Carbonate apatite bone filler granules, their preparation methods and uses

Abstract

This invention provides a carbonate apatite bone filler particle, its preparation method, and its uses. The carbonate apatite bone filler particle is characterized by meeting the conditions (a) to (e): (a) crystallinity of 50% to 80% and amorphous content of 20% to 50%; (b) total porosity of 55% to 85%; (c) specific surface area of ​​20 m² / g to 85 m² / g; (d) surface atomic percentage (at.%) measured by X-ray photoelectron spectroscopy (XPS): Ca: 16 to 26, P: 10 to 15, O: 50 to 60, C: 5 to 12; and (e) after immersing the carbonate apatite bone filler particle in simulated body fluid (SBF) for 24 hours at 37°C, in a 5% CO₂ incubator, and with an immersion ratio of 0.2 g / mL, the |ΔCa| / |ΔP| of the SBF is 0.4 to 2.2. The carbonate apatite bone-filling particles of this invention have high porosity and osteogenic differentiation-promoting properties.

Claims

1. A carbonate apatite bone filler particle, characterized in that the carbonate apatite bone filler particle meets the conditions (a) to (e): (a) crystallinity of 50% to 80% and amorphous content of 20% to 50%; (b) total porosity of 55% to 85%; (c) specific surface area of ​​20 m² / g to 85 m² / g; (d) surface atomic percentage measured by X-ray photoelectron spectroscopy (XPS) of: Ca: 16 at.% to 26 at.%, P: 10 at.% to 15 at.%, O: 50 at.% to 60 at.%, C: 5 at.% to 12 at.%; and (e) incubated at 37°C in a 5% CO₂ incubator with an immersion ratio of 0.

2. Under the condition of g / mL, after the carbonate apatite bone filler particles were immersed in simulated body fluid (SBF) for 24 hours, the |ΔCa| / |ΔP| of the SBF was 0.4 to 2.

2.

2. The carbonate apatite bone filler particles as described in claim 1, wherein, After the carbonated apatite bone filler particles were immersed in simulated body fluid (SBF) for 24 hours at 37°C, 5% CO₂ in an incubator, and an immersion ratio of 0.2 g / mL, the ΔpH of the SBF was -0.35 to -0.

50.

3. The carbonate apatite bone filler particles as described in claim 1, wherein, After the carbonated apatite bone filler particles were immersed in simulated body fluid (SBF) for 24 hours at 37°C, 5% CO₂ in an incubator, and an immersion ratio of 0.2 g / mL, the ΔCa of the SBF was 1.0 mM to 1.5 mM and the ΔP was 0.7 mM to 0.9 mM.

4. The carbonate apatite bone filler particles as described in claim 1, wherein, The zeta potential of the carbonate apatite bone-filling particles is -1 mV to -4 mV.

5. The carbonate apatite bone filler particles as described in claim 1, wherein, The pore size distribution of the multiple pores in the carbonate apatite filler particles ranges from 0.01 µm to 5 µm and from 10 µm to 600 µm.

6. The carbonate apatite bone filler particles as described in claim 1, wherein, When bovine serum albumin (BSA) was used as a model protein for protein adsorption experiments, measurable amounts of protein adsorbed were observed at 1 hour, 4 hours and 24 hours.

7. A method for preparing carbonate apatite bone-filling particles as described in claim 1, comprising the following steps: (a) providing porous particles containing carbonate and calcium ions; (b) placing the porous particles in an aqueous solution containing phosphate and performing a hydrothermal reaction at a hydrothermal temperature of 80°C to 200°C, so that the porous particles are at least partially converted into a carbonate-substituted apatite phase (CO₃Ap); and (c) washing and drying to obtain the carbonate apatite bone-filling particles.

8. The preparation method as described in claim 7, wherein, Step (a) includes: (a1) providing calcium carbonate powder and pressing it into a molded body; (a2) calcining and / or sintering the molded body to shape it and form a porous structure; and (a3) ​​mechanically crushing the shaped porous structure to obtain the porous particles containing carbonate and calcium ions.

9. The preparation method as described in claim 7, wherein, Step (a) comprises: (a1') providing calcium carbonate powder, mixing it with a photocurable resin or monomer system and a photoinitiator to form a photocurable slurry; (a2') using photocurable 3D printing technology to print the photocurable slurry into a molded body with a predetermined pore geometry; (a3') degreasing the molded body to remove the organic phase, and further calcining and / or sintering it to set the shape and form a porous structure; and (a4') mechanically fracturing the set porous structure to obtain the porous particles containing carbonate and calcium ions.

10. The preparation method as described in claim 9, wherein, The preset pore geometry includes porous gyroid structures, honeycomb structures, or combinations thereof.

11. The preparation method as described in claim 9, wherein, The photocurable resin or monomer system is acrylic, methacrylic, epoxyacrylic, or a combination thereof.

12. The preparation method as described in claim 8 or 9, wherein, This fragmentation includes crushing, pulverizing, or a combination thereof.

13. The preparation method as described in claim 7, wherein, Prior to the hydrothermal reaction in step (b), the porous particles are further immersed in a carbonate-containing solution for recarbonation treatment, thereby forming or regenerating the CaCO₃ phase on their surface and / or within their pores.

14. The preparation method as described in claim 13, wherein, The carbonate-containing solution includes ammonium carbonate solution, bicarbonate solution, carbonate solution, or a combination thereof.

15. Use of the carbonate apatite bone-filling granules as described in claim 1, wherein the carbonate apatite bone-filling granules are applied to bone defects or cavities in mammals to promote new bone formation.

16. The use as described in claim 15, wherein, The carbonate apatite bone-filling particles, combined with a medically acceptable carrier, form an injectable or malleable composition.

17. The use as described in claim 16, wherein, The carrier contains biocompatible polymers.

18. The use as described in claim 16, wherein, This composition includes growth factors, small molecule drugs, antibiotics, stem cells, or combinations thereof.

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