A structure-bionic bone repair material and its application

Abstract

The present invention relates to the technical field of biomedical materials, and particularly relates to a structure-bionic bone repair material and its application. The porosity of the structure-bionic bone repair material is 83-95%, and the pore size distribution is 0-400 um, wherein the pore size of 50-175 um accounts for 70-95%. Compared with other allogeneic bone or xenogeneic bone materials, the structure-bionic bone repair material obtained in the present invention is not likely to cause an immune reaction biologically, has high biocompatibility after being implanted into the body, and has excellent bone regeneration activity and antibacterial effect. It can further promote bone healing while not easily showing cracks, fissures and discoloration, and has high mechanical strength, overcoming the problem of bone brittleness caused by the introduction of fluorides. In addition, it also has good biological properties of osteoblast binding and ingrowth effects, and mechanical properties to achieve self-support in a wet environment.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and particularly relates to a structure-bionic bone repair material and its application. Background Art

[0002] In natural bone, the main inorganic and organic components are hydroxyapatite and collagen respectively. Taking teeth as an example, teeth include dental pulp, cementum, dentin and enamel. Among them, the main part is dentin. In dentin, inorganic salts account for about 70% by weight, mainly hydroxyapatite, calcium phosphate, etc., and organic matter accounts for about 30% by weight, mainly collagen.

[0003] The patent with patent number CN100341588C discloses a preparation method of a porous collagen composite nano-hydroxyapatite artificial bone. After separately preparing collagen and nano-hydroxyapatite, they are mixed. This method is easy to control the ratio of collagen and hydroxyapatite, but can only achieve compositional bionics and cannot achieve structural bionics. The patent with patent number CN114832159B records a mineralized collagen material, its preparation method and application. A second solution composed of NaOH, Na3PO4 and glycerol is added to a first solution composed of CaCl2, C2H5OH and collagen to obtain a highly mineralized collagen gel that is bionic in both composition and structure. Although the literature mentions that it can be freeze-dried to obtain a bulk material, when the material is implanted, it is usually in a wet environment in the human body, and the bulk material will still transform into a gel state. As a bone implant material, the gel material is prone to diffusion and leakage, and the probability of causing immune reactions and infections is higher. At the same time, after injury and infection, acids will be produced, which will further affect bone healing. Moreover, the literature does not mention the pore size of the obtained gel material, and the pore size of bone graft materials has a great influence on mechanical properties and biological properties. Summary of the Invention

[0004] In order to overcome the above problems, on the premise of ensuring that the bone graft material is in a wet environment, is not prone to diffusion and leakage, has a certain antibacterial effect, and also has good biological properties of osteoblast binding and ingrowth effects, and mechanical properties of self-support in a wet environment, the first aspect of the present invention provides a structure-bionic bone repair material. The bone repair material is a porous material with a porosity of 83 - 95%, a pore size distribution of 0 - 400 μm, and among them, the pores with a pore size of 50 - 175 μm account for 70 - 95%.

[0005] Preferably, the porosity of the bone repair material is 83 - 92%.

[0006] Preferably, the pore size distribution of the bone repair material is 0 - 350 μm, and among them, the pores with a pore size of 50 - 175 μm account for 70 - 95%.

[0007] Further preferably, the pore size distribution of the bone repair material is 0 - 350 μm, wherein the pores with a pore size of 50 - 175 μm account for 70 - 90%.

[0008] As a preferred embodiment, the median pore size of the structure - bionic bone repair material is 70 - 100 μm.

[0009] Preferably, the median pore size of the bone repair material is 70 - 90 μm.

[0010] The median pore size refers to the pore size value corresponding to the vertex of the pore size distribution spectrum, that is, the pore size of the pores with the largest number in the pore network. The median pore size is of great significance for the study of porous materials with asymmetric pore size distributions.

[0011] Green D et al. have found through research that for porous bone repair materials, pores with a size of 15 - 50 μm can induce the ingrowth of fibrous tube tissue, pores with a size of 50 - 150 μm can stimulate the formation of osteoid tissue, and pores with a size of 150 - 500 μm can directly induce the formation of mineralized bone. In addition, although repair materials with larger pore sizes can directly stimulate the formation of mineralized bone, if relying solely on the direct formation of mineralized bone, it may cause a certain degree of imbalance in the ratio of organic matter and inorganic matter in the osteogenic site, increase the risk of physical properties such as cracks and brittleness in the osteogenic site, and also affect the repair speed. Therefore, it is necessary to control the pore size distribution in the bone repair material, especially the proportion of pores with a smaller pore size (pores with a size of 50 - 150 μm), so as to control the behavior of inducing the formation of osteoid tissue to account for a larger proportion on the basis of the original defect during bone healing, thereby making the final osteogenic part have a higher structural matching.

[0012] Preferably, the bulk density of the structure - bionic bone repair material is 0.2 - 0.3 g / cm 3 。

[0013] As a preferred embodiment, the structure - bionic bone repair material is obtained by adding water - soluble calcium salt - fluoride for in - situ pretreatment on an acellular tissue matrix (ACTM) template, then continuing to add phosphate for in - situ mineralization growth, followed by freeze - drying, cross - linking, washing, and then secondary freeze - drying.

[0014] As a preferred embodiment, the structure - bionic bone repair material is obtained by adding water - soluble calcium salt - fluoride for in - situ pretreatment on an ACTM template for 30 - 60 min, then continuing to add phosphate for in - situ mineralization growth for 19 - 24 h, followed by freeze - drying, cross - linking, washing, and then secondary freeze - drying.

[0015] As a preferred embodiment, the in - situ pretreatment is carried out in an atmosphere with pH = 10.6 - 11.4.

[0016] Preferably, the atmosphere with pH = 10.6 - 11.4 is adjusted by ammonia water.

[0017] Generally speaking, when reacting phosphate salts and calcium salts under alkaline conditions, various products may be formed, such as hydroxyapatite, dicalcium hydrogen phosphate dihydrate, tricalcium phosphate, octacalcium phosphate, etc. By controlling the pH, the formed products can be controlled. When pH = 9 - 11, among various products, hydroxyapatite has the smallest solubility, so the product is mainly hydroxyapatite at this time. In the present invention, in addition to calcium salts, fluorides are introduced into the reaction system. Since fluorapatite has a smaller solubility than hydroxyapatite, the reaction proceeds in the direction of decreasing solubility, forming partial fluorapatite and hydroxides, so that the solution still maintains an alkaline environment, and at the same time, fluorine in fluorapatite exists in the form of ions.

[0018] During the process of bone tissue healing, once bacteria invade, acids will be produced, which will have a negative impact on the healing. In order to avoid the generation of local acidic conditions, the inventors introduce fluorides into the system, which can not only enhance the resistance to acids, but also fluoride ions have a certain antibacterial effect. However, at the same time, the introduction of fluorides may also cause damage to the osteogenic site, such as the occurrence of bone brittleness, such as the appearance of cracks and fissures, and even fractures.

[0019] As a preferred embodiment, the reaction temperature of the in-situ pretreatment and in-situ mineralization is 35 - 39 °C.

[0020] Preferably, the reaction temperature of the in-situ pretreatment and in-situ mineralization is 37 °C.

[0021] In order to control the porosity and pore size distribution of the bone repair material, the inventors conducted a large number of exploratory experiments and found that for the mineralization system of acellular matrix - calcium salt - fluoride - phosphate, the control of the temperature and pH of the in-situ pretreatment before the mineralization reaction has an important impact on the porosity and pore size distribution of the finally obtained bone repair material. By controlling the pH of 10.6 - 11.4 and the in-situ pretreatment reaction temperature of 35 - 39 °C, the porosity of the bone repair material is 83 - 92%, and the pore size distribution is 0 - 350 μm, among which the pore size of 50 - 175 μm accounts for 70 - 95%. On the basis of the in-situ pretreatment, further controlling the temperature of 35 - 39 °C during the in-situ mineralization reaction not only strengthens the controllability of the above-mentioned pore size distribution, but also unexpectedly makes the repaired osteogenic site not prone to cracks and discoloration, which to a certain extent indicates that it may overcome the problem of bone brittleness caused by the introduction of fluorides. The inventors guess that the above-mentioned condition control affects the crystallinity and deposition behavior of hydroxyapatite, and the minerals with the obtained specific crystallinity may be more deposited outside the fiber skeleton of the ACTM template, so that the material is not prone to mechanical phenomena of stretching and shrinking.

[0022] As a preferred embodiment, the volume-mass ratio of the ACTM template to the water-soluble calcium salt-fluoride is (23-40) mL:(1.8-6.4) g.

[0023] Preferably, the water-soluble calcium salt-fluoride is composed of a water-soluble calcium salt and a water-soluble fluoride.

[0024] Preferably, in the water-soluble calcium salt-fluoride, the molar mass ratio of the water-soluble calcium salt to the water-soluble fluoride is 100:(1-50).

[0025] More preferably, in the water-soluble calcium salt-fluoride, the molar mass ratio of the water-soluble calcium salt to the water-soluble fluoride is 100:(1-15) or 100:(39-50).

[0026] Preferably, the water-soluble calcium salt is one or more of calcium nitrate, calcium acetate, calcium chloride, calcium bicarbonate, or calcium citrate.

[0027] More preferably, the water-soluble calcium salt is calcium acetate.

[0028] Preferably, the water-soluble fluoride is one or more of sodium fluoride, potassium fluoride, or calcium fluoride

[0029] More preferably, the water-soluble fluoride is sodium fluoride or potassium fluoride.

[0030] As a preferred embodiment, the mass ratio of the water-soluble calcium salt-fluoride to the phosphate is (2.12-2.43):1.

[0031] The phosphate is one or more of diammonium hydrogen phosphate, dipotassium hydrogen phosphate, or disodium hydrogen phosphate;

[0032] As a preferred embodiment, the ACTM template is a decellularized matrix slurry.

[0033] Preferably, the decellularized matrix slurry is prepared by mixing a decellularized matrix and an aqueous solution of acidic protease.

[0034] The decellularized matrix slurry is prepared by mixing a decellularized matrix and an aqueous solution of acidic protease, wherein the initial feeding concentration of the decellularized matrix in the decellularized matrix slurry is 0.01-0.2 g / ml.

[0035] The aqueous solution of acidic protease can be an aqueous solution of acidic pepsin.

[0036] The process for obtaining the decellularized matrix refers to the description in the patent content of the patent No. CN106075583B.

[0037] The decellularized matrix source includes at least one of the submucosa, basement membrane, pericardium, dermis, etc. of the hollow organs such as the intestine, esophagus, and stomach of humans and mammals.

[0038] The collagen contained in the acellular matrix exists in the form of fibers, which is beneficial to cell adhesion, proliferation and differentiation, can promote tissue regeneration and repair, and is rich in fibronectin, which plays an adhesive role between cells and between cells and the matrix, and plays an important role in angiogenesis and regulating information transmission between cells and the matrix. In recent years, it has been widely studied and applied in the important repair of various tissues and organs. Research shows that the acellular matrix biomaterial has a guiding effect on osteocytes and has good biocompatibility.

[0039] Preferably, the structure-bionic bone repair material is obtained by in-situ pretreatment with a water-soluble calcium salt-fluoride on the ACTM template for 30-60 min, then continuing to add phosphate for in-situ mineralization growth for 19-24 h, freeze-drying, immersing in a 0.1-2 mol / L cross-linking agent aqueous solution for cross-linking, and then secondary freeze-drying after washing with distilled water.

[0040] The cross-linking agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) or glutaraldehyde.

[0041] The second aspect of the present invention provides the application of a structure-bionic bone repair material in dental repair materials, jaw repair materials, spinal repair materials, joint repair materials, and pelvic repair materials. Beneficial effects

[0042] (1) The bonding of the acellular matrix ACTM template and hydroxyapatite at the molecular level forms a composite material, which bionically simulates the structure and composition of natural bone tissue, is beneficial for human cells and macromolecules to recognize it, and improves the biological activity of the material after implantation in the body. The present invention controls the pore size distribution in the bone repair material, especially the proportion of pores with smaller pore sizes, so as to control the behavior of induced generation of osteoid tissue on the basis of the original defect during bone healing, so that the final matching of the osteogenic part structure is higher.

[0043] (2) Compared with other allogeneic bone or xenogeneic bone (demineralized bone matrix DBM) materials, the structure-bionic bone repair material obtained by the present invention is not easy to cause an immune response, has high biocompatibility after implantation in the body, and has excellent bone regeneration activity.

[0044] (3) It has high liquid hygroscopicity, can better adsorb endogenous growth factors, and improves osteogenic activity.

[0045] (4) The antibacterial effect of the material is improved, which further promotes bone healing, and is not easy to appear cracks, fissures and discoloration, and has high mechanical strength, overcoming the problem of bone brittleness caused by the introduction of fluoride.

[0046] (5) It has good biological properties of osteoblast binding and ingrowth effects, and mechanical properties to achieve self-support in a wet environment. Description of the Drawings

[0047] Figure 1 It is a bone repair material with structure bionics obtained in Example 1.

[0048] Figure 2 XRD spectrum of the bone repair material with structure bionics obtained in Example 1.

[0049] Figure 3 Infrared spectrum of the bone repair material with structure bionics obtained in Example 1. Specific Embodiments

[0050] Example 1

[0051] This example provides a bone repair material with structure bionics, such as Figure 1 , after adding water-soluble calcium salt - fluoride on the ACTM template and performing in-situ pretreatment for 60 min at 37 °C and pH = 11.4 (adjusted by ammonia water), continue to add phosphate and perform in-situ mineralization growth for 22 h in a 37 °C environment, then freeze-dry, immerse in a 1.5 mol / L cross-linking agent (EDC) aqueous solution for cross-linking for 24 h, and obtain it after washing with distilled water and secondary freeze-drying.

[0052] The volume-mass ratio of the ACTM template to the water-soluble calcium salt - fluoride is 30 mL: 2.6 g.

[0053] The water-soluble calcium salt - fluoride is composed of a water-soluble calcium salt and a water-soluble fluoride. In the water-soluble calcium salt - fluoride, the molar mass ratio of the water-soluble calcium salt to the water-soluble fluoride is 100:15.

[0054] The mass ratio of the water-soluble calcium salt - fluoride to the phosphate is 2.25:1.

[0055] The water-soluble calcium salt is calcium acetate, the water-soluble fluoride is sodium fluoride, and the phosphate is diammonium hydrogen phosphate.

[0056] The ACTM template is a decellularized matrix slurry, which is prepared by mixing a decellularized matrix (derived from porcine small intestinal submucosa) and an acidic pepsin aqueous solution (purchased from Qingdao Jieshikang, which is a 0.4% pepsin aqueous solution). The initial feeding concentration of the decellularized matrix in the decellularized matrix slurry is 0.02 g / ml.

[0057] The obtaining process of the decellularized matrix refers to the patent content recorded in the patent No. CN106075583B.

[0058] Example 2

[0059] This example provides a structure - bionic bone repair material. Different from Example 1, after adding water - soluble calcium salt - fluoride to the ACTM template and performing in - situ pretreatment at 37 °C and pH = 10.6 (adjusted with ammonia water) for 40 min, phosphate is continuously added, and after in - situ mineralization growth at 37 °C for 24 h, it is freeze - dried, immersed in a 1 mol / L cross - linker (EDC) aqueous solution for cross - linking for 24 h, and then washed with distilled water and freeze - dried again to obtain it.

[0060] The volume - mass ratio of the ACTM template to the water - soluble calcium salt - fluoride is 30 mL:1.9 g. The molar mass ratio of the water - soluble calcium salt to the water - soluble fluoride is 100:39.

[0061] Example 3

[0062] This example provides a structure - bionic bone repair material. Different from Example 1, after adding water - soluble calcium salt - fluoride to the ACTM template and performing in - situ pretreatment at 37 °C and pH = 11 (adjusted with ammonia water) for 60 min, phosphate is continuously added, and after in - situ mineralization growth at 37 °C for 21 h, it is freeze - dried, immersed in a 0.8 mol / L cross - linker (EDC) aqueous solution for cross - linking for 24 h, and then washed with distilled water and freeze - dried again to obtain it.

[0063] The volume - mass ratio of the ACTM template to the water - soluble calcium salt - fluoride is 40 mL:4.1 g.

[0064] The mass ratio of the water - soluble calcium salt - fluoride to the phosphate is 2.36:1.

[0065] Comparative Example 1

[0066] This example provides a structure - bionic bone repair material. Different from Example 1, after adding water - soluble calcium salt - fluoride to the ACTM template and performing in - situ pretreatment at 39 °C and pH = 9 (adjusted with ammonia water) for 50 min, phosphate is continuously added, and after in - situ mineralization growth at 37 °C for 24 h, it is freeze - dried, immersed in a 1 mol / L cross - linker (EDC) aqueous solution for cross - linking for 24 h, and then washed with distilled water and freeze - dried again to obtain it.

[0067] Comparative Example 2

[0068] This example provides a structure - bionic bone repair material. Different from Example 1, after adding water - soluble calcium salt - fluoride to the ACTM template and performing in - situ pretreatment at 25 °C and pH = 11 (adjusted with ammonia water) for 60 min, phosphate is continuously added, and after in - situ mineralization growth at 25 °C for 24 h, it is freeze - dried, immersed in a 1 mol / L cross - linker (EDC) aqueous solution for cross - linking for 24 h, and then washed with distilled water and freeze - dried again to obtain it.

[0069] Comparative Example 3

[0070] This example provides a structurally bionic bone repair material. Different from Example 1, the volume-mass ratio of the ACTM template to the water-soluble calcium salt-fluoride is 30 mL: 1.3 g. In the water-soluble calcium salt-fluoride, the molar mass ratio of the water-soluble calcium salt to the water-soluble fluoride is 100:8.

[0071] The mass ratio of the water-soluble calcium salt-fluoride to the phosphate is 2.12:1.

[0072] Comparative Example 4

[0073] This example provides a structurally bionic bone repair material. Different from Example 1, the volume-mass ratio of the ACTM template to the water-soluble calcium salt-fluoride is 35 mL: 3.2 g. In the water-soluble calcium salt-fluoride, the molar mass ratio of the water-soluble calcium salt to the water-soluble fluoride is 100:9.

[0074] The mass ratio of the water-soluble calcium salt-fluoride to the phosphate is 1.73:1.

[0075] Comparative Example 5

[0076] This example provides a structurally bionic bone repair material. Different from Example 3, the volume-mass ratio of the ACTM template to the water-soluble calcium salt-fluoride is 40 mL: 5.3 g. In the water-soluble calcium salt-fluoride, the molar mass ratio of the water-soluble calcium salt to the water-soluble fluoride is 100:20.

[0077] The mass ratio of the water-soluble calcium salt-fluoride to the phosphate is 2.79:1.

[0078] Comparative Example 6

[0079] This example provides a structurally bionic bone repair material. Different from Example 1, after adding the water-soluble calcium salt-fluoride to the ACTM template for in-situ pretreatment at 37 °C and pH = 11.4 (adjusted with ammonia water) for 60 min, phosphate is continuously added, and in-situ mineralization growth is carried out in a 37 °C environment for 22 h, followed by washing with distilled water and freeze-drying to obtain.

[0080] It was found that the uncrosslinked sample obtained in this example had a loose macroscopic structure and was not easy to form when observed with the naked eye.

[0081] Performance Test

[0082] 1. Porosity, pore size distribution test, and material bulk density test: The porosity of the structure-bionic bone repair materials obtained in Examples 1-3 and Comparative Examples 1-5 was tested using the drainage method, and the results are shown in Table 1. The pore size distribution of the materials was tested using a V-Sorb X800(DM) dual-module multifunctional specific surface and pore size analyzer, and the results are shown in Table 1; the bulk density of the materials was tested in accordance with GB / T-1966, and the results are shown in Table 1.

[0083] Table 1

[0084]

[0085] The bulk density can reflect the compactness of the material. A high bulk density indicates that the arrangement between molecules is more compact, and its mechanical properties will be better, but its flexibility will also decrease. For bone repair materials, if the bulk density is too high, it is not easy for tissue cells to grow in; if the bulk density is too low, its mechanical support performance is poor.

[0086] 2. XRD characterization: The structure-bionic bone repair material obtained in Example 1 was subjected to X-ray diffraction testing, and the results are as Figure 2 , as can be seen from the figure, there are two diffraction peaks. There is a first characteristic single peak at 2θ = 25 - 27° (consistent with the characteristic peak of the fluorapatite standard), and a second characteristic single peak at 2θ = 31 - 33° (consistent with the characteristic peak of the hydroxyapatite standard). In addition, according to the patent record of Patent No. JP5553396B2, the peak at 2θ = 31 - 35° is completely separated into four peaks, indicating that the crystal of hydroxyapatite has high crystallinity. The lower the peak overlap degree here, the lower the crystallinity and the more it tends to be amorphous. Hydroxyapatite with lower crystallinity helps to improve the osteogenic efficiency, and at the same time its surface is rougher, which is beneficial to cell adhesion, but there may be a problem that the degradation is too fast, resulting in poor final bone repair effect. In the present invention, while ensuring the osteogenic efficiency, there is no phenomenon of poor osteogenic repair effect.

[0087] 3. Infrared test: The structure-bionic bone repair material obtained in Example 1 was subjected to infrared testing, as Figure 3 , the upper line graph in the figure represents the infrared spectrum of the structure-bionic bone repair material obtained in Example 1, and the lower line graph in the figure represents the standard infrared spectrum of small intestinal submucosa acellular matrix (SIS). As can be seen from the figure, the intensity of the peak belonging to the amide bond in the sample spectrum of Example 1 is weakening, indicating that chemical bonding occurs between hydroxyapatite and SIS, and hydroxyapatite grows in situ on SIS rather than physical compounding.

[0088] 4. Hydrophilicity test: The surface hydrophilicity of the materials obtained in Examples 1-3 and Comparative Examples 1-6 was determined by the dye adsorption method using the hydrophilic dye Nile blue (NB). The results showed that the hydrophilicity of the materials in Examples 1-3 was significantly greater than that of the samples in Comparative Examples 1-5. Good hydrophilicity indicates that the diffusion and leakage of the materials in a wet environment may be reduced.

[0089] 5. Wet-state self-supporting performance test: The bone repair materials obtained in Examples 1-3 and Comparative Examples 1-5 were left standing at 37 °C and saturated humidity. After 6 h, they were compressed to 50% in height under a universal testing machine at a compression rate of 15 mm / min for 100 cycles, and their compressive strengths when compressed to 50% were tested. The higher the compressive strength, the better the wet-state self-supporting performance. The results are shown in Table 2.

[0090] Table 2

[0091] Example Compressive strength (MPa) Example 1 16.2 Example 2 14.1 Example 3 16.8 Comparative Example 1 6.9 Comparative Example 2 5.1 Comparative Example 3 4.5 Comparative Example 4 2.1 Comparative Example 5 2.7

[0092] 6. Antibacterial performance: The antibacterial performance of the bone repair materials obtained in Examples 1-3 and Comparative Examples 1-5 was tested by the inhibition zone method using Staphylococcus aureus and Streptococcus mutans (Streptococcus mutans is one of the main components of dental plaque and also the main pathogenic bacterium of dental caries). 70 μL of bacterial suspension (1×10 8 CFU / mL) was spread on an LB agar plate, and sterile gauze and the bone repair materials obtained in Examples 1-3 and Comparative Examples 1-5 were placed on the agar surface. After incubation at 37 °C for 24 h, the diameter of the inhibition zone was measured. The larger the diameter of the inhibition zone, the higher the antibacterial performance. The results are shown in Table 3. Then, incubation was continued for 7 days to observe whether there were cracks in the bone repair materials and whether the color turned yellow. The results are shown in Table 4.

[0093] Table 3

[0094] Example Inhibitory zone diameter of Staphylococcus aureus (mm) Inhibitory zone diameter of Streptococcus mutans (mm) Example 1 19 8 Example 2 21 7 Example 3 17 7 Comparative Example 1 7 4 Comparative Example 2 5 4 Comparative Example 3 9 1 Comparative Example 4 5 2 Comparative Example 5 8 3

[0095] Table 4

[0096] Example Appearance of the material after 7-day continuous incubation after antibacterial performance test Example 1 No cracks appeared and the color did not turn yellow Example 2 No cracks appeared and the color did not turn yellow Example 3 No cracks appeared and the color did not turn yellow Comparative Example 1 No cracks appeared and the color turned yellow Comparative Example 2 Cracks appeared and the color did not turn yellow Comparative Example 3 No cracks appeared and the color did not turn yellow Comparative Example 4 Cracks appeared and the color turned yellow Comparative Example 5 Cracks appeared and the color turned yellow

Claims

1. A structural bionic bone repair material, wherein the structural bionic bone repair material is a porous material, characterized in that: The porosity of the structural bionic bone repair material is 83-95%, and the pore size distribution is 0-400um, of which the pore size of 50-175um accounts for 70-95%; the median pore size of the structural bionic bone repair material is 70-100um; The structural bionic bone repair material is obtained by adding water-soluble calcium salt-fluoride to the ACTM template for in-situ pretreatment, then adding phosphate for in-situ mineralization growth, freeze-drying, cross-linking, washing, and then freeze-drying again; The volume mass ratio of the ACTM template and the water-soluble calcium salt-fluoride is (23-40) mL: (1.8-6.4) g; The mass ratio of the water-soluble calcium salt-fluoride and the phosphate is (2.12-2.43):1; The ACTM template is a decellularized matrix slurry, which is prepared by mixing a decellularized matrix and an acidic protease aqueous solution; the decellularized matrix slurry is prepared by mixing a decellularized matrix and an acidic protease aqueous solution, wherein the initial concentration of the decellularized matrix in the decellularized matrix slurry is 0.01-0.2 g / ml; The in-situ pretreatment is carried out in an atmosphere of pH=10.6-11.4; the reaction temperature of the in-situ pretreatment and in-situ mineralization is 35-39°C.

2. The structural bionic bone repair material according to claim 1, characterized in that: The structural bionic bone repair material is obtained by adding water-soluble calcium and water-soluble fluorine to the ACTM template for in-situ pretreatment for 30-60 minutes, adding phosphate to carry out in-situ mineralization growth for 19-24 hours, freeze-drying, cross-linking, washing and then freeze-drying again.

3. An application of the structural bionic bone repair material according to claim 1 in tooth repair materials, jaw repair materials, spine repair materials, joint repair materials, and pelvic repair materials.

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