A polyaryletherketone composite implant material and a preparation method and application thereof

Abstract

The application discloses a kind of polyaryletherketone composite implant materials and preparation method and application, and belongs to medical material technical field, wherein, the preparation method of the polyaryletherketone composite implant material includes the following steps: preparation surface has recess structure and the carbon fiber reinforced polyaryletherketone base of conductivity;Based on precipitation method, white brushite is prepared using calcium compound, magnesium compound and phosphoric acid aqueous solution;White brushite is surface modified using polydopamine, to obtain modified white brushite;Modified white brushite is mixed with degradable piezoelectric polymer into solvent, to obtain mixed solution;Mixed solution is coated on carbon fiber reinforced polyaryletherketone base, after drying, annealing treatment, form coating, to obtain polyaryletherketone composite implant material.The application constructs white brushite doped degradable piezoelectric composite coating with piezoelectric characteristics and ion release capacity simultaneously, realizes the dual bionics of electric signal and chemical signal in bone healing microenvironment.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical materials, in particular to a polyaryletherketone composite implant material and a preparation method and application thereof. BACKGROUND

[0002] In the field of bone tissue engineering, the understanding of bone healing mechanism is deepening from single factor regulation to systematic bionics. Bone repair is essentially a complex multi-signal synergistic regulation process involving the combined action of mechanical signals, electrical signals, chemical signals and other factors. Polyether ether ketone and its carbon fiber reinforced composite material as an important load-bearing bone implant material, its surface functionalization design needs to more comprehensively simulate the complex microenvironment of natural bone healing. The bioelectric environment and ionic microenvironment jointly maintain the balance and stability of bone metabolism. In the physiological state, the endogenous electric field generated by the piezoelectric effect of the skeleton and the calcium, phosphorus and other ionic signals in the local microenvironment cooperate to form a dynamic bone regeneration regulation microenvironment, effectively promoting the proliferation and differentiation of osteoblasts and matrix mineralization.

[0003] In the prior art, single electrical stimulation strategy or ion release strategy has been proved to have certain osteogenic effect. The Chinese patent with publication number CN117339018A realizes the inhibition of inflammation and promotion of bone integration by loading strontium ions on the surface of the implant. However, these single signal strategies have obvious limitations: pure electrical stimulation lacks the necessary biochemical signal support, and pure ion release cannot provide effective physical signal guidance. More importantly, the synergistic effect of electrical signals and ionic signals originally present in the natural bone healing process cannot be fully utilized in these single strategies, resulting in limited effect of promoting bone integration.

[0004] Therefore, the development of a material with both electrical properties and ionic regulation ability provides a new technical path for breaking through the limitations of traditional single-function bionics, achieving a leap to systematic bionics, and improving the effect of bone repair. SUMMARY

[0005] The purpose of the present application is to provide a polyaryletherketone composite implant material and a preparation method and application thereof to solve the problems raised in the background art.

[0006] To achieve the above purpose, the present application provides the following technical solutions:

[0007] A preparation method of a polyaryletherketone composite implant material, comprising the following steps:

[0008] Preparation of a carbon fiber reinforced polyaryletherketone substrate with a groove structure and electrical conductivity on the surface;

[0009] Based on the precipitation method, white brushite is prepared by using calcium compounds, magnesium compounds and aqueous phosphoric acid;

[0010] Surface modification of the whitlockite by polydopamine to obtain modified whitlockite;

[0011] Mixing the modified whitlockite and the degradable piezoelectric polymer in a solvent to obtain a mixed solution;

[0012] Coating the mixed solution on the carbon fiber reinforced polyaryletherketone substrate, drying and annealing to form a whitlockite-doped degradable piezoelectric composite coating, and obtaining a polyaryletherketone composite implant material.

[0013] Further, the step of preparing the carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity comprises:

[0014] Melt blending the carbon fiber and the polyaryletherketone according to a mass ratio of (0.1-1.5):1, then injection molding, and then laser processing to obtain the carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity.

[0015] Further, the step of preparing the whitlockite based on the precipitation method using calcium compounds, magnesium compounds and aqueous phosphoric acid solution comprises:

[0016] Dissolving the calcium compounds and the magnesium compounds in water according to a molar ratio of (1-5):1, heating and stirring, then adding the aqueous phosphoric acid solution dropwise for reaction, and then centrifuging, drying, grinding and calcining to obtain the whitlockite.

[0017] Further, the calcium compounds are one or more of calcium hydroxide, calcium chloride, calcium nitrate, calcium acetate, calcium sulfate and calcium dihydrogen phosphate; and the magnesium compounds are one or more of magnesium hydroxide, magnesium chloride, magnesium sulfate, magnesium nitrate, magnesium acetate, magnesium carbonate and magnesium bicarbonate.

[0018] Further, the calcination temperature is 600-800℃.

[0019] Further, the concentration of the aqueous phosphoric acid solution is 0.1-1 mol / L.

[0020] Further, the degradable piezoelectric polymer is one or more of polylactic acid and its copolymer, silk fibroin, cellulose, collagen, poly-β-hydroxybutyric acid and 3-hydroxybutyric acid-3-hydroxyvaleric acid copolymer; and the solvent is one or more of hexafluoroisopropanol, hexaoxacyclohexane, dichloromethane and trichloromethane.

[0021] Further, the preparation method of the polyaryletherketone composite implant material further comprises the following steps:

[0022] Carrying out corona polarization treatment on the polyaryletherketone composite implant material to enhance the surface potential.

[0023] Another object of the present application is to provide a polyaryletherketone composite implant material prepared by the above preparation method.

[0024] Another object of the present application is to provide an application of the above polyaryletherketone composite implant material in preparing bone defect repair materials.

[0025] The preparation method of the polyaryletherketone composite implant material provided by the present application realizes the dual biomimicry of the electrical signal and the chemical signal in the bone healing microenvironment by constructing a white whitlockite-doped degradable piezoelectric composite coating with both piezoelectric properties and ion release capacity on the surface of the carbon fiber reinforced polyaryletherketone substrate. This synergistic system not only generates bioelectric signals similar to natural bone through piezoelectric effect, but also continuously releases key ions such as calcium and magnesium with osteogenic activity, thereby synergistically regulating the osteogenic behavior of cells from multiple signal levels. This system represents an important progress in the design of bone implant materials from single function biomimicry to systematic biomimicry, and provides a new solution for improving bone repair effect. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 Scanning electron microscope image of the carbon fiber reinforced polyaryletherketone substrate after laser processing in Example 1.

[0027] Figure 2 Transmission electron microscope (a) and EDX Mapping (b) images of WH prepared in Example 1.

[0028] Figure 3 Transmission electron microscope (a) and EDX Mapping (b) images of WH@PDA in Example 1.

[0029] Figure 4 Fourier transform infrared spectrograms of WH and WH@PDA in Example 1.

[0030] Figure 5 Piezoelectric coefficient of WH and WH@PDA in Example 1.

[0031] Figure 6 Calcium ion (a) and magnesium ion (b) release performance of the polyaryletherketone composite implant material prepared in Examples 1-3.

[0032] Figure 7 MC3T3-E1 cell toxicity detection chart of the polyaryletherketone composite implant material prepared in Examples 1-3 and Comparative Example 1.

[0033] Figure 8 MC3T3-E1 cell proliferation detection chart of the polyaryletherketone composite implant material prepared in Examples 1-3 and Comparative Example 1 after corona polarization treatment.

[0034] Figure 9 Figure 1 shows the MC3T3-E1 cell osteogenic differentiation detection diagram of the polyaryletherketone composite implant material prepared according to Examples 1-3 and Comparative Example 1 after corona polarization treatment. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0036] In an embodiment of the present application, a polyaryletherketone composite implant material is provided, and the preparation method thereof specifically comprises the following steps:

[0037] S1, preparing a carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity: melt blending carbon fibers and polyaryletherketone according to a mass ratio of (0.1-1.5):1, and then preparing a circular sheet with a diameter of 5-12 mm through a micro injection molding machine; sequentially immersing and washing the injection molded material in acetone, ethanol and water for 10-30 min through ultrasonic immersion, and repeating the immersion and washing for 2-3 times; and then drying the material in a blast oven at 60-100℃ for 1-2 h. In order to enhance the adhesion of the coating and the polarization effect, the material is then subjected to laser processing to obtain a carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity.

[0038] S2, preparing whitlockite based on a precipitation method using calcium compounds, magnesium compounds and aqueous phosphoric acid solution: dissolving calcium compounds and magnesium compounds in water according to a molar ratio of (1-5):1, heating and stirring at 60-100℃ for 30-60 min, then adding 0.1-1 mol / L aqueous phosphoric acid solution at a speed of 5-20 mL / min, continuing to react at 80-100℃ for 6-12 h, then centrifuging after standing and aging at room temperature for 12-24 h, then washing with deionized water until neutral, then drying at 100-120℃ for 1-2 d, grinding after drying, and calcining at a temperature of 600-800℃ for 2-5 h to obtain whitlockite.

[0039] S3, in order to prepare a uniform piezoelectric composite coating, the above white whitlockite is surface modified by using a polydopamine solution, specifically, 0.5-1.5 g of white whitlockite is added to 200 mL of Tris-HCl aqueous solution (10 mM, pH=8.6), ultrasonic dispersion for 0.5-1.5 h, then 0.04-4 g of DA-HCl (dopamine hydrochloride) is added for stirring for 6-18 h, finally centrifugal filtration, deionized water washing to neutral, drying at 70-90℃ for 6-18 h, to obtain modified white whitlockite.

[0040] S4, the above modified white whitlockite is mixed with degradable piezoelectric polymer according to a mass ratio of (0.01-9):1 to obtain a mixed solution with a degradable piezoelectric polymer concentration of 0.05-0.12 g / mL.

[0041] S5, the above mixed solution is coated (including but not limited to casting, doctor blade coating, spin coating, spraying, etc.) on the above carbon fiber reinforced polyaryletherketone substrate in an amount of 10-90 μL, after natural air drying at room temperature for 12-24 h, solvent removal is performed by washing with anhydrous ethanol and deionized water for 12-24 h, then vacuum drying at 60-100℃ for 12-24 h, followed by annealing treatment at 120-150℃ for 8-10 h, to form a white whitlockite doped degradable piezoelectric composite coating, thereby obtaining a polyaryletherketone composite implant material.

[0042] S6, the above obtained polyaryletherketone composite implant material is subjected to corona polarization treatment using a corona polarization device to generate a surface potential. In the process of corona polarization treatment, the polarization voltage is 22-25 kV, the polarization temperature is 10-40℃, and the polarization time is 20-40 min.

[0043] Preferably, the polyaryletherketone includes but is not limited to one or more of polyether ether ketone, polyether ketone, polyether ether ketone ketone and polyether ketone ether ether ketone; the laser source for laser processing is femtosecond, picosecond or nanosecond light source, etc.; the calcium compound includes but is not limited to one or more of calcium hydroxide, calcium chloride, calcium nitrate, calcium acetate, calcium sulfate and calcium dihydrogen phosphate; the magnesium compound includes but is not limited to one or more of magnesium hydroxide, magnesium chloride, magnesium sulfate, magnesium nitrate, magnesium acetate, magnesium carbonate and magnesium bicarbonate; the degradable piezoelectric polymer is one or more of polylactic acid and its copolymer, silk fibroin, cellulose, collagen, poly-β-hydroxybutyric acid and 3-hydroxybutyric acid-3-hydroxyvaleric acid copolymer; the solvent is one or more of hexafluoroisopropanol, hexaoxacyclohexane, dichloromethane and trichloromethane; the mass ratio of modified white whitlockite to degradable piezoelectric polymer is preferably (0.1-0.5):1.

[0044] The polyaryletherketone composite implant material provided by the embodiment of the present application can simultaneously simulate the bioelectric microenvironment and the ion microenvironment in the natural bone healing process, realize effective synergy of electric signals and chemical signals, and promote the proliferation, differentiation and mineralization of osteoblasts from multiple aspects and multiple dimensions, thereby accelerating bone integration.

[0045] Embodiment 1: The embodiment provides a polyaryletherketone composite implant material, and a preparation method thereof specifically includes the following steps:

[0046] S1, carbon fibers and polyether ether ketone are melt-blended according to a mass ratio of 3:7, and then a circular sheet with a diameter of 12 mm is prepared by a micro injection molding machine; the injection-molded material is sequentially immersed in acetone, ethanol and water for ultrasonic washing for 30 min, and the immersion washing is repeated for 3 times; then the material is dried at 100℃ in a blast oven for 1 h. In order to enhance the adhesion and polarization effect of the coating, the material is then subjected to femtosecond laser processing, and a carbon fiber reinforced polyaryletherketone substrate (denoted as CP) with a grooved structure and electrical conductivity on the surface is obtained.

[0047] The scanning electron microscope image of the carbon fiber reinforced polyaryletherketone substrate after laser processing is as shown in Figure 1 It can be seen from Figure 1 that the carbon fiber reinforced polyaryletherketone substrate after laser processing has a clear grooved structure.

[0048] S2, 2.2g of calcium hydroxide (0.03mol) and 0.8g of magnesium hydroxide (0.013mol) are dissolved in 80mL of water, heated and stirred at 80℃ for 60min, then 50mL of 1mol / L phosphoric acid aqueous solution is added at a speed of 10mL / min, and the reaction is continued at 80℃ for 9h, then the solution is centrifuged after standing and aging at room temperature for 24h, washed with deionized water until neutral, then dried at 120℃ for 1d, ground after drying, and calcined at 650℃ for 3h to obtain white whitlockite (denoted as WH).

[0049] The scanning electron microscope and EDX Mapping images of the white whitlockite WH prepared in the embodiment are as shown in Figure 2 It can be seen from Figure 2 that the WH contains elements of Ca, Mg, P and O.

[0050] S3. The above-mentioned white calcium phosphite was surface modified using polydopamine (PDA) solution. 1g of white calcium phosphite was added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6) and ultrasonically dispersed for 1h. Then, 0.4g of DA-HCl (dopamine hydrochloride) was added and stirred for 12h. Finally, the mixture was centrifuged and filtered, washed with deionized water until neutral, and dried at 80℃ for 12h to obtain modified white calcium phosphite (denoted as WH@PDA).

[0051] The scanning electron microscope and EDX mapping images of the modified white phosphatidylcholine WH@PDA prepared in this embodiment are as follows: Figure 3 As shown, by Figure 3 It can be seen that WH@PDA contains the element N, proving that the PDA was successfully encapsulated. Furthermore, the Fourier transform infrared spectra of WH and WH@PDA are as follows: Figure 4 As shown, by Figure 4 It can be seen that the modified white phosphogypsum is at 1610 cm⁻¹ -1 A new characteristic absorption peak appeared at [location], attributed to the -NH- stretching vibration, which also proves the successful coating of PDA. The piezoelectric coefficients of WH and WH@PDA are as follows: Figure 5 As shown, WH exhibits piezoelectric properties with a piezoelectric coefficient of 5.8 pC / N. The piezoelectric coefficient of WH@PDA decreases slightly, but it still retains piezoelectric properties.

[0052] S4. The modified white calcium phosphite and 0.8 g of polylactic acid were added to 10 mL of hexafluoroisopropanol at a mass ratio of 2:8 to obtain a mixed solution.

[0053] S5. The above mixed solution is cast into the carbon fiber reinforced polyaryletherketone substrate at a casting volume of 60 μL. After air drying at room temperature for 24 h, it is washed with anhydrous ethanol and deionized water for 24 h in sequence to remove solvent. Then it is vacuum dried at 80°C for 24 h, and then annealed at 140°C for 10 h to form a biodegradable piezoelectric composite coating doped with leucoxane, thus obtaining the polyaryletherketone composite implant material (denoted as CPW20).

[0054] S6. The polyaryletherketone composite implant material obtained above is subjected to corona polarization treatment using a corona polarization device to generate a surface potential, thereby obtaining the corona-polarized polyaryletherketone composite implant material, denoted as CPW20(P). The polarization voltage in the corona polarization treatment process is 25kV, the polarization temperature is 25℃, and the polarization time is 25min.

[0055] Example 2: This example provides a polyaryletherketone composite implant material, the preparation method of which specifically includes the following steps:

[0056] S1, the modified white phosphor calcium stone is mixed with 0.8g polylactic acid according to a mass ratio of 1:9 into 10mL hexafluoroisopropanol to obtain a mixed solution;

[0057] S2, the mixed solution is cast on the carbon fiber reinforced polyaryletherketone substrate prepared in the above embodiment 1 according to a casting amount of 60μL, and after natural air drying at room temperature for 24h, solvent removal is performed by washing with anhydrous ethanol and deionized water for 24h, then vacuum drying is performed at 80℃ for 24h, and then annealing treatment is performed at 140℃ for 10h, to form a white phosphor calcium stone doped degradable piezoelectric composite coating, i.e. to obtain a polyaryletherketone composite implant material (denoted as CPW10).

[0058] S3, the obtained polyaryletherketone composite implant material is subjected to corona polarization treatment using a corona polarization device to generate a surface potential, to obtain a corona polarization treated polyaryletherketone composite implant material, denoted as CPW10(P). In the corona polarization treatment process, the polarization voltage is 25kV, the polarization temperature is 25℃, and the polarization time is 25min.

[0059] Embodiment 3: The embodiment provides a polyaryletherketone composite implant material, and the preparation method thereof specifically includes the following steps:

[0060] S1, the modified white phosphor calcium stone is mixed with 0.8g polylactic acid according to a mass ratio of 1:9 into 10mL hexafluoroisopropanol to obtain a mixed solution;

[0061] S2, the mixed solution is cast on the carbon fiber reinforced polyaryletherketone substrate prepared in the above embodiment 1 according to a casting amount of 60μL, and after natural air drying at room temperature for 24h, solvent removal is performed by washing with anhydrous ethanol and deionized water for 24h, then vacuum drying is performed at 80℃ for 24h, and then annealing treatment is performed at 140℃ for 10h, to form a white phosphor calcium stone doped degradable piezoelectric composite coating, i.e. to obtain a polyaryletherketone composite implant material (denoted as CPW30).

[0062] S3, the obtained polyaryletherketone composite implant material is subjected to corona polarization treatment using a corona polarization device to generate a surface potential, to obtain a corona polarization treated polyaryletherketone composite implant material, denoted as CPW30(P). In the corona polarization treatment process, the polarization voltage is 25kV, the polarization temperature is 25℃, and the polarization time is 25min.

[0063] Embodiment 4: The embodiment provides a polyaryletherketone composite implant material, and the preparation method thereof specifically includes the following steps:

[0064] S1, melt blend carbon fiber and polyether ketone according to the mass ratio of 1:10, then prepare a circular sheet with a diameter of 5mm through a micro injection molding machine; the injection molded material is sequentially immersed in acetone, ethanol and water for ultrasonic washing for 10min, and the immersion washing is repeated twice; then dry in a blast oven at 60℃ for 2h. In order to enhance the adhesion of the coating and the polarization effect, the material is then processed by picosecond laser, and a carbon fiber reinforced polyaryletherketone substrate with a grooved structure and conductivity on the surface is obtained.

[0065] S2, dissolve 0.03mol of calcium chloride and 0.006mol of magnesium chloride in 100mL of water, heat and stir at 60℃ for 30min, then add 50mL of 0.1mol / L phosphoric acid aqueous solution at a speed of 5mL / min, continue to react at 80℃ for 6h, then centrifuge after standing at room temperature for 12h, then wash with deionized water until neutral, then dry at 100℃ for 1d, grind after drying, and calcine at 600℃ for 2h to obtain white brushite.

[0066] S3, the white brushite is surface modified by using a polydopamine solution. Specifically, 0.5g of white brushite is added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6), ultrasonic dispersion is performed for 0.5h, then 0.04g of DA-HCl (dopamine hydrochloride) is added for stirring for 6h, finally centrifugal filtration is performed, deionized water is used for washing until neutral, and 70℃ drying is performed for 6h to obtain modified white brushite.

[0067] S4, the modified white brushite and 0.5g of silk fibroin are added to 10mL of hexahydroxycyclohexane according to a mass ratio of 1:100 for mixing to obtain a mixed solution.

[0068] S5, the mixed solution is spin-coated on the carbon fiber reinforced polyaryletherketone substrate according to a use amount of 10μL, air dried at room temperature for 12h, then washed with anhydrous ethanol and deionized water for 12h for solvent removal, then vacuum dried at 60℃ for 12h, and then annealed at 120℃ for 8h to form a white brushite doped degradable piezoelectric composite coating, so that a polyaryletherketone composite implant material is obtained.

[0069] S6, the obtained polyaryletherketone composite implant material is subjected to corona polarization treatment by using a corona polarization device to generate a surface potential. In the corona polarization treatment process, the polarization voltage is 22kV, the polarization temperature is 10℃, and the polarization time is 20min.

[0070] Example 5: The example provides a polyaryletherketone composite implant material, and the preparation method thereof specifically includes the following steps:

[0071] S1, melt blend carbon fiber and polyether ether ketone ketone according to the mass ratio of 6:4, then prepare a circular sheet with a diameter of 12mm through a micro injection molding machine; the injection molded material is sequentially immersed in acetone, ethanol and water for ultrasonic washing for 30min, and the immersion washing is repeated for 3 times; then dry in a blast oven at 100℃ for 2h. In order to enhance the adhesion of the coating and the polarization effect, the material is then processed by femtosecond laser, and a carbon fiber reinforced polyaryletherketone substrate with grooved structure and conductivity on the surface is obtained.

[0072] S2, dissolve 0.03mol of calcium sulfate and 0.03mol of magnesium sulfate in 100mL of water, heat and stir at 100℃ for 60min, then add 1mol / L phosphoric acid aqueous solution at a speed of 20mL / min, continue to react at 100℃ for 12h, then centrifuge after standing at room temperature for 24h, then wash with deionized water until neutral, then dry at 120℃ for 2d, grind after drying, and calcine at 800℃ for 5h to obtain white phosphor calcite.

[0073] S3, the surface of the above white phosphor calcite is modified by using polydopamine solution. Specifically, 1.5g of white phosphor calcite is added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6), ultrasonic dispersion is carried out for 1.5h, then 4g of DA-HCl (dopamine hydrochloride) is added for stirring for 18h, finally centrifugal filtration is carried out, deionized water is used for washing until neutral, and 90℃ drying is carried out for 18h to obtain modified white phosphor calcite.

[0074] S4, the above modified white phosphor calcite is mixed with 1.2g of cellulose according to a mass ratio of 9:1 in 10mL of dichloromethane to obtain a mixed solution.

[0075] S5, the above mixed solution is cast on the above carbon fiber reinforced polyaryletherketone substrate according to a casting amount of 80μL, after natural air drying at room temperature for 24h, solvent removal is carried out by washing with anhydrous ethanol and deionized water for 24h, then vacuum drying is carried out at 100℃ for 24h, and then annealing treatment is carried out at 150℃ for 10h, to form a white phosphor calcite doped degradable piezoelectric composite coating, so that a polyaryletherketone composite implant material is obtained.

[0076] S6, the above obtained polyaryletherketone composite implant material is subjected to corona polarization treatment by using a corona polarization device to generate surface potential. In the process of corona polarization treatment, the polarization voltage is 25kV, the polarization temperature is 40℃, and the polarization time is 40min.

[0077] Example 6: The example provides a polyaryletherketone composite implant material, which is different from example 1 only in the following steps, and the rest are the same:

[0078] Carbon fiber and polyether ketone ether ether ketone were melt blended according to a mass ratio of 3:7, and then a circular sheet with a diameter of 10 mm was prepared by a micro injection molding machine; the injection-molded material was sequentially immersed in acetone, ethanol, and water for ultrasonic washing for 20 min, and the immersion washing was repeated 3 times; then the material was dried in a blast oven at 80°C for 1.5 h. In order to enhance the adhesion of the coating and the polarization effect, the material was then subjected to nanosecond laser processing, and a carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity on the surface was obtained.

[0079] Example 7: The example provides a polyaryletherketone composite implant material, which is different from example 1 only in the following steps, and the rest are the same:

[0080] 0.03 mol of calcium dihydrogen phosphate and 0.015 mol of magnesium bicarbonate were dissolved in 90 mL of water, heated and stirred at 80°C for 40 min, then 50 mL of 0.5 mol / L phosphoric acid aqueous solution was added dropwise at a speed of 15 mL / min, and the reaction was continued at 90°C for 9 h, then the solution was centrifuged after standing at room temperature for 18 h, washed with deionized water until neutral, and then dried at 110°C for 1.5 d. After drying, the material was ground and calcined at 700°C for 3.5 h to obtain white brushite.

[0081] The above white brushite was surface modified using a polydopamine solution with a concentration of 100 mg / mL to obtain modified white brushite.

[0082] Example 8: The example provides a polyaryletherketone composite implant material, which is different from example 1 only in the following steps, and the rest are the same:

[0083] 0.03 mol of calcium dihydrogen phosphate and 0.015 mol of magnesium bicarbonate were dissolved in 90 mL of water, heated and stirred at 80°C for 40 min, then 50 mL of 0.5 mol / L phosphoric acid aqueous solution was added dropwise at a speed of 15 mL / min, and the reaction was continued at 90°C for 9 h, then the solution was centrifuged after standing at room temperature for 18 h, washed with deionized water until neutral, and then dried at 110°C for 1.5 d. After drying, the material was ground and calcined at 700°C for 3.5 h to obtain white brushite.

[0084] Example 9: The example provides a polyaryletherketone composite implant material, which is different from example 1 only in the following steps, and the rest are the same:

[0085] The modified white brushite prepared in example 1 was mixed with 1 g of poly-β-hydroxybutyric acid in a mass ratio of 1:10 in 10 mL of chloroform to obtain a mixed solution.

[0086] Example 10: This example provides a polyaryletherketone composite implant material, which is different from example 1 only in that the following step is different, and the rest are the same:

[0087] The modified white phosphor calcium stone prepared in example 1 was mixed with 1g of 3-hydroxybutyric acid-3-hydroxyvaleric acid copolymer in a mass ratio of 5:10 in 10mL of chloroform to obtain a mixed solution.

[0088] Example 11: This example provides a polyaryletherketone composite implant material, which is different from example 1 only in that the following step is different, and the rest are the same:

[0089] The above mixed solution was cast onto the carbon fiber reinforced polyaryletherketone substrate prepared in example 1 at a casting amount of 70μL, and after natural air drying at room temperature for 18h, solvent removal was performed by washing with anhydrous ethanol and deionized water for 18h, followed by vacuum drying at 90℃ for 18h, and then annealing treatment at 130℃ for 9h, to form a white phosphor calcium stone doped degradable piezoelectric composite coating, thereby obtaining a polyaryletherketone composite implant material.

[0090] The polyaryletherketone composite implant material obtained above was subjected to corona polarization treatment using a corona polarization device to generate a surface potential. In the corona polarization treatment process, the polarization voltage was 23kV, the polarization temperature was 30℃, and the polarization time was 30min.

[0091] Example 12: This example provides a polyaryletherketone composite implant material, which is different from example 1 only in that the following step is different, and the rest are the same:

[0092] The above mixed solution was cast onto the carbon fiber reinforced polyaryletherketone substrate prepared in example 1 at a casting amount of 100μL, and after natural air drying at room temperature for 15h, solvent removal was performed by washing with anhydrous ethanol and deionized water for 15h, followed by vacuum drying at 80℃ for 15h, and then annealing treatment at 140℃ for 9h, to form a white phosphor calcium stone doped degradable piezoelectric composite coating, thereby obtaining a polyaryletherketone composite implant material.

[0093] The polyaryletherketone composite implant material obtained above was subjected to corona polarization treatment using a corona polarization device to generate a surface potential. In the corona polarization treatment process, the polarization voltage was 24kV, the polarization temperature was 25℃, and the polarization time was 30min.

[0094] Comparative Example 1: This comparative example provides a polyaryletherketone composite implant material, and the preparation method thereof specifically includes the following steps:

[0095] S1, 0.8g of polylactic acid was added to 10mL of hexafluoroisopropanol to obtain a mixed solution;

[0096] S2. The above mixed solution is cast into the carbon fiber reinforced polyaryletherketone substrate prepared in Example 1 at a casting volume of 60 μL. After air drying at room temperature for 24 h, it is washed with anhydrous ethanol and deionized water for 24 h in sequence to remove solvent. Then it is vacuum dried at 80°C for 24 h, and then annealed at 140°C for 10 h to form a biodegradable piezoelectric composite coating doped with leucoxane, thus obtaining the polyaryletherketone composite implant material (denoted as CPA).

[0097] S3. The polyaryletherketone composite implant material obtained above is subjected to corona polarization treatment using a corona polarization device to generate a surface potential, thereby obtaining the corona-polarized polyaryletherketone composite implant material, denoted as CPA(P). The polarization voltage in the corona polarization treatment process is 25kV, the polarization temperature is 25℃, and the polarization time is 25min.

[0098] Experimental Testing: 1. The ion release performance of the polyaryletherketone composite implant materials prepared in Examples 1-3 was tested, and the results are as follows: Figure 6 As shown, by Figure 6 It can be seen that the polyaryletherketone composite implant materials prepared in the embodiments of the present invention all exhibit Ca... 2+ and Mg 2+ The continuous release of WH results in an increased cumulative release concentration as the WH content increases.

[0099] II. The cytotoxicity of the polyaryletherketone composite implant materials and carbon fiber reinforced polyaryletherketone substrates (CP) prepared in Examples 1-3 and Comparative Example 1 was determined using a live / dead cell double staining kit. Specifically, the materials were sterilized by immersing in 75% ethanol for 30 min, and then placed in 12-well plates. 1 mL of complete culture medium and 2 × 10⁻⁶ ppm of ethanol were added to each well. 4 MC3T3-E1 cell suspensions were cultured per well at 37°C for 24 h in a CO2 incubator. After 24 h of culture, 200 μL of staining working solution was added to each well and incubated for 20 min. Calcein-AM could penetrate the membrane of living cells and produce green fluorescence under the action of intracellular esterases, while PI could only enter through the damaged membrane structure of dead cells and bind to DNA, producing red fluorescence. The results were observed using an inverted fluorescence microscope. Figure 7 As shown. By Figure 7 It can be seen that no red-stained dead cells were found in the polyaryletherketone composite implant material co-cultured with MC3T3-E1 cells for 24 hours, proving that the polyaryletherketone composite implant material prepared in the embodiments of the present invention has no cytotoxicity.

[0100] Three, using commercially available CCK-8 kit to determine the cell proliferation ability of polyaryletherketone composite implant material and carbon fiber reinforced polyaryletherketone base (CP) and other materials prepared in the above examples 1-3 and comparative example 1. After 1, 4, 7 days of co-culture, 100 μL of CCK-8 reagent was added to each well for 2 h of incubation, and the absorbance at 450 nm was detected using a microplate reader, and the cell proliferation rate was calculated: cell proliferation rate = (sample absorbance-blank absorbance) / (control absorbance-blank absorbance) x 100%; the results are shown in Figure 8 As can be seen from Figure 8 After 1, 4, 7 days of co-culture with MC3T3-E1 cells, the cell proliferation of the polyaryletherketone composite implant material prepared in the examples of the present application was higher than that of the pure carbon fiber reinforced polyaryletherketone base, which proved that the polyaryletherketone composite implant material prepared in the examples of the present application had good cell activity and could provide a suitable microenvironment for cells, effectively promoting cell proliferation.

[0101] Four, using commercially available alkaline phosphatase (ALP) kit to determine the early osteogenic differentiation ability of polyaryletherketone composite implant material and carbon fiber reinforced polyaryletherketone base (CP) and other materials prepared in the above examples 1-3 and comparative example 1. After 7, 14 days of co-culture, 1 mL of 4% paraformaldehyde was used to fix the cells at room temperature for 30 min; after fixation, 1 mL of prepared working solution was incubated at room temperature for 4 h; 1 mL of water was used to wash twice to stop the reaction, and the stereomicroscope was photographed, and the results are shown in Figure 9 As can be seen from Figure 9 After 7, 14 days of co-culture with MC3T3-E1 cells, the ALP activity of the polyaryletherketone composite implant material prepared in the examples of the present application was higher than that of the pure carbon fiber reinforced polyaryletherketone base, which proved that the polyaryletherketone composite implant material prepared in the examples of the present application had the ability to promote cell osteogenic differentiation.

[0102] Based on the above ideal embodiments according to the present application, through the above description, relevant personnel can make various changes and modifications without deviating from the technical idea of the present application. The technical scope of the present application is not limited to the contents of the specification.

Claims

1. A method for the preparation of a polyaryletherketone composite implant material, characterized in that, The method comprises the following steps: Preparation of a carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity on the surface; Preparation of whitlockite based on a precipitation method using a calcium compound, a magnesium compound and an aqueous phosphoric acid solution; Surface modification of the whitlockite using polydopamine to obtain modified whitlockite; Mixing of the modified whitlockite and a degradable piezoelectric polymer in a solvent to obtain a mixed solution; Coating of the mixed solution on the carbon fiber reinforced polyaryletherketone substrate, drying and annealing to form a degradable piezoelectric composite coating doped with whitlockite, thereby obtaining a polyaryletherketone composite implant material.

2. The method for preparing the polyaryletherketone composite implant material according to claim 1, characterized in that, The step of preparing a carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity on the surface comprises: Melt blending of carbon fibers and polyaryletherketone at a mass ratio of (0.1-1.5):1, followed by injection molding and then laser processing to obtain a carbon fiber reinforced polyaryletherketone substrate with a grooved structure and electrical conductivity on the surface.

3. The method for preparing the polyaryletherketone composite implant material according to claim 1, characterized in that, The step of preparing whitlockite based on a precipitation method using a calcium compound, a magnesium compound and an aqueous phosphoric acid solution comprises: Dissolution of the calcium compound and the magnesium compound in water at a molar ratio of (1-5):1, followed by heating and stirring, dropwise addition of the aqueous phosphoric acid solution for reaction, centrifugation, drying, grinding and calcination to obtain whitlockite.

4. The method for preparing the polyaryletherketone composite implant material according to claim 3, characterized in that, The calcium compound is one or more of calcium hydroxide, calcium chloride, calcium nitrate, calcium acetate, calcium sulfate and calcium dihydrogen phosphate; the magnesium compound is one or more of magnesium hydroxide, magnesium chloride, magnesium sulfate, magnesium nitrate, magnesium acetate, magnesium carbonate and magnesium bicarbonate.

5. The method for preparing the polyaryletherketone composite implant material according to claim 3, characterized in that, The calcination temperature is 600-800 DEG C.

6. The method for preparing the polyaryletherketone composite implant material according to claim 3, characterized in that, The concentration of the aqueous phosphoric acid solution is 0.1-1 mol / L.

7. The method for preparing the polyaryletherketone composite implant material according to claim 1, characterized in that, The degradable piezoelectric polymer is one or more of polylactic acid and its copolymer, silk fibroin, cellulose, collagen, poly-beta-hydroxybutyric acid and 3-hydroxybutyric acid-3-hydroxyvaleric acid copolymer; the solvent is one or more of hexafluoroisopropanol, hexaoxacyclohexane, dichloromethane and trichloromethane.

8. The method of producing a polyaryletherketone composite implant material according to any one of claims 1 to 7, characterized in that, The method further comprises the following steps: Corona polarization treatment of the polyaryletherketone composite implant material to enhance the surface potential. 9.A polyaryletherketone composite implant material prepared by the method of any one of claims 1-8. 10.Use of the polyaryletherketone composite implant material of claim 9 in the preparation of a bone defect repair material.

Images