Tantalum nano-material, preparation method thereof and application of tantalum nano-material in bone defect repair

Abstract

The invention relates to a tantalum nano material, a preparation method thereof and application of the tantalum nano material in bone defect repair. Specifically, the invention relates to a tantalum nano material, and the tantalum nano material comprises a hollow nanosphere skeleton and a Ta-N4 monatomic coordination structure formed on the surface of the hollow nanosphere skeleton. The tantalum nano material can promote repair of bone defects, has good biocompatibility on both the cell level and the animal level, and has good commercial value and social benefits.

Description

Technical Field

[0001] This invention relates to the field of nanomaterials technology, specifically to a tantalum nanomaterial, its preparation method, and its application in bone defect repair. Background Technology

[0002] Currently, research on bone defect repair mainly focuses on materials for bone defects. As the gold standard for bone grafting, autologous bone is the best choice, using the patient's own bone as the graft material and transplanting it to the bone defect site to promote healing. Autologous bone contains the patient's own cells and growth factors, thus reducing rejection reactions. However, autologous bone grafting requires creating a second surgical site, causing donor site trauma, and is complex and time-consuming. Furthermore, if the bone defect is too large, the donor site may be limited, failing to provide sufficient bone, thus greatly restricting its clinical application. Allogeneic bone has more sources than autologous bone, using bone from other individuals as the graft material, providing a scaffold for new bone formation. However, its disadvantages include the potential for host immune rejection and the risk of infectious diseases. Synthetic bone uses artificially synthesized materials such as tricalcium phosphate, calcium sulfate, and hydroxyapatite to fill bone defects. These materials generally have good biocompatibility and certain osteogenic activity, allowing for better synthesis of bone graft substitutes that closely resemble the morphology of the defective bone. However, for larger bone defects, there may be issues with insufficient osteogenic activity and inadequate mechanical strength. In recent years, the rapid development of osteoinductive materials has brought new hope to bone defect repair. This method typically involves using specific culture media under laboratory conditions to induce autologous or allogeneic osteoprogenitor cells to differentiate into osteogenic cells. These cells are then implanted into the bone defect site, where they differentiate and participate in bone remodeling, ultimately forming new bone to repair the defect. This method allows for precise control of key factors such as growth factor concentration and cellular microenvironment during bone regeneration, achieving relatively satisfactory experimental results. Summary of the Invention

[0003] To address the problems and shortcomings of the existing technologies, such as cumbersome procedures, the present invention aims to provide a tantalum nanomaterial, its preparation method, and its application in bone defect repair.

[0004] The tantalum nanomaterials of this invention exhibit good biocompatibility at both the cellular and animal levels, and can promote the repair of bone defects, thus possessing significant commercial value and social benefits.

[0005] To achieve the purpose of this invention, this invention provides a tantalum nanomaterial comprising a hollow nanosphere framework and a Ta-N4 single-atom coordination structure formed on its surface.

[0006] In one embodiment, the hollow nanosphere framework is a nitrogen-doped carbon spherical framework with a hollow structure.

[0007] Optionally, the hollow nanosphere framework is a hollow spherical framework polymerized from nitrogen-containing heterocyclic compound monomers; preferably, the nitrogen-containing heterocyclic compound monomers are C3-C 10 A nitrogen-containing heterocyclic compound monomer, wherein the number of N atoms is an integer in the range of 1-6; further, the nitrogen-containing heterocyclic compound monomer is pyrrole, imidazole, thiazole, oxazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, or piperazine.

[0008] In one embodiment, the hollow nanosphere framework is a hollow spherical framework formed from polypyrrole.

[0009] In one embodiment, the Ta-N4 single-atom coordination structure is a coordination between an exogenous tantalum atom and a N atom on the surface of the hollow spherical structure.

[0010] In one embodiment, the Ta-N4 single-atom coordination structure is in the shape of a square pyramid.

[0011] In one embodiment, the diameter of the hollow spherical structure is 100~500nm, preferably 200~400nm.

[0012] In one embodiment, the tantalum nanomaterial has sites that can adsorb oxygen anions.

[0013] This invention also provides a method for preparing tantalum nanomaterials, comprising the following steps: In the presence of an inert gas in a solvent, nitrogen-source nanospheres with a hollow structure react with tantalum salts to form tantalum nanomaterials.

[0014] In one embodiment, the nitrogen source nanospheres are nanospheres polymerized from nitrogen-containing heterocyclic compound monomers or polypyrrole nanospheres.

[0015] In one embodiment, the nitrogen source nanospheres have a particle size of 100-500 nm, preferably 200-400 nm.

[0016] In one embodiment, the tantalum salt is a tantalum halide.

[0017] Furthermore, the tantalum salt is tantalum chloride.

[0018] The inert gas is a conventional inert gas in the art, such as argon.

[0019] In one embodiment, the reaction needs to be carried out at 600–900°C, preferably 750–900°C, for example 800°C.

[0020] In one embodiment, the reaction time is 0.5 to 3 hours, preferably 1 to 3 hours, for example, 1 hour or 2 hours.

[0021] In one embodiment, the solvent is water.

[0022] In one embodiment, the molar ratio of N atoms in the nitrogen source nanospheres to tantalum atoms in the tantalum salt is (2~5):1, preferably 4:1.

[0023] In one embodiment, the nitrogen source nanospheres are prepared by the following method: In a dispersed system, using decomposable nanospheres as the core, a chemical oxidation method is used to form a polypyrrole shell on the surface of the nanosphere core with pyrrole monomers, which then reacts with acid to obtain hollow polypyrrole nanospheres.

[0024] The decomposable nanospheres are conventional acid-decomposable nanospheres in the art, preferably organosilicon nanospheres, more preferably organosilicon nanospheres, such as nanospheres formed from vinyltrimethoxysilane (o-SiO2).

[0025] In one embodiment, the particle size of the decomposable nanospheres is 100-500 nm, for example, 200-400 nm.

[0026] In one particular scheme, the chemical oxidation of polypyrrole involves the reaction of sodium dodecyl sulfate and ammonium persulfate.

[0027] Optionally, the molar ratio of the pyrrole monomer, sodium dodecyl sulfate and ammonium persulfate is (24-27):1:(17-20).

[0028] In one particular scheme, the acid is an inorganic acid.

[0029] Optionally, the concentration of the acid is 5% to 10%.

[0030] Furthermore, the acid is HF, HCl or H2SO4, preferably HF.

[0031] In one embodiment, the chemical oxidation of the polypyrrole involves a reaction time of 8-15 hours, for example, 12 hours.

[0032] In one embodiment, the reaction is based on the complete erosion of o-SiO2 nanospheres by acid. Preferably, the reaction time after adding acid is 30-50 h, for example, 35 h, 36 h, 37 h, 38 h, 39 h, 40 h or 45 h.

[0033] In one embodiment, the biodegradable nanospheres are prepared by the following method: In solution, alkali is mixed with organosilicon and reacted to obtain organosilicon nanospheres.

[0034] In one embodiment, the solution is an aqueous solution, preferably deionized water.

[0035] In one particular scheme, the base is an inorganic base.

[0036] Furthermore, the alkali is NaOH, KOH, or NH4OH, preferably NH4OH.

[0037] In one embodiment, the alkali exists in the system in the form of a solution; preferably, it is an aqueous solution of the alkali; more preferably, it is an aqueous solution of ammonium hydroxide.

[0038] Furthermore, the concentration of the aqueous solution of the alkali is 10-50 wt%, for example 20 wt%, 30 wt.% or 40 wt%.

[0039] In one embodiment, the organosilicon is an organosilane, preferably vinyltrimethoxysilane.

[0040] In one embodiment, the volume-to-mass ratio of the solution to the organosilicon is 30-80 mL / g, preferably 40 mL / g, 50 mL / g, 60 mL / g, or 70 mL / g, for example, 50 mL / g.

[0041] In one embodiment, the molar ratio of the alkali to the organosilicon is (1~5):1, preferably (2~3):1.

[0042] In one embodiment, the reaction temperature is 15-30°C, for example, 25°C.

[0043] In one particular scheme, the reaction time is 4 to 8 hours, for example, 6 hours.

[0044] The present invention also provides a tantalum nanomaterial prepared by the preparation method described above.

[0045] The present invention also provides a repair material comprising tantalum nanomaterials as described above or repair materials prepared by the preparation method as described above, and pharmaceutical excipients.

[0046] In one embodiment, the pharmaceutical excipient is gelatin sponge.

[0047] The present invention also provides the application of the tantalum nanomaterial as described above, the repair material prepared by the preparation method as described above, or the repair material as described above in bone defect repair.

[0048] The beneficial effects of the present invention are as follows: (1) In the present invention, the structure identification determines that tantalum exists in the form of a single atomic site in the tantalum nanomaterial, forming a four-coordinate structure with nitrogen. Its surface has active sites modified by oxygen adsorption, forming a hybrid coordination structure between tantalum nitride and tantalum oxide. This specific square pyramid-shaped TaN4 geometry structure enables it to function stably and efficiently in vivo; (2) In the present invention, the activity test of tantalum nanomaterial shows that it has good biocompatibility, ensuring that it can exist safely in vivo, providing a basic condition for subsequent osteogenic formation. Furthermore, at the cellular level, its osteogenic differentiation effect is verified to be significant, and it has excellent ability to promote bone marrow mesenchymal stem cell osteogenic formation; (3) In the present invention, the in vivo activity test of tantalum nanomaterial shows that after implantation into the skull defect area of ​​mice, it can efficiently generate new bone-like tissue, indicating that tantalum nanomaterial has significant in vivo osteogenic potential; (4) The preparation method of the present invention is simple and efficient, does not require complex post-processing, has low production cost, and has certain commercial value. Attached Figure Description

[0049] One or more embodiments are illustrated by way of example with reference to the accompanying drawings, and these illustrative examples are not intended to limit the embodiments. The term "illustrative" as used herein means "serving as an example, embodiment, or illustration." Any embodiment illustrated herein as "illustrative" is not necessarily to be construed as superior to or better than other embodiments.

[0050] Figure 1 Figure 1 shows the structural characterization of tantalum nanomaterials in Example 1. Figure a is a SEM image of tantalum nanomaterials with a scale bar of 200 nm, Figure b is a SEM image of tantalum nanomaterials with a scale bar of 5 nm, Figure c is the energy dispersive spectrum (EDS) of tantalum nanomaterials, Figure d is the energy dispersive spectrum (EDS) of carbon nanomaterials, where χμ(E) represents the absorption coefficient in the spectrum, Figure e is the energy dispersive spectrum (EDS) of carbon nanomaterials, where |χ(R)| represents the FT of EXAFS, and Figure f is the FT-EXAFS spectrum fitting diagram of Ta-ALP.

[0051] Figure 2 The figures shown are characterization diagrams of the coordination structure of tantalum nanomaterials in Example 1. Figure a is the 4f XPS spectrum of each sample, figure b is the k2 weighted EXAFS spectrum, and figures c to e are the wavelet transform spectra of tantalum nanomaterials, Ta3N5 and Ta2O5 samples.

[0052] Figure 3Figure 1 shows the experimental results of tantalum nanomaterials promoting osteogenic differentiation of bone marrow mesenchymal stem cells in Example 2. Figure 2a shows the alkaline phosphatase (ALP) staining and activity detection results of bone marrow mesenchymal stem cells after 7 days of different treatments; Figure 3b shows the ALP activity results of tantalum nanomaterials in Example 2; Figure 4c shows the alkaline phosphatase staining and activity detection results of bone marrow mesenchymal stem cells after 14 days of different treatments; Figure 5d shows the alizarin red staining quantitative analysis results of bone marrow mesenchymal stem cells after 14 days of different treatments; Figures 6-7g are schematic diagrams of qRT-PCR results of the relative expression levels of RUNX2 mRNA, OCN mRNA, and OSX mRNA of tantalum nanomaterials in Example 2. p < 0.01; In the figure, the PBS group is the blank control, the treatment of the C group is 10 μg / ml hollow carbon nanospheres without Ta-ALP loading, the treatment of the Ta group is 10 μg / ml tantalum powder, and the treatment of the Ta-ALP group is 10 μg / ml Ta-ALP; PM represents ordinary proliferation medium (DMEM + 10% FBS + 1% penicillin and antibiotics), and OM represents osteogenic induction medium (DMEM + 10% FBS + 1% penicillin and antibiotics + 100 nM dexamethasone + 0.2 mM ascorbic acid + 10 mM sodium β-glycerophosphate).

[0053] Figure 4 Figure 3 shows the experimental results of tantalum nanomaterials promoting the repair of skull defects in mice. Figure a is a schematic diagram of the operation of carbon nanomaterials in Example 3 for repairing skull injuries in mice; Figure b is a top-down panoramic view (left) and coronal cross-section of a Micro-CT image; Figures c-e show the effects of tantalum nanomaterials in Example 3 on bone volume / total volume (%), bone density (g / cm3), and trabecular bone number (1 / mm) in repairing bone injuries in mice; Figure f shows the histological staining results of the coronal cross-section of the mouse skull 4 weeks after implantation of different materials. p < 0.01; In the figure, the treatment process of the PBS group was to immerse the gelatin sponge in the PBS group as a blank control group, the treatment process of the C group was to immerse the gelatin sponge in a 10 μg / ml solution of hollow carbon nanospheres without Ta-ALP, the treatment process of the Ta group was to immerse the gelatin sponge in 10 μg / ml tantalum powder, and the treatment process of the Ta-ALP group was to immerse the gelatin sponge in 10 μg / ml Ta-ALP. Detailed Implementation

[0054] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprising of," etc., will be understood to include the stated elements or components, and does not exclude other elements or other components.

[0055] Furthermore, to better illustrate the present invention, numerous specific details are provided in the following detailed embodiments. Those skilled in the art should understand that the present invention can be practiced without certain specific details. In some embodiments, materials, elements, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0056] The term "pharmaceutical excipients" refers to the excipients and additives used in the production of pharmaceuticals and the preparation of prescriptions. They are all substances contained in pharmaceutical preparations, excluding the active ingredient.

[0057] Unless otherwise specified, all raw materials used in this invention are commercially available products.

[0058] Example 1: Preparation of tantalum nanomaterials S1: Preparation of Organosilicon Nanospheres To prepare organosilicon (o-SiO2) nanospheres as hard templates, 1 mL of ammonium hydroxide solution (approximately 30 wt%, Sigma-Aldrich) was added to 50 mL of water, followed by the addition of 1 mL of vinyltrimethoxysilane (98%, Sigma-Aldrich). After reacting at 25°C for 6 hours, the mixture was centrifuged, washed with water, dried, and the o-SiO2 nanospheres were collected.

[0059] S2: Preparation of polypyrrole nanospheres The prepared o-SiO2 nanospheres were used as the core for polypyrrole (PPy) shell deposition and dispersed in 60 mL of H2O. Then, 75 μL of pyrrole monomer (98%, Sigma-Aldrich), 12 mg of sodium dodecyl sulfate (>99%, Alfa Aesar), and ammonium persulfate solution (180 mg dissolved in 5 mL of H2O, >98%, Sigma-Aldrich) were added to the suspension sequentially. After stirring for 12 hours, the centrifuged powder was immersed in 100 mL of hydrofluoric acid solution (10 wt.%, Aladdin) for 36 hours to remove the o-SiO2 cores, thereby forming hollow PPy nanospheres.

[0060] S3: Preparation of tantalum nanomaterials Hollow PPy nanospheres were mixed with a 20% aqueous solution of tantalum pentachloride (TaCl5, 99.8%, Sigma-Aldrich), and then heat-treated at 800°C for 1 hour in an argon atmosphere to further prepare tantalum nanomaterials (Ta-ALP).

[0061] The sample (tantalum nanomaterials prepared in Example 1) was characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray absorption fine structure spectroscopy (XAFS). The results are shown in the figure. Figure 1 .in, Figure 1 Figure a in the middle and Figure 1 Figures b in the image are SEM images of tantalum nanomaterials. Figure 1 The scale bar of figure a in the image is 200 nm. Figure 1 Figure b in the image has a scale bar of 5 nm, and it can be seen that the tantalum nanomaterials exhibit a distinct hollow spherical structure with a particle size of 200–400 nm. Figure 1 Figure c in the figure shows the energy dispersive spectroscopy (EDS) results of the tantalum nanomaterial, demonstrating the correspondence between the sample composition and structure. Figure 1 d in the diagram ~ Figure 1 Figure f in the figure shows the X-ray absorption fine structure spectrum of tantalum nanomaterials, where Ta SAzyme is the tantalum nanomaterial (Ta-ALP) prepared in Example 1 of this invention. Figure 1 In the d-plot, χμ(E) represents the absorption coefficient in the spectrum. Figure 1 The e-plot in the figure is the Fourier transform (FT) of the k³-weighted EXAFS spectrum, where |χ(R)| represents the FT of EXAFS. Figure 1 The f-figure in the figure shows the FT-EXAFS spectral fitting results of Ta-ALP, including the FT-EXAFS spectral fitting curves for both the real and imaginary parts. Figure 1 Figures d in Figure 1 to f in Figure 1 show that tantalum exists as a single atom in the tantalum nanomaterial and forms a four-coordinate structure with nitrogen. These characterization results demonstrate that the embodiments of this invention successfully prepared tantalum nanomaterials.

[0062] Meanwhile, the coordination structure in the tantalum nanomaterials was characterized, and the results are shown in [the table below]. Figure 2 . Figure 2 Figure a in the figure shows the 4f XPS spectra of each sample. Figure 2 Image b in the middle~ Figure 2 The e-plot in the figure is the Ta-K-side Fourier transform EXAFS spectrum of the sample, where, Figure 2 Figure b in the diagram shows the k2-weighted EXAFS spectrum. Figure 2 Figure c in the middle~ Figure 2Figure e shows the wavelet transform spectra of tantalum nanomaterials (corresponding to TaSAzyme in the figure), Ta3N5, and Ta2O5 samples. The above characterization shows that oxygen adsorption-modified active sites are formed on the surface of the tantalum nanomaterials, indicating that the tantalum nanomaterials of this invention possess a hybrid coordination structure intermediate between tantalum nitride and tantalum oxide.

[0063] Example 2: Study on the effect of tantalum nanomaterials on promoting osteogenic differentiation of bone marrow mesenchymal stem cells The toxicity of tantalum nanomaterials was determined by cell viability staining and CCK-8 assay. In this invention, the CCK-8 assay was performed using a commercially available CCK-8 test kit (purchased from Beyotime) and the procedure was followed according to the instructions. The results showed that the tantalum nanomaterials of this invention have good biocompatibility and can be used for subsequent osteogenic studies.

[0064] The effects of tantalum nanomaterials on osteogenic differentiation of bone marrow mesenchymal stem cells were detected by alkaline phosphatase staining, alizarin red staining, and qPCR experiments. The experimental method was as follows: bone marrow mesenchymal stem cells were cultured to the logarithmic growth phase in PM ordinary proliferation medium (DMEM + 10% FBS + 1% penicillin antibody) and OM osteogenic induction medium (DMEM + 10% FBS + 1% penicillin antibody + 100 nM dexamethasone + 0.2 mM ascorbic acid + 10 mM β-glycerophosphate sodium), respectively. Each group was divided into four groups for treatment. All experimental groups were diluted with PBS. The treatment methods were as follows: Group C used 10 μg / ml hollow carbon nanospheres without Ta-ALP loading (i.e., the hollow PPy nanospheres in step S2 of Example 1); Group Ta was treated with 10 μg / ml tantalum powder; and Group Ta-ALP was treated with 10 μg / ml tantalum nanomaterials prepared in Example 1. Cells were cultured at 37°C, with the culture medium changed every two days. Cells were harvested on days 7 and 14 for alkaline phosphatase staining. The results are as follows: Figure 3 As shown in e~3g, cells from day 7 were used to detect the comparative expression levels of RUNX2 mRNA, OCN mRNA, and OSX mRNA using qPCR (the primers used in the qPCR in this application were synthesized by a company commissioned by the inventor, and their primer sequences can be found in the literature Jin C, Shuai T, Tang Z. HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway. Stem Cell Res Ther. 2020 Oct 23;11(1):450), and the results are shown in Table 1 and Figure 3 As shown.

[0065] Table 1. Effects of tantalum nanomaterials on promoting osteogenic differentiation of bone marrow mesenchymal stem cells Group RUNX2 mRNA relative expression level OCN mRNA relative expression level OSX mRNA relative expression level PBS 1.0 1.0 1.0 C 0.95 1.1 0.9 Ta 1.3 1.4 1.1 Ta-ALP 3.4 4.2 8.2 ; Figure 3 Figure a in the middle and Figure 3 Figure b shows the results of alkaline phosphatase staining and activity detection of bone marrow mesenchymal stem cells after 7 days of different treatments, indicating that the ALP staining intensity and activity in the Ta-ALP group were significantly higher than those in other groups. Figure 3 Figure c in the middle and Figure 3 Figure d shows the results of alizarin red staining and quantitative analysis of bone marrow mesenchymal stem cells after 14 days of different treatments, indicating that calcium nodule formation was most significant in the Ta-ALP group. Figure 4 Figure e in the middle, Figure 4 f-graph and Figure 4 Figure g in the table shows the qRT-PCR results of osteogenic differentiation-related gene expression (RUNX2, an early marker of osteogenic differentiation), OCN (bone matrix protein), and OSX (osteoblast maturation marker) in bone marrow mesenchymal stem cells 7 days after different treatments. (Based on Table 1 and...) Figure 3 The records indicate that the expression of Ta-ALP-related genes is upregulated. The results of this embodiment demonstrate that Ta-ALP has a significant ability to promote osteogenic formation of bone marrow mesenchymal stem cells at the cellular level.

[0066] Example 3: Study on the effect of tantalum nanomaterials on promoting the repair of skull defects in mice Methods for establishing a mouse model of skull defects: Eight-week-old male C57BL / 6 mice were used to establish a skull defect model. All animal experiments were approved by the Animal Care and Use Committee of Peking University and performed in accordance with institutional animal experiment guidelines. Under general anesthesia, a circular defect area with a diameter of 4 mm was prepared in the parietal bone region of each mouse using a treble drill. Special care was taken to avoid damaging brain tissue during the operation. Different implant materials were filled into the right defect area, and the left defect area served as a blank control. After the implantation operation, the skin incision was sutured and the wound was disinfected. The mice were placed on a warming pad until they woke up. The formation of new bone tissue in the defect area was assessed at 4 and 8 weeks postoperatively. Eight weeks postoperatively, the animals were sacrificed and major organs such as the heart, liver, spleen, lungs, and kidneys were collected to evaluate the biosafety of the implant materials. The results are shown in Table 2. Figure 4 .

[0067] Table 2. Effects of tantalum nanomaterials on promoting the repair of skull defects in mice. ;

[0068] Figure 4Figure a in the figure shows the experimental procedure for studying the effect of tantalum nanomaterials on the repair of skull defects in mice. Gelatin sponges soaked in Ta-ALP solution were implanted into the skull defect sites of mice, and samples from the skull defect sites were collected. The bone regeneration effect was evaluated by micro-computed tomography (Micro-CT) and histological analysis. Figure 4 The treatment process for the PBS group was as follows: gelatin sponge was immersed in the PBS group as a blank control group. The treatment process for the C group was as follows: gelatin sponge was immersed in a 10 μg / ml solution of hollow carbon nanospheres without Ta-ALP loading. The treatment process for the Ta group was as follows: gelatin sponge was immersed in a 10 μg / ml solution of tantalum powder. The treatment process for the Ta-ALP group was as follows: gelatin sponge was immersed in a 10 μg / ml solution of Ta-ALP. The immersion time for each group was 30 min. 4W represents 4 weeks after the implantation surgery of the above different materials, and 8W represents 8 weeks after the implantation surgery of the above different materials. Figure 4 Figure b in the image shows a top-view panoramic view (left) and a coronal cross-sectional view (right) of the Micro-CT image. Figure 4 Figure c in the middle~ Figure 4 Figure e in the figure shows the quantitative analysis results of different detection indicators of bone volume / tissue volume ratio, bone density, and number of trabeculae by Micro-CT. Figure 4 Figure f in the figure shows the histological staining results of the coronal cross-section of the mouse skull 4 weeks after implantation with different materials. Two staining methods were used: hematoxylin-eosin (HE) staining and Masson's trichrome staining. The results of this example show that the implantation of tantalum nanomaterials into the defect area of ​​the mouse skull resulted in the most newly formed osteoid tissue, indicating that tantalum nanomaterials have significant in vivo osteogenic potential.

[0069] As can be seen from the above data, the tantalum nanomaterials prepared in the embodiments of the present invention have good biocompatibility and a significant ability to promote osteogenic formation.

[0070] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A tantalum nanomaterial comprising a hollow nanosphere framework and a Ta-N4 single-atom coordination structure formed on its surface.

2. The tantalum nanomaterial according to claim 1, characterized in that, The hollow nanosphere framework is selected from one or more of the following: (1) A nitrogen-doped carbon spherical framework with a hollow structure; (2) Hollow spherical framework formed by the polymerization of nitrogen-containing heterocyclic compound monomers; (3) Hollow spherical skeleton formed by polypyrrole.

3. The tantalum nanomaterial according to claim 1 or 2, characterized in that, It satisfies one or more of the following conditions: (1) The Ta-N4 single-atom coordination structure is formed by the coordination of exogenous tantalum atoms with N atoms on the surface of the hollow nanosphere framework; (2) The Ta-N4 single-atom coordination structure is a square pyramid shape; (3) The diameter of the hollow spherical structure is 100~500nm or 200~400nm; (4) The tantalum nanomaterial has sites that can adsorb oxygen anions.

4. A method for preparing tantalum nanomaterials, comprising the following steps: In the presence of an inert gas and in a solvent, nitrogen-source nanospheres with a hollow structure react with tantalum salts to form tantalum nanomaterials.

5. The preparation method according to claim 4, characterized in that, It satisfies one or more of the following conditions: (1) The nitrogen source nanospheres are nanospheres polymerized from nitrogen-containing heterocyclic compound monomers or polypyrrole nanospheres; (2) The particle size of the nitrogen source nanospheres is 100~500nm, or 200~400nm; (3) The tantalum salt is tantalum halide or tantalum pentachloride; (4) The reaction needs to be carried out at 600–900°C or 750–900°C; (5) The reaction time is 0.5~3h or 1~3h; (6) The solvent is water; (7) The molar ratio of N atoms in the nitrogen source nanospheres to tantalum atoms in the tantalum salt is (2~5):1 or 4:

1.

6. The preparation method according to claim 4, characterized in that, The nitrogen source nanospheres were prepared by the following method: In a dispersed system, using decomposable nanospheres as the core, a chemical oxidation method is used to form a polypyrrole shell on the surface of the nanosphere core with pyrrole monomers, which then reacts with acid to obtain hollow polypyrrole nanospheres.

7. The preparation method according to claim 6, characterized in that, It satisfies one or more of the following conditions: (1) The decomposable nanosphere core is an organosilicon nanosphere, an organosilicon nanosphere, or a nanosphere formed of vinyltrimethoxysilane; (2) The particle size of the decomposable nanosphere core is 100-500 nm, or 200-400 nm; (3) In the chemical oxidation method of polypyrrole, sodium dodecyl sulfate and ammonium persulfate are used, wherein the molar ratio of pyrrole monomer, sodium dodecyl sulfate and ammonium persulfate is (24-27):1:(17-20); (4) The acid is an inorganic acid or hydrofluoric acid, wherein the concentration of the acid is 5% to 10%; (5) In the chemical oxidation method of polypyrrole, the reaction time is 8-15h, or 12h; (6) The reaction time after adding acid is 30-50h, or 35h, 36h, 37h, 38h, 39h, 40h or 45h.

8. The preparation method according to claim 7, characterized in that, The biodegradable nanosphere core is prepared by the following method: In solution, an alkali is mixed with organosilicon and reacted to obtain organosilicon nanospheres that satisfy one or more of the following conditions: (1) The solution is an aqueous solution, or deionized water; (2) The alkali is an inorganic alkali or ammonium hydroxide; (3) The organosilicon is an organosilane or a vinyltrimethoxysilane; (4) The volume-to-mass ratio of the solution to the organosilicon is 30~80mL / g, or 40mL / g, 50mL / g, 60mL / g or 70mL / g; (5) The molar ratio of the alkali to the organosilicon is (1~5):1, or (2~3):1; (6) The reaction temperature is 15~30°C, or 25°C; (7) The reaction time is 4~8h.

9. A repair material comprising tantalum nanomaterials as described in any one of claims 1-3 or tantalum nanomaterials prepared by the preparation method as described in any one of claims 4 to 8, and pharmaceutical excipients.

10. The use of a tantalum nanomaterial as described in any one of claims 1-3, a tantalum nanomaterial prepared by the preparation method according to any one of claims 4 to 8, or a repair material as described in claim 9 in the preparation of bone defect repair products.

Images