Cu2+ / CO3 < 2-> double-doped hydroxyapatite nanowire and preparation method thereof

Abstract

The invention relates to the technical field of biological materials, in particular to a Cu < 2 + > / CO3 < 2-> double-doped hydroxyapatite nanowire and a preparation method thereof. According to the preparation method, Cu < 2 + > and CO3 < 2-> are successfully doped into hydroxyapatite by controlling the dosage of oleic acid, oleylamine and ethanol, controlling the amount of substances of calcium element in calcium chloride, copper element in copper nitrate, phosphorus element in disodium hydrogen phosphate and carbon element in sodium carbonate, and the like, so that the Cu < 2 + > / CO3 < 2-> double-doped hydroxyapatite nanowire is successfully prepared. The Cu < 2 + > / CO3 < 2-> double-doped hydroxyapatite nanowire is of a nanowire-shaped structure, is uniform and controllable in morphology and good in dispersity, has good cytocompatibility and excellent antibacterial performance, and also has excellent angiogenesis promoting capacity and cell migration promoting capacity; the method is simple to operate, rich in preparation raw material source, low in cost, environment-friendly in process and easy to amplify, and has wide application prospect and market value.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomaterials, and particularly relates to a Cu 2+ / CO3 2- doped hydroxyapatite nanowire and a preparation method thereof. BACKGROUND

[0002] Hydroxyapatite (HAp) has a broad application prospect in the fields of bone tissue engineering and dental repair due to its excellent bioactivity and bone conduction as the main component of human hard tissue. However, the pure HAp has a single function (such as lacking antibacterial performance), which limits its application in complex clinical scenarios.

[0003] In recent years, in terms of morphology, the nanoscale design of material morphology provides a new idea for the functionalization of HAp: the nanowire has a one-dimensional slender structure and rich surface active sites, which provides an ideal platform for ion doping, surface modification and the like; compared with nanoparticles, the nanowire has a controllable length-diameter ratio and a continuous topological structure, and excellent mechanical properties. In terms of structure, ion doping can endow HAp with new biological functions, for example, carbonate (CO3 2- ) doping can improve the degradation rate and biocompatibility of HAp, so that it is closer to natural bone apatite; copper ion (Cu 2+ ) doping can endow HAp with antibacterial function and pro-angiogenic ability. However, the preparation of ion-doped HAp nanowire in the prior art still faces significant challenges: (1) single ion doping often cannot meet the functional requirements in many aspects; (2) it is difficult to simultaneously dope Cu 2+ and CO3 2- into HAp due to the large difference in ionic radius, which may cause HAp lattice distortion or phase separation, and it is difficult to obtain a nanowire structure.

[0004] Therefore, it is an urgent problem in the field to develop a method for successfully preparing Cu 2+ / CO3 2- doped hydroxyapatite nanowire. SUMMARY

[0005] The present application provides a preparation method of Cu 2+ / CO3 2- doped hydroxyapatite nanowire. The Cu 2+ / CO3 2- doped hydroxyapatite nanowire prepared by the method has a nanowire structure, uniform and controllable morphology, good dispersibility, good cell compatibility, excellent antibacterial performance, excellent pro-angiogenic ability and pro-cell migration ability.

[0006] The present application also provides a Cu 2+ / CO3 2- Dual-doped hydroxyapatite nanowires, the Cu 2+ / CO3 2- The double-doped hydroxyapatite nanowires were prepared by the above method, therefore the Cu 2+ / CO3 2- Double-doped hydroxyapatite nanowires have the advantages of good cell compatibility, excellent antibacterial properties, excellent angiogenesis promotion ability, and excellent cell migration promotion ability.

[0007] The present invention also provides a Cu obtained by the above preparation method. 2+ / CO3 2- Double-doped hydroxyapatite nanowires or the above-mentioned Cu 2+ / CO3 2- The application of dual-doped hydroxyapatite nanowires in the preparation of antibacterial products, wherein the bacteria are at least one of Gram-negative and Gram-positive bacteria; the Gram-negative bacteria include *Escherichia coli*, and the Gram-positive bacteria include *Staphylococcus aureus*. The research of this invention shows that Cu nanowires prepared using the method of this invention... 2+ / CO3 2- Double-doped hydroxyapatite nanowires can significantly inhibit the growth of Escherichia coli and Staphylococcus aureus. Therefore, this Cu... 2+ / CO3 2- Double-doped hydroxyapatite nanowires can be used to prepare antibacterial products.

[0008] The present invention also provides a Cu obtained by the above preparation method. 2+ / CO3 2- Double-doped hydroxyapatite nanowires or the above-mentioned Cu 2+ / CO3 2- Application of dual-doped hydroxyapatite nanowires in the preparation of formulations for promoting angiogenesis. The research of this invention demonstrates that Cu nanowires prepared using the method of this invention… 2+ / CO3 2- Double-doped hydroxyapatite nanowires can effectively promote angiogenesis and have excellent pro-angiogenic ability. Therefore, this Cu... 2+ / CO3 2- Double-doped hydroxyapatite nanowires can be used to prepare formulations that promote angiogenesis.

[0009] The present invention also provides a Cu obtained by the above preparation method. 2+ / CO3 2- Double-doped hydroxyapatite nanowires or the above-mentioned Cu 2+ / CO3 2-The application of the double-doped hydroxyapatite nanowire in the preparation of a preparation for promoting cell migration, the cell being a human umbilical vein endothelial cell. 2+ / CO3 2- The double-doped hydroxyapatite nanowire can significantly promote the migration of a human umbilical vein endothelial cell (HUVEC cell) and has excellent cell migration promotion ability. Therefore, the Cu 2+ / CO3 2- The double-doped hydroxyapatite nanowire can be prepared into a preparation for promoting cell migration.

[0010] The application provides a Cu 2+ / CO3 2- The application provides a preparation method of a double-doped hydroxyapatite nanowire, which comprises the following steps:

[0011] The calcium chloride, the disodium hydrogen phosphate and the sodium carbonate are sequentially added into a mixed solution prepared from oleic acid, oleylamine and ethanol to obtain a reaction raw material;

[0012] The reaction raw material is subjected to a first hydrothermal reaction under a closed condition to obtain a reaction product liquid;

[0013] The copper nitrate is added into the reaction product liquid, and a second hydrothermal reaction is performed under a closed condition to collect a first precipitate;

[0014] The first precipitate is dispersed in a sodium hyaluronate aqueous solution, and a stirring reaction is performed under a closed condition. A second precipitate after the stirring reaction is collected and washed with deionized water to obtain the Cu 2+ / CO3 2- The double-doped hydroxyapatite nanowire.

[0015] The Cu 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanowire, wherein the volume ratio of the oleic acid, the oleylamine and the ethanol in the mixed solution is (2-6):(0.5-3):16.

[0016] The Cu 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanowire, wherein the ratio of the amount of substance of the calcium element in the calcium chloride to the total amount of substance of the phosphorus element in the disodium hydrogen phosphate and the carbon element in the sodium carbonate is (1.5-1.7):1, and the ratio of the amount of substance of the phosphorus element in the disodium hydrogen phosphate to the carbon element in the sodium carbonate is 1:(0.3-6).

[0017] And / or, the ratio of the amount of substance of the calcium element in the calcium chloride to the copper element in the copper nitrate is (5-15):1.

[0018] Cu 2+ / CO3 2- The application provides a preparation method of double-doped hydroxyapatite nanowires. 2+ / CO3 2- The zeta potential of the double-doped hydroxyapatite nanowires is -13 to -23 mV.

[0019] Cu 2+ / CO3 2- The application provides a preparation method of double-doped hydroxyapatite nanowires, and the concentration of the sodium hyaluronate aqueous solution is 0.01 to 0.1 g / mL.

[0020] The mass of the sodium hyaluronate in the sodium hyaluronate aqueous solution is 4 to 20 times of the mass of the first precipitate.

[0021] Cu 2+ / CO3 2- The application provides a preparation method of double-doped hydroxyapatite nanowires, and the temperature of the first hydrothermal reaction is 90 to 210 DEG C, and the time is 10 to 30 h.

[0022] And / or, the temperature of the second hydrothermal reaction is 90 to 210 DEG C, and the time is 10 to 30 h.

[0023] And / or, the temperature of the stirring reaction is 0 to 50 DEG C, and the time is 4 to 24 h.

[0024] The application provides a Cu 2+ / CO3 2- The application provides double-doped hydroxyapatite nanowires prepared by the preparation method.

[0025] The application provides a Cu 2+ / CO3 2- The application provides double-doped hydroxyapatite nanowires or the Cu 2+ / CO3 2- The application provides application of the double-doped hydroxyapatite nanowires in preparation of antibacterial products, and the bacteria are at least one of gram-negative bacteria and gram-positive bacteria.

[0026] The gram-negative bacteria include Escherichia coli, and the gram-positive bacteria include Staphylococcus aureus.

[0027] The application provides a Cu 2+ / CO3 2- The application provides double-doped hydroxyapatite nanowires or the Cu 2+ / CO3 2-Use of double-doped hydroxyapatite nanowires in the preparation of a preparation for promoting angiogenesis.

[0028] The application provides a Cu 2+ / CO3 2- double-doped hydroxyapatite nanowire or the Cu 2+ / CO3 2- Use of double-doped hydroxyapatite nanowires in the preparation of a preparation for promoting cell migration, the cells being human umbilical vein endothelial cells.

[0029] The application has at least the following effects:

[0030] The application provides a Cu 2+ / CO3 2- The application provides a preparation method of double-doped hydroxyapatite nanowires, which successfully dopes Cu 2+ and CO3 2- into hydroxyapatite by controlling the amount of oleic acid, oleylamine and ethanol, controlling the amount of substance of calcium elements in calcium chloride, copper elements in copper nitrate, phosphorus elements in disodium hydrogen phosphate and carbon elements in sodium carbonate, and obtaining Cu 2+ / CO3 2- double-doped hydroxyapatite nanowires. 2+ / CO3 2- The Cu 2+ / CO3 2- double-doped hydroxyapatite nanowires have a nanowire structure, uniform and controllable morphology, good dispersibility, good cell compatibility and excellent antibacterial performance, and also have excellent angiogenesis promotion ability and cell migration promotion ability; the method is simple in operation, rich in raw material sources, low in cost, friendly to the environment, easy to scale up, and has wide application prospect and market value. BRIEF DESCRIPTION OF DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiment or prior art description. Obviously, the drawings in the following description only constitute some embodiments of the application, and for those skilled in the art, other drawings can also be obtained without creative labor on the basis of these drawings.

[0032] Figure 1 TEM image of Cu 2+ / CO3 2- double-doped hydroxyapatite nanowires (Example 1);

[0033] Figure 2 TEM image of Cu 2+ / CO3 2-TEM image of the double-doped hydroxyapatite nanomaterial (Comparative Sample 2);

[0034] Figure 3 Cu for Comparative Example 3 of the present application 2+ / CO3 2- TEM image of the double-doped hydroxyapatite nanomaterial (Comparative Sample 3);

[0035] Figure 4 Cu for Comparative Example 4 of the present application 2+ / CO3 2- TEM image of the double-doped hydroxyapatite nanomaterial (Comparative Sample 4);

[0036] Figure 5 Cu for Example 1 of the present application 2+ / CO3 2- Cu in the double-doped hydroxyapatite nanowire (Example Sample 1) and Comparative Sample 1 2+ / CO3 2- XRD image of the double-doped hydroxyapatite nanomaterial (Comparative Sample 1);

[0037] Figure 6 Cu for Example 1 of the present application 2+ / CO3 2- XPS image of the double-doped hydroxyapatite nanowire;

[0038] Figure 7 Cu for Example 1 of the present application 2+ / CO3 2- Cu in the double-doped hydroxyapatite nanowire (Example Sample 1) and Comparative Sample 5 2+ / CO3 2- Zeta potential image of the double-doped hydroxyapatite nanomaterial (Comparative Sample 5);

[0039] Figure 8 Cu for Example 1 of the present application 2+ / CO3 2- Cell compatibility test results of the double-doped hydroxyapatite nanowire;

[0040] Figure 9 Cu for Example 1 of the present application 2+ / CO3 2- Cu in the double-doped hydroxyapatite nanowire (Example Sample 1) and Comparative Sample 6 2+ / CO3 2- Antibacterial performance test results of the double-doped hydroxyapatite nanomaterial (Comparative Sample 6);

[0041] Figure 10 Cu for Example 1 of the present application 2+ / CO32- Cu in the double-doped hydroxyapatite nanowires (Example 1) and Comparative Example 6 2+ / CO3 2- Test results of the pro-angiogenic ability of the double-doped hydroxyapatite nanomaterial (Comparative Example 6);

[0042] Figure 11 Cu in the double-doped hydroxyapatite nanowires (Example 1) and Comparative Example 6 2+ / CO3 2- Cu in the double-doped hydroxyapatite nanowires (Example 1) and Comparative Example 6 2+ / CO3 2- Test results of the pro-angiogenic ability of the double-doped hydroxyapatite nanomaterial (Comparative Example 6); DETAILED DESCRIPTION

[0043] To make the objectives, technical solutions and advantages of the present application clearer, the following will combine the embodiments of the present application to make a clear and complete description of the technical solutions in the embodiments of the present application. Obviously, the described embodiments are some embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of protection of the present application. If the specific technology or condition is not specified in the embodiments, it is performed according to the technology or condition described in the literature in the art or according to the product instruction. If the reagent or instrument is not specified by the manufacturer, it is a conventional product that can be obtained from the market.

[0044] In the following description, the term "and / or" is used to describe the association relationship of the associated objects, which means that there can be three kinds of relationships, for example, A and / or B, which can represent the cases of A alone, B alone and A and B existing at the same time. Wherein A and B can be singular or plural.

[0045] Those skilled in the art should understand that in the following description of the embodiments of the present application, the order of the serial numbers does not mean the order of execution, and some or all steps can be executed in parallel or in sequence, and the execution order of each process should be determined according to its function and inherent logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0046] Those skilled in the art should understand that the numerical range in the embodiments of the present application should be understood as also specifically disclosing each intermediate value between the upper limit and the lower limit of the range. Each smaller range between any stated value or intermediate value in a stated range and any other stated value or intermediate value in the stated range is also included in the present application. The upper limit and the lower limit of these smaller ranges can be independently included or excluded from the range.

[0047] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, the preferred methods and materials are described. All documents mentioned herein are incorporated by reference to disclose and describe in full the methods and / or materials which are described therein. In case of conflict, the content of the present specification will control.

[0048] The present application provides a Cu 2+ / CO3 2- The present application provides a method for preparing a Cu

[0049] (1) adding calcium chloride, sodium phosphate dibasic and sodium carbonate into a mixed solution made of oleic acid, oleylamine and ethanol in sequence to obtain a reaction raw material;

[0050] (2) performing a first hydrothermal reaction on the reaction raw material under a closed condition to obtain a reaction product liquid;

[0051] (3) adding copper nitrate into the reaction product liquid and performing a second hydrothermal reaction under a closed condition to collect a first precipitate;

[0052] (4) dispersing the first precipitate into a sodium hyaluronate aqueous solution, performing a stirring reaction under a closed condition, collecting a second precipitate after the stirring reaction and washing the second precipitate with deionized water to obtain the Cu 2+ / CO3 2- nanowire.

[0053] The present application provides a Cu 2+ / CO3 2- nanowire. Specifically, the present application first mixes oleic acid, oleylamine and ethanol uniformly to make a mixed solution; then adds calcium chloride (CaCl2), sodium phosphate dibasic (Na2HPO4) and sodium carbonate (Na2CO3) into the mixed solution in sequence, stirs uniformly to obtain a reaction raw material; then performs a first hydrothermal reaction on the reaction raw material under a closed condition to obtain a reaction product liquid; then adds copper nitrate into the reaction product liquid and performs a second hydrothermal reaction under a closed condition, centrifugates the reaction product liquid after the second hydrothermal reaction and collects a first precipitate; finally disperses the first precipitate into a sodium hyaluronate aqueous solution, performs a stirring reaction under a closed condition, centrifugates the reaction product liquid after the stirring reaction, collects a second precipitate and washes the second precipitate with deionized water to remove soluble impurity ions, unreacted small molecule precursors and by-products, thereby obtaining the Cu 2+ / CO3 2-Double-doped hydroxyapatite nanowires.

[0054] The application provides a Cu 2+ / CO3 2- A method for preparing double-doped hydroxyapatite nanowires is provided. 2+ and CO3 2- The double-doped hydroxyapatite nanowires are prepared. 2+ / CO3 2- The double-doped hydroxyapatite nanowires are prepared. 2+ / CO3 2- The double-doped hydroxyapatite nanowires have a nanowire structure, uniform and controllable morphology, good dispersibility, good cell compatibility, excellent antibacterial performance, excellent pro-angiogenic ability and pro-cell migration ability; the method is simple to operate, and has rich raw material sources, low cost, friendly process environment and easy scale-up, and has wide application prospect and market value.

[0055] In an embodiment, the volume ratio of oleic acid, oleylamine and ethanol in the mixed solution is (2-6):(0.5-3):16, for example, 2:1:16, 3:1:16, 4:1:16, 5:1:16, 6:1:16, 2:2:16, 3:2:16, 4:2:16, 5:2:16, 6:2:16, etc.

[0056] When the volume ratio of oleic acid, oleylamine and ethanol in the mixed solution is within the above range, the mixed solution as a reaction solvent can provide a synergistic effect, which helps to realize morphology control, dispersion stability improvement and crystal type optimization of hydroxyapatite (HAp).

[0057] In an embodiment, the ratio of the amount of substance of calcium in the calcium chloride to the total amount of substance of phosphorus in the disodium hydrogen phosphate and carbon in the sodium carbonate is (1.5-1.7):1, and the ratio of the amount of substance of phosphorus in the disodium hydrogen phosphate to the amount of substance of carbon in the sodium carbonate is 1:(0.3-6).

[0058] During the growth of HAp crystals, anions (CO3 2- ) replace part of the phosphate groups into the HAp crystals and control the growth direction of the crystals. When the amounts of substance of calcium in the calcium chloride, phosphorus in the disodium hydrogen phosphate and carbon in the sodium carbonate satisfy the above conditions, CO3 2- doped hydroxyapatite nanowires are generated.

[0059] In an embodiment, the molar ratio of calcium in the calcium chloride to copper in the copper nitrate is (5-15):1.

[0060] Cation (Cu 2+ ) doping can cause lattice distortion of HAp crystals, resulting in changes in crystal morphology or the generation of other impurities. When the molar ratio of calcium in the calcium chloride to copper in the copper nitrate is in the above range, Cu 2+ / CO3 2- doped hydroxyapatite nanowires can be generated while maintaining the morphology.

[0061] In an embodiment, the zeta potential of the Cu 2+ / CO3 2- doped hydroxyapatite nanowires is -13 to -23 mV, indicating that the Cu 2+ / CO3 2- doped hydroxyapatite nanowires prepared by the present application have a negative charge on the surface.

[0062] In an embodiment, the concentration of the sodium hyaluronate aqueous solution is 0.01-0.1 g / mL; the mass of sodium hyaluronate in the sodium hyaluronate aqueous solution is 4-20 times the mass of the first precipitate.

[0063] In an embodiment, the temperature of the first hydrothermal reaction is 90-210°C, and the time is 10-30 h.

[0064] For example, the temperature of the first hydrothermal reaction can be any one or a range consisting of any two of 90°C, 110°C, 130°C, 150°C, 170°C, 190°C, and 210°C.

[0065] The time can be any one or a range consisting of any two of 10 h, 15 h, 20 h, 25 h, and 30 h.

[0066] In an embodiment, the temperature of the second hydrothermal reaction is 90-210°C, and the time is 10-30 h.

[0067] For example, the temperature of the second hydrothermal reaction can be any one or a range consisting of any two of 90°C, 110°C, 130°C, 150°C, 170°C, 190°C, and 210°C.

[0068] The time can be any one or a range consisting of any two of 10 h, 15 h, 20 h, 25 h, and 30 h.

[0069] In a specific embodiment, the temperature of the stirring reaction is 0-50℃, and the time is 4-24h.

[0070] Illustratively, the temperature of the stirring reaction can be any one of 0℃, 5℃, 10℃, 20℃, 30℃, 40℃, 50℃, or a range consisting of any two of them.

[0071] The time can be any one of 4h, 8h, 12h, 16h, 20h, 24h, or a range consisting of any two of them.

[0072] In some embodiments, before dispersing the first precipitate in the aqueous sodium hyaluronate solution, the first precipitate is further subjected to a washing treatment to wash away unreacted impurity ions, small molecule precursors and by-products. The washing treatment comprises sequentially washing the first precipitate with cyclohexane and ethanol.

[0073] In a second aspect, the application provides a Cu 2+ / CO3 2- doubly-doped hydroxyapatite nanowire prepared by the preparation method.

[0074] In a third aspect, the application provides a Cu 2+ / CO3 2- doubly-doped hydroxyapatite nanowire prepared by the preparation method. 2+ / CO3 2- doubly-doped hydroxyapatite nanowire.

[0075] In a fourth aspect, the application provides a Cu 2+ / CO3 2- doubly-doped hydroxyapatite nanowire prepared by the preparation method. 2+ / CO3 2- doubly-doped hydroxyapatite nanowire.

[0076] In a fifth aspect, the application provides a Cu 2+ / CO3 2- doubly-doped hydroxyapatite nanowire prepared by the preparation method. 2+ / CO3 2- doubly-doped hydroxyapatite nanowire.

[0077] The application will be further described below through specific examples.

[0078] Embodiment 1

[0079] The embodiment provides a Cu 2+ / CO3 2- A preparation method of double-doped hydroxyapatite nanowires comprises the following steps:

[0080] (1) 4 mL of oleic acid, 1 mL of oleylamine and 16 mL of anhydrous ethanol are uniformly mixed to prepare a mixed solution;

[0081] Calcium chloride (CaCl2) is dissolved in deionized water to prepare a CaCl2 solution with a concentration of 0.25 mol / L; sodium hydrogen phosphate (Na2HPO4) is dissolved in deionized water to prepare a Na2HPO4 solution with a concentration of 0.15 mol / L; and sodium carbonate (Na2CO3) is dissolved in deionized water to prepare a Na2CO3 solution with a concentration of 0.15 mol / L;

[0082] 7 mL of the CaCl2 solution, 1.4 mL of the Na2HPO4 solution and 5.6 mL of the Na2CO3 solution are sequentially added to the mixed solution, and stirred uniformly to obtain a reaction raw material; in the reaction raw material, the ratio of the amount of substance of calcium to the total amount of substance of phosphorus and carbon is 1.67:1, and the ratio of the amount of substance of phosphorus to carbon is 1:4;

[0083] (2) The reaction raw material is sealed in a reaction bottle and subjected to a hydrothermal reaction in an oven at 150 ℃ for 12 h to obtain a reaction product liquid;

[0084] (3) Copper nitrate (Cu(NO3)2) is dissolved in deionized water to prepare a Cu(NO3)2 solution with a concentration of 0.25 mol / L;

[0085] 0.7 mL of the Cu(NO3)2 solution is added to the reaction product liquid, and after being stirred uniformly, the mixture is sealed and subjected to a hydrothermal reaction in an oven at 150 ℃ for 12 h; the reaction product liquid after the second hydrothermal reaction is subjected to centrifugation, and a first precipitate is collected; the first precipitate is sequentially washed with cyclohexane and anhydrous ethanol to obtain a washed first precipitate;

[0086] (4) 0.1 g of the washed first precipitate is dispersed in a sodium hyaluronate aqueous solution (0.04 g / mL, 20 mL), and after being subjected to ultrasonic treatment for 30 min, the mixture is sealed and subjected to a stirring reaction at 25 ℃ for 24 h; the reaction product liquid after the stirring reaction is subjected to centrifugation, a second precipitate is collected and washed with deionized water to obtain a Cu 2+ / CO3 2-The double-doped hydroxyapatite nanowires (Cu-CHAp NWs) are denoted as Example 1.

[0087] Example 2

[0088] The Cu-CHAp NWs prepared in this example are denoted as Example 2. 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanowires is basically the same as that of Example 1, except that:

[0089] In step (1), 1.4 mL of the Na2HPO4 solution and 5.6 mL of the Na2CO3 solution are replaced by 4.9 mL of the Na2HPO4 solution and 2.1 mL of the Na2CO3 solution.

[0090] The Cu-CHAp NWs prepared in this example are denoted as Example 2. 2+ / CO3 2- The Cu-CHAp NWs prepared in this example are denoted as Example 2.

[0091] Example 3

[0092] The Cu-CHAp NWs prepared in this example are denoted as Example 2. 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanowires is basically the same as that of Example 1, except that:

[0093] In step (1), 1 mL of oleylamine is replaced by 2 mL of oleylamine.

[0094] The Cu-CHAp NWs prepared in this example are denoted as Example 2. 2+ / CO3 2- The Cu-CHAp NWs prepared in this example are denoted as Example 2.

[0095] Comparative Example 1

[0096] The Cu-CHAp NWs prepared in this example are denoted as Example 2. 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanowires is basically the same as that of Example 1, except that:

[0097] In step (1), 1.4 mL of the Na2HPO4 solution and 5.6 mL of the Na2CO3 solution are replaced by 0.7 mL of the Na2HPO4 solution and 6.3 mL of the Na2CO3 solution.

[0098] The Cu-CHAp NWs prepared in this example are denoted as Example 2. 2+ / CO3 2- The Cu-CHAp NWs prepared in this example are denoted as Example 2.

[0099] Comparative Example 2

[0100] The Cu-CHAp NWs prepared in this example are denoted as Example 2. 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanomaterial is basically the same as that of Embodiment 1, except that:

[0101] In step (1), 1.4 mL of the Na2HPO4 solution and 5.6 mL of the Na2CO3 solution are replaced by 6.3 mL of the Na2HPO4 solution and 0.7 mL of the Na2CO3 solution.

[0102] The Cu 2+ / CO3 2- The double-doped hydroxyapatite nanomaterial is referred to as Comparative Sample 2.

[0103] Comparative Example 3

[0104] The Cu 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanomaterial is basically the same as that of Embodiment 1, except that:

[0105] In step (1), 1 mL of oleylamine is replaced by 6 mL of oleylamine.

[0106] The Cu 2+ / CO3 2- The double-doped hydroxyapatite nanomaterial is referred to as Comparative Sample 3.

[0107] Comparative Example 4

[0108] The Cu 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanomaterial is basically the same as that of Embodiment 1, except that:

[0109] In step (1), 4 mL of oleic acid is replaced by 8 mL of oleic acid.

[0110] The Cu 2+ / CO3 2- The double-doped hydroxyapatite nanomaterial is referred to as Comparative Sample 4.

[0111] Comparative Example 5

[0112] The Cu 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanomaterial is basically the same as that of Embodiment 1, except that: the operation of step (4) is not performed. Specifically, the Cu 2+ / CO3 2- The preparation method of the double-doped hydroxyapatite nanomaterial comprises the following steps:

[0113] (1) 4 mL of oleic acid, 1 mL of oleylamine and 16 mL of anhydrous ethanol were mixed uniformly to prepare a mixed solution;

[0114] Calcium chloride (CaCl2) was dissolved in deionized water to prepare a CaCl2 solution with a concentration of 0.25 mol / L; sodium hydrogen phosphate (Na2HPO4) was dissolved in deionized water to prepare a Na2HPO4 solution with a concentration of 0.15 mol / L; sodium carbonate (Na2CO3) was dissolved in deionized water to prepare a Na2CO3 solution with a concentration of 0.15 mol / L;

[0115] 7 mL of the CaCl2 solution, 1.4 mL of the Na2HPO4 solution and 5.6 mL of the Na2CO3 solution were sequentially added to the mixed solution, and stirred uniformly to obtain a reaction raw material; in the reaction raw material, the ratio of the amount of substance of calcium element to the total amount of substance of phosphorus element and carbon element was 1.67:1, and the ratio of the amount of substance of phosphorus element to carbon element was 1:4;

[0116] (2) The reaction raw material was sealed in a reaction bottle and subjected to a hydrothermal reaction in an oven at 150°C for 12 h to obtain a reaction product liquid;

[0117] (3) Copper nitrate (Cu(NO3)2) was dissolved in deionized water to prepare a Cu(NO3)2 solution with a concentration of 0.25 mol / L;

[0118] 0.7 mL of the Cu(NO3)2 solution was added to the reaction product liquid, which was stirred uniformly and sealed, and subjected to a hydrothermal reaction in an oven at 150°C for 12 h; the reaction product liquid after the second hydrothermal reaction was centrifuged to collect a first precipitate; the first precipitate was washed with cyclohexane and anhydrous ethanol in sequence to obtain Cu 2+ / CO3 2- The second hydrothermal reaction was repeated to obtain a second precipitate, which was washed with cyclohexane and anhydrous ethanol in sequence to obtain Cu

[0119] Comparative Example 6

[0120] The comparative example provides a CO3 2- The preparation method of the doped hydroxyapatite nanomaterial includes the following steps:

[0121] (1) 4 mL of oleic acid, 1 mL of oleylamine and 16 mL of anhydrous ethanol were mixed uniformly to prepare a mixed solution;

[0122] Calcium chloride (CaCl2) was dissolved in deionized water to prepare a CaCl2 solution with a concentration of 0.25 mol / L; sodium hydrogen phosphate (Na2HPO4) was dissolved in deionized water to prepare a Na2HPO4 solution with a concentration of 0.15 mol / L; and sodium carbonate (Na2CO3) was dissolved in deionized water to prepare a Na2CO3 solution with a concentration of 0.15 mol / L;

[0123] The CaCl2 solution, the Na2HPO4 solution and the Na2CO3 solution were sequentially added to the mixed solution to obtain a reaction raw material; in the reaction raw material, the ratio of the amount of substance of calcium to the total amount of substance of phosphorus and carbon was 1.67:1, and the ratio of the amount of substance of phosphorus to carbon was 1:4;

[0124] (2) The reaction raw material was sealed in a reaction bottle and subjected to a hydrothermal reaction in an oven at 150°C for 12 h to obtain a reaction product liquid; the reaction product liquid was centrifuged to collect a first precipitate; the first precipitate was washed with cyclohexane and anhydrous ethanol in sequence to obtain a washed first precipitate;

[0125] (3) 0.1 g of the washed first precipitate was dispersed in a sodium hyaluronate aqueous solution (0.04 g / mL, 20 mL), and after ultrasonic treatment for 30 min, the mixture was sealed and subjected to a stirring reaction at 25°C for 24 h; the reaction product liquid after the stirring reaction was centrifuged to collect a second precipitate which was washed with deionized water to obtain CO3 2- A hydroxyapatite nanomaterial doped with calcium and carbon (Cu

[0126] Performance test

[0127] 1. Morphology test

[0128] The Cu 2+ / CO3 2- doped hydroxyapatite nanowire in Example 1 of the present application was subjected to a transmission electron microscope (TEM) test, and the result is shown in FIG. 1. 2+ / CO3 2- doped hydroxyapatite nanowire in Example 1 of the present application was subjected to a transmission electron microscope (TEM) test, and the result is shown in FIG. 1. Figures 1-4 Figure 1 The Cu 2+ / CO3 2- doped hydroxyapatite nanowire in Example 1 of the present application was subjected to a transmission electron microscope (TEM) test, and the result is shown in FIG. 1. Figure 2 The Cu 2+ / CO3 2- doped hydroxyapatite nanowire in Example 1 of the present application was subjected to a transmission electron microscope (TEM) test, and the result is shown in FIG. 1.​Figure 3 Cu in Comparative Example 3 of this invention 2+ / CO3 2- TEM image of the double-doped hydroxyapatite nanomaterial (comparative sample 3); Figure 4 Cu in Comparative Example 4 of this invention 2+ / CO3 2- TEM image of the double-doped hydroxyapatite nanomaterial (comparative sample 4).

[0129] Depend on Figure 1 It can be seen that Cu in Example 1 2+ / CO3 2- The double-doped hydroxyapatite nanowires exhibit a nanowire structure with uniform and controllable morphology and good dispersibility.

[0130] Depend on Figure 2 It can be seen that Cu in Comparative Example 2 2+ / CO3 2- The double-doped hydroxyapatite nanomaterial (comparative sample 2) has a nanorod structure.

[0131] Depend on Figure 3 It can be seen that Cu in Comparative Example 3 2+ / CO3 2- The double-doped hydroxyapatite nanomaterial (comparative sample 3) has a nanoparticle structure.

[0132] Depend on Figure 4 It can be seen that Cu in Comparative Example 4 2+ / CO3 2- The double-doped hydroxyapatite nanomaterial (comparative sample 4) exhibits a nanorod-like structure.

[0133] Comparing Example 1 and Comparative Example 2, it was found that when the molar ratio of phosphorus in disodium hydrogen phosphate to carbon in sodium carbonate was 9:1, a nanowire-structured hydroxyapatite material could not be obtained. Comparing Example 1 and Comparative Example 3, it was found that when too much oleylamine was used, a nanowire-structured hydroxyapatite material could not be obtained. Comparing Example 1 and Comparative Example 4, it was found that when too much oleic acid was used, a nanowire-structured hydroxyapatite material could not be obtained.

[0134] 2. X-ray diffraction analysis

[0135] Cu in Example 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Cu-CHAp NWs) and Cu in control sample 1 2+ / CO3 2- X-ray diffraction (XRD) analysis was performed on the double-doped hydroxyapatite nanomaterials, and the results are as follows: Figure 5 As shown. Figure 5Cu in Embodiment 1 of the present invention 2+ / CO3 2- Cu in double-doped hydroxyapatite nanowires (Example 1) and control sample 1 2+ / CO3 2- XRD pattern of double-doped hydroxyapatite nanomaterial (comparative sample 1).

[0136] Depend on Figure 5 It can be seen that the characteristic peaks of sample 1 match those of the hydroxyapatite standard card (PDF 09-0432), and the crystal phase is hydroxyapatite. Although the hydroxyapatite crystal phase also appeared in the comparison sample 1, it also showed characteristic peaks other than the hydroxyapatite crystal phase, indicating that when the molar ratio of phosphorus in disodium hydrogen phosphate to carbon in sodium carbonate is 1:9, impurity phases are generated.

[0137] 3. Elemental Analysis

[0138] Cu in Example 1 of the present invention 2+ / CO3 2- X-ray photoelectron spectroscopy (XPS) analysis of double-doped hydroxyapatite nanowires (Cu-CHAp NWs) yielded the following results: Figure 6 As shown. Figure 6 Cu in Embodiment 1 of the present invention 2+ / CO3 2- XPS image of dual-doped hydroxyapatite nanowires.

[0139] Depend on Figure 6 It can be seen that Cu-CHAp NWs contain C, Ca, P, O, and Cu elements, indicating that Cu has been successfully doped into hydroxyapatite. 2+ and CO3 2- Cu was successfully produced 2+ / CO3 2- Double-doped hydroxyapatite nanowires.

[0140] 4. Zeta potential analysis

[0141] Cu in Example 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 5 2+ / CO3 2- Zeta potential analysis was performed on the dual-doped hydroxyapatite nanomaterials (comparative sample 5), and the results are as follows: Figure 7 As shown. Figure 7 Cu in Embodiment 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 5 2+ / CO32- Zeta potential graph of the double-doped hydroxyapatite nanomaterial (comparative example 5).

[0142] By Figure 7 It can be seen that the Cu 2+ / CO3 2- The double-doped hydroxyapatite nanowire surface is negatively charged, and the Zeta potential is -14.6±1.5mV; the Cu 2+ / CO3 2- The double-doped hydroxyapatite nanomaterial surface is positively charged, and the Zeta potential is +8.2±1.3mV.

[0143] 5. Cell compatibility test

[0144] The Cu 2+ / CO3 2- The double-doped hydroxyapatite nanowire (example 1) as the sample to be tested was subjected to a cell compatibility test, and the specific steps were as follows:

[0145] After the sample to be tested was subjected to cobalt 60 irradiation sterilization treatment, it was dispersed in DMEM complete culture medium (containing 10% serum and 1% double antibody), and was immersed in a 37°C incubator for 72h to obtain sample immersion liquids with concentration gradients of 0μg / mL, 150μg / mL, 200μg / mL, 250μg / mL, 300μg / mL, 350μg / mL, 400μg / mL, 450μg / mL and 500μg / mL, respectively;

[0146] Human umbilical vein endothelial cells (HUVECs, 1×10 5 The cells were cultured in DMEM complete culture medium for 24h until the cells adhered, and then the experimental group and the control group were set up: the experimental group was replaced with sample immersion liquids with different concentrations (0μg / mL, 150μg / mL, 200μg / mL, 250μg / mL, 300μg / mL, 350μg / mL, 400μg / mL, 450μg / mL and 500μg / mL), and the control group was replaced with fresh DMEM complete culture medium; after the HUVEC cells were cultured for 24h, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide MTT (50μL / well) was added, and the liquid was aspirated after 3h of further incubation and dimethyl sulfoxide (150μL / well) was added, and the absorbance value OD 490 at 490nm of the DMEM complete culture medium, the experimental group and the control group was measured, and the cell survival rate was calculated by the following formula:

[0147] Cell survival rate = [(A 样 -A 空) / (A 对 -A 空 )]×100%, where A 样 A represents the absorbance value of the experimental group. 空 A represents the absorbance value of DMEM complete culture medium. 对 The absorbance value is for the control group.

[0148] Figure 8 Cu in Embodiment 1 of the present invention 2+ / CO3 2- Cell compatibility test results of dual-doped hydroxyapatite nanowires.

[0149] Depend on Figure 8 It can be seen that in Cu 2+ / CO3 2- Double-doped hydroxyapatite nanowires exhibit good cell compatibility with human umbilical vein endothelial cells (HUVECs) within a concentration range of less than 500 μg / mL.

[0150] 6. Antibacterial performance test

[0151] Cu in Example 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 6 2+ / CO3 2- The antibacterial properties of the dual-doped hydroxyapatite nanomaterials (comparative sample 6) were tested as the test samples. The specific steps are as follows:

[0152] Experimental group: The samples to be tested were sterilized by cobalt-60 irradiation and then dispersed in LB medium to obtain a sample solution with a concentration of 200 mg / mL.

[0153] Add 2 mL of sample solution to E. coli (E. coli) bacterial suspension (1×10⁻⁶). 5 (cFU / mL) and Staphylococcus aureus (S. aureus) bacterial suspension (1×10⁻⁶) 5 After co-culturing in a biochemical incubator at 37℃ for 24 h (number of cells / mL), the culture medium was obtained, and the absorbance value (OD) of the culture medium at 600 nm was measured. 600 ;

[0154] Control group: Escherichia coli (E. coli) bacterial suspension (1×10⁻⁶) 5 (cFU / mL) and Staphylococcus aureus (S. aureus) bacterial suspension (1×10⁻⁶) 5 (The samples were) were placed in a 37℃ biochemical incubator and incubated for 24 h to obtain the culture medium. The absorbance (OD) of the culture medium at 600 nm was measured. 600 ;

[0155] Blank group: The absorbance (OD) of LB medium at 600 nm was measured. 600 ;

[0156] Bacterial survival rate is calculated using the following formula:

[0157] Bacterial survival rate (%) = [(A 样 -A 空 ) / (A 对 -A 空 )]×100%, where A 样 For A 样 A represents the absorbance value of the experimental group. 空 A represents the absorbance value of LB medium. 对 The absorbance value is for the control group.

[0158] Figure 9 Cu in Embodiment 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 6 2+ / CO3 2- Test results of antibacterial properties of double-doped hydroxyapatite nanomaterials (comparative sample 6).

[0159] Depend on Figure 9 It can be seen that Cu in Example 1 2+ / CO3 2- After co-culturing dual-doped hydroxyapatite nanowires (Example 1) with *E. coli* or *S. aureus*, the survival rate of *E. coli* was 32.8 ± 0.9%, and the survival rate of *S. aureus* was 47.6 ± 0.5%. The Cu in Comparative Example 6 was also tested. 2+ / CO3 2- After co-culturing the double-doped hydroxyapatite nanomaterial (Reference Sample 6) with Escherichia coli or Staphylococcus aureus, the survival rate of Escherichia coli was 96.8±1.2%, and the survival rate of Staphylococcus aureus was 98.7±0.8%. These results indicate that, compared with Reference Sample 6, Sample 1 can significantly inhibit the growth of Escherichia coli and Staphylococcus aureus, and has excellent antibacterial properties.

[0160] 7. Angiogenesis Promotion Capacity Test

[0161] Cu in Example 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 6 2+ / CO3 2- The dual-doped hydroxyapatite nanomaterials (comparative sample 6) were used as test samples to test their angiogenesis-promoting ability. The specific steps are as follows:

[0162] After sterilization by cobalt-60 irradiation, the sample was dispersed in DMEM complete medium (containing 2% serum and 1% antibiotics) and extracted in an incubator at 37°C for 72 hours to obtain a sample extract with a concentration of 500 μg / mL.

[0163] Human umbilical vein endothelial cells (HUVECs, 3×10⁻⁶) were used. 4 Cells were seeded per well in 48-well plates containing matrix gel, with experimental and control groups set up: the experimental group was treated with sample extract, and the control group was treated with the same volume of DMEM complete culture medium as the experimental group; after incubation in a cell culture incubator for 8 hours, angiogenesis was observed under an inverted microscope, and the results are as follows. Figure 10 As shown.

[0164] Figure 10 Cu in Embodiment 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 6 2+ / CO3 2- Test results of the angiogenesis-promoting ability of the double-doped hydroxyapatite nanomaterial (comparative sample 6).

[0165] Depend on Figure 10 It can be seen that, compared with the control group and control sample 6, sample 1 can effectively promote angiogenesis and shows excellent pro-angiogenic ability.

[0166] 8. Cell migration promotion ability test

[0167] Cu in Example 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 6 2+ / CO3 2- The dual-doped hydroxyapatite nanomaterials (comparative sample 6) were used as test samples to test their cell migration promotion ability. The specific steps are as follows:

[0168] After sterilization by cobalt-60 irradiation, the sample was dispersed in DMEM complete medium (containing 2% serum and 1% antibiotics) and extracted in an incubator at 37°C for 72 hours to obtain a sample extract with a concentration of 500 μg / mL.

[0169] Human umbilical vein endothelial cells (HUVECs, 1×10⁻⁶) were used. 6Cells (number per well) were seeded in 6-well plates and cultured for 24 h. Cell scratches were created in the wells using a 200 μL sterile pipette tip. After rinsing off the cells with PBS, experimental and control groups were set up: the experimental group received 2 mL of sample extract, and the control group received the same volume of DMEM complete culture medium as the experimental group. Cells were continued to be cultured in an incubator. The scratch area was observed and photographed under a microscope at 0 h and 12 h, and the results are recorded as follows: Figure 11 As shown.

[0170] Figure 11 Cu in Embodiment 1 of the present invention 2+ / CO3 2- Double-doped hydroxyapatite nanowires (Example 1) and Cu in Comparative Example 6 2+ / CO3 2- Results of cell migration promotion test of double-doped hydroxyapatite nanomaterials (comparative sample 6).

[0171] Depend on Figure 11 It can be seen that, compared with the control group and control sample 6, the cell scratch area of ​​sample 1 was significantly reduced, demonstrating excellent cell migration promotion ability.

[0172] In summary, Cu obtained by the method of this invention 2+ / CO3 2- The double-doped hydroxyapatite nanowires have a nanowire structure with uniform and controllable morphology and good dispersibility. They exhibit good cell compatibility and excellent antibacterial properties, as well as excellent angiogenesis and cell migration promotion capabilities. This method is simple to operate, the raw materials are abundant and inexpensive, the process environment is friendly, and it is easy to scale up, thus having broad application prospects and market value.

[0173] 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 or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Cu 2+ / CO3 2- The method for preparing dual-doped hydroxyapatite nanowires is characterized by, Includes the following steps: Calcium chloride, disodium hydrogen phosphate, and sodium carbonate were added sequentially to a mixed solution made of oleic acid, oleylamine, and ethanol to obtain the reaction raw materials. The reactants are subjected to a first hydrothermal reaction under closed conditions to obtain a reaction product liquid. Copper nitrate was added to the reaction product liquid, and a second hydrothermal reaction was carried out under closed conditions to collect the first precipitate. The first precipitate was dispersed in an aqueous solution of sodium hyaluronate, and the reaction was carried out under closed conditions with stirring. The second precipitate after stirring was collected and washed with deionized water to obtain the Cu. 2+ / CO3 2- Double-doped hydroxyapatite nanowires.

2. The Cu according to claim 1 2+ / CO3 2- The method for preparing dual-doped hydroxyapatite nanowires is characterized by, In the mixed solution, the volume ratio of oleic acid, oleylamine and ethanol is (2-6):(0.5-3):

16.

3. The Cu according to claim 1 2+ / CO3 2- The method for preparing dual-doped hydroxyapatite nanowires is characterized by, The ratio of the amount of calcium in the calcium chloride to the total amount of phosphorus in the disodium hydrogen phosphate and carbon in the sodium carbonate is (1.5-1.7):1, and the ratio of the amount of phosphorus in the disodium hydrogen phosphate to carbon in the sodium carbonate is 1:(0.3-6). And / or, the molar ratio of calcium in the calcium chloride to copper in the copper nitrate is (5-15):

1.

4. The Cu according to claim 1 2+ / CO3 2- The method for preparing dual-doped hydroxyapatite nanowires is characterized by, The Cu 2+ / CO3 2- The zeta potential of the double-doped hydroxyapatite nanowires is -13 to -23 mV.

5. The Cu according to claim 1 2+ / CO3 2- The method for preparing dual-doped hydroxyapatite nanowires is characterized by, The concentration of the sodium hyaluronate aqueous solution is 0.01–0.1 g / mL; The mass of sodium hyaluronate in the sodium hyaluronate aqueous solution is 4 to 20 times the mass of the first precipitate.

6. The Cu according to claim 1 2+ / CO3 2- The method for preparing dual-doped hydroxyapatite nanowires is characterized by, The temperature of the first hydrothermal reaction is 90–210℃ and the time is 10–30 h; And / or, the temperature of the second hydrothermal reaction is 90–210°C and the time is 10–30 h; And / or, the temperature of the stirring reaction is 0–50°C and the time is 4–24 h.

7. A Cu 2+ / CO3 2- Dual-doped hydroxyapatite nanowires, characterized in that, It is prepared by the preparation method described in any one of claims 1 to 6.

8. A Cu obtained by the preparation method according to any one of claims 1 to 6 2+ / CO3 2- Double-doped hydroxyapatite nanowires or the Cu as described in claim 7 2+ / CO3 2- The application of dual-doped hydroxyapatite nanowires in the preparation of antibacterial products is characterized by, The bacteria are at least one of Gram-negative bacteria and Gram-positive bacteria; The Gram-negative bacteria include Escherichia coli, and the Gram-positive bacteria include Staphylococcus aureus.

9. A Cu obtained by the preparation method according to any one of claims 1 to 6 2+ / CO3 2- Double-doped hydroxyapatite nanowires or the Cu as described in claim 7 2+ / CO3 2- Application of double-doped hydroxyapatite nanowires in the preparation of formulations to promote angiogenesis.

10. A Cu obtained by the preparation method according to any one of claims 1 to 6 2+ / CO3 2- Double-doped hydroxyapatite nanowires or the Cu as described in claim 7 2+ / CO3 2- The application of dual-doped hydroxyapatite nanowires in the preparation of formulations for promoting cell migration is characterized by, The cells in question are human umbilical vein endothelial cells.

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