CN109364304A - A kind of method that 3D printing prepares degradable homogeneity multifunctional bio biomimetic scaffolds - Google Patents
A kind of method that 3D printing prepares degradable homogeneity multifunctional bio biomimetic scaffolds Download PDFInfo
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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
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
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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
- A61L27/58—Materials at least partially resorbable by the body
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/10—Processes of additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/30—Auxiliary operations or equipment
- B29C64/307—Handling of material to be used in additive manufacturing
- B29C64/314—Preparation
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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
- B33Y10/00—Processes of additive manufacturing
-
- 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
- B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
-
- 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
- B33Y70/00—Materials specially adapted for additive manufacturing
-
- 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
- A61L2300/414—Growth factors
-
- 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 present invention provides a kind of method for preparing the inorganic doping material for Bone Defect Repari, it include: the double screw extruder that polyester and multi-carboxy compound are uniformly added to mixed material in a looping fashion afterwards with solid phase mixing, wherein the molar ratio of multi-carboxy compound and polyester is 0.1-20, temperature of charge is controlled at 50~150 DEG C, 5~200min of continuous extrusion material under the vacuum condition of 1~100KPa obtains the polyester that end is modified by carboxylated；Inorganic bone induction material particle is added into double screw extruder again, inorganic bone induction material additive amount is the 1-30% of weight polyester, temperature of charge is controlled at 50~150 DEG C, 5~200min of continuous extrusion material, finally obtains the inorganic doping material that can be used for Bone Defect Repari under vacuum conditions.The present invention also provides a kind of methods for preparing Bone Defect Repari biomimetic scaffolds with the inorganic doping material 3D printing.Method of the invention realizes the evenly dispersed of inorganic material nanoscale under solvent-free conditions, and simple process, production cost is low, and no three wastes generates, environmentally protective, is suitble to industrialization, continuous production.
Description
Technical field
The present invention relates to biomedical materials fields, and in particular to a kind of side of 3D printing preparation homogeneity biomimetic scaffolds
Method.
Background technique
Degradable biomaterial such as polylactic acid (PLA), polylactide (PLGA) etc. have good bio-compatible
Property, huge advantage is presented in terms of tissue or organ reparation.In bone tissue reparation, in order to accelerate osteanagenesis speed, usually
The inorganic constituents such as hydroxyapatite (HA), bata-tricalcium phosphate (TCP) can be introduced.Common technological means is that having solvent or nothing
Physical blending is directly carried out under solvent, but inorganic material cannot reach evenly dispersed in high molecular material, will lead to skeletonization
The disadvantages of speed is slow, bone density is relatively low, new bone malformation.
Inorganic doping bio-medical material bracket can be prepared by a variety of methods.Most common method is composite material sol
It is spontaneously dried after pore-foaming agent such as sodium chloride are added in liquid or freeze-drying, mutually separation adjoint sometimes generates additional gap.No
Foot place is that the connectivity in hole is poor, will affect migration, the differentiation of cell, and then influences internal repairing effect.As improved
Method can obtain the bracket with clear open architecture using 3D printing molding, such as solution cryosphere accumulation molding well
It is (molten using TissForm low temperature rapid shaping instrument 3D printing bone renovating material as disclosed in patent document CN 102824657A
Liquid can form the three-dimensional hole configurations being mutually communicated).
Zhang Jian etc. discloses a kind of ionic species micella casting method in Advanced materials 2017,29
The method for obtaining uniform bracket, first by the end group of poly- (lactic acid-co-glycolic acid) (PLGA) in the case that catalyst there are benefit
Carboxylated modification is carried out with succinic anhydride, is self-assembled into Isosorbide-5-Nitrae-dioxane solution with nano-grade hydroxy apatite (HA)
Even stable ionic species micelle precursor is then added sodium chloride pore-foaming agent and obtains homogenization stock support by freeze-drying,
Good internal bone defect healing effect is shown, speed is fast, bone density is high, new bone rule such as repaired.
But above-mentioned inorganic doping bio-medical material end group only introduces a carboxylic group and the bonding of inorganic material is strong
It spends low, and has used Organic chemical solvents, not only preparation efficiency is low, and volume production is difficult, and pressure is big in environmental protection；And molding equipment
Somewhat expensive is also that emphasis is needed to consider the problems of.Therefore it needs to find from industrialization angle more economical, more efficient, more environmentally friendly
Alternative solution.
The present invention is directed to realize inorganic material matrix polymerization in it is evenly dispersed and with chemical bond form and basis material
High strength bond, at the same time it is wished that assigning bracket multifunction.
Summary of the invention
It is an object of the invention to: a kind of simple process is provided, is not needed using organic solvent, pollution-free, system at low cost
The method of standby homogeneity biomimetic scaffolds, is not only able to significantly improve the performance of biomimetic scaffolds, and can significantly improve preparation side
The industrial application value of method.
Above-mentioned purpose of the invention is achieved through the following technical solutions:
Firstly, providing a kind of method for preparing the inorganic doping material for Bone Defect Repari, comprising: will first there is good biological phase
Esterification occurs under solvent-free conditions for the polyester and multi-carboxy compound of capacitive, obtains end and is gathered by what carboxylated was modified
Ester；It is crosslinked, is obtained under solvent-free conditions with the carboxyl of the polyester after the calcium ion of inorganic bone induction material and modification again
Favorable dispersibility and the high inorganic doping material of inorganic material bond strength.
Method of the present invention specifically includes the following steps:
1) mixture in a looping fashion is uniformly added with solid phase mixing in biocompatibility polyester and multi-carboxy compound afterwards
The double screw extruder of material, wherein the molar ratio of multi-carboxy compound and polyester is 0.1-20, controls temperature of charge 50~150
DEG C, 5~200min of continuous extrusion material under the vacuum condition of 1~100KPa obtains the polyester that end is modified by carboxylated；
2) inorganic bone induction material particle after the reaction was completed to step 1), then into the double screw extruder is added,
The inorganic bone induction material additive amount is the 1-30% of the weight polyester of step 1) addition, controls temperature of charge 50~150
DEG C, 5~200min of continuous extrusion material, finally obtains the inorganic doping material that can be used for Bone Defect Repari under vacuum conditions.
The biocompatibility polyester that can be used for the method for the present invention includes but are not limited to any one in following polyester: line
Property polyester, example includes linear polylactic acid, linear poly (glycolide-co-lactide), linear polyglycolide, linear polycaprolactone, linear poly-
Lactide caprolactone, linear poly (glycolide-co-lactide) caprolactone, linear polylactide polyethylene glycol or the poly- second of linear polycaprolactone
Glycol；Or branched polyester, example include that branched polylactic acid, branching poly (glycolide-co-lactide), branching polyglycolide, branching gather oneself
Lactone, branched polylactide caprolactone, branching poly (glycolide-co-lactide) caprolactone, branched polylactide polyethylene glycol or branching are poly-
Caprolactone polyethylene glycol；Preferred branched polyester of the present invention；Most preferably branched polycaprolactone polyethylene glycol.
Can be used for multi-carboxy compound carboxyl quantity n >=2 of the method for the present invention, type include but is not limited to citric acid,
Tartaric acid, oxalic acid, succinic acid, glutaric acid, adipic acid, decanedioic acid, succinic anhydride, glutaric anhydride, adipic anhydride, polymalic acid,
Any one in poly-aspartate or polymalic acid aspartic acid；It is preferred that succinic anhydride, polymalic acid, poly-aspartate or poly-
Any one in malate-aspartate；Most preferably polymalic acid or poly-aspartate of the carboxyl quantity in 10-20.
The polymalic acid, poly-aspartate or polymalic acid aspartic acid are preferably by D, L MALIC ACID, L MALIC ACID, D-
Malic acid, L-Aspartic acid are monomer preparation.
In the method for the present invention, lubricant is added with the inorganic bone induction material particle preferably in step 2), with
Promote dispersibility of the inorganic material in polyester material.
The lubricant that can be used for the method for the present invention includes but is not limited to stearic acid, tristerin, polyethylene glycol, polyester
Any one in ethylene glycol copolymer or citroflex A-4 or two or more mixtures, the lubricant
Weight accounts for the 0.3%-50% of the step 1) weight polyester, preferably accounts for the 0.3%-20% of the weight polyester.
The inorganic bone induction material that can be used for the method for the present invention can be selected from any one in hydroxyapatite, tricalcium phosphate
Kind or two kinds of composition；The preferred hydroxyapatite of the present invention；Most preferably nano-grade hydroxy apatite.
In more preferable scheme of the invention, the water content of the hydroxyapatite is controlled in 0.1-10wt%.
In the solution of the present invention, the multi-carboxy compound and polyester molar ratio are preferably 0.1-15；More preferable 1.05.
In the solution of the present invention, the particle size of the inorganic bone induction material is preferably 20nm-5 μm, more preferably
20-200nm。
In preferred embodiments of the present invention, the double-screw extruder screw diameter is in 2-75mm；Draw ratio is more than or equal to
10, more preferable 25~40；Revolving speed is at 60~1000 revs/min.
In a kind of currently preferred embodiment, the method for inorganic doping material of the preparation for Bone Defect Repari, packet
Include following steps:
1) branched polycaprolactone polyethylene glycol and succinic anhydride is uniform with the molar ratio solid phase mixing of 1:1.05, then plus
The double screw extruder for entering mixed material in a looping fashion carries out extrusion shearing, and the double-screw extruder screw diameter is in 2-
75mm；Draw ratio 25~40,60~1000 revs/min of revolving speed；Temperature of charge is controlled at 80~100 DEG C, in the vacuum of 1~100KPa
Under the conditions of continuous extrusion 5~20min of material, obtain the branched polycaprolactone polyethylene glycol that end is modified by carboxylated；
2) the hydroxyl phosphorus of 20-200nm partial size after the reaction was completed to step 1), then into the double screw extruder is added
Limestone particles and stearic acid, the hydroxyapatite additive amount are the branched polycaprolactone polyethylene glycol weight of step 1) addition
1-30%, the stearic acid additive amount are the 0.3-20% of the branched polycaprolactone polyethylene glycol weight of step 1) addition；Control
Temperature of charge is at 80~100 DEG C, and 5~20min of continuous extrusion material, finally obtains the nothing that can be used for Bone Defect Repari under vacuum conditions
Machine dopant material.
In currently preferred another embodiment, the method for inorganic doping material of the preparation for Bone Defect Repari,
The following steps are included:
1) branched polycaprolactone, polymalic acid is uniform with the molar ratio solid phase mixing of 1:1.05, it is then added to recycle
The double screw extruder of mode mixed material carries out extrusion shearing, and the double-screw extruder screw diameter is in 2-75mm；It is long
Diameter is than 25~40, and 60~1000 revs/min of revolving speed；Temperature of charge is controlled at 80~120 DEG C, continuous extrusion material 30 under normal pressure~
50min obtains the branched polycaprolactone that end is modified by carboxylated；
2) the hydroxyl phosphorus of 20-200nm partial size after the reaction was completed to step 1), then into the double screw extruder is added
Limestone particles, the hydroxyapatite additive amount are the 10~15% of the branched polycaprolactone weight of step 1) addition, control object
Material temperature degree is at 80~120 DEG C, and 30~50min of continuous extrusion material, finally obtains the nothing that can be used for Bone Defect Repari under vacuum conditions
Machine dopant material.
In currently preferred another embodiment, the method for inorganic doping material of the preparation for Bone Defect Repari,
The following steps are included:
1) poly (glycolide-co-lactide), poly-aspartate is uniform with the molar ratio solid phase mixing of 1:1.05, be then added with
The double screw extruder of endless form mixed material carries out extrusion shearing, and the double-screw extruder screw diameter is in 2-
75mm；Draw ratio 25~40,150~250 revs/min of revolving speed；Temperature of charge is controlled at 120~150 DEG C, in the true of 1~1.5KPa
15~20min of continuous extrusion material under empty condition obtains the poly (glycolide-co-lactide) that end is modified by carboxylated；
2) hydroxyl of 100-200nm partial size after the reaction was completed to step 1), then into the double screw extruder is added
Apatite particle, the hydroxyapatite additive amount are the 8~10% of the poly (glycolide-co-lactide) weight of step 1) addition, control
Temperature of charge is at 120~150 DEG C, and 5~10min of continuous extrusion material, finally obtains and can be used for Bone Defect Repari under vacuum conditions
Inorganic doping material.
On this basis, the method the present invention further provides a kind of 3D printing preparation for the biomimetic scaffolds of Bone Defect Repari,
The following steps are included:
1. the direct wire drawing of inorganic doping material that can be used for Bone Defect Repari prepared by the method for the invention is prepared into diameter
0.1-5 millimeters of microfilament；
2. by step, 1. the obtained microfilament is formed by solid phase 3D printing, obtains the biomimetic scaffolds for Bone Defect Repari.
In the solution of the present invention, the diameter of the step 1. microfilament is preferably 1.5-3 millimeters.
In the solution of the present invention, 2. the 3D printer is conventional commercial specification to step, and preferably precision is not less than
0.02mm。
Compared with prior art, method of the invention have following several respects the utility model has the advantages that
1. preparation process is simple, any organic solvent is not needed.In existing inorganic material doping techniques, whether to polyester
Modified or 3D forming method is required using organic solvent, and production process is complicated, leads to production cost and environmental protection pressure
Power is all high, and the economic benefit of acquisition is very limited, is highly detrimental to investment industrialized production.The present inventor is found by experiment that
Promote polyester to be esterified a step of going forward side by side with polyol generation solid-state using mechanical force to hand over inorganic bone induction material with solid-state
The ingenious method of connection, this method can not only realize that inorganic material is evenly dispersed in high molecular material, and process is very
Simply, it is often more important that not needing the direct Cheng Sihou of the product obtained using any solvent can be used as solid 3D printing material,
Compared with the Bone Defect Repari 3D printing material of liquid in the prior art, applicable print resolution is significantly improved, and can be saved
Vacuum processing technique in printing shaping process.Above-mentioned various improve carrys out the medical materials industrialized production such as Bone Defect Repari
It says significant, significantly reduces the production cost of inorganic doping bio-medical bracket, substantially increase the Environmental security of technique
Property, there is very high industrial application value.
2. in method of the invention, polyester and multi-carboxy compound include extruding force and cut what double screw extruder provided
Esterification is had occurred with solid-state under the mechanisms such as shear force, introduces multiple carboxyl functional groups in polyester end, and to ester
Change adds inorganic material after the reaction was completed and is crosslinked.Experiment discovery, the mode of this stepwise reaction of the present invention and disposable
Be added polyester, carboxy-modified dose compared with the blending reaction mode of inorganic material, can allow the more carboxyls and inorganic material of polyester
Calcium ion be more fully crosslinked, can not only reunite to avoid inorganic material, allow inorganic material in the polyester very
Disperse evenly, and inorganic material can be with chemical bond form and polyester material high strength bond, therefore obtains than the prior art
More excellent modified effect.
3. after rack forming, the remaining carboxyl not crosslinked of material surface can be used for coupling activity growth because
Son further increases the biocompatibility of material, or for being coupled hydroxyl drug, for reparation and therapeutic purposes.
4. in a preferred embodiment of the invention, materials processing temperature can also be significantly reduced using branched polyester.And root
It is controlled according to branching arm number and molecular weight of polyesters, the continuously adjustable of processing temperature and material mechanical performance may be implemented.In short, this hair
Bright method production cost is low, and no three wastes generates, environmentally protective, is suitble to industrialization, continuous production.
Detailed description of the invention
Fig. 1 is four arm polycaprolactones in the embodiment of the present invention 11HNMR structural characterization figure.
Fig. 2 is that the carboxylated prepared in the embodiment of the present invention 1 modifies four arm polycaprolactones1HNMR structural characterization figure.
Fig. 3 is the appearance optical photograph in kind of the composite material biological support of 2 method of embodiment of the present invention preparation.
Fig. 4 is the low power electromicroscopic photograph of the composite material biological support of 2 method of embodiment of the present invention preparation.
Fig. 5 is the electromicroscopic photograph of the magnification at high multiple of the composite material biological support of 2 method of embodiment of the present invention preparation.
Specific embodiment
Present invention will be further explained below with reference to specific examples, but this should not be interpreted as according to the present invention
Theme is only limitted to following embodiments.
All compounds and reagent used in following embodiment are existing product, or can be prepared by existing method
Product.
The preparation of 1: four arm polycaprolactone of embodiment/hydroxyapatite composite material bracket
(1) preparation of polymalic acid
By 10g D, L-type malic acid is put into 3 mouthfuls of flasks, and logical nitrogen is protected, and reaction temperature is controlled at 130 DEG C, electricity
Magnetic is stirred to react 4 hours, through molecular weight determination, Mn=2420.
The preparation of (2) four arm polycaprolactones/hydroxyapatite composite material microfilament
It is straight that polymalic acid prepared by tetra- arm polycaprolactone (Mn=80,000) of 8g and 0.042g step (1) is added to screw rod
In the feed bin of the double screw extruder (L/D=20) of diameter Φ=10mm, revolving speed is 200 revs/min, controls reaction temperature: 80 DEG C, passing through
Naturally it is vented, makes material be extruded, shear in double screw extruder in a looping fashion, successive reaction 30min.Then not
In the case of shutdown, 1g nano-grade hydroxy apatite (water content 1.2%) is added in feed inlet, material continues in a looping fashion in machine
It is extruded, shears in device, successive reaction 30min obtains four arm polycaprolactones/hydroxyapatite composite material.
The four arm polycaprolactones and carboxylated of the present embodiment are modified into four arm polycaprolactones and are dissolved in CDCl3It carries out1HNMR table
Sign, as a result as shown in Figure 1, 2, the two hydrogen nuclear magnetic spectrogram is significantly different, and the peak shown in Fig. 2 near 7.2ppm is polymalic acid
Fumaric acid end group characteristic peak, show polymalic acid and polycaprolactone reacted chemical bonding reaction.
(3) it directly carries out above-mentioned four arms polycaprolactone/hydroxyapatite composite material to be extruded into silk using wire drawing machine, control
The diameter of throwing is at 1.75 millimeters.
(4) four arm polycaprolactones/hydroxyapatite composite material bracket preparation
Using commercial FDM 3D printer, nozzle temperature is set as 80 DEG C, and hott bed temperature is 25 DEG C, and print speed is set as
30mm/s finally obtains smooth complete 3D porous support, and overall appearance and microstructure are as shown in Fig. 3-5.
It is very complete to can see bracket overall structure manufactured in the present embodiment from the optical photograph of Fig. 3；From the low power of Fig. 4
Electromicroscopic photograph can see the overall structure of the bracket being more clear；It then can see this from the high power electromicroscopic photograph of Fig. 5
Inorganic salts are evenly distributed in the bracket of embodiment preparation.In addition, being obtained through mechanics properties testing, bracket manufactured in the present embodiment
Compared with pure four arms polycaprolactone bracket, compressive strength improves at least 143.6% under same deformational displacement.
Embodiment 2: poly (glycolide-co-lactide) (PLGA)/hydroxyapatite composite material bracket preparation
(1) preparation of poly-aspartate
10g L-Aspartic acid is put into 3 mouthfuls of flasks, logical nitrogen is protected, and reaction temperature control is at 130 DEG C, electromagnetism
It is stirred to react 4 hours, through molecular weight determination, Mn=2600.
(2) poly (glycolide-co-lactide) (PLGA)/hydroxyapatite composite material filament preparation
10g PLGA (Mn=75,000) and 0.025g poly-aspartate are added to screw diameter Φ=10mm twin-screw
In the feed bin of extruder (L/D=20), 200 revs/min of rotary speed, control reaction temperature: 150 DEG C, control vacuum degree exists
1.2KPa makes material reaction 20min in a looping fashion.1g nano-grade hydroxy apatite (water content then is added in feed inlet
And (Mn=1.2 × 10 lubricant PEG2000-PCL of 2g 1.2%)4), 5min is reacted in continuation in machine in a looping fashion,
Discharging, pelletizing.
Composite material is carried out to be extruded into silk using wire drawing machine, controls the diameter of silk at 1.75 millimeters.
(3) poly (glycolide-co-lactide) (PLGA)/hydroxyapatite composite material bracket preparation
Using commercial FDM 3D printer, nozzle temperature is set as 160 DEG C, and hott bed temperature is 45 DEG C, print speed setting
For 30mm/s, the smooth composite porous bracket of complete 3D is finally obtained.
Embodiment 3: four arm polycaprolactones/hydroxyapatite composite material bracket system of supported active growth factor RGD
It is standby
First configuration concentration is 0.5%RGD aqueous solution, adds NHS and EDI, and the 3D branch that embodiment 1 obtains is placed on
It states in solution and hatches for 24 hours.Then three times with distilled water rinsing, the composite material bracket of RGD modification is obtained.
Claims (10)
1. a method of the inorganic doping material for Bone Defect Repari is prepared, specifically includes the following steps:
1) biocompatibility polyester and multi-carboxy compound are uniformly added to mixed material in a looping fashion afterwards with solid phase mixing
Double screw extruder, wherein the molar ratio of multi-carboxy compound and polyester is 0.1-20, preferably 0.1-15；More preferable 1.05；Control
For temperature of charge processed at 50~150 DEG C, 5~200min of continuous extrusion material under the vacuum condition of 1~100KPa obtains end quilt
The polyester of carboxylated modification；
2) inorganic bone induction material particle after the reaction was completed to step 1), then into the double screw extruder is added, it is described
Inorganic bone induction material additive amount be step 1) addition weight polyester 1-30%, control temperature of charge at 50~150 DEG C,
5~200min of continuous extrusion material under vacuum condition finally obtains the inorganic doping material that can be used for Bone Defect Repari.
2. method described in claim 1, which is characterized in that the polyester is selected from linear polylactic acid, linear polyglycolide third
Lactide, linear polyglycolide, linear polycaprolactone, linear polylactide caprolactone, linear poly (glycolide-co-lactide) caprolactone, line
Property polylactide polyethylene glycol or linear polycaprolactone polyethylene glycol；Or branched polylactic acid, branching poly (glycolide-co-lactide), branch
Change polyglycolide, branched polycaprolactone, branched polylactide caprolactone, branching poly (glycolide-co-lactide) caprolactone, branching poly- third
Lactide polyethylene glycol or branched polycaprolactone polyethylene glycol；Preferred branched polyester；Most preferably branched polycaprolactone polyethylene glycol.
3. method described in claim 1, which is characterized in that multi-carboxy compound carboxyl quantity n >=2 are selected from lemon
Acid, tartaric acid, oxalic acid, succinic acid, glutaric acid, adipic acid, decanedioic acid, succinic anhydride, glutaric anhydride, adipic anhydride, poly- apple
Any one in acid, poly-aspartate or polymalic acid aspartic acid；It is preferred that succinic anhydride, polymalic acid or poly- asparagus fern ammonia
Acid；Most preferably polymalic acid or poly-aspartate of the carboxyl quantity in 10-20.
4. method described in claim 1, which is characterized in that with the inorganic bone induction material particle one in the step 2)
It rises and lubricant is added, additional amount accounts for the 0.3%-50% of the step 1) weight polyester；It is preferred that accounting for the step 1) weight polyester
0.3%-20%.
5. method as claimed in claim 4, which is characterized in that the lubricant is selected from stearic acid, tristerin, poly- second
Any one in glycol, polyester ethylene glycol copolymer or citroflex A-4 or two or more mixtures.
6. method described in claim 1, which is characterized in that the double-screw extruder screw diameter is in 2-75mm；Major diameter
Than being more than or equal to 10, more preferable 25~40；Revolving speed is at 60~1000 revs/min.
7. the method for inorganic doping material of the preparation described in claim 1 for Bone Defect Repari, comprising the following steps:
1) branched polycaprolactone polyethylene glycol and succinic anhydride is uniform with the molar ratio solid phase mixing of 1:1.05, be then added with
The double screw extruder of endless form mixed material carries out extrusion shearing, and the double-screw extruder screw diameter is in 2-
75mm；Draw ratio 25~40,60~1000 revs/min of revolving speed；Temperature of charge is controlled at 80~100 DEG C, in the vacuum of 1~100KPa
Under the conditions of continuous extrusion 5~20min of material, obtain the branched polycaprolactone polyethylene glycol that end is modified by carboxylated；
2) hydroxyapatite of 20-200nm partial size after the reaction was completed to step 1), then into the double screw extruder is added
Particle and stearic acid, the hydroxyapatite additive amount are the 1- of the branched polycaprolactone polyethylene glycol weight of step 1) addition
30%, the stearic acid additive amount is the 0.3-20% of the branched polycaprolactone polyethylene glycol weight of step 1) addition；Control object
Material temperature degree is at 80~100 DEG C, and 5~20min of continuous extrusion material, finally obtains and can be used for the inorganic of Bone Defect Repari under vacuum conditions
Dopant material.
8. the method for inorganic doping material of the preparation described in claim 1 for Bone Defect Repari, comprising the following steps:
1) branched polycaprolactone and polymalic acid is uniform with the molar ratio solid phase mixing of 1:1.05, it is then added in a looping fashion
The double screw extruder of mixed material carries out extrusion shearing, and the double-screw extruder screw diameter is in 2-75mm；Draw ratio
25~40,60~1000 revs/min of revolving speed；Control temperature of charge is at 80~120 DEG C, 30~50min of continuous extrusion material under normal pressure,
Obtain the branched polycaprolactone that end is modified by carboxylated；
2) hydroxyapatite of 20-200nm partial size after the reaction was completed to step 1), then into the double screw extruder is added
Particle, the hydroxyapatite additive amount are the 10~15% of the branched polycaprolactone weight of step 1) addition, control material temperature
Degree is at 80~120 DEG C, 30~50min of continuous extrusion material under vacuum conditions, and finally obtaining can be used for the inorganic of Bone Defect Repari and mix
Miscellaneous material.
9. the method for inorganic doping material of the preparation described in claim 1 for Bone Defect Repari, comprising the following steps:
1) poly (glycolide-co-lactide) and poly-aspartate is uniform with the molar ratio solid phase mixing of 1:1.05, it is then added to recycle
The double screw extruder of mode mixed material carries out extrusion shearing, and the double-screw extruder screw diameter is in 2-75mm；It is long
Diameter is than 25~40, and 150~250 revs/min of revolving speed；Temperature of charge is controlled at 120~150 DEG C, under the vacuum condition of 1~1.5KPa
Continuous extrusion 15~20min of material obtains the poly (glycolide-co-lactide) that end is modified by carboxylated；
2) hydroxy-apatite of 100-200nm partial size after the reaction was completed to step 1), then into the double screw extruder is added
Stone particle, the hydroxyapatite additive amount are the 8~10% of the poly (glycolide-co-lactide) weight of step 1) addition, control material
Temperature is at 120~150 DEG C, and 5~10min of continuous extrusion material, finally obtains and can be used for the inorganic of Bone Defect Repari under vacuum conditions
Dopant material.
10. a kind of method of biomimetic scaffolds of 3D printing preparation for Bone Defect Repari, comprising the following steps:
1. the direct wire drawing of inorganic doping material that can be used for Bone Defect Repari prepared by claim 1 the method is prepared into diameter
0.1-5 millimeters, preferably 1.5-3 millimeters of microfilament；
2. by step, 1. the obtained microfilament is formed by solid phase 3D printing, obtains the biomimetic scaffolds for Bone Defect Repari.
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