Surface with magnetoelectric coupling effect and construction method and application thereof

Abstract

The application discloses a surface with magnetoelectric coupling effect and a construction method and application thereof, and belongs to the technical field of medical materials, wherein the construction method of the surface with magnetoelectric coupling effect comprises the following steps: based on a sol-gel method, magnetoelectric coupling composite materials are prepared by using organic titanium compounds, magnetostrictive materials and barium acetate; the magnetoelectric coupling composite materials are surface-modified by using polydopamine; the modified magnetoelectric coupling composite materials and piezoelectric polymers are added into a solvent for mixing to obtain a slurry; the slurry is coated on a substrate, and after drying and annealing treatment, the surface with magnetoelectric coupling effect is formed. Based on the characteristics that the magnetoelectric coupling effect can realize conversion of magnetic field energy into polarized charges, the application designs and constructs a surface which can be activated by an external magnetic field on demand and can periodically maintain electrical activity. The surface retains excellent mechanical properties of the substrate, and realizes the function of wireless charging by using an applied magnetic field.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, specifically to a surface with magnetoelectric coupling effect, its construction method, and its application. Background Technology

[0002] Polyetheretherketone (PEEK) and its carbon fiber reinforced composite (CFRPEEK) have become an ideal choice for weight-bearing bone implants due to their elastic modulus matching bone and excellent mechanical properties. However, the inherent bioinertness of CFRPEK materials severely restricts their integration efficiency with host bone, directly affecting the long-term stability of the implant. Traditional surface modification strategies often focus on introducing physicochemical signals, neglecting the indispensable role of the physiological microenvironment in bone integration, especially endogenous micropotential. The endogenous micropotential generated by bone under physiological stress plays a decisive role in key biological behaviors such as the directional migration, proliferation, and differentiation of osteoblasts. In bone defect areas, the endogenous electrical microenvironment is damaged due to the interruption of mechanical conduction pathways, hindering bone regeneration. Therefore, the bone integration effect can be improved by reconstructing a biomimetic electrical microenvironment at the implant-tissue interface. Chinese patent CN118436853A promotes bone integration of bone implant prostheses by constructing a piezoelectric polylactic acid fiber coating layer on the surface of a metal implant.

[0003] However, although piezoelectric materials can convert mechanical energy into electrical signals to achieve passive electrical stimulation and avoid dependence on external devices, in actual clinical repair processes, the defect site is fixed and cannot be moved or exercised. This results in insufficient mechanical stress input, making it difficult to continuously activate piezoelectric materials to generate effective electrical signals. This limitation makes it impossible for traditional piezoelectric strategies to provide a durable and stable electrical microenvironment during the critical period of bone healing.

[0004] Therefore, developing a material that can maintain effective electrical stimulation for a long time without the need for external wires has become the key to breaking through the current technological bottleneck and achieving reliable and long-lasting osseointegration. Summary of the Invention

[0005] The purpose of this invention is to provide a surface with magnetoelectric coupling effect, a method for constructing the surface, and its application, in order to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A method for constructing a surface with magnetoelectric coupling effect includes the following steps: Based on the sol-gel method, magnetoelectric coupling composite materials were prepared using organotitanium compounds, magnetostrictive materials, and barium acetate. The surface of the magnetoelectric coupling composite material was modified using polydopamine; The modified magnetoelectric coupling composite material and the piezoelectric polymer were added to a solvent and mixed to obtain a slurry; The slurry is coated onto a substrate, and after drying and annealing, a surface with a magnetoelectric coupling effect is formed.

[0007] Furthermore, the steps for preparing magnetoelectric coupling composite materials using the sol-gel method with organotitanium compounds, magnetostrictive materials, and barium acetate specifically include: An organotitanium compound was dissolved in a monohydroxy alcohol, and acetic acid was added and stirred to obtain a titanium solution. The magnetostrictive material was dispersed in a titanium solution and then reacted by adding a barium acetate aqueous solution to form a dry gel. The dry gel was calcined to obtain a magnetoelectric coupling composite material; the calcination temperature was 600-800℃.

[0008] Furthermore, the organotitanium compound is one or more of isopropyl titanate, titanium n-propoxide, tetrabutyl titanate, and tetraethyl titanate; the monohydroxy alcohol is one or more of ethanol, n-propanol, isopropanol, n-butanol, and isobutanol; and the magnetostrictive material is one or more of cobalt ferrite, bismuth ferrite, nickel ferrite, bismuth manganate, zinc ferrite, terbium-dysprosium-iron alloy, and terbium-iron alloy.

[0009] Furthermore, the molar ratio of the organotitanium compound, the magnetostrictive material, and barium acetate is 3:(2-3):(2-3).

[0010] Furthermore, the piezoelectric polymer is one or more of polylactic acid, poly-β-hydroxybutyric acid, 3-hydroxybutyric acid-3-hydroxyvalerate copolymer, polyvinylidene fluoride and its copolymers, and nylon; the solvent is one or more of hexafluoroisopropanol, dichloromethane, trichloromethane, N,N-dimethylformamide, and tetrahydrofuran.

[0011] Furthermore, the method for constructing a surface with magnetoelectric coupling effect further includes the following steps: The surface with the magnetoelectric coupling effect is subjected to corona polarization treatment and / or an external magnetic field is applied to enhance the surface potential; the magnetic field is a static magnetic field provided by a permanent magnet or a dynamic magnetic field provided by an electromagnet.

[0012] Another object of the present invention is to provide a surface with a magnetoelectric coupling effect obtained by the above-described construction method.

[0013] Another object of the present invention is to provide an application of the above-mentioned surface with magnetoelectric coupling effect in the preparation of implant materials for bone defect repair, wherein the surface with magnetoelectric coupling effect can generate and enhance polarization charge on the surface through magnetoelectric coupling effect under the action of an external magnetic field, thereby establishing a long-lasting electrical microenvironment that promotes bone integration at the implant material-bone interface.

[0014] Another object of the present invention is to provide an implant material for bone defect repair, comprising a substrate, wherein the substrate is provided with the aforementioned surface having a magnetoelectric coupling effect.

[0015] Furthermore, the substrate is carbon fiber reinforced polyaryletherketone.

[0016] This invention provides a method for constructing a surface with a magnetoelectric coupling effect. Based on the characteristic that magnetoelectric coupling can convert magnetic field energy into polarization charge, a surface is designed and constructed that can be activated on demand by an external magnetic field and can periodically maintain its electrical activity. This surface retains the excellent mechanical properties of the substrate while enabling wireless charging using an external magnetic field. This surface can be applied to implant materials for bone defect repair, ensuring that the implant material-bone interface can continuously maintain an effective microelectrical environment that promotes osteogenesis during the critical period of bone healing, thus providing an innovative solution for achieving reliable and long-lasting bone integration. Attached Figure Description

[0017] Figure 1 This is a scanning electron microscope image of the substrate after laser processing in Example 1.

[0018] Figure 2 Transmission electron microscope (a) and EDX mapping (b) images of the CF@BT prepared in Example 1.

[0019] Figure 3 The images are transmission electron microscope (a) and EDX mapping (b) images of the CF@BT@PDA in Example 1.

[0020] Figure 4 The X-ray photoelectron spectra of CF@BT and CF@BT@PDA in Example 1 are shown.

[0021] Figure 5 The images show physical pictures of the implant materials (CPA, CPCB10, CPCB20, CPCB30) provided in Examples 1-3 and Comparative Example 1.

[0022] Figure 6 The magnetoelectric coupling properties of the implant materials provided in Examples 1-3.

[0023] Figure 7The images show the MC3T3-E1 cytotoxicity detection results of the implantation materials provided in Examples 1-3 and Comparative Example 1.

[0024] Figure 8 The images show the proliferation of MC3T3-E1 cells after corona polarization treatment and magnetic field treatment of the implanted materials provided in Examples 1-3 and Comparative Example 1.

[0025] Figure 9 The images show the osteogenic differentiation of MC3T3-E1 cells after corona polarization treatment and magnetic field treatment of the implant materials provided in Examples 1-3 and Comparative Example 1. Detailed Implementation

[0026] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0027] In one embodiment of the present invention, an implant material for bone defect repair is provided, comprising a substrate, wherein the substrate has a surface having a magnetoelectric coupling effect, and the method for constructing the surface specifically includes the following steps: S1. Provide a substrate: Carbon fiber and polyaryletherketone are melt-blended at a mass ratio of (0.25-1):1, and then prepared into circular sheets with a diameter of 0.5-1.5 cm by a micro injection molding machine. The injection temperature during the injection molding process is 300-430℃, and the mold temperature is 180-250℃. The injection-molded material is ultrasonically immersed in acetone, anhydrous ethanol, and deionized water for 30-60 min in sequence, and then dried in a forced-air oven at 40℃-80℃ for 30-60 min. After being taken out and cooled, it is then laser-processed to obtain a carbon fiber reinforced polyaryletherketone substrate with microstructure and conductivity on the surface, so as to enhance the coating adhesion and polarization effect. The laser processing parameters are as follows: spot diameter is 10-100μm, scanning frequency is 1-13kHz, rated power is 0.1-10W, wavelength range is 240-2600nm, pulse width is 10-130fs, and scanning speed is 1-30mm / s.

[0028] S2. Based on the sol-gel method, a magnetoelectric coupling composite material was prepared using an organotitanium compound, a magnetostrictive material, and barium acetate: The organotitanium compound was dissolved in a monohydroxy alcohol and stirred vigorously for 30-60 min. Acetic acid was then added and stirred vigorously for another 30-60 min to obtain a titanium solution. The magnetostrictive material was added to the titanium solution and ultrasonically dispersed for 30-60 min. The mixture was then mechanically stirred vigorously for 1-2 h. A barium acetate aqueous solution was then slowly added dropwise to the continuously stirred titanium solution. The reaction was carried out at 60-100℃ until a dry gel was formed. After the reaction, stirring was continued and the mixture was cooled to room temperature. The dry gel was washed 2-4 times with anhydrous ethanol and deionized water, dried at 80-120℃ for 12-24 h, ground, and then calcined at 600-800℃ for 3-6 h to obtain the magnetoelectric coupling composite material. The molar ratio of the organotitanium compound, the magnetostrictive material, and barium acetate was 3:(2-3):(2-3).

[0029] S3. To prepare a uniform composite coating, the surface of the above magnetoelectric coupling composite material was modified using polydopamine. Specifically, 0.5-1.5g of the magnetoelectric coupling composite material was added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6), ultrasonically dispersed for 0.5-1.5h, and then 0.04-4g of dopamine hydrochloride (DA-HCl) was added and stirred for 6-18h. Finally, the mixture was centrifuged, filtered, washed with deionized water until neutral, and dried at 70-90℃ for 6-18h to obtain the modified magnetoelectric coupling composite material. Then, the modified magnetoelectric coupling composite material and the piezoelectric polymer were added to the solvent at a mass ratio of (0.01-9):1 to mix and obtain a slurry with a piezoelectric polymer concentration of 0.06-0.1g / mL.

[0030] S4. Apply the above slurry to the above substrate at a dosage of 50-100 μL, allow it to air dry naturally at room temperature, wash it sequentially with anhydrous ethanol and deionized water for 12-24 h to replace the solvent, then place it in a vacuum dryer at 60-80℃ for 12-24 h to remove water, and then place it in an annealing treatment at 100-150℃ for 7-12 h to form a surface with a magnetoelectric coupling effect; wherein, the coating method includes, but is not limited to, casting, scraping, spin coating or spraying.

[0031] S5. The surface with magnetoelectric coupling effect obtained above is subjected to corona polarization treatment using a corona polarization device to generate a surface potential. To achieve wireless charging, an external static or dynamic magnetic field can be applied to the corona-polarized surface with magnetoelectric coupling effect to enhance the surface potential. Specifically, the polarization voltage in the corona polarization treatment process is 20-25kV, the polarization temperature is 10-50℃, and the polarization time is 20-40min; the applied magnetic field strength is preferably 50-200mT.

[0032] Preferably, the polyaryletherketone includes, but is not limited to, polyetheretherketone, polyetherketone, etc.; the organotitanium compound includes, but is not limited to, one or more of isopropyl titanate, titanium n-propoxide, tetrabutyl titanate, and tetraethyl titanate; the monohydroxy alcohol includes, but is not limited to, one or more of ethanol, n-propanol, isopropanol, n-butanol, and isobutanol; the magnetostrictive material includes, but is not limited to, one or more of cobalt ferrite, bismuth ferrite, nickel ferrite, bismuth manganate, zinc ferrite, terbium-dysprosium-iron alloy, and terbium-iron alloy; the piezoelectric polymer includes, but is not limited to, polylactic acid, One or more of poly-β-hydroxybutyric acid, 3-hydroxybutyric acid-3-hydroxyvalerate copolymer, polyvinylidene fluoride and its copolymers, and nylon (such as nylon 11); solvents including but not limited to one or more of hexafluoroisopropanol, dichloromethane, trichloromethane, N,N-dimethylformamide, and tetrahydrofuran; permanent magnets including but not limited to one or more of neodymium iron boron, samarium cobalt, barium ferrite, and strontium ferrite; in addition, electromagnets can also be used instead of permanent magnets to apply a dynamic magnetic field to surfaces with magnetoelectric coupling effects.

[0033] This invention uses carbon fiber reinforced polyaryletherketone (PAEK) as a substrate. By coating the substrate surface with a slurry composed of a core-shell structure (a magnetostrictive core and a piezoelectric shell) and a piezoelectric polymer, a surface exhibiting magnetoelectric coupling effect can be formed. This surface, under the influence of an external magnetic field, can generate and enhance polarization charges through magnetoelectric coupling, thereby establishing an electrical microenvironment at the implant material-bone interface that promotes osseointegration.

[0034] Example 1: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect, and the method for constructing the surface specifically includes the following steps: S1. Carbon fiber and polyetheretherketone (PEEK) were melt-blended at a mass ratio of 3:7, and then prepared into circular sheets with a diameter of 1.2 cm using a micro-injection molding machine. The injection temperature during injection molding was 370℃, and the mold temperature was 220℃. The injection-molded material was then ultrasonically washed sequentially with acetone, anhydrous ethanol, and deionized water for 60 min, followed by drying in a forced-air oven at 60℃ for 60 min. After removal and cooling, it was then subjected to femtosecond laser processing to obtain a CFRPEEK substrate (denoted as CP) with a microstructure and conductivity on the surface. The process parameters for femtosecond laser processing were as follows: spot diameter of 20 μm, scanning frequency of 4 kHz, rated power of 1 W, wavelength range of 800 nm, pulse width of 40 fs, and scanning speed of 15 mm / s.

[0035] The scanning electron microscope image of the CFRPEEK substrate obtained in this embodiment is as follows: Figure 1 As shown, by Figure 1It can be seen that the surface of the CFRPEEEK substrate after laser processing has a distinct groove structure.

[0036] S2. Dissolve 0.03 mol of isopropyl titanate in 30 mL of isopropanol and stir vigorously for 60 min. Then add 10 mL of acetic acid and stir vigorously for 60 min to obtain a titanium solution. Add 0.025 mol of cobalt ferrite (CF) to the above titanium solution and disperse ultrasonically for 60 min. Stir vigorously mechanically for 2 h. Then slowly add 15 mL of an aqueous solution containing 0.03 mol of barium acetate to the above titanium solution while stirring continuously. React at 80 °C until a dry gel is formed. After the reaction is completed, continue stirring and cool to room temperature. Wash the dry gel three times with anhydrous ethanol and deionized water in turn. Dry it at 120 °C for 12 h. After grinding, calcine it at 800 °C for 4 h to obtain a cobalt ferrite-barium titanate magnetoelectric coupling composite material (denoted as CF@BT).

[0037] Transmission electron microscopy and EDX mapping images of the magnetoelectric coupling composite material CF@BT prepared in this embodiment are as follows: Figure 2 As shown, by Figure 2 It can be seen that the magnetoelectric coupling composite material prepared in the embodiments of the present invention has a core-shell structure, where the core is a magnetostrictive phase and the shell is a piezoelectric phase.

[0038] S3. The surface of the above magnetoelectric coupling composite material was modified using polydopamine (PDA) solution. Specifically, 1 g of CF@BT was added to 200 mL of Tris-HCl aqueous solution (10 mM, pH=8.6) and ultrasonically dispersed for 1 h. Then, 0.4 g of dopamine hydrochloride (DA-HCl) was added and stirred for 12 h. Finally, the mixture was centrifuged, filtered, washed with deionized water until neutral, and dried at 80 °C for 12 h to obtain the modified magnetoelectric coupling composite material (denoted as CF@BT@PDA). Then, the modified magnetoelectric coupling composite material was mixed with 0.6 g of polylactic acid (PLA) at a mass ratio of 2:8 in 10 mL of hexafluoroisopropanol to obtain a slurry with a polylactic acid concentration of 0.06 g / mL.

[0039] Transmission electron microscopy and EDX mapping images of the modified magnetoelectric coupling composite material CF@BT@PDA prepared in this embodiment are shown below. Figure 3 As shown, by Figure 3 It can be seen that the embodiments of the present invention successfully coated a PDA layer on the outside of the magnetoelectric coupling composite material.

[0040] In addition, the X-ray photoelectron spectra of CF@BT and CF@BT@PDA prepared in this embodiment are as follows: Figure 4 As shown, by Figure 4 It can be seen that the modified magnetoelectric coupling composite material introduces the N element, proving the successful encapsulation of PDA.

[0041] S4. 70 μL of the above slurry is cast onto the above CFRPEEK substrate. After air drying at room temperature, it is washed with anhydrous ethanol and deionized water for 24 h to replace the solvent. Then, it is placed at 80°C for vacuum drying for 24 h to remove water. Finally, it is placed at 150°C for annealing for 12 h to form a surface with magnetoelectric coupling effect, thus obtaining the implant material (denoted as CPCB20).

[0042] S5. The surface with magnetoelectric coupling effect obtained above is subjected to corona polarization treatment using a corona polarization device to generate surface potential. The polarization voltage is 20kV, the polarization temperature is 30℃, and the polarization time is 30min. The polarized material is named CPCB20-P. Then, an external magnetic field with an intensity of 150mT is applied to the surface using a neodymium iron boron permanent magnet to enhance the surface potential. The material subjected to the magnetic field is named CPCB20-M.

[0043] Example 2: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect, and the method for constructing the surface specifically includes the following steps: S1. The modified magnetoelectric coupling composite material obtained in Example 1 was mixed with 0.6g of polylactic acid in a mass ratio of 1:9 in 10mL of hexafluoroisopropanol to obtain a slurry with a concentration of 0.06g / mL.

[0044] S2. 70 μL of the above slurry was cast onto the CFRPEEK substrate prepared in Example 1. After air drying at room temperature, it was washed with anhydrous ethanol and deionized water for 24 h to replace the solvent. Then it was placed at 80°C for vacuum drying for 24 h to remove water. Finally, it was placed at 150°C for annealing for 12 h to form a surface with magnetoelectric coupling effect, thus obtaining the implant material (denoted as CPCB10).

[0045] S3. The surface with magnetoelectric coupling effect obtained above is subjected to corona polarization treatment using a corona polarization device to generate surface potential. The polarization voltage is 20kV, the polarization temperature is 30℃, and the polarization time is 30min. The polarized material is named CPCB10-P. Then, an external magnetic field with an intensity of 150mT is applied to the surface of a neodymium iron boron permanent magnet to enhance the surface potential. The material subjected to the magnetic field is named CPCB10-M.

[0046] Example 3: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect, and the method for constructing the surface specifically includes the following steps: S1. The modified magnetoelectric coupling composite material obtained in Example 1 was mixed with 0.6g of polylactic acid in a mass ratio of 3:7 in 10mL of hexafluoroisopropanol to obtain a slurry with a concentration of 0.06g / mL.

[0047] S2. 70 μL of the above slurry was cast onto the CFRPEEK substrate prepared in Example 1. After air drying at room temperature, it was washed with anhydrous ethanol and deionized water for 24 h to replace the solvent. Then it was placed at 80°C for vacuum drying for 24 h to remove water. Finally, it was placed at 150°C for annealing for 12 h to form a surface with magnetoelectric coupling effect, thus obtaining the implant material (denoted as CPCB30).

[0048] S3. The surface with magnetoelectric coupling effect obtained above is subjected to corona polarization treatment using a corona polarization device to generate surface potential. The polarization voltage is 20kV, the polarization temperature is 25℃, and the polarization time is 30min. The polarized material is named CPCB30-P. Then, an external magnetic field with an intensity of 150mT is applied to the surface using a neodymium iron boron permanent magnet to enhance the surface potential. The material subjected to the magnetic field is named CPCB30-M.

[0049] Example 4: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect, and the method for constructing the surface specifically includes the following steps: S1. Carbon fiber and polyetheretherketone (PEEK) are melt-blended at a mass ratio of 2:8, and then prepared into circular sheets with a diameter of 0.5 cm using a micro-injection molding machine. The injection temperature during injection molding is 300℃, and the mold temperature is 180℃. The injection-molded material is then ultrasonically washed sequentially with acetone, anhydrous ethanol, and deionized water for 30 min, followed by drying in a forced-air oven at 40℃ for 30 min. After removal and cooling, it is then subjected to femtosecond laser processing to obtain a CFRPEEK substrate with a microstructure and conductivity on the surface. The process parameters for femtosecond laser processing are as follows: spot diameter of 10 μm, scanning frequency of 1 kHz, rated power of 0.1 W, wavelength range of 240 nm, pulse width of 10 fs, and scanning speed of 1 mm / s.

[0050] S2. Dissolve 0.03 mol of titanium n-propoxide in 30 mL of ethanol, stir vigorously for 30 min, add 10 mL of acetic acid, and stir vigorously for 30 min to obtain a titanium solution; add 0.02 mol of bismuth ferrite to the above titanium solution, sonicate for 30 min, stir vigorously mechanically for 1 h, then slowly add 15 mL of an aqueous solution containing 0.02 mol of barium acetate to the continuously stirred titanium solution, react at 60 °C until a dry gel is formed, continue stirring and cool to room temperature after the reaction is completed; wash the dry gel twice with anhydrous ethanol and deionized water, dry at 80 °C for 12 h, grind, and then calcine at 600 °C for 3 h to obtain a magnetoelectric coupling composite material.

[0051] S3. The above magnetoelectric coupling composite material was surface modified using polydopamine. Specifically, 0.5g of the magnetoelectric coupling composite material was added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6) and ultrasonically dispersed for 0.5h. Then, 0.04g of DA-HCl was added and stirred for 6h. Finally, the mixture was centrifuged, filtered, washed with deionized water until neutral, and dried at 70℃ for 6h to obtain the modified magnetoelectric coupling composite material. Then, the modified magnetoelectric coupling composite material was mixed with 1g of poly-β-hydroxybutyric acid in 10mL of dichloromethane at a mass ratio of 0.01:1 to obtain a slurry.

[0052] S4. 50 μL of the above slurry is cast onto the above CFRPEEK substrate. After air drying at room temperature, it is washed with anhydrous ethanol and deionized water for 12 h in sequence to replace the solvent. Then it is placed at 60°C for vacuum drying for 24 h to remove water. Finally, it is placed at 100°C for annealing for 7 h to form a surface with magnetoelectric coupling effect, thus obtaining the implant material.

[0053] S5. The surface with magnetoelectric coupling effect obtained above is subjected to corona polarization treatment using a corona polarization device to generate surface potential. The polarization voltage is 25kV, the polarization temperature is 10℃, and the polarization time is 20min. Then, an external magnetic field with an intensity of 50mT is applied to the surface using a strontium ferrite permanent magnet to enhance the surface potential.

[0054] Example 5: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect, and the method for constructing the surface specifically includes the following steps: S1. Carbon fibers were melt-blended with polyaryletherketone (PAEK) at a 1:1 mass ratio, and then prepared into circular sheets with a diameter of 1.5 cm using a micro-injection molding machine. The injection temperature during injection molding was 430℃, and the mold temperature was 250℃. The injection-molded material was then ultrasonically washed sequentially with acetone, anhydrous ethanol, and deionized water for 40 min, followed by drying in a forced-air oven at 80℃ for 40 min. After removal and cooling, it was then subjected to femtosecond laser processing to obtain a CFRPEEK substrate with a microstructure and conductivity on the surface. The process parameters for femtosecond laser processing were as follows: spot diameter of 100 μm, scanning frequency of 13 kHz, rated power of 10 W, wavelength range of 2600 nm, pulse width of 130 fs, and scanning speed of 30 mm / s.

[0055] S2. Dissolve 0.03 mol tetrabutyl titanate in 30 mL n-propanol and stir vigorously for 40 min. Then add 10 mL acetic acid and stir vigorously for 40 min to obtain a titanium solution. Add 0.03 mol nickel ferrite to the above titanium solution and disperse ultrasonically for 40 min. Stir vigorously mechanically for 1.5 h. Then slowly add 15 mL of aqueous solution containing 0.03 mol barium acetate to the above titanium solution while stirring continuously. React at 100 °C until a dry gel is formed. After the reaction is completed, continue stirring and cool to room temperature. Wash the dry gel with anhydrous ethanol and deionized water four times in sequence, dry at 100 °C for 18 h, grind, and then calcine at 700 °C for 6 h to obtain a magnetoelectric coupling composite material.

[0056] S3. The above magnetoelectric coupling composite material was surface modified using polydopamine. Specifically, 1.5g of the magnetoelectric coupling composite material was added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6) and ultrasonically dispersed for 1.5h. Then, 4g of DA-HCl was added and stirred for 18h. Finally, the mixture was centrifuged, filtered, washed with deionized water until neutral, and dried at 90℃ for 18h to obtain the modified magnetoelectric coupling composite material. Then, the modified magnetoelectric coupling composite material was mixed with 0.8g of polyvinylidene fluoride in a mass ratio of 9:1 in 10mL of N,N-dimethylformamide to obtain a slurry.

[0057] S4. Spin-coat 100 μL of the above slurry onto the above CFRPEEK substrate. After air drying at room temperature, wash with anhydrous ethanol and deionized water for 18 h to replace the solvent. Then, vacuum dry at 70°C for 18 h to remove water. Finally, anneal at 120°C for 9 h to form a surface with magnetoelectric coupling effect, and obtain the implant material.

[0058] S5. The surface with magnetoelectric coupling effect obtained above is subjected to corona polarization treatment using a corona polarization device to generate surface potential. The polarization voltage is 22kV, the polarization temperature is 50℃, and the polarization time is 40min. Then, an external magnetic field with an intensity of 200mT is applied to the surface using a barium ferrite permanent magnet to enhance the surface potential.

[0059] Example 6: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: 0.03 mol tetrabutyl titanate was dissolved in 30 mL isopropanol and stirred vigorously for 60 min. Then, 10 mL acetic acid was added and stirred vigorously for another 60 min to obtain a titanium solution. 0.025 mol cobalt ferrite was added to the titanium solution and ultrasonically dispersed for 60 min. The solution was then vigorously mechanically stirred for 2 h. Then, 15 mL of an aqueous solution containing 0.03 mol barium acetate was slowly added dropwise to the continuously stirred titanium solution. The reaction was carried out at 80 °C until a dry gel was formed. After the reaction was completed, the solution was stirred and cooled to room temperature. The dry gel was washed three times with anhydrous ethanol and deionized water, dried at 120 °C for 12 h, ground, and then calcined at 800 °C for 4 h to obtain a magnetoelectric coupling composite material.

[0060] Example 7: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: 0.03 mol of isopropyl titanate was dissolved in 30 mL of n-butanol and stirred vigorously for 60 min. Then, 10 mL of acetic acid was added and stirred vigorously for another 60 min to obtain a titanium solution. 0.025 mol of cobalt ferrite was added to the titanium solution and ultrasonically dispersed for 60 min. The solution was then vigorously mechanically stirred for 2 h. Then, 15 mL of an aqueous solution containing 0.03 mol of barium acetate was slowly added dropwise to the continuously stirred titanium solution. The reaction was carried out at 80 °C until a dry gel was formed. After the reaction was completed, the solution was stirred and cooled to room temperature. The dry gel was washed three times with anhydrous ethanol and deionized water, dried at 120 °C for 12 h, ground, and then calcined at 800 °C for 4 h to obtain a magnetoelectric coupling composite material.

[0061] Example 8: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: 0.03 mol of isopropyl titanate was dissolved in 30 mL of isopropanol and stirred vigorously for 60 min. Then, 10 mL of acetic acid was added and stirred vigorously for another 60 min to obtain a titanium solution. 0.025 mol of cobalt ferrite was added to the titanium solution and ultrasonically dispersed for 60 min. The solution was then vigorously mechanically stirred for 2 h. Then, 15 mL of an aqueous solution containing 0.025 mol of barium acetate was slowly added dropwise to the continuously stirred titanium solution. The reaction was carried out at 80 °C until a dry gel was formed. After the reaction was completed, the solution was stirred and cooled to room temperature. The dry gel was washed three times with anhydrous ethanol and deionized water, dried at 120 °C for 12 h, ground, and then calcined at 800 °C for 4 h to obtain a magnetoelectric coupling composite material.

[0062] Example 9: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: 0.03 mol of isopropyl titanate was dissolved in 30 mL of isopropanol and stirred vigorously for 60 min. Then, 10 mL of acetic acid was added and stirred vigorously for another 60 min to obtain a titanium solution. 0.025 mol of terbium-dysprosium-iron alloy (TD) was added to the titanium solution and ultrasonically dispersed for 60 min. The mixture was then vigorously mechanically stirred for 2 h. Then, 15 mL of an aqueous solution containing 0.03 mol of barium acetate was slowly added dropwise to the continuously stirred titanium solution. The mixture was reacted at 80 °C until a dry gel was formed. After the reaction was completed, the mixture was stirred and cooled to room temperature. The dry gel was washed three times with anhydrous ethanol and deionized water, dried at 120 °C for 12 h, ground, and then calcined at 800 °C for 4 h to obtain a magnetoelectric coupling composite material.

[0063] Example 10: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: 0.03 mol of isopropyl titanate was dissolved in 30 mL of isobutanol and stirred vigorously for 60 min. Then, 10 mL of acetic acid was added and stirred vigorously for another 60 min to obtain a titanium solution. 0.025 mol of terbium-iron alloy was added to the titanium solution and ultrasonically dispersed for 60 min. The mixture was then vigorously mechanically stirred for 2 h. Then, 15 mL of an aqueous solution containing 0.03 mol of barium acetate was slowly added dropwise to the continuously stirred titanium solution. The mixture was reacted at 80 °C until a dry gel was formed. After the reaction was completed, the mixture was stirred and cooled to room temperature. The dry gel was washed three times with anhydrous ethanol and deionized water, dried at 120 °C for 12 h, ground, and then calcined at 700 °C for 4 h to obtain a magnetoelectric coupling composite material.

[0064] Example 11: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: 0.03 mol tetraethyl titanate was dissolved in 30 mL n-butanol and stirred vigorously for 60 min. Then, 10 mL acetic acid was added and stirred vigorously for another 60 min to obtain a titanium solution. 0.03 mol zinc ferrite was added to the titanium solution and ultrasonically dispersed for 60 min. The solution was then vigorously mechanically stirred for 2 h. Then, 15 mL of an aqueous solution containing 0.03 mol barium acetate was slowly added dropwise to the continuously stirred titanium solution. The reaction was carried out at 80 °C until a dry gel was formed. After the reaction was completed, the solution was stirred and cooled to room temperature. The dry gel was washed three times with anhydrous ethanol and deionized water, dried at 120 °C for 12 h, ground, and then calcined at 700 °C for 4 h to obtain a magnetoelectric coupling composite material.

[0065] Example 12: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: The surface of the above magnetoelectric coupling composite material was modified using polydopamine. Specifically, 1g of the magnetoelectric coupling composite material was added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6) and ultrasonically dispersed for 1h. Then, 2g of DA-HCl was added and stirred for 12h. Finally, the mixture was centrifuged, filtered, washed with deionized water until neutral, and dried at 80℃ for 12h to obtain the modified magnetoelectric coupling composite material. Then, the modified magnetoelectric coupling composite material was mixed with 0.8g of 3-hydroxybutyric acid-3-hydroxyvalerate copolymer in 1:1 mass ratio in 10mL of chloroform to obtain a slurry.

[0066] Example 13: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: The surface of the above magnetoelectric coupling composite material was modified using polydopamine. Specifically, 1g of the magnetoelectric coupling composite material was added to 200mL of Tris-HCl aqueous solution (10mM, pH=8.6) and ultrasonically dispersed for 1h. Then, 1g of DA-HCl was added and stirred for 12h. Finally, the mixture was centrifuged, filtered, washed with deionized water until neutral, and dried at 80℃ for 12h to obtain the modified magnetoelectric coupling composite material. Then, the modified magnetoelectric coupling composite material was mixed with 0.7g of nylon 11 in a mass ratio of 4:6 in 10mL of tetrahydrofuran to obtain a slurry.

[0067] Example 14: This example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect. The method of constructing this surface differs from that of Example 1 only in the following steps; all other steps are the same: The surface with magnetoelectric coupling effect is corona polarized using a corona polarization device to generate a surface potential. The polarization voltage is 22kV, the polarization temperature is 30℃, and the polarization time is 30min. Then, an external magnetic field with an intensity of 80mT is applied to the surface using a barium ferrite permanent magnet to enhance the surface potential.

[0068] Comparative Example 1: This comparative example provides an implant material for bone defect repair, including a substrate, wherein the substrate has a surface with a magnetoelectric coupling effect, and the method for constructing the surface specifically includes the following steps: S1. Add 0.6g of polylactic acid to 10mL of hexafluoroisopropanol and mix to obtain a slurry with a concentration of 0.06g / mL.

[0069] S2. 70 μL of the above slurry was cast onto the CFRPEEK substrate prepared in Example 1. After air drying at room temperature, it was washed with anhydrous ethanol and deionized water for 24 h to replace the solvent. Then it was placed at 80°C for vacuum drying for 24 h to remove water. Finally, it was placed at 150°C for annealing for 12 h to form a surface with magnetoelectric coupling effect, thus obtaining the implant material (denoted as CPA).

[0070] S3. The surface with magnetoelectric coupling effect obtained above is subjected to corona polarization treatment using a corona polarization device to generate surface potential. The polarization voltage is 20kV, the polarization temperature is 30℃, and the polarization time is 30min. The polarized material is named CPA-P. Then, an external magnetic field with an intensity of 150mT is applied to the surface using a neodymium iron boron permanent magnet to enhance the surface potential. The material subjected to the magnetic field is named CPA-M.

[0071] Experimental testing: I. Physical images of the implant materials provided in Examples 1-3 and Comparative Example 1 are shown below. Figure 5 As shown, by Figure 5 It can be seen that as the doping amount of the magnetoelectric coupling composite material increases, the surface color of the implanted material gradually deepens.

[0072] II. The magnetoelectric coupling performance test results of the implant materials provided in Examples 1-3 and Comparative Example 1 are as follows: Figure 6 As shown, by Figure 6 It can be seen that as the doping amount of the magnetoelectric coupling composite material increases, the magnetoelectric coupling performance of the implanted material first increases and then decreases, reaching a maximum value at 20%.

[0073] III. The cytotoxicity of the implantation materials and CFRPEEK substrates (CP) provided 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 on the surface of a series of different implantation materials after co-culturing with MC3T3-E1 cells for 24 hours, proving that the implantation materials provided in the embodiments of the present invention are all non-cytotoxic.

[0074] IV. Cell proliferation capacity was determined using a commercially available CCK-8 assay kit, employing the implantation materials and CFRPEEK substrate (CP) provided in Examples 1-3 and Comparative Example 1. Following the same cell seeding steps as described above, cells were co-cultured for 1, 4, and 7 days. 100 μL of CCK-8 reagent was added to each well and incubated for 2 hours. The absorbance at 450 nm was measured using a microplate reader. The results are as follows: Figure 8 As shown. By Figure 8 It can be seen that the cell proliferation on the surfaces of a series of different implantation materials co-cultured with MC3T3-E1 cells for 1, 4, and 7 days was higher than that on the pure CFRPEEK substrate group, which proves that the implantation material provided in the embodiments of the present invention has good cell activity, can provide a suitable microenvironment for cells, effectively promote cell proliferation, and the surface with the strongest magnetoelectric coupling effect has the best effect under the action of an external magnetic field.

[0075] V. The early osteogenic differentiation capacity of the implant materials and CFRPEEK substrate (CP) provided in Examples 1-3 and Comparative Example 1 was determined using a commercially available alkaline phosphatase (ALP) kit. Following the same cell seeding steps as described above, cells were co-cultured for 7 and 14 days, respectively. 500 μL of trypsin-EDTA digestion solution was added to each well for 3 min. Cells were centrifuged to obtain a cell pellet, and cell lysis buffer was added to lyse the cells to obtain the test sample. The working solution was added to the test sample according to the ALP detection kit instructions for measurement. The results are as follows: Figure 9 As shown. By Figure 9It can be seen that the ALP activity on the surface of a series of different implant materials was higher than that of the pure CFRPEEK substrate group when co-cultured with MC3T3-E1 cells for 7 and 14 days. This proves that the implant material prepared in the embodiments of the present invention has the ability to promote osteogenic differentiation of cells, and the implant material with the strongest magnetoelectric coupling effect has the best effect under the action of external magnetic field, which can reach 5 times that of the pure CFRPEEK substrate group.

[0076] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification.

Claims

1. A method for constructing a surface with a magnetoelectric coupling effect, characterized in that, Includes the following steps: A substrate is provided, and the surface of the substrate is made conductive to make the surface of the substrate conductive; Based on the sol-gel method, a core-shell structured magnetoelectric coupling composite material was prepared using organotitanium compounds, magnetostrictive materials, and barium acetate. The surface of the magnetoelectric coupling composite material is modified with polydopamine to form a polydopamine coating layer; The polydopamine-modified magnetoelectric coupling composite material was mixed with polylactic acid, a biodegradable piezoelectric polymer, in a solvent at a mass ratio of 2:8 to obtain a slurry. The slurry is coated onto the surface of a substrate that has undergone conductive treatment, and then dried and annealed to form a coating with a magnetoelectric coupling effect on the substrate surface. The step of preparing magnetoelectric coupling composite materials using organotitanium compounds, magnetostrictive materials, and barium acetate based on the sol-gel method specifically includes: An organotitanium compound was dissolved in a monohydroxy alcohol, and acetic acid was added and stirred to obtain a titanium solution. The magnetostrictive material was dispersed in a titanium solution and then reacted by adding a barium acetate aqueous solution to form a dry gel. The dry gel was calcined to obtain a magnetoelectric coupling composite material; the calcination temperature was 600-800℃. The method for conductive treatment of the substrate surface includes laser processing, and the process parameters of the laser processing are as follows: spot diameter is 10-100μm, scanning frequency is 1-13kHz, rated power is 0.1-10W, wavelength range is 240-2600nm, pulse width is 10-130fs, and scanning speed is 1-30mm / s. The method also includes the following steps: corona polarization treatment and / or application of an external magnetic field to the surface with the magnetoelectric coupling effect to enhance the surface potential; the magnetic field is a static magnetic field provided by a permanent magnet or a dynamic magnetic field provided by an electromagnet.

2. The method for constructing a surface with magnetoelectric coupling effect according to claim 1, characterized in that, The organotitanium compound is one or more of isopropyl titanate, titanium n-propoxide, tetrabutyl titanate, and tetraethyl titanate; the monohydroxy alcohol is one or more of ethanol, n-propanol, isopropanol, n-butanol, and isobutanol; the magnetostrictive material is one or more of cobalt ferrite, bismuth ferrite, nickel ferrite, bismuth manganate, zinc ferrite, terbium-dysprosium-iron alloy, and terbium-iron alloy.

3. The method for constructing a surface with magnetoelectric coupling effect according to claim 1, characterized in that, The molar ratio of the organotitanium compound, the magnetostrictive material, and the barium acetate is 3:(2-3):(2-3).

4. The method for constructing a surface with magnetoelectric coupling effect according to claim 1, characterized in that, The piezoelectric polymer is one or more of polylactic acid, poly-β-hydroxybutyric acid, and 3-hydroxybutyric acid-3-hydroxyvalerate copolymer; the solvent is one or more of hexafluoroisopropanol, dichloromethane, and trichloromethane.

5. A surface with magnetoelectric coupling effect obtained by the construction method of claim 1, characterized in that, The surface is a coating structure attached to a conductive substrate.

6. The application of a surface with magnetoelectric coupling effect as described in claim 5 in the preparation of implant materials for bone defect repair, characterized in that, The surface with the magnetoelectric coupling effect can generate and enhance polarization charge on the surface through the magnetoelectric coupling effect under the action of an external magnetic field, thereby establishing a long-lasting electrical microenvironment that promotes bone integration at the implant material-bone interface; the external magnetic field is a non-contact wireless activation method.

7. An implant material for repairing bone defects, characterized in that, It includes a substrate and a surface with a magnetoelectric coupling effect as described in claim 5, which is attached to the surface of the substrate; the substrate is conductively treated to make its surface conductive; the surface with the magnetoelectric coupling effect is a coating structure.

8. The implant material for bone defect repair according to claim 7, characterized in that, The substrate is carbon fiber reinforced polyaryletherketone.

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