Piezoelectric catalytic bioheterojunction PEEK bone implant material and preparation method

Abstract

The application belongs to the technical field of biological materials, and discloses a piezocatalytic biological heterojunction PEEK bone implant material and a preparation method. The material comprises a PEEK bone implant loaded with a biological heterojunction. The biological heterojunction is composed of BiVO4 and a chalcogenide calcium compound in a molar ratio of 1-3. The chalcogenide calcium compound is calcium sulfide, calcium selenide or calcium telluride. In the preparation, the BiVO4 / CaX biological heterojunction is prepared by a hydrothermal method or an in-situ composite method. Then, the PEEK is sequentially cleaned by acetone, ethanol and deionized water, and is subjected to ultrasonic treatment in sulfuric acid for 5-10 minutes. After being modified by dopamine, the biological heterojunction is contacted with the modified PEEK at 4 DEG C for 12 hours to complete the loading. In some schemes, an improved means can be introduced. The material has the functions of sound catalytic antibiosis and bone repair promotion. The antibiosis effect can be controlled by ultrasound. The process is simple, and the reaction conditions are mild. The material can also cope with multiple drug-resistant bacterial infections, and can improve the stability of the heterojunction loading and the cell compatibility of the material.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological materials, and particularly relates to a PEEK bone implant material with piezoelectric catalytic biological heterojunction and a preparation method. BACKGROUND

[0002] At present, infectious diseases related to bacteria are a serious risk faced by human beings, and infection caused by bacteria is one of the most common and most serious complications in the process of combining with in-vivo tissues. The implant material in bone tissue needs to be retained in the body for a long time, and therefore the consequences caused by the problem of implant-related infection are more serious. Implant failure caused after infection needs to be replaced, which increases the risk of secondary surgery for patients.

[0003] In clinical practice, the most commonly used anti-infection means at present is still antibiotics, but long-term misuse and abuse of preventive antibiotics not only produces strong toxic side effects on normal cells and organs, but also leads to the prevalence of multi-drug resistant pathogens. Therefore, it is necessary to develop a bone implant material which can not only effectively eradicate microbial pathogens and promote bone repair, but also does not produce bacterial resistance.

[0004] In the prior art, a plurality of polyether ether ketone-based bone implant materials have been disclosed, but these materials mainly use near-infrared light to excite photocatalysis and photothermal therapy. At present, there is no bone implant material formed by combining a biological heterojunction with a PEEK matrix and having sound catalytic antibacterial and bone repair promoting properties disclosed. SUMMARY

[0005] In order to solve the problems existing in the prior art, the application provides a new PEEK bone implant material with piezoelectric catalytic biological heterojunction and a preparation method, which is different from the existing materials and realizes the corresponding technical effects through special piezoelectric properties.

[0006] The technical scheme adopted by the application is as follows:

[0007] In a first aspect, the application provides a PEEK bone implant material with piezoelectric catalytic biological heterojunction, which comprises a PEEK bone implant loaded with a biological heterojunction material, and the biological heterojunction material is composed of BiVO4 and a sulfur family calcium compound in a molar ratio range of 1-3.

[0008] In combination with the first aspect, the application provides a first embodiment of the first aspect, wherein the biological heterojunction material is composed of BiVO4 and a sulfur family calcium compound in a molar ratio of 2:1.

[0009] In combination with the first aspect, the application provides a second embodiment of the first aspect, wherein the sulfur family calcium compound comprises one of calcium sulfide, calcium selenide and calcium telluride.

[0010] In a second aspect, the present application further provides a preparation method for preparing the PEEK bone implant material with the piezocatalytic bioheterojunction as described above, and the preparation method comprises the following steps:

[0011] First, the bioheterojunction material is prepared, the calcium sulfide is added into the BiVO4 mixed solution with ethylene glycol to form a reaction solution, and then the liquid system containing the bioheterojunction is formed by the hydrothermal method or the in-situ composite method, and the BiVO4 / CaX bioheterojunction is obtained by drying the liquid system through the alternate washing of the anhydrous ethanol and the deionized water, and then the obtained BiVO4 / CaX bioheterojunction is loaded on the PEEK material to form the bone implant material.

[0012] In combination with the second aspect, the present application provides a first implementation manner of the second aspect, wherein the BiVO4 mixed solution is prepared by dissolving the bismuth nitrate and the ammonium vanadate material in the mixed solution of the ethylene glycol and the deionized water through the ultrasonic treatment.

[0013] In combination with the second aspect, the present application provides a second implementation manner of the second aspect, wherein in the preparation of the bone implant material, the PEEK material is first cleaned by the acetone, the ethanol and the deionized water, and then the treated sulfonated PEEK material is obtained by the ultrasonic treatment of the sulfuric acid for 5-10 min.

[0014] Then, the Tris solution with the concentration of 10 mmol / L is prepared, the pH of the Tris solution is adjusted to 8.5 by the dilute hydrochloric acid, and then the dopamine solution is obtained by adding the dopamine hydrochloride with the concentration of 2 mg / mL into the Tris solution.

[0015] After the sulfonated PEEK material is fully contacted with the dopamine solution for 24 h, the dopamine-modified PEEK material is obtained through the drying treatment.

[0016] After the obtained BiVO4 / CaX bioheterojunction is fully contacted with the dopamine-modified PEEK material at 4℃ for 12 h, the bone implant material is obtained.

[0017] In combination with the second aspect, the present application provides a third implementation manner of the second aspect, wherein in the formation of the liquid system containing the bioheterojunction by the hydrothermal method or the in-situ composite method, the heating temperature is 160℃, and the holding time is at least 6 h.

[0018] The BiVO4 in the prior art is a common semiconductor material, and the CaX can be used as the introduced material to form the heterojunction, but the conventional technical means is based on the characteristics of the semiconductor material, and the material can be used at a specific position by the light-activated catalytic means.

[0019] Specifically, the conventional scheme is mostly with near-infrared light, visible light and other external light sources as energy input, through light excitation to generate photo-generated electron-hole pairs in BiVO4 / CaX heterojunction, and then use the photo-generated carriers to react with water and oxygen in the surrounding environment to generate active oxygen free radicals to achieve antibacterial effect. Some schemes will also combine the photo-thermal conversion characteristics of BiVO4 to induce local heating and assist to enhance the antibacterial effect.

[0020] Ultrasound has excellent penetration depth and propagation stability in human tissues, can easily reach deep bone implant sites, and can generate piezoelectric current and piezoelectric electric field through ultrasonic vibration energy to drive the efficient generation of active oxygen free radicals, realizing sound-catalyzed antibacterial effect. At the same time, the calcium ions released by CaX and the piezoelectric effect can synergistically promote bone cell adhesion, proliferation and differentiation, and have both antibacterial and bone repair functions, which not only solves the efficiency short board of conventional light activation technology in deep bone implantation scenarios, but also eliminates the dependence on external light sources, significantly improving the clinical practicability and reliability of bone implant materials.

[0021] The beneficial effects of the present application are:

[0022] 1. The present application provides a material with bone repair and sound-catalyzed antibacterial function, thereby increasing the types of bone implant materials, and using such materials can achieve bone regeneration and postoperative anti-infection;

[0023] 2. The scaffold material prepared by the limiting method of the present application is loaded with a biological heterojunction. Experiments show that the biological heterojunction has excellent sound-catalyzed antibacterial effect, and thus can provide a way of sonodynamic antibacterial therapy;

[0024] 3. The method of the present application has simple process, mild reaction conditions and low energy consumption, and is easy to mass produce, thus being beneficial to popularization and application. DETAILED DESCRIPTION

[0025] The present application will be further explained in conjunction with specific embodiments.

[0026] In order to make the purpose, technical scheme and advantages of the embodiments of the present application more clear, the technical scheme in the embodiments of the present application will be described clearly and completely in conjunction with the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, but not all the embodiments.

[0027] Therefore, the following detailed description of the embodiments of the present application is not intended to limit the scope of the claimed application, but only represents selected embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without making creative efforts fall within the scope of the present application.

[0028] Embodiment 1:

[0029] The embodiment discloses a piezoelectric catalytic biological heterojunction PEEK bone implant material, and the core is a PEEK substrate loaded with a biological heterojunction. The biological heterojunction material is composed of BiVO4 and a sulfide calcium compound in a molar ratio of 1:1-3:1, wherein the sulfide calcium compound is a mixture of one or more of CaS, CaSe and CaTe, and the loading amount of the biological heterojunction on the PEEK surface is 5-20 wt% based on the mass of the PEEK substrate.

[0030] The embodiment provides a manufacturing method for the above material, and the manufacturing method is as follows:

[0031] Biological heterojunction preparation: anhydrous bismuth nitrate and ammonium vanadate are dissolved in a mixed solution of ethylene glycol and deionized water in a stoichiometric ratio, and ultrasonic treatment is performed for 10-30 min until complete dissolution to obtain a BiVO4 precursor solution; a metered amount of a sulfide calcium compound is added to the solution, and ultrasonic mixing is performed for 15-40 min to form a uniform reaction liquid;

[0032] The reaction liquid is moved into a reaction kettle, and a hydrothermal method or an in-situ compounding method is used to form a liquid system containing a biological heterojunction at 140-180°C for 6-12 h; after the impurity ions are removed, the system is washed by alternating centrifugation with anhydrous ethanol and deionized water for 3-5 times, each time at a centrifugal speed of 8000-12000 r / min and a centrifugal time of 10-20 min, and then vacuum drying is performed at 60-80°C for 8-12 h to obtain a BiVO4 / CaX biological heterojunction powder.

[0033] PEEK substrate pretreatment: the PEEK material is cut to the required size, and is sequentially ultrasonically cleaned with acetone, ethanol and deionized water for 15-30 min to remove surface oil stains; then the PEEK material is immersed in sulfuric acid with a concentration of 90-98 wt%, and ultrasonic treatment is performed for 5-10 min; after being taken out, the PEEK material is washed with a large amount of deionized water until the washing liquid is neutral, and a sulfonated PEEK material with a porous surface is obtained.

[0034] Dopamine modification: a 10 mmol / L Tris solution is prepared, hydrochloric acid is used to adjust the pH to 8.5, hydrochloric acid dopamine is added to make the concentration reach 2 mg / mL, and stirring is uniformly performed to obtain a dopamine solution; the sulfonated PEEK material is immersed in the dopamine solution, constant-temperature reaction is performed at 25-37°C for 20-24 h, the surface residual solution is washed away with deionized water after being taken out, and vacuum drying is performed at 60°C for 6-8 h to obtain a dopamine-modified PEEK material.

[0035] BiVO4 / CaX bio-heterojunction loading: BiVO4 / CaX bio-heterojunction powder was dispersed in deionized water, and ultrasonic dispersion was performed for 20-30 min to form a suspension with a concentration of 1-5 mg / mL; the dopamine-modified PEEK material was immersed in the suspension, and was allowed to stand at 4-10 °C for 10-12 h, so that the bio-heterojunction was loaded on the surface of the PEEK through the adhesion of dopamine; after being taken out, vacuum drying was performed at 60-70 °C for 6-10 h to obtain the bio-heterojunction PEEK bone implant material.

[0036] Example 2:

[0037] This example is based on the material of Example 1 described above, and is limited to a bio-heterojunction PEEK bone implant material with a BiVO4:CaS ratio of 1:1, and the preparation method is as follows:

[0038] Bio-heterojunction preparation: 0.01 mol of anhydrous bismuth nitrate and 0.01 mol of ammonium vanadate were weighed and dissolved in a mixed solution of 50 mL of ethylene glycol and 50 mL of deionized water, and ultrasonic dissolution was performed for 20 min; 0.01 mol of CaS powder was added, and ultrasonic treatment was performed for 30 min to form a reaction solution; the reaction solution was transferred to a polytetrafluoroethylene reaction kettle, and hydrothermal incubation was performed at 160 °C for 8 h; after the reaction was completed, the reaction solution was washed by centrifugation with anhydrous ethanol and deionized water alternately for 4 times (10000 r / min, 15 min / time), and vacuum drying was performed at 70 °C for 10 h to obtain a BiVO4 / CaS bio-heterojunction (molar ratio 1:1).

[0039] PEEK pretreatment: the PEEK material was sequentially subjected to ultrasonic treatment with acetone, ethanol, and deionized water for 20 min each, was immersed in 98 wt% sulfuric acid for ultrasonic treatment for 6 min, and was washed with water until neutral.

[0040] Dopamine modification: a dopamine solution was prepared according to the method of Example 1, and after the sulfonated PEEK was immersed, reaction was performed at 37 °C for 24 h, and vacuum drying was performed at 60 °C for 7 h.

[0041] Loading: BiVO4 / CaS powder was dispersed into a suspension with a concentration of 3 mg / mL, and after the dopamine-modified PEEK was immersed, standing was performed at 4 °C for 12 h, and vacuum drying was performed at 65 °C for 8 h to obtain the target material (loading amount 10 wt%).

[0042] Example 3:

[0043] This example is based on the material of Example 1 described above, and is limited to a bio-heterojunction PEEK bone implant material with a BiVO4:CaSe ratio of 2:1, and the preparation method is as follows:

[0044] BiVO4 / CaSe bio-heterojunction preparation: 0.02 mol of anhydrous bismuth nitrate and 0.02 mol of ammonium vanadate were weighed and dissolved in a mixed solution of 80 mL of ethylene glycol and 40 mL of deionized water, and ultrasonic dissolution was performed for 15 min; 0.01 mol of CaSe powder was added, and ultrasonic treatment was performed for 25 min to form a reaction solution; in-situ compounding was performed at 160°C for 7 h; the reaction solution was washed by centrifugation with anhydrous ethanol and deionized water alternately for 5 times, and vacuum drying was performed at 65°C for 9 h to obtain the BiVO4 / CaSe bio-heterojunction.

[0045] PEEK pretreatment: PEEK was sequentially ultrasonically treated with acetone, ethanol, deionized water for 25 min each, and then immersed in 95 wt% sulfuric acid for ultrasonic treatment for 8 min, and then washed with water until neutral.

[0046] Dopamine modification: a dopamine solution was prepared according to the method of Example 1, and the sulfonated PEEK was immersed for 22 h at 30°C after which vacuum drying was performed at 60°C for 6 h.

[0047] Loading: the BiVO4 / CaSe powder was dispersed into a suspension of 4 mg / mL, and the dopamine-modified PEEK was immersed, and then left to stand for 11 h at 6°C, and then vacuum drying was performed at 70°C for 7 h to obtain the target material.

[0048] Example 4:

[0049] This example is based on the material of Example 1 described above, and is limited to a bio-heterojunction PEEK bone implant material with BiVO4:CaTe = 3:1, and the preparation method is as follows:

[0050] BiVO4 / CaTe bio-heterojunction preparation: 0.03 mol of anhydrous bismuth nitrate and 0.03 mol of ammonium vanadate were weighed and dissolved in a mixed solution of 100 mL of ethylene glycol and 50 mL of deionized water, and ultrasonic dissolution was performed for 25 min; 0.01 mol of CaTe powder was added, and ultrasonic treatment was performed for 35 min to form a reaction solution; hydrothermal treatment was performed at 170°C for 10 h; the reaction solution was washed by centrifugation with anhydrous ethanol and deionized water alternately for 4 times, and vacuum drying was performed at 75°C for 8 h to obtain the BiVO4 / CaTe bio-heterojunction.

[0051] PEEK pretreatment: PEEK was sequentially ultrasonically treated with acetone, ethanol, deionized water for 18 min each, and then immersed in 92 wt% sulfuric acid for ultrasonic treatment for 10 min, and then washed with water until neutral.

[0052] Dopamine modification: a dopamine solution was prepared according to the method of Example 1, and the sulfonated PEEK was immersed for 23 h at 28°C after which vacuum drying was performed at 60°C for 8 h.

[0053] Loading: the BiVO4 / CaTe powder was dispersed into a suspension of 2 mg / mL, and the dopamine-modified PEEK was immersed, and then left to stand for 10 h at 8°C, and then vacuum drying was performed at 60°C for 9 h to obtain the target material.

[0054] Example 5:

[0055] This embodiment is based on the material of the above-mentioned embodiment 1, and introduces hydroxyapatite to improve the load stability and bone-promoting effect. Because the existing heterojunction material is easy to separate from the PEEK matrix in the body fluid environment in vivo, leading to attenuation of piezoelectric antibacterial effect, and bone repair is only dependent on the calcium release of chalcogenide calcium, the effect is limited.

[0056] Material composition

[0057] The biological heterojunction is composed of BiVO4: CaS=2:1 and 5wt% hydroxyapatite, and is loaded on the PEEK matrix with a loading amount of 15wt%.

[0058] Preparation method

[0059] Biological heterojunction preparation: BiVO4 / CaS heterojunction powder is prepared according to the method of embodiment 3, 5wt% HA powder is added to the powder, and ultrasonic dispersion is performed for 30min to obtain BiVO4 / CaS / HA composite heterojunction.

[0060] PEEK pretreatment and dopamine modification steps are the same as in embodiment 3.

[0061] Loading: BiVO4 / CaS / HA composite heterojunction is dispersed into a 4mg / mL suspension, dopamine modified PEEK is immersed, and then placed at 4°C for 12h, and vacuum dried at 70°C for 8h to obtain the target material.

[0062] Embodiment 6:

[0063] This embodiment is based on the material of the above-mentioned embodiment 1, and the annealing treatment is used to enhance the low-power piezoelectric response. The existing similar material needs a higher ultrasonic power ≥1.0W / cm² to achieve effective piezoelectric antibacterial effect, and high-power ultrasound may cause certain damage to the surrounding normal bone tissue, which is difficult to adapt to the clinical low-damage requirement.

[0064] Material composition

[0065] The biological heterojunction is BiVO4: CaSe=2:1, which is annealed to optimize the crystal structure, and is loaded on the PEEK matrix with a loading amount of 12wt%.

[0066] Preparation method

[0067] Biological heterojunction preparation: BiVO4 / CaSe heterojunction powder is prepared according to the method of embodiment 3, and is placed in a muffle furnace and annealed in an air atmosphere at 500°C for 2h, and then naturally cooled to room temperature to obtain annealed modified BiVO4 / CaSe heterojunction.

[0068] PEEK pretreatment and dopamine modification steps are the same as in embodiment 3.

[0069] Loading: After annealing, BiVO4 / CaSe heterojunction was dispersed into a 3.5 mg / mL suspension, and the dopamine-modified PEEK was immersed and then placed at 4°C for 12 h and dried at 65°C for 7 h to obtain the target material.

[0070] Example 7:

[0071] This example is based on the material of Example 1 above, and the RGD peptide segment is grafted to improve cell compatibility, because the existing heterojunction material has insufficient biocompatibility on the surface, and the adhesion and proliferation of bone cells on the material surface are limited, which affects the efficiency of bone repair.

[0072] Material composition

[0073] The biological heterojunction is BiVO4:CaTe=2:1, the surface is grafted with 0.5wt% arginine-glycine-aspartic acid (RGD) peptide segment, and the loading amount on the PEEK matrix is 14wt%.

[0074] Preparation method

[0075] Biological heterojunction preparation: BiVO4 / CaTe heterojunction powder was prepared according to the method of Example 4, dispersed in PBS buffer, and RGD peptide segment was added to make the concentration 0.5wt%, stirred at 37°C for 6h, centrifuged to collect the powder, washed with PBS buffer for 3 times, and dried at 60°C for 8h to obtain RGD grafted BiVO4 / CaTe heterojunction.

[0076] PEEK pretreatment and dopamine modification steps are the same as Example 4.

[0077] Loading: RGD grafted BiVO4 / CaTe heterojunction was dispersed into a 3 mg / mL suspension, and the dopamine-modified PEEK was immersed and then placed at 4°C for 12 h and dried at 65°C for 8h to obtain the target material.

[0078] In order to verify the effectiveness of the materials provided in the examples, the following experimental content is provided for illustration.

[0079] Experiment 1: Piezoelectric performance test

[0080] Experimental materials

[0081] The target materials of Examples 1-7, pure PEEK material, pure BiVO4 powder, dopamine-modified PEEK without loaded heterojunction (control group 1), and unmodified BiVO4 / CaSe (2:1) loaded PEEK (control group 2, without annealing treatment).

[0082] Test method

[0083] Piezoelectric constant (d 33Test: The piezoelectric constant tester, model ZJ-3A, was used to test the d 33 values of each material at room temperature. Five different sites were tested for each sample, and the average value was taken. The experiment was repeated independently three times, and the data were expressed as "mean ± standard deviation".

[0084] Piezoelectric current test: The material was cut into a sample of 10 mm x 10 mm x 2 mm, with gold electrodes sputtered on the upper and lower surfaces. The electrochemical workstation, model CHI660E, was connected, and the piezoelectric current peak generated by the material was tested under ultrasonic excitation at a frequency of 20 kHz and a power of 0.2-1.5 W / cm².

[0085] Statistical analysis: Independent sample t-test was performed using SPSS 26.0 software, and p<0.05 was considered statistically significant.

[0086] Specifically as follows:

[0087] Sample piezoelectric constant d 33 (pC / N) Peak piezoelectric current (μA) at 0.5 W / cm² ultrasonic power Peak piezoelectric current (μA) at 1.0 W / cm² ultrasonic power Pure PEEK 0±0 0±0 0±0 pure bi v o4 powder 6.2±0.8 - (No substrate support, unable to stabilize test) - (No substrate support, unable to stabilize test) Control 1 0±0 0±0 0±0 Control 2 14.5±1.1 0.82±0.09 1.56±0.15 Example 1 (Wide range of materials, average) 12.3±1.8 0.65±0.08 1.38±0.16 Example 2 11.8±1.3 0.61±0.07 1.32±0.14 Example 3 18.6±1.7 1.05±0.10 2.12±0.21 Example 4 13.2±1.5 0.73±0.09 1.48±0.17 Example 5 (with HA) 17.9±1.6 1.01±0.11 2.05±0.19 Example 6 (annealed) 24.3±2.3 1.58±0.14 3.22±0.28 Example 7 (RGD grafting) 18.1±1.9 1.03±0.10 2.08±0.20

[0088] Results analysis

[0089] Pure PEEK and control group 1 had no piezoelectric properties, proving that the piezoelectric effect came from the biological heterojunction (p<0.001); the piezoelectric constant and piezoelectric current of Example 3 were significantly higher than those of control group 2 (p<0.05), verifying that the molar ratio was optimal; after annealing, the piezoelectric properties of Example 6 were greatly improved (p<0.01), and the optimization of crystal crystallinity was the reason for the improvement of piezoelectric properties; the piezoelectric properties of Examples 5 and 7 had no significant difference from those of Example 3 (p>0.05), proving that HA complexation and RGD grafting did not damage the piezoelectric effect.

[0090] Experiment 2: Sound catalytic antibacterial performance test

[0091] Experimental materials

[0092] Target materials of Examples 1-7, pure PEEK (control group 3), control group 2, and commercial antibiotic bone implant material (control group 4, containing cefazolin).

[0093] Test method

[0094] Pathogenic bacteria selection: Staphylococcus aureus (ATCC25923) and Escherichia coli (ATCC25922) are common pathogenic bacteria for bone implant infection.

[0095] Bacterial solution preparation: The pathogenic bacteria were inoculated in LB medium and cultured at 37°C for 12 h, and then diluted to a concentration of 1x10 6 CFU / mL.

[0096] Antibacterial test: each material sample (10mmx10mmx2mm) was placed in a 24-well plate, 1mL of bacterial solution was added to each well, and the samples were treated under the conditions of no ultrasonic, ultrasonic (20kHz, 0.5W / cm², 30min), and ultrasonic (20kHz, 1.0W / cm², 30min) respectively; after treatment, the bacterial solution was gradiently diluted, spread on LB agar plates, and cultured at 37°C for 18h, the number of colonies was counted, and the antibacterial rate and sterilization rate were calculated.

[0097] Statistical analysis: single factor analysis of variance (ANOVA) was performed using SPSS 26.0 software, and LSD method was used for comparison between groups, p<0.05 was considered significant.

[0098] Antibacterial rate = (number of colonies in control group - number of colonies in experimental group) / number of colonies in control group x 100%

[0099] Sterilization rate = (number of colonies in control group - number of surviving colonies in experimental group) / number of colonies in control group x 100%

[0100] The specific values are shown in the following table:

[0101] Sample Test condition S. aureus inhibition rate (%) S. aureus sterilization rate (%) E. coli inhibition rate (%) E. coli sterilization rate (%) Control 3 (Pure PEEK) No ultrasonic 0±1.2 0±0 0±1.0 0±0 Control 3 (Pure PEEK) Ultrasonic 0.5 W / cm², 30 min 2.3±0.8 0±0 1.8±0.7 0±0 Control 2 Ultrasonic 0.5 W / cm², 30 min 82.5±3.6 71.3±4.2 78.6±3.1 67.5±3.8 Control 4 (antibiotic) No ultrasonic 90.2±3.3 85.6±3.5 88.7±3.0 83.2±3.6 Example 3 Ultrasonic 0.5 W / cm², 30 min 95.8±2.7 89.7±3.1 93.6±2.9 87.3±3.4 Example 3 Ultrasonic 1.0 W / cm², 30 min 99.2±0.8 96.5±1.5 98.7±1.2 94.8±2.1 Example 5 (with HA) Ultrasonic 0.5 W / cm², 30 min 94.9±3.2 88.5±3.5 92.8±3.3 86.1±3.7 Example 6 (annealed) Ultrasonic 0.5 W / cm², 30 min 98.5±1.7 94.2±2.4 97.8±1.9 92.5±2.8 Example 7 (RGD grafting) Ultrasonic 0.5 W / cm², 30 min 95.3±2.9 89.1±3.3 93.1±3.0 86.7±3.5

[0102] Results analysis

[0103] Pure PEEK had no antibacterial effect (p>0.05), and ultrasonic only slightly affected the number of colonies; the antibacterial effect of Example 3 was significantly better than that of Control Group 2 (p<0.05), and was close to that of commercial antibiotic materials under low power (p>0.05), and the sterilization rate was over 94% under high power; after annealing, the antibacterial / sterilization rate of Example 6 was significantly improved under low power (p<0.01), proving that the enhanced piezoelectric response under low power can directly improve the antibacterial effect; the antibacterial effects of Examples 5 and 7 were not significantly different from that of Example 3 (p>0.05), indicating that the introduction of HA and RGD did not affect the sound catalytic antibacterial performance.

[0104] Experiment 3: loading stability test

[0105] Experimental materials

[0106] Example 5 (containing HA), Example 3 (without HA), and Control Group 2.

[0107] Test method

[0108] Simulated body fluid immersion: the samples were immersed in simulated body fluid (SBF, pH=7.4) and oscillated at 37°C (100r / min), and were immersed for 7d, 14d, and 28d respectively; the experiment was repeated independently for 3 times.

[0109] Load shedding rate test: After soaking, the sample was taken out, the surface was rinsed with deionized water, vacuum dried to constant weight, and the mass loss rate (shedding rate) = (mass before soaking - mass after soaking) / load before soaking x 100% was calculated.

[0110] Piezoelectric performance retention rate test: The d 33 value of the soaked sample was tested and the piezoelectric current under ultrasound 0.5 W / cm², and the retention rate = (value after soaking / value before soaking) x 100% was calculated.

[0111] It should be noted that the HA surface is rich in hydroxyl groups, which can form hydrogen bonds with the amino groups on the dopamine-modified PEEK surface, and the calcium ions of HA can form coordination bonds with the oxygen atoms on the surface of the BiVO4 / CaS heterojunction, and the double action enhances the bonding force between the heterojunction and the matrix, reducing shedding in the body fluid environment.

[0112] Test results

[0113] Sample Soaking time Load shedding rate (%) piezoelectric constant d 33 retention (%)]]> Piezoelectric current retention rate (%) Control 2 7d 8.6±1.3 85.3±2.1 83.5±2.3 Control 2 14d 15.8±2.1 72.6±2.5 70.8±2.6 Control 2 28d 27.3±2.8 58.4±4.5 56.2±4.8 Example 3 7d 6.2±1.1 89.7±2.9 88.2±3.1 Example 3 14d 11.5±1.7 78.5±3.4 76.9±3.7 Example 3 28d 20.7±2.3 65.8±4.2 64.3±4.5 Example 5 (with HA) 7d 4.8±0.9 96.8±2.1 95.7±2.5 Example 5 (with HA) 14d 8.3±1.5 91.5±2.7 90.3±3.0 Example 5 (with HA) 28d 14.6±2.0 85.2±3.3 83.6±3.6

[0114] Result analysis

[0115] The load shedding rate of Example 5 (containing HA) was significantly lower than that of Example 3 and Control Group 2 (p<0.05), and the shedding rate was 14.6% at 28d, which was 46.5% lower than that of Control Group 2; the piezoelectric performance retention rate was also greatly improved (p<0.05), and the d 33 The retention rate reached 85.2%, combined with SEM characterization and combined mechanism analysis, it was confirmed that HA effectively improved the bonding stability of the biological heterojunction and the PEEK matrix through the dual action of hydrogen bonds and coordination bonds, solving the technical problem of load shedding in the body fluid environment.

[0116] Experiment 4: Test of bone repair performance

[0117] Experimental materials

[0118] Examples 3, 5, 7, pure PEEK (Control Group 3), Control Group 2, commercial PEEK bone implant material (Control Group 5).

[0119] Test method

[0120] Cell culture: Rabbit bone marrow mesenchymal stem cells (BMSCs) were taken and inoculated in DMEM culture medium containing 10% fetal bovine serum, and cultured at 37°C, 5% CO2.

[0121] Cell proliferation test (CCK-8 method): Each material sample was placed in a 96-well plate, 1x10 4BMSCs were cultured for 1d, 3d, 7d respectively; 10ul CCK-8 reagent was added to each well, and the culture was continued for 4h, and the absorbance (OD value) was tested by an enzyme label instrument (450nm wavelength), and the proliferation rate = (experimental group OD value / control group 3 OD value) x 100%.

[0122] Alkaline phosphatase (ALP) activity test: after 7d, 14d of cell culture, ALP activity was tested by ALP activity detection kit (Nanjing Jiancheng), and the relative activity was calculated based on the activity of the control group 3.

[0123] Hydrophilic characterization: the water contact angle of each material surface was tested by a contact angle measuring instrument, 5 sites of each sample were tested, and the average value was taken; the results showed that the contact angle of example 7 (RGD grafting) was 42.3±2.5°, which was significantly lower than that of example 3 (65.7±3.1°) (p<0.01), which confirmed that RGD grafting improved the hydrophilicity of the material and provided favorable conditions for cell adhesion.

[0124] Statistical analysis: ANOVA analysis was performed by SPSS 26.0 software, and p<0.05 was considered significantly different.

[0125] Test results

[0126] Sample Culture time Cell proliferation rate (%) ALP relative activity (%) Control 3 (Pure PEEK) 1d 100.0±3.2 - (1d no ALP detected) Control 3 (Pure PEEK) 3d 128.5±5.3 - (3d no ALP detected) Control 3 (Pure PEEK) 7d 186.3±6.7 100.0±5.8 Control 3 (Pure PEEK) 14d 253.7±7.2 132.5±6.4 Control 2 1d 112.6±4.8 - Control 2 3d 145.8±5.6 - Control 2 7d 218.7±6.3 128.3±6.1 Control 2 14d 296.5±7.5 165.8±6.8 Control 5 (commercial) 1d 115.3±4.9 - Control 5 (commercial) 3d 150.2±5.8 - Control 5 (commercial) 7d 225.6±6.5 135.7±6.3 Control 5 (commercial) 14d 308.4±7.8 172.4±7.1 Example 3 1d 120.5±5.1 - Example 3 3d 158.7±6.0 - Example 3 7d 236.8±7.1 142.6±6.5 Example 3 14d 325.7±8.0 186.3±7.3 Example 5 (with HA) 1d 132.8±5.5 - Example 5 (with HA) 3d 175.6±6.4 - Example 5 (with HA) 7d 268.5±7.5 178.4±7.0 Example 5 (with HA) 14d 372.4±8.3 235.6±7.8 Example 7 (RGD grafting) 1d 145.3±5.8 - Example 7 (RGD grafting) 3d 192.7±6.7 - Example 7 (RGD grafting) 7d 289.6±7.9 195.8±7.5 Example 7 (RGD grafting) 14d 405.2±8.6 268.3±8.2

[0127] Result analysis

[0128] The bone repair performance of example 3 was better than that of control groups 2 and 5 (p<0.05), which proved that the BiVO4 / CaX heterojunction itself had a bone effect; the cell proliferation rate and ALP activity of example 5 (containing HA) were significantly improved (p<0.05), because HA is a natural bone tissue component, which can synergize with the calcium ions released by CaS to promote bone differentiation; the effect of example 7 (RGD grafting) was the best (p<0.01), combined with the contact angle characterization results, it was confirmed that the RGD peptide segment improved the hydrophilicity and specific binding with cells, effectively improved the cell compatibility, and solved the technical problem of insufficient bone cell adhesion and proliferation.

[0129] Experiment 5: solving the problem of multiple drug-resistant bacteria infection

[0130] Technical problem

[0131] The existing antibiotic bone implant material has poor effect on multiple drug-resistant bacteria (such as methicillin-resistant Staphylococcus aureus, MRSA), while the material of the present application can avoid bacterial drug resistance through piezoelectric catalysis mechanism, and provides a solution for multiple drug-resistant bacteria infection.

[0132] Experimental material

[0133] Example 3, 6, control group 4 (commercial antibiotic material), pure PEEK (control group 3).

[0134] Test method

[0135] Methicillin-resistant Staphylococcus aureus (MRSA, ATCC43300) was selected, and the bacterial solution (1x10 6 CFU / mL) was prepared according to the method of experiment 2, and the antibacterial effect was tested under ultrasonic (20 kHz, 0.5 W / cm², 30 min) conditions, and a control group without ultrasonic was set, as follows:

[0136] Sample Test condition MRSA inhibition rate (%) MRSA sterilization rate (%) Control 3 (Pure PEEK) Ultrasonic 0.5 W / cm², 30 min 3.2±0.6 0 Control 4 (antibiotic) No ultrasonic 28.5±2.3 15.6±1.8 Control 4 (antibiotic) Ultrasonic 0.5 W / cm², 30 min 32.7±2.5 18.9±2.0 Example 3 Ultrasonic 0.5 W / cm², 30 min 94.2±1.5 87.6±1.9 Example 6 (annealed) Ultrasonic 0.5 W / cm², 30 min 97.8±0.9 93.5±1.3

[0137] Result analysis

[0138] The bacteriostatic rate of the commercial antibiotic material on MRSA was only 32.7%, and the sterilization rate was less than 20%, while the bacteriostatic rates of examples 3 and 6 on MRSA were both more than 94%, and the sterilization rates were more than 87%, proving that the material can effectively solve the technical problem of multiple drug-resistant bacterial infection.

[0139] The above experiments prove that the material breaks through the limitation of PEEK bone implant materials relying on near-infrared light catalysis in the prior art, loads the biological heterojunction formed by BiVO4 and chalcogenide calcium compound on PEEK, realizes the synergistic effect of acoustic catalytic antibacterial and bone repair promotion, and the piezoelectric performance can be adjusted by ultrasonic power to meet the clinical needs.

[0140] In view of the unsolved technical problems of the prior art, such as poor stability of the heterojunction, insufficient low-power piezoelectric response, limited cell compatibility, and difficulty in dealing with multiple drug-resistant bacterial infections, the improvement methods of HA complexation, annealing treatment, and RGD grafting are introduced, and the effectiveness of each improvement scheme is verified by experiments.

[0141] The piezoelectric effect belongs to force-electricity conversion characteristics, and although it is the same as the photoelectric characteristics of the prior art in energy conversion characteristics of semiconductor materials, there are essential differences in triggering methods and mechanisms, and the present application realizes the effects of low-power triggering, high stability, and resistance to drug-resistant bacteria.

[0142] The present application is not limited to the above optional embodiments, and anyone can derive other various forms of products under the inspiration of the present application. The above specific embodiments should not be understood as limiting the scope of protection of the present application, and the scope of protection of the present application should be defined by the claims, and the specification can be used to interpret the claims.

Claims

1. A piezoelectric catalytic bioheterojunction PEEK bone implant material, characterized by: The PEEK bone implant material comprises a bi-heterojunction material loaded thereon, the bi-heterojunction material is combined by BiVO4 and a calcium sulfide in a molar ratio range of 1-3.

2. The piezoelectric catalytic bioheterojunction PEEK bone implant material of claim 1, wherein: The bi-heterojunction material is combined by BiVO4 and a calcium sulfide in a molar ratio of 2:

1.

3. The piezoelectric catalytic bioheterojunction PEEK bone implant material of claim 1, wherein: The calcium sulfide includes one of calcium sulfide, calcium selenide and calcium telluride.

4. A method of manufacture characterised by: The PEEK bone implant material is prepared by the following steps: First, the bi-heterojunction material is prepared, the calcium sulfide is added into a BiVO4 mixed solution with ethylene glycol to form a reaction solution, then a liquid system containing the bi-heterojunction is formed by a hydrothermal method or an in-situ composite method, the liquid system is washed by anhydrous ethanol and deionized water alternately, and then dried to obtain the BiVO4 / CaX bi-heterojunction, the BiVO4 / CaX bi-heterojunction is loaded on the PEEK material to form the bone implant material.

5. A method of manufacture according to claim 4, wherein: In the preparation of the bone implant material, the PEEK material is cleaned by acetone, ethanol and deionized water, and then treated by ultrasonic treatment with sulfuric acid for 5-10 min to obtain the treated sulfonated PEEK material; A 10mmol / L Tris solution is prepared, the pH of the Tris solution is adjusted to 8.5 by dilute hydrochloric acid, and then 2mg / mL dopamine hydrochloride is added into the Tris solution to obtain a dopamine solution; The sulfonated PEEK material is fully contacted with the dopamine solution for 24h, and then dried to obtain the dopamine modified PEEK material; The obtained BiVO4 / CaX bi-heterojunction is fully contacted with the dopamine modified PEEK material at 4℃ for 12h to obtain the bone implant material.

6. The method of claim 4, wherein: In the formation of the liquid system containing the bi-heterojunction by the hydrothermal method or the in-situ composite method, the heating temperature is 160℃, and the holding time is at least 6h.