1. A preparation method of borosilicate bioactive glass containing bismuth is used for preparing the borosilicate bioactive glass containing bismuth, and is characterized by comprising the following steps:

step S1, at least Bi is contained₂O₃The preparation raw materials are uniformly mixed with absolute ethyl alcohol, the mixture is melted in a high-temperature furnace after being sequentially subjected to ball milling and drying to obtain glass liquid, the glass liquid is poured into a mold, and the mixture is cooled to room temperature to obtain the borosilicate bioactive glassGlass;

step S2, sequentially crushing, ball-milling, drying and sieving the borosilicate bioactive glass to obtain borosilicate bioactive glass powder with the size distribution of 0.5-2 μm;

and step S3, performing heat treatment on the borosilicate bioactive glass powder for 60 to 400 minutes in a reducing atmosphere at the temperature of between 400 and 700 ℃ to separate bismuth elementary substance microcrystals from the borosilicate bioactive glass, so as to obtain the borosilicate bioactive glass containing the bismuth elementary substance microcrystals.

2. The method of preparing a bismuth-containing borosilicate bioactive glass according to claim 1, wherein:

wherein the borosilicate bioactive glass comprises 6 mol% Na₂O、8mol％K₂O、8mol％MgO、16mol％CaO、(54-x-y)mol％B₂O₃、2mol％P₂O₅、x mol％SiO₂6 mol% SrO and y mol% Bi₂O₃，

In the formula, x is more than or equal to 0 and less than or equal to 54, y is more than 0 and less than or equal to 6, and x + y is more than 0 and less than or equal to 54.

3. The method of preparing a bismuth-containing borosilicate bioactive glass according to claim 1, wherein:

wherein the preparing of the borosilicate bioactive glass in the step S1 is introduced by the following preparing raw materials: 4 mol% of Na₂CO₃、8mol％K₂CO₃、8mol％(MgCO₃)₄·Mg(OH)₂·5H₂O、1.6mol％MgCO₃、16mol％CaCO₃、2*(54-x-y)mol％H₃BO₃、4mol％NaH₂PO₃、x mol％SiO₂、6mol％SrCO₃And ymol% Bi₂O₃，

In the formula, x is more than or equal to 0 and less than or equal to 54, y is more than 0 and less than or equal to 6, and x + y is more than 0 and less than or equal to 54.

4. The method of preparing a bismuth-containing borosilicate bioactive glass according to claim 1, wherein:

wherein the volume of the absolute ethanol in the step S1 is 1.2 times to 1.5 times of the volume of the preparation raw material,

the ball milling time in the step S1 is 3h-5 h.

5. The method of preparing a bismuth-containing borosilicate bioactive glass according to claim 1, wherein:

wherein the melting temperature of the high-temperature furnace in the step S1 is 1100-1500 ℃, the melting time is 1-3 h,

the temperature rising rate of the high-temperature furnace is 1-5 ℃/min, and the temperature reducing rate is 1-3 ℃/min.

6. The method of preparing a bismuth-containing borosilicate bioactive glass according to claim 1, wherein:

wherein the reducing atmosphere in the step S3 is a hydrogen reducing atmosphere or a reducing atmosphere provided by carbon powder.

7. The method of preparing a bismuth-containing borosilicate bioactive glass according to claim 1, wherein:

wherein the size of the bismuth elementary substance microcrystal in the step S3 is 2nm-10 nm.

8. The method of preparing a bismuth-containing borosilicate bioactive glass according to claim 1, wherein:

the borosilicate bioactive glass containing bismuth elementary substance microcrystals in the step S3 is used in any one of bulk glass, glass microspheres, glass fibers, glass cement and glass ceramic scaffolds.

9. A borosilicate bioactive glass containing bismuth, characterized in that: the method of making a bismuth-containing borosilicate bioactive glass according to any of claims 1 to 8.

10. Use of the bismuth-containing borosilicate bioactive glass of claim 9 for the postoperative adjuvant treatment of tumors.

Background

Bone tumors are one of the serious diseases that threaten human health and reduce quality of life. Surgical resection is the most common treatment for the disease, but it causes damage to bone tissue and it is difficult to ensure complete removal of residual bone tumor cells. Therefore, the common solution is to inject bone cement or landfill biological material at the focus to repair the bone defect, and simultaneously, to kill the residual bone tumor cells by methods such as chemotherapy and radiotherapy. However, the toxic and side effects of chemotherapy and radiotherapy generally increase the physical and mental burden of patients. Therefore, the development of a multifunctional biological material with good bone repair, bone reconstruction and safe auxiliary treatment effects has important application prospect. Compared with normal cells, tumor cells have the characteristics of poor heat resistance, large tissue vascular aberration osmotic pressure and the like, so that the photothermal therapy which can kill the tumor cells and protect the normal tissue cells is realized by absorbing the energy irradiated by laser and then converting the energy into heat, and compared with the traditional methods such as chemotherapy, radiotherapy and the like, the photothermal therapy has the characteristics of higher safety, convenience in operation and the like.

The laser used for photothermal therapy is typically a near infrared laser at 808nm in the biological window. Near infrared light of 808nm has a relatively deep penetration depth, and can transmit energy to the photo-thermal agent through the skin. There are many kinds of photo-thermal agents, and the photo-thermal agents generally need to have the performances of biocompatibility, no cytotoxicity, good photo-thermal conversion efficiency and the like. Bismuth is a trace element essential to human body, and has no cytotoxicity in low concentration range, and bismuth-containing photothermal agent such as Bi₂S₃，Bi₂Se₃The nano semiconductor particles have good photo-thermal effect and tumor cell killing effect. However, such nanoparticles are not degradable, adding to the potential risk. The bismuth-containing germanate glass can absorb laser with the wavelength of 808nm and emit infrared light with the wavelength of 1300nm, photon energy is converted into phonon energy by quenching the emission of near infrared light, the local temperature is raised, however, the process needs higher laser power to be raised to 42-45 ℃, and the photo-thermal conversion efficiency is lower.

Disclosure of Invention

In order to solve the problems, the invention provides a preparation method and application of borosilicate bioactive glass containing bismuth, and adopts the following technical scheme:

the invention provides a preparation method of borosilicate bioactive glass containing bismuth, which is characterized by comprising the following steps: step S1, at least Bi is contained₂O₃The preparation raw materials are uniformly mixed with absolute ethyl alcohol, and are melted in a high-temperature furnace after being sequentially subjected to ball milling and drying to obtain glass liquid, and then the glass liquid is poured into a mold and is cooled to room temperature to obtain borosilicate bioactive glass; step S2, sequentially crushing, ball-milling, drying and sieving the borosilicate bioactive glass to obtain borosilicate bioactive glass powder with the size distribution of 0.5-2 μm; and step S3, performing heat treatment on the borosilicate bioactive glass powder for 60 to 400 minutes in a reducing atmosphere at the temperature of between 400 and 700 ℃ to separate bismuth elementary substance microcrystals from the borosilicate bioactive glass, so as to obtain the borosilicate bioactive glass containing the bismuth elementary substance microcrystals.

The method for preparing the borosilicate bioactive glass containing bismuth provided by the invention can also have the characteristic that the borosilicate bioactive glass comprises 6 mol% of Na₂O、8mol％K₂O、8mol％MgO、16mol％CaO、(54-x-y)mol％B₂O₃、2mol％P₂O₅、x mol％SiO₂6 mol% SrO and y mol% Bi₂O₃In the above formula, x is more than or equal to 0 and less than or equal to 54 and 0<y≤6，0<x+y≤54。

The method for preparing the borosilicate bioactive glass containing bismuth provided by the invention can also be characterized in that the borosilicate bioactive glass prepared in the step S1 is introduced by the following preparation raw materials: 4 mol% of Na₂CO₃、8mol％K₂CO₃、8mol％(MgCO₃)₄·Mg(OH)₂·5H₂O、1.6mol％MgCO₃、16mol％CaCO₃、2*(54-x-y)mol％H₃BO₃、4mol％NaH₂PO₃、x mol％SiO₂And 6 mol% SrCO₃，y mol％Bi₂O₃In the above formula, x is more than or equal to 0 and less than or equal to 54 and 0<y≤6，0<x+y≤54。

The preparation method of the borosilicate bioactive glass containing bismuth provided by the invention can also be characterized in that the volume of the absolute ethyl alcohol in the step S1 is 1.2-1.5 times of the volume of the raw materials, and the ball milling time in the step S1 is 3-5 h.

The preparation method of the borosilicate bioactive glass containing bismuth, provided by the invention, can also have the characteristics that the melting temperature of the high-temperature furnace in the step S1 is 1100-1500 ℃, the melting time is 1-3 h, the temperature rising rate of the high-temperature furnace is 1-5 ℃/min, and the temperature reduction rate is 1-3 ℃/min.

The method for preparing the borosilicate bioactive glass containing bismuth provided by the invention can also have the characteristic that the reducing atmosphere in the step S3 is a hydrogen reducing atmosphere or a reducing atmosphere provided by carbon powder.

The preparation method of the borosilicate bioactive glass containing bismuth provided by the invention can also have the characteristic that the size of bismuth elementary substance microcrystal in the step S3 is 2nm-10 nm.

The method for preparing the bismuth-containing borosilicate bioactive glass provided by the invention can also be characterized in that the borosilicate bioactive glass containing bismuth elementary crystallites obtained in the step S3 is used in any one of bulk glass, glass microspheres, glass fibers, glass bone cement and glass ceramic scaffolds.

The invention also provides borosilicate bioactive glass containing bismuth, which is characterized in that: the method of making a bismuth-containing borosilicate bioactive glass according to any of claims 1 to 8.

The invention also provides application of the borosilicate bioactive glass containing bismuth in postoperative adjuvant therapy of tumors.

Action and Effect of the invention

According to the preparation method of the bismuth-containing borosilicate bioactive glass, provided by the invention, bismuth elementary substance microcrystal is separated from the bismuth-doped borosilicate bioactive glass in a reducing atmosphere by adopting a high-temperature heat treatment process, and the photo-thermal effect of the bismuth-containing borosilicate bioactive glass is enhanced by utilizing the plasma effect of the bismuth elementary substance microcrystal while the performance of the borosilicate bioactive glass is adjusted. Therefore, the borosilicate bioactive glass containing bismuth prepared by the preparation method has better biological performance and tissue repair capability.

According to the application of the borosilicate bioactive glass containing bismuth in the postoperative adjuvant therapy of tumors, ions such as B, Ca and Mg and Si and B ion groups can be released in the degradation process of the borosilicate bioactive glass containing bismuth single substance microcrystals, so that the gene expression of osteoblasts can be effectively up-regulated, and the borosilicate bioactive glass containing bismuth has the potential of promoting directional differentiation and bone tissue repair. On the basis of maintaining good biological performance of the borosilicate bioactive glass, the bismuth-containing borosilicate bioactive glass with stronger photothermal effect can protect normal tissues such as skin and muscle under milder conditions and kill residual tumor cells. Therefore, the borosilicate bioactive glass containing bismuth has wide application prospect in the field of bone tissue engineering and the field of tumor treatment.

Drawings

FIG. 1 is an XRD diffraction pattern of bioglass powder in a first embodiment of the invention;

FIG. 2 is a transmission electron microscope image of bioglass powder according to a first embodiment of the present invention;

FIG. 3 is a graph of photothermal effect temperature rise of a bioglass cement bar in an SBF solution for five cycles in accordance with a second embodiment of the present invention;

FIG. 4 is a scanning electron microscope image of hydroxyapatite formed by ion release and mineralization after the bioglass bone cement is soaked in the SBF solution in the second embodiment of the invention;

FIG. 5 is a scanning electron microscope image of bioglass fibers in a fourth example of the invention.

Detailed Description

The preparation method of the borosilicate bioactive glass containing bismuth comprises the following steps:

step one, Na is added₂CO₃、K₂CO₃、(MgCO₃)₄·Mg(OH)₂·5H₂O、MgCO₃、CaCO₃、H₃BO₃、KH₂PO₃、SiO₂、SrCO₃And Bi₂O₃The prepared raw materials are uniformly mixed with absolute ethyl alcohol with the volume 1.2-1.5 times of the volume of the prepared raw materials. Ball-milling the preparation raw material mixed with the absolute ethyl alcohol for 3-5 h, drying, putting the dried raw material into a platinum crucible, and melting in a high-temperature furnace at 1100-1500 ℃ for 1-3 h to obtain the glass liquid, wherein the heating rate of the high-temperature furnace is 1-5 ℃/min, and the cooling rate is 1-3 ℃/min. And pouring the glass liquid into a mold, and cooling to room temperature to obtain the borosilicate bioactive glass. Wherein the borosilicate bioactive glass comprises 6 mol% Na₂O、8mol％K₂O、8mol％MgO、16mol％CaO、(54-x-y)mol％B₂O₃、2mol％P₂O₅、x mol％SiO₂6 mol% SrO and ymol% Bi₂O₃Wherein x is more than or equal to 0 and less than or equal to 54 and 0<y≤6，0<x + y is less than or equal to 54, and the total molar weight is 100 mol%. Wherein, KH₂PO₃Can be replaced by NaH₂PO₃。

And step two, sequentially crushing, ball-milling, drying and sieving the borosilicate bioactive glass obtained in the step one to obtain the borosilicate bioactive glass powder with the size distribution of 0.5-2 mu m.

And step three, carrying out heat treatment on the borosilicate bioactive glass powder obtained in the step two for 60-400 minutes in a reducing atmosphere at the temperature of 400-700 ℃ to separate out 2-10nm bismuth elementary substance microcrystal from the borosilicate bioactive glass, so as to obtain the borosilicate bioactive glass containing the bismuth elementary substance microcrystal.

The borosilicate bioactive glass containing bismuth elementary substance microcrystal prepared by the preparation method can be further processed to obtain bioactive glass-ceramic powder, bioactive glass-bone cement, a 3D printed bioactive glass-ceramic bracket, bioactive glass fiber and bioactive glass microspheres.

The borosilicate bioactive glass containing bismuth single substance microcrystal prepared by the preparation method can be applied to postoperative adjuvant therapy of tumors and can kill postoperative residual tumor cells. The bioactive glass bone cement obtained by further processing can be applied to the fields of bone tissue engineering and tumor treatment, has a promoting effect on bone tissue regeneration, and has an auxiliary effect on postoperative bone tumor treatment.

In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the following embodiments are specifically described in the preparation method of the borosilicate bioactive glass containing bismuth in the invention with reference to the attached drawings.

< example one >

The embodiment provides a preparation method of borosilicate bioactive glass containing bismuth, which specifically comprises the following steps:

step one, taking 30g of preparation raw material (containing Na)₂CO₃、K₂CO₃、(MgCO₃)₄·Mg(OH)₂·5H₂O、CaCO₃、H₃BO₃、KH₂PO₃、SiO₂、SrCO₃And Bi₂O₃) The mixture was ball milled and mixed for 1 hour, dried at 60 ℃ and then placed in a 100mL platinum crucible. The platinum crucible containing the raw material is placed in a high temperature furnace preheated to 1200 ℃. After 2 hours of heat preservation, the platinum crucible was taken out to obtain molten glass, which was poured onto an iron plate and cooled to room temperature to obtain Na having a chemical composition of 6 mol% Na₂O、8mol％K₂O、8mol％MgO、16mol％CaO、48mol％B₂O₃、2mol％P₂O₅、0mol％SiO₂6 mol% SrO and 6 mol% Bi₂O₃The borosilicate bioactive glass of (1).

And step two, crushing the borosilicate bioactive glass, and then carrying out alcohol ball milling to obtain 3B-4Bi glass powder.

And step three, cleaning and drying the obtained glass powder, adopting a double-crucible method, providing reducing atmosphere with the carbon powder, carrying out heat treatment at 600 ℃ for 5 hours to obtain the 3B-4Bi-h bioactive glass ceramics, and crushing and ball-milling the glass ceramics to obtain the bioactive glass ceramics powder containing bismuth single substance microcrystal. Wherein the heating rate is 1 ℃/min, and the cooling rate is 1 ℃/min.

FIG. 1 is an XRD diffraction pattern of bioglass powder in a first embodiment of the invention; fig. 2 is a transmission electron microscope image of the bioglass powder in the first embodiment of the invention, wherein the crystallite diffraction interplanar spacing is 0.328 nm.

As shown in fig. 1 and fig. 2, the preparation method of this example obtains bioactive microcrystalline glass powder containing bismuth elementary crystallites, and the size of the bioactive microcrystalline glass powder is 2-10 nm.

< example two >

The embodiment provides a preparation method of borosilicate bioactive glass containing bismuth, which is used for preparing bioactive glass bone cement, and specifically comprises the following steps:

step one, preparing raw materials (containing Na)₂CO₃、K₂CO₃、(MgCO₃)₄·Mg(OH)₂·5H₂O、CaCO₃、H₃BO₃、KH₂PO₃、SiO₂、SrCO₃And Bi₂O₃) Ball milling and mixing for 1 hour, drying at 60 ℃, and placing in a platinum crucible of 100 mL. The platinum crucible containing the raw material is placed in a high temperature furnace preheated to 1450 ℃. After 3 hours of heat preservation, the platinum crucible was taken out to obtain molten glass, which was poured onto an iron plate and cooled to room temperature to obtain Na having a chemical composition of 6 mol% Na₂O、8mol％K₂O、8mol％MgO、16mol％CaO、0mol％B₂O₃、2mol％P₂O₅、48mol％SiO₂6 mol% SrO and 6 mol% Bi₂O₃The borosilicate bioactive glass of (1).

And step two, crushing the borosilicate bioactive glass, and then carrying out alcohol ball milling to obtain glass powder.

And step three, cleaning and drying the obtained glass powder, carrying out heat treatment in a tube furnace, supplying reducing atmosphere by hydrogen, carrying out heat treatment at 600 ℃ for 6 hours to obtain the bioactive microcrystalline glass containing the bismuth single substance microcrystal, and crushing and ball-milling the bioactive microcrystalline glass to obtain the bioactive microcrystalline glass powder containing the bismuth single substance microcrystal. Wherein the heating rate is 1 ℃/min, and the cooling rate is 1 ℃/min.

And step four, mixing the bioactive microcrystalline glass powder containing the bismuth single substance microcrystal and a sodium alginate solution according to a certain solid-to-liquid ratio to obtain the plasticine-shaped bioactive glass bone cement.

According to the preparation method of the borosilicate bioactive glass containing bismuth, the prepared bioactive glass bone cement can be applied to postoperative adjuvant therapy of tumors.

FIG. 3 is a photothermal effect temperature rise curve of five cycles of bioglass bone cement in SBF solution in the second embodiment of the present invention.

As shown in FIG. 3, the laser wavelength used was 808nm, and the laser power density was 1.25W/cm²The near-infrared laser of (2) irradiates the bioglass bone cement of the embodiment in the SBF solution, and the temperature rise time required when the temperature rises to 42-45 ℃ is shorter. It can be seen that the preparation method of the present example enhances the photothermal effect of borosilicate bioactive glass. Therefore, the bioactive glass has good photothermal effect, can convert laser energy of 808nm into heat, enables the local temperature to be raised, and further kills tumor cells.

Fig. 4 is a scanning electron microscope image of hydroxyapatite formed by ion release and mineralization after the bioglass bone cement is soaked in the SBF solution in the second embodiment of the invention.

As shown in fig. 4, the bioglass bone cement of the present embodiment in the SBF solution is gradually degraded, and Ca, B, P, Mg, etc. are released to form hydroxyapatite, which has the potential ability to stimulate regeneration of surrounding tissues and blood vessels. It can be seen that the bioglass bone cement of the present embodiment also retains the bioactivity of borosilicate bioactive glass.

< example three >

The embodiment provides a preparation method of borosilicate bioactive glass containing bismuth, which is used for preparing a bioactive glass ceramic bracket for 3D printing and specifically comprises the following steps:

step one, preparing raw materials (containing Na)₂CO₃、K₂CO₃、(MgCO₃)₄·Mg(OH)₂·5H₂O、CaCO₃、H₃BO₃、KH₂PO₃、SiO₂、SrCO₃And Bi₂O₃) Ball milling and mixing for 1 hour, drying at 60 ℃, and placing in a platinum crucible of 100 mL. The platinum crucible containing the raw material is placed in a high temperature furnace preheated to 1450 ℃. After 3 hours of heat preservation, the platinum crucible was taken out to obtain molten glass, which was poured onto an iron plate and cooled to room temperature to obtain Na having a chemical composition of 6 mol% Na₂O,8mol％K₂O,8mol％MgO,16mol％CaO,0mol％B₂O₃,2mol％P₂O₅,53mol％SiO₂,6mol％SrO,1mol％Bi₂O₃The borosilicate bioactive glass of (1).

And step two, crushing the borosilicate bioactive glass, and then carrying out alcohol ball milling to obtain glass powder.

And step three, cleaning and drying the obtained glass powder, providing a reducing atmosphere by hydrogen by adopting a double-crucible method, carrying out heat treatment for 6 hours at 600 ℃ to obtain the bioactive microcrystalline glass containing the bismuth elementary substance microcrystal, and crushing and ball-milling the bioactive microcrystalline glass to obtain the bioactive microcrystalline glass powder containing the bismuth elementary substance microcrystal. Wherein the heating rate is 1 ℃/min, and the cooling rate is 1 ℃/min.

And step four, uniformly stirring the bioactive microcrystalline glass powder containing the bismuth single substance microcrystal and ethyl cellulose ethanol according to a certain proportion to obtain bioactive glass slurry containing the bismuth single substance microcrystal, performing 3D printing on the bioactive glass slurry to obtain a preliminary bioactive glass ceramic support, and sintering the preliminary support at 550 ℃ for 6 hours to obtain the final bioactive glass ceramic support.

< example four >

The embodiment provides a preparation method of borosilicate bioactive glass containing bismuth, which is used for preparing bioactive glass fiber and specifically comprises the following steps:

step one, 30g of preparation raw material (containing Na)₂CO₃、K₂CO₃、(MgCO₃)₄·Mg(OH)₂·5H₂O、CaCO₃、H₃BO₃、KH₂PO₃、SiO₂、SrCO₃And Bi₂O₃) Ball milling and mixing for 1 hour, drying at 60 ℃, and placing in a platinum crucible of 100 mL. The platinum crucible containing the raw material is placed in a high temperature furnace preheated to 1200 ℃. After 2 hours of heat preservation, the platinum crucible was taken out to obtain Na with a chemical composition of 6 mol%₂O,8mol％K₂O,8mol％MgO,16mol％CaO,53mol％B₂O₃,2mol％P₂O₅,0mol％SiO₂,6mol％SrO,1mol％Bi₂O₃The borosilicate bioactive glass liquid.

And step two, taking out the borosilicate bioactive glass liquid obtained in the step one, cooling the borosilicate bioactive glass liquid in the air for a certain time to ensure that the glass liquid has a certain viscosity, and blowing the borosilicate bioactive glass liquid to the glass liquid through high-speed airflow to obtain the glass fiber.

And step three, placing the glass fiber in a reducing atmosphere provided by hydrogen, and carrying out heat treatment for 6 hours at 600 ℃ to obtain the bioactive glass fiber containing the bismuth single substance microcrystal. Wherein the heating rate is 1 ℃/min, and the cooling rate is 1 ℃/min.

FIG. 5 is a scanning electron microscope image of bioglass fibers in a fourth example of the invention.

As shown in FIG. 5, the bioglass fiber prepared by the preparation method of this example has good flexibility, the size of the fiber is 50-250 μm, the strength is high, and after heat treatment, the surface of the fiber gradually loses transparency, which indicates that a large amount of microcrystals are generated on the surface. Finally obtaining the biological glass fiber containing the Bi single substance microcrystal.

< example five >

The embodiment provides a preparation method of borosilicate bioactive glass containing bismuth, which is used for preparing bioactive glass microspheres and specifically comprises the following steps:

step one, 30g of preparation raw material (containing Na)₂CO₃、K₂CO₃、(MgCO₃)₄·Mg(OH)₂·5H₂O、CaCO₃、H₃BO₃、KH₂PO₃、SiO₂、SrCO₃And Bi₂O₃) Ball milling and mixing for 1 hour, drying at 60 ℃, and placing in a platinum crucible of 100 mL. The platinum crucible containing the raw material was placed in a high temperature furnace preheated to 1250 ℃. After 2.5 hours of heat preservation, the platinum crucible was taken out to obtain molten glass, which was quenched to obtain Na having a chemical composition of 6 mol%₂O,8mol％K₂O,8mol％MgO,16mol％CaO,53mol％B₂O₃,2mol％P₂O₅,16mol％SiO₂,6mol％SrO,4mol％Bi₂O₃The borosilicate bioactive glass of (1).

And step two, crushing and ball-milling the borosilicate bioactive glass for 24 hours to obtain glass powder.

And step three, carrying out heat treatment on the glass powder for 180 minutes at 500 ℃ in a reducing atmosphere provided by carbon powder to obtain the glass powder with the Bi elementary substance microcrystal, and screening to obtain the glass powder with 200-500 meshes. Burning the screened glass powder by oxyhydrogen flame to obtain the bioactive glass microspheres.

The above embodiments are preferred examples of the present invention, and are not intended to limit the scope of the present invention.