Method for preparing wolf tooth rod-like calcium phosphate based on ion coordination regulation and directional nucleation

Abstract

The application discloses a method for preparing wolf tooth rod-shaped calcium phosphate based on ion coordination regulation and directional nucleation, and the method uses calcium chloride as a calcium source, di-ammonium hydrogen phosphate as a phosphorus source, and polyethylene glycol-6000 as a morphology regulator; through a hydrothermal reaction combined with a high-temperature calcination process, wolf tooth rod-shaped calcium phosphate with high monomodal preferential orientation is prepared; EDS energy spectrum scanning proves that the product is calcium phosphate and has excellent biocompatibility, and can be widely applied to bone tissue engineering scaffolds, drug carriers, biological coatings and other fields; the process steps are simple, the reaction conditions are controllable, and the cost is low, so that the application provides a new idea for preparation of high-performance calcium phosphate materials.

Description

Technical Field

[0001] This invention relates to the field of biomedical material preparation technology, specifically to a method for preparing wolf-tooth-shaped calcium phosphate based on ion coordination-regulated directional nucleation. Background Technology

[0002] Calcium phosphate (CPC) is an inorganic biomaterial with excellent biocompatibility, biodegradability, and osteoconductivity. Its chemical properties are similar to those of the inorganic components in human bone tissue, and it can be gradually degraded by osteoclasts in vivo. The degradation products (Ca) 2＋ PO4 3— It can participate in the metabolism and regeneration of bone tissue, and therefore has broad application prospects in biomedical fields such as bone defect repair, controlled drug release, and dental filling.

[0003] The properties of calcium phosphate are closely related to its morphology and crystal structure. Among them, the wolf-tooth-shaped structure, due to its one-dimensional morphology similar to natural bone fibers, can provide a biomimetic growth microenvironment for cells, promoting cell adhesion, proliferation, and osteogenic differentiation. At the same time, the high aspect ratio can improve the mechanical strength (such as compressive and flexural strength) and dispersion stability of the material, preventing rapid aggregation in the body fluid environment. The crystal structure with high unimodal selectivity means that the crystals are highly oriented along a specific direction, which can further optimize the mechanical and biological activity of the material and enhance its performance in specific application scenarios.

[0004] Existing methods for preparing calcium phosphate have several limitations: the large-scale use of ammonia in traditional industrial production has brought serious environmental pressures and safety hazards. While the traditional hydrothermal method can prepare a serrated structure, it struggles to achieve high single-peak selectivity and has a long reaction cycle (24-48 hours) and high energy consumption. The sol-gel method is prone to irregular product morphology due to gel drying shrinkage. Template methods rely on expensive organic templates (such as carbon nanotubes and surfactants), and template residues can affect the biosafety of the material, making it difficult to balance morphological regularity and crystal selectivity. Therefore, developing a method for preparing calcium phosphate that simultaneously achieves a serrated morphology, high single-peak selectivity, and excellent biocompatibility is of great significance for promoting its application in high-performance biomedical fields. Summary of the Invention

[0005] To address the problems of existing technologies, this invention provides a method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation. By optimizing the product morphology control synthesis technique to achieve ion-oriented nucleation regulation, the method achieves a club-shaped morphology, high single-peak selectivity, high compressive strength, and good biocompatibility in the product. Furthermore, the process is simple, low-cost, and suitable for large-scale production. This invention uses ammonia to adjust the pH of the system, yet still stably produces qualified products, achieving a clean production process that is ammonia-free, low-odor, safer, and more environmentally friendly.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] The method for preparing wolf-tooth-shaped calcium phosphate based on ion coordination-regulated directional nucleation includes the following steps:

[0008] Step 1, Preparation of calcium source-PEG composite solution:

[0009] Polyethylene glycol-6000 was added to ethanol and stirred until completely dissolved to obtain a PEG-6000 ethanol solution; calcium chloride was added to the PEG-6000 ethanol solution and stirred until the calcium chloride was completely dissolved to obtain a calcium source-PEG composite solution.

[0010] Step 2, Preparation of phosphorus source aqueous solution:

[0011] Add diammonium hydrogen phosphate to deionized water and stir until completely dissolved to obtain an aqueous solution of phosphorus source;

[0012] Step 3, Preparation of calcium phosphate precursor solution:

[0013] Under rapid stirring conditions, the phosphorus source aqueous solution prepared in step 2 was slowly added dropwise to the calcium source-PEG composite solution prepared in step 1. After the addition was completed, stirring was continued to obtain a calcium phosphate precursor solution.

[0014] Step 4, Preparation of calcium phosphate precursor powder by hydrothermal method:

[0015] The calcium phosphate precursor solution prepared in step 3 was stirred vigorously and then transferred to a stainless steel reactor lined with a polytetrafluoroethylene liner. It was heated at 200°C for 12 hours and then naturally cooled to room temperature. The resulting product was centrifuged, the precipitate was washed with anhydrous ethanol and deionized water, and then dried at 60°C for 12 hours to obtain calcium phosphate precursor powder.

[0016] Step 5: High-temperature calcination to prepare wolf-tooth-shaped calcium phosphate:

[0017] The calcium phosphate precursor powder prepared in step 4 was placed in a muffle furnace and calcined at 900°C for 1 hour. After cooling to room temperature with the furnace, the wolf-tooth-shaped calcium phosphate was obtained.

[0018] Furthermore, in step 3, the rapid stirring speed is 800-1000 rpm, and the phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 1-2 mL / min.

[0019] Furthermore, the heating rate of the reactor in step 4 is 5-10℃ / min.

[0020] Furthermore, in step 4, the centrifugation speed is 8000-10000 rpm, and the centrifugation time is 10-15 minutes.

[0021] Furthermore, in step 5, the heating rate of the muffle furnace is 2-5℃ / min.

[0022] The calcium phosphate prepared by the above method based on ion coordination-regulated directional nucleation for preparing club-shaped calcium phosphate has a club-shaped morphology with a length of 30-35 μm and high single-peak preference.

[0023] Based on the above applications of wolf-tooth-shaped calcium phosphate in bone tissue engineering scaffold materials, drug sustained-release carriers, and biomedical coatings.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] 1. Modulated Synthesis of Wolf-tooth-shaped Morphology Product: The prepared calcium phosphate exhibits a wolf-tooth-shaped morphology and good preferred orientation. This wolf-tooth-shaped structure possesses excellent cell compatibility and compressive strength four times higher than commercial powders. High unimodal preference optimizes the material's anisotropy and bioactivity, ensuring the matching degree between biodegradation rate and bone regeneration. The synergy of these three factors results in a material with significantly superior overall performance compared to traditional calcium phosphate.

[0026] 2. Ion-directed nucleation regulation: By synergistic regulation of PEG-6000 and ethanol solvent, ion-directed nucleation growth is achieved to obtain a wolf-tooth-shaped morphology;

[0027] 3. PEG-6000 with a long chain structure can be used as a template to complex with calcium ions at its active sites. The hydroxyl groups of ethanol play a regulatory role in the interaction between PEG-6000 and calcium ions, so that calcium ions are directionally adsorbed onto PEG-6000. Phosphate and calcium ions nucleate and grow in a directional manner to obtain a wolf-tooth-shaped morphology.

[0028] 4. Significant cost and environmental advantages: The raw materials used (CaCl2, (NH4)2HPO4, PEG-6000, ethanol) are all conventional chemical raw materials, which are inexpensive and do not require expensive equipment or special reagents; there is no emission of toxic gases during the reaction process, and the washing wastewater can meet the discharge standards after neutralization and filtration. The calcination of the precursor only produces CO2 and H2O, which is environmentally friendly.

[0029] 5. Broad application prospects: The calcium carbonate prepared by this method has a wolf-tooth-shaped structure and high single-peak selectivity, which makes it have significant application advantages in the fields of bone tissue engineering scaffolds, drug sustained-release carriers, and biomedical coatings, and can meet the high-performance requirements of different scenarios. Attached Figure Description

[0030] Figure 1 This is a schematic diagram of the method for preparing wolf-tooth-shaped calcium phosphate based on ion coordination-regulated directional nucleation according to the present invention;

[0031] Figure 2 The magnified metallographic image and length analysis diagram of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of this invention;

[0032] Figure 3 The X-ray diffraction patterns of the wolf-tooth-shaped calcium phosphate prepared in Examples 1-3 of this invention are shown below.

[0033] Figure 4 This is a scanning electron microscope image of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of the present invention;

[0034] Figure 5 The EDS spectrum of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of this invention;

[0035] Figure 6 This is a schematic diagram of the binding energy obtained by Gauss16 simulation calculation in Embodiment 1 of the present invention;

[0036] Figure 7 Isothermal adsorption-desorption curve of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of this invention;

[0037] Figure 8 This is a staining image of live and dead cells after co-culturing with MC3T3-E1 cells prepared in Example 1 of this invention;

[0038] Figure 9 The compressive strength curve and bar graph of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of the present invention compared with that of commercial powder pressed into column shape;

[0039] Figure 10 Scanning electron microscope images of calcium phosphate prepared according to proportions 1-2. Detailed Implementation

[0040] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and 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.

[0041] The present invention provides a method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation, such as... Figure 1 As shown in the flowchart, the specific operation steps are as follows:

[0042] Step 1, Preparation of calcium source-PEG composite solution:

[0043] Polyethylene glycol-6000 (PEG-6000) was added to ethanol and stirred until completely dissolved to obtain a PEG-6000 ethanol solution; calcium chloride (CaCl2) was added to the PEG-6000 ethanol solution and stirred until CaCl2 was completely dissolved to obtain a calcium source-PEG composite solution.

[0044] Step 2, Preparation of phosphorus source aqueous solution:

[0045] Add diammonium hydrogen phosphate (NH4)2HPO4 to deionized water and stir until completely dissolved to obtain an aqueous phosphorus source solution.

[0046] Step 3, Preparation of calcium phosphate precursor solution:

[0047] Under rapid stirring conditions (stirring speed of 800-1000 rpm), the phosphorus source aqueous solution prepared in step 2 is slowly added dropwise to the calcium source-PEG composite solution prepared in step 1. The phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 1-2 mL / min. After the addition is completed, stirring is continued for 10 minutes to obtain the calcium phosphate precursor solution.

[0048] Step 4, Preparation of calcium phosphate precursor powder by hydrothermal method:

[0049] The calcium phosphate precursor solution prepared in step 3 was stirred vigorously for 30 minutes, and then transferred to a 50 mL stainless steel reactor lined with polytetrafluoroethylene (Teflon). The reactor was heated at a rate of 5-10 °C / min and kept at 200 °C for 12 hours, and then allowed to cool naturally to room temperature. The product was centrifuged (centrifugation speed of 8000-10000 rpm, centrifugation time of 10-15 minutes), the precipitate was washed twice with anhydrous ethanol, then washed twice with deionized water, and then dried at 60 °C for 12 hours to obtain calcium phosphate precursor powder.

[0050] Step 5: High-temperature calcination to prepare wolf-tooth-shaped calcium phosphate:

[0051] The calcium phosphate precursor powder prepared in step 4 was placed in a muffle furnace. The heating rate of the muffle furnace was 2-5℃ / min. The powder was calcined at 900℃ for 1 hour and then cooled to room temperature with the furnace to obtain the wolf-tooth-shaped calcium phosphate. The prepared calcium phosphate had a wolf-tooth-shaped morphology with a length of 30-35μm and high single-peak selectivity.

[0052] The wolf-tooth-shaped calcium phosphate prepared by this invention can be used in bone tissue engineering scaffold materials, drug sustained-release carriers, and biomedical coatings.

[0053] Example 1

[0054] A method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation includes the following steps:

[0055] Step 1: Add 1g of PEG-6000 to 14mL of anhydrous ethanol, place in a 25℃ constant temperature water bath, and stir at 300rpm for 30 minutes until PEG-6000 is completely dissolved; add 0.33g of CaCl2, and continue stirring at 25℃ and 300rpm for 20 minutes to obtain a transparent calcium source-PEG composite solution.

[0056] Step 2: Add 0.264g of (NH4)2HPO4 to 10mL of deionized water and stir at 200rpm for 10 minutes at room temperature until (NH4)2HPO4 is completely dissolved to obtain a transparent phosphorus source aqueous solution.

[0057] Step 3: Place the calcium source-PEG composite solution on a magnetic stirrer and adjust the stirring speed to 800 rpm. Use a pipette to slowly add the phosphorus source aqueous solution to the composite solution. During the addition process, a white suspension gradually appears in the solution. The phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 1 mL / min. After the addition is completed, keep stirring at 800 rpm for 10 minutes to obtain a homogeneous calcium phosphate precursor solution.

[0058] Step 4: The calcium phosphate precursor solution prepared in Step 3 was stirred vigorously for 30 minutes, then transferred to a 50 mL Teflon-lined stainless steel reactor and heated to 200 °C at a heating rate of 5 °C / min. The reactor was kept at this temperature for 12 hours and then allowed to cool naturally to room temperature. The product in the reactor was transferred to a centrifuge tube and centrifuged at 8000 rpm for 10 minutes. The white precipitate at the bottom was collected. The precipitate was washed twice with anhydrous ethanol and then twice with deionized water. The washed precipitate was dried in a 60 °C oven for 12 hours to obtain approximately 0.3 g of white calcium phosphate precursor powder.

[0059] Step 5: Place the calcium phosphate precursor powder in a corundum boat, put it in a muffle furnace, heat it to 900°C at a heating rate of 5°C / min, and calcine it for 1 hour; after cooling to room temperature in the furnace, take it out to obtain white, wolf-tooth-shaped calcium phosphate.

[0060] Example 2

[0061] Compared with Example 1, both increasing the sample preparation size by 3 times and 9 times yielded wolf-tooth-shaped calcium phosphate.

[0062] A method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation includes the following steps:

[0063] Step 1: Add 3g of PEG-6000 to 42mL of anhydrous ethanol, place in a 25℃ constant temperature water bath, and stir at 300rpm for 30 minutes until PEG-6000 is completely dissolved; add 0.99g of CaCl2, and continue stirring at 25℃ and 300rpm for 20 minutes to obtain a transparent calcium source-PEG composite solution.

[0064] Step 2: Add 0.795g (NH4)2HPO4 to 30mL of deionized water and stir at 200rpm for 10 minutes at room temperature until (NH4)2HPO4 is completely dissolved to obtain a transparent phosphorus source aqueous solution.

[0065] Step 3: Place the calcium source-PEG composite solution on a magnetic stirrer and adjust the stirring speed to 900 rpm. Use a pipette to slowly add the phosphorus source aqueous solution to the composite solution. During the addition process, a white suspension gradually appears in the solution. The phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 2 mL / min. After the addition is completed, keep stirring at 900 rpm for 10 minutes to obtain a homogeneous calcium phosphate precursor solution.

[0066] Step 4: The calcium phosphate precursor solution prepared in Step 3 was stirred vigorously for 30 minutes, then transferred to a 50 mL LFlon-lined stainless steel reactor. The reactor was heated to 200 °C at a heating rate of 8 °C / min and reacted at this temperature for 12 hours. The mixture was then allowed to cool naturally to room temperature. The product in the reactor was transferred to a centrifuge tube and centrifuged at 9000 rpm for 13 minutes. The white precipitate at the bottom was collected. The precipitate was washed twice with anhydrous ethanol and then twice with deionized water. The washed precipitate was dried in a 60 °C oven for 12 hours to obtain approximately 0.9 g of white calcium phosphate precursor powder.

[0067] Step 5: Place the calcium phosphate precursor powder in a corundum boat, put it in a muffle furnace, heat it to 900°C at a heating rate of 2°C / min, and calcine it for 1 hour; after cooling to room temperature in the furnace, take it out to obtain white, wolf-tooth-shaped calcium phosphate.

[0068] Example 3

[0069] A method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation includes the following steps:

[0070] Step 1: Add 9g of PEG-6000 to 126mL of anhydrous ethanol, place in a 25℃ constant temperature water bath, and stir at 300rpm for 30 minutes until PEG-6000 is completely dissolved; add 2.97g of CaCl2, and continue stirring at 25℃ and 300rpm for 20 minutes to obtain a transparent calcium source-PEG composite solution.

[0071] Step 2: Add 2.376g of (NH4)2HPO4 to 90mL of deionized water and stir at 200rpm for 10 minutes at room temperature until (NH4)2HPO4 is completely dissolved to obtain a transparent phosphorus source aqueous solution.

[0072] Step 3: Place the calcium source-PEG composite solution on a magnetic stirrer and adjust the stirring speed to 1000 rpm. Use a pipette to slowly add the phosphorus source aqueous solution to the composite solution. During the addition process, a white suspension gradually appears in the solution. The phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 2 mL / min. After the addition is completed, keep stirring at 1000 rpm for 10 minutes to obtain a homogeneous calcium phosphate precursor solution.

[0073] Step 4: The calcium phosphate precursor solution prepared in Step 3 is stirred vigorously for 30 minutes, then transferred to a 50 mL LFlon stainless steel reactor with a heating rate of 10 °C / min to 200 °C, and reacted at a constant temperature for 12 hours. The mixture is then allowed to cool naturally to room temperature. The product in the reactor is transferred to a centrifuge tube and centrifuged at 10,000 rpm for 15 minutes. The white precipitate at the bottom is collected. The precipitate is washed twice with anhydrous ethanol and then twice with deionized water. The washed precipitate is dried in a 60 °C oven for 12 hours to obtain white calcium phosphate precursor powder.

[0074] Step 5: Place the calcium phosphate precursor powder in a corundum boat, put it in a muffle furnace, heat it to 900°C at a heating rate of 2°C / min, and calcine it for 1 hour; after cooling to room temperature in the furnace, take it out to obtain white, wolf-tooth-shaped calcium phosphate.

[0075] Comparative Example 1

[0076] Step 1: Add 1g of PEG-2000 to 14mL of anhydrous ethanol, place in a 25℃ constant temperature water bath, and stir at 300rpm for 30 minutes until PEG-6000 is completely dissolved; add 0.33g of CaCl2, and continue stirring at 25℃ and 300rpm for 20 minutes to obtain a transparent calcium source-PEG composite solution.

[0077] Step 2: Add 0.264g of (NH4)2HPO4 to 10mL of deionized water and stir at 200rpm for 10 minutes at room temperature until (NH4)2HPO4 is completely dissolved to obtain a transparent phosphorus source aqueous solution.

[0078] Step 3: Place the calcium source-PEG composite solution on a magnetic stirrer and adjust the stirring speed to 800 rpm. Use a pipette to slowly add the phosphorus source aqueous solution to the composite solution. During the addition process, a white suspension gradually appears in the solution. The phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 1 mL / min. After the addition is completed, keep stirring at 800 rpm for 10 minutes to obtain a homogeneous calcium phosphate precursor solution.

[0079] Step 4: The calcium phosphate precursor solution prepared in Step 3 was stirred vigorously for 30 minutes, then transferred to a 50 mL LFlon-lined stainless steel reactor and heated to 200 °C at a heating rate of 5 °C / min. The reactor was kept at this temperature for 12 hours and then allowed to cool naturally to room temperature. The product in the reactor was transferred to a centrifuge tube and centrifuged at 8000 rpm for 10 minutes. The white precipitate at the bottom was collected. The precipitate was washed twice with anhydrous ethanol and then twice with deionized water. The washed precipitate was dried in a 60 °C oven for 12 hours to obtain approximately 0.3 g of white calcium phosphate precursor powder.

[0080] Step 5: Place the calcium phosphate precursor powder in a corundum boat, put it in a muffle furnace, heat it to 900°C at a heating rate of 5°C / min, and calcine it for 1 hour; after cooling to room temperature in the furnace, take it out to obtain calcium phosphate.

[0081] Comparative Example 2

[0082] Step 1: Add 1g of PEG-6000 to 14mL of deionized water, place in a 25℃ constant temperature water bath, and stir at 300rpm for 30 minutes until PEG-6000 is completely dissolved; add 0.33g of CaCl2, and continue stirring at 25℃ and 300rpm for 20 minutes to obtain a transparent calcium source-PEG composite solution.

[0083] Step 2: Add 0.264g of (NH4)2HPO4 to 10mL of deionized water and stir at 200rpm for 10 minutes at room temperature until (NH4)2HPO4 is completely dissolved to obtain a transparent phosphorus source aqueous solution.

[0084] Step 3: Place the calcium source-PEG composite solution on a magnetic stirrer and adjust the stirring speed to 800 rpm. Use a pipette to slowly add the phosphorus source aqueous solution to the composite solution. During the addition process, a white suspension gradually appears in the solution. The phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 1 mL / min. After the addition is completed, keep stirring at 800 rpm for 10 minutes to obtain a homogeneous calcium phosphate precursor solution.

[0085] Step 4: The calcium phosphate precursor solution prepared in Step 3 was stirred vigorously for 30 minutes, then transferred to a 50 mL LFlon-lined stainless steel reactor and heated to 200 °C at a heating rate of 5 °C / min. The reactor was kept at this temperature for 12 hours and then allowed to cool naturally to room temperature. The product in the reactor was transferred to a centrifuge tube and centrifuged at 8000 rpm for 10 minutes. The white precipitate at the bottom was collected. The precipitate was washed twice with anhydrous ethanol and then twice with deionized water. The washed precipitate was dried in a 60 °C oven for 12 hours to obtain approximately 0.3 g of white calcium phosphate precursor powder.

[0086] Step 5: Place the calcium phosphate precursor powder in a corundum boat, put it in a muffle furnace, heat it to 900°C at a heating rate of 5°C / min, and calcine it for 1 hour; after cooling to room temperature in the furnace, take it out to obtain calcium phosphate.

[0087] Figure 2 The magnified metallographic image and length analysis diagram of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of this invention are shown. The morphology of the material prepared in this example was observed using a metallographic microscope, revealing a uniformly distributed wolf-tooth-shaped structure. Figure 2 As shown in (a1); particle size analysis revealed that its length was basically distributed in the range of 30-35 μm, as... Figure 2 As shown in (a2), it conforms to the morphology and size requirements obtained in this invention.

[0088] Figure 3 The X-ray diffraction patterns of the club-shaped calcium phosphate prepared in Examples 1-3 of this invention are shown below. Figure 3 As can be seen from the diffraction peaks of Examples 1 to 3, they all exhibit a phase with extremely strong single-peak selectivity, which is consistent with the phase obtained in this invention, and the batch repeatability is good.

[0089] Figure 4 This is a scanning electron microscope image of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of the present invention. Figure 4 (a1) is a SEM image of a single rod-shaped structure magnified 500 times in Example 1. Figure 4 (a2) is a SEM image magnified 2000 times. Figure 4 (b1) is a SEM image of the rod-shaped intercalation in Example 1 magnified 500 times. Figure 4 (b2) is a SEM image magnified 2000 times. As can be seen from the image, the rod-shaped calcium phosphate synthesized by the method of the present invention has both the toughening effect of a single rod and the ability of multiple rods to intercalate to increase the porosity of the material to a certain extent, which is beneficial to the subsequent application of cells in biomaterials for cell adhesion and growth.

[0090] Figure 5 The image shows the EDS spectrum of the club-shaped calcium phosphate prepared in Example 1 of this invention. The presence of calcium and phosphorus elements in the sample is evident from the image.

[0091] Figure 6 This is a schematic diagram of the binding energy obtained by Gauss16 simulation calculation in Embodiment 1 of the present invention. Figure 6 (a) is a schematic diagram of the binding energy of PEG-6000 obtained from Gauss16 simulation calculations. Figure 6 (b) is a schematic diagram of the binding energy of PEG-6000 complexed with calcium ions obtained after Gauss16 simulation calculation. It can be seen that the energy of the PEG-6000 molecule itself is negative, and the energy becomes more negative after complexing with calcium ions, indicating that the reaction is easier to proceed, which proves that PEG-6000 has the effect of complexing and modifying calcium ions.

[0092] Figure 7 The isothermal adsorption-desorption curve of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of this invention has a BET of 0.8172 m² / g. When this calcium phosphate with low specific surface area / low pore volume is used as bone cement, it will be more dense after solidification and have stronger mechanical strength, thus achieving good mechanical properties.

[0093] Figure 8 The image shows the staining of live and dead cells after co-culturing the wolf-tooth-shaped calcium phosphate prepared in Example 1 of this invention with MC3T3-E1, demonstrating the good biocompatibility of this material.

[0094] Figure 9 The graphs and bar charts show the compressive strength curves and bar graphs of the wolf-tooth-shaped calcium phosphate prepared in Example 1 of this invention compared to commercial powder after being pressed into a column. The graphs confirm that the compressive strength of the wolf-tooth-shaped calcium phosphate is nearly 4 times higher than that of the commercial powder.

[0095] Figure 10 The images shown are scanning electron microscope (SEM) images of the calcium phosphate prepared in Comparative Examples 1-2. Figure 10 (a) is a SEM image of Comparative Example 1 magnified 5000 times. Figure 10 (b) is a SEM image magnified 1000 times from Comparative Example 2. Figure 10 It can be seen that calcium phosphate prepared without PEG-6000 or ethanol cannot exhibit a rod-like morphology.

[0096] Rod-shaped calcium phosphate has important applications in the biomedical field due to its anisotropic structure similar to natural bone minerals and its excellent biocompatibility: in bone tissue engineering, it can enhance the mechanical properties of scaffolds and promote the directional growth of osteoblasts and bone integration; as a drug sustained-release carrier, it can achieve efficient drug loading and controlled release; in medical coatings, it can enhance the bioactivity and stability of implant surfaces, thereby accelerating the bone repair and fusion process.

[0097] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation, characterized in that, Specifically, the following steps are included: Step 1, Preparation of calcium source-PEG composite solution: Polyethylene glycol-6000 was added to ethanol and stirred until completely dissolved to obtain a PEG-6000 ethanol solution; calcium chloride was added to the PEG-6000 ethanol solution and stirred until the calcium chloride was completely dissolved to obtain a calcium source-PEG composite solution. Step 2, Preparation of phosphorus source aqueous solution: Add diammonium hydrogen phosphate to deionized water and stir until completely dissolved to obtain an aqueous solution of phosphorus source; Step 3, Preparation of calcium phosphate precursor solution: Under rapid stirring conditions, the phosphorus source aqueous solution prepared in step 2 was slowly added dropwise to the calcium source-PEG composite solution prepared in step 1. After the addition was completed, stirring was continued to obtain a calcium phosphate precursor solution. Step 4, Preparation of calcium phosphate precursor powder by hydrothermal method: The calcium phosphate precursor solution prepared in step 3 was stirred vigorously and then transferred to a stainless steel reactor lined with a polytetrafluoroethylene liner. It was heated at 200°C for 12 hours and then naturally cooled to room temperature. The resulting product was centrifuged, the precipitate was washed with anhydrous ethanol and deionized water, and then dried at 60°C for 12 hours to obtain calcium phosphate precursor powder. Step 5: High-temperature calcination to prepare wolf-tooth-shaped calcium phosphate: The calcium phosphate precursor powder prepared in step 4 was placed in a muffle furnace and calcined at 900°C for 1 hour. After cooling to room temperature with the furnace, the wolf-tooth-shaped calcium phosphate was obtained.

2. The method for preparing wolf-tooth-shaped calcium phosphate based on ion coordination-regulated directional nucleation according to claim 1, characterized in that, In step 3, the rapid stirring speed is 800-1000 rpm, and the phosphorus source aqueous solution is added to the calcium source-PEG composite solution at a rate of 1-2 mL / min.

3. The method for preparing wolf-tooth-shaped calcium phosphate based on ion coordination-regulated directional nucleation according to claim 1, characterized in that, The heating rate of the reactor in step 4 is 5-10℃ / min.

4. The method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation according to claim 1, characterized in that, In step 4, the centrifugation speed is 8000-10000 rpm, and the centrifugation time is 10-15 minutes.

5. The method for preparing club-shaped calcium phosphate based on ion coordination-regulated directional nucleation according to claim 1, characterized in that, In step 5, the heating rate of the muffle furnace is 2-5℃ / min.

6. The calcium phosphate prepared by the method for preparing wolf-tooth-shaped calcium phosphate based on ion coordination-regulated directional nucleation according to any one of claims 1-5 has a wolf-tooth-shaped morphology, a length of 30-35 μm, and high single-peak preference.

7. The application of the wolf-tooth-shaped calcium phosphate according to claim 6 in bone tissue engineering scaffold materials, drug sustained-release carriers, and biomedical coatings.

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