for 2 hours, centrifuge to separate the solid, and then disperse the solid in a methylamine chloride solution, stir and centrifuge, repeat this process several times, and finally calcine the solid at 400°C for 12 hours to obtain hydroxyapatite nanotubes, referred to as HA nanotubes.

[0014] Preferably, in step S33, the aqueous solution is preheated to 80°C, and then the organic amine solution is added dropwise to the aqueous solution using a peristaltic pump within 16 hours.

[0015] S4. Constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone, the method is as follows:

[0016] S41. Dopamine is dissolved in Tris-HCl buffer to form dopamine solution A; another dopamine solution of the same concentration is prepared and HA nanotubes and antimicrobial peptides are added to obtain mixed solution B.

[0017] S42. Completely immerse the prepared PEKK-S in dopamine solution A, and then simultaneously place the dopamine solution A and the mixed solution B in a vibrator and vibrate at 37° C. for 12-24 hours.

[0018] S43. Remove PEKK-S from dopamine solution A, wash and dry it, then completely immerse it in mixed solution B and place it in a vibrator at 37°C for 12-24 hours. Finally, remove it, wash it, and dry it to obtain a polyetherketoneketone having a nanotube hydroxyapatite coating with antimicrobial peptides on its surface, referred to as PEKK-SHL.

[0019] In step S41, the concentration of dopamine solution A is 2-4 mg / mL. In mixed solution B, the concentration of HA nanotubes is 10-20 mg / mL, and the concentration of antimicrobial peptide is 1-2 mg / mL.

[0020] The dopamine (DA) mainly plays a bonding role, and is used for bonding between HA nanotubes and antimicrobial peptides, as well as bonding between PEKK and HA nanotubes. Under alkaline conditions, DA can firmly adhere HA nanotubes with surface-deposited antimicrobial peptides to the surface of the PEKK substrate without the need for pretreatment. DA forms a polydopamine layer through in-situ polymerization by self-oxidation to play a bonding role. During the polymerization reaction, dopamine will not block the tubular structure of the HA nanotubes, ensuring that the antimicrobial peptides can enter the interior of the HA nanotubes while maintaining the high specific surface area advantage of the HA nanotubes.

[0021] Compared with the prior art, the present invention is beneficial in that:

[0022] (1) The HA nanotubes prepared in the present invention have a large specific surface area, which can provide more binding sites for loading active factors or drugs. The active factors or drugs are mainly loaded inside the HA nanotubes for encapsulation. The nanotubular HA has the ability to enter cells and can enter the cells through endocytosis, that is, intracellular delivery through HA nanotubes. While exerting its inherent osteogenic effect, it is also a very potential drug delivery system; this is a function that ordinary HA nanorods or nanosphere particles do not have, so HA nanotubes are an ideal platform for loading and releasing antibacterial drugs.

[0023] (2) The nanotube hydroxyapatite drug-loaded antibacterial coating constructed on the PEKK surface by the method of the present invention has multiple functional effects: in terms of antibacterial properties, the coating combines the physical killing effect of the HA structure and the selective toxicity of the antimicrobial peptide, and has a good bactericidal effect on Staphylococcus aureus and Escherichia coli; in terms of cell compatibility, cells on the surface of the material covered with the coating grow normally in culture, proving that the modified material has good cell compatibility; in terms of osteogenesis, the coating can upregulate the expression of multiple osteogenesis-related genes and proteins, and promote cell osteogenic differentiation.

[0024] (3) The present invention utilizes the structural advantages of nanotubes to improve the adsorption capacity of antimicrobial peptides, allowing for stable and sustained release of antimicrobial peptides, and has good clinical application prospects. Moreover, the preparation process of the nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone is simple, and the raw materials are cheap and readily available.

[0025] Other advantages, objectives and features of the present invention will be reflected in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the TEM result of the HA nanotubes prepared in Example 1.

[0027] Figure 2 This is the SEM result of the HA nanotube coating loaded with antimicrobial peptide LL37 (PEKK-SHL) prepared in Example 1.

[0028] Figure 3 It is a comparison chart of the release curves of the HA nanotube coating loaded with the antimicrobial peptide LL37 of Example 1 and the HA nanorod coating loaded with LL37 of Comparative Example 1.

[0029] Figure 4 These are the CCK8 result graphs of polyetherketoneketone PEKK, sulfonated polyetherketoneketone PEKK-SH covered with HA nanotube coating, and sulfonated polyetherketoneketone PEKK-SHL coated with HA nanotubes loaded with antimicrobial peptide LL37.

[0030] Figure 5 These are the qPCR results of polyetherketoneketone PEKK, sulfonated polyetherketoneketone PEKK-SH covered with HA nanotube coating, and sulfonated polyetherketoneketone PEKK-SHL coated with HA nanotube loaded with antimicrobial peptide LL37.

[0031] Figure 6 It is a protein immunoblotting result diagram of the polyetherketoneketone PEKK of the present invention, the sulfonated polyetherketoneketone PEKK-SH covered with the HA nanotube coating, and the sulfonated polyetherketoneketone PEKK-SHL coated with the HA nanotube coating loaded with the antimicrobial peptide LL37.

[0032] Figure 7 This is a TEM image of cells taking up HA nanotubes.

[0033] Figure 8 These are the in vitro antibacterial test results of polyetherketoneketone PEKK, sulfonated polyetherketoneketone PEKK-SH covered with HA nanotube coating, and sulfonated polyetherketoneketone PEKK-SHL coated with HA nanotubes loaded with antimicrobial peptide LL37. DETAILED DESCRIPTION

[0034] The preferred embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0035] Example 1

[0036] A method for constructing a nanotube hydroxyapatite coating carrying an antimicrobial peptide on a polyetherketoneketone surface, comprising the following steps:

[0037] Step 1: Polish and clean the PEKK sheet;

[0038] The PEKK sheet with a size of Φ14×1.5mm was ground with 1200-grit sandpaper and polished with 1200-grit sandpaper in sequence. It was then ultrasonically cleaned with acetone, ethanol, and ultrapure water for 10 minutes at a cleaning temperature of 25°C, an ultrasonic power of 120W, and an ultrasonic frequency of 40KHz. Finally, it was placed in a drying oven at 60°C for 1 hour for subsequent surface modification.

[0039] Step 2: Sulfonate the PEKK sheet in concentrated sulfuric acid under magnetic stirring for 2-4 minutes. Rinse the sulfonated material in deionized water and, after the acid-etched areas have been fully leached, ultrasonically clean the sheet at 25°C, 120W of ultrasonic power, and 40kHz for 15-20 minutes. Dry the thoroughly cleaned sulfonated PEEK in a drying oven at 60°C for 2 hours to obtain sulfonated PEKK (abbreviated as PEKK-S) for subsequent preparation.

[0040] Step 3: Preparation of HA nanotubes

[0041] First, 1.01g of Ca(H2PO4)2 and 0.629g of CaCl2 were added to 80mL of water and stirred to dissolve to obtain an aqueous solution. Then, in another container, 3.089g of dodecylamine and 0.503g of hexadecylamine were dissolved in 24mL of anhydrous ethanol to obtain an organic amine solution. The organic amine solution was added dropwise to the preheated aqueous solution at 80°C using a peristaltic pump over 16 hours. After a hydrothermal reaction at 120°C for 48 hours, the solid product was centrifuged and washed with water and anhydrous ethanol. The solid product was then dispersed in a 10% aqueous solution of methylamine chloride, stirred for 2 hours, and centrifuged to obtain the solid. The solid product was then dispersed in a 10% aqueous solution of methylamine chloride, stirred for 2 hours, and centrifuged to obtain the solid. This process was repeated six times. Finally, the solid product was calcined at 400°C for 12 hours to obtain HA nanotubes. Figure 1 TEM image of HA nanotubes.

[0042] Step 4: constructing a HA nanotube coating loaded with antimicrobial peptide LL37 on the surface of the sulfonated polyetherketoneketone obtained in step 2;

[0043] First, dissolve DA in Tris-HCl (pH 8.5) buffer to prepare a 2 mg / mL dopamine solution A. Prepare another dopamine solution of the same concentration using the same method and add 20 mg / mL HA nanotube powder and 1 mg / mL antimicrobial peptide LL37 to form mixed solution B. Completely immerse the PEKK-S from step 2 in dopamine solution A. Then, place both dopamine solution A and mixed solution B in a shaker (37°C, 25 rpm) for 12-24 hours. Remove the PEKK-S from dopamine solution A, wash, dry, and completely immerse it in mixed solution B. Place it in a shaker (37°C, 25 rpm) for 12-24 hours. After taking out the sample from mixed solution B, it was first rinsed with deionized water, then ultrasonically cleaned (temperature 25°C, ultrasonic power 120W, ultrasonic frequency 40KHz) for 5-10 minutes, and finally placed in a high-temperature drying oven at 60°C for 2 hours to obtain sulfonated PEKK (PEKK-SHL) coated with HA nanotubes loaded with antimicrobial peptide LL37.

[0044] Figure 2 This is a SEM image of the PEKK-SHL prepared in Example 1. The SEM results show that PEKK can adhere well to the HA nanotubes loaded with LL37 through the in-situ polymerization of DA by self-oxidation.

[0045] Comparative Example 1

[0046] Based on the preparation method of Example 1, step 3 is changed. Step 3 is used to prepare HA nanorods. Step 3 is specifically as follows:

[0047] 1.01g of Ca(H2PO4)2 and 0.629g of CaCl2 were added to 80mL of water and stirred to dissolve to form an aqueous solution. Then, in a separate container, 3.089g of dodecylamine and 0.503g of hexadecylamine were dissolved in 24mL of anhydrous ethanol to form an organic amine solution. The organic amine solution was added dropwise to the aqueous solution using a peristaltic pump over 16 hours. After a hydrothermal reaction at 120°C for 48 hours, the solid product was centrifuged and washed with water and anhydrous ethanol. The solid product was then dispersed in a 10% aqueous solution of methylamine chloride, stirred for 2 hours, and centrifuged to separate the solid. The solid product was then dispersed in a 10% aqueous solution of methylamine chloride, stirred for 2 hours, and centrifuged to separate the solid. This process was repeated six times. Finally, the solid product was calcined at 400°C for 12 hours to produce HA nanorods.

[0048] In the subsequent step 4, the HA nanotubes were replaced with an equal amount of HA nanorods, and other conditions remained unchanged to prepare sulfonated PEKK coated with HA nanorods loaded with the antimicrobial peptide LL37.

[0049] The performance test is as follows:

[0050] (1) The PEKK-SHL of Example 1 was immersed in 1.5 mL of PBS solution (pH 7.4) and incubated at 37°C and 25 rpm for different time periods (4, 8, 12, 24, 48, 96, and 168 h). 0.1 mL of supernatant was collected and then PBS was added to keep the total volume constant. The concentration of LL37 was determined using a BCA protein assay kit. The product prepared in Comparative Example 1 was tested using the same method. The test results are shown in Figure 2. Figure 3 As shown in the figure, the release curve shows that the HA nanotube group LL37 of Example 1 is rapidly released within the first 8 hours, then slowly released within 14 days, and finally released about 200 μg, which is higher than the release of LL37 in the nanorod group, indicating that the HA nanotube structure can increase the carrying capacity and release amount of LL37.

[0051] (2) Cell proliferation experiments were conducted using the original PEKK sheet (Φ14 × 1.5 mm) before treatment in step 1 of Example 1, sulfonated polyetherketoneketone coated with HA nanotubes (PEKK-SH), and sulfonated polyetherketoneketone coated with HA nanotubes loaded with antimicrobial peptide LL37 (PEKK-SHL). The preparation method of PEKK-SH was as follows: Steps 1-3 were the same as in Example 1, except that in step 4, 1 mg / mL antimicrobial peptide LL37 was not added to Solution B. Other conditions remained unchanged, resulting in sulfonated polyetherketoneketone coated with HA nanotubes (PEKK-SH).

[0052] Rat bone marrow mesenchymal stem cells (BMSCs) were cultured directly at a cell density of 2×10 5 Cell proliferation was assessed using CCK-8 after 1, 4, and 7 days of co-culture with cells. The culture medium was aspirated and rinsed twice with PBS. Then, 1 mL of 10% CCK-8 solution was added to each well. After incubation at 37°C in the dark for 1 hour, 200 μL of the supernatant was transferred to a 96-well plate and absorbance was measured at 450 nm. Figure 4 The CCK8 assay results are shown in Figure 2. The CCK8 data show significant differences between PEKK, PEKK-SH, and PEKK-SHL on the first day of inoculation, likely due to the HA coating reducing cell adhesion. However, at the 7-day mark, no significant differences were found among the three groups, indicating good cell compatibility between PEKK-SH and PEKK-SHL.

[0053] On days 1, 4, and 7, BMSCs were collected from different groups and the expression of osteogenesis-related genes, including alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), type I collagen (COL1A1), osteogenin (OPN), osteocalcin (OCN), and bone morphogenetic protein (BMP), was measured using qPCR. Data were analyzed using the 2-ΔΔCT method, and gene expression was normalized using GAPDH as a reference. Figure 5 The following figure shows the qPCR results. The results show that on day 4, the expression of ALPL, RUNX2, and OPN was upregulated in PEKK-SH and PEKK-SHL, and COL1A1 was upregulated in PEKK-SHL. On day 7, RUNX2 and COL1A1 were upregulated in PEKK-SH and PEKK-SHL, and OCN was upregulated in PEKK-SH. This confirms that HA coating can promote osteogenic activity.

[0054] On day 7, BMSCs were harvested from the samples for total protein extraction and quantification using a BCA protein assay kit. Western blotting was performed according to standard procedures to detect protein expression of COL1A1, ALPL, RUNX2, and OPN. Protein levels were then quantified using ImageJ software and normalized to β-actin. Figure 6 This is the result of Western blotting experiment. Figure 6 The development bands in (A) showed that the expression of the four histones of PEKK-SH and PEKK-SHL were significantly increased. Figure 6 Quantitative analysis in (B) also confirmed this conclusion, and it was found that the expression of COL1A1 and OPN in PEKK-SH and PEKK-SHL was significantly different from that in PEKK.

[0055] The HA nanotubes prepared in step 3 of Example 1 were added to BMSCs at a concentration of 50 μg / mL, and after culturing for 1 day, the samples were fixed and observed. Figure 7 The two images in the middle are TEM images of HA cell uptake, showing that HA nanotubes can enter OBMSCs via endocytosis and exert their effects within the cells. This finding suggests that the endocytic ability of HA nanotubes may be a key factor in their promotion of OBMSC proliferation and osteogenic differentiation, and also demonstrates the great potential of HA nanotubes as a drug delivery system.

[0056] The original PEKK sheet (Φ14×1.5 mm) before treatment in step 1 of Example 1, sulfonated polyetherketoneketone coated with HA nanotubes (PEKK-SH), and sulfonated polyetherketoneketone coated with HA nanotubes loaded with antimicrobial peptide LL37 (PEKK-SHL) were used for in vitro antibacterial experiments. 660 μL of a suspension of cfu / ml bacteria was dropped onto each sample. After incubation at 37°C for an appropriate time, the bacterial suspension was placed in a sterile centrifuge tube containing 4 mL of PBS. The tube was placed under ultrasound for 3 minutes to separate the bacteria from the surface. The dissociated bacterial suspension was then serially diluted, and 100 μL of the diluted bacterial suspension was introduced into standard Luria-Bertani (LB) agar and incubated at 37°C for 24 hours. The results are shown in Table 1. Figure 8 . Figure 8 (A) is a schematic diagram of the in vitro antibacterial effects of different materials. Figure 8 (B) shows the survival rates of Staphylococcus aureus and Escherichia coli on different materials. In vitro antibacterial experiments show that PEKK-SH exhibits inherent antibacterial activity, likely due to the physical killing properties of the HA nanotube structure. When loaded with LL37, the resulting PEKK-SHL exhibits significant antibacterial activity. Quantitative calculations of colony counts on the plates revealed that PEKK-SHL exhibited an antibacterial rate of 93% against S. aureus and 98% against E. coli.

[0057] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment as above, it is not intended to limit the present invention. Any technician familiar with this profession can make some changes or modifications to equivalent embodiments of the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone, characterized in that: The following steps are involved: S1, PEEK surface polishing and cleaning treatment; S2, using concentrated sulfuric acid to perform acid etching and sulfonation treatment on the surface of polyetherketoneketone to obtain sulfonated PEKK, referred to as PEKK-S; S3, preparing hydroxyapatite nanotubes, referred to as HA nanotubes; S4. Constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone, the method is as follows: S41, dissolving dopamine in Tris-HCl buffer to form dopamine solution A; preparing another dopamine solution of the same concentration and adding HA nanotubes and antimicrobial peptide to obtain mixed solution B; S42. Completely immerse PEKK-S in dopamine solution A, then place dopamine solution A and mixed solution B in a vibrator at 37°C for 12-24 hours. S43. Remove PEKK-S from dopamine solution A, wash and dry it, then completely immerse it in mixed solution B and place it in a vibrator at 37°C for 12-24 hours. Finally, remove it, wash it, and dry it to obtain a polyetherketoneketone having a nanotube hydroxyapatite coating with antimicrobial peptides on its surface, referred to as PEKK-SHL.

2. The method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone according to claim 1, characterized in that: Step S3, the method for preparing hydroxyapatite nanotubes is as follows: S31, adding Ca(H2PO4)2 and CaCl2 into water, stirring and dissolving to obtain an aqueous solution; S32, dissolving dodecylamine and hexadecylamine in anhydrous ethanol to obtain an organic amine solution; S33. Preheat the aqueous solution to 80°C, then add the organic amine solution dropwise to the aqueous solution, heat to 120°C for hydrothermal reaction for 48 hours, centrifuge to obtain a solid, wash with water and anhydrous ethanol, then disperse the solid in a methylammonium chloride solution, stir for 2 hours, centrifuge to separate the solid, then disperse the solid in a methylammonium chloride solution, stir and centrifuge, repeat this process several times, and finally calcine the solid at 400°C for 12 hours to obtain HA nanotubes.

3. The method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone according to claim 2, characterized in that: In step S33 , the aqueous solution is preheated to 80° C., and then the organic amine solution is added dropwise to the aqueous solution using a peristaltic pump over 16 hours.

4. The method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone according to claim 1, characterized in that: In step S43, the solid matter obtained by centrifugation is first rinsed with deionized water, then ultrasonically cleaned for 5-10 minutes, and finally dried at 60°C.

5. The method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone according to claim 1, characterized in that: The specific method of step S2 is: immersing the polyetherketoneketone in concentrated sulfuric acid under stirring conditions for acid etching and sulfonation, and the sulfonation time is 2-4 minutes; rinsing the sulfonated polyetherketoneketone with deionized water, ultrasonically cleaning for 15-20 minutes after the acid-etched part is fully leached, and then drying at 60°C to obtain PEKK-S.

6. The method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone according to claim 1, characterized in that: The antimicrobial peptide is antimicrobial peptide LL37.

7. The method for constructing a nanotube hydroxyapatite coating carrying antimicrobial peptides on the surface of polyetherketoneketone according to claim 1, characterized in that: Specifically, step S1 is to process the polyetherketoneketone into a sheet, polish it with 1200 grit sandpaper, and then ultrasonically clean it with acetone, ethanol and ultrapure water in sequence.

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