CN102432180A - Preparation method of bioactive glass ceramic material for bone defect repair - Google Patents

Abstract

The present invention discloses a method for preparing a bioactive glass ceramic material for repairing bone defects, and the steps are as follows: screening bioglass powder, adding polyacrylamide solution, ball milling and mixing to obtain bioglass slurry, pouring the slurry into a polymer reverse mold by centrifugal grouting, curing, drying, calcining at 900-1000°C under program temperature control to remove the polymer reverse mold, and preparing the bioactive glass ceramic material for repairing bone defects. The shape of the bioactive glass ceramic material prepared by the present invention can be determined according to clinical needs, has good mechanical strength, biocompatibility and degradability, high compressive strength, good anti-collapse performance, good activity, and the degradation time can be regulated. The preparation method of the present invention has a simple process and low cost.

Description

Preparation method of bioactive glass-ceramic material for bone defect repair

technical field

The invention belongs to the field of bioactive materials, and relates to bone tissue repair, filling and tissue engineering repair materials, in particular to a preparation method of bioactive glass-ceramic materials used for bone defect repair.

Background technique

Skeletal lesion is a clinical common disease and frequently-occurring disease. Through the development of bone repair and bone substitute materials, it can help patients repair defective or missing bone tissue and better restore the function of human tissue. In bone tissue engineering, an ideal repair material should meet the following conditions: good biocompatibility, biodegradability, plasticity, three-dimensional porous and interconnected pore structure and certain mechanical strength. In the field of bone defect repair research, there is an urgent need for scaffold materials that match the mechanical strength of human bone, have good cell compatibility, and promote the growth of new bone tissue.

Bioactive materials are materials used for diagnosing, treating, repairing or replacing diseased tissues and organs of living organisms or improving their functions. Typical representatives of bioactive materials include calcium phosphate cement, apatite, and bioglass. When these bioactive materials are used in the clinical application of bone tissue repair and bone tissue engineering, due to their different composition, structure and strength, they still have large differences compared with human bone, resulting in their biocompatibility, degradability The performance is not ideal, which directly affects the repair effect of bone tissue. For example, the calcium phosphate bone cement material will solidify when it is injected into the body, which will generate a lot of heat and destroy its surrounding tissues. Apatite is widely used clinically in the form of blocks and granules for hard tissue repair and replacement. However, due to the brittleness of block ceramics, the particles are easy to move and shift, and it is difficult to shape, which limits its use. In clinical application.

Bioglass has good bioactivity and biocompatibility, and can be used as a material for human tissue repair and regeneration. The fused bioglass composed of Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ quaternary components, and CaO The sol-gel bioglass with -SiO ₂ -P ₂ O ₅ components has achieved good clinical bone repair effects, and its biological activity, degradability and mechanical properties can be adjusted by changing the content of each component. performance, meet different clinical requirements, and promote the differentiation and proliferation of osteoblasts by activating some genes of osteoblasts. However, traditional bioglass scaffolds generally have the disadvantages of high brittleness and low mechanical strength.

Contents of the invention

The object of the present invention is to provide a method for preparing a bioactive glass-ceramic material for bone defect repair in view of the shortcomings of current bone defect repair materials and their preparation techniques. The shape and pore size of the bone defect repair material prepared in the present invention can be adjusted according to clinical needs, and the shapes include porous cylinders, porous cubes and irregular blocks.

In order to achieve the above object, the present invention adopts the following technical solutions.

A method for preparing a bioactive glass-ceramic material for bone defect repair, comprising the following steps:

(1) Pass the biological glass powder through a 200-mesh sieve, add polyacrylamide solution, and ball mill to mix to obtain biological glass slurry;

(2) Add the bioglass slurry obtained in step (1) dropwise to the polymer counter-mold, perform centrifugal grouting on the polymer counter-mold in a centrifuge, and solidify in a water bath at 70-75°C for 1-2 hours. Dry at 50~70℃ for 48~72h to obtain solid material;

(3) Calcining the solid material obtained in step (2) at 900-1000° C. under programmed temperature control to remove the polymer anti-mold to prepare a bioactive glass-ceramic material for bone defect repair.

The biological glass powder in the present invention is Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder and/or CaO-SiO ₂ -P ₂ O ₅ biological glass powder.

_The material composition mass percentage of the _Na2O -CaO-SiO2 _-P2O5 biological glass powder of the present invention is: calcium oxide 20-25%, phosphorus pentoxide 5-7%, _sodium oxide 20-25% , silicon dioxide 43~49%; the material composition mass percentage of the CaO-SiO ₂ -P ₂ O biological glass powder is: calcium oxide 14~33%, phosphorus pentoxide 0~9%, silicon dioxide 58% ~80%.

The volume fraction of the biological glass powder in the biological glass slurry of the present invention is 50-60%.

The pore size of the polymer counter-mold in the present invention is 500-1000 microns, and the geometric shape is cube, cuboid or cylinder.

The process of programmed temperature control of the present invention comprises following three stages:

(1) Heating stage: raise the temperature of the solid material to 900~1000℃ at a rate of 2~3℃/min;

(2) Heat preservation stage: keep the temperature of the solid material at 900~1000℃ for 1~2h;

(3) Cooling stage: natural cooling to 10~30°C.

The volume fraction of polyacrylamine in the polyacrylamine solution of the present invention is 4-8%.

The rotational speed of the centrifugal grouting in the present invention is 800~1200r/min.

The polymer counter-mold of the present invention is a photosensitive resin counter-mold or a polymer counter-mold; the photosensitive resin counter-mold adopts photocuring molding technology and is prepared with photosensitive resin as a raw material; the polymer counter-mold adopts three-dimensional printing technology to Polymers are prepared as raw materials.

The photosensitive resin of the present invention is an unsaturated polyester resin, including polymesolactic acid or polycaprolactone; the polymer is polylactic acid-glycolic acid copolymer or acrylonitrile-butadiene-styrene copolymer ( Abbreviation: ABS resin).

The preparation process of Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder described in the present invention refers to Lefebvre L et al [Lefebvre L., Chevalier J., Gremillard L. Structural transformations of bioactive glass 45S5 with thermal treatments . Acta Materiala, 2007, 55 (10), 3305 ~ 3313] literature, specifically comprises the following steps: after weighing and fully mixing the analytically pure sodium carbonate, calcium carbonate, tricalcium phosphate and silicon dioxide in proportion, Put it into a platinum crucible and melt it at 1400°C for 120min; then pour the molten glass into deionized water and water quench to obtain an amorphous phase bioactive glass; filter the water and dry at 60°C for 24h, then ball mill at 480rpm for 3h, Pass through a 200-mesh sieve to obtain Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder.

The preparation process of CaO-SiO ₂ -P ₂ O ₅ biological glass powder described in the present invention refers to Zhong J. et al [Zhong J., Greenspan DC Processing and properties of sol-gel bioactive glasses. J Biomed Mater Res., 2000 ,53(6):694~701] and Chen X. et al. [Chen X., Meng Y., Li Y., et al. Investigation on bio-mineralization of melt and sol-gel derived bioactive glasses. Applied Surface Science, 2008,.255(2): 562~564], specifically comprising the following steps: adding deionized water, 2mol/L hydrochloric acid catalyst and ethyl orthosilicate in a beaker, stirring and hydrolyzing at room temperature for 30min, Add triethyl phosphate and continue to stir for 30 minutes, then add calcium nitrate tetrahydrate, and stir well to obtain a transparent, uniform and stable sol; the sol is statically aged at room temperature for a certain period of time, so that the hydrolysis-polycondensation reaction can fully proceed and form a wet gel; The wet gel was dried at 140°C for 2 days to obtain the dry gel after evaporating the solvent; the dry gel was heat-treated and solidified at 650°C to obtain granular sol-gel bioactive glass; ball milled at 480rpm for 3h, passed 200 Mesh sieve to obtain CaO-SiO ₂ -P ₂ O ₅ biological glass powder.

The shape of the bioactive glass-ceramic material prepared by the present invention can be determined according to clinical needs, the internal pores are 500-1000 μm, and the porosity is 45-65%.

Compared with the prior art, the present invention has the following advantages and remarkable effects:

(1) The bioglass-ceramic bone repair material prepared by the present invention has a variety of shape options, which can be adapted to fill bone defects in different parts and shapes; the chemical composition of the material can be adjusted, so that the physical and chemical properties and process performance of the material can be within a certain range Adjustment; the preparation process is simple and easy, the process parameters are easy to control, and the output is large;

(2) The shape and internal pore structure of the bioglass-ceramic bone repair material prepared by the present invention are conducive to the ingrowth of new bone tissue and the repair of bone defects.

(3) The bioglass-ceramic bone defect repair material prepared by the present invention has good mechanical strength, biocompatibility and certain biodegradability.

Description of drawings

Fig. 1 is a micro-CT photo of the bioactive glass-ceramic material prepared in Example 1 of the present invention.

FIG. 2 is a scanning electron microscope (abbreviation: SEM) photograph of the surface of the bioactive glass-ceramic material prepared in Example 1 of the present invention.

Detailed ways

The present invention will be further described in detail below in conjunction with the examples, but the protection scope of the present invention is not limited thereto.

Example 1

Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder is used.

(1) After fully mixing 58.63g sodium carbonate, 52.33g calcium carbonate, 18.36g tricalcium phosphate and 63.00g silicon dioxide, put them into a platinum crucible and melt at 1400°C for 120min, then pour the molten glass into deionized water Quenching with water to obtain amorphous phase bioactive glass. After filtering out the water, dry in an electric blast drying oven at 60°C for 24 hours, ball mill in a planetary ball mill at a speed of 480rpm for 3 hours, and pass through a 200-mesh sieve to obtain Na ₂ O -CaO-SiO ₂ -P ₂ O ₅ biological glass powder, each material is composed of: 24.5% calcium oxide, 6g phosphorus pentoxide, 24.5% sodium oxide, 45% silicon dioxide;

(2) Add 100g Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder into 100mL polyacrylic acid amine solution with a volume fraction of 6%, and mix it by ball milling for 3 hours to obtain a biological glass powder with a volume fraction of 50%. glass paste;

(3) Add the bioglass slurry obtained in step (1) dropwise into the unsaturated polyester resin counter-mold, and perform centrifugal grouting on the polymer counter-mold in a Xiangyi L550 centrifuge at 800r/min, and place Cured in a water bath at 70°C for 2 hours, placed in a drying oven at 50°C for 72 hours to obtain a solid material;

(4) Put the solid material into a zirconia sagger, raise the temperature of the solid material to 900 °C at a rate of 2 °C/min and keep it for 2 hours; naturally cool down to 10 °C to obtain the biological activity for bone defect repair Glass-ceramic material.

Example 2

A mixture of Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder and CaO-SiO ₂ -P ₂ O ₅ biological glass powder is used, wherein Na ₂ O-CaO-P ₂ O ₅ -SiO ₂ biological The mass fraction of the glass powder is 99%, and the mass fraction of the CaO-P ₂ O ₅ -SiO ₂ biological glass powder is 1%.

(1) Mix 59.82g of sodium carbonate, 53.40g of calcium carbonate, 15.30g of tricalcium phosphate and 63.00g of silicon dioxide, put them into a platinum crucible and melt at 1400°C for 120min, then pour the molten glass into deionized Quenching in water to obtain amorphous bioactive glass. After filtering the water, dry it in an electric blast drying oven at 60°C for 24 hours, ball mill it in a planetary ball mill at a speed of 480rpm for 3 hours, and pass through a 200-mesh sieve to obtain Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder, each material composition is: 25% calcium oxide, 5g phosphorus pentoxide, 25% sodium oxide, 45% silicon dioxide;

(2) Add 18.72mL of deionized water, 3.12mL of 2mol/L hydrochloric acid catalyst and 25.56mL of ethyl orthosilicate to the beaker, stir and hydrolyze for 30min at room temperature, then add 2.61mL of triethyl phosphate and continue to stir for 30min. Then add 16.24g of calcium nitrate tetrahydrate and stir well to obtain a transparent, uniform and stable sol; let the sol stand and age at room temperature for 48 hours, so that the hydrolysis-polycondensation reaction can fully proceed and form a wet gel; the wet gel is placed at 140°C Dry for 2 days to evaporate the solvent to obtain xerogel; heat-treat the xerogel at 650°C to obtain granular sol-gel bioactive glass; ball mill at 480rpm for 3 hours, and pass through a 200-mesh sieve to obtain CaO- SiO ₂ -P ₂ O ₅ biological glass powder, the material composition is: 33% calcium oxide, 9% phosphorus pentoxide and 58% silicon dioxide;

(3) Mix 99g Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ bioglass powder and 1g CaO-SiO ₂ -P ₂ O ₅ bioglass powder, add 100mL polyacrylamide with a volume fraction of 6% solution, ball milled for 3 hours and mixed to obtain a bioglass slurry with a volume fraction of 50%;

(4) Add the bioglass slurry obtained in step (1) dropwise to the ABS resin counter-mold, perform centrifugal grouting on the counter-mold in a Xiangyi L550 centrifuge at 1000r/min, and place it in a 75°C water bath for curing After 1 hour, place in a drying oven at 70°C and dry for 48 hours to obtain a solid material;

(5) Put the solid material into a zirconia sagger, raise the temperature of the solid material to 1000 °C at a rate of 3 °C/min and keep it for 1 hour; naturally cool down to 30 °C to obtain the biological activity for bone defect repair Glass-ceramic material.

Example 3

A mixture of Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder and CaO-SiO ₂ -P ₂ O ₅ biological glass powder is used, wherein Na ₂ O-CaO-P ₂ O ₅ -SiO ₂ biological The mass fraction of the glass powder is 50%, and the mass fraction of the CaO-P ₂ O ₅ -SiO ₂ biological glass powder is 50%.

(1)) After fully mixing 39.32g sodium carbonate, 35.09g calcium carbonate, 13.11g tricalcium phosphate and 48.00g silicon dioxide, put them into a platinum crucible and melt at 1400°C for 120min, then pour the molten glass into Quenching in ionized water to obtain amorphous phase bioactive glass. After filtering the water, dry it in an electric blast drying oven at 60°C for 24 hours, ball mill it in a planetary ball mill at a speed of 480rpm for 3 hours, and pass through a 200-mesh sieve to obtain Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder, each material composition is: 23% calcium oxide, 6% phosphorus pentoxide, 23% sodium oxide and 48% silicon dioxide;

(2) Add 93.6mL deionized water, 15.57mL 2mol/L hydrochloric acid catalyst and 127.80mL tetraethyl orthosilicate to the beaker, stir and hydrolyze for 30min at room temperature, then add 13.03mL triethyl phosphate and continue stirring for 30min, Then add 81.21g of calcium nitrate tetrahydrate and stir well to obtain a transparent, uniform and stable sol; let the sol stand and age at room temperature for 48 hours to fully carry out the hydrolysis-polycondensation reaction and form a wet gel; store the wet gel at 140°C Dry for 2 days to evaporate the solvent to obtain xerogel; heat-treat the xerogel at 650°C to obtain granular sol-gel bioactive glass; ball mill at 480rpm for 3 hours, and pass through a 200-mesh sieve to obtain CaO- SiO ₂ -P ₂ O ₅ biological glass powder, the composition of each material is: 14% calcium oxide, 9% phosphorus pentoxide and 77% silicon dioxide;

(3) Mix 50g of Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ bioglass powder and 50g of CaO-SiO ₂ -P ₂ O ₅ bioglass powder, and add to 82mL polyacrylamine solution with a volume fraction of 6%. , ball milled for 3 hours and mixed to obtain a bioglass slurry with a volume fraction of 55%;

(4) Add the bioglass slurry obtained in step (1) dropwise into the counter mold of polylactic acid-glycolic acid copolymer, and perform centrifugal grouting on the counter mold in Xiangyi L550 centrifuge at 1200r/min, and place in After curing in a water bath at 72°C for 1.5h, place it in a drying oven and dry at 60°C for 60h to obtain a solid material;

(5) Put the solid material into a zirconia saggar, raise the temperature of the solid material to 950 °C at a rate of 2 °C/min and keep it for 1.5 h; naturally cool down to 20 °C to obtain a biological material for bone defect repair. Active glass-ceramic material.

Example 4

A mixture of Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder and CaO-SiO ₂ biological glass powder is used, wherein the mass of Na ₂ O-CaO-P ₂ O ₅ -SiO ₂ biological glass powder The fraction is 1%, and the mass fraction of CaO- _SiO2 bioglass powder is 99%.

(1) After fully mixing 37.61g sodium carbonate, 33.57g calcium carbonate, 15.30g tricalcium phosphate and 49.00 g silicon dioxide, put them into a platinum crucible and melt at 1400°C for 120min, then pour the molten glass into deionized Quenching in water to obtain amorphous bioactive glass. After filtering the water, dry it in an electric blast drying oven at 60°C for 24 hours, ball mill it in a planetary ball mill at a speed of 480rpm for 3 hours, and pass through a 200-mesh sieve to obtain Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ biological glass powder, the composition of each material is: 22% calcium oxide, 7% phosphorus pentoxide, 22% sodium oxide and 49% silicon dioxide;

(2) Add 249.6mL deionized water, 38.40mL 2mol/L hydrochloric acid catalyst and 400.00mL tetraethyl orthosilicate to the beaker, stir and hydrolyze for 30min at room temperature, then add 103.76g calcium nitrate tetrahydrate, stir well After uniformity, a transparent, uniform and stable sol was obtained; the sol was aged at room temperature for 48 hours, so that the hydrolysis-polycondensation reaction fully proceeded, and a wet gel was formed; the wet gel was dried at 140°C for 2 days, and the dry coagulation was obtained after the solvent evaporated. Glue; the dry gel is heat-treated and solidified at 650°C to obtain granular sol-gel bioactive glass; ball milled at a speed of 480 rpm for 3 hours, and passed through a 200-mesh sieve to obtain CaO-SiO ₂ bio-glass powder. : 20% calcium oxide and 80% silicon dioxide;

(3) Mix 1gNa ₂ O-CaO-SiO ₂ -P ₂ O ₅ bioglass powder and 99gCaO-SiO ₂ bioglass powder, add to 67mL polyacrylamide solution with a volume fraction of 6%, and ball mill for 3 hours to mix. Uniformly, obtain the bioglass slurry that volume fraction is 60%;

(4) Add the bioglass slurry obtained in step (1) dropwise into the unsaturated polyester resin polymer counter-form, and perform centrifugal grouting on the counter-form in a Xiangyi L550 centrifuge at 1000r/min, and place After curing in a water bath at 72°C for 1.5h, place it in a drying oven and dry at 60°C for 60h to obtain a solid material;

(5) Put the solid material into a zirconia saggar, raise the temperature of the solid material to 950 °C at a rate of 2 °C/min and keep it for 1.5 h; naturally cool down to 20 °C to obtain a biological material for bone defect repair. Active glass-ceramic material.

Figure 1 is a micro-CT photo of the bioactive glass-ceramic bone repair material prepared in Example 1 of the present invention. It can be seen that the bone repair material of the present invention has a stacked channel structure, and such a microstructure is conducive to the growth of tissues and nutrient transport and metabolism.

Fig. 2 is an SEM photograph of the surface of the bioactive glass-ceramic bone repair material prepared in Example 1 of the present invention. It can be seen that the material is partially crystallized, which makes the material have better mechanical properties.

Claims (10)

1. be used for the preparation method of the biological activated glass ceramic material of bone defect repair, it is characterized in that, comprise the steps:

(1) the bio-vitric powder is sieved, add the ROHM amine aqueous solution, milling mixing obtains the bio-vitric slurry;

(2) the bio-vitric slurry that step (1) is obtained dropwise adds in the polymer reverse, and the polymer reverse is carried out centrifugal grouting in whizzer, in 70 ~ 75 ℃ of water-baths, solidify 1 ~ 2h after, 50 ~ 70 ℃ of drying 48 ~ 72h obtain solid material;

(3) solid material that step (2) is obtained is removed the polymer reverse in 900 ~ 1000 ℃ of calcinings under temperature programmed control, make the biological activated glass ceramic material that is used for the bone defect repair.

2. preparation method according to claim 1 is characterized in that, said bio-vitric powder is Na ₂O-CaO-SiO ₂-P ₂O ₅Bio-vitric powder and/or CaO-SiO ₂-P ₂O ₅The bio-vitric powder.

3. preparation method according to claim 2 is characterized in that, said Na ₂O-CaO-SiO ₂-P ₂O ₅The material of bio-vitric powder is formed mass percent: quicklime 20 ~ 25%, Vanadium Pentoxide in FLAKES 5 ~ 7%, sodium oxide 20 ~ 25%, silicon-dioxide 43 ~ 49%; Said CaO-SiO ₂-P ₂The material of O bio-vitric powder is formed mass percent: quicklime 14 ~ 33%, Vanadium Pentoxide in FLAKES 0 ~ 9%, silicon-dioxide 58 ~ 80%.

4. preparation method according to claim 3 is characterized in that, the volume(tric)fraction of bio-vitric powder is 50 ~ 60% in the said bio-vitric slurry.

5. preparation method according to claim 4 is characterized in that, the pore dimension of said polymer reverse is 500 ~ 1000 microns, and geometrical shape is cubes, rectangular parallelepiped or right cylinder.

6. according to the described preparation method of one of claim 1 ~ 5, it is characterized in that the process of said temperature programmed control comprises following three phases:

(1) temperature rise period: the temperature of solid material is risen to 900 ~ 1000 ℃ with the speed of 2 ~ 3 ℃/min;

(2) holding stage: the temperature of solid material is kept 1 ~ 2h at 900 ~ 1000 ℃;

(3) temperature-fall period: be cooled to 10 ~ 30 ℃ naturally.

7. preparation method according to claim 6 is characterized in that, the volume(tric)fraction of poly amic acid is 4 ~ 8% in the said ROHM amine aqueous solution.

8. preparation method according to claim 7 is characterized in that, the rotating speed of said centrifugal grouting is 800 ~ 1200r/min.

9. preparation method according to claim 8 is characterized in that, said polymer reverse is photosensitive resin reverse or polymkeric substance reverse.

10. preparation method according to claim 9 is characterized in that said photosensitive resin is a unsaturated polyester resin, comprises gathering meso lactic acid or polycaprolactone; Said polymkeric substance is polylactic acid-glycolic guanidine-acetic acid multipolymer or acrylonitrile-butadiene-styrene copolymer.

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