WO2020151261A1

WO2020151261A1 - Cotton-like fiber scaffold as well as preparation method therefor and application thereof

Info

Publication number: WO2020151261A1
Application number: PCT/CN2019/110974
Authority: WO
Inventors: 李子樵; 周杰; 徐嘉麟
Original assignee: 蓝怡科技集团股份有限公司; 浙江蓝怡医药有限公司
Priority date: 2019-01-25
Filing date: 2019-10-14
Publication date: 2020-07-30
Also published as: CN109594195A; CN109594195B

Abstract

A cotton-like fiber scaffold as well as a preparation method therefor and an application thereof. A cotton-like fiber scaffold having a compression ratio as high as 45%, recovery rate as high as 80% and quite high adaptability may be prepared by using an electrostatic spinning method to blend and spin polylactic acid and bioactive materials such as bioglass, beta-tricalcium phosphate or calcium sulfate. The prepared cotton-like fiber scaffold has smaller fiber diameter, higher flexibility and higher porosity and specific surface area, and may provide more attachment points for osteoblasts and shorten rehabilitation time. The scaffold further has excellent biological activity, biocompatibility and biodegradability. An inorganic part in the scaffold may be degraded in vivo to generate elements essential for osteogenesis, and an inorganic part polylactic acid therein has good biodegradability and biocompatibility and may be degraded to generate lactic acid, and then the lactic acid is converted into carbon dioxide and water under the action of enzyme. The cotton-like fiber scaffold has no toxic side effects on a human body.

Description

Cotton-like fiber support and preparation method and application thereof

Technical field

This application belongs to the field of biomedical composite materials, and in particular relates to a cotton-like fiber scaffold and its preparation method and application.

Background technique

In daily activities, bone defects caused by trauma, infection, tumors and congenital diseases are very common. The treatment and repair of bone defects is one of the common clinical difficulties in orthopedics. The existing bone repair materials mainly include autogenous bone , Allogeneic bone and artificial bone substitutes. Autologous bone has the problem of inconvenience and limited sources. Allogeneic bone has tissue incompatibility and rejection. Artificial bone substitutes are plastic, histocompatibility, and biodegradability. There are high requirements, and the limitations of the above conditions make it difficult for the artificial bone substitutes obtained in the prior art to meet the needs of clinical applications.

Electrospinning is a commonly used method for preparing fiber filaments. The size of the fibers obtained by electrospinning is of nanometer or submicron level. It has the advantages of large specific surface area, high porosity, and good spatial connectivity, so it is often used Used in the field of biological tissue engineering. In bone repair, electrospun fiber has considerable advantages. Its excellent flexibility can be suitable for bone defects of various shapes and fully fill the defect. The ultra-high specific surface area and porosity are conducive to the migration of osteoblasts in large numbers. In addition, its ultra-high porosity and good connectivity can not only facilitate the migration of osteoblasts, but also promote the formation of blood vessels and the transportation of nutrients. .

In the field of bone repair, bioactive materials are also a research hotspot, especially materials such as bioglass and β-tricalcium phosphate (β-TCP). Due to their good biocompatibility, bioactivity and osteoconductivity, they can be It produces hydroxyapatite which is very similar to the composition of bone tissue and has excellent biodegradability. The elements such as Ca and P produced by degradation in the body can participate in and promote the formation of new bone in the body. It is a relatively mature Osteogenic material.

Polylactic acid (PLLA) material has good biocompatibility, biodegradability and mechanical properties, and has the advantages of easy processing. It is also a hot material in the field of bone tissue repair, but its disadvantages are poor biological activity and lack of osteogenic ability. Therefore, using electrospinning technology to synthesize bioactive ceramic particles and polylactic acid to prepare a composite material, theoretically, an active bone repair material with excellent mechanical and biological properties can be obtained. For example, CN106983910A discloses a method for preparing a polylactic acid composite bioglass tissue repair material, which dissolves polylactic acid particles in chloroform to obtain a polylactic acid solution, and then combines polyethylene oxide-polypropylene oxide- Polyethylene oxide triblock polymer is dissolved in ethanol, and ethyl silicate, triethyl phosphate, calcium nitrate, hydrochloric acid and other components are added to it to obtain a mixed liquid. The polylactic acid solution is mixed and electrospinning is performed to obtain the polylactic acid composite bioglass tissue repair material. In the above-mentioned prior art methods, most of the materials obtained are film-like materials. Moreover, the process of preparing bioglass by sol-gel method and re-spinning does not undergo a heat treatment step, which may cause a large amount of organic impurities in the product. The human body has a toxic effect, and the obtained bone implant material is of a fixed shape. It requires post-processing before the operation and the operation is cumbersome. After implantation, there will be a certain gap at the seam, making the implant material unable to contact the host bone , Thereby reducing the speed of bone repair.

Therefore, on the basis of the existing technology, those skilled in the art need to develop a biological bone material with high biological activity that can adapt to various bone defects and an efficient, convenient, and environmentally friendly preparation method to make it It has high compressibility and high resilience similar to cotton to perfectly adapt to various bone defect shapes and realize the repair of damaged bones or teeth and other hard tissues.

Summary of the invention

In view of the deficiencies in the prior art, the purpose of this application is to provide a biological bone material with high biological activity that can adapt to various bone defects and an efficient, convenient, and environmentally friendly preparation method, so that it has a similar cotton The high compressibility and high resilience of the product can perfectly adapt to various bone defect shapes and realize the repair of damaged bones or teeth and other hard tissues.

To achieve this objective, one of the objectives of the present application is to provide a cotton-like fiber scaffold, the cotton-like fiber scaffold comprising a composite fiber obtained by blending a bioactive material with polylactic acid and spinning the composite fiber. The obtained fiber scaffold has the compressibility and higher compression recovery rate like cotton.

The bioactive material includes any one of bioglass, β-tricalcium phosphate and calcium sulfate or a mixture of at least two materials.

The cotton-like fiber scaffold obtained by using the above-mentioned biologically active material in this application combines the biocompatibility and degradability of the biologically active material with the excellent mechanical properties of polylactic acid material, its cotton-like appearance and sufficient compressibility to make it in After being implanted in the body, it can perfectly adapt to various bone defect shapes, produce osteogenic elements during the degradation process, promote the generation of osteogenic factors, and achieve the repair of damaged bones or teeth and other hard tissues.

Preferably, in the composite fiber, the weight ratio of the bioactive material to the polylactic acid is 0.4 to 1.5:1, for example, 0.45:1, 0.50:1, 0.55:1, 0.60:1, 0.65:1, 0.70:1 , 0.75:1, 0.80:1, 0.85:1, 0.90:1, 0.95:1, 1.00:1, 1.05:1, 1.10:1, 1.15:1, 1.20:1, 1.25:1, 1.30:1, 1.35 : 1, 1.4:1 or 1.45:1, etc. Under the above ratio, the obtained composite fiber has better mechanical properties, compressibility, recovery performance, biological activity, degradation performance and biocompatibility, and is more preferably 0.65～1:1.

Preferably, the bioactive material is bioglass.

Preferably, the bioglass is a bioglass containing silica, calcium oxide, phosphorus pentoxide and additives, and the additives are any of sodium oxide, potassium oxide, magnesium oxide, aluminum oxide, and calcium fluoride. One or a mixture of at least two.

Preferably, the bioglass is any one or a mixture of at least two of 45S5 type, AW type, Bioverit type, Ceravital type and 58S type bioglass.

Preferably, the biological glass is ball-milled and has a particle size of 0.5-30 μm, such as 0.6 μm, 0.8 μm, 1.2 μm, 2 μm, 4 μm, 6 μm, 8 μm, 10 μm, 12 μm, 14 μm, 16 μm, 18 μm, 20 μm, 22 μm. , 24μm, 26μm, 28μm or 29μm, etc., the bioglass in the above particle size range has excellent spinning and fiberizing ability. If the particle size of the bioglass is too high, it is difficult to fiberize, and the particle size is too low, which will easily cause the bioglass to spin The obtained composite fiber is unevenly distributed, which reduces the mechanical properties and degradation performance of the composite fiber.

Those skilled in the art can obtain composite fibers of any diameter by appropriately adjusting the molecular weight of polylactic acid or the process parameters of electrospinning according to requirements. Preferably, the diameter of the composite fibers is 1-50 μm, for example, 2 μm, 4 μm. , 6μm, 10μm, 15μm, 20μm, 25μm, 30μm, 35μm, 40μm, 45μm or 48μm etc.

Preferably, the number average molecular weight of the polylactic acid is 100,000 to 1,000,000, such as 105,000, 125,000, 150,000, 200,000, 250,000, 300,000, 350,000, 400000, 450,000, 500,000, 550,000, 600000, 650,000, 700000, 750,000, 800000, 850,000, 900,000, 950,000 or 980000, etc.

The second objective of the present application is to provide a method for preparing the cotton-like fiber scaffold, which includes the following steps:

Step (1): mixing the bioactive material with polylactic acid, and dissolving the mixture with an organic solvent to obtain a spinning dope;

Step (2): Electrospin the spinning dope obtained in step (1) using an electrostatic spinning device, and collect the electrostatic spinning product with alcohol; and

Step (3): Take out the coagulated composite fiber filaments in the alcohol of step (2), and dry them to obtain the cotton-like fiber scaffold.

Preferably, the organic solvent described in step (1) is chloroform.

Preferably, calculated as a percentage by weight, the content of polylactic acid in the spinning dope described in step (1) is 8-14% by weight, such as 8.5% by weight, 9% by weight, 9.5% by weight, 10% by weight, 10.5% by weight, 11wt%, 11.5wt%, 12wt%, 12.5%, 13wt%, 13.5wt% or 13.8wt%, etc.

Preferably, in the electrospinning process in step (2), the extrusion speed of the spinning dope in the electrospinning equipment is 0.05 to 0.4 mL/min, for example, 0.08 mL/min, 0.1 mL/min, 0.13 mL /min, 0.15mL/min, 0.18mL/min, 0.20mL/min, 0.25mL/min, 0.30mL/min, 0.35mL/min or 0.38mL/min, etc.

Preferably, the voltage of the electrospinning in step (2) is 10-30kV, such as 12kV, 14kV, 16kV, 18kV, 20kV, 22kV, 24kV, 26kV or 28kV.

Preferably, in the electrostatic spinning device described in step (2), the distance between the spinning nozzle and the spinning receiving device is 5-30 cm, for example, 6 cm, 8 cm, 10 cm, 12 cm, 14 cm, 16 cm, 18 cm, 20cm, 22cm, 24cm, 26cm or 28cm, etc.

Preferably, the alcohol mentioned in step (2) is ethanol.

Preferably, the drying described in step (3) is performed in a fume hood.

Preferably, the drying temperature in step (3) is room temperature, and the drying time is 24-48h, such as 25h, 27h, 29h, 31h, 33h, 35h, 37h, 39h, 41h, 43h, 45h or 47h, etc. .

Preferably, the preparation method includes the following steps:

Step (1): The bioglass is mixed with ethanol, the mixture is ball milled, dried and sieved to obtain a pretreated bioglass with a particle size of 0.5-30μm, and then the pretreated bioglass and polylactic acid are weighted Mix at a ratio of 0.4 to 1.5:1, and dissolve the mixture with chloroform to obtain a spinning dope with a polylactic acid content of 8 to 14 wt%;

Step (2): Inject the spinning stock solution obtained in step (1) into the syringe of the electrospinning equipment, control the voltage of the electrospinning equipment to 10-30kV, and extrude the syringe at an extrusion speed of 0.05-0.4mL/min The spinning dope is output, the distance between the spinning nozzle and the spinning receiving device is 5-30cm, and the spinning receiving device is filled with absolute ethanol to collect the product of electrospinning; and

Step (3): Take out the composite fiber filaments coagulated in absolute ethanol in the spinning receiving equipment collected in step (2), transfer them to a fume hood, and dry them at room temperature for 24 to 48 hours. The cotton-like fiber scaffold is obtained.

The third purpose of the present application is to provide an application of the cotton-like fiber scaffold in the field of bone repair or tooth hard tissue repair.

The numerical range described in this application not only includes the above-exemplified point values, but also includes any point value between the above-mentioned numerical ranges that are not exemplified. Due to the limitation of space and for the sake of brevity, this application will not exhaustively list all the points. The specific point value included in the stated range.

Compared with the prior art, the beneficial effects of this application are:

(1) This application uses the method of electrospinning to obtain a highly adaptable cotton-like fiber scaffold with a compression rate of up to 45% and a recovery rate of up to 80%. Compared with the traditional drawing method, this The cotton-like fiber scaffold prepared by the application has a smaller fiber diameter, stronger flexibility, and higher porosity and specific surface area, which can provide more attachment points for osteoblasts, shorten the recovery time, and is suitable for various shapes The bone defect is completely repaired internally and on the surface.

(2) The cotton-like fiber scaffold prepared in this application also has excellent biological activity, biocompatibility and biodegradability. The inorganic part of it can be degraded in the body to produce calcium, phosphorus and other basic nutrients required for bone formation. Promote bone repair in the defect. The organic part of polylactic acid has good degradability and biocompatibility. It will be degraded into lactic acid in the body, and then converted into carbon dioxide and water under the action of enzymes. Toxic side effects.

Description of the drawings

Figure 1 is a physical photo of the cotton-like fiber scaffold 1 obtained in Example 1 in the specific implementation of the application.

Figure 2 is a physical photo of the cotton-like fiber scaffold 2 obtained in Example 2 of the specific implementation of the application.

Figure 3 is a physical photo of the cotton-like fiber scaffold 3 obtained in Example 3 in the specific implementation of the application.

FIG. 4 is a physical photo of the cotton-like fiber scaffold 4 obtained in Example 4 in the specific embodiment of the application.

FIG. 5 is a physical photo of the cotton-like fiber scaffold 5 obtained in Example 5 in the specific embodiment of the application.

Fig. 6 is an SEM photograph of the cotton-like fiber scaffold 2 obtained in Example 2 in the specific embodiment of the application after the biological activity test.

Fig. 7 shows the XRD spectra of the cotton-like fiber scaffolds 1 to 3 obtained in Examples 1 to 3 in the specific embodiment of the application after the biological activity test.

Fig. 8 is a curve of the weight loss of the cotton-like fiber scaffolds 1 to 4 obtained in Examples 1 to 4 in the specific embodiments of the application in the degradation performance experiment over time.

detailed description

The technical solution of the present application will be further explained through specific implementations below.

The bioglass selected in this application is any one of 45S5, AW, Bioverit, Ceravital and 58S bioglasses or a mixture of at least two bioglasses. The detailed components of each type of bioglass are as follows: Shown in Table 1.

Table 1 Detailed composition and content comparison table of various types of bioglass

Wherein "/" means that the component is not included.

The performance test methods of the cotton-like fiber scaffolds obtained in each embodiment and comparative example in this application are as follows:

Compression rate and recovery rate test: Take 0.05g of the prepared cotton-like fiber scaffold and place it in a glass tube with an inner diameter of 22mm. Place a round glass cover (weight 1g) with the same diameter in the glass tube. On the cotton-like fiber support, measure the height from the bottom of the round glass cover to the bottom of the glass tube and record it as h _0. Then, place a 10g weight on the glass cover and let it stand for 30 minutes. The height is recorded as h ₁ , finally, the weight is gently removed, and after standing for 30 minutes, the height from the bottom of the glass cover to the bottom of the glass tube is tested again, recorded as h ₂ , to obtain the compression rate of the cotton-like fiber support to be tested =[ (h ₀ -h ₁ )×100%]/h ₀ , the response rate=[(h ₂ -h ₁ )×100%]/(h ₀ -h ₁ ).

Fiber diameter test: Use the JSM-2100F scanning electron microscope (SEM) produced by Rigaku Corporation to test the microscopic morphology of the cotton-like fiber scaffold, and calculate the average fiber diameter, and record it as the cotton-like fiber scaffold The diameter of the fiber.

Example 1

Prepare cotton-like fiber scaffold 1 through the following steps:

Step (1): Take 30g of 45S5 type bioglass and mix with 10mL of grinding liquid ethanol. The mixture is subjected to ball milling treatment to obtain a pretreated bioglass with a particle size of 15μm. Then, the pretreated bioglass and 70g number average molecular weight 350,000 polylactic acid is mixed, and the mixture is dissolved in chloroform to obtain a spinning dope with a polylactic acid content of 12 wt%;

Step (2): Inject the spinning dope obtained in step (1) into the syringe of the electrostatic spinning equipment, control the voltage of the electrostatic spinning equipment to 20kV, and the syringe extrudes the spinning dope at an extrusion speed of 0.2mL/min , The distance between the spinning nozzle and the spinning receiving device is 20cm, and the spinning receiving device is filled with anhydrous ethanol to collect the products of electrospinning;

Step (3): Take out the composite fiber filaments coagulated in absolute ethanol in the spinning receiving equipment collected in step (2) to obtain a wet cotton-like fiber mass, which is transferred to a fume hood, and at room temperature After drying for 24 to 48 hours, the cotton-like fiber scaffold 1 (BG/PLLA=3/7) is obtained after drying.

The cotton-like fiber scaffold 1 obtained in Example 1 has a compression rate of 35% and a recovery rate of 35% after testing, and the fiber diameter is 35 μm.

Example 2

Prepare cotton-like fiber scaffold 2 through the following steps:

The only difference from Example 1 is that the amount of bioglass added in step (1) is 40g, the amount of polylactic acid added is 60g, and the content of polylactic acid in the spinning dope is still 12wt%.

In Example 2, a cotton-like fiber scaffold 2 (BG/PLLA=4/6) was obtained. After testing, the compression rate was 45%, the recovery rate was 75%, and the fiber diameter was 38 μm.

Example 3

Prepare cotton-like fiber scaffold 3 through the following steps:

The only difference from Example 1 is that the amount of bioglass added in step (1) is 50g, the amount of polylactic acid added is 50g, and the content of polylactic acid in the spinning dope is still 12wt%.

In Example 3, a cotton-like fiber scaffold 3 (BG/PLLA=5/5) was obtained. The compression rate was 40%, the recovery rate was 80%, and the fiber diameter was 40 μm.

Example 4

Prepare cotton-like fiber scaffold 4 through the following steps:

The only difference from Example 1 is that the amount of bioglass added in step (1) is 60g, the amount of polylactic acid added is 40g, and the content of polylactic acid in the spinning dope is still 12wt%.

In Example 4, a cotton-like fiber scaffold 4 (BG/PLLA=6/4) was obtained. The compression rate was 20%, the recovery rate was 60%, and the fiber diameter was 44 μm.

Example 5

Prepare cotton-like fiber scaffold 5 through the following steps:

The only difference from Example 2 is that the bioglass in step (1) is replaced with β-tricalcium phosphate.

In Example 5, a cotton-like fiber scaffold 5 was obtained. After testing, the compression rate was 40% and the recovery rate was 40%, and the fiber diameter was 42 μm.

Example 6

Prepare cotton-like fiber scaffold 6 through the following steps:

The only difference from Example 2 is that the bioglass in step (1) is replaced with calcium sulfate.

In Example 6, a cotton-like fiber scaffold 6 was obtained. The compression rate was 40% and the recovery rate was 45% after testing, and the fiber diameter was 38 μm.

Example 7

Prepare cotton-like fiber scaffold 7 through the following steps:

The only difference from Example 2 is that the bioglass in step (1) is replaced with a mixture of AW, Bioverit, and Ceravital bioglass at a weight ratio of 1:1:1.

The cotton-like fiber scaffold 7 was obtained in Example 7. The compression rate was 44%, the recovery rate was 72%, and the fiber diameter was 40 μm.

Example 8

Prepare cotton-like fiber scaffold 8 through the following steps:

The only difference from Example 2 is that the bioglass in step (1) is ball milled to obtain a pretreated bioglass with a particle size of 0.5μm. The voltage of the electrospinning equipment in step (2) is 10kV, and the syringe Extrude the spinning dope at an extrusion speed of 0.4mL/min, and the distance between the spinning nozzle and the spinning receiving device is 30cm,

The cotton-like fiber scaffold 8 was obtained in Example 8. The compression rate was 35%, the recovery rate was 71%, and the fiber diameter was 2 μm.

Example 9

The cotton-like fiber scaffold 9 is prepared by the following steps:

The only difference from Example 2 is that the bioglass in step (1) is ball milled to obtain pretreated bioglass with a particle size of 28μm. In step (2), the voltage of the electrospinning equipment is 30kV, and the syringe is The extrusion speed of 0.08mL/min extrudes the spinning dope, and the distance between the spinning nozzle and the spinning receiving device is 5cm.

The cotton-like fiber scaffold 9 was obtained in Example 9. The compression rate was 44%, the recovery rate was 55%, and the fiber diameter was 50 μm.

Example 10

The cotton-like fiber scaffold 10 is prepared by the following steps:

The only difference from Example 8 is that the bioglass in step (1) is ball milled to obtain a pretreated bioglass with a particle size of 0.1 μm.

The cotton-like fiber scaffold 10 was obtained in Example 10. The compression rate was 20%, the recovery rate was 42%, and the fiber diameter was 1.5 m.

Example 11

The cotton-like fiber scaffold 11 is prepared by the following steps:

The only difference from Example 2 is that the number average molecular weight of polylactic acid in step (1) is 1,000,000, and the content of polylactic acid in the obtained spinning dope is 8 wt%.

The cotton-like fiber scaffold 11 was obtained in Example 11. The compression rate was 48%, the recovery rate was 72%, and the fiber diameter was 48 μm.

Example 12

The cotton-like fiber scaffold 12 is prepared by the following steps:

The only difference from Example 2 is that the number average molecular weight of polylactic acid in step (1) is 100,000, and the content of polylactic acid in the obtained spinning dope is 14 wt%.

In Example 12, a cotton-like fiber scaffold 12 was obtained. The compression rate was 42% and the recovery rate was 68% after testing, and the fiber diameter was 36 μm.

The cotton-like fiber scaffolds 1 to 4 obtained in the foregoing Examples 1 to 4 were tested as follows to characterize their biological activity and degradation performance.

(1) Biological activity test

Take 1g each of the cotton-like fiber scaffolds 1 to 4 obtained in Examples 1 to 4 and place them in 100 mL of simulated body fluid (SBF solution) to simulate the effect of the internal environment. After soaking for 2 months, take them out and pass them through SEM and X respectively. XRD was used to observe the microstructure and mineralization ability of cotton-like fiber scaffolds 1-4.

(2) Degradation performance test

Take 1g each of the cotton-like fiber scaffolds 1 to 4 obtained in Examples 1 to 4, and place them in 100 mL Tris-HCl buffer solution to test the weight loss at different times to characterize the biodegradability of the cotton-like fiber scaffolds 1 to 4.

Figures 1 to 5 are the actual photos of the cotton-like fiber scaffolds 1 to 5 obtained in Examples 1 to 5 of this application. It can be seen from them that the appearance of the cotton-like fiber scaffolds obtained in Examples 2 and 3 of this application is better than other cottons. The cotton-like fiber scaffolds are more fluffy, and the cotton-like fiber scaffolds 1 to 4 obtained by mixing bioglass and polylactic acid are more bulky than the cotton-like fiber scaffold 5 obtained by mixing β-tricalcium phosphate and polylactic acid.

Fig. 6 is an SEM photograph of the cotton-like fiber scaffold 2 obtained in Example 2 of the application after the biological activity test, and Fig. 7 is the cotton-like fiber scaffold 1 to 3 obtained in Examples 1 to 3 of the application after the biological activity test It can be clearly seen from the XRD spectrum that the cotton-like fiber scaffold obtained in this application can self-mineralize in the body fluid environment because it contains a variety of Ca and P elements required for mineralization. The formation of hydroxyapatite (HA) can be clearly seen, and when the weight ratio of the bioactive material to polylactic acid is 0.65 to 1:1, the mineralization effect is optimal.

Fig. 8 is a curve of the weight loss of the cotton-like fiber scaffolds 1 to 4 obtained in Examples 1 to 4 of the application over time in the degradation performance experiment. It can be seen from this that when the content of bioactive materials in the cotton-like fiber scaffold is When there is more, the obtained cotton-like fiber scaffold has stronger degradability.

In summary, this application uses the method of electrospinning to prepare a composite material of bio-glass, β-tricalcium phosphate or calcium sulfate and other bioactive materials and polyemulsion, which can obtain a compression rate of up to 45% and recovery A cotton-like fiber scaffold with extremely high adaptability with a rate of up to 80%. Compared with the traditional drawing method, the cotton-like fiber scaffold prepared in this application has smaller fiber diameter, stronger flexibility and higher porosity And specific surface area, it can provide more attachment points for osteoblasts, shorten the recovery time, and is suitable for the comprehensive repair of various shapes of bone defects inside and on the surface. The cotton-like fiber scaffold prepared in this application also has excellent biological properties. Activity, biocompatibility and biodegradability, the inorganic part of it can be degraded in the body to produce calcium, phosphorus and other basic nutrients required for bone formation, and promote bone repair at the defect. The organic part of polylactic acid has a good Degradability and biocompatibility. The final degradation products are carbon dioxide and water, which have no toxic side effects to the human body and are environmentally friendly.

The applicant declares that the above are only specific implementations of this application, but the scope of protection of this application is not limited to this, and those skilled in the art should understand that any person skilled in the art disclosed in this application Any changes or substitutions that can be easily conceived within the technical scope fall within the scope of protection and disclosure of this application.

Claims

A cotton-like fiber scaffold, which comprises composite fibers obtained by spinning bioactive materials and polylactic acid after blending;

Wherein, the bioactive material includes any one material or a mixture of at least two materials among bioglass, β-tricalcium phosphate and calcium sulfate.
The cotton-like fiber scaffold according to claim 1, wherein the weight ratio of the bioactive material to the polylactic acid in the composite fiber is 0.4 to 1.5:1.
The cotton-like fiber scaffold according to claim 1, wherein the weight ratio of the bioactive material to the polylactic acid in the composite fiber is 0.65 to 1:1.
The cotton-like fiber scaffold according to any one of claims 1 to 3, wherein the bioactive material is bioglass.
The cotton-like fiber scaffold according to claim 4, wherein the bioglass is a bioglass containing silicon dioxide, calcium oxide, phosphorus pentoxide and additives, wherein the additives are sodium oxide, potassium oxide , Any one or a mixture of at least two of magnesium oxide, aluminum oxide and calcium fluoride.
The cotton-like fiber scaffold according to claim 4, wherein the bioglass is any one or a mixture of at least two of 45S5 type, AW type, Bioverit type, Ceravital type and 58S type bioglass.
The cotton-like fiber scaffold according to claim 4, wherein the bioglass is ball milled and has a particle size of 0.5-30 μm.
The cotton-like fiber scaffold according to any one of claims 1 to 7, wherein the diameter of the composite fiber is 1 to 50 μm.
The cotton-like fiber scaffold according to any one of claims 1 to 8, wherein the number average molecular weight of the polylactic acid is 100,000 to 1,000,000.
A method for preparing the cotton-like fiber scaffold according to any one of claims 1-9, which comprises the following steps:

Step (1): mixing the bioactive material with polylactic acid, and dissolving the mixture with an organic solvent to obtain a spinning dope;

Step (2): Electrospin the spinning dope obtained in step (1) using an electrostatic spinning device, and collect the electrostatic spinning product with alcohol; and

Step (3): Take out the coagulated composite fiber filaments in the alcohol of step (2), and dry them to obtain the cotton-like fiber scaffold.
The preparation method according to claim 10, wherein the organic solvent in step (1) is chloroform; and

Calculated by weight percentage, the content of polylactic acid in the spinning dope described in step (1) is 8-14 wt%.
The preparation method according to claim 10 or 11, wherein, in the electrospinning process in step (2), the extrusion speed of the spinning dope in the electrospinning equipment is 0.05 to 0.4 mL/min;

The voltage of the electrospinning in step (2) is 10-30kV;

In the electrostatic spinning device described in step (2), the distance between the spinning nozzle and the spinning receiving device is 5 to 30 cm; and

The alcohol mentioned in step (2) is ethanol.
The preparation method according to any one of claims 10-12, wherein the drying in step (3) is performed in a fume hood; and

The drying temperature in step (3) is room temperature, and the drying time is 24 to 48 hours.
The preparation method according to any one of claims 10-13, wherein the preparation method comprises the following steps:

Step (1): The bioglass is mixed with ethanol, the mixture is ball milled, dried and sieved to obtain pretreated bioglass with a particle size of 0.5-30μm, and then press the pretreated bioglass with polylactic acid Mix at a weight ratio of 0.4 to 1.5:1, and dissolve the mixture with chloroform to obtain a spinning dope with a polylactic acid content of 8 to 14 wt%;

Step (2): Inject the spinning stock solution obtained in step (1) into the syringe of the electrospinning equipment, and control the voltage of the electrospinning equipment to 10-30kV, and the syringe will extrude at an extrusion speed of 0.05-0.4mL/min The spinning dope is output, the distance between the spinning nozzle and the spinning receiving device is 5-30cm, and the spinning receiving device is filled with absolute ethanol to collect the product of electrospinning; and

Step (3): Take out the composite fiber filaments coagulated in absolute ethanol in the spinning receiving equipment collected in step (2), transfer them to a fume hood, and dry them at room temperature for 24 to 48 hours. The cotton-like fiber scaffold is obtained.
Application of the cotton-like fiber scaffold according to any one of claims 1 to 9 in the field of bone repair or tooth hard tissue repair.