CN-121974313-A - Micron-sized elliptic hydroxyapatite microsphere and preparation method thereof

CN121974313ACN 121974313 ACN121974313 ACN 121974313ACN-121974313-A

Abstract

The invention provides a preparation method of a micron-sized elliptic hydroxyapatite microsphere, which comprises the steps of S1 adding hydroxyapatite powder into a first solution, sequentially adding a binder and a dispersing agent to obtain hydroxyapatite precursor slurry, S2 dripping the hydroxyapatite precursor slurry into a crosslinking solution, crosslinking and solidifying to form a spherical hydroxyapatite microsphere precursor, S3 washing and drying the spherical hydroxyapatite microsphere precursor, spreading the spherical hydroxyapatite precursor on the surface of a constant-temperature heating plate for preheating treatment, and then carrying out calendaring treatment to obtain the micron-sized elliptic hydroxyapatite microsphere. The invention realizes the stable and controllable preparation of the monodisperse elliptic hydroxyapatite microsphere under the micron scale by the step strategy of 'spherical forming-stable shaping-thermoplastic secondary calendaring'.

Inventors

ZHU ZHILING
LIU DONG
CHEN XUEJUN
GAO JIA
ZHANG ZIQI
LIU JING
GAO YUBO

Assignees

青岛科技大学
美潮(海宁)医疗器械有限公司

Dates

Publication Date: 20260505
Application Date: 20260202

Claims (9)

1. A method for preparing micron-sized elliptic hydroxyapatite microspheres, which is characterized by comprising the following steps: S1, preparing hydroxyapatite precursor slurry, namely adding hydroxyapatite powder into a first solution, sequentially adding a binder and a dispersing agent, and stirring and mixing to obtain the hydroxyapatite precursor slurry; S2, preparing spherical hydroxyapatite microspheres, namely dripping the hydroxyapatite precursor slurry into a crosslinking solution, and crosslinking and solidifying the hydroxyapatite precursor slurry in a liquid phase balling mode to form spherical hydroxyapatite microsphere precursors; S3, preparing micron-sized elliptic hydroxyapatite microspheres, namely washing and drying the spherical hydroxyapatite microsphere precursor, spreading the spherical hydroxyapatite microsphere precursor on the surface of a constant-temperature heating plate for preheating treatment to obtain preheated spherical hydroxyapatite microspheres, calendaring the preheated spherical hydroxyapatite microspheres, and cooling to room temperature to obtain micron-sized elliptic hydroxyapatite microspheres.
2. The preparation method according to claim 1, wherein in the step S1, the average particle size of the hydroxyapatite powder is nano-scale or submicron-scale, the mass ratio of the hydroxyapatite powder, the binder and the dispersant is 50:5:1, and the first solution is deionized water or a deionized water-ethanol mixed solution.
3. The preparation method according to claim 1, wherein the binder in the step S1 is any one or more of polyvinyl alcohol, gelatin and sodium alginate, the dispersing agent is any one or more of polyacrylate and sodium citrate, and the polyacrylate is sodium polyacrylate or potassium polyacrylate.
4. The method according to claim 1, wherein the stirring and mixing process in step S1 comprises magnetic stirring at room temperature for 20-30min, followed by uniform dispersion under ultrasonic conditions for 10-20min.
5. The preparation method according to claim 1, wherein the concentration of the crosslinking solution in the 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 deionized water-ethanol mixed solvent, wherein the ethanol content is 0-10%, and the borate is sodium tetraborate.
6. The preparation method of the hydroxyapatite according to claim 1, wherein the volume ratio of the hydroxyapatite precursor slurry to the crosslinking solution in the step S2 is 1 (5-20), the crosslinking and curing mode is standing and crosslinking or uniformly magnetically stirring at the rotating speed of 500-200 rpm for crosslinking, and the reaction temperature of the crosslinking and curing is 10-30 ℃ and the time is 10-30min.
7. The method according to claim 1, wherein the preheating treatment in step S3 is performed at a temperature of 80 to 120 ℃ for a time of 3 to 5 minutes.
8. The method according to claim 1, wherein the rolling treatment is specifically carried out by applying a uniform pressure of 0.5 to 5MPa to the preheated spherical hydroxyapatite microspheres in a single direction and rolling at a constant speed of 1 to 3 min.
9. A micron-sized oval-shaped hydroxyapatite microsphere prepared by the preparation method according to any one of claims 1 to 8.

Description

Micron-sized elliptic hydroxyapatite microsphere and preparation method thereof Technical Field The invention relates to the technical field of inorganic biological materials and functional ceramic materials, in particular to a micron-sized elliptic hydroxyapatite microsphere and a preparation method thereof. Background Hydroxyapatite (Ca 10(PO4)6(OH)2) is used as an important biological inorganic material, and has wide application in the fields of bone repair materials, biomedical fillers, drug delivery carriers, chromatographic fillers, functional composite materials and the like due to excellent biocompatibility, bioactivity and chemical stability. Spherical hydroxyapatite microspheres are currently the most common morphology. However, the traditional spherical hydroxyapatite microsphere has the defects of single morphology, limited specific surface area, single interface action mode and the like, has certain limitations in the aspects of directional assembly, anisotropic mechanical enhancement, interface regulation and the like, and limits the further application of the microsphere in bionic materials, tissue engineering scaffolds and functional composite materials. The micron-sized elliptic hydroxyapatite microsphere has obvious advantages in the aspects of specific surface area, particle stacking mode and interface contact behavior due to the non-spherical and anisotropic geometric structure characteristics. The elliptic structure endows the microspheres with curvature distribution in different directions, so that the microspheres are easier to be directionally arranged under the action of a shearing field or an external field, and the anisotropic structure material is favorably constructed. Meanwhile, the oval microspheres can enhance the mechanical embedding effect between particles and a matrix in a composite system, thereby improving the overall mechanical property. However, the existing hydroxyapatite microsphere preparation method can only obtain spherical particles, and under the premise of keeping monodispersity and structural integrity, controllable preparation of non-spherical and anisotropic microspheres is difficult to realize under the micron scale. Especially, the existing liquid phase balling, spray balling and microfluidic balling processes are difficult to directly obtain oval microspheres with regular morphology in the balling stage. Therefore, the preparation method of the micron-sized elliptic hydroxyapatite microsphere, which has simple and convenient process and controllable morphology and is suitable for large-scale preparation, has important scientific significance and application value. Disclosure of Invention Aiming at the technical problems in the prior art, the invention provides the micron-sized elliptic hydroxyapatite microsphere and the preparation method thereof, and the stable and controllable preparation of the monodisperse elliptic hydroxyapatite microsphere under the micron scale is realized by the step-by-step strategy of 'spherical forming-stable shaping-thermoplastic secondary calendaring'. The first aim of the invention is to provide a preparation method of micron-sized elliptic hydroxyapatite microspheres, which comprises the following steps: S1, preparing hydroxyapatite precursor slurry, namely adding hydroxyapatite powder into deionized water or a deionized water-ethanol mixed solvent, sequentially adding a binder and a dispersing agent, and stirring and mixing to obtain the hydroxyapatite precursor slurry; S2, preparing spherical hydroxyapatite microspheres, namely dripping the hydroxyapatite precursor slurry into a crosslinking solution, and crosslinking and solidifying the hydroxyapatite precursor slurry in a liquid phase balling mode to form spherical hydroxyapatite microsphere precursors; S3, preparing micron-sized elliptic hydroxyapatite microspheres, namely washing and drying the spherical hydroxyapatite microsphere precursor, spreading the spherical hydroxyapatite microsphere precursor on the surface of a constant-temperature heating plate for preheating treatment to obtain preheated spherical hydroxyapatite microspheres, calendaring the preheated spherical hydroxyapatite microspheres, and cooling to room temperature to obtain micron-sized elliptic hydroxyapatite microspheres. Specifically, the average particle size of the hydroxyapatite powder in the step S1 is nano-scale or submicron-scale, and the mass ratio of the hydroxyapatite powder to the binder to the dispersing agent is 50:5:1. Specifically, in the step S1, the binder is any one or more of polyvinyl alcohol, gelatin and sodium alginate, the dispersing agent is any one or more of polyacrylate and sodium citrate, and the polyacrylate is sodium polyacrylate or potassium polyacrylate. Specifically, the stirring and mixing treatment in the step S1 comprises the steps of magnetically stirring for 20-30min at room temperature, and then uniformly dispersing for 10-20min under ultrasonic conditions.