CN107213517B

CN107213517B - Composite bone cement and preparation method thereof

Info

Publication number: CN107213517B
Application number: CN201710347469.6A
Authority: CN
Inventors: 赵基源; 张迟; 诸进晋; 李梅; 钟怡
Original assignee: Ningbo University
Current assignee: Ningbo University
Priority date: 2017-05-17
Filing date: 2017-05-17
Publication date: 2020-03-27
Anticipated expiration: 2037-05-17
Also published as: CN107213517A

Abstract

The invention discloses a composite bone cement, which consists of a solid phase and a liquid phase,wherein the solid phase comprises SIS particles and PMMA bone cement powder; the liquid phase comprises the following components in percentage by mass: 96.0-99.8% of methyl methacrylate monomer, 0.6-1.5% of N, N-dimethyl-p-toluidine and 0.035-0.01% of hydroquinone, wherein the total mass percentage of the components is 100%; in the composition of the composite bone cement, the mass of the SIS particles is recorded as a gram, the mass of the PMMA bone cement powder is recorded as b gram, the volume of a liquid phase is recorded as Vmicroliter, and a, b and V meet the following conditions: a/b is more than or equal to 0.05 and less than or equal to 0.4

The composite bone cement disclosed by the invention has proper compression modulus while maintaining the strength of the bone cement, has larger pore size and adjustable mechanical property, is favorable for cell and tissue ingrowth after being applied to bone injury repair, and meanwhile, the SIS has osteogenesis conductivity and osteogenesis inducibility so as to accelerate the repair of the bone injury.

Description

Composite bone cement and preparation method thereof

Technical Field

The invention relates to the technical field of bone injury repair and tissue engineering in biomedical engineering, in particular to composite bone cement and a preparation method thereof.

Background

Polymethyl methacrylate (PMMA) bone cement is a commonly used bone cement filling material in clinical surgery, and has been used in clinical Percutaneous Vertebroplasty (PVP) for decades. Although its safety and effectiveness are widely recognized clinically, two key issues have raised concerns for clinicians and researchers:

1. too high an elastic modulus. The compression modulus of normal vertebral body cancellous bone of a human body is 50-800 MPa, while the compression modulus of PMMA bone cement which is widely used clinically at present is 1000-4000 MPa and is far higher than that of the normal vertebral body cancellous bone of the human body, and the obvious mechanical property difference between the PMMA bone cement and a human body native bone interface is easy to cause the adjacent vertebral body segment to be fractured again.

2. The biological activity is insufficient. PMMA is a biological inert material and can not be degraded and absorbed in vivo, the occupied space of PMMA not only hinders the formation and the growth of new bones, but also can not form better tissue fusion with the interface of the primary bones, micro-motion is very easy to occur between bone cement and bone tissues, and fine scraps generated by the micro-motion can stimulate the organism to generate immune reaction, so that the local bone dissolution of an implanted part is caused, and the implant is loosened and even falls off.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: aiming at the defects of the prior art, the composite bone cement and the preparation method thereof are provided, the composite bone cement has proper compression modulus while maintaining the strength of the bone cement, has larger pore size and adjustable mechanical property, is beneficial to cell and tissue ingrowth after being applied to bone injury repair, and meanwhile, the SIS has osteogenesis conductivity and osteogenesis inducibility which can accelerate the repair of the bone injury. The composite bone cement of the invention is an ideal substitute material for the traditional PMMA bone cement.

The technical scheme adopted by the invention for solving the technical problems is as follows: a composite bone cement, which consists of a solid phase and a liquid phase, wherein the solid phase comprises SIS particles and PMMA bone cement powder; the liquid phase comprises the following components in percentage by mass: 96.0-99.8% of methyl methacrylate monomer, 0.6-1.5% of N, N-dimethyl-p-toluidine and 0.035-0.01% of hydroquinone, wherein the total mass percentage of the components is 100%; in the composition of the composite bone cement, the mass of the SIS particles is recorded as a gram, the mass of the PMMA bone cement powder is recorded as b gram, the volume of the liquid phase is recorded as Vmicroliter, and a, b and V meet the following conditions:

0.05≤a/b≤0.4

small Intestinal Submucosa (SIS), the most studied natural extracellular matrix material at present, has been approved by the FDA in the united states and is widely used to construct soft tissues such as artificial bladder, artificial urethra, artificial esophagus, artificial blood vessel, and artificial skin. Most of the currently used SIS are completely decellularized porcine small intestine submucosa, and the SIS implanted into a human body has almost no immunological rejection. SIS 90% of the component is collagen, very similar to the organic component of human bone. SIS has a three-dimensional porous structure, the three-dimensional structure taking collagen as a framework can provide a supporting environment for cell growth, proliferation and migration, and the SIS also contains growth factors such as FGF-2 and VEGF which can promote angiogenesis. SIS is stable and easy to store, the thickness of a single layer is about 0.1mm, the thickness of the single layer is about 0.155mm after the single layer is fully soaked on a culture medium, and nutrients can fully enter the culture medium to be suitable for cell culture. It can be seen that SIS is a potentially very excellent scaffold material for bone tissue engineering.

According to the invention, the SIS particles and PMMA bone cement powder are creatively combined as a solid phase and a liquid phase to construct the composite bone cement, the strength of the bone cement is maintained, the composite bone cement has a proper compression modulus, the composite bone cement has a large pore size and adjustable mechanical properties, after the composite bone cement is applied to bone injury repair, the composite bone cement is beneficial to cell and tissue ingrowth, and meanwhile, the osteogenesis conductivity and the osteogenesis inductivity of the SIS can accelerate the repair of the bone injury. The composite bone cement of the invention is an ideal substitute material for the traditional PMMA bone cement.

Preferably, the PMMA bone cement powder comprises the following components in percentage by mass: 60-85% of polymethyl methacrylate, 25-35% of barium sulfate and 2-3.5% of benzoyl peroxide, wherein the sum of the mass percentages of the components is 100%.

Preferably, the particle size of the SIS particles is less than 100 μm.

The preparation method of the composite bone cement comprises the following steps:

(1) extraction of SIS tablets:

the method comprises the steps of obtaining fresh small pig intestines from a pig body with the age of 5-7 months and the weight of 90-120 kg, repeatedly washing the small pig intestines for 5-10 times in clear water, longitudinally cutting the small pig intestines after washing, cutting the small pig intestines into a plurality of small sections with the length of 8-12 cm, tearing off serosa and sarcolemma, turning over a mucous membrane part, and scraping off a mucous membrane layer and a mucous muscle layer;

washing the SIS 5-10 times by using a PBS solution, quickly washing the SIS twice by using 70% alcohol, soaking the SIS in the PBS solution, oscillating the SIS on a shaking table for two days, and replacing the PBS solution once every 12 hours during oscillation; after the oscillation is finished, soaking the SIS in a mixed solution formed by mixing methanol and chloroform in a volume ratio of 1:1 for 10-15 h, then taking out the SIS from the mixed solution, washing the SIS for 3-5 times by using a PBS solution, and removing the methanol and the chloroform;

at 37 ℃, placing the SIS in 0.05% EDTA solution containing 0.05% trypsin, taking out the SIS after 10-15 h, washing the SIS with PBS solution for 3-5 times, and removing the trypsin; then placing the SIS in a descaling agent, wherein the descaling agent is a 0.9% sodium chloride solution containing 0.5% SDS, oscillating the solution on a shaking table for 3-6 hours, and carrying out deep descaling treatment on the SIS; repeatedly cleaning the SIS for 5-10 times by using a PBS solution to remove the scale remover; soaking the treated SIS in a PBS solution, placing the treated SIS on a shaking table again, and shaking for 3-6 hours for deep cleaning;

soaking the SIS in 70% alcohol for 20-50 min, sterilizing, washing with PBS solution, and drying with a freeze dryer to obtain dried SIS tablet;

(2) preparation of SIS particles: cutting the SIS slices into pieces, and crushing the pieces by using a medicine crusher to obtain SIS particles;

(3) preparation of solid phase: mixing the SIS particles and the PMMA bone cement powder to obtain a solid phase, wherein the mass of the SIS particles is recorded as a gram, the mass of the PMMA bone cement powder is recorded as b gram, and a and b meet the following conditions:

0.05≤a/b≤0.4

(4) preparation of liquid phase: uniformly mixing methyl methacrylate monomer, N-dimethyl-p-toluidine and hydroquinone to obtain a liquid phase, wherein the liquid phase comprises the following components in percentage by mass: 96.0-99.8% of methyl methacrylate monomer, 0.6-1.5% of N, N-dimethyl-p-toluidine and 0.035-0.01% of hydroquinone, wherein the total mass percentage of the components is 100%;

(5) forming the composite bone cement: adding the prepared liquid phase to the prepared solid phase, and recording the volume of the liquid phase as Vmicroliter, wherein V satisfies the following condition:

and mixing the liquid phase and the solid phase, and stirring for 3-5 minutes to obtain the dough-like bone cement, wherein the curing time is 10-20 min.

Preferably, the pH value of the PBS solution is 7-7.4, and the rotating speed of the shaking table is 25-35 rpm.

Compared with the prior art, the invention has the advantages that: the composite bone cement disclosed by the invention creatively combines SIS particles and PMMA bone cement powder as a solid phase and a liquid phase to construct the composite bone cement, the strength of the bone cement is maintained, the composite bone cement has a proper compression modulus, the composite bone cement has a large pore size and adjustable mechanical properties, after the composite bone cement is applied to bone injury repair, cell and tissue ingrowth is facilitated, and meanwhile, the osteogenesis conductivity and the osteogenesis inductivity of the SIS can accelerate the repair of a bone injury part. The composite bone cement of the invention is an ideal substitute material for the traditional PMMA bone cement.

Drawings

FIG. 1 is a comparison of scanning electron microscope images of the surface of cured samples of the composite bone cement of the first embodiment, the third embodiment and the fifth embodiment with the traditional PMMA bone cement under different magnifications;

FIG. 2 is a graph showing pore size distribution of cured samples of the composite bone cement of examples one, three and five;

FIG. 3 shows the results of compression modulus measurements of conventional PMMA bone cement and the composite bone cement cylinder samples of examples one to five;

FIG. 4 is a comparison of the effect of promoting ALP expression of the conventional PMMA bone cement and the composite bone cements of examples one and five;

FIG. 5 is a comparison of the effect of promoting mineral deposition of the conventional PMMA bone cement and the composite bone cements of the first and fifth embodiments;

FIG. 6 is an X-piece of conventional PMMA bone cement and the composite bone cement of the first and fifth embodiments for repairing a spinal defect;

FIG. 7 is a graph of the HE staining of the bone-repair material interface after repair of a spinal defect with conventional PMMA bone cement and the composite bone cements of examples one and five;

fig. 8 is a graph showing HE staining of the inside of a spinal defect repaired by using a conventional PMMA bone cement and the composite bone cements of the first and fifth embodiments.

Detailed Description

The invention is described in further detail below with reference to the accompanying examples.

The preparation method of the composite bone cement of the first embodiment comprises the following steps:

(1) extraction of SIS tablets:

obtaining a fresh small intestine of a pig from a pig body with the age of 6 months and the weight of 100kg, repeatedly washing the small intestine of the pig in clear water for 5-10 times, longitudinally cutting the small intestine of the pig after washing, cutting the small intestine of the pig into a plurality of small sections with the length of 10cm, tearing off serosa and sarcolemma, turning over a mucous membrane part, and scraping off a mucous membrane layer and a mucous muscle layer;

washing the SIS 5-10 times by using a PBS solution, quickly washing the SIS twice by using 70% alcohol, soaking the SIS in the PBS solution, oscillating for two days on a shaking table at the rotating speed of 30rpm, and replacing the PBS solution once every 12 hours during oscillation; after the oscillation is finished, soaking the SIS in a mixed solution formed by mixing methanol and chloroform in a volume ratio of 1:1 for 12 hours, then taking out the SIS from the mixed solution, washing the SIS for 3-5 times by using a PBS solution, and removing the methanol and the chloroform;

at 37 ℃, placing the SIS in 0.05% EDTA solution containing 0.05% trypsin, taking out the SIS after 12 hours, washing the SIS for 3-5 times by using PBS solution, and removing the trypsin; then, the SIS is placed in a descaling agent which is a 0.9% sodium chloride solution containing 0.5% SDS, and the SIS is subjected to deep descaling treatment by oscillating for 4 hours on a shaking table at the rotating speed of 30 rpm; repeatedly cleaning the SIS for 5-10 times by using a PBS solution to remove the scale remover; soaking the processed SIS in a PBS solution, placing the processed SIS on a shaker again, and oscillating the processed SIS for 4 hours at the rotating speed of 30rpm to carry out deep cleaning;

soaking SIS in 70% alcohol for 30min, sterilizing, cleaning with PBS solution, and drying SIS with freeze drier to obtain dried SIS tablet;

(2) preparation of SIS particles: cutting SIS slices into pieces, and pulverizing with a medicine pulverizer to obtain SIS particles with particle size less than 100 μm;

(3) preparation of solid phase: mixing 0.167 g of SIS particles and 0.833 g of PMMA bone cement powder to obtain a solid phase;

(4) preparation of liquid phase: uniformly mixing methyl methacrylate monomer, N-dimethyl-p-toluidine and hydroquinone to obtain a liquid phase, wherein the liquid phase comprises the following components in percentage by mass: 99.0925% of methyl methacrylate monomer, 0.9% of N, N-dimethyl-p-toluidine and 0.0075% of hydroquinone, wherein the sum of the mass percentages of the components is 100%;

(5) forming the composite bone cement: and adding 1000 microliters of the prepared liquid phase into the prepared solid phase, mixing the liquid phase and the solid phase, and stirring for 3-5 minutes to obtain the dough-like bone cement, wherein the curing time is 10-20 min.

The preparation method of the composite bone cement of the second embodiment comprises the following steps:

(1) extraction of SIS tablets:

obtaining a fresh small pig intestine from a pig body with the age of 5 months and the weight of 90kg, repeatedly washing the small pig intestine in clear water for 5-10 times, longitudinally cutting the small pig intestine after washing, cutting the small pig intestine into a plurality of small sections with the length of 8cm, tearing off serosa and sarcolemma, turning over a mucous membrane part, and scraping off the mucous membrane layer and the muscularis mucosae;

at 37 ℃, placing the SIS in 0.05% EDTA solution containing 0.05% trypsin, taking out the SIS after 12 hours, washing the SIS for 3-5 times by using PBS solution, and removing the trypsin; then, the SIS is placed in a descaling agent which is a 0.9% sodium chloride solution containing 0.5% SDS, and the descaling agent is vibrated for 3 hours on a shaking table at the rotating speed of 30rpm to carry out deep descaling treatment on the SIS; repeatedly cleaning the SIS for 5-10 times by using a PBS solution to remove the scale remover; soaking the processed SIS in a PBS solution, placing the processed SIS on a shaker again, and oscillating the processed SIS for 5 hours at the rotating speed of 30rpm to carry out deep cleaning;

soaking SIS in 70% alcohol for 25min, sterilizing, cleaning with PBS solution, and drying SIS with freeze drier to obtain dried SIS tablet;

(3) preparation of solid phase: mixing 0.048 g of SIS particles and 0.952 g of PMMA bone cement powder to obtain a solid phase;

(4) preparation of liquid phase: uniformly mixing methyl methacrylate monomer, N-dimethyl-p-toluidine and hydroquinone to obtain a liquid phase, wherein the liquid phase comprises the following components in percentage by mass: 98.79 percent of methyl methacrylate monomer, 1.2 percent of N, N-dimethyl-p-toluidine and 0.01 percent of hydroquinone, wherein the sum of the mass percentages of the components is 100 percent;

(5) forming the composite bone cement: and adding 632 microliters of prepared liquid phase into the prepared solid phase, mixing the liquid phase and the solid phase, and stirring for 3-5 minutes to obtain the dough-shaped bone cement, wherein the curing time is 10-20 min.

The preparation method of the composite bone cement of the third embodiment comprises the following steps:

(1) extraction of SIS tablets:

obtaining a fresh small pig intestine from a pig body with the age of 6 months and the weight of 105kg, repeatedly washing the small pig intestine in clear water for 5-10 times, longitudinally cutting the small pig intestine after washing, cutting the small pig intestine into a plurality of small sections with the length of 12cm, tearing off serosa and sarcolemma, turning over a mucous membrane part, and scraping off the mucous membrane layer and the muscularis mucosae;

at 37 ℃, placing the SIS in 0.05% EDTA solution containing 0.05% trypsin, taking out the SIS after 12 hours, washing the SIS for 3-5 times by using PBS solution, and removing the trypsin; then, the SIS is placed in a descaling agent which is a 0.9% sodium chloride solution containing 0.5% SDS, and the SIS is subjected to deep descaling treatment by oscillating for 5 hours on a shaking table at the rotating speed of 30 rpm; repeatedly cleaning the SIS for 5-10 times by using a PBS solution to remove the scale remover; soaking the processed SIS in a PBS solution, placing the processed SIS on a shaker again, and oscillating the processed SIS for 5 hours at the rotating speed of 30rpm to carry out deep cleaning;

soaking SIS in 70% alcohol for 40min, sterilizing, cleaning with PBS solution, and drying SIS with freeze drier to obtain dried SIS tablet;

(3) preparation of solid phase: mixing 0.091 g of SIS particles and 0.909 g of PMMA bone cement powder to obtain a solid phase;

(4) preparation of liquid phase: uniformly mixing methyl methacrylate monomer, N-dimethyl-p-toluidine and hydroquinone to obtain a liquid phase, wherein the liquid phase comprises the following components in percentage by mass: 99.1925% of methyl methacrylate monomer, 0.8% of N, N-dimethyl-p-toluidine and 0.0075% of hydroquinone, wherein the sum of the mass percentages of the components is 100%;

(5) forming the composite bone cement: adding 778 microliter of the prepared liquid phase into the prepared solid phase, mixing the liquid phase and the solid phase, and stirring for 3-5 minutes to obtain the dough-like bone cement, wherein the curing time is 10-20 min.

The method for preparing a composite bone cement of example four, comprising the steps of:

(1) extraction of SIS tablets:

obtaining a fresh small pig intestine from a 7-month-old pig with the weight of 120kg, repeatedly washing the small pig intestine in clear water for 5-10 times, longitudinally cutting the small pig intestine after washing, cutting the small pig intestine into a plurality of small sections with the length of 10cm, tearing off serosa and sarcolemma, turning over a mucous membrane part, and scraping off the mucous membrane layer and the muscularis mucosae;

at 37 ℃, placing the SIS in 0.05% EDTA solution containing 0.05% trypsin, taking out the SIS after 12 hours, washing the SIS for 3-5 times by using PBS solution, and removing the trypsin; then, the SIS is placed in a descaling agent which is a 0.9% sodium chloride solution containing 0.5% SDS, and the SIS is subjected to deep descaling treatment by oscillating for 6 hours on a shaking table at the rotating speed of 30 rpm; repeatedly cleaning the SIS for 5-10 times by using a PBS solution to remove the scale remover; soaking the processed SIS in a PBS solution, placing the processed SIS on a shaker again, and oscillating the processed SIS for 3 hours at the rotating speed of 30rpm to carry out deep cleaning;

(3) preparation of solid phase: mixing 0.13 g of SIS particles and 0.87 g of PMMA bone cement powder to obtain a solid phase;

(4) preparation of liquid phase: uniformly mixing methyl methacrylate monomer, N-dimethyl-p-toluidine and hydroquinone to obtain a liquid phase, wherein the liquid phase comprises the following components in percentage by mass: 98.545% of methyl methacrylate monomer, 1.45% of N, N-dimethyl-p-toluidine and 0.005% of hydroquinone, wherein the sum of the mass percentages of the components is 100%;

(5) forming the composite bone cement: adding the 941 microliter prepared liquid phase into the prepared solid phase, mixing the liquid phase and the solid phase, and stirring for 3-5 minutes to obtain the dough-like bone cement, wherein the curing time is 10-20 min.

The preparation method of the composite bone cement of the embodiment five comprises the following steps:

(1) extraction of SIS tablets:

at 37 ℃, placing the SIS in 0.05% EDTA solution containing 0.05% trypsin, taking out the SIS after 12 hours, washing the SIS for 3-5 times by using PBS solution, and removing the trypsin; then, the SIS is placed in a descaling agent which is a 0.9% sodium chloride solution containing 0.5% SDS, and the SIS is subjected to deep descaling treatment by shaking for 3.5 hours on a shaking table at the rotating speed of 30 rpm; repeatedly cleaning the SIS for 5-10 times by using a PBS solution to remove the scale remover; soaking the treated SIS in a PBS solution, placing the treated SIS on a shaker again, oscillating the SIS for 3.5 hours at the rotating speed of 30rpm, and carrying out deep cleaning;

(3) preparation of solid phase: mixing 0.286 g of SIS particles and 0.714 g of PMMA bone cement powder to obtain a solid phase;

(4) preparation of liquid phase: uniformly mixing methyl methacrylate monomer, N-dimethyl-p-toluidine and hydroquinone to obtain a liquid phase, wherein the liquid phase comprises the following components in percentage by mass: 99.294% of methyl methacrylate monomer, 0.7% of N, N-dimethyl-p-toluidine and 0.006% of hydroquinone, wherein the sum of the mass percentages of the components is 100%;

(5) forming the composite bone cement: and adding 2167 microliters of the prepared liquid phase into the prepared solid phase, mixing the liquid phase and the solid phase, and stirring for 3-5 minutes to obtain the dough-like bone cement, wherein the curing time is 10-20 min.

The PBS solutions used in the above examples all had a pH of 7.4.

Firstly, the in vitro evaluation of the composite bone cement of the invention:

1. surface morphology and pore size distribution of composite bone cement

The surface morphology of the PMMA bone cement cured sample and the composite bone cement cured samples of examples one to five were observed by comparing a conventional PMMA bone cement (commercially available Mendec Spine bone cement). The observation shows that the surface roughness of the composite bone cement sample is obviously increased compared with the traditional PMMA bone cement sample, the aperture is obviously increased, the size of the aperture is also increased along with the increase of the SIS proportion in the solid phase of the composite bone cement, and the structure of the composite bone cement is more beneficial to the adhesion and the migration of cells. The scanning electron microscope pictures of the surface of the cured samples of the composite bone cement of the first embodiment, the third embodiment and the fifth embodiment and the traditional PMMA bone cement under different magnifications are shown in figure 1. Fig. 2 is a pore size distribution diagram of a cured sample of the composite bone cement of example one, example three, and example five.

2. Mechanical properties of composite bone cements

The conventional PMMA bone cement and the composite bone cements of examples one to five were prepared into cylindrical samples having a diameter of 5mm and a height of 7.5mm, respectively, and the compression modulus was measured, and the results are shown in fig. 3. As can be seen from figure 3, with the increase of the mass ratio of the SIS particles to the PMMA bone cement powder, the compression modulus is continuously reduced, and the compression modulus range of 50-800 MPa of the whole human spinal bone is covered, so that in actual operation, the composite bone cement with proper SIS proportion can be selected according to the strength of the required replacement and repair bone, and the adjustment of mechanical properties is realized.

3. Biological activity of composite bone cement

Respectively preparing traditional PMMA bone cement and the composite bone cement of the first embodiment and the fifth embodiment into cylindrical samples with the diameter of 5mm and the height of 1mm, solidifying, respectively placing various solidified bone cements into a 96-well plate, collecting mouse bone marrow mesenchymal stem cells (BMSCs) with the confluence degree of 70-80%, adjusting the concentration of cell suspension, adding the same amount of cell suspension to various bone cements, adding 100 mu L of cell suspension into each well, wherein the cell density is 1 multiplied by 10⁵Each cell/well was cultured in a 37 ℃ cell culture chamber. After 14 days of culture, various bone cements were subjected to ALP and Alizarin red S staining, and the expression level and the mineralized deposition level of the marker ALP during osteogenic differentiation were examined, and the ALP expression promoting effect pair is shown in FIG. 4, and the mineralized deposition promoting effect pair is shown in FIG. 5. As can be seen from fig. 4 and 5, the composite bone cement can significantly promote ALP expression and mineralized nodule formation, and effectively promote osteogenic differentiation of stem cells, compared to the conventional PMMA bone cement.

Second, in vivo evaluation of the composite bone cement of the present invention:

taking 12-week-old SD male rats (with the weight of about 350 g), constructing a spinal injury model, which specifically comprises the following steps: firstly, forming 2 multiplied by 5mm defects at an L2 spinal column by using a slow drill, and filling the defects with the traditional PMMA bone cement in a dough shape and the composite bone cement of the first embodiment and the fifth embodiment; then, the inside of the rat was sterilized with medical iodophor, surgical intermittent suture (muscle and skin suture, respectively) was performed with a cosmetic thread, the rat was intramuscularly injected with penicillin within one week after the operation, the rat was sacrificed after four weeks, and imaging and histological studies were performed on the tissue at the defect.

The traditional PMMA bone cement and the X-ray plate for repairing spinal defects by using the composite bone cement of the first embodiment and the fifth embodiment are shown in fig. 6, and the X-ray plate result shows that the signal intensity of the defects of the traditional PMMA bone cement group is far greater than that of normal bone tissues, and the occupied PMMA material is not degraded. The signal intensity of the composite bone cement group defect is very close to that of the surrounding bone tissues, so that the density of the composite repair material is obviously reduced, and the growth of new bone is prompted.

Fig. 7 shows HE staining patterns of the bone-repair material interface after the conventional PMMA bone cement and the composite bone cements of the first and fifth examples repair the spinal defect. FIG. 7 is a histological HE slice showing that in the composite bone cement set, the interface of the material and bone is fused and a large number of small bone neoformations are formed inside the defect; the boundary of the traditional PMMA bone cement group is clear, and the growth condition of the defect bone-free tissue is avoided.

After the traditional PMMA bone cement and the composite bone cement of the first embodiment and the fifth embodiment repair the spinal defect, the staining pattern of the HE inside the defect is shown in figure 8. As can be seen from FIG. 8, a large amount of new bone tissue appeared in the composite bone cement group (the star in the figure represents the appearance of new bone tissue); whereas the conventional PMMA bone cement group has substantially no tissue in-growth.

Claims

1. The composite bone cement is characterized by comprising a solid phase and a liquid phase, wherein the solid phase comprises SIS particles and PMMA bone cement powder, and the particle size of the SIS particles is less than 100 mu m; the liquid phase comprises the following components in percentage by mass: 96.0-99.8% of methyl methacrylate monomer, 0.6-1.5% of N, N-dimethyl-p-toluidine and 0.035-0.01% of hydroquinone, wherein the total mass percentage of the components is 100%; in the composition of the composite bone cement, the mass of the SIS particles is recorded as a gram, the mass of the PMMA bone cement powder is recorded as b gram, the volume of the liquid phase is recorded as Vmicroliter, and a, b and V meet the following conditions:

0.05≤a/b≤0.4

2. the composite bone cement of claim 1, wherein the PMMA bone cement powder comprises, by mass: 60-85% of polymethyl methacrylate, 25-35% of barium sulfate and 2-3.5% of benzoyl peroxide, wherein the sum of the mass percentages of the components is 100%.

3. A method of preparing a composite bone cement according to any one of claims 1-2, characterised in that it comprises the steps of:

(1) extraction of SIS tablets:

0.05≤a/b≤0.4

4. The method for preparing a composite bone cement as claimed in claim 3, wherein the pH of the PBS solution is 7-7.4, and the rotation speed of the shaker is 25-35 rpm.