Magnetoelectric hydrogel microneedle as well as preparation method and application thereof

Abstract

The invention belongs to the field of biomedical materials, and discloses a magnetoelectric hydrogel microneedle, the magnetoelectric hydrogel microneedle comprises a backing and a microneedle array, the backing comprises hydrogel containing magnetic ionic liquid Fe-IL and thiolated chitosan, and the microneedle array comprises magnetoelectric nanoparticles and hydrogel; the magnetoelectric nano-particles are CB core-shell structure nano-particles of which the surface of magnetic nano cobalt ferrite (CFO) is coated with a piezoelectric responsive barium titanate (BTO) shell layer. The invention further discloses a preparation method of the magnetoelectric hydrogel microneedle and application of the magnetoelectric hydrogel microneedle in preparation of products for treating bone tissue repair. During preparation, CB gradient distribution is regulated and controlled through an external magnetic field, the magnetoelectric response efficiency is enhanced, when the magnetoelectric hydrogel is applied to preparation of products for treating bone tissue repair, the osteogenesis efficiency can be improved, the adaptability of the magnetoelectric hydrogel to the bone tissue can be enhanced, and efficient electrical stimulation repair of the bone tissue is achieved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a magnetoelectric hydrogel microneedle and a preparation method and application thereof. BACKGROUND

[0002] Bone defect repair is an important challenge in clinical orthopedics, especially in the scenario of complex trauma or bone disease leading to bone tissue continuity interruption. The demand for efficient bone regeneration and safety of repair is prominent. At present, in the commonly used bone repair strategy in clinic, autologous bone transplantation has good biocompatibility and bone induction activity, but has the problems of limited supply area, secondary trauma and postoperative complication risk; allogeneic or xenogeneic bone transplantation faces the problems of immune rejection, infection transmission and insufficient bone integration efficiency. Although metal, bioceramic and polymer substitute biomaterials have been applied in the field of bone tissue engineering, they generally have defects such as mismatch between mechanical properties and bone tissue, toxicity of degradation products or insufficient shape adaptability, which are difficult to meet the needs of irregular bone defect sites.

[0003] In recent years, bone regeneration strategies based on physiological electrical microenvironment regulation have become a research hotspot. By reconstructing the electrical signals at the injury site, the activity of osteoblasts can be effectively activated, and angiogenesis and bone-vascular co-regeneration can be promoted. Existing electrical stimulation materials mostly rely on external power supply or implanted electrodes, which have the problems of large trauma, high risk of infection and insufficient regulation flexibility. New types of stimulus-responsive materials, such as magnetoelectric composite materials, can achieve non-invasive electrical property regulation through an external magnetic field. However, the substrates of these materials are mostly synthetic polymers, and their biocompatibility and bone tissue adaptability need to be improved. Moreover, the interface contact efficiency of traditional film or block structures is low in complex bone defect sites, which affects signal transmission and bone formation.

[0004] Hydrogel materials are ideal biomedical carriers due to their biomimetic extracellular matrix structure, high biocompatibility and adjustable mechanical properties. Microneedle structures can enhance the interface contact between the material and the bone tissue and improve the local signal transmission efficiency. For example, the Chinese patent with publication number CN116159042A discloses a SOD-containing patch for protecting bone joints and cartilage tissue, which has a polymer microneedle structure and includes a base layer and a needle tip layer. The needle tip layer includes microneedles arranged in an array on the base layer, and the microneedles contain SOD. The base material of the microneedles is a high molecular compound containing sodium hyaluronate and chondroitin sulfate.

[0005] The hydrogel is combined with the microneedle to construct a composite microneedle system with magnetoelectric response characteristics. By using the high interface coupling efficiency of the multi-phase magnetoelectric material, the electrical properties of the material are remotely regulated by an external magnetic field to activate the osteogenesis in situ. The advantages of non-invasive electrical stimulation, shape adaptability, minimally invasive intervention and biocompatibility can be considered, which provides a new idea for bone defect repair. However, the existing materials still have problems such as low osteogenesis efficiency and insufficient adaptability to bone tissue in the model. Therefore, it is of great significance to develop a magnetoelectric response biomaterial based on hydrogel microneedles to realize efficient electrical stimulation repair of skull defects by optimizing the substrate and structure design, which promotes the clinical transformation of bone regeneration materials. SUMMARY

[0006] The purpose of the present application is to provide a magnetoelectric hydrogel microneedle and its preparation method and application. The CB gradient distribution is regulated by an external magnetic field during preparation to enhance the magnetoelectric response efficiency. The magnetoelectric hydrogel is applied to the preparation of products for treating bone tissue repair, which can improve the osteogenesis efficiency and enhance the adaptability to bone tissue, so as to realize the efficient electrical stimulation repair of bone tissue.

[0007] The first aspect of the present application provides a magnetoelectric hydrogel microneedle, which comprises a backing and a microneedle array. The backing comprises a hydrogel containing magnetic ionic liquid Fe-IL and mercapto chitosan. The microneedle array comprises magnetoelectric nanoparticles and hydrogel. The magnetoelectric nanoparticles are CB (CFO@BTO) core-shell structure nanoparticles with a magnetic nanometer cobalt ferrite CFO surface coated with a piezoelectric response barium titanate BTO shell layer.

[0008] The magnetoelectric hydrogel microneedle of the present application is composed of CB, Fe-IL and CS hydrogel substrate. The core design is to apply stress to the surface-coated piezoelectric barium titanate (BTO) shell layer through the magnetostriction effect of the magnetic nanometer cobalt ferrite (CFO) core to generate a piezoelectric signal, which is suitable for magnetoelectric response materials. The CS hydrogel microneedle serves as a carrier for CB nanoparticles, providing the required structural support and directional conduction of electrical signals during intervention. The ionic conductivity is optimized by combining Fe-IL ionic liquid, and finally realizing the synergistic effect of electrical stimulation and bone repair.

[0009] The second aspect of the present application provides a preparation method of a magnetoelectric hydrogel microneedle, comprising the following steps: S1. Preparation of magnetoelectric nanoparticles: a BTO shell layer is coated on the surface of CFO by sol-gel method to obtain CB core-shell structure nanoparticles; S2. Preparation of magnetic ionic liquid: FeCl3 is mixed with 1-vinyl-3-butyl imidazole bromide salt, and stirred at room temperature to form a supramolecular magnetic ionic liquid Fe-IL; S3. Preparing hydrogel precursor solution: mixing the magnetic ionic liquid Fe-IL of S2 with the thiolated chitosan to form a hydrogel solution; S4. Constructing microneedle array: dispersing the CB core-shell structure nanoparticles of S1 in a part of the hydrogel solution of S3, obtaining a mixed solution by regulating the gradient distribution of the nanoparticles through an external magnetic field, introducing the mixed solution into a mold, and forming a microneedle array after cross-linking and solidification; S5. Composite backing: coating another part of the hydrogel solution of S3 on the bottom of the microneedle array, and forming a backing after solidification, to obtain the magnetoelectric hydrogel microneedle.

[0010] In step S1, the sol-gel method is specifically as follows: dispersing CFO nanoparticles in a tetrabutyl titanate ethanol solution, adjusting the pH to 3-5, stirring and reacting at 60-80 °C for 4-6 hours, centrifuging and drying, and calcining at 600-800 °C for 2-3 hours to obtain CB core-shell structure nanoparticles.

[0011] The CB core-shell structure nanoparticles obtained by the above method have a diameter of 50-150 nm, which is beneficial to enhancing the magnetic response ability of the composite hydrogel, and the piezoelectric signal is generated by changing the external magnetic field.

[0012] Further, in step S2, the molar ratio of FeCl3 to 1-vinyl-3-butylimidazole bromide salt is 1:1.2.

[0013] Further, in step S3, the mass ratio of the magnetic ionic liquid to the thiolated chitosan is 1:2-20, and the ionic conductivity of the hydrogel solution is adjusted by regulating the content of the magnetic ionic liquid in the hydrogel.

[0014] Further, in step S4, the addition amount of the CB core-shell structure nanoparticles is 0.1-1% w / v of the hydrogel solution. The application realizes that the magnetoelectric hydrogel microneedle generates a suitable electric signal under the action of the external magnetic field by adjusting the addition amount of the CB core-shell structure nanoparticles.

[0015] Further, in step S4, the external magnetic field strength is 100-300 mT, and the regulation time is 5-15 minutes; the cross-linking and solidification conditions are constant temperature at 37 °C for 0.5-2 hours.

[0016] Further, in step S5, the thickness of the backing is 1-2 mm, and the backing is integrally formed with the microneedle array by a coating and solidification process.

[0017] The third aspect of the application provides a use of the above-mentioned magnetoelectric hydrogel microneedle or the magnetoelectric hydrogel microneedle obtained by the above-mentioned preparation method in preparing a product for treating bone tissue repair.

[0018] The radio stimulation is carried out under the action of an external magnetic field.

[0019] The application adopts a sol-gel method to prepare magnetoelectric nanoparticles with good magnetoelectric response characteristics, and controls the spatial distribution of the magnetic particles in the hydrogel microneedle through an external magnetic field to realize spatial driving of the microneedle and generation of a directional electric potential gradient; the composite material prepared in the application significantly increases the contact area of the material and the tissue interface by constructing a microneedle structure with a large specific surface area, effectively improves the electric stimulation efficiency, and promotes tissue repair by inducing directional cell proliferation through a directional electric potential gradient, and has great application value in the field of skull repair and other tissue regeneration.

[0020] Compared with the prior art, the application has the following beneficial effects: The magnetoelectric hydrogel microneedle provided by the application has the functions of non-invasive electric stimulation and structural support; the addition of Fe-IL significantly improves the ionic conductivity of the hydrogel, provides an efficient electrical carrier for electric signal transmission, and thus improves the electric stimulation output efficiency; at the same time, the antibacterial property of the ionic liquid can effectively reduce the risk of postoperative infection, and further ensure the repair effect in the field of bone tissue regeneration such as skull repair; the biocompatibility of the hydrogel and the structural support function of the microneedle synergistically promote tissue repair.

[0021] The preparation method provided by the application takes magnetoelectric nanoparticles and hydrogel as main components, and prepares a magnetoelectric hydrogel microneedle through microneedle structure design under mild conditions; the microneedle controls the CB gradient distribution under the action of an external magnetic field, enhances the magnetoelectric response efficiency, and thus can realize spatial driving and directional distribution of electric potential, and provides controllable physical stimulation basis for skull repair.

[0022] The magnetoelectric hydrogel microneedle provided by the application, when applied to bone tissue repair, generates a local electric signal through a magnetoelectric effect under the action of an external magnetic field, realizes non-invasive wireless electric stimulation, and thus realizes the synergistic effect of magnetic field-mechanical-electric stimulation through the action of an external magnetic field, effectively promotes skull repair. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 is a preparation flowchart of the magnetoelectric nanoparticles CB in the embodiment of the application; Figure 2 is a micro-morphology diagram of the magnetoelectric nanoparticles CB in the embodiment of the application; Figure 3 is an XRD diagram of the magnetoelectric nanoparticles CB in the embodiment of the application; Figure 4 is a magnetization curve diagram of the magnetoelectric nanoparticles CB in the embodiment of the application; Figure 5 is a magnetic response diagram of the magnetoelectric nanoparticles CB in the embodiment of the application; Figure 6 is a preparation flow chart of the magneto-electric ionic hydrogel in the embodiment of the present application; Figure 7 is a SEM image of the magneto-electric ionic hydrogel in the embodiment of the present application; Figure 8 is an electrical conductivity image of the magneto-electric ionic hydrogel in the embodiment of the present application; Figure 9 is a time scanning image of the magneto-electric ionic hydrogel in the embodiment of the present application; Figure 10 is a stress-strain image of the magneto-electric ionic hydrogel in the embodiment of the present application; Figure 11 is a magneto-electric response performance image of the magneto-electric ionic hydrogel in the embodiment of the present application; Figure 12 is a cell compatibility image of the magneto-electric hydrogel in the embodiment of the present application; Figure 13 is a preparation schematic diagram of the magneto-electric hydrogel microneedle in the embodiment of the present application; Figure 14 is a schematic diagram and a photo of the magneto-electric hydrogel microneedle implanted into the skull defect area of a rat in the embodiment of the present application; Figure 15 is an effect evaluation image of the magneto-electric hydrogel microneedle for repairing the skull model in the embodiment of the present application. DETAILED DESCRIPTION

[0024] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application are described in detail below with reference to the drawings.

[0025] It should be understood that the terms described in the present application are only for describing the specific embodiments, and are not used to limit the present application. In addition, for the numerical range in the present application, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Each smaller range between any stated value or intermediate value in the stated range and any other stated value or intermediate value in the stated range is also included in the present application. The upper limit and the lower limit of these smaller ranges can be independently included or excluded from the range.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although preferred methods and materials are described, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials in connection with which the documents are concerned. In the event of any conflict between the content of this specification and any document incorporated by reference, the content of this specification will control.

[0027] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This application specification and embodiments are merely exemplary.

[0028] Example 1 Preparation of magnetoelectric nanoparticles CB like Figure 1 The diagram shows the preparation process of the magnetoelectric nanoparticles CB in this embodiment. 5 g of nano-cobalt ferrite was added to 80 mL of sodium oleate aqueous solution and sonicated for 30 minutes. Then, the mixture was stirred at 500 rpm for 1 hour to form a stable suspension. 1 mol / L hydrochloric acid was added dropwise to the suspension, and the pH was monitored and adjusted to 5.0 ± 0.1 using a pH meter. The solution was then transferred to a 60°C constant temperature water bath and stirred at 300 rpm for 30 minutes to promote the adsorption and assembly of sodium oleate molecules on the particle surface. After the reaction was complete, magnetic separation was performed using a neodymium iron boron magnet. The precipitate was washed three times with anhydrous ethanol, and each time it was sonicated for 10 minutes before magnetic separation. The solid product was collected and placed in a vacuum drying oven and dried at 60°C for 20 hours to obtain sodium oleate-coated CFO nanoparticles.

[0029] Tetrabutyl titanate was dissolved in anhydrous ethanol and ultrasonically stirred for 30 minutes to form a transparent solution. Simultaneously, the sodium oleate-modified CFO nanoparticles were dispersed in anhydrous ethanol and ultrasonically treated until uniformly dispersed. The two ethanol dispersions were mixed and mechanically stirred for 30 minutes. Then, barium acetate and acetic acid were added sequentially, adjusting the pH of the system to 3-4 by adding acetic acid dropwise at a rate of 1 drop / second. Distilled water was then slowly added at a rate of 3 drops / second, and the mixture was stirred in a 60 °C water bath until a stable sol was formed. The temperature was further increased to 90 °C, and stirring continued until the sol transformed into a gel. The gel was transferred to a petri dish, completely dried in a 120 °C oven, and then ground into powder. The powder was placed in a muffle furnace and calcined at 500 °C for 6 hours to remove organic matter, such as sodium oleate and residual solvent. After cooling, the powder was ground again and then calcined at 800 °C for 2 hours to optimize the crystal structure, ultimately obtaining CB core-shell structured nanoparticles.

[0030] like Figure 2 The image shown is a microscopic morphology diagram of the magnetoelectric nanoparticles CB in this embodiment. SEM and TEM images show that CFO exists in an irregular aggregated state, and the prepared CB also exists in an aggregated spherical structure with a single particle diameter of approximately 100 nm.

[0031] like Figure 3 The image shown is the XRD pattern of the magnetoelectric nanoparticles CB in this embodiment. Comparison with the standard card verifies the successful preparation of CB.

[0032] As shown in Figure 4 , it is the magnetization curve diagram of the magneto-electric nanoparticles CB in the present embodiment. It can be known from the magnetization curve that the coercivity H c of CFO particles is about 1779.78 Oe, the remanence B r is about 5.90 emu g -1 ; the coercivity H c of CB particles is about 956.05 Oe, the remanence B r is about 1.77 emu g -1 , it can be judged that CB particles have greater magnetic permeability.

[0033] As shown in Figure 5 , it is the magnetic response diagram of the magneto-electric nanoparticles CB in the present embodiment. Under the action of an external magnetic field intensity of 150 mT, CB particles are converted from the original random aggregation state to the directional distribution state.

[0034] (2) Preparation of magneto-electric hydrogel As shown in Figure 6 , it is the preparation flow chart of the magneto-electric hydrogel in the present embodiment. First, anhydrous ferric chloride and 1-vinyl-3-butylimidazole bromide [C4min]Br are mixed in a molar ratio of 1:1.2, stirred at a speed of 900 rpm under a nitrogen atmosphere at room temperature for 24 hours, until the reaction system is completely converted into a deep red liquid; then the product is washed with a small amount of water and anhydrous ethanol in turn, and [C4min]FeBrCl3 intermediate is obtained after vacuum drying. Then, 5 mg [C4min]FeBrCl3 (0.5 wt %) and 40 mg thiolated chitosan (4 wt %) are added to 1 mL aqueous solution and mixed uniformly, a photoinitiator I 2959 is added and irradiated with ultraviolet light for 30 minutes, and a magnetic hydrogel is obtained by photopolymerization. While adding 0.5 % w / v CB particles in the precursor, the magneto-electric hydrogel I can be prepared after the photopolymerization is completed.

[0035] As shown in Figure 7 , it is the SEM diagram of the magneto-electric hydrogel I in the present embodiment. The SEM diagram shows that the magneto-electric hydrogel I has a porous structure.

[0036] As shown in Figure 8 , it is the conductivity diagram of the magnetic ionic hydrogel in the present embodiment. The mass fraction of Fe-IL in the 4 wt % thiolated chitosan hydrogel precursor is controlled to be 0, 0.2, 0.5, 1, and 2 wt %, and the resistance of the magnetic ionic hydrogel gradually decreases, indicating that Fe-IL improves the ionic conductivity of the hydrogel. In order to balance the mechanical and conductive properties of the hydrogel, 0.5 wt % is the optimal condition, and this content is selected for subsequent research.

[0037] As shown in Figure 9 , it is the time scanning diagram of magnetoelectric hydrogel I in this embodiment. After adding 0.5% w / v CB particles (CMC), the modulus of magnetoelectric hydrogel I is significantly improved.

[0038] As shown in Figure 10 , it is the stress-strain diagram of magnetoelectric hydrogel in this embodiment. The stress-strain curve shows that after adding 0.5% w / v CB particles (CMC), the stress value of magnetoelectric hydrogel I is significantly higher than that of magnetic ionic hydrogel without CB particles (CM), and the mechanical properties are improved.

[0039] As shown in Figure 11 , it is the magnetoelectric response performance diagram of magnetoelectric hydrogel in this embodiment. The magnetic field strength is set to 150 mT, the action time is 1 s and 5 s respectively, and the magnetic field distance is 1-10 cm. The changes of piezoelectric voltage and current signal can be realized.

[0040] As shown in Figure 12 (CMC is magnetoelectric hydrogel I, CM is magnetic ionic hydrogel without CB particles, and CL is chitosan hydrogel grafted with thioctic acid), it is the cell compatibility diagram of magnetoelectric hydrogel I in this embodiment. The cell compatibility test results show that after co-incubation with L929 cells for 2 days, the cell compatibility of the magnetoelectric hydrogel reaches 90%, fully proving that it has good biocompatibility.

[0041] (3) Preparation of magnetoelectric hydrogel microneedle As shown in Figure 13 , it is a schematic diagram of the preparation of magnetoelectric hydrogel microneedle in this embodiment: a part of the above magnetoelectric hydrogel I precursor solution is introduced into the PDMS microneedle mold, and the mold microneedle height is 950 μm and the diameter is 440 μm; then N35 magnet is placed below the mold to continuously provide magnetic field guidance, and ultraviolet light is used for irradiation for about 30 minutes for photopolymerization reaction, finally forming magnetoelectric hydrogel microneedle.

[0042] The remaining hydrogel I solution is coated on the bottom of the microneedle array, and after solidification, a 2 mm backing is formed, obtaining the magnetoelectric hydrogel microneedle.

[0043] (3) Application of magnetoelectric hydrogel microneedle As shown in Figure 14The diagram shows a schematic and photograph of the implantation of magnetoelectric hydrogel microneedles into the skull defect area of ​​a rat in this embodiment. Seven-week-old male SD rats were selected and anesthetized with isoflurane. The rat skull was then surgically exposed, and the skull defect area consisted of two circular or square full-thickness bone defects with a diameter of 5-10 mm. In this embodiment, two 5 mm circular full-thickness bone defects were prepared to establish a skull defect model (skull drilling method), and the material was implanted into the skull defect site. After the rats recovered (1-3 days post-surgery), a magnetic plate with a magnetic intensity of 2.5 mT was placed on the rat cage, and a magnetic field was applied daily.

[0044] The cranial repair effect in rats at 4 and 12 weeks post-implantation was evaluated using Micro-CT and HE staining (CT imaging and histopathology). Specifically: CT imaging assessment: Micro-CT scans of the defect area were performed at 4 and 12 weeks post-operation to calculate the new bone volume fraction (BV / TV) and bone mineral density (BMD); Histopathological assessment: Skull tissue from the defect area was harvested at 4 and 12 weeks post-operation for HE staining to observe the integrity of the newly formed trabecular bone structure.

[0045] like Figure 15 The image shown is an evaluation diagram of the effect of the magnetoelectric hydrogel microneedles on the skull model repair in this embodiment. Both results show that the magnetoelectric hydrogel has a good repair effect after 12 weeks of treatment. The above experimental results indicate that the magnetoelectric hydrogel microneedles have good magnetoelectric response characteristics and exhibit good therapeutic effects in skull repair.

[0046] While the present invention has been disclosed above, its scope of protection is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of this disclosure, and all such changes and modifications will fall within the scope of protection of this invention.

Claims

1. A magnetoelectric hydrogel microneedle, characterized in that, The magnetoelectric hydrogel microneedle comprises a backing and a microneedle array, the backing comprises a hydrogel containing magnetic ionic liquid Fe-IL and mercapto chitosan, and the microneedle array comprises magnetoelectric nanoparticles and hydrogel; the magnetoelectric nanoparticles are CB core-shell structure nanoparticles with a BTO shell layer coated on the surface of magnetic CFO.

2. A method of preparing the magneto-electric hydrogel microneedle of claim 1, wherein, The method comprises the following steps: S1. Preparing magnetoelectric nanoparticles: coating a BTO shell layer on the surface of CFO by a sol-gel method to obtain CB core-shell structure nanoparticles; S2. Preparing magnetic ionic liquid: mixing FeCl3 and 1-vinyl-3-butyl imidazole bromide salt, stirring thoroughly at room temperature to form a supermolecular magnetic ionic liquid Fe-IL; S3. Preparing hydrogel precursor solution: mixing the magnetic ionic liquid Fe-IL of S2 and mercapto chitosan to form a hydrogel solution; S4. Constructing a microneedle array: dispersing the CB core-shell structure nanoparticles of S1 in a part of the hydrogel solution of S3, obtaining a mixed solution by controlling the gradient distribution of nanoparticles through an external magnetic field, introducing the mixed solution into a mold, and forming a microneedle array after cross-linking and solidification; S5. Compounding a backing: coating another part of the hydrogel solution of S3 at the bottom of the microneedle array, and forming a backing after solidification to obtain a magnetoelectric hydrogel microneedle.

3. The method of claim 2, wherein the magnetoelectric hydrogel microneedle is prepared by the steps of: In step S1, the sol-gel method specifically comprises: dispersing CFO nanoparticles in a tetrabutyl titanate ethanol solution, adjusting the pH to 3-5, stirring at 60-80 °C for 4-6 hours, drying by centrifugation, and calcining at 600-800 °C for 2-3 hours to obtain CB core-shell structure nanoparticles.

4. The method of claim 2, wherein the magnetoelectric hydrogel microneedle is prepared by the steps of: In step S3, the mass ratio of the magnetic ionic liquid to mercapto chitosan is 1:2-20.

5. The method of claim 2, wherein the magnetoelectric hydrogel microneedle is prepared by the steps of: In step S4, the addition amount of the CB core-shell structure nanoparticles is 0.1-1 % w / v of the hydrogel solution.

6. The method of claim 2, wherein the magnetoelectric hydrogel microneedle is prepared by the steps of: In step S4, the external magnetic field strength is 100-300 mT, and the control time is 5-15 minutes.

7. The method of claim 2, wherein the magnetoelectric hydrogel microneedle is prepared by the steps of: In step S5, the thickness of the backing is 1-2 mm, and the backing is integrally formed with the microneedle array by a coating and solidification process.

8. Use of the magnetoelectric hydrogel microneedle of claim 1 or the magnetoelectric hydrogel microneedle prepared by any one of claims 2-7 in the preparation of a product for treating bone tissue repair.

9. Use according to claim 8, characterized in that, In the application, a local electric signal is generated by the magnetoelectric effect under the action of an external magnetic field to achieve non-invasive wireless electric stimulation.

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