A magnetoresponsive artificial periosteum and its preparation method and application

Abstract

The present invention discloses a magnetoresponsive artificial periosteum and its preparation method and application, which includes magnetic drive layers at both ends in the length direction of the artificial periosteum and a stretching layer disposed between the magnetic drive layers; the magnetic drive layer is composed of a hydrogel formed by photocrosslinking gelatin methacrylate loaded with magnetic nanoparticles; the stretching layer is composed of a hydrogel formed by photocrosslinking after the composite of decellularized periosteum matrix methacrylate and gelatin methacrylate. The artificial periosteum of the present invention is close to the natural periosteum biological microenvironment and specific structure, not only having a natural bone-like three-dimensional network structure, which is beneficial to cell adhesion and growth; but also having magnetoresponsive ability, generating strain in the artificial periosteum through an external magnetic field, simulating the elasticity of the natural periosteum, and having osteoconduction and osteoinductive effects, which is beneficial to repairing damaged tissues and promoting bone regeneration. The artificial periosteum of the present invention can achieve the repair and regeneration of bone through external mechanical stimulation and has good application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of tissue engineering materials, and particularly to a magnetoresponsive artificial periosteum and its preparation method and application. Background Art

[0002] Bone defect is a common disease in orthopedic clinics, which can be caused by various factors such as trauma, infection and tumors. Although the human skeletal system has the ability of self-renewal, non-union fractures are still a major clinical challenge. Currently, the commonly used clinical treatment method is bone transplantation, that is, using a bone scaffold to fill the bone defect and induce bone regeneration. Bone is the second most common transplanted tissue after blood. More than 1 million bone transplants are performed in the United States every year, and this number is expected to increase to 1.5 million by 2026. There is still a gap in the orthopedic implant medical device market in China, and the market scale is increasing year by year. However, after the bone scaffold is implanted, its repair process is basically a passive connection and filling process, lacking active perception of the defect environment. Although some scaffolds are supplemented with exogenous cytokines, which can play a certain role in promoting angiogenesis and bone regeneration, it is still difficult to simulate the in vivo bone reconstruction process, so satisfactory treatment effects have not been obtained.

[0003] In the past, people have paid too much attention to bone defects themselves and ignored the importance of the periosteum. The periosteum is a highly vascularized dense connective tissue membrane that wraps around almost all cortical bones except at joints. The natural periosteum consists of two parts. The outer layer is a fibrous layer rich in blood vessels, nerves and collagen; the inner layer is a formative layer rich in osteoblasts and having a bone growth promoting effect. In addition, the periosteum can sense the mechanical changes on the bone and change accordingly with the change of stress. The mechanical stress applied to the periosteum will ultimately be converted into a cellular response. Cells can sense external mechanical stimuli through integrins, cadherins and growth factor receptors, etc. And osteoblasts rearrange along the direction of tension decomposition. Under the action of mechanical stimuli, the periosteum can also induce changes in the gene expression of the BMP signaling pathway and various cytokines, jointly promoting the differentiation and osteogenesis of osteoblasts. Studies have shown that after bone injury, the mechanical properties of the periosteum change, and the periosteum area shrinks by about 50%. The periosteal response can be detected within 24 to 48 hours after injury. The cells in the periosteum rapidly proliferate and secrete cytokines, recruit host cells, and stimulate angiogenesis and osteogenesis. However, the current artificial periosteum does not consider the impact of such external mechanical stimuli on bone repair and regeneration. Magnetoresponsive biomaterials are a kind of potential materials that can be remotely actuated non-invasively after transplantation, can achieve cell stimulation in vitro and in vivo, and then control cell biological behaviors such as in vitro angiogenesis. The operation of integrin-attached magnetic particles and internalized particles has been shown to induce intracellular calcium signaling in human osteoblasts and mesenchymal stem cells.

[0004] The acellular periosteum matrix (dPEM) and acellular periosteum matrix gel are also a kind of potential materials. It removes immunogenicity and retains the spatial structure of ECM and a large number of extracellular signaling molecules. However, the acellular periosteum scaffold has low cell permeability due to its dense collagen fiber network. The acellular periosteum matrix gel improves this shortcoming because the hydrogel has a high water content, so they are often used as carriers for cell delivery and encapsulation. The acellular periosteum matrix gel not only has the biochemical cues, specific structure and microenvironment of natural ECM, but also exhibits highly tunable mechanical properties, bioactivity and biodegradability. Specific components in the acellular periosteum matrix gel can reduce inflammation and accelerate tissue repair by promoting the transformation of M1 macrophages into M2 macrophages. However, the pure acellular matrix gel has weak mechanical properties, which limits its use in bone repair. Summary of the Invention

[0005] Aiming at the above deficiencies of the prior art, the purpose of the present invention is to provide a magnetoresponsive artificial periosteum and its preparation method and application, which can remotely and non-invasively apply mechanical stress to the artificial periosteum in vitro or in vivo by applying an external magnetic field, realize the stimulation of cells on the artificial periosteum, simulate the mechanical environment of the natural periosteum, and solve the problems such as insufficient osteogenic ability of the current artificial periosteum.

[0006] To solve the above technical problems, the present invention adopts the following technical solutions: A magnetoresponsive artificial periosteum, comprising magnetic drive layers arranged at both ends in the length direction of the artificial periosteum and a stretching layer placed between the magnetic drive layers; if the magnetic drive layers and the stretching layer are distributed in a layered structure in the length direction, on the one hand, the stress and stretching are uneven, and on the other hand, due to the excessive length of the magnetic drive layer, a uniform magnetic field cannot be provided for the entire magnetic drive layer; the magnetic drive layer is composed of a hydrogel formed by photocrosslinking a gelatin methacrylate solution loaded with magnetic nanoparticles; the stretching layer is composed of a hydrogel formed by photocrosslinking a composite of a methacrylic acid acellular periosteum matrix solution and a gelatin methacrylate solution. In this way, gelatin can be modified with methacrylic anhydride to graft acrylate groups onto the collagen in gelatin, making it have unsaturated bonds. The synthesized gelatin methacryloyl (GelMA) can be photocrosslinked in the presence of a photoinitiator to form a three-dimensional structure under ultraviolet light irradiation. In view of the fact that dPEM contains more collagen, methacrylic anhydride capable of reacting with the hydroxyl groups on the collagen is used to graft methacrylate groups onto dPEM to form dPEMMA. The resulting dPEMMA has better mechanical strength, rapid gelation and other characteristics compared with the dPEM gel after photocrosslinking, and it has also been reported that a high density of methacrylic groups can have a protective effect on the incorporated cells. Mixing dPEMMA with GelMA can adjust its mechanical properties and has better formability.

[0007] Preferably, the artificial periosteum is rectangular or dumbbell-shaped in the length direction. In this way, the dumbbell-shaped one with arc transition and large fillet radius can reduce stress concentration during stretching, enable stress to be evenly distributed on the material, be more evenly stressed, and is beneficial for subsequent cells to be evenly stressed.

[0008] Preferably, the length of the magnetic drive layer is 0.1 - 1 mm; the length of the stretching layer is 0.1 - 1 mm; the thickness of the artificial periosteum is 0.1 - 1 mm.

[0009] Preferably, the magnetic nanoparticles are magnetite nanoparticles, and the particle size of the magnetite nanoparticles is 10 nm - 50 nm.

[0010] Another object of the present invention also lies in providing a preparation method of the above-mentioned magnetoresponsive artificial periosteum, comprising the following steps:

[0011] 1) Dispersing magnetic nanoparticles in a PBS solution containing gelatin methacrylate, and then adding a photoinitiator to obtain a precursor solution of the magnetic drive layer;

[0012] 2) Mixing a PBS solution containing decellularized bone matrix methacrylate with a gelatin methacrylate solution evenly, and then adding a photoinitiator to obtain a precursor solution of the stretching layer;

[0013] 3) Dropping the precursor solution of the magnetic drive layer obtained in step 1) into a self-made mold, then covering a glass slide above the mold, covering a mask plate above the stretching layer, irradiating with ultraviolet light to form a gel, and removing the residual solution to obtain a glass slide adhered with the magnetic drive layer;

[0014] 4) Dropping the precursor solution of the stretching layer obtained in step 2) into the self-made mold in step 3), then covering the glass slide adhered with the magnetic drive layer, placing the magnetic drive layer at both ends of the mold, and irradiating with ultraviolet light to form a gel to obtain the magnetoresponsive artificial periosteum.

[0015] Preferably, in step 1), the mass ratio of gelatin methacrylate, magnetic nanoparticles and photoinitiator is 10 - 20:1 - 5:0.05 - 1; in step 2), the mass ratio of gelatin methacrylate, decellularized bone matrix methacrylate and photoinitiator is 10 - 20:1 - 5:0.05 - 1.

[0016] Preferably, the photoinitiator is Irgacure 2925 or LAP; the wavelength of the ultraviolet light is 250 - 370 nm, the lamp power of the ultraviolet light is 10 - 50 W, and the irradiation time of the ultraviolet light is 1 - 15 min.

[0017] Preferably, the methacrylic acid decellularized periosteal matrix is prepared by the following steps: After the decellularized periosteum is crushed, a pepsin solution dissolved in glacial acetic acid is added, and stirring is continued until dissolution. The pH is adjusted to 8-9, methacrylic anhydride is added dropwise, and magnetic stirring is carried out for 4-8 hours under ice bath conditions. After dialysis and freeze-drying, the methacrylic acid decellularized periosteal matrix is obtained.

[0018] Preferably, the mass-volume ratio of the decellularized periosteum to methacrylic anhydride is 1 g: 2-8 mL.

[0019] Another object of the present invention also lies in providing the application of the above-mentioned magnetoresponsive artificial periosteum or the magnetoresponsive artificial periosteum prepared by the above method in the preparation of bone tissue regeneration and repair materials.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1. The artificial periosteum of the present invention has a multi-layer three-dimensional structure. The magnetic drive layer is composed of a hydrogel formed by photocrosslinking of methacrylated gelatin loaded with iron oxide nanoparticles. The magnetic drive layer is distributed at both ends of the artificial periosteum, which not only endows the artificial periosteum with magnetoresponsive ability to simulate the elasticity of the natural periosteum, but also reduces the toxicity of high-concentration magnetic particles to cells. The stretching layer is composed of a hydrogel formed by photocrosslinking after the composite of methacrylic acid decellularized periosteal matrix and methacrylated gelatin. The stretching layer is distributed in the middle of the artificial periosteum and is loaded with cells, and is also the main area where magnetic stretching generates strain. At the same time, this part has good biocompatibility. The artificial periosteum of the present invention can generate mechanical tensile strain under the condition of an external magnetic field, simulate the mechanical environment of the natural periosteum, and the mechanical stress applied to the periosteum will ultimately be converted into a cell response. Osteoblasts are rearranged along the direction of tension decomposition, and these stimuli are transduced by cells to stimulate biochemical pathways and effective cell processes such as differentiation, proliferation, and tissue development. Cells can sense external mechanical stimuli through integrins, cadherins, catenins, and growth factor receptors. It has been found that cells under the influence of a certain mechanical strain significantly exhibit higher osteogenic ability than the unstretched control group, can promote the expression of cytoskeleton-related genes such as α-actin and extracellular matrix type I collagen. Under the action of mechanical stimulation, the periosteum can also induce changes in the gene expression of the BMP signaling pathway and various cytokines, jointly promoting the differentiation and osteogenesis of osteoblasts. Therefore, the artificial periosteum of the present invention can achieve the repair and regeneration of bone through external mechanical stimulation.

[0022] 2. The artificial periosteum provided by the present invention has a sandwich structure composed of a stretching layer and a magnetic drive layer. Since each layer contains methacrylic acid groups, it gels through a similar principle of photocrosslinking. The adjacent layers are tightly connected, and the overall structure is stable. Among them, in the magnetic drive layer, magnetite nanoparticles are dispersed in the hydrogel precursor solution to avoid oxidation and aggregation. After photocrosslinking, the magnetite nanoparticles are encapsulated in the gaps of the hydrogel network, endowing the gel with magnetism, simulating the mechanical environment of the natural periosteum, preparing an artificial periosteum material that can be remotely and non-invasively controlled, realizing cell stimulation in vitro and in vivo, regulating the biochemical and mechanical properties of the cell microenvironment, and further regulating cell biological behavior. It has been proven that magnetic biomaterials made of magnetite nanoparticles can promote the osteogenic differentiation of stem cells. It is reported that magnetite nanoparticles can promote the migration of mesenchymal stem cells to the inflammatory site without applying an external magnetic field, indicating their clinical potential in promoting the transition of the bone injury site from the inflammatory stage to the repair stage.

[0023] 3. The artificial periosteum of the present invention uses methacrylated gelatin as the raw material, forms a microscopic three-dimensional structure under ultraviolet light irradiation, and is compounded with the decellularized periosteum matrix solution, enabling it to obtain a biological microenvironment and specific structure similar to the natural periosteum, facilitating the proliferation and differentiation of osteoblasts and osteoprogenitor cells, and further promoting the formation of new bone, which can accelerate the repair of bone defects. And methylacrylic acid decellularized periosteum matrix (dPEMMA) is obtained. Compared with the hydrogel after photocrosslinking of the obtained dPEMMA and the periosteum matrix gel, the formability and mechanical strength of the artificial periosteum are significantly improved, and the stiffness and elasticity of the stretching layer can be adjusted by changing the solution concentration, photoinitiator concentration, photocrosslinking conditions, etc., further regulating cell fate, promoting cell proliferation and differentiation, and then promoting the formation of new bone. And the present invention uses the method of photocrosslinking to gel, and can prepare an artificial periosteum with a suitable shape and size according to the actual situation. The geometric shape of the present invention can reduce stress concentration and make the stress evenly distributed on the material. The matrix material of the artificial periosteum provided by the present invention has high biocompatibility and does not need to be removed by a second operation after being implanted into the body. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 dPEMMA prepared according to the present invention; (a) Schematic diagram of the chemical synthesis of dPEMMA; (b) Physical picture of dPEMMA.

[0025] Figure 2 Schematic diagram for preparing the artificial periosteum of the present invention; (a) Preparation process of the magnetic drive layer; (b) Preparation process of the stretching layer.

[0026] Figure 3 Effect of ultraviolet light irradiation time on the gelling of dPEMMA.

[0027] Figure 4 The effect of dPEMMA concentration on gel formation.

[0028] Figure 5 The figure is a physical picture of the artificial periosteum of the present invention. From left to right are Example 1, Example 2, Example 3 and Comparative Example 1.

[0029] Figure 6 Magnetic stretching properties of the artificial periosteum of the present invention; (a) magnetic field strength and distribution of the N35 NdFeB permanent magnet used for stretching; (b) actual pictures of Example 2 before and after magnetic stretching. DETAILED DESCRIPTION

[0030] The present invention is further described in detail below with reference to the examples. The reagents used in the examples are commercially available unless otherwise specified.

[0031] Example 1

[0032] A magnetically responsive artificial periosteum is prepared by the following method:

[0033] 1) Under sterile conditions, the periosteal tissue (fresh pig femur from slaughterhouse) was washed with deionized water and subjected to freeze-thaw cycles (-80°C, 37°C) three times. Thereafter, the periosteal tissue was treated with 1% Triton X-100, 1% sodium dodecyl sulfate, and 50U / mL DNase I in sequence. Before freeze-drying, the obtained tissue was thoroughly washed and sterilized. The freeze-dried decellularized tissue was then ground into powder and digested in 1mg / mL pepsin in glacial acetic acid solution under constant stirring for 24h, and the undigested particulate residues were removed by filtration to obtain dPEM.

[0034] 2) The pH of the dPEM solution was adjusted to 9 under constant stirring, and methacrylic anhydride was added dropwise to the solution under constant stirring in an ice bath, as follows: Figure 1 As shown in (a), methacrylate groups were grafted onto the collagen chains of dPEM. After 5 h of reaction, the unreacted methacrylic anhydride was removed from the solution by dialysis with deionized water for 5 days. The solution was then filtered, freeze-dried and stored at -80 °C for future use to obtain dPEMMA in the form of white floccules, as shown in Figure 1 (b) as shown.

[0035] 3) 10 g of gelatin was dissolved in 100 ml of phosphate buffered saline (PBS) and heated to 60°C, and then 8 ml of methacrylic anhydride was slowly added dropwise under vigorous stirring. After reacting for 3 h, 300 ml of PBS was added to stop the reaction, and dialyzed with deionized water at 50°C in a dialysis bag for 7 days to remove any unreacted methacrylic anhydride. The solution was then freeze-dried for 4 days to produce fibrous white foamy gelatin methacrylate (GelMA).

[0036] 4) Mix iron oxide nanoparticles with a particle size of 10 nm to 50 nm, GelMA obtained in step 3), and photoinitiator I2595 in a mass ratio of 5:20:1 and disperse them in PBS solution to obtain a precursor solution for the magnetic drive layer.

[0037] 5) Mix dPEMMA obtained in step 2), GelMA obtained in step 3), and photoinitiator I2595 in a mass ratio of 2:20:0.5 and disperse them in PBS solution to obtain a precursor solution for the stretching layer.

[0038] 6) As Figure 2 For the self-made mold of the invention, it mainly consists of a silicone mold at the bottom, a glass sheet and a photomask plate in the middle, and a 20W ultraviolet lamp with a wavelength of 365 nm at the top. The silicone mold at the bottom can make the gel form a specific shape and has precise dimensions and thickness. The ultraviolet lamp at the top provides the necessary light conditions for photocrosslinking. The photomask plate can block the passage of part of the ultraviolet light, facilitating the formation of a layered structure of the gel. After adding the gel precursor solution to the silicone mold at the bottom, the gel will adhere to the middle glass after being irradiated with ultraviolet light. First, drop the precursor solution for the magnetic drive layer obtained in step 4) into the self-made dumbbell-shaped mold, then cover a glass sheet above the mold, and then cover a mask plate above the stretching layer. Irradiate with ultraviolet light for 10 min. The photomask plate can block the passage of part of the ultraviolet light, facilitating the formation of the magnetic drive layer gel at both ends of the mold, and obtaining a glass sheet with magnetic drive layers with a length of 500 μm and a thickness of 500 μm adhered to both ends, as Figure 2 a. Then, clean the remaining solution on the glass sheet and the mold, add the precursor solution for the stretching layer obtained in step 5) to the mold, then cover the glass sheet adhered with the magnetic drive layer, remove the photomask plate and irradiate with ultraviolet light again for 10 min, clean the excess solution, scrape off the obtained artificial perichondrium glass sheet, and there is a stretching layer with a length of 500 μm and a thickness of 500 μm between the magnetic drive layers, that is, the dumbbell-shaped artificial perichondrium is obtained, sterilized and sealed for storage.

[0039] Example 2

[0040] In this example, the dumbbell-shaped mold is replaced with a rectangular mold, and other experimental steps are the same as those in Example 1.

[0041] Example 3

[0042] In this example, dPEMMA, GelMA, and photoinitiator I2595 are used to prepare the precursor solution for the stretching layer in a mass ratio of 1:20:0.5, and other experimental steps are the same as those in Example 1.

[0043] Comparative Example 1

[0044] Replace dPEMMA with dPEM, and the other steps are the same as in Example 1.

[0045] II. Performance Detection

[0046] 1. Verify the performance of the dPEMMA prepared by the present invention. Prepare 2% dPEMMA using PBS and add a photoinitiator, and irradiate with ultraviolet light for different crosslinking times, as Figure 3 shown. The results show that: dPEMMA can basically form a gel in 10 seconds, indicating that the material has the ability of photocrosslinking, and initially proving that acrylate groups are grafted onto dPEM. Prepare 1%, 2%, and 3% dPEMMA using PBS in sequence, add a photoinitiator and irradiate with ultraviolet light until complete gelation, as Figure 4 shown. The results show that: the solution becomes thicker as the concentration of dPEMMA increases, and the formed gel has better formability as the concentration of dPEMMA increases.

[0047] 2. Observe the artificial periosteums prepared in Examples 1-3 and Comparative Example 1, and the results are as Figure 5 shown. The results show that: the artificial periosteum prepared by the present invention has precise thickness and dimensions. Compared with the gel formed by the photocrosslinking of dPEM and GelMA, the gel formed by the photocrosslinking of dPEMMA and GelMA of the present invention is more transparent, has better toughness, and has better formability, solving the limitations of dPEM in bone repair applications.

[0048] 3. Place the artificial periosteum prepared in Example 2 into a container filled with PBS, fix one end of the artificial periosteum with a glass slide, and place a neodymium iron boron permanent magnet (N35, 50*10*5 mm) at the other end. Apply magnetic stretching to the obtained artificial periosteum to simulate the stress situation of the natural periosteum. Use FEMM software to perform finite element modeling and analysis on the magnetic field strength and distribution of the neodymium iron boron permanent magnet used in the experiment, as Figure 6 (a) shown, and photograph the stretching process of the artificial bone prepared in Example 2. The results are as Figure 6(as shown in (b). The results show that the artificial periosteum changes from 2.5 mm before stretching to 3 mm after stretching. The artificial periosteum prepared in Example 1 also has a similar effect, and the geometric shape of Example 1 is more uniformly stressed, which is beneficial for subsequent cells to be uniformly stressed. It can be seen that the artificial periosteum deforms under the external static magnetic field, which can simulate the mechanical environment of the natural periosteum; furthermore, it is expected that the mechanical stress applied to the artificial periosteum will ultimately be converted into a cellular response, and osteoblasts will rearrange along the direction of tension decomposition, and these stimuli are transduced by the cells to stimulate biochemical pathways and effective cellular processes such as differentiation, proliferation, and tissue development. Cells can sense external mechanical stimuli through integrins, cadherins, catenins, and growth factor receptors. Under the action of mechanical stimuli, this artificial periosteum is also expected to induce changes in the gene expression of the BMP signaling pathway and various cytokines, jointly promoting the differentiation and osteogenesis of osteoblasts. Therefore, the artificial periosteum of the present invention can achieve bone repair and regeneration through external mechanical stimuli.)

[0049] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.)

Claims

1. A magnetoresponsive artificial periosteum, characterized in that, It includes a magnetic drive layer provided at both ends in the length direction of the artificial periosteum and a stretching layer placed between the magnetic drive layers; the magnetic drive layer is composed of a hydrogel formed by photocrosslinking a gelatin methacrylate solution loaded with magnetic nanoparticles; the stretching layer is composed of a hydrogel formed by photocrosslinking a composite of a decellularized periosteum matrix methacrylate solution and a gelatin methacrylate solution; the artificial periosteum is rectangular or dumbbell-shaped in the length direction.

2. The magnetoresponsive artificial periosteum according to claim 1, characterized in that, The length of the magnetic drive layer is 0.1 - 1 mm; the length of the stretching layer is 0.1 - 1 mm; the thickness of the artificial periosteum is 0.1 - 1 mm.

3. The magnetoresponsive artificial perichondrium according to claim 1, wherein The magnetic nanoparticles are magnetite nanoparticles, and the particle size of the magnetite nanoparticles is 10 nm - 50 nm.

4. A method for preparing a magnetoresponsive artificial periosteum according to any one of claims 1 to 3, characterized in that, It includes the following steps: 1) Disperse magnetic nanoparticles in a PBS solution containing gelatin methacrylate, and then add a photoinitiator to obtain a precursor solution for the magnetic drive layer. 2) Mix a PBS solution containing a decellularized periosteum matrix methacrylate evenly with a gelatin methacrylate solution, and then add a photoinitiator to obtain a precursor solution for the stretching layer. 3) Drop the precursor solution for the magnetic drive layer obtained in step 1) into a self-made mold, then cover a glass slide above the mold, and then cover a mask plate above the stretching layer. After photocuring with ultraviolet light, remove the residual solution to obtain a glass slide adhered with the magnetic drive layer. 4) Drop the precursor solution for the stretching layer obtained in step 2) into the self-made mold in step 3), then cover the glass slide adhered with the magnetic drive layer, place the magnetic drive layers at both ends of the mold respectively, and photocure with ultraviolet light to obtain the magnetic-responsive artificial periosteum.

5. The preparation method of the magnetoresponsive artificial perichondrium according to claim 4, characterized in that, In step 1), the mass ratio of gelatin methacrylate, magnetic nanoparticles and photoinitiator is 10 - 20:1 - 5:0.05 - 1; in step 2), the mass ratio of gelatin methacrylate, decellularized periosteum matrix methacrylate and photoinitiator is 10 - 20:1 - 5:0.05 - 1.

6. The preparation method of the magnetoresponsive artificial perichondrium according to claim 4, characterized in that The photoinitiator is Irgacure 2925 or LAP; the wavelength of the ultraviolet light is 250 - 370 nm, the lamp power of the ultraviolet light is 10 - 50 W, and the irradiation time of the ultraviolet light is 1 - 15 min.

7. The preparation method of the magnetoresponsive artificial perichondrium according to claim 4, characterized in that, The decellularized periosteum matrix methacrylate is prepared by the following steps: After crushing the decellularized periosteum, add a pepsin solution dissolved in glacial acetic acid, continuously stir until dissolved, adjust the pH to 8 - 9, dropwise add methacrylic anhydride and magnetically stir for 4 - 8 hours under ice bath conditions, and obtain the decellularized periosteum matrix methacrylate after dialysis and freeze-drying.

8. The preparation method of the magnetoresponsive artificial perichondrium according to claim 7, wherein The mass-volume ratio of the decellularized periosteum to methacrylic anhydride is 1 g:2 - 8 mL.

9. Use of the magnetic-responsive artificial periosteum according to any one of claims 1 - 3 or the magnetic-responsive artificial periosteum prepared by the method according to claims 5 - 8 in the preparation of bone tissue regeneration and repair materials.

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