CN109381744A - A kind of calcium orthophosphate base bone repairing support and preparation method thereof - Google Patents
A kind of calcium orthophosphate base bone repairing support and preparation method thereof Download PDFInfo
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- CN109381744A CN109381744A CN201811079429.9A CN201811079429A CN109381744A CN 109381744 A CN109381744 A CN 109381744A CN 201811079429 A CN201811079429 A CN 201811079429A CN 109381744 A CN109381744 A CN 109381744A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings comprising two or more layers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
The invention discloses a kind of calcium orthophosphate base bone repairing supports and preparation method thereof.The present invention is using calcium phosphate bone cement as raw material, the calcium phosphate cement bracket with connection macropore is obtained in conjunction with 3D printing technique, and processing is modified to rack surface using dopamine solution, dopamine passes through autoxidation under alkaline condition and forms poly-dopamine layer in rack surface, poly-dopamine has good stickiness and biocompatibility, coating can be sticked as BMP-2, improve the content of fixed BMP-2, promote cell adherence and proliferation；The BMP-2 loaded in bracket can also effectively facilitate the proliferation and Osteoblast Differentiation of mesenchymal stem cell.Calcium orthophosphate base bone repairing support prepared by the present invention has connection macropore, meets the mechanical strength requirement of cancellous bone, has excellent biocompatibility, can effectively facilitate bone tissue regeneration, has potential using value in bone tissue reparation field.
Description
Technical field
The present invention relates to bone renovating material technical fields, and in particular to a kind of calcium orthophosphate base bone repairing support and its preparation side
Method.
Background technique
The bone tissue important as human body, although have osteanagenesis and self-reparing capability, for tumour, wound,
Bone defect caused by bone misgrowth is needed in the case where that can not heal by bone selfreparing merely by implantation material
Assist the reparation and recovery from illness of disrupted tissue.From the perspective of bone tissue self-healing, ideal bone repairing support needs to have good
Good biocompatibility, biological degradability, 3 D stereo porous structure and the complex appearance to match with defect.Porous bone
Recovery support specific surface area with higher and space grow conducive to the load of active factors, cell adherence, extracellular matrix sinks
Product, nutrition and oxygen enter and metabolite discharge, blood vessel are grown into.Further, since bracket need to provide branch for cambium
Support is until cambium has own biological mechanical characteristic, and therefore, good plasticity and mechanical strength are also to measure bone tissue
One big important indicator of bracket performance superiority and inferiority.The preparation method of conventional porous timbering material is manual operation, poor repeatability；Addition
Perforating agent there are potential toxic side effects, hole connectivity is poor, or is unable to control pore size, it is even more impossible to manufacture have it is multiple
The bone repairing support of miscellaneous shape.
Summary of the invention
It is an object of the invention to provide in place of overcome the deficiencies in the prior art a kind of calcium orthophosphate base bone repairing support and
Preparation method.
To achieve the above object, the technical solution adopted by the present invention is as follows:
A kind of preparation method of calcium orthophosphate base bone repairing support, comprising the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, obtains calcium phosphate bone cement slurry after mixing evenly；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9,30
DEG C~40 DEG C of dryings after, obtain poly-dopamine modification calcium phosphate cement bracket；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, chilled after standing 2~4h
It is dried to obtain the calcium orthophosphate base bone repairing support.
The present invention obtains the calcium phosphate cement bracket with connection macropore using 3D printing technique, using dopamine solution
Processing is modified to rack surface, dopamine passes through autoxidation under alkaline condition and forms poly-dopamine layer in rack surface,
Poly-dopamine is conducive to enhance the mechanical strength of bracket, and poly-dopamine has good stickiness and biocompatibility, Neng Gouzuo
For the coating that sticks of BMP-2, the modification of poly-dopamine not only increases the content of fixed BMP-2, while also promoting cell adherence
And proliferation；On the other hand, the BMP-2 loaded in bracket can also effectively facilitate the proliferation and skeletonization point of mesenchymal stem cell
Change.Calcium orthophosphate base bone repairing support prepared by the present invention has connection macropore, has excellent biocompatibility, can effectively promote
Into bone tissue regeneration, there is potential using value in bone tissue reparation field.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the solid phase powder
End includes polyethylene glycol, tetracalcium phosphate, bata-tricalcium phosphate, type alpha tricalcium phosphate, calcium carbonate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, phosphoric acid
At least one of eight calcium, unformed calcium phosphate.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the solid phase powder
End includes polyethylene glycol, type alpha tricalcium phosphate, mixes strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, strontium
With the molar ratio of calcium are as follows: strontium: calcium=0.1~1.6:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.1~
1.4:1。
The incorporation of strontium ion peomotes bone cement hydration reaction in bone cement, enhances the mechanical strength of bracket；And bone
Strontium ion can be steadily released in cement, promote new bone formation by promoting cell Proliferation and osteoblast differentiation.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the solid phase powder
The mass fraction of polyethylene glycol is 0.5%~0.8% in end.
The mouldability that polyethylene glycol can be effectively improved slurry is added in solid phase powder, avoids occurring in print procedure
It is separated by solid-liquid separation.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the solidify liquid
Including hydroxypropyl methyl cellulose and carboxymethyl chitosan, the mass fraction of hydroxypropyl methyl cellulose is in the solidify liquid
0.2%~0.5%；The mass fraction of carboxymethyl chitosan is 0.1%~1% in the solidify liquid.
It is compounded in solidify liquid using hydroxypropyl methyl cellulose and carboxymethyl chitosan, and controls the content of the two, energy
The phenomenon that viscosity for enough increasing slurry, improves the mouldability of slurry, avoids the occurrence of separation of solid and liquid or deformation of timbering collapsing；Another party
It is compounded between two kinds of polysaccharide of face hydroxypropyl methyl cellulose and carboxymethyl chitosan, is easy to form three-dimensional network knot in bone cement
Structure enhances bone cement mechanical property.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the solidify liquid
The mass ratio of middle hydroxypropyl methyl cellulose and carboxymethyl chitosan is 1:2.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the dopamine
The mass fraction of dopamine is 5%~15% in alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5；The BMP-2 is molten
The concentration of BMP-2 is 2~6mg/mL in liquid.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the step
(2) in, print parameters are set are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；Platform
Temperature: room temperature；Barrel temperature is 37 DEG C；Set the parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm.
Calcium phosphate cement bracket by setting the above print parameters preparation has equally distributed intercommunicating pore, and duct is big
Small is respectively 300~400 μm, and interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
The preferred embodiment of preparation method as calcium orthophosphate base bone repairing support of the present invention, the step
(1) in, the solid-to-liquid ratio of orthophosphate skeleton cement solid powder and solidify liquid is 1g:0.45~0.6mL.
Inventor has found that the solid-to-liquid ratio of orthophosphate skeleton cement solid powder and solidify liquid is excessive by repetition test, can lead
Slurry is caused to be easy blocking syringe needle；Solid-to-liquid ratio is too small to be easy to cause bracket to be difficult to form or cause bracket that Collapse Deformation occurs, Gu
Liquor ratio control is 1g:0.45~0.6mL, and the mouldability by the bracket calcium phosphate cement bracket of 3D printing acquisition is preferable.
The present invention also provides a kind of calcium orthophosphate base bone repairing supports being prepared according to the above method.
Compared with prior art, the invention has the benefit that
The present invention, as raw material, the calcium phosphate with connection macropore is obtained in conjunction with 3D printing technique using calcium phosphate bone cement
Cement bracket, and be modified processing to rack surface using dopamine solution, dopamine is under alkaline condition by from oxygen
Change and form poly-dopamine layer in rack surface, poly-dopamine has good stickiness and biocompatibility, can be as BMP-2's
Stick coating, improve the load capacity of BMP-2 on bracket, promotes cell adherence and proliferation, facilitate New born formation；It is born in bracket
The BMP-2 of load can also effectively facilitate the proliferation and Osteoblast Differentiation of mesenchymal stem cell.Calcium orthophosphate base bone prepared by the present invention
Recovery support has connection macropore, meets the mechanical strength requirement of cancellous bone, has excellent biocompatibility, can effectively promote
Into bone tissue regeneration, there is potential using value in bone tissue reparation field.
Detailed description of the invention
Fig. 1 is the Cell proliferation results figure of embodiment 3~5, embodiment 8 and comparative example 1~3.
Fig. 2 is the ALP activity figure of embodiment 3~5, embodiment 8 and comparative example 1~3.
Specific embodiment
Purposes, technical schemes and advantages in order to better illustrate the present invention, below in conjunction with specific embodiment to the present invention
It further illustrates.It will be appreciated by those skilled in the art that described herein, specific examples are only used to explain the present invention, not
For limiting the present invention.
In embodiment, used experimental method is conventional method unless otherwise specified, material used, reagent etc.,
It is commercially available unless otherwise specified.
Embodiment 1
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.45mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.1:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.1:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.5%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.5% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.1%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 5% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 2mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 2
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.45mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.6%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.2% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.8%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 5% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 2mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 3
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.7%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.4% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.8%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 8% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 4mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 4
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.7%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.4% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.6%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 8% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 5mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 5
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.7%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.5% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.7%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 10% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 4mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 6
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.6mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.8%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.4% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.8%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 10% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 4mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 7
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.6mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.8%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.2% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 1%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 12% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 6mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 8
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=1.6:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.4:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.8%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.2% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 1%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 15% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 6mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Embodiment 9
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, tetracalcium phosphate and calcium phosphate dibasic anhydrous；The molar ratio of tetracalcium phosphate and calcium phosphate dibasic anhydrous is 1:1；In the solid phase powder
The mass fraction of polyethylene glycol is 0.8%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.2% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 1%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 15% in dopamine alkaline aqueous solution, and the pH of dopamine alkaline aqueous solution is 8.5,30 DEG C~40
After DEG C dry, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 6mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of the present embodiment has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Comparative example 1
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.7%；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.4% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.8%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
Set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 400 μm；It is flat
Platform temperature: room temperature；Barrel temperature is 37 DEG C；
The parameter of 3D printing bracket: fibre diameter: 400 μm；Fiber spacing: 400 μm；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is immersed in BMP-2 solution, BMP-2's is dense in the BMP-2 solution
Degree is 4mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of this comparative example has equally distributed intercommunicating pore, and duct size is respectively
300~400 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
Comparative example 2
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate mix strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, the molar ratio of strontium and calcium
Are as follows: strontium: calcium=0.7:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.3:1；Gather in the solid phase powder
The mass fraction of ethylene glycol is 0.7%；
Carboxymethyl chitosan is dissolved in the citric acid solution of 0.5mol/L and obtains solidify liquid, carboxymethyl in the solidify liquid
The mass fraction of chitosan is 1.2%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 8% in dopamine alkaline aqueous solution, after 30 DEG C~40 DEG C dryings, obtains poly-dopamine modification
Calcium phosphate cement bracket；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 4mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of this comparative example has equally distributed intercommunicating pore, and duct size is respectively
300~500 μm, interlayer arrangement slightly deforms.
Comparative example 3
A kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, orthophosphate skeleton cement solid powder and solidify liquid
Solid-to-liquid ratio is 1g:0.5mL, obtains calcium phosphate bone cement slurry after mixing evenly, wherein the solid phase powder includes poly- second two
Alcohol, type alpha tricalcium phosphate, calcium carbonate and calcium dihydrogen phosphate；The mass fraction of polyethylene glycol is 0.7% in the solid phase powder；
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are dissolved in the citric acid solution of 0.5mol/L and obtain solidify liquid,
The mass fraction of hydroxypropyl methyl cellulose is 0.4% in the solidify liquid；The quality of carboxymethyl chitosan in the solidify liquid
Score is 0.8%；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, the environment that relative humidity is 95%~100%
Calcium phosphate cement bracket of the middle aquation after 1~4 day, in 30 DEG C~40 DEG C dryings, after being solidified；
(4) calcium phosphate cement bracket after solidification is placed in the dopamine alkaline aqueous solution that pH value is 8~9, it is described
The mass fraction of dopamine is 8% in dopamine alkaline aqueous solution, after 30 DEG C~40 DEG C dryings, obtains poly-dopamine modification
Calcium phosphate cement bracket；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, in the BMP-2 solution
The concentration of BMP-2 is 4mg/mL, freeze-dried to obtain the calcium orthophosphate base bone repairing support after standing 2~4h.
The calcium phosphate cement bracket of the printing of this comparative example has equally distributed intercommunicating pore, and duct size is respectively
300~500 μm, interlayer arrangement uniformly, is well combined, no division and collapse phenomenon.
The calcium orthophosphate base bone repairing support prepared to Examples 1 to 9 and comparative example 1~3 carries out following performance detection.
1, compression strength
The compression strength of calcium orthophosphate base bone repairing support sample, loading speed 1mm/ are tested by universal testing machine
Min, the results are shown in Table 1.
2, porosity
Using dehydrated alcohol as liquid phase medium, by specific gravity balance, the hole of sample is measured according to Archimedes's drainage
Rate, the results are shown in Table 1.
Table 1
As seen from the results in Table 1, processing is modified to rack surface using dopamine solution, dopamine is under alkaline condition
Poly-dopamine layer is formed in rack surface by autoxidation, the mechanical property of bracket can be enhanced；Solidify liquid hydroxypropyl methyl is fine
Addition in dimension element and carboxymethyl chitosan is conducive to the mechanical property for enhancing bracket；And strontium calcium octahate phosphate is mixed as Sr2+Source,
Bone cement aquation is peomoted, to improve the compression strength of bracket.
3, cell Proliferation
Using the calcium orthophosphate base bone repairing support of embodiment 3~5 and embodiment 8 as experimental group, with the sample of comparative example 1~3
Product as a control group, the increasing of cell (Marrow Mesenchymal Stem Cells, ATCC CRL-12424) are detected using CCK-8 kit
Situation is grown, is placed a sample into 48 orifice plates, inoculating cell quantity is 1 × 104The hole cell/, changes liquid every other day, at 37 DEG C, 5%CO2's
Cultivate 1 in incubator respectively, 3, after 7d, by absorbance value of the microplate reader at 450nm, as a result as shown in Figure 1.
4, Osteoblast Differentiation
Using the calcium orthophosphate base bone repairing support of embodiment 3~5 and embodiment 8 as experimental group, with the sample of comparative example 1~3
As a control group, calcium orthophosphate base bone repairing support sample is placed in 48 orifice plates for product, in microsphere sample between culture mouse bone marrow cells
Mesenchymal stem cells, inoculating cell quantity are 5 × 104The hole cell/, changes liquid every other day, at 37 DEG C, 5%CO2Incubator in train respectively
After supporting 7,10d, ALP determination of activity is carried out according to kit, as a result as shown in Figure 2.
By Fig. 1 and Fig. 2 result it is found that poly-dopamine can stick coating as BMP-2, help to improve on bracket
The load capacity of BMP-2 so as to improve the bioactivity of bracket, and can steadily release strontium ion, pass through rush in bone cement
Promote new bone formation into cell Proliferation and osteoblast differentiation.
In conclusion calcium orthophosphate base bone repairing support prepared by the present invention has connection macropore, meet the mechanics of cancellous bone
Intensity requirement has excellent biocompatibility, can effectively facilitate bone tissue regeneration, has in bone tissue reparation field potential
Application value.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention
The limitation of range is protected, although the invention is described in detail with reference to the preferred embodiments, those skilled in the art should
Understand, it can be with modification or equivalent replacement of the technical solution of the present invention are made, without departing from the essence of technical solution of the present invention
And range.
Claims (10)
1. a kind of preparation method of calcium orthophosphate base bone repairing support, which comprises the following steps:
(1) orthophosphate skeleton cement solid powder and solidify liquid are mixed, obtains calcium phosphate bone cement slurry after mixing evenly；
(2) calcium phosphate bone cement slurry is printed by 3D printing technique and obtains calcium phosphate cement bracket；
(3) calcium phosphate cement bracket is placed in temperature is 30 DEG C~40 DEG C, water in the environment that relative humidity is 95%~100%
After changing 1~4 day, the calcium phosphate cement bracket in 30 DEG C~40 DEG C dryings, after being solidified；
(4) by the calcium phosphate cement bracket after solidification be placed in pH value be 8~9 dopamine alkaline aqueous solution in, 30 DEG C~
After 40 DEG C of dryings, the calcium phosphate cement bracket of poly-dopamine modification is obtained；
(5) calcium phosphate cement bracket by poly-dopamine modification immerses in BMP-2 solution, freeze-dried after standing 2~4h
Obtain the calcium orthophosphate base bone repairing support.
2. the preparation method of calcium orthophosphate base bone repairing support according to claim 1, which is characterized in that the solid phase powder
Including polyethylene glycol, tetracalcium phosphate, bata-tricalcium phosphate, type alpha tricalcium phosphate, calcium carbonate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, phosphoric acid eight
At least one of calcium, unformed calcium phosphate.
3. the preparation method of calcium orthophosphate base bone repairing support according to claim 1, which is characterized in that the solid phase powder
Including polyethylene glycol, type alpha tricalcium phosphate, mixes strontium calcium octahate phosphate and/or mix strontium amorphous calcium phosphate；In the solid phase powder, strontium and
The molar ratio of calcium are as follows: strontium: calcium=0.1~1.6:1；The molar ratio of the sum of the calcium and strontium and phosphorus are as follows: calcium+strontium: phosphorus=1.1~
1.4:1。
4. the preparation method of calcium orthophosphate base bone repairing support according to claim 2, which is characterized in that the solid phase powder
The mass fraction of middle polyethylene glycol is 0.5%~0.8%.
5. the preparation method of calcium orthophosphate base bone repairing support according to claim 1, which is characterized in that the solidify liquid packet
Hydroxypropyl methyl cellulose and carboxymethyl chitosan are included, the mass fraction of hydroxypropyl methyl cellulose is in the solidify liquid
0.2%~0.5%；The mass fraction of carboxymethyl chitosan is 0.1%~1% in the solidify liquid.
6. the preparation method of calcium orthophosphate base bone repairing support according to claim 5, which is characterized in that in the solidify liquid
The mass ratio of hydroxypropyl methyl cellulose and carboxymethyl chitosan is 1:2.
7. the preparation method of calcium orthophosphate base bone repairing support according to claim 1, which is characterized in that the DOPA amine base
Property aqueous solution in the mass fraction of dopamine be 5%~15%, the pH of dopamine alkaline aqueous solution is 8.5；The BMP-2 solution
The concentration of middle BMP-2 is 2~6mg/mL.
8. the preparation method of calcium orthophosphate base bone repairing support according to claim 1, which is characterized in that the step (2)
In, set print parameters are as follows: squeeze out air pressure: 0.25MPa；Print speed: 3mm/s；Needle sizes internal diameter: 500 μm；Platform temperature
Degree: room temperature；Barrel temperature is 37 DEG C；Set the parameter of 3D printing bracket: fibre diameter: 500 μm；Fiber spacing: 400 μm.
9. the preparation method of calcium orthophosphate base bone repairing support according to claim 1, which is characterized in that the step (1)
In, the solid-to-liquid ratio of orthophosphate skeleton cement solid powder and solidify liquid is 1g:0.45~0.6mL.
10. a kind of calcium orthophosphate base bone repairing support that the method for any one according to claim 1~9 is prepared.
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