Micron-sized elliptical hydroxyapatite microsphere and preparation method thereof

Abstract

The invention provides a preparation method of micron-sized elliptical hydroxyapatite microspheres, which comprises the following steps: S1, adding hydroxyapatite powder into a first solution, and sequentially adding a binder and a dispersant to obtain hydroxyapatite precursor slurry; s2, dropwise adding the hydroxyapatite precursor slurry into a cross-linking solution, and cross-linking and curing to form a spherical hydroxyapatite microsphere precursor; and S3, washing and drying the spherical hydroxyapatite microsphere precursor, spreading the spherical hydroxyapatite microsphere precursor on the surface of a constant-temperature heating plate, carrying out preheating treatment, and carrying out calendering treatment to obtain the micron-sized elliptical hydroxyapatite microsphere. According to the preparation method disclosed by the invention, stable and controllable preparation of the monodisperse elliptical hydroxyapatite microspheres under the micron scale is realized through a step-by-step strategy of spherical forming, stable shaping and thermoplastic secondary calendering.

Description

Technical Field

[0001] This invention relates to the field of inorganic biomaterials and functional ceramic materials, and in particular to a micron-sized elliptical hydroxyapatite microsphere and its preparation method. Background Technology

[0002] Hydroxyapatite (Ca 10 (PO4)6(OH)2, as an important bio-inorganic material, has wide applications in bone repair materials, biomedical fillers, drug delivery carriers, chromatographic fillers, and functional composite materials due to its excellent biocompatibility, bioactivity, and chemical stability. Currently, spherical hydroxyapatite microspheres are the most common morphology. However, traditional spherical hydroxyapatite microspheres have limitations such as monotonous morphology, limited specific surface area, and limited interfacial interaction modes, which restricts their further application in biomimetic materials, tissue engineering scaffolds, and functional composite materials.

[0003] Micron-sized elliptical hydroxyapatite microspheres exhibit significant advantages in specific surface area, particle packing patterns, and interfacial contact behavior due to their non-spherical and anisotropic geometric structure. The elliptical structure imparts curvature distributions in different directions to the microspheres, making them more prone to directional alignment under shear or external fields, which is beneficial for constructing anisotropic materials. Simultaneously, elliptical microspheres can enhance the mechanical interlocking between particles and between particles and the matrix in composite systems, thereby improving overall mechanical properties. However, existing methods for preparing hydroxyapatite microspheres can only obtain spherical particles, and it is difficult to achieve controllable preparation of non-spherical, anisotropic microspheres at the micron scale while maintaining monodispersity and structural integrity. In particular, existing liquid-phase microsphere formation, spray microsphere formation, and microfluidic microsphere formation processes struggle to directly obtain regularly shaped elliptical microspheres during the microsphere formation stage.

[0004] Therefore, developing a simple, morphology-controllable, and scalable method for preparing micron-sized elliptical hydroxyapatite microspheres is of significant scientific importance and application value. Summary of the Invention

[0005] To address the technical problems in the prior art, this invention provides a micron-sized elliptical hydroxyapatite microsphere and its preparation method. This invention achieves stable and controllable preparation of monodisperse elliptical hydroxyapatite microspheres at the micron scale through a step-by-step strategy of "spherical forming-stabilization-thermoplastic secondary calendering".

[0006] The primary objective of this invention is to provide a method for preparing micron-sized elliptical hydroxyapatite microspheres, the method comprising: S1 Preparation of hydroxyapatite precursor slurry: Add hydroxyapatite powder to deionized water or a deionized water-ethanol mixed solvent, then add binder and dispersant in sequence, and stir and mix to obtain hydroxyapatite precursor slurry; S2 Preparation of spherical hydroxyapatite microspheres: The hydroxyapatite precursor slurry is dropped into a crosslinking solution and crosslinked and solidified by liquid phase spheroidization to form a spherical hydroxyapatite microsphere precursor; S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: After washing and drying the spherical hydroxyapatite microsphere precursor, it is spread on the surface of a constant temperature heating plate for preheating treatment to obtain preheated spherical hydroxyapatite microspheres; then the preheated spherical hydroxyapatite microspheres are rolled and cooled to room temperature to obtain micron-sized elliptical hydroxyapatite microspheres.

[0007] Specifically, the average particle size of the hydroxyapatite powder in step S1 is in the nanometer or submicrometer range; the mass ratio of the hydroxyapatite powder, binder and dispersant is 50:5:1.

[0008] Specifically, the binder in step S1 is any one or more of polyvinyl alcohol, gelatin, and sodium alginate; the dispersant is any one or more of polyacrylate and sodium citrate; and the polyacrylate is sodium polyacrylate or potassium polyacrylate.

[0009] Specifically, the stirring and mixing process in step S1 includes: magnetic stirring at room temperature for 20-30 minutes, followed by uniform dispersion under ultrasonic conditions for 10-20 minutes.

[0010] Specifically, the concentration of the crosslinking solution in step S2 is 0.05-0.5 mol / L, the solute in the crosslinking solution is any one of calcium chloride, barium chloride, magnesium chloride, boric acid, and borate; the solvent in the crosslinking solution is a mixed solvent of deionized water and ethanol, wherein the ethanol content is 0-10%; and the borate is sodium tetraborate.

[0011] Specifically, in step S2, the volume ratio of the hydroxyapatite precursor slurry to the crosslinking solution is 1:(5-20); the crosslinking and curing method is static crosslinking or uniform magnetic stirring at a speed of 500-200 rpm; the reaction temperature for crosslinking and curing is 10-30℃, and the time is 10-30 min.

[0012] Specifically, the preheating treatment in step S3 is performed at a temperature of 80-120°C for 3-5 minutes.

[0013] Specifically, the calendering process involves applying a uniform pressure of 0.5-5 MPa to the preheated spherical hydroxyapatite microspheres in a single direction and then rolling them at a constant speed for 1-3 minutes.

[0014] The second objective of this invention is to provide a micron-sized elliptical hydroxyapatite microsphere prepared by the preparation method described above.

[0015] Compared with the prior art, the beneficial effects of the present invention include: (1) The present invention adopts a secondary morphology control strategy of liquid phase spheroidization combined with thermoplastic assisted directional calendering. Under the premise of not destroying the overall integrity and monodispersity of the microspheres, the stable transformation of spherical hydroxyapatite microspheres into elliptical microspheres is achieved. The elliptical hydroxyapatite microspheres have obvious geometric anisotropy and show more outstanding technical effects than spherical microspheres in terms of specific surface area, interfacial contact mode and mechanical interlocking. Under the same particle size conditions, elliptical microspheres can form a composite interface structure of "combination of surface contact and line contact", thereby improving the interface utilization efficiency. (2) Compared with existing technologies that directly form spheres through spray drying, microfluidic atomization, etc., this invention does not attempt to obtain non-spherical structures during the droplet forming stage; instead, it avoids the problem of spontaneous spheroidization of morphology caused by interfacial tension during the droplet forming process by adopting a step-by-step strategy of "spheroid forming-stabilization-thermoplastic secondary calendering". Thus, it achieves stable and controllable preparation of monodisperse elliptical hydroxyapatite microspheres at the micrometer scale for the first time. (3) The micron-sized elliptical hydroxyapatite microspheres prepared by the present invention are applied to the composite material system. After the elliptical hydroxyapatite microspheres are introduced into the matrix as filler phase, the rotation and slip behavior of the filler can be effectively suppressed, the stress transmission path can be improved, and the overall modulus, crack resistance and anisotropic mechanical response of the composite material are significantly improved. Attached Figure Description

[0016] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description are merely exemplary, and those skilled in the art can derive other embodiments based on the provided drawings without creative effort.

[0017] Figure 1 A scanning electron microscope image of the elliptical hydroxyapatite microspheres prepared in Example 1 of this invention; Figure 2 The particle size distribution diagram of the elliptical hydroxyapatite microspheres prepared in Example 1 of the present invention is shown. Figure 3 This is a macroscopic morphology diagram of the elliptical hydroxyapatite microsphere dispersion prepared in Example 1 of the present invention; Figure 4(ab) are the specific surface area diagrams of the elliptical hydroxyapatite microspheres prepared in Example 1 of the present invention and the spherical hydroxyapatite microspheres prepared in Comparative Example 1, respectively. Figure 5 A bar chart comparing the elastic modulus of the composite material prepared using elliptical hydroxyapatite microspheres as filler in Example 1 of the present invention, the composite material prepared using hydroxyapatite microspheres as filler in Comparative Example 1, and the pure matrix material. Figure 6 The polar coordinate comparison diagram of the anisotropic mechanical response of the composite material prepared by using elliptical hydroxyapatite microspheres as filler in Example 1 of the present invention, the composite material prepared by using hydroxyapatite microspheres as filler in Comparative Example 1, and the pure matrix material is shown. Detailed Implementation

[0018] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. 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. Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing specific embodiments only and is not intended to limit the present invention. Example 1

[0019] S1 Preparation of hydroxyapatite precursor slurry: Add 5.0 g of hydroxyapatite powder (average particle size of about 200 nm) to 100 mL of deionized water or water-ethanol mixed solvent, then add 0.5 g of polyvinyl alcohol (PVA, as a binder) and 0.1 g of sodium citrate (as a dispersant) in sequence. Stir magnetically at room temperature for 30 min, and then treat under ultrasonic conditions for 15 min to obtain a uniformly dispersed hydroxyapatite precursor slurry without obvious agglomeration. S2 Preparation of spherical hydroxyapatite microspheres: 100 mL of the hydroxyapatite precursor slurry was dropped into 1000 mL of crosslinking solution (solute is calcium chloride, solvent is deionized water, concentration is 0.1 mol / L), and the crosslinking was cured at 30 °C for 20 min by liquid phase spheroidization to form spherical hydroxyapatite microsphere precursors. S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: The spherical hydroxyapatite microsphere precursor was washed three times with deionized water, then dried in a vacuum drying oven at 60°C for 8 hours. After drying, it was spread on the surface of a constant temperature heating plate and preheated at 80°C for 4 minutes to obtain preheated spherical hydroxyapatite microspheres. The preheated spherical hydroxyapatite microspheres were then subjected to a pressure of 1 MPa in a single direction and rolled at a uniform speed for 2 minutes for calendering. After cooling to room temperature, the micron-sized elliptical hydroxyapatite microspheres prepared in Example 1 were obtained. Example 2

[0020] S1 Preparation of hydroxyapatite precursor slurry: Add 5.0 g of hydroxyapatite powder (average particle size of about 100 μm) to 100 mL of deionized water or water-ethanol mixed solvent, then add 0.5 g of gelatin (as binder) and 0.1 g of sodium polyacrylate (as dispersant) in sequence. Stir magnetically at room temperature for 20 min, and then treat under ultrasonic conditions for 10 min to obtain a uniformly dispersed hydroxyapatite precursor slurry without obvious agglomeration. S2 Preparation of spherical hydroxyapatite microspheres: 100 mL of the hydroxyapatite precursor slurry was dropped into 500 mL of crosslinking solution (concentration of 0.05 mol / L, solute of barium chloride, solvent of deionized water-ethanol mixed solvent, wherein ethanol content is 5%), and crosslinked and cured at 20 °C for 30 min by liquid phase spheroidization to form spherical hydroxyapatite microsphere precursors; S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: The spherical hydroxyapatite microsphere precursor was washed twice with deionized water, then placed in a vacuum drying oven and dried at 60°C for 8 hours. After drying, it was spread on the surface of a constant temperature heating plate and preheated at 100°C for 3 minutes to obtain preheated spherical hydroxyapatite microspheres. The preheated spherical hydroxyapatite microspheres were then subjected to a pressure of 2 MPa in a single direction and rolled at a uniform speed for 3 minutes for calendering. After cooling to room temperature, the micron-sized elliptical hydroxyapatite microspheres prepared in Example 2 were obtained. Example 3

[0021] S1 Preparation of hydroxyapatite precursor slurry: Add 5.0 g of hydroxyapatite powder (average particle size of about 500 nm) to 100 mL of deionized water or water-ethanol mixed solvent, then add 0.5 g of sodium alginate (as binder) and 0.1 g of potassium polyacrylate (as dispersant) in sequence. Stir magnetically at room temperature for 25 min, and then treat under ultrasonic conditions for 20 min to obtain a uniformly dispersed hydroxyapatite precursor slurry without obvious agglomeration. S2 Preparation of spherical hydroxyapatite microspheres: 100 mL of the hydroxyapatite precursor slurry was dropped into 2000 mL of crosslinking solution (concentration of 0.2 mol / L, solute of magnesium chloride, solvent of deionized water-ethanol mixed solvent (ethanol content of 10%)), and crosslinked and cured for 20 min at 30 °C and 500 rpm under magnetic stirring by liquid phase spheroidization to form spherical hydroxyapatite microsphere precursors; S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: The spherical hydroxyapatite microsphere precursor was washed twice with deionized water, then dried in a vacuum drying oven at 60°C for 8 hours. After drying, it was spread on the surface of a constant temperature heating plate and preheated at 120°C for 3 minutes to obtain preheated spherical hydroxyapatite microspheres. The preheated spherical hydroxyapatite microspheres were then subjected to a pressure of 0.8 MPa in a single direction and rolled at a uniform speed for 3 minutes for calendering. After cooling to room temperature, the micron-sized elliptical hydroxyapatite microspheres prepared in Example 3 were obtained.

[0022] Example 4 S1 Preparation of hydroxyapatite precursor slurry: Add 5.0 g of hydroxyapatite powder (average particle size of about 10 μm) to 100 mL of deionized water or water-ethanol mixed solvent, then add 0.5 g of polyvinyl alcohol (PVA, as a binder) and 0.1 g of sodium citrate (as a dispersant) in sequence. Stir magnetically at room temperature for 30 min, and then treat under ultrasonic conditions for 15 min to obtain a uniformly dispersed hydroxyapatite precursor slurry without obvious agglomeration. S2 Preparation of spherical hydroxyapatite microspheres: 100 mL of the hydroxyapatite precursor slurry was dropped into 1000 mL of crosslinking solution (solute is boric acid, solvent is deionized water, concentration is 0.1 mol / L), and the crosslinking was cured at 30 °C for 20 min by liquid phase spheroidization to form spherical hydroxyapatite microsphere precursors. S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: The spherical hydroxyapatite microsphere precursor was washed three times with deionized water, then dried in a vacuum drying oven at 60°C for 8 hours. After drying, it was spread on the surface of a constant temperature heating plate and preheated at 80°C for 4 minutes to obtain preheated spherical hydroxyapatite microspheres. The preheated spherical hydroxyapatite microspheres were then subjected to a pressure of 0.6 MPa in a single direction and rolled at a uniform speed for 2 minutes for calendering. After cooling to room temperature, the micron-sized elliptical hydroxyapatite microspheres prepared in Example 4 were obtained. Example 5

[0023] S1 Preparation of hydroxyapatite precursor slurry: Add 5.0 g of hydroxyapatite powder (average particle size of about 2 μm) to 100 mL of deionized water or water-ethanol mixed solvent, then add 0.5 g of gelatin (as binder) and 0.1 g of sodium citrate (as dispersant) in sequence. Stir magnetically for 30 min at room temperature, and then treat under ultrasonic conditions for 15 min to obtain a uniformly dispersed hydroxyapatite precursor slurry without obvious agglomeration. S2 Preparation of spherical hydroxyapatite microspheres: 100 mL of the hydroxyapatite precursor slurry was dropped into 500 mL of crosslinking solution (solute is sodium tetraborate, solvent is deionized water, concentration is 0.5 mol / L), and the crosslinking was cured at 30 °C for 20 min by liquid phase spheroidization to form spherical hydroxyapatite microsphere precursors. S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: The spherical hydroxyapatite microsphere precursor was washed three times with deionized water, then dried in a vacuum drying oven at 60°C for 8 hours. After drying, it was spread on the surface of a constant-temperature heating plate and preheated at 80°C for 4 minutes to obtain preheated spherical hydroxyapatite microspheres. The preheated spherical hydroxyapatite microspheres were then subjected to a pressure of 0.7 MPa in a single direction and rolled at a uniform speed for 2 minutes for calendering. After cooling to room temperature, the micron-sized elliptical hydroxyapatite microspheres prepared in Example 5 were obtained. Comparative Example 1

[0024] S1 Preparation of hydroxyapatite precursor slurry: Add 5.0 g of hydroxyapatite powder (average particle size of about 200 nm) to 100 mL of deionized water or water-ethanol mixed solvent, then add 0.5 g of polyvinyl alcohol (PVA, as a binder) and 0.1 g of sodium citrate (as a dispersant) in sequence. Stir magnetically at room temperature for 30 min, and then treat under ultrasonic conditions for 15 min to obtain a uniformly dispersed hydroxyapatite precursor slurry without obvious agglomeration. S2 Preparation of spherical hydroxyapatite microspheres: 100 mL of the hydroxyapatite precursor slurry was dropped into 1000 mL of crosslinking solution (solute is calcium chloride, solvent is deionized water, concentration is 0.1 mol / L), and the crosslinking was cured at 30 °C for 20 min by liquid phase spheroidization to form spherical hydroxyapatite microsphere precursors. S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: The spherical hydroxyapatite microsphere precursor was washed three times with deionized water, then placed in a vacuum drying oven and dried at 60°C for 8 hours. After drying, it was spread on the surface of a constant temperature heating plate and heat-treated at 80°C for 4 minutes to obtain the spherical hydroxyapatite microspheres prepared in Comparative Example 1.

[0025] Performance testing The obtained elliptical hydroxyapatite microspheres were observed using a scanning electron microscope. Figure 1 A scanning electron microscope image of the elliptical hydroxyapatite microspheres prepared in Example 1 of this invention; from Figure 1 It can be seen that the prepared hydroxyapatite particles have a regular morphology, with a uniform elliptical structure, smooth and continuous surface, and no obvious breakage or aggregation. This indicates that the hot rolling process can achieve a stable morphological transformation while maintaining the integrity of the particles. Figure 2 This is a particle size distribution diagram of the elliptical hydroxyapatite microspheres prepared in Example 1 of the present invention; from Figure 2 It can be seen that the prepared elliptical hydroxyapatite microspheres have a concentrated particle size distribution, with the vast majority of particles distributed in the range of 30-40 μm, showing good monodispersity, indicating that the hot rolling morphology conversion process did not introduce obvious particle size dispersion. Figure 3 This is a macroscopic morphology image of the elliptical hydroxyapatite microsphere dispersion prepared in Example 1 of this invention; as shown. Figure 3 As shown, the obtained elliptical hydroxyapatite microspheres exhibit a uniform white dispersion in the dispersion medium, and no obvious sedimentation or agglomeration was observed, indicating that they have good macroscopic dispersion stability. Figure 4 (ab) are the specific surface area diagrams of the elliptical hydroxyapatite microspheres prepared in Example 1 and the spherical hydroxyapatite microspheres prepared in Comparative Example 1, respectively; Figure 4 As shown, the specific surface area of ​​the elliptical hydroxyapatite microspheres is 2.3 m². 2 / g, while the specific surface area of ​​spherical hydroxyapatite microspheres of the same size is 1.9 m². 2 / g, the former has a significantly increased specific surface area, which may be beneficial for providing more effective interfaces in composite materials or biological bone substitutes.

[0026] To evaluate the influence of elliptical hydroxyapatite microsphere morphology on the mechanical properties of composite materials, elliptical hydroxyapatite microspheres were used as fillers to prepare composite materials, which were then compared with composite materials filled with spherical hydroxyapatite microspheres and pure matrix materials. The specific composite material preparation method is as follows: Poly(L-lactic acid) (PLLA, molecular weight 100,000) was selected as the matrix material. A certain amount of PLLA particles was dissolved in dichloromethane to prepare a polymer solution with a concentration of 10 wt%. Elliptical hydroxyapatite microspheres prepared in Example 1 and spherical hydroxyapatite microspheres prepared in Comparative Example 1 were weighed out at 10 wt% and added to the PLLA solution. The mixture was magnetically stirred for 2 hours under ultrasonic dispersion assistance to ensure uniform dispersion of the microspheres in the matrix solution. Subsequently, the mixed slurry was poured into a polytetrafluoroethylene mold, and the solvent was allowed to evaporate naturally at room temperature for 24 hours using a solution casting method. Then, it was dried in a vacuum drying oven for 48 hours to completely remove residual solvent, resulting in a hydroxyapatite / PLLA composite film of uniform thickness. Finally, the composite film was cut into standard strips for mechanical property testing.

[0027] Figure 5 This is a bar chart comparing the elastic moduli of the composite material prepared using elliptical hydroxyapatite microspheres as fillers in Example 1 of this invention, the composite material prepared using hydroxyapatite microspheres as fillers in Comparative Example 1, and the pure matrix material. Figure 5 It can be seen that, under the same filler conditions, the composite material filled with elliptical hydroxyapatite microspheres prepared in Example 1 of this invention exhibits a significantly higher elastic modulus than the pure matrix material and the composite material filled with spherical hydroxyapatite microspheres, indicating that the elliptical particle morphology is beneficial to improving the overall stiffness of the composite material. This modulus improvement is mainly attributed to the anisotropic geometry introduced by the elliptical hydroxyapatite microspheres, which helps to form a more effective mechanical interlocking effect in the matrix, thereby improving the interfacial stress transfer efficiency. In addition, the mechanical properties of hydroxyapatite microsphere composite materials with different filler morphologies under different loading directions were tested, and the results are as follows: Figure 6 As shown. Figure 6 The polar coordinate comparison diagram of the anisotropic mechanical response of the composite material prepared by using elliptical hydroxyapatite microspheres as filler in Example 1 of the present invention, the composite material prepared by using hydroxyapatite microspheres as filler in Comparative Example 1, and the pure matrix material is shown. Figure 6It can be seen that the composite material filled with spherical hydroxyapatite microspheres exhibits relatively small changes in mechanical properties under different loading directions, demonstrating an approximately isotropic mechanical response. In contrast, the composite material filled with elliptical hydroxyapatite microspheres shows significant differences in mechanical properties under different loading directions. It exhibits higher mechanical properties in the loading direction parallel to the long axis of the elliptical hydroxyapatite microspheres, while its mechanical properties are relatively lower in the perpendicular direction, showing a significant anisotropic mechanical response. This indicates that the geometric anisotropy of the elliptical hydroxyapatite microspheres can effectively control the directionality of the composite material's mechanical response.

[0028] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing micron-sized elliptical hydroxyapatite microspheres, characterized in that, The preparation method includes: S1 Preparation of hydroxyapatite precursor slurry: Hydroxyapatite powder is added to the first solution, followed by the addition of binder and dispersant, and the mixture is stirred and mixed to obtain hydroxyapatite precursor slurry; S2 Preparation of spherical hydroxyapatite microspheres: The hydroxyapatite precursor slurry is dropped into a crosslinking solution and crosslinked and solidified by liquid phase spheroidization to form a spherical hydroxyapatite microsphere precursor; S3 Preparation of micron-sized elliptical hydroxyapatite microspheres: After washing and drying the spherical hydroxyapatite microsphere precursor, it is spread on the surface of a constant temperature heating plate for preheating treatment to obtain preheated spherical hydroxyapatite microspheres; then the preheated spherical hydroxyapatite microspheres are rolled and cooled to room temperature to obtain micron-sized elliptical hydroxyapatite microspheres.

2. The preparation method according to claim 1, characterized in that, The average particle size of the hydroxyapatite powder in step S1 is nanometer or submicron; the mass ratio of the hydroxyapatite powder, binder and dispersant is 50:5:1; the first solution is deionized water or a mixture of deionized water and ethanol.

3. The preparation method according to claim 1, characterized in that, The binder in step S1 is any one or more of polyvinyl alcohol, gelatin, and sodium alginate; the dispersant is any one or more of polyacrylate and sodium citrate; and the polyacrylate is sodium polyacrylate or potassium polyacrylate.

4. The preparation method according to claim 1, characterized in that, The stirring and mixing process described in step S1 includes: magnetic stirring at room temperature for 20-30 minutes, followed by uniform dispersion under ultrasonic conditions for 10-20 minutes.

5. The preparation method according to claim 1, characterized in that, In step S2, the concentration of the crosslinking solution is 0.05-0.5 mol / L, and the solute in the crosslinking solution is any one of calcium chloride, barium chloride, magnesium chloride, boric acid, and borate; the solvent in the crosslinking solution is a mixed solvent of deionized water and ethanol, wherein the ethanol content is 0-10%; and the borate is sodium tetraborate.

6. The preparation method according to claim 1, characterized in that, In step S2, the volume ratio of the hydroxyapatite precursor slurry to the crosslinking solution is 1:(5-20); the crosslinking curing method is static crosslinking or uniform magnetic stirring at 500-200 rpm; the crosslinking curing reaction temperature is 10-30℃ and the time is 10-30 min.

7. The preparation method according to claim 1, characterized in that, The preheating treatment in step S3 is performed at a temperature of 80-120℃ for 3-5 minutes.

8. The preparation method according to claim 1, characterized in that, The calendering process specifically involves applying a uniform pressure of 0.5-5 MPa to the preheated spherical hydroxyapatite microspheres in a single direction and then rolling them at a constant speed for 1-3 minutes.

9. Micrometer-sized elliptical hydroxyapatite microspheres prepared by the preparation method according to any one of claims 1-8.

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