KR102660274B1 - Magnesium ion-containing curing agent for synthetic bone and synthetic bone composition comprising the same - Google Patents

Abstract

A bone graft material containing magnesium ions is provided.

Description

Bone graft material containing magnesium ions and curing solution therefor {Magnesium ion-containing curing agent for synthetic bone and synthetic bone composition comprising the same}

The present invention relates to a bone graft material containing magnesium ions and a curing solution for the same.

In addition to the mechanical function of supporting the human body and performing movements, bones also serve as a storehouse of calcium by regulating calcium ion concentration in the body, and also have an important physiological function of producing red blood cells and white blood cells necessary for the human body in the bone marrow.

Bones can be damaged due to aging and other physiological reasons, or from various accidents.

Bone transplantation includes transplanting the patient's own tissue (autologous bone transplant) and transplanting the bone of another person (allogeneic bone) or animal (xenogeneic bone). However, if immunological rejection occurs when transplanting another person's tissue, or if the damaged area is large and there is not enough material available in the patient's body, artificial bone graft material (bone substitute) is used.

Most bone graft materials currently used are calcium sulfate and calcium phosphate, but there are limits to the effectiveness of autologous bone grafting.

Calcium phosphate is an inorganic material that is receiving considerable attention as a bone substitute due to its similarity to natural bone composition and excellent bone conductivity.

Brown et al. studied porous hydroxy-apatite (HA), an absorbable inorganic material, and Wolfe studied beta-tricalcium phosphate (β-TCP) for the inorganic components and structure of natural bone. It is said that because the bone is similar, it gradually decomposes and is replaced by new bone.

Chow et al. reported on the osteoconductivity of β-TCP. In addition, Posset et al. reported research on tetracalcium phosphate, and Frankenburg et al. reported research on calcium phosphate cement. There is also research on making bone cement by mixing various inorganic materials rather than using only inorganic materials.

In particular, these bone graft materials paste the main ingredient in powder form with saline solution, etc., and all bone graft materials available to date have simply used saline solution as the liquid ingredient used in this paste. Therefore, there is a need to develop new curing fluids and new technologies that can improve the physical properties of bone graft materials after curing using them.

1. Non-patent document 1 Chow, L. C. (1991). Development of self-setting calcium phosphate cements. Journal of the Ceramic society of Japan, 99(1154), 954-964. 2. Non-patent document 2 Posset, U., Locklin, E., Thull, R., & Kiefer, W. (1998). Vibrational spectroscopic study of tetracalcium phosphate in pure polycrystalline form and as a constituent of a self-setting bone cement. Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and the Australian Society for Biomaterials, 40(4), 640-645. 3. Non-patent document 3 Moore, D. C., Frankenburg, E. P., Goulet, J. A., & Goldstein, S. A. (1997). Hip screw augmentation with an in situ-setting calcium phosphate cement: an in vitro biomechanical analysis. Journal of orthopedic trauma, 11(8), 577-583.

Therefore, the problem to be solved by the present invention is to provide a novel bone graft material with excellent strength and regenerative properties, and a curing solution for producing the same.

In order to solve the above problems, the present invention provides a bone graft material containing magnesium ions.

In one embodiment of the present invention, the curing agent for bone graft material further includes sodium ions.

In one embodiment of the present invention, the molar ratio (Mg/Na) of magnesium ions and sodium ions is 0.01 to 0.5.

In one embodiment of the present invention, the bone graft material is manufactured by mixing bone graft material powder containing at least one of calcium phosphate or calcium sulfate with a curing solution and then curing it.

In one embodiment of the present invention, the magnesium ions are contained in the curing liquid and mixed with the bone graft material powder, and the bone graft material powder further includes betaTCP.

The present invention also relates to the above-described curing liquid for bone grafting materials, wherein the curing fluid contains both sodium and magnesium ions, and the molar ratio (Mg/Na) of the magnesium ions and sodium ions is 0.01 to 0.5. Provides a curing liquid.

According to the present invention, a bone graft material composition is prepared by mixing a solution containing magnesium ions and bone graft material powder (apatite). As a result, the excellent bone regeneration effect of magnesium can be utilized.

Figure 1 is a graph quantifying physical property data of bone graft material hardened according to an embodiment of the present invention.

The objectives, specific advantages and novel features of the present invention will become more apparent from the following detailed description and preferred embodiments taken in conjunction with the accompanying drawings. Additionally, the terms used are terms defined in consideration of the functions in the present invention, and may vary depending on the intention or custom of the user operator. Therefore, definitions of these terms should be made based on the overall content of this specification.

The present invention uses a bone graft material containing magnesium ions to solve the above-mentioned problems. Here, the bone graft material refers to a material obtained by mixing bone graft material powder (for example, containing at least one phase of calcium phosphate or calcium sulfate) and a curing liquid, and then curing the bone graft material. In particular, the invention greatly improved the physical properties and in vivo effects of the bone graft material by using magnesium in a specific content range in the curing solution mixed with the bone graft material, which will be described in more detail below.

Example

In one embodiment of the present invention, an apatite bone graft material powder containing calcium sulfate hemihydrate (CSH), beta-tricalcium phosphate (β-TCP), and monocalcium phosphate monohydrate (MCPM) is used, and the weight ratio of CSH:β-TCP:MCPM is 7: A powder ratio of 2:1 was prepared. Afterwards, the powder was mixed with the curing liquid at a weight ratio of 1:0.35 and cured at room temperature for 10 to 20 minutes. In the present invention, in particular, Mg (mmol)/Na (mmol) was adjusted by mixing NaCl (0.9 wt%) and MgCl2 in various ratios in the curing solution. Table 1 below shows the composition ratio of Mg and Na of bone graft material according to the curing solution. am.

main ingredient Bone graft material composition ratio
Mg (mmol)/Na (mmol) Comparative Example 1 0.000 Example 1 0.010 Example 2 0.049 Example 3 0.243 Comparative example 2 1.216 Comparative Example 3 6.082

Experimental Example Table 2 below is a table summarizing the physical properties of bone graft materials cured according to the above examples, and Figure 1 is a graph quantifying the data in Table 1 below.

main ingredient Bone graft material
compressive strength Cell proliferation rate based on bone graft material
(MC3T3-cell) Bone graft material-based ALP
(Skin driven MSC) hardener
osmotic pressure hardener
electrical conductivity (unit) MPa Drainage Drainage mOsm mS/cm Comparative Example 1 10.28 1.00 1.00 291.75 16.20 Example 1 11.95 1.19 1.22 295.89 16.42 Example 2 11.11 1.66 1.25 312.44 17.31 Example 3 11.26 1.68 1.19 395.22 21.70 Comparative example 2 9.95 0.81 1.22 809.10 42.30 Comparative Example 3 4.7 Not implemented Not implemented 2878.52 111.91

The experimental method is as follows. Compressive strength:

It was performed according to ASTM D695 (Standard Test Method for Compressive Properties of Rigid Plastics), the universal testing equipment was MTS's Landmark machine, and the sample was cylindrical with a diameter of 6.19 mm and a height of 13.96 mm. The load applied while compressing at a crosshead speed of 1 mm/min was obtained using a computer. Measurements were repeated 6 times per sample.

Cell viability:

MC3T3-1 cells, an osteoblast-like cell line from C57B/6 mouse calvaria, were distributed at 1x102 cells/well in a 96 well plate, and the samples were eluted for 3 days. (Alpha-minimal essential media) 100 (microliter) and incubate for 24 hours. After removing Media, new Media 100 + MTT solution 10 Add and incubate at 37°C for 4 hours. 85 After removal, DMSO 50 Put in 10min, 37 Incubation proceeds. Measure absorbance at 450 nm.

ALP(Alkaline Phosphatase Activity):

Stem cells derived from the skin were distributed at 1x102 cells/well in a 24 well plate, and the sample was eluted for 3 days. Add 1 ml of (Alpha-minimal essential media) and culture for 7 days. After removing the culture medium, wash with PBS. Lysis buffer 100 After cell lysis, 50 lysate + 100 Mix p-NPP and incubate at 37°C for 20 min. Measure the absorbance at 405 nm.

Osmotic pressure: Measurements were repeated three times per sample using Gonotec's OSMOMAT 3,000 equipment.

Electrical conductivity: Measured once per sample using Mettler Toledo's SevenCompact 3220 equipment.

Referring to the results in Table 2, it can be seen that when magnesium is added, the compressive strength increases to the range of Examples 1 to 3. In particular, in the case of comparison outside the range of Example 3 (the molar ratio of magnesium to sodium is 1.216), it can be seen that the compressive strength is rather reduced. Therefore, in terms of compressive strength, the molar ratio of magnesium to sodium is preferably 0.01 to 1.0 or less, more preferably 0.01 to 0.5, and most preferably 0.01 to 0.3 or less.

From the results in Table 2 above, it can be seen that the ALP level generated when stem cells differentiate into chondrocytes also increases as the ratio of magnesium and sodium increases, and the cell proliferation rate also increases in the range of Examples 1 to 3. Able to know.

Therefore, the above results show that in terms of cell proliferation rate, the molar ratio of magnesium to sodium is 1.0 or less, preferably 0.5 or less, and most preferably 0.3 or less.

The above results show that by using magnesium chloride in the curing solution, magnesium ions penetrate into the porous structure of the bone graft material during the curing process, facilitating internal penetration of ionic components necessary for actual bone formation, and at the same time utilizing the excellent bone regeneration effect of magnesium ions. This strongly proves that it helps bone regeneration and improves the regenerative effect along with mechanical properties.

Claims (7)

As a hardening agent for bone graft materials,
The curing agent contains both magnesium ions and sodium ions,
The molar ratio (Mg/Na) of the magnesium ion and sodium ion is 0.01 to 0.5,
The bone graft material is a curing agent for bone graft material, characterized in that it contains at least one of calcium phosphate or calcium sulfate. According to clause 1,
The bone graft material has a porous structure, and the compressive strength of the bone graft material increases in the range of the molar ratio (Mg/Na) of magnesium ions and sodium ions. delete delete delete delete delete