Polyether ether ketone composite material for repairing animal bones and preparation method thereof

Abstract

The application discloses an animal bone repair polyether ether ketone composite material and a preparation method thereof, and relates to the technical field of biomedical materials. The animal bone repair polyether ether ketone composite material is prepared by the following steps: weighing polyether ether ketone, hydroxyapatite, bioactive glass and a silane coupling agent; reacting the hydroxyapatite and the bioactive glass after cleaning with the silane coupling agent to obtain modified inorganic materials; stirring and uniformly mixing the polyether ether ketone and the modified inorganic materials, and extruding to obtain a preform; cleaning and drying the preform, and then performing carboxylation modification to obtain a carboxylated composite material; and reacting the carboxylated composite material with an antibacterial agent to obtain the animal bone repair polyether ether ketone composite material. The prepared composite material not only retains the high-strength characteristics of the polyether ether ketone, but also improves the adhesion and proliferation capacity of osteoblasts, and is suitable for animal weight-bearing bone defect repair.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a polyether ether ketone composite material for animal bone repair and a preparation method thereof. BACKGROUND

[0002] Polyether ether ketone (PEEK) is a high-performance polymer material with high mechanical strength, good thermal stability, wear resistance and corrosion resistance, which gradually becomes a main implant material to replace metal, especially in the orthopedic and trauma fields. Although PEEK material has many advantages, it still has some disadvantages. The first step of bone integration is the adsorption of adhesion proteins such as fibronectin and vitronectin on the surface of the material. These proteins contain hydrophilic groups and are more easily adsorbed on hydrophilic surfaces. As a hydrophobic material, PEEK has biological inertness, which limits cell adhesion and protein absorption, thereby reducing its bone integration ability. In addition, the problem of bacterial infection after surgery cannot be ignored, which may cause serious complications. By improving the biological activity of PEEK and enhancing its antibacterial ability, it is expected to better achieve the purpose of animal bone repair.

[0003] A Chinese invention patent with publication number CN 112972764 A discloses a polyether ether ketone bone repair material with multi-scale pores and a preparation method thereof. The invention hot-presses polyether ether ketone granules into a plate, washes and dries, then gets a partially foamed polyether ether ketone plate in a foaming device, and then performs sulfonation in a mixed acid solution of concentrated sulfuric acid and methane sulfonic acid, and gets it after hydrothermal treatment and vacuum drying. The small-sized micro-nano pores obtained by sulfonation are beneficial to the adhesion of early osteoblasts, and the large-sized micropores obtained by foaming are beneficial to the ingrowth of later bone tissue, but its antibacterial performance is poor. SUMMARY

[0004] In view of the deficiencies of the prior art, the present application aims to provide a polyether ether ketone composite material for animal bone repair and a preparation method thereof.

[0005] To achieve the above-mentioned purpose, the present application realizes the following technical scheme:

[0006] A preparation method of a polyether ether ketone composite material for animal bone repair, comprising the following steps:

[0007] S1: weigh the following components by weight parts: polyether ether ketone 60-85 parts, hydroxyapatite 10-30 parts, bioactive glass 1-5 parts, and silane coupling agent 1-3 parts;

[0008] S2: after washing the hydroxyapatite and bioactive glass, put them into an NMP solution of silane coupling agent, add deionized water, heat to 60-100 DEG C and react for 12-20 hours, and then obtain the modified inorganic material after post-treatment;

[0009] S3: The polyether ether ketone and modified inorganic material are added into a high-speed mixer and stirred to mix uniformly, and then passed through a twin-screw extruder to obtain a preform;

[0010] S4: After the preform is cleaned and dried, it is immersed in dichloromethane, and anhydrous aluminum chloride and succinic anhydride are sequentially added, and refluxed for 6-10 hours, and then treated to obtain a carboxylated composite material; in the reaction, the benzene ring of the polyether ether ketone undergoes a Friedel-Crafts acylation reaction with succinic anhydride under the catalysis of anhydrous aluminum chloride;

[0011] S5: The carboxylated composite material is immersed in an EDC solution, an antibacterial agent is added, and the reaction is carried out for 12-24 hours, and then treated to obtain a polyether ether ketone composite material for animal bone repair; in the reaction, the carboxyl groups on the surface of the carboxylated composite material are activated by EDC, and then undergo a condensation reaction with the amino groups on the surface of the antibacterial agent to generate an amide.

[0012] The silane coupling agent is prepared by the following method:

[0013] M1: L-phenylalaninol reacts with 4-phenoxybenzoic acid to generate an ester compound; the reaction equation is as follows:

[0014] ;

[0015] M2: The ester compound reacts with 3-(methacryloyloxy)propyltrimethoxysilane to generate a silane coupling agent; the reaction equation is as follows:

[0016] ;

[0017] In step M1, the molar ratio of the L-phenylalaninol to the 4-phenoxybenzoic acid is 1:(1-1.3); in step M2, the molar ratio of the ester compound to the 3-(methacryloyloxy)propyltrimethoxysilane is 1:(1-1.5).

[0018] The antibacterial agent is prepared by the following method:

[0019] N1: Chitosan reacts with methacrylic anhydride to generate acylated chitosan; the reaction equation is as follows:

[0020] ;

[0021] Wherein, o = m + n;

[0022] N2: The acylated chitosan reacts with vanillin to generate a Schiff base chitosan; the reaction equation is as follows:

[0023] ;

[0024] Wherein, m = p + q;

[0025] N3: Schiff base chitosan, acrylic acid and 2-isopropenyl aniline are reacted under the action of initiator AIBN to generate an antibacterial agent.

[0026] In step N1, the mass ratio of chitosan to methacrylic anhydride is 6:1.

[0027] In step N2, the mass ratio of acylated chitosan to vanillin is 5:2.

[0028] In step N3, the mass ratio of Schiff base chitosan, acrylic acid and 2-isopropenyl aniline is 10:1:2.

[0029] In step S4, the molar ratio of anhydrous aluminum chloride to succinic anhydride is (2-2.5):1.

[0030] In step S5, the EDC solution is 1-ethyl-(3-dimethylaminopropyl) carbonyl diimide hydrochloride aqueous solution, and the concentration is 0.5-1wt%; the mass ratio of EDC to antibacterial agent is 1:(1-5).

[0031] A polyether ether ketone composite material for animal bone repair is prepared by the above method.

[0032] Due to the above technical solutions, the beneficial effects of the present application include:

[0033] (1) The silicon methoxy group of the silane coupling agent prepared by the present application forms a covalent bond or a hydrogen bond with inorganic materials, improving the dispersion performance; the rigid benzene ring improves the heat resistance and the compatibility with the PEEK matrix, and the synergistic effect of the two improves the mechanical properties of the material and prolongs the service life of the material as an animal bone repair implant.

[0034] (2) The antibacterial agent prepared by the present application contains a large number of hydrophilic functional groups (such as hydroxyl groups and carboxyl groups), which helps to promote cell adhesion and growth and improve the biocompatibility of the material; and the antibacterial agent can effectively inhibit bacterial growth by destroying bacterial cell membranes and inhibiting the activity of enzymes in bacterial cells, reducing the risk of postoperative infection in animals. BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 The nuclear magnetic hydrogen spectrum of the ester-based compound prepared in step M1 of Example 1 is shown in the figure;

[0036] Figure 2 The nuclear magnetic hydrogen spectrum of the silane coupling agent prepared in step M2 of Example 1 is shown in the figure. DETAILED DESCRIPTION

[0037] The present application will be further described below in conjunction with examples, but the present application is not limited to these examples.

[0038] Preparation of silane coupling agent in Example 1:

[0039] M1: 600 ml of toluene, 0.1 mol of L-phenylalaninol, 0.1 mol of 4-phenoxybenzoic acid, and 5 g of p-toluenesulfonic acid were sequentially added to a reaction kettle, stirred and mixed, heated to 100°C for 8 h, and the water produced in the reaction was separated by a water trap. The reaction mixture was cooled to room temperature, the pH was adjusted to 7 using a 1M NaOH solution, the organic phase was washed with deionized water three times (400 ml each time), dried with 30 g of anhydrous sodium sulfate, filtered, and distilled at 60°C under reduced pressure for 3 h to obtain an ester compound. The nuclear magnetic resonance hydrogen spectrum data of the ester compound are as follows: 1 HNMR (300 MHz, Chloroform- d ) δ 8.14 - 8.04 (m, 2H), 7.41 - 7.30 (m, 2H), 7.30- 7.23 (m, 3H), 7.20 - 7.10 (m, 3H), 7.07 - 6.94 (m, 4H), 4.35 (dd, J = 12.4,4.3 Hz, 1H), 4.10 (dd, J = 12.4, 4.3 Hz, 1H), 3.48 (pt, J = 6.7, 4.3 Hz, 1H),2.99 (ddt, J = 14.6, 6.6, 0.9 Hz, 1H), 2.73 (ddt, J = 14.6, 6.5, 0.9 Hz, 1H),2.13 (s, 2H);

[0040] M2: 200 ml of anhydrous methanol and 0.1 mol of the ester compound were placed in a reaction bottle under ice bath, stirred and mixed, and 300 ml of anhydrous methanol containing 0.1 mol of 3-(methacryloyloxy)propyltrimethoxysilane was added dropwise under nitrogen protection. After 30 min of dropwise addition, the reaction was carried out at room temperature for 10 h, and then distilled at 50°C under reduced pressure for 3 h to obtain a silane coupling agent. The nuclear magnetic resonance hydrogen spectrum data of the silane coupling agent are as follows: 1 H NMR (300MHz, Chloroform- d) δ 8.14 - 8.04 (m, 2H), 7.41 - 7.31 (m, 2H), 7.30 - 7.24(m, 3H), 7.21 - 7.13 (m, 3H), 7.05 - 6.96 (m, 4H), 4.29 (dd, J = 11.7, 4.4Hz, 1H), 4.21 - 3.98 (m, 3H), 3.75 (dt, J = 8.5, 5.5 Hz, 1H), 3.59 (s, 9H),3.40 (dtt, J = 8.7, 6.7, 4.4 Hz, 1H), 3.04 - 2.82 (m, 2H), 2.79 - 2.51 (m,3H), 1.80 - 1.62 (m, 2H), 1.06 (d, J = 7.3 Hz, 3H), 0.72 (t, J = 9.8 Hz, 2H)。

[0041] Example 2 Preparation of silane coupling agent:

[0042] M1: 600ml of toluene, 0.1mol of L-phenylalaninol, 0.12mol of 4-phenoxybenzoic acid, and 5g of p-toluenesulfonic acid were sequentially added to a reaction kettle, stirred and mixed, heated to 95°C for 10h, and the water produced in the reaction was separated by a water trap. After cooling to room temperature, the pH was adjusted to 7 using a 1M NaOH solution, the organic phase was washed with deionized water three times (400ml each time), dried with 30g of anhydrous sodium sulfate, filtered, and distilled at 60°C under reduced pressure for 3h to obtain an ester compound;

[0043] M2: 200ml of anhydrous methanol and 0.1mol of the ester compound were placed in a reaction bottle under ice bath, stirred and mixed, and 400ml of anhydrous methanol containing 0.13mol of 3-(methacryloyloxy)propyltrimethoxysilane was added dropwise under nitrogen protection. After 30min of dropwise addition, the reaction was carried out at room temperature for 15h, and then distilled at 50°C under reduced pressure for 3h to obtain a silane coupling agent.

[0044] Example 3 Preparation of silane coupling agent:

[0045] M1: 600ml of toluene, 0.1mol of L-phenylalaninol, 0.13mol of 4-phenoxybenzoic acid, and 5g of p-toluenesulfonic acid were sequentially added to a reaction kettle, stirred and mixed, heated to 90°C for 12h, and the water produced in the reaction was separated by a water trap. After cooling to room temperature, the pH was adjusted to 7 using a 1M NaOH solution, the organic phase was washed with deionized water three times (400ml each time), dried with 30g of anhydrous sodium sulfate, filtered, and distilled at 60°C under reduced pressure for 3h to obtain an ester compound;

[0046] M2: 200 ml of anhydrous methanol, 0.1 mol of an ester-based compound were put into a reaction bottle under ice bath, stirred and mixed, 400 ml of an anhydrous methanol solution containing 0.15 mol of 3-(methacryloyloxy)propyl trimethoxysilane was added dropwise under nitrogen protection, 30 min after dropping, the reaction was carried out at room temperature for 18 h, and 3 h of distillation at 50°C under reduced pressure was carried out to obtain a silane coupling agent.

[0047] Preparation of the antibacterial agent in Example 4:

[0048] N1: 1200 ml of a mixed solution of methanol and water (volume ratio 1:1), 60 g of chitosan were put into a reaction kettle, 0.1 M HCl was added dropwise to pH = 6, stirred and dissolved, 8 g of triethylamine was slowly added dropwise, adjusted to pH = 7.5, 10 g of methacrylic anhydride was added dropwise under ice bath, 30 min after dropping, the temperature was raised to 50°C, the reaction was carried out for 4 h, the reaction solution was cooled to room temperature, and the reaction solution was loaded into a dialysis bag (MWCO 10K) and dialyzed with deionized water for 36 h (water was changed every 6 h), and freeze-dried at -36°C for 48 h to obtain acylated chitosan;

[0049] N2: 800 ml of a mixed solution of ethanol and water (volume ratio 1:1), 50 g of acylated chitosan were put into a reaction kettle, 0.1 M HCl was added dropwise to pH = 5, stirred and dissolved, 120 ml of an ethanol solution containing 20 g of vanillin was added, the reaction was carried out at room temperature for 24 h, the reaction solution was loaded into a dialysis bag (MWCO 10K) and dialyzed with deionized water for 36 h (water was changed every 6 h), and freeze-dried at -36°C for 48 h to obtain Schiff base chitosan;

[0050] N3: 800 ml of DMF, 100 g of Schiff base chitosan, 10 g of acrylic acid, 20 g of 2-isopropenylphenyl aniline and 2 g of AIBN were sequentially added into a reaction kettle, stirred and mixed, the temperature was raised to 60°C, the reaction was carried out for 5 h, the reaction solution was cooled to room temperature, the reaction solution was loaded into a dialysis bag (MWCO 10K) and dialyzed with deionized water for 48 h (water was changed every 6 h), and freeze-dried at -36°C for 48 h to obtain an antibacterial agent.

[0051] Preparation of polyether ether ketone composite material for repairing animal bones in Example 5:

[0052] S1: polyether ether ketone 600 g, hydroxyapatite 100 g, bioactive glass 10 g, silane coupling agent (prepared in Example 1) 10 g were weighed;

[0053] S2: 100 g of hydroxyapatite, 10 g of bioactive glass were immersed in 500 ml of acetone, and after ultrasonic treatment for 30 min, filtered, vacuum dried at 50℃ for 6 h, then put into 500 ml of NMP solution containing 10 g of silane coupling agent, added 5 ml of deionized water, heated to 60℃, stirred for 20 h, cooled to room temperature, filtered, washed with deionized water three times (200 ml each time), vacuum dried at 80℃ for 10 h, to obtain a modified inorganic material;

[0054] S3: 600 g of polyether ether ketone and the modified inorganic material prepared in S2 were added to a high-speed mixer and stirred for 20 min at a temperature of 140℃ and a speed of 500 rpm, then extruded through a twin-screw extruder, the screw speed of the twin-screw extruder was 10 r / s, the conveying section temperature of the twin-screw extruder was 340℃, the melting section temperature was 360℃, the mixing section temperature was 360℃, and the homogenization section temperature was 360℃, to obtain a preform;

[0055] S4: The preform was sequentially immersed in 100 ml of acetone and 100 ml of deionized water for 20 min of ultrasonic treatment, vacuum dried at 80℃ for 6 h, then immersed in 100 ml of dichloromethane, and under nitrogen protection, 0.2 mol of anhydrous aluminum chloride and 0.1 mol of succinic anhydride were sequentially added, and refluxed for 6 h, cooled to room temperature, and the sample was taken out, sequentially immersed in 100 ml of acetone and 100 ml of deionized water for 20 min of ultrasonic treatment, vacuum dried at 80℃ for 6 h, to obtain a carboxylated composite material;

[0056] S5: The carboxylated composite material was soaked in 100 g of 0.5wt% EDC solution for 2 h, 0.5 g of an antibacterial agent (prepared in Example 4) was added, and reacted at room temperature for 12 h, then immersed in 100 ml of deionized water for 20 min of ultrasonic treatment, repeated three times, and vacuum dried at 80℃ for 18 h, to obtain a polyether ether ketone composite material for animal bone repair.

[0057] Example 6 Preparation of a polyether ether ketone composite material for animal bone repair:

[0058] S1: Weigh: polyether ether ketone 750 g, hydroxyapatite 200 g, bioactive glass 30 g, silane coupling agent (prepared in Example 2) 20 g;

[0059] S2: 200 g of hydroxyapatite, 30 g of bioactive glass were immersed in 500 ml of acetone, and after ultrasonic treatment for 30 min, filtered, vacuum dried at 50℃ for 6 h, then put into 500 ml of NMP solution containing 20 g of silane coupling agent, added 5 ml of deionized water, heated to 80℃, stirred for 18 h, cooled to room temperature, filtered, washed with deionized water three times (200 ml each time), vacuum dried at 80℃ for 10 h, to obtain a modified inorganic material;

[0060] S3: 750 g of polyether ether ketone and modified inorganic material prepared in S2 were added into a high-speed mixer and stirred for 20 min at a temperature of 145 ℃ and a speed of 500 rpm, and then extruded through a twin-screw extruder at a screw speed of 10 r / s, a conveying section temperature of 340 ℃, a melting section temperature of 360 ℃, a mixing section temperature of 360 ℃, and a homogenizing section temperature of 360 ℃, to obtain a preform;

[0061] S4: The preform was sequentially immersed in 100 ml of acetone and 100 ml of deionized water for ultrasonic washing for 20 min, vacuum dried at 80 ℃ for 6 h, and then immersed in 100 ml of dichloromethane, 0.23 mol of anhydrous aluminum chloride and 0.1 mol of succinic anhydride were sequentially added under nitrogen protection, and refluxed for 8 h, cooled to room temperature, and the sample was taken out, sequentially immersed in 100 ml of acetone and 100 ml of deionized water for ultrasonic washing for 20 min, and vacuum dried at 80 ℃ for 6 h, to obtain a carboxylated composite material;

[0062] S5: The carboxylated composite material was immersed in 100 g of a 0.8 wt% EDC solution for 2 h, 3.5 g of an antibacterial agent (prepared in Example 4) was added, and reacted at room temperature for 20 h, and then immersed in 100 ml of deionized water for ultrasonic washing for 20 min, repeated three times, and vacuum dried at 60 ℃ for 18 h, to obtain a polyether ether ketone composite material for animal bone repair.

[0063] Example 7: Preparation of a polyether ether ketone composite material for animal bone repair

[0064] S1: 850 g of polyether ether ketone, 300 g of hydroxyapatite, 50 g of bioactive glass, and 30 g of silane coupling agent (prepared in Example 3) were weighed;

[0065] S2: 300 g of hydroxyapatite and 50 g of bioactive glass were immersed in 500 ml of acetone, ultrasonically washed for 30 min, filtered, vacuum dried at 50 ℃ for 6 h, and then placed in 500 ml of an NMP solution containing 30 g of silane coupling agent, 5 ml of deionized water was added, the temperature was raised to 100 ℃, and the mixture was stirred and reacted for 12 h, cooled to room temperature, filtered, washed with deionized water three times (200 ml each time), and vacuum dried at 80 ℃ for 10 h, to obtain a modified inorganic material;

[0066] S3: 850 g of polyether ether ketone and modified inorganic material prepared in S2 were added into a high-speed mixer and stirred for 20 min at a temperature of 145 ℃ and a speed of 500 rpm, and then extruded through a twin-screw extruder at a screw speed of 10 r / s, a conveying section temperature of 340 ℃, a melting section temperature of 360 ℃, a mixing section temperature of 360 ℃, and a homogenizing section temperature of 360 ℃, to obtain a preform;

[0067] S4: The preform was sequentially immersed in 100 ml of acetone, 100 ml of deionized water for 20 min under ultrasonic, vacuum dried at 80°C for 6 h, then it was immersed in 100 ml of dichloromethane, under nitrogen protection, 0.25 mol of anhydrous aluminum chloride and 0.1 mol of succinic anhydride were sequentially added, refluxed for 10 h, cooled to room temperature, the sample was taken out, sequentially immersed in 100 ml of acetone, 100 ml of deionized water for 20 min under ultrasonic, vacuum dried at 80°C for 6 h, to obtain a carboxylated composite material;

[0068] S5: The carboxylated composite material was soaked in 100 g of 1 wt% EDC solution for 2 h, 5 g of the antibacterial agent (prepared in Example 4) was added, reacted at room temperature for 24 h, after taking out, immersed in 100 ml of deionized water for 20 min under ultrasonic, repeated three times, vacuum dried at 60°C for 18 h, to obtain a polyether ether ketone composite material for animal bone repair.

[0069] Comparative Example 1

[0070] The raw material composition and process of the polyether ether ketone composite material for animal bone repair were basically the same as those of Example 6, except that the silane coupling agent (prepared in Example 2) added in the components was replaced by the same mass of a silane coupling agent prepared by the following method:

[0071] Under ice bath, 500 ml of methanol and 0.1 mol of L-phenylalaninol were put into a reaction bottle and stirred uniformly, 300 ml of a methanol solution containing 0.13 mol of 3-(methacryloyloxy)propyl trimethoxysilane was added dropwise under nitrogen protection, reacted at room temperature for 15 h, distilled at 50°C under reduced pressure for 3 h, to obtain a silane coupling agent.

[0072] Comparative Example 2

[0073] The raw material composition and process of the polyether ether ketone composite material for animal bone repair were basically the same as those of Example 6, except that the silane coupling agent (prepared in Example 2) added in the components was replaced by the same mass of a silane coupling agent prepared by the following method:

[0074] The preparation method of the silane coupling agent was basically the same as that of Example 2, except that 4-phenoxybenzoic acid in step M1 was replaced by the same molar amount of 4-phenylbenzoic acid.

[0075] Comparative Example 3

[0076] The raw material composition and process of the polyether ether ketone composite material for animal bone repair were basically the same as those of Example 6, except that the silane coupling agent (prepared in Example 2) added in the components was replaced by the same mass of a silane coupling agent prepared by the following method:

[0077] The preparation method of the silane coupling agent is basically the same as that in Embodiment 2, except that L-phenylalaninol in step M1 is replaced by isopropanolamine in an equal molar amount.

[0078] Comparative Example 4

[0079] The raw material composition and process of the polyether ether ketone composite for repairing animal bones are basically the same as those in Embodiment 6, except that the antibacterial agent (prepared in Embodiment 4) added in the components is replaced by an antibacterial agent prepared in the following method in an equal mass:

[0080] The preparation method of the antibacterial agent is basically the same as that in Embodiment 4, except that 2-isopropenyl phenyl aniline in step N3 is not added.

[0081] Comparative Example 5

[0082] The raw material composition and process of the polyether ether ketone composite for repairing animal bones are basically the same as those in Embodiment 6, except that the antibacterial agent (prepared in Embodiment 4) added in the components is replaced by an antibacterial agent prepared in the following method in an equal mass:

[0083] The preparation method of the antibacterial agent is basically the same as that in Embodiment 4, except that 2-isopropenyl phenyl aniline in step N3 is replaced by acrylamide in an equal weight.

[0084] Comparative Example 6

[0085] The raw material composition and process of the polyether ether ketone composite for repairing animal bones are basically the same as those in Embodiment 6, except that the antibacterial agent (prepared in Embodiment 4) added in step S4 is replaced by an antibacterial agent prepared in the following method in an equal mass:

[0086] N1: 1200 ml of a mixed solution of methanol and water (volume ratio 1:1), 60 g of chitosan were added into a reaction kettle, 0.1 M HCl was added dropwise to pH=6, stirred and dissolved, 8 g of triethylamine was slowly added dropwise, adjusted to pH=7.5, 10 g of methacrylic anhydride was added dropwise under ice bath, 30 min after dropwise addition, the temperature was raised to 50℃, and the reaction was carried out for 4 h, then the reaction solution was cooled to room temperature, and the reaction solution was loaded into a dialysis bag (MWCO 10K) and dialyzed with deionized water for 36 h (water was changed every 6 h), and then freeze-dried at -36℃ for 48 h to obtain acylated chitosan;

[0087] N2: 800 ml of DMF, 100 g of acylated chitosan, 10 g of acrylic acid, 20 g of 2-isopropenyl phenyl aniline and 2 g of AIBN were sequentially added into a reaction kettle, stirred and mixed, the temperature was raised to 60℃, and the reaction was carried out for 5 h, then the reaction solution was cooled to room temperature, and the reaction solution was loaded into a dialysis bag and dialyzed with deionized water for 48 h (water was changed every 6 h), and then freeze-dried at -36℃ for 48 h to obtain an antibacterial agent.

[0088] The polyether ether ketone used in the present application is AKSO PEEK® Natural produced by Jiangsu Junhua Special Polymer Material Co., Ltd.; the hydroxyapatite is HAP04-20 produced by Nanjing Junzhu Biological Technology Co., Ltd.; the bioactive glass is Vitryxx® MD01; the chitosan has a molecular weight Mw = 50000 and is produced by Shanghai Mokang Biological Technology Co., Ltd.

[0089] The polyether ether ketone composite materials for repairing animal bones prepared in Examples 5-7 and Comparative Examples 1-6 were subjected to tensile strength, bending strength, antibacterial property and hydrophilicity tests.

[0090] The tensile strength was tested according to GB / T 1040.2-2022 on 1A dumbbell-shaped samples at a speed of 10 mm / min; the bending strength was tested according to GB / T 9341-2008 three-point bending method; the antibacterial property was tested according to GB / T 31402-2015, and the bacteria used were Staphylococcus aureus, and the antibacterial rate was calculated by the following formula: R (%) = (U-A) / U x 100%, wherein U is the logarithmic average of the number of bacteria after 24 h inoculation of the polyether ether ketone composite material for repairing animal bones without adding an antibacterial agent, and A is the logarithmic average of the number of bacteria after 24 h inoculation of the polyether ether ketone composite material for repairing animal bones prepared in Examples 5-7 and Comparative Examples 1-6; the hydrophilicity test was performed according to ISO 15989-2004 contact angle method; and the test results are shown in Table 1.

[0091] Table 1 Performance test data table

[0092]

[0093] As can be seen from Examples 5, 6 and 7 in Table 1, the polyether ether ketone composite material for repairing animal bones prepared in the present application has excellent tensile strength, bending strength and antibacterial property, achieving a synergistic improvement in mechanical properties and antibacterial property, and providing a high-performance solution for repairing animal bones.

[0094] The silicon methoxyl in the silane coupling agent prepared in the present application hydrolyzes to form silicon hydroxyl, which dehydrates and condenses with the hydroxyl on the surface of the hydroxyapatite and the bioactive glass to form a covalent bond or a hydrogen bond, thereby improving the interfacial bonding strength between the PEEK matrix and the inorganic filler and inhibiting phase separation; the rigid benzene ring can provide thermal stability and form a face-to-face stacking with the benzene ring in the PEEK backbone, thereby enhancing the interfacial bonding energy; the silane coupling agent prepared in the present application contains an ether bond, which can provide flexibility and improve the bending strength. The good mechanical properties enable the polyether ether ketone composite material to have better durability and prolong the service life of implantation.

[0095] The amino group in the antibacterial agent prepared by the application can interact with the negatively charged groups on the surface of the microbial cell membrane, destroy the integrity of the cell membrane. The phenolic hydroxyl structure can interact with the phospholipid bilayer on the bacterial cell membrane, change the membrane permeability, cause imbalance of ions in the cell, and achieve the purpose of antibacterial. The phenolic hydroxyl group can play an anti-inflammatory role by removing free radicals, interfering with inflammatory signaling pathways, etc. The Schiff base can inhibit the activity of enzymes in the bacteria, thereby interfering with the metabolic process of the bacteria, hindering the growth and reproduction of the bacteria, and improving the antibacterial effect. The antibacterial agent prepared in the application contains a large number of hydrophilic functional groups (such as hydroxyl, carboxyl, etc.) which are helpful to promote the adhesion and growth of cells, improve the biocompatibility of the material, and improve the bone repair performance of animals; and the antibacterial agent can effectively inhibit the growth of bacteria, reduce the risk of postoperative infection of animals.

[0096] The above is only the preferred embodiment of the application and is not used to limit the application; but for ordinary skilled persons in the art, some minor changes, modifications and equivalent changes of the above disclosed technical content without departing from the scope of the technical scheme of the application can be made, and all the equivalent embodiments of the application are equivalent embodiments of the application; at the same time, any equivalent changes, modifications and evolution of the above embodiments according to the essential technology of the application are still within the protection scope of the technical scheme of the application.

Claims

1. A method for producing a polyether ether ketone composite material for animal bone repair, characterized by, The method comprises the following steps: S1: weighing by weight parts: polyether ether ketone 60-85 parts, hydroxyapatite 10-30 parts, bioactive glass 1-5 parts, silane coupling agent 1-3 parts; S2: after washing the hydroxyapatite and bioactive glass, put them into the NMP solution of the silane coupling agent, add deionized water, heat to 60-100 DEG C, and react for 12-20 hours to obtain modified inorganic materials; S3: put the polyether ether ketone and modified inorganic materials into a high-speed mixer and stir to mix uniformly, then extrude through a double screw extruder to obtain a preform; S4: after washing and drying the preform, immerse it in dichloromethane, add anhydrous aluminum chloride and succinic anhydride in sequence, and reflux for 6-10 hours to obtain a carboxylated composite material; S5: immerse the carboxylated composite material in an EDC solution, add an antibacterial agent and react for 12-24 hours to obtain a polyether ether ketone composite material; The silane coupling agent is prepared by the following method: M1: L-phenylalaninol reacts with 4-phenoxybenzoic acid to form an ester compound; M2: the ester compound reacts with 3-(methacryloyloxy) propyl trimethoxysilane to obtain a silane coupling agent.

2. The method for preparing a polyetheretherketone composite material for animal bone repair according to claim 1, characterized in that, In step M1, the molar ratio of L-phenylalaninol to 4-phenoxybenzoic acid is 1:(1-1.3); in step M2, the molar ratio of the ester compound to 3-(methacryloyloxy) propyl trimethoxysilane is 1:(1-1.5).

3. The method for preparing a polyetheretherketone composite material for animal bone repair according to claim 1, characterized in that, The antibacterial agent is prepared by the following method: N1: chitosan reacts with methacrylic anhydride to form acylated chitosan; N2: acylated chitosan reacts with vanillin to form Schiff base chitosan; N3: Schiff base chitosan, acrylic acid and 2-isopropenyl aniline react under the action of initiator AIBN to form an antibacterial agent.

4. The method for preparing a polyetheretherketone composite material for animal bone repair according to claim 3, characterized in that, In step N1, the mass ratio of chitosan to methacrylic anhydride is 6:

1.

5. The method for preparing a polyetheretherketone composite material for animal bone repair according to claim 3, characterized in that, In step N2, the mass ratio of acylated chitosan to vanillin is 5:

2.

6. The method for preparing a polyetheretherketone composite material for animal bone repair according to claim 3, characterized in that, In step N3, the mass ratio of Schiff base chitosan, acrylic acid and 2-isopropenyl aniline is 10:1:

2.

7. The method for preparing a polyetheretherketone composite material for animal bone repair according to claim 1, characterized in that, In step S4, the molar ratio of anhydrous aluminum chloride to succinic anhydride is (2-2.5):

1.

8. The method for preparing a polyetheretherketone composite material for animal bone repair according to claim 1, characterized in that, In step S5, the EDC solution is a 1-ethyl-(3-dimethylaminopropyl) carbonyl diimide hydrochloride aqueous solution with a concentration of 0.5-1 wt%; the mass ratio of EDC to antibacterial agent is 1:(1-5).

9. A polyether ether ketone composite material for animal bone repair, characterized by, The method is prepared by any one of claims 1 to 8.

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