METHOD FOR COATING CALCIUM SILICATE FOR PREPARING BONE GRAFTING MATERIAL HAVING IMPROVED BIOCOMPATIBILITY

Abstract

The present invention relates to a method for preparing a glass-ceramic composite, in which a bioactive material is uniformly coated on the surface of a ceramic molded body; a glass-ceramic composite, in which a bioactive material is uniformly coated on the surface of a ceramic molded body; a bone grafting material comprising the glass-ceramic composite; and a bone grafting kit comprising the glass-ceramic composite.

Claims

1. A method for preparing a glass-ceramic composite, comprising: Step 1 of preparing a slurry containing a ceramic powder; Step 2 of forming a pore in a molded body by casting the slurry; Step 3 of removing moisture by freeze-drying the molded body having the pore; Step 4 of subjecting the molded body from which moisture is removed to primary sintering at 900 C. to 1100 C.; Step 5 of coating the primary sintered molded body with a bioactive material; and Step 6 of subjecting the coated molded body to secondary sintering at 1100 C. to 1300 C.

2. The method of claim 1, wherein the bioactive material in Step 5 comprises at least one selected from the group consisting of calcium silicate, bioglass, and tricalcium phosphate (TCP).

3. The method of claim 2, wherein the bioactive material is pulverized by a wet-pulverizing method.

4. The method of claim 3, wherein the pulverized bioactive material has an average particle size of 10 m or less.

5. The method of claim 2, wherein Step 5 is performed by using a solution containing the bioactive material at a concentration of 0.01 wt % to 0.5 wt %.

6. The method of claim 1, wherein the ceramic powder in Step 1 comprises at least one selected from the group consisting of hydroxyapatite (HA), biphasic calcium phosphate (BCP), tricalcium phosphate, and zirconia.

7. A glass-ceramic composite having a structure in which a bioactive material is coated on the surface of the ceramic molded body, wherein the bioactive material has an average particle size of 10 m or less and is embedded in the surface of a ceramic molded body.

8. The glass-ceramic composite of claim 7, wherein the glass-ceramic composite is prepared by the preparation method of any one of claims 1 to 6.

9. A bone grafting material comprising the glass-ceramic composite of claim 7.

10. A bone grafting kit comprising the glass-ceramic composite of claim 7.

11. The kit of claim 10, further comprising a means for injecting into the body.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0054] FIG. 1 is a schematic representation of the preparation method of the present invention.

[0055] FIG. 2 shows the particle size distribution of calcium silicate powder according to the pulverization time.

[0056] FIG. 3 shows the surface of the coating layer of the present invention and the prior art by comparison.

[0057] FIG. 4 shows the pH of the glass-ceramic composites prepared using the coating solution at various concentrations according to the elution time.

[0058] FIG. 5 shows the surface of the glass-ceramic composites coated with the coating solution at various concentrations before coating.

[0059] FIG. 6 shows the SEM images of the surface of the molded body prepared with biphasic calcium phosphate powder before coating and the surface of the glass-ceramic composite coated with bioglass.

[0060] FIG. 7 shows the SEM images of the surface of the molded body prepared with biphasic calcium phosphate powder before coating and the surface of the glass-ceramic composite coated with calcium silicate.

[0061] FIG. 8 shows the SEM images of the surface of the molded body prepared with hydroxyapatite powder before coating and the surface of the glass-ceramic composite coated with calcium silicate and bioglass.

[0062] FIG. 9 shows the SEM images of the surface of the molded body prepared with zirconia powder before coating and the surface of the glass-ceramic composite coated with bioglass.

[0063] FIG. 10 shows the SEM images of the surface of the molded body prepared with biphasic calcium phosphate powder before coating and the surface of the glass-ceramic composite coated with calcium silicate.

[0064] FIG. 11 shows the specimens implanted with the bone grafting material prepared by coating with the coating solution at various concentrations.

[0065] FIG. 12 shows the result of evaluating bone-forming ability after implantation of the bone grafting material prepared by coating with the coating solution at various concentrations.

DETAILED DESCRIPTION OF EMBODIMENTS

[0066] Hereinafter, preferred Examples are provided to help understanding of the present invention. However, these Examples are given for illustrative purposes only to help understanding of the present invention and the scope of the invention is not intended to be limited to or by these Examples.

PREPARATION EXAMPLE 1

Preparation of Ceramic Powder

[0067] A ceramic powder, in which biphasic calcium phosphate (BCP), hydroxyapatite (HA), -tricalcium phosphate (-TCP) and zirconia, and hydroxyapatite and -tricalcium phosphate were mixed in a ratio of 6:4, was prepared.

PREPARATION EXAMPLE 2

Preparation of Coating Solution

[0068] Calcium silicate was prepared as a bioactive material. The thus-prepared calcium silicate was subjected to wet-pulverization to have an average particle size of 2 m and a maximum particle size of 10 m or less (FIG. 2). Polyvinyl butyral (PVB) was added as a solvent, and the mixture was stirred for 8 hours to 48 hours to obtain calcium silicate solution at concentrations of 0.1 wt %, 0.2 wt %, 0.3 wt %, 0.4 wt %, 0.5 wt %, and 1.0 wt %.

[0069] When the average particle size was 2 m and the maximum particle size was 10 m or less, the bioactive material did not sink even if the solvent concentration was lowered and thus no aggregation of the coating solution was observed, and also, the drying time was shortened. Further, it was confirmed that the uniformity was the highest, when the stirring time was 48 hours.

[0070] Bioglass and -tricalcium phosphate were prepared as bioactive materials.

Example 1

Preparation of Glass-Ceramic Composites

[0071] A slurry was prepared using the ceramic powder, in which hydroxyapatite and -trisodium phosphate were mixed at a ratio of 6:4. The thus-prepared slurry was casted to form pores in the molded body, and then freeze-dried to remove moisture. After subjecting the molded body from which moisture was removed to primary pre-sintering at 1,000 C., and the pre-sintered molded body was coated with the calcium silicate solution at concentrations of 0.1 wt %, 0.2 wt %, 0.3 wt %, 0.4 wt %, 0.5 wt % and 1.0 wt % prepared in Preparation Example 2. The coated molded body was dried and then subjected to secondary sintering at 1,150 C. for 4 hours to prepare a glass-ceramic composite (a schematic representation of FIG. 1). The SEM image of the surface of the prepared glass-ceramic composite is shown in FIG. 5.

[0072] Glass-ceramic composites were prepared in the same manner as described above, except that the slurry was prepared using biphasic calcium phosphate, hydroxyapatite, -tricalcium phosphate, or zirconia as a ceramic powder.

[0073] Glass-ceramic composites were prepared as described above except that the molded body was coated with bioglass, -tricalcium phosphate or bioglass, and silicate instead of calcium silicate.

[0074] Among the glass-ceramic composites prepared above, representatively, the SEM images of the surfaces of the glass-ceramic composite prepared by coating the molded body prepared using biphasic calcium phosphate powder with bioglass, the glass-ceramic composite prepared by coating the molded body prepared using biphasic calcium phosphate with calcium silicate, the glass-ceramic composite prepared by coating the molded body prepared using hydroxyapatite powder with calcium silicate and bioglass, the glass-ceramic composite prepared by coating the molded body prepared using zirconia powder with bioglass, and the glass-ceramic composite prepared by coating the molded body prepared using biphasic calcium phosphate powder with calcium silicate are shown in FIGS. 6 to 10, respectively.

Comparative Example 1

Preparation of Glass-Ceramic Composite in which the Temperature of Pre-sintering is Higher Than the Temperature of Complete Sintering

[0075] A glass-ceramic composite, in which the molded body prepared using a ceramic powder prepared by mixing hydroxyapatite and -tricalcium phosphate at a ratio of 6:4 was coated with calcium silicate, was prepared in the same manner as in Example 1, except the molded body from which moisture is removed was subjected to primary pre-sintering at 1,200 C. instead of 1,000 C.

[0076] As shown in FIG. 3, in the case of the glass-ceramic composite prepared in Example 1, in which the molded body prepared using a ceramic powder prepared by mixing hydroxyapatite and -tricalcium phosphate at a ratio of 6:4 was coated with calcium silicate, it was confirmed that the surface of the glass-ceramic composite was uniformly coated without aggregation as compared with the glass ceramic composite of Comparative Example 1 prepared by performing pre-sintering at a temperature higher that the temperature of complete sintering. Further, it was confirmed that the coating was most uniform at a low concentration (concentration of 0.2 wt % or less), and the bonding force was also high (FIG. 5).

Experimental Example 1

pH Analysis

[0077] In order to analyze the excessive increase of pH due to the material eluted from the coated glass-ceramic composites as time elapsed, the pH of the glass-ceramic composites coated with the calcium silicate solution at concentrations of 0.1 wt %, 0.2 wt %, 0.3 wt %, 0.4 wt %, 0.5 wt % and 1.0 wt % was analyzed. When the glass-ceramic composites were coated with the calcium silicate solution at a concentration of 0.3 wt % or less, the pH was 10 or less, while when the composites were coated with the calcium silicate solution at concentrations of 0.4 wt % and 0.5 wt %, the pH excessively rose to 10 or more (FIG. 4). In particular, it was confirmed that the pH excessively rose to 11 when the glass-ceramic composite was coated with the calcium silicate solution at a concentration of 1.0 wt %.

Experimental Example 2

Confirmation of Inflammation Reaction

[0078] In rabbit calvarial defect models, inflammation reaction of the bone grafting material was evaluated by 4- and 8-week animal studies. As a result of implanting the bone grafting material prepared using the glass-ceramic composites of Example 1 coated with the calcium silicate solution at concentrations of 0.1 wt %, 0.2 wt %, 0.3 wt %, 0.4 wt %, 0.5 wt % and 1.0 wt %, it was confirmed that no inflammation reaction occurred in all specimens (FIG. 11).

Experimental Example 3

Analysis of Osteogenic Capacity

[0079] In rabbit calvarial defect models, the analysis of osteogenic capacity was evaluated by 4- and 8-week animal studies. As a result of implanting the bone grafting material prepared using the ceramic powder (OSTEON 3) prepared by mixing hydroxyapatite and -tricalcium phosphate at a ratio of 6:4 and the calcium silicate solution at concentrations of 0.2 wt %, 0.5 wt % and 1.0 wt %, it was confirmed that bone formation was excellent in all specimens (FIG. 12). In particular, it was confirmed that the osteogenic capacity was the highest in case of Example 1 coated with 0.2 wt % of calcium silicate solution.

ACKNOWLEDGEMENT

[0080] This work has been supported by the Innopolis Foundation grant funded by the Korea government(MSIT)(No. 2017-DD-RD-0030-02).