CN109316627A - A kind of novel artificial bone material and its preparation method and application - Google Patents
A kind of novel artificial bone material and its preparation method and application Download PDFInfo
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Abstract
The invention discloses a kind of novel artificial bone material, the artificial bone is the PMMA bone material of two-component system, and the two-component system is made of powder component and liquid component, and the weight ratio of the powder component and liquid component is 1:2.5~4.5.The present invention also provides the preparation method and applications of the artificial bone.Present invention acquisition has both high compressive strength and low elastic modulus, and the artificial stock of good biocompatibility is just old.In mechanical properties, the mechanical characteristic of the more simple PMMA bone cement of the new material more composite human body bone tissue reduces the risk that autologous bone is worn, also it is possible to prevente effectively from implantation prosthese is damaged because of extruding.In terms of biocompatibility, modified mineralized collagen composite material can be conducive to improve bone bonding and packing material in the stability of implant site, so that the use more secure and reliable of the new material with self bon e formation synostosis.
Description
Technical field
The present invention relates to medical material tech fields, and in particular to a kind of novel artificial bone material and preparation method thereof and answers
With.
Background technique
Bone cement is a kind of medical material for being widely used in bone surgery, and bone cement is usually by solid powder and solidify liquid two
Part forms, and being mixed in a certain ratio can be cured at room temperature, places it in the position of replacement joint or filling,
To which arthrodesis or bone defect can be repaired after reaction.Since bone cement has syringeability, can reduce to greatest extent
The area of minor operation wound accelerates rehabilitation speed, mitigates patient suffering, so it is usually used in the packing material and bracket material of bone tissue
Material, plays a supporting role, is the indispensable a member of bone tissue application material.From early 1960s bone cement come out with
Come, main bone cement type has polymethyl methacrylate (PMMA) bone cement, calcium sulfate bone cement and calcium phosphate bone cement.
Polymethyl methacrylate (PMMA) bone cement belongs to acrylic material, and level of residual monomers is low, with low resistance to
Fatigability and stress cracking resistance and high tensile strength and plasticity.PMMA bone cement has in medicine field of orthopedic surgery
It is widely applied.Gear division, skull and other Bone Defect Reparis field just it have been applied to early in the forties.Esters of acrylic acid bone water
Mud is performed the operation for tissue, has at home and abroad applied as many as hundreds of thousands of examples in clinic so far.But poly-methyl methacrylate
Ester bone cement lacks bioactivity, cannot firmly be chemically bonded with host's bon e formation, can not directly induce bone growth, with
Interface binding power between host bone is low, is easy to loosen, forms excessively high heat localization temperature when solidifying and easily cause surrounding tissue
And spinal cord injury, even result in tissue necrosis.
Calcium sulfate is simplest implantation, and applies and have been over 100 years in bone renovating material,
There is longest clinical application history.Calcium sulfate has good human tolerance, degradable, is self in the research in one's early years
The important alternative materials of bone collection.The solid phase mainstream of calcium sulfate bone cement is anhydrous slufuric acid calcium powder, liquid phase be physiological saline and
Some other aqueous solutions.When solid phase and liquid phase mix, hydration reaction occurs for calcium sulfate, and it is brilliant to generate acicular calcium sulphate dihydrate
Must, mutual bridging and accumulation, to be solidified into the accumulation body with certain shapes and intensity.Calcium sulfate bone cement also lacks biology
Activity, after implanting, calcium sulfate bone cement can rapidly be absorbed, and infiltration rate is much larger than the reproduction speed of bone tissue,
Therefore hole can be left in defect, is unfavorable for the Regeneration and Repair of bone.
Calcium phosphate bone cement is a kind of novel bone impairment renovation material, has excellent biocompatibility, bioactivity
With osteoconductive energy.Calcium phosphate bone cement is usually made of solid phase pulvis and solidify liquid.The solid-phase component one of calcium phosphate bone cement
As by two or more synthos powder constituent, such as tricalcium phosphate, tetracalcium phosphate and calcium monohydrogen phosphate；Solidify liquid can
To be water, dilute phosphoric acid solution, sodium radio-phosphate,P-32 solution, physiological saline and ammonium phosphate salt solution etc..With traditional ceramic mould hydroxyl phosphorus
Lime stone is compared, and calcium phosphate bone cement has many advantages, such as that preparation is simple, random-shaping.Compared with traditional PMMA bone cement, phosphoric acid
Calcium bone cement has better biocompatibility, and the heat release of solidification process is lower, will not generate thermal damage to surrounding tissue.
Currently, calcium phosphate bone cement has had a wide range of applications in terms of dentistry, plastic surgery and cranial surgery, it is bio-medical material
One of the research hotspot in field.
Although people have done some explorations, current modified PMMA bone on PMMA bone cement study on the modification at present
Cement still has elasticity modulus height, easily causes adjacent vertebral secondary fracture, according to clinical the sending out of pertinent literature report secondary fracture
Sick rate is 12.4%~27.7%；The probability that adjacent vertebral occurs is 4.62 times of non-adjacent vertebral；It needs to continue to refracture
Centrum row vertebroplasty, increases the operation pain and financial burden of patient, and continues to bring postoperative complications.Also on the one hand,
Current modified PMMA bone cement may loosen the danger even slipped, to spinal cord there is also poor biocompatibility in centrum
Cause the risk of compressing higher, it is necessary to take out bone cement lump by performing the operation again.
Summary of the invention
The problem of in order to improve PMMA bone cement modulus height and poor biocompatibility, the purpose of the present invention is to provide one kind
Novel artificial bone material.
A further object of the invention is to provide the preparation method and application of the novel artificial bone material.
To achieve the above object, present invention firstly provides a kind of novel artificial bone material, the artificial bone is double groups
The PMMA bone material of part system, the two-component system are made of powder component and liquid component, the powder component and liquid
The weight ratio of component is 1:2.5~4.5；
Wherein, in the powder component, by weight, including modified 30-35 parts of mineralized collagen powder, poly- methyl-prop
25-40 parts of e pioic acid methyl ester powder, 10-15 parts of 1,3- butadiene powder, 10-15 parts of styrene powder, 5-10 parts of strontium boride, nitric acid
5-10 parts of magnesium, 5-10 parts of silver nitrate, molecular weight are in 2x105~3x10510-20 parts of carboxymethyl chitosan；
The liquid portion includes dimethyl terephthalate (DMT) solution and methylbenzene e pioic acid methyl ester solution, wherein to benzene
The weight ratio of dicarboxylic acid dimethyl ester solution and methylbenzene e pioic acid methyl ester solution is 1:50-100, in dimethyl terephthalate (DMT) solution
The mass fraction of dimethyl terephthalate (DMT) is ‰~6wt of 4wt ‰, methyl methacrylate in methyl methacrylate solution
Mass fraction is 99.4wt%~99.6wt%.
Preferably, the modified mineralized collagen is collagen/hydroxyapatite complex solid powder.
Preferably, nano silver 3-5 parts is also contained in the powder component.
Preferably, DBM, BMP, antibiotic or 1-5 parts of chemotherapeutics are also added in the powder component.Bones morphology occurs
Albumen (BMP), decalcified bone matrix (DBM).
Include further following operating procedure the present invention provides a kind of preparation method of modified mineralized collagen:
Step S1, collagen is dissolved in any one of hydrochloric acid, nitric acid or acetic acid, is configured to the acid solution of collagen, wherein
Collagen concentration is 5.0 × 10-5~5.0 × 10-3g/mL；
Step S2, continue whipping step S1 acquired solution, the solution of calcium ions is slowly added dropwise, the additional amount of calcium ion is
Every gram of collagen is corresponding to be added 0.01~0.16mol of calcium ion；
Step S3, continue whipping step S2 acquired solution, the solution of phosphorus-containing acid ion is slowly added dropwise, phosphate anion
The molar ratio of additional amount and calcium ion additional amount in step S2 is Ca/P=1/1~2/1；
Step S4, continue whipping step S3 acquired solution, NaOH solution is slowly added dropwise to mixed system pH=6~8, works as pH
When=5~6, mixed system starts to precipitate, and as pH=7, white suspension occurs in mixed system；
Step S5, mixed system obtained by step S4 is stood 24~120 hours, isolates and precipitates and wash away foreign ion,
It is then freeze-dried, mineralized collagen powder is obtained after grinding；
Step S6, the mineralized collagen powder that a certain amount of step S5 is obtained is weighed, is fitted into mold, then applies to mold and presses
Power, and the pressure being applied on mineralized collagen powder is made to reach 900~1200MPa, it is kept for pressure 30~300 seconds, demoulding obtains
Mineralized collagen block；
Step S7, mineralized collagen block made from step S6 is ground, obtains mineralized collagen powder；
Step S8 configures silver nitrate, magnesium nitrate, the strontium boride solution of same concentrations, and the concentration of solution is 0.5mol/L；It will
Three kinds of solution are pumped into reaction vessel simultaneously, and being pumped into speed is 1~30mL/min, and three kinds of solution terminate to be pumped into, be pumped into simultaneously
Time is 10~30min, obtains white emulsion, is continuesd to mix uniformly；Ammonium hydroxide is added, has white precipitate to be gradually precipitated, adjusts pH
Value is 10~12, is continuesd to mix uniformly；White precipitate is separated from liquid, white precipitate is transferred to equipped with mineralized collagen
In barrier box, for control barrier box on liquid upper layer, liquid just immersion precipitation, is 150~250 DEG C in temperature, pressure is 1~
Reaction 4 under conditions of 2MPa~for 24 hours, it is cleaning, dry, last 500~1000 DEG C, it is sintered 3~12h, cooling, grinding obtains 5~
200 μm of modification mineralized collagen powder.
Further, the present invention provides the preparation methods of the artificial bone, the method comprises the following steps:
(1) preparation of modified mineralized collagen is same as above；
(2) modified poly (methyl methacrylate) is prepared using suspension polymerization, experimental material includes: methyl methacrylate
(MMA), methyl acrylate (MA), dibenzoyl peroxide (BPO), polyvinyl alcohol (PVA), preparation step is as follows: in a reservoir,
Distilled water is added, polymethyl methacrylate is added under stiring, 1,3-butadiene and styrene monomer is added after 10min,
Rise to 80 DEG C in 10-20min, continue to heat up, in 20-30min, rise to 90 DEG C, then rise in 70-80min 100 DEG C with
On, continue 30-100min；It stands, is filtered with 80 DEG C of washings of distilled water, in triplicate；Then filtered product will be washed to set
It is dry in 40 DEG C of baking oven, it is ground up, sieved to obtain modified PMMA white fine powder particle after dry；
(3) remaining component is weighed according to weight point；The carboxymethyl chitosan is dissolved in acid solution and forms carboxymethyl shell
Glycan solution；The carboxymethyl chitosan solution and step (1) (2) resulting materials and remaining component modification calcined mixed are formed
Mixture obtains the powder component of artificial bone；
(4) dimethyl terephthalate (DMT) solution and methylbenzene alkene is added in artificial bone powder component obtained by step (3)
Sour methyl ester solution, stirring is to thick, in inspiration syringe, slowly pushes and removes bubble, be then slowly injected into cylindrical glass
In mold, solidify at room temperature for 24 hours to get artificial bone.
Further, the application the present invention provides the artificial bone in clinical medicine bone grafting filler.
Beneficial effects of the present invention are as follows:
Present invention acquisition has both high compressive strength and low elastic modulus, and the artificial stock of good biocompatibility is just old.In machine
Tool aspect of performance, the mechanical characteristic of the more simple PMMA bone cement of the new material more composite human body bone tissue, reduces autologous bone
The risk being worn, also it is possible to prevente effectively from implantation prosthese is damaged because of extruding.In terms of biocompatibility, modified mine
Changing collagen composite materials can be conducive to improve bone bonding and packing material in implant site with self bon e formation synostosis
Stability, so that the use more secure and reliable of the new material.Furthermore artificial bone of the invention is non-toxic.Therefore,
The compound PMMA bone of modified mineralized collagen provided by the invention bonds and packing material is with the obvious advantage, can effectively reduce current PMMA
The generation of bone cement complication, has broad application prospects.
Detailed description of the invention
The cytotoxicity CCK8 test of artificial bone of the present invention 3 shown in Fig. 1 and control PMMA bone cement；
72 hours mouse livers of Fig. 2 acute systemic toxicity and renal histology slice；Wherein 1 liver, 2 liver headers
Area, 3 cortex renis, 4 kidney medullas.
Specific embodiment
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..Unless otherwise specified, embodiment
Used in the conventional means that are well known to those skilled in the art of technological means.
The preparation of the modified mineralized collagen of embodiment 1
Step S1, collagen is dissolved in any one of hydrochloric acid, nitric acid or acetic acid, is configured to the acid solution of collagen, wherein
Collagen concentration is 5.0 × 10-5~5.0 × 10-3g/mL；
Step S2, continue whipping step S1 acquired solution, the solution of calcium ions is slowly added dropwise, the additional amount of calcium ion is
Every gram of collagen is corresponding to be added 0.01~0.16mol of calcium ion；
Step S3, continue whipping step S2 acquired solution, the solution of phosphorus-containing acid ion is slowly added dropwise, phosphate anion
The molar ratio of additional amount and calcium ion additional amount in step S2 is Ca/P=1/1~2/1；
Step S4, continue whipping step S3 acquired solution, NaOH solution is slowly added dropwise to mixed system pH=6~8, works as pH
When=5~6, mixed system starts to precipitate, and as pH=7, white suspension occurs in mixed system；
Step S5, mixed system obtained by step S4 is stood 24~120 hours, isolates and precipitates and wash away foreign ion,
It is then freeze-dried, mineralized collagen powder is obtained after grinding；
Step S6, the mineralized collagen powder that a certain amount of step S5 is obtained is weighed, is fitted into mold, then applies to mold and presses
Power, and the pressure being applied on mineralized collagen powder is made to reach 900~1200MPa, it is kept for pressure 30~300 seconds, demoulding obtains
Mineralized collagen block；
Step S7, mineralized collagen block made from step S6 is ground, obtains mineralized collagen powder；
Step S8 configures silver nitrate, magnesium nitrate, the strontium boride solution of same concentrations, and the concentration of solution is 0.5mol/L；It will
Three kinds of solution are pumped into reaction vessel simultaneously, and being pumped into speed is 1~30mL/min, and three kinds of solution terminate to be pumped into, be pumped into simultaneously
Time is 10~30min, obtains white emulsion, is continuesd to mix uniformly；Ammonium hydroxide is added, has white precipitate to be gradually precipitated, adjusts pH
Value is 10~12, is continuesd to mix uniformly；White precipitate is separated from liquid, white precipitate is transferred to equipped with mineralized collagen
In barrier box, for control barrier box on liquid upper layer, liquid just immersion precipitation, is 150~250 DEG C in temperature, pressure is 1~
Reaction 4 under conditions of 2MPa~for 24 hours, it is cleaning, dry, last 500~1000 DEG C, it is sintered 3~12h, cooling, grinding obtains 5~
200 μm of modification mineralized collagen powder.
The preparation 1 of the modified mineralized collagen artificial bone of embodiment 2
The artificial bone is the PMMA bone material of two-component system, and the two-component system is by powder component and liquid
Component is constituted, and the weight ratio of the powder component and liquid component is 1:2.5；
Wherein, in the powder component, by weight, including modified 30 parts of mineralized collagen powder, polymethyl
40 parts of sour methacrylate powder, 10 parts of 1,3- butadiene powder, 10 parts of styrene powder, 6 parts of strontium boride, 6 parts of magnesium nitrate, silver nitrate 7
Part, molecular weight are in 2x105~3x10512 parts of carboxymethyl chitosan；
The liquid portion includes dimethyl terephthalate (DMT) solution and methylbenzene e pioic acid methyl ester solution, wherein to benzene
The weight ratio of dicarboxylic acid dimethyl ester solution and methylbenzene e pioic acid methyl ester solution is 1:60, to benzene in dimethyl terephthalate (DMT) solution
The mass fraction of dicarboxylic acid dimethyl ester is ‰~6wt of 4wt ‰, the quality of methyl methacrylate in methyl methacrylate solution
Score is 99.4wt%~99.6wt%.
The preparation method is as follows:
(1) preparation of modified mineralized collagen is same as above；
(2) modified poly (methyl methacrylate) is prepared using suspension polymerization, experimental material includes: methyl methacrylate
(MMA), methyl acrylate (MA), dibenzoyl peroxide (BPO), polyvinyl alcohol (PVA), preparation step is as follows: in a reservoir,
Distilled water is added, polymethyl methacrylate is added under stiring, 1,3-butadiene and styrene monomer is added after 10min,
Rise to 80 DEG C in 10-20min, continue to heat up, in 20-30min, rise to 90 DEG C, then rise in 70-80min 100 DEG C with
On, continue 30-100min；It stands, is filtered with 80 DEG C of washings of distilled water, in triplicate；Then filtered product will be washed to set
It is dry in 40 DEG C of baking oven, it is ground up, sieved to obtain modified PMMA white fine powder particle after dry；
(3) remaining component is weighed according to weight point；The carboxymethyl chitosan is dissolved in acid solution and forms carboxymethyl shell
Glycan solution；The carboxymethyl chitosan solution and step (1) (2) resulting materials and remaining component modification calcined mixed are formed
Mixture obtains the powder component of artificial bone；
(4) dimethyl terephthalate (DMT) solution and methylbenzene alkene is added in artificial bone powder component obtained by step (3)
Sour methyl ester solution, stirring is to thick, in inspiration syringe, slowly pushes and removes bubble, be then slowly injected into cylindrical glass
In mold, solidify at room temperature for 24 hours to get artificial bone 1.
The preparation 2 of the modified mineralized collagen artificial bone of embodiment 3
The artificial bone is the PMMA bone material of two-component system, and the two-component system is by powder component and liquid
Component is constituted, and the weight ratio of the powder component and liquid component is 1:3；
Wherein, in the powder component, by weight, including modified 35 parts of mineralized collagen powder, polymethyl
30 parts of sour methacrylate powder, 12 parts of 1,3- butadiene powder, 14 parts of styrene powder, 11 parts of strontium boride, 12 parts of magnesium nitrate, silver nitrate
8 parts, molecular weight is in 2x105~3x10515 parts of carboxymethyl chitosan；
The liquid portion includes dimethyl terephthalate (DMT) solution and methylbenzene e pioic acid methyl ester solution, wherein to benzene
The weight ratio of dicarboxylic acid dimethyl ester solution and methylbenzene e pioic acid methyl ester solution is 1:60, to benzene in dimethyl terephthalate (DMT) solution
The mass fraction of dicarboxylic acid dimethyl ester is ‰~6wt of 4wt ‰, the quality of methyl methacrylate in methyl methacrylate solution
Score is 99.4wt%~99.6wt%.
The preparation method is as follows:
(1) preparation of modified mineralized collagen is same as above；
(2) modified poly (methyl methacrylate) is prepared using suspension polymerization, experimental material includes: methyl methacrylate
(MMA), methyl acrylate (MA), dibenzoyl peroxide (BPO), polyvinyl alcohol (PVA), preparation step is as follows: in a reservoir,
Distilled water is added, polymethyl methacrylate is added under stiring, 1,3-butadiene and styrene monomer is added after 10min,
Rise to 80 DEG C in 10-20min, continue to heat up, in 20-30min, rise to 90 DEG C, then rise in 70-80min 100 DEG C with
On, continue 30-100min；It stands, is filtered with 80 DEG C of washings of distilled water, in triplicate；Then filtered product will be washed to set
It is dry in 40 DEG C of baking oven, it is ground up, sieved to obtain modified PMMA white fine powder particle after dry；
(3) remaining component is weighed according to weight point；The carboxymethyl chitosan is dissolved in acid solution and forms carboxymethyl shell
Glycan solution；The carboxymethyl chitosan solution and step (1) (2) resulting materials and remaining component modification calcined mixed are formed
Mixture obtains the powder component of artificial bone；
(4) dimethyl terephthalate (DMT) solution and methylbenzene alkene is added in artificial bone powder component obtained by step (3)
Sour methyl ester solution, stirring is to thick, in inspiration syringe, slowly pushes and removes bubble, be then slowly injected into cylindrical glass
In mold, solidify at room temperature for 24 hours to get artificial bone 2.
The preparation 3 of the modified mineralized collagen artificial bone of embodiment 4
The artificial bone is the PMMA bone material of two-component system, and the two-component system is by powder component and liquid
Component is constituted, and the weight ratio of the powder component and liquid component is 1:4；
Wherein, in the powder component, by weight, including modified 35 parts of mineralized collagen powder, polymethyl
35 parts of sour methacrylate powder, 12 parts of 1,3- butadiene powder, 12 parts of styrene powder, 8 parts of strontium boride, 8 parts of magnesium nitrate, silver nitrate 8
Part, molecular weight are in 2x105~3x10515 parts of carboxymethyl chitosan；
The liquid portion includes dimethyl terephthalate (DMT) solution and methylbenzene e pioic acid methyl ester solution, wherein to benzene
The weight ratio of dicarboxylic acid dimethyl ester solution and methylbenzene e pioic acid methyl ester solution is 1:50-100, in dimethyl terephthalate (DMT) solution
The mass fraction of dimethyl terephthalate (DMT) is ‰~6wt of 4wt ‰, methyl methacrylate in methyl methacrylate solution
Mass fraction is 99.4wt%~99.6wt%.
The preparation method is as follows:
(1) preparation of modified mineralized collagen is same as above；
(2) modified poly (methyl methacrylate) is prepared using suspension polymerization, experimental material includes: methyl methacrylate
(MMA), methyl acrylate (MA), dibenzoyl peroxide (BPO), polyvinyl alcohol (PVA), preparation step is as follows: in a reservoir,
Distilled water is added, polymethyl methacrylate is added under stiring, 1,3-butadiene and styrene monomer is added after 10min,
Rise to 80 DEG C in 10-20min, continue to heat up, in 20-30min, rise to 90 DEG C, then rise in 70-80min 100 DEG C with
On, continue 30-100min；It stands, is filtered with 80 DEG C of washings of distilled water, in triplicate；Then filtered product will be washed to set
It is dry in 40 DEG C of baking oven, it is ground up, sieved to obtain modified PMMA white fine powder particle after dry；
(3) remaining component is weighed according to weight point；The carboxymethyl chitosan is dissolved in acid solution and forms carboxymethyl shell
Glycan solution；The carboxymethyl chitosan solution and step (1) (2) resulting materials and remaining component modification calcined mixed are formed
Mixture obtains the powder component of artificial bone；
(4) dimethyl terephthalate (DMT) solution and methylbenzene alkene is added in artificial bone powder component obtained by step (3)
Sour methyl ester solution, stirring is to thick, in inspiration syringe, slowly pushes and removes bubble, be then slowly injected into cylindrical glass
In mold, solidify at room temperature for 24 hours to get artificial bone 3.
The detection of 5 artificial bone of embodiment
Artificial bone 1,2 and 3 prepared by the present invention is detected, control selection Germany Heraeus is respectively labeled as
The PMMA bone cement of Palacos MV production
Curing time and syringeability measurement: the solidification of each bone cement sample is measured with similar Fred Gilmore needle indentation method
Time, experiment are repeated 5 times；
Compressive strength determination: it by the mold of artificial bone slurry filling Φ 10mm × 5mm, takes out, is placed in after 0.5h
72h is conserved in 37 DEG C of water-baths, is tested using omnipotent mechanics machine, load 900N, pressing speed 1mm/min, meter
Compression strength is calculated, the artificial bone cement of each component is all made of 5 Duplicate Samples, and calculated result is averaged；
Anti-microbial property detection: artificial bone slurry is made to the cylindrical body of Φ 5mm × 2mm, the large intestine bar purchased from ATCC
Bacterium (35218) and staphylococcus aureus (25923) are used as strain, and the biocidal property of each sample is tested using plate inhibition zone method
Can, experiment is repeated 3 times.
The characterization of 1 artificial bone of table
| Performance characterization | Embodiment 2 | Embodiment 3 | Embodiment 4 | Control |
| Curing time/min | 11 | 12 | 10 | 10 |
| Injectable coefficient | 96 | 90 | 98 | 65 |
| Compression strength/MPa | 25 | 23 | 28 | 20 |
| Antibacterial loop diameter/mm | 7 | 8 | 9 | 5 |
Artificial bone prepared by the present invention, curing time are basically unchanged as shown in Table 1, and the operation for not changing doctor is practised
It is used；
In addition, artificial bone syringeability provided by the invention is good, be conducive to doctor's operation, and anti-microbial property is excellent
Different, compression strength is good, has a vast market foreground.The artificial bone that especially prepared by the embodiment of the present invention 4 is had excellent performance.
3 performance test of artificial bone of 6 embodiment 4 of embodiment preparation
The in vitro resisting pull out forces of artificial bone 3 test-of the invention injects artificial bone and control bone cement respectively
Enter after sheep centrum and after pedicle screw resisting pull out forces mechanical property evaluation: withdrawal force 250N, artificial bone 3 of the invention
Extracting force data is 1.75 ± 0.55, and compare as 1.02 ± 0.41 the result shows that, in the in vitro resisting pull out forces experiment of sheep centrum,
Artificial bone 3 of the invention is significantly better than control.
Artificial bone 3 of the present invention shown in Fig. 1 and the cytotoxicity CCK8 for compareing PMMA bone cement are tested (with MG63 cell
The result of interaction).The result shows that activity reduction is unobvious after artificial bone 3 of the invention and MG63 cytosis,
Illustrate artificial bone 3 of the invention does not have cytotoxicity.
Acute systemic toxicity: mouse peritoneal is modified according to 50mL/kg injecting normal saline (control group) and the present invention
PMMA leaching liquor observes liver and renal histology slice after 72 hours, as a result animal as shown in Figure 2 is without dead, object poisoning table
Existing, body weight increase indifference.
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, fall within the scope of the claimed invention without departing from theon the basis of the spirit of the present invention.
Claims (7)
1. a kind of novel artificial bone material, which is characterized in that the artificial bone is the PMMA bone material of two-component system, institute
Two-component system is stated to be made of powder component and liquid component, the weight ratio of the powder component and liquid component be 1:2.5~
4.5；
Wherein, in the powder component, by weight, including modified 30-35 parts of mineralized collagen powder, polymethylacrylic acid
25-40 parts of methacrylate powder, 10-15 parts of 1,3- butadiene powder, 10-15 parts of styrene powder, 5-10 parts of strontium boride, magnesium nitrate 5-
10 parts, 5-10 parts of silver nitrate, molecular weight is in 2x105~3x10510-20 parts of carboxymethyl chitosan；
The liquid portion includes dimethyl terephthalate (DMT) solution and methylbenzene e pioic acid methyl ester solution, wherein terephthaldehyde
The weight ratio of dimethyl phthalate solution and methylbenzene e pioic acid methyl ester solution is 1:50-100, to benzene in dimethyl terephthalate (DMT) solution
The mass fraction of dicarboxylic acid dimethyl ester is ‰~6wt of 4wt ‰, the quality of methyl methacrylate in methyl methacrylate solution
Score is 99.4wt%~99.6wt%.
2. artificial bone as described in claim 1, which is characterized in that also add DBM, BMP, antibiosis in the powder component
Element or 1-5 parts of chemotherapeutics.Bone morphogenetic protein (BMP), decalcified bone matrix (DBM).
3. artificial bone as described in claim 1, which is characterized in that also contain nano silver 3-5 parts in the powder component.
4. artificial bone as described in claim 1, which is characterized in that the modified mineralized collagen is collagen/hydroxy-apatite
Stone complex solid powder.
5. the preparation method of artificial bone described in Claims 1 to 4 any one, the method comprises the following steps:
(1) preparation of modified mineralized collagen；
(2) modified poly (methyl methacrylate) is prepared using suspension polymerization, experimental material includes: methyl methacrylate
(MMA), methyl acrylate (MA), dibenzoyl peroxide (BPO), polyvinyl alcohol (PVA), preparation step is as follows: in a reservoir,
Distilled water is added, polymethyl methacrylate is added under stiring, 1,3-butadiene and styrene monomer is added after 10min,
Rise to 80 DEG C in 10-20min, continue to heat up, in 20-30min, rise to 90 DEG C, then rise in 70-80min 100 DEG C with
On, continue 30-100min；It stands, is filtered with 80 DEG C of washings of distilled water, in triplicate；Then filtered product will be washed to set
It is dry in 40 DEG C of baking oven, it is ground up, sieved to obtain modified PMMA white fine powder particle after dry；
(3) remaining component is weighed according to weight point；The carboxymethyl chitosan is dissolved in acid solution and forms carboxymethyl chitosan
Solution；The carboxymethyl chitosan solution is mixed with step (1) (2) resulting materials and the formation of remaining component modification calcined mixed
Object obtains the powder component of artificial bone；
(4) dimethyl terephthalate (DMT) solution and methylbenzene olefin(e) acid first is added in artificial bone powder component obtained by step (3)
Ester solution, stirring is to thick, in inspiration syringe, slowly pushes and removes bubble, be then slowly injected into cylindrical glass mold
In, solidify at room temperature for 24 hours to get artificial bone.
6. preparation method as claimed in claim 5, which is characterized in that the preparation method of step (1) the modified mineralized collagen
Including following operating procedure:
Step S1, collagen is dissolved in any one of hydrochloric acid, nitric acid or acetic acid, is configured to the acid solution of collagen, wherein collagen
Concentration is 5.0 × 10-5~5.0 × 10-3g/mL；
Step S2, continue whipping step S1 acquired solution, the solution of calcium ions is slowly added dropwise, the additional amount of calcium ion is every gram
Collagen is corresponding to be added 0.01~0.16mol of calcium ion；
Step S3, continue whipping step S2 acquired solution, the solution of phosphorus-containing acid ion, the addition of phosphate anion is slowly added dropwise
The molar ratio of amount and calcium ion additional amount in step S2 is Ca/P=1/1~2/1；
Step S4, continue whipping step S3 acquired solution, NaOH solution is slowly added dropwise to mixed system pH=6~8, works as pH=5
When~6, mixed system starts to precipitate, and as pH=7, white suspension occurs in mixed system；
Step S5, mixed system obtained by step S4 is stood 24~120 hours, isolates and precipitate and wash away foreign ion, then
It is freeze-dried, mineralized collagen powder is obtained after grinding；
Step S6, the mineralized collagen powder that a certain amount of step S5 is obtained is weighed, is fitted into mold, then applies pressure to mold,
And the pressure being applied on mineralized collagen powder is made to reach 900~1200MPa, it is kept for pressure 30~300 seconds, demoulding obtains mineralising
Collagen block；
Step S7, mineralized collagen block made from step S6 is ground, obtains mineralized collagen powder；
Step S8 configures silver nitrate, magnesium nitrate, the strontium boride solution of same concentrations, and the concentration of solution is 0.5mol/L；By three kinds
Solution is pumped into reaction vessel simultaneously, and being pumped into speed is 1~30mL/min, and three kinds of solution terminate to be pumped into simultaneously, is pumped into the time
For 10~30min, white emulsion is obtained, is continuesd to mix uniformly；Ammonium hydroxide is added, has white precipitate to be gradually precipitated, adjustment pH value is
10~12, it continuess to mix uniformly；White precipitate is separated from liquid, white precipitate is transferred to the isolation equipped with mineralized collagen
In box, for control barrier box on liquid upper layer, liquid just immersion precipitation, is 150~250 DEG C in temperature, pressure is 1~2MPa's
Under the conditions of reaction 4~for 24 hours, it is cleaning, dry, last 500~1000 DEG C, be sintered 3~12h, cooling, grinding obtains 5~200 μm
Modified mineralized collagen powder.
7. application of the artificial bone described in Claims 1 to 4 any one in clinical medicine bone grafting filler.
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