CN107303397B - A kind of biologically active Injectable compound bone cement and its preparation method and application - Google Patents

Abstract

The invention relates to an injectable composite bone cement with bioactivity, its preparation method and application. The bone cement is composed of solid phase powder and solidification liquid; wherein, the solid phase powder is composed of phosphosilicate bioactive glass and calcium sulfate, and the solidification liquid contains chitosan and sodium β-glycerophosphate. Mix the solid phase powder and the curing liquid according to a certain ratio, stir evenly, and form a composite bone cement after curing at room temperature. The bone cement of the invention has good injectability, collapse resistance and mechanical properties. At the same time, the bone cement of the present invention has excellent bioactivity, biocompatibility and biodegradability, and there is no problem of calcium phosphate (CPC) or calcium sulfate (CSC) bone cement collapse in the later stage, which can provide the necessary nutrients for cell growth. The "bridge" can be used for fracture treatment, preparation of bone filling materials and biomedical materials for bone repair and regeneration.

Description

A bioactive injectable composite bone cement and its preparation method and application

technical field

The invention belongs to the technical field of biomedical materials, and relates to a bioactive bone cement and its preparation method and application.

Background technique

With the increasing aging trend of our population, the incidence of osteoporotic vertebral compression fracture (OVCF) is increasing year by year, which has become one of the thorny problems in clinical practice. Percutaneous kyphoplasty (PKP) or minimally invasive vertebroplasty (VP) is the main method for the treatment of OVCF. At present, the commonly used materials in PKP or VP include polymethyl methacrylate bone cement (PMMA), calcium phosphate bone cement (CPC) and calcium sulfate bone cement (CSC), but these materials all have obvious defects.

There is an obvious heating problem during the curing process of PMMA, and the hard solid formed after injection into the vertebral body is not biodegradable and has no biological activity; CPC and CSC bone cement have no heat generation effect similar to PMMA, have good biocompatibility, and can be degraded However, this type of material is easy to collapse, has no osteoinductive activity, has limited effect on promoting bone tissue formation, and the degradation rate does not match the growth rate of human bone, so it cannot provide long enough support for OVCF treatment. For example, currently on the market for PKP Bone cement (CSC and β-TCP composite bone cement), some patients had obvious vertebral height collapse during follow-up, and the formation of trabecular bone structure was slow. Therefore, it is necessary to seek a kind of bone tissue that has good biological activity, can induce the repair and regeneration of bone tissue, has good collapse resistance and appropriate degradation rate, and can provide sufficient long-term support for cell growth in the process of new bone growth and repair. Bone repair materials have become an urgent clinical problem to be solved.

Phosphosilicate bioactive glass (SPBG) is a kind of bone repair material with good bioactivity, degradable absorbability and biocompatibility. In the body fluid environment, it can form hydroxyapatite (HA) on the surface of the material that is similar to the composition of bone tissue, thereby forming a strong chemical bond between the bone tissue and the material, and inducing the formation of new bone tissue; in addition, its precipitated Si, P, and Ca ions can also promote the adhesion, proliferation, and differentiation of bone cells. After being implanted in the body for a certain period of time, SPBG can not only exhibit excellent osteoinductivity and osteogenesis, provide a biocompatible bone formation interface, but also provide a place for the free osteoblast stem cells in the surgical area to colonize. Bioactive surface that promotes the formation of new bone tissue. Currently, bioglass As a filling or restorative material, it has been widely used in clinical treatments such as dentistry and plastic surgery.

From the perspective of biology and chemistry, SPBG and calcium sulfate are complementary to a certain extent. The combination of the two may improve the osteoinductivity of the material, promote the formation of bone tissue, and solve the problem of late collapse of absorbable materials. However, the traditional compounding method usually uses calcium sulfate hemihydrate as the curing matrix, water or saline as the curing agent, and SPBG is introduced into the system in the form of filler. The content of SPBG in the system is too small, and the calcium sulfate itself as the main body degrades quickly, so there are problems that the system is easy to collapse and the degradation rate is too fast, which makes it difficult to provide enough for the growth of bone tissue cells in the bone repair process. Effective support of time.

Contents of the invention

The purpose of the present invention is to provide a novel injectable composite bone cement and its preparation method. The composite bone cement has good injectability, collapse resistance and mechanical properties, and also has excellent biological activity and biocompatibility and biodegradability.

To achieve the above object, the present invention adopts the following technical solutions:

An injectable composite bone cement with biological activity is composed of solid phase powder and solidification liquid; wherein, the solid phase powder is composed of phosphosilicate bioactive glass mixed with calcium sulfate, and the solid phase powder contains chitosan Sugar and sodium beta-glycerophosphate.

According to the present invention, the mass-to-volume ratio (solid-liquid ratio) of the solid phase powder to the solidified liquid is 1:1 to 3:1 (g/ml), preferably 1.5:1 to 2:1 (g/ml ).

According to the present invention, the sodium β-glycerophosphate is sodium β-glycerophosphate pentahydrate.

According to the present invention, the solid phase powder is composed of the following components in weight percent:

Phosphosilicate bioactive glass: greater than or equal to 20wt.% but not 100wt.%, preferably 25wt.% to 99wt.%, also preferably 30wt.% to 90wt.%;

Calcium sulfate: less than or equal to 80wt.% but not 0wt.%, preferably 1wt.%-75wt.%, more preferably 10wt.%-70wt.%.

According to the present invention, the composition of the phosphosilicate bioactive glass is: x(SiO ₂ )·y(CaO)·m(P ₂ O ₅ )·n(Na ₂ O), wherein, x, y, m, The range (mol.%) of n is as follows: x is 45mol.%～80mol.%, y is 15mol.%～40mol.%, m is 0mol.%～11mol.%, n is 0mol.%～25mol.%.

According to the present invention, the calcium sulfate is one or more of α-calcium sulfate hemihydrate, β-calcium sulfate hemihydrate, calcium sulfate dihydrate, anhydrous calcium sulfate and the like.

According to the present invention, the mass percentage of chitosan in the solidification liquid is 1wt.%～5wt.%, and the mass percentage of β-glycerophosphate sodium (preferably pentahydrate β-glycerophosphate sodium) is 4wt.%. ~9wt.%.

According to the present invention, the solidified liquid also contains an acid-containing aqueous solution, specifically, the solidified liquid is composed of the following components in mass percentage:

Chitosan 1wt.%～5wt.%

Sodium β-glycerophosphate (preferably sodium β-glycerophosphate pentahydrate) 4wt.%～9wt.%

Acidic aqueous solution 86wt.% ~ 95wt.%.

According to the present invention, the acid-containing aqueous solution is one of acetic acid aqueous solution, hydrochloric acid aqueous solution and citric acid aqueous solution with a concentration of 0.1-1 mol/L.

The preparation method of above-mentioned injectable composite bone cement, it comprises the following steps:

(1) Preparation of solid phase powder

Making phosphosilicate bioactive glass material into powder; adding calcium sulfate to the bioactive glass powder, and mixing uniformly to obtain solid phase powder;

(2) Preparation of solidification solution

mixing chitosan and sodium β-glycerophosphate in the solidification liquid with other components in the solidification liquid to obtain the solidification liquid;

(3) Preparation of composite bone cement

Blending the solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) to obtain the composite bone cement.

According to the present invention, in step (1), the weight percent content of phosphosilicate bioactive glass and calcium sulfate is:

Phosphosilicate bioactive glass: greater than or equal to 20wt.% but not 100wt.%, preferably 25wt.% to 99wt.%, also preferably 30wt.% to 90wt.%;

Calcium sulfate: less than or equal to 80wt.% but not 0wt.%, preferably 1wt.%-75wt.%, more preferably 10wt.%-70wt.%.

According to the present invention, step (2) is specifically: the solidified liquid is composed of the following components in mass percentage: chitosan 1wt.%～5wt.%, sodium β-glycerophosphate (preferably sodium β-glycerophosphate pentahydrate) 4wt.%～9wt.%, and 86wt.%～95wt.% of the acid-containing aqueous solution; according to the above solidification liquid ratio, chitosan accounting for 1wt.%～5wt.% of the total solidification liquid is added to the acid-containing aqueous solution, Stir and mix until it is clear and transparent to obtain an aqueous solution of chitosan; then, β-sodium glycerophosphate (preferably sodium β-glycerophosphate pentahydrate) accounting for 4wt.% to 9wt.% of the total amount of the solidified solution is dissolved in the acid-containing aqueous solution , and then dropwise into the chitosan aqueous solution under the action of stirring to obtain the solidified solution.

According to the present invention, in step (3), the solid phase powder and the solidified liquid are mixed according to the mass volume ratio (solid-liquid ratio) of 1:1 to 3:1 (g/ml), preferably 1.5:1 to 2:1 (g/ml).

The bioactive injectable composite bone cement prepared by the invention has good injectability, collapse resistance and mechanical properties. At the same time, it has excellent bioactivity, biocompatibility and biodegradability, and there is no problem of late collapse of calcium phosphate (CPC) and calcium sulfate (CSC) bone cement, which can provide effective support for a long time and can be used It is used for the treatment of osteoporotic vertebral body compression fractures or vertebral body collapse (that is, for the preparation of biomedical materials for the treatment of osteoporotic vertebral body compression fractures or vertebral body collapse), and can also be used for the preparation of bone filling materials and biomedical materials for bone repair. materials or biomedical materials for bone regeneration.

Compared with other prior art, the present invention has the following characteristics:

1. The solidifying solution in the composite bone cement of the present invention contains chitosan and sodium β-glycerophosphate. Chitosan is a kind of natural macromolecular material, has good adhesion, degradability and biocompatibility, has good adhesion to osteoblast, it is introduced in the solidification liquid of the present invention It can be used as a strong bonding phase to improve the curing performance of the material and greatly improve the collapse resistance of the material. Sodium β-glycerophosphate is a commonly used phosphorus supplement for the human body. In addition, introducing weakly alkaline β-sodium glycerophosphate into the solidification solution can make the solidification solution tend to be neutral; at the same time, sodium β-glycerophosphate The glycerol group in the water molecule can form a bonded water around the chitosan molecular chain through hydrogen bonding to prevent chitosan from being separated out from the solution; moreover, β-sodium glycerophosphate can regulate the sol-gel of the solidified solution. The transformation process affects the curing rate and other properties of the system.

2. The existing method can only introduce a small amount of silicate bioactive glass into the calcium sulfate bone cement system, but the bone cement prepared by the method of the present invention can introduce a high content of phospho-silicate bioactive glass, which can more effectively Play the respective functions of the two components in the bone cement solid phase powder of the present invention. Among them, the bioactive glass has good biocompatibility and bioactivity, and can be firmly combined with the surrounding skeletal tissue; in the body fluid environment, it quickly releases Si, P, Ca plasma, and promotes the formation of osteoblasts. The internal response of the metabolic cells, while improving the degradation performance of the material; after implantation in the body, it can induce the formation of HA similar to the composition of bone tissue on the surface of the material, thereby forming a strong chemical bond between the bone tissue and the material, and inducing new bone. tissue formation, so that the composite bone cement has excellent biological activity. The calcium sulfate has been widely used in the fields of bone repair and medicine, and can regulate the mechanical properties and degradation rate of the composite bone cement. And based on the improvement of the content of the bioactive glass, combined with the chitosan added in the above-mentioned solidification solution, while the anti-collapse property of the bone cement of the present invention is significantly improved, its degradation rate is significantly compatible with the growth rate of human bone improve.

3. The composite bone cement of the present invention has excellent bioactivity, biocompatibility and biodegradability. In simulated body fluid (SBF) culture, HA formed on the surface of the composite bone cement; after 12 weeks of culture, the initial shape of the composite bone cement remained unchanged when almost all calcium sulfate was degraded, and it had a certain mechanical support strength. There is a problem of late collapse of CPC and CSC bone cement, which can provide the necessary "bridge" for the growth of bone tissue cells, and has a good clinical application prospect.

4. The composite bone cement of the present invention has excellent injectability and collapse resistance, and can be injected into the bone repair site with a common syringe, and can be used for minimally invasive surgical treatment.

Description of drawings

Figure 1 is a picture of the appearance of the composite bone cement in Example 1 after solidification and demoulding.

Fig. 2 is the injection rate of composite bone cement at different solid-liquid ratios in Example 1.

Fig. 3 is the compressive strength of the composite bone cement in Examples 2-4.

Fig. 4 is a scanning electron micrograph of the surface morphology of the composite bone cement in Example 3 at different times in the in vitro activity test. The time in picture a is 0 days, the time in picture b is 1 week, the time in picture c is 3 weeks, and the time in picture d is 8 weeks.

Fig. 5 is an X-ray diffraction pattern of the composite bone cement in Example 6 cultured in simulated body fluid for 8 weeks.

Fig. 6 is a comparison of the in vitro degradation rate (weight loss) of the composite bone cement in Example 3 and the existing calcium sulfate bone cement at different time points.

Figure 7 is a comparison of the in vitro degradation rate (diameter change) of the composite bone cement in Example 3 and the existing calcium sulfate bone cement at different time points, the picture a is calcium sulfate bone cement, the picture b is composite bone cement, and the picture c is Comparison chart of statistical results of calcium sulfate bone cement and composite bone cement diameter change.

Fig. 8 is the cell proliferation experiment of the composite bone cement in Example 2 and Example 3 and the existing calcium sulfate bone cement: the cells are MG-63 cells, which are detected by MTT method after 1 day of culture.

Figure 9 is the cell adhesion experiment of the composite bone cement in Example 3: the cells are MG-63 cells.

Detailed ways

As mentioned above, the traditional compounding method usually uses calcium sulfate hemihydrate as the curing matrix, water or saline as the curing agent, and phosphosilicate bioactive glass (SPBG) is introduced into the system in the form of filler. The study found that since SPBG itself does not have the characteristics of self-solidification, the above-mentioned system can only introduce a small amount of SPBG, otherwise, a large amount of SPBG will seriously damage the structure formed when calcium sulfate hemihydrate is solidified, resulting in the failure of the system to solidify or the strength after solidification. The request cannot be met. In addition, the reason why the traditional system degrades too fast is that the calcium sulfate itself degrades very quickly, and the SPBG content in the system is relatively small. "Collapse" in granular form.

Based on this, the present invention provides a kind of novel injectable composite bone cement and preparation method thereof, by introducing the method for chitosan, β-glycerophosphate sodium (preferably pentahydrate β-glycerophosphate sodium) in solidification liquid, can greatly Increase the content of SPBG in the SPBG/calcium sulfate composite bone cement, so that the composite bone cement not only has good bioactivity and mechanical properties, but also has excellent collapse resistance and biodegradability, effectively overcoming the shortcomings of traditional methods, It has important application prospects. A non-limiting, possible mechanism is that if the SPBG content is high enough, HA formed on the surface of SPBG in body fluids will connect them to each other to form a block network, so that after the calcium sulfate is completely degraded, it can still provide Certain support, thereby solving the problem that the system in the prior art degrades too fast and cannot provide a "bridge" for cell growth.

Further, the early stage curing of the system of the present invention mainly relies on the sol-gel transition of the solidifying liquid and the interaction between the solidifying liquid and the solid phase powder, and the later stage mainly relies on the formation of a connected network between the SPBG and the HA generated on the surface of the SPBG to maintain the shape, providing Mechanical support and cell growth "bridge", not only suitable for adding calcium sulfate hemihydrate, but also calcium sulfate anhydrous and calcium sulfate dihydrate. The traditional system solidification mainly depends on the crystalline transformation of calcium sulfate hemihydrate into calcium sulfate dihydrate, and only calcium sulfate hemihydrate can be used.

Below in conjunction with accompanying drawing and example further elaborate the present invention. However, those skilled in the art understand that the protection scope of the present invention is not limited to the following examples. According to the content disclosed in the present invention, those skilled in the art will recognize that without departing from the technical characteristics and scope of the technical solution of the present invention, making many changes and modifications to the following embodiments belongs to the protection scope of the present invention. The raw materials used in the following examples are commercially available unless otherwise specified.

Example 1

(1) According to the composition ratio of bioactive glass, ethyl orthosilicate, triethyl phosphate, calcium nitrate tetrahydrate, and sodium nitrate are respectively used as precursors of silicon, phosphorus, calcium, and sodium, and nitric acid is used as a catalyst. - 46.1% SiO ₂ -26.9% CaO-2.6% P ₂ O ₅ -24.4% Na ₂ O (mol.%) bulk material prepared by gel method. After crushing and screening, the powder is prepared for use. The above powder is added into calcium sulfate hemihydrate according to 50% of the total amount of the solid phase powder, and mixed evenly to obtain the solid phase powder.

(2) Preparation of solidification solution

Preparation contains 2.5% chitosan, the solidification solution of 8% sodium β-glycerophosphate pentahydrate: 2.5g chitosan is dissolved in 74.5g acetic acid solution (1mol/L), stirs until clear and transparent, obtains chitosan aqueous solution . Weigh 8g of sodium β-glycerophosphate pentahydrate and dissolve it in 15g of acetic acid solution (1mol/L), and then add it dropwise into the above-mentioned chitosan aqueous solution under the action of stirring to obtain the solidified solution of the composite bone cement.

(3) Preparation of composite bone cement

Mix the solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) according to the solid-to-liquid ratio of 1:1, 2:1, and 3:1 (g/ml) for 1 min, and blend into a paste Pour into the mold and solidify. The curing time measured by the Vicat instrument was 80 min, 36 min, and 24 min, respectively. After curing at room temperature, the mold was demoulded and taken out to obtain a cylinder with a smooth surface (Figure 1), that is, the composite bone cement of the present invention.

To characterize the injectability of injectable composite bone cement using a medical syringe. Accurately weigh the weight M ₀ of the syringe before the test, the mass M ₁ after filling the blended paste into the syringe, and the weight M ₂ after extruding the composite bone cement slurry out of the medical syringe, and use the formula (1) to calculate the composite bone Cement injection rate (Fig. 2).

Formula (1): Injection rate J%=[(M ₁ -M ₂ )÷(M ₁ -M ₀ )]*100%

It can be seen from Figure 2 that with the increase of the solid-to-liquid ratio of bone cement, the injectability of bone cement decreases. The solid-liquid ratio can be adjusted so that the composite bone cement has good injectability and is used for minimally invasive surgery to treat bone injuries.

Example 2

(1) Preparation of solid phase powder

According to the composition ratio of bioactive glass, 54.2% SiO ₂ -35% CaO was prepared by sol-gel method using ethyl orthosilicate, phytic acid, and calcium nitrate tetrahydrate as the precursors of silicon, phosphorus, and calcium respectively. - 10.8% P ₂ O ₅ (mol.%) bulk material. After crushing and screening, the powder is obtained for later use. The above-mentioned bioactive glass powder is added into calcium sulfate hemihydrate according to 30% of the total amount of the solid phase powder, and mixed uniformly to obtain the solid phase powder.

(2) Prepare a solidified solution containing 1.75% chitosan and 7% sodium β-glycerophosphate pentahydrate: dissolve 1.75g chitosan in 77.25g acetic acid solution (1mol/L), stir until clear and transparent, and obtain shell Polysaccharide aqueous solution. Weigh 7g of sodium β-glycerophosphate pentahydrate and dissolve it in 14g of acetic acid solution (1mol/L), and then drop it into the above-mentioned chitosan aqueous solution under the action of stirring, which is the solidified solution of the composite bone cement.

(3) Preparation of composite bone cement

The solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) are fully stirred for 1 min according to the solid-to-liquid ratio of 2:1 (g/ml), and blended into a paste. The reconciled paste is injected into the mold with a syringe, cured at room temperature and removed from the mold to obtain a cylinder with a smooth surface. The curing time is 35min. The compressive strength after curing was 6.04±0.43Mpa (Figure 3), which was within the range of compressive strength (2-12Mpa) of cancellous bone reported in the literature; the compressive modulus was 362±149MPa, which also met the requirements of cancellous bone ( 100-500MPa), indicating that this composite bone cement is expected to be used as a substitute or repair material for cancellous bone to treat bone damage. The composite bone cement was not cytotoxic (Fig. 8).

Example 3

(1) Same as Example 2, prepare 54.2% SiO ₂ -35% CaO-10.8% P ₂ O ₅ (mol.%) bioactive glass powder. It is added into calcium sulfate hemihydrate according to 55% of the total amount of the solid phase powder, and mixed evenly to obtain the solid phase powder.

(2) with step (2) in embodiment 2

(3) Preparation of composite bone cement

The solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) are fully stirred for 1 min according to the solid-to-liquid ratio of 2:1 (g/ml), and blended into a paste. Compared with Example 2, the mechanical strength after curing was reduced, but still met the requirements of cancellous bone (Fig. 3). After 1 week of culture in SBF, the compressive strength reached 15.5 ± 2.8 Mpa, and a large amount of hydroxyapatite (HA) deposition was detected (Fig. 4). Compared with before culture, the strength after culture is greatly improved, which may be due to the formation of interconnected structures between deposited HA and bioactive glass, or between HA and HA. At the same time, a large amount of HA was deposited, indicating that the bone cement had biological activity in vitro. After soaking in SBF for 8 weeks, dense HA (Fig. 4) formed on the surface without collapse, and the compressive strength was 3.4±1.2Mpa, which can provide effective mechanical support and provide a "bridge" for the growth of bone tissue cells to promote bone repair .

After soaking in SBF for 12 weeks, the quality of the composite bone cement was degraded by about 50% (Figure 6), and the diameter did not change significantly (Figure 7). There was no existing layer-by-layer peeling problem of calcium sulfate bone cement, and it is expected to be used in the treatment of bone injuries Provide long-term support and solve the problem that the existing bone cement can not provide support for cell growth in the late collapse. The composite bone cement has no cytotoxicity (Fig. 8), and cells can adhere to its surface well (Fig. 9).

Example 4

(1) Same as Example 2, prepare 54.2% SiO ₂ -35% CaO-10.8% P ₂ O ₅ bioactive glass powder. It is added into the calcium sulfate hemihydrate according to 75% and 99% of the total amount of the solid phase powder, and mixed uniformly to obtain the solid phase powder.

(2) with step (2) in embodiment 2

(3) Preparation of composite bone cement

The solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) were fully stirred for 1 min according to the solid-to-liquid ratio of 2:1 (g/ml), blended into a paste, and injected into the mold to solidify. The compressive strength of composite bone cement after solidification is respectively 2.74 ± 0.45Mpa, 2.48 ± 0.80Mpa (Fig. 3), comprehensive embodiment 2, the data of compressive strength in embodiment 3, shows that mechanical strength after solidification increases with bioglass in solid phase powder. decreased with increasing content. After soaking SBF, HA was produced and showed in vitro activity.

Example 5

(1) The sol-gel method is used to prepare the bioactive glass block material with the composition of 58% SiO ₂ -38% CaO-4% P ₂ O ₅ , which is pulverized and screened to obtain powder for later use. Add the above-mentioned powder into anhydrous calcium sulfate according to 75% of the total amount of the solid-phase powder, and mix uniformly to obtain the solid-phase powder.

(2) Preparation of solidification solution

Preparation of a solidified solution containing 5% chitosan and 9% sodium β-glycerophosphate pentahydrate: 5 g of chitosan was dissolved in 68 g of hydrochloric acid solution (1 mol/L), and stirred evenly to obtain an aqueous solution of chitosan. Weigh 9g of sodium β-glycerophosphate pentahydrate and dissolve it in 18g of hydrochloric acid solution (1mol/L), and then drop it into the above-mentioned chitosan aqueous solution under the action of stirring, which is the solidified solution of the composite bone cement.

(3) Preparation of composite bone cement

The solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) are fully stirred for 1 min according to the solid-to-liquid ratio of 2.5:1 (g/ml), and blended into a paste, and the surface is smooth and flat after curing Cylindrical composite bone cement.

The collapse resistance of the composite bone cement was tested with phosphate buffered saline (PBS). Inject 2 g of the reconciled paste into phosphate buffered saline (PBS) with a syringe, and place in an environment of 37°C. Observed after 24 hours, the composite bone cement has no obvious collapse phenomenon, take out the uncollapsed part, freeze-dry, and weigh (W ₂ ), take another 2g of the reconciled paste, freeze-dry, weigh (W ₁ ), use the formula (2) Calculate the collapse resistance D of the composite bone cement to be 93%. Compared with the existing calcium sulfate bone cement (alpha-calcium sulfate hemihydrate and normal saline are reconciled at a solid-to-liquid ratio of 2:1g/ml), the large area collapses and small particles fall to the bottom of the container. Composite bone cement has good collapse resistance.

Formula (2): Collapse resistance D%=W ₂ /W ₁ *100%

Wherein, W ₁ is the dry weight of 2 g of bone cement (not soaked in PBS), and W ₂ is the dry weight of bone cement soaked in PBS.

Example 6

(1) The sol-gel method is used to prepare the bioactive glass block material with the composition of 70% SiO ₂ -30% CaO, and the powder is prepared by ball milling and screening for later use. Add the above-mentioned powder into anhydrous calcium sulfate according to 60% of the total amount of solid-phase powder, and mix uniformly to obtain solid-phase powder.

(2) Preparation of solidification solution

Preparation of a solidified solution containing 1% chitosan and 4% sodium β-glycerophosphate pentahydrate: 1 g of chitosan was dissolved in 85 g of acetic acid solution (0.1 mol/L), and stirred until clear and transparent to obtain an aqueous solution of chitosan. Weigh 4g of sodium β-glycerophosphate pentahydrate and dissolve it in 10g of acetic acid solution (0.1mol/L), and then drop it into the above-mentioned chitosan aqueous solution under the action of stirring, which is the solidified solution of the composite bone cement.

(3) Preparation of composite bone cement

The solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) are fully stirred for 1 min according to the solid-liquid ratio of 2:1 (g/ml), blended into a paste, injected into the mold, and kept at room temperature After curing, it is demoulded and taken out to obtain a cylinder with a smooth surface. In the in vitro SBF test of the composite bone cement, compact HA accumulations were formed on the surface, showing in vitro activity (Figure 5).

Example 7

(1) The sol-gel method is used to prepare the bioactive glass block material with the composition of 80% SiO ₂ -16% CaO-4% P ₂ O ₅ , and the powder is prepared by ball milling and screening for future use. The above powder is added into calcium sulfate dihydrate according to 50% of the total amount of the solid phase powder, and mixed uniformly to obtain the solid phase powder.

(2) Preparation of solidification solution

Prepare a solidified solution containing 3% chitosan and 8% sodium β-glycerophosphate pentahydrate: dissolve 3 g of chitosan in 74 g of acetic acid solution (0.6 mol/L), stir until clear and transparent, and obtain an aqueous solution of chitosan. Weigh 8g of β-glycerophosphate sodium pentahydrate and dissolve it in 15g of acetic acid solution (0.6mol/L), and then drop it into the above-mentioned chitosan aqueous solution under the action of stirring, which is the solidified solution of composite bone cement

(3) Preparation of composite bone cement

The solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) are fully stirred for 1 min according to the solid-liquid ratio of 1.75:1 (g/ml), blended into a paste, injected into the mold, and kept at room temperature After curing, it is demoulded and taken out to obtain a cylinder with a smooth surface. After 8 weeks of immersion in SBF, the composite bone cement has no significant change in diameter, no peeling or collapse, and is expected to provide long-term support for cell growth when used as a bone filling material.

Claims (14)

1. An injectable composite bone cement with bioactivity is characterized in that, the bone cement is composed of solid phase powder and solidification liquid; wherein, the solid phase powder is composed of phosphosilicate bioactive glass and sulfuric acid Calcium mixed composition, the solidification solution contains chitosan and β-sodium glycerophosphate; The mass-to-volume ratio (solid-to-liquid ratio) of the solid phase powder to the solidified liquid is 1:1 to 3:1 (g/ml); Described solid phase powder is made up of the component of following weight percentage content: Phosphosilicate bioactive glass: greater than or equal to 20wt.% but not 100wt.%; Calcium sulfate: less than or equal to 80wt.% but not 0wt.%; The mass percent content of chitosan in the solidified liquid is 1wt.%-5wt.%, and the mass percent content of beta-glycerophosphate sodium is 4wt.%-9wt.%. 2. The injectable composite bone cement according to claim 1, wherein the mass-to-volume ratio (solid-liquid ratio) of the solid phase powder to the solidifying liquid is 1.5:1˜2:1 (g/ml). 3. The injectable composite bone cement according to claim 1, wherein the sodium β-glycerophosphate is sodium β-glycerophosphate pentahydrate. 4. The injectable composite bone cement according to claim 1, wherein the solid phase powder is composed of the following components in weight percent: Phosphosilicate bioactive glass: 25wt.% to 99wt.%; Calcium sulfate: 1wt.%～75wt.%. 5. The injectable composite bone cement according to claim 4, wherein the solid phase powder is composed of the following components in weight percent: Phosphosilicate bioactive glass: 30wt.%～90wt.%; Calcium sulfate: 10wt.%～70wt.%. 6. The injectable composite bone cement according to claim 1, wherein the composition of the phospho-silicate bioactive glass is: x(SiO ₂ )·y(CaO)·m(P ₂ O ₅ )·n( Na ₂ O), wherein, x, y, m, n range (mol.%) is as follows: x is 45mol.%～80mol.%, y is 15mol.%～40mol.%, m is 0mol.%～11mol. %, n is 0mol.%～25mol.%. 7. The injectable composite bone cement according to claim 1, wherein the calcium sulfate is one of α-calcium sulfate hemihydrate, β-calcium sulfate hemihydrate, calcium sulfate dihydrate, calcium sulfate anhydrous or Various. 8. The injectable composite bone cement according to claim 1, characterized in that, the solidification solution also contains an acid-containing aqueous solution. 9. The injectable composite bone cement according to claim 8, wherein the solidifying solution is composed of the following components in mass percentage: Chitosan 1wt.%～5wt.% Sodium β-glycerophosphate 4wt.%～9wt.% Acidic aqueous solution 86wt.% ~ 95wt.%. 10. The injectable composite bone cement according to claim 8 or 9, wherein the acid-containing aqueous solution is one of acetic acid aqueous solution, hydrochloric acid aqueous solution, and citric acid aqueous solution with a concentration of 0.1-1 mol/L. 11. The preparation method of the injectable composite bone cement according to any one of claims 1-10, characterized in that, the method comprises the following steps: (1) Preparation of solid phase powder Making phosphosilicate bioactive glass material into powder; adding calcium sulfate to the bioactive glass powder, and mixing uniformly to obtain solid phase powder; (2) Preparation of solidification solution mixing chitosan and sodium β-glycerophosphate in the solidification liquid with other components in the solidification liquid to obtain the solidification liquid; (3) Preparation of composite bone cement Blending the solid phase powder prepared in step (1) and the solidified liquid prepared in step (2) to obtain the composite bone cement. 12. The preparation method according to claim 11, characterized in that, step (2) is specifically: the solidification liquid is composed of the following components in mass percentage: chitosan 1wt.%～5wt.%, β-glycerol Sodium phosphate 4wt.% ~ 9wt.%, and acid-containing aqueous solution 86wt.% ~ 95wt.%. According to the above solidification liquid ratio, chitosan accounting for 1wt.% ~ 5wt.% of the total solidification liquid is added to the acid-containing aqueous solution , stir and mix until clear and transparent to obtain an aqueous solution of chitosan; then, dissolve β-sodium glycerophosphate accounting for 4wt.% to 9wt.% of the total solidified solution in the acid-containing aqueous solution, and then drop by drop under the action of stirring drop into the chitosan aqueous solution to obtain the solidified liquid. 13. The use of the injectable composite bone cement according to any one of claims 1-10, characterized in that it is used to prepare biomedical materials for treating osteoporotic vertebral body compression fractures or vertebral body collapse. 14. The use of the injectable composite bone cement according to any one of claims 1-10, characterized in that it is used to prepare bone filling materials, biomedical materials for bone repair, or biomedical materials for bone regeneration.