CN102886076A - Bone repair porous bracket and rapid forming method - Google Patents
Bone repair porous bracket and rapid forming method Download PDFInfo
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- CN102886076A CN102886076A CN2012103657995A CN201210365799A CN102886076A CN 102886076 A CN102886076 A CN 102886076A CN 2012103657995 A CN2012103657995 A CN 2012103657995A CN 201210365799 A CN201210365799 A CN 201210365799A CN 102886076 A CN102886076 A CN 102886076A
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Abstract
The invention relates to a bone repair porous bracket, which comprises a substrate with a bionic porous structure and growth factor controlled-release microspheres, wherein the growth factor controlled-release microspheres are adsorbed into gaps of the bionic porous structure on the substrate or are dispersed into the substrate by being uniformly mixed with substrate raw material in a substrate forming process. The invention further provides a rapid forming method for the bone repair porous bracket. The method comprises the following steps of: preparing growth factor controlled-release microspheres; forming a substrate; and adsorbing. The invention further provides another rapid forming method for the bone repairing porous bracket. The method comprises a step for preparing growth factor controlled-release microspheres and a step for forming a substrate. The growth factor controlled-release microspheres are introduced into the bracket, bone growth can be induced under the action of the controlled release of growth factors, and inward bone tissue growth is facilitated through a porous structure formed by degradation of the controlled-release microspheres, so that bone tissue regeneration repair is achieved, and bone healing is facilitated effectively. Three-dimensional printing is performed by adding controlled-release microspheres and adopting a rapid forming technology, and a forming process is simple and rapid.
Description
Technical field
The present invention relates to bio-medical material technology and biomedical engineering field, or rather, the present invention relates to a kind of bone repair porous scaffold and quick molding method thereof.
Background technology
At present, because wound, tumor resection, infection and abnormal development etc. are former thereby cause the damaged sickness rate of bone higher, in the existing method, the autologous bone transplanting source is few, and can bring certain misery to patient clinically; There is the rejection problem in allogenic bone transplantation, and restricted by ethics, and its application is restricted.And brought new principle take the generation of biomaterial as basic bone tissue engineer as the new type bone timbering material, for orthopedic and repairing bone defect problem have been brought hope.But the composition of existing artificial bone repair porous scaffold is single, is difficult to satisfy the requirement that bone is repaired.
In addition, rapid shaping technique (Rapid Prototyping, RP) 3 D-printing is applied to the inevitable outcome that the development of personalized bone renovating bracket material is the multidisciplinary mutual cross developments such as biomedicine, material science and Modern Manufacturing Technology, and its maximum driving force is from the urgent needs of clinical treatment.This technology has not only shortened the construction cycle of biomaterial, has reduced R ﹠ D Cost, has solved simultaneously the science and technology difficult problem of some great accurate three-dimensional reconstructions in the clinical medicine invasive techniques in modern age.Particularly more demonstrate its unique advantage at the manufacture view of the artificial bone substitute of complicated shape, solve well skeleton because of individual, age and position diversity, complexity and the accuracy problem in shape and size, can require to produce the bone renovating material that is applicable to its specific (special) requirements arbitrary shape according to patient's Extraordinary.Foreign study mechanism and institution of higher learning have dropped into a large amount of funds and have carried out rapid shaping technique in the research of the aspects such as biomaterial and medical apparatus and instruments processing and manufacturing technology and the exploitation of product, have begun at present to enter clinical use.But existing rapid shaping technique also only for being used for making the single bone holder material of composition, is difficult to satisfy the application demand complicated and changeable of clinical treatment.
Summary of the invention
Technical problem to be solved by this invention is, a kind of bone repair porous scaffold is provided, and can have long-acting bone-inducting active, effectively promotes bone defect healing.
Technical problem to be solved by this invention is, a kind of quick molding method of bone repair porous scaffold is provided, and goes out to have the bone repair porous scaffold of good bone repairing effect with rapid shaping.
For solving the problems of the technologies described above, the invention provides following technical scheme: a kind of bone repair porous scaffold, comprise matrix and growth factor slow-release microsphere with biomimetic porous structure, described growth factor slow-release microsphere is adsorbed in the hole of biomimetic porous structure of matrix or disperse is distributed in the matrix with the matrix material mixing in the matrix forming process.
Further, the raw material of described matrix is the homomixture of polyesters high molecular polymer and inorganic material, wherein, described polyesters high molecular polymer is at least a in the following material: polylactic acid, polyglycolic acid, poly lactic coglycolic acid, polyhydroxyalkanoate, polycaprolactone; Described inorganic material is at least a in the following material: calcium phosphate, calcium sulfate, degradable biological glass.
Further, the carrier microballoons raw material of described growth factor slow-release microsphere is at least a in the following polyesters macromolecular material: polylactic acid, polyglycolic acid, poly lactic coglycolic acid, polyhydroxyalkanoate, polycaprolactone; Perhaps the carrier microballoons raw material of described growth factor slow-release microsphere is at least a in the following polysaccharide macromolecular material: chitosan, hyaluronic acid, hyaluronate, alginic acid, alginate.
Further, described somatomedin is following any one bone morphogenetic protein: BMP-1, BMP-2, BMP-3, BMP-7, BMP-14; Perhaps described somatomedin is following any one transforming growth factor: TGF-α, TGF-β.
Further, the mean diameter of described growth factor slow-release microsphere is 100nm～800 μ m, and carrying drug ratio is 0.005% ~ 20%.
Further, the porosity 50% ~ 99% of described matrix, including macropore and the aperture that the aperture is 200 ~ 1000 μ m is the aperture of 1 ~ 100 μ m.
On the other hand, the present invention also provides a kind of quick molding method for preparing above each described bone repair porous scaffold, comprises the steps:
Preparation growth factor slow-release microsphere step adopts conventional growth factor slow-release microspheres to make the growth factor slow-release microsphere for subsequent use;
The matrix forming step is mixed with slurry with matrix material, and is the matrix with biomimetic porous structure with described sizing material forming with three-dimensional printing technology;
Adsorption step, the growth factor slow-release microsphere is scattered in formation sustained-release micro-spheres suspension in the suitable solvent, the matrix of forming is soaked in this sustained-release micro-spheres suspension, under the negative pressure-pumping condition, the growth factor slow-release microsphere is adsorbed enter in the hole in the biomimetic porous structure of matrix, namely obtains to be loaded with the bone repair porous scaffold of growth factor slow-release microsphere.
Further, in the matrix forming step, when 3 D-printing, the hole of adjacent layer is staggered and mutually corresponding connection.
Aspect another, the present invention also provides a kind of quick molding method for preparing above each described bone repair porous scaffold, comprises the steps:
Preparation growth factor slow-release microsphere step adopts conventional growth factor slow-release microspheres to make the growth factor slow-release microsphere for subsequent use;
The matrix forming step is mixed with slurry with matrix material and growth factor slow-release microsphere mixing, and is the bone repair porous scaffold with biomimetic porous structure with described sizing material forming with three-dimensional printing technology.
Further, in the matrix forming step, when 3 D-printing, the hole of adjacent layer is staggered and mutually corresponding connection.
After adopting technique scheme, the present invention has following beneficial effect at least: the present invention is by introducing the current increasingly extensive growth factor slow-release microsphere of using in biomedical materials field in bone repair porous scaffold, the slow release of somatomedin can long-acting induction of bone growth, and the loose structure that the sustained-release micro-spheres degraded forms makes things convenient for osseous tissue to grow into, thereby reach the osteanagenesis reparation, effectively promote knitting.By adopting polyester macromolecule material and inorganic material composite as the raw material of making matrix, can improve the wherein deficiency during a kind of material of independent use, such as large, the anti-folding of fragility and the shortcoming such as shock resistance is poor, mechanical property is inadequate.The biomaterials such as polyester macromolecule material and inorganic material have good biocompatibility and can form firmly biochemistry key combination with osseous tissue, conduct simultaneously the growth of bone.
And add sustained-release micro-spheres and rapid shaping technique 3 D-printing by using, and can adopt the low temperature rapid forming equipment to prepare the bone support, the moulding process simple and fast, the bone repair porous scaffold bone repairing effect that forms out is good.
The specific embodiment
Need to prove, in the situation that do not conflict, embodiment and the feature among the embodiment among the application can mutually combine, and below in conjunction with specific embodiment the present invention are described in further detail.
The invention provides a kind of bone repair porous scaffold, comprise matrix and growth factor slow-release microsphere with biomimetic porous structure, described growth factor slow-release microsphere is adsorbed in the hole of biomimetic porous structure of matrix or disperse is distributed in the matrix with the matrix material mixing in the matrix forming process.
The raw material of described matrix is the homomixture of polyesters high molecular polymer and inorganic material, wherein, described polyesters high molecular polymer is at least a in the following material: polylactic acid (PLA), polyglycolic acid (PLG), poly lactic coglycolic acid (PLGA), polyhydroxyalkanoate (PHA), polycaprolactone (PCL); Described inorganic material is at least a in the following material: calcium phosphate, calcium sulfate, degradable biological glass, calcium phosphate wherein can be hydroxyapatite (HA), tricalcium phosphate (TCP), calcium metaphosphate (CMP) etc.
The carrier microballoons raw material of described growth factor slow-release microsphere is at least a in the following polyesters macromolecular material: polylactic acid, polyglycolic acid, poly lactic coglycolic acid, polyhydroxyalkanoate, polycaprolactone.In addition, the raw material of described growth factor slow-release microsphere also can be at least a in the following polysaccharide macromolecular material: chitosan, hyaluronic acid, hyaluronate, alginic acid, alginate.
Described somatomedin is following any one bone morphogenetic protein (bone morphogenetic proteins, BMPs): BMP-1, BMP-2, BMP-3, BMP-7, BMP-14; Perhaps described somatomedin is following any one transforming growth factor (transforming growth factor, TGF): TGF-α, TGF-β.
Bone repair porous scaffold of the present invention has biomimetic porous structure, its porosity 50% ~ 99%, forward square hole edge length wherein can be limited between 200 X200 μ m ~ 1000 X1000 μ m, the sidewise hole length of side is limited between 350 X, 200 μ m ~ 350 X, 1000 μ m, and being preset with in addition macropore and the aperture that the aperture is 200 ~ 1000 μ m is the aperture of 1 ~ 100 μ m.
The mass percent of the inorganic matter in the bone repair porous scaffold of forming is 2% ~ 95%, and the mass percent of high molecular polymer is 5% ~ 98%, and the quality of growth factor slow-release microsphere is 0.01% ~ 20% of inorganic matter and high molecular polymer summation quality.The mean diameter of growth factor slow-release microsphere is 100nm～800 μ m, and carrying drug ratio is 0.005% ~ 20%, and the somatomedin that slow release goes out keeps active.
On the other hand, the present invention also provides the quick molding method of more than one each described bone repair porous scaffold, comprises the steps:
Preparation growth factor slow-release microsphere step adopts conventional growth factor slow-release microspheres to make the growth factor slow-release microsphere for subsequent use;
The matrix forming step is mixed with slurry with matrix material, and is the matrix with biomimetic porous structure with described sizing material forming with three-dimensional printing technology;
Adsorption step, the growth factor slow-release microsphere is scattered in formation sustained-release micro-spheres suspension in the suitable solvent, the matrix of forming is soaked in this sustained-release micro-spheres suspension, under the negative pressure-pumping condition, the growth factor slow-release microsphere is adsorbed enter in the hole in the biomimetic porous structure of matrix, namely obtains to be loaded with the bone repair porous scaffold of growth factor slow-release microsphere.
Wherein, in the matrix forming step, when 3 D-printing, the hole of adjacent layer is staggered and mutually corresponding connection.
Aspect another, the present invention also provides the quick molding method of above each the described bone repair porous scaffold of another preparation, comprises the steps:
Preparation growth factor slow-release microsphere step;
The matrix forming step is mixed with slurry with matrix material and growth factor slow-release microsphere mixing, and is the matrix with biomimetic porous structure with described sizing material forming with three-dimensional printing technology, namely obtains to be loaded with the bone repair porous scaffold of growth factor slow-release microsphere.
Wherein, in the matrix forming step, when 3 D-printing, the hole of adjacent layer is staggered and mutually corresponding connection.
Further illustrate the quick molding method of above-mentioned bone repair porous scaffold below in conjunction with embodiment.
Embodiment 1
1, the PLGA microsphere of rhBMP-2 is carried in preparation
Get the PLGA(molecular weight 50kDa of ultra-pure water solution to ten parts by volume of rhBMP-2 of the 50mg/mL of a parts by volume, lactic acid and glycolic polymerization mol ratio are 75/25) dichloromethane (DCM) solution, with the rotating speed emulsifying of 3000rpm 60 seconds, make interior emulsion (w/o) with high speed disperser; In the 30mL deionized water, add the 0.3mL Tween 80, be stirred to and be uniformly dispersed, make outer water; Interior emulsion is added outer water, and the usefulness high speed disperser makes double emulsion (w/o/w) with the rotating speed emulsifying of 5000rpm 60 seconds; DCM volatilization, standing over night were treated in this liquid middling speed stirring in 3 ~ 5 hours.After centrifugal, wash three times, obtain carrying the PLGA microsphere suspension of rhBMP-2, obtain dry microspheres after the lyophilization for subsequent use.
2, preparation PLA/TCP three-dimensional rack matrix
Get three mass parts PLA(molecular weight 100kDa) be dissolved in an amount of dioxane solution, bata-tricalcium phosphate (TCP) powder that adds a mass parts, PLA:TCP=3:1) after the dispersed with stirring composite homogenate is added in the TissFormTM biomaterial former storage tank, default nozzle diameter 0.35mm, forward aperture 600 μ m * 300 μ m; The side direction aperture is 100 μ m * 350 μ m, under the NET document control, carry out N shell scanning, the path of the X of Control Nozzle, Y direction under instrumentation makes its 1/2nd positions of laterally vertically staggering, and makes the matrix with three-dimensional bionic loose structure after the cumulative drying layer by layer.
3, preparation rhBMP-2 Composite Bone support
The rhBMP-2 microsphere disperse is formed the microsphere suspension with alcoholic solution, with printing and matrix be immersed in the microsphere suspension, use negative pressure-pumping, microsphere is adsorbed enters in the hole of matrix, lyophilization or drying at room temperature obtain the rhBMP-2 compound support frame material.
Embodiment 2
1, the microsphere of preparation chitosan-loaded BMP-14
Get chitosan (the molecular weight 250kDa of 1500 mass parts, deacetylation 90%) is dissolved in the acetic acid solution of an amount of 20ml/L, the BMP-14 that gets 1 mass parts is dissolved in the HCl solution of an amount of 4mol/L, the span-80(5ml that slowly adds 90 ~ 200ml after mixing) in the octanol solution, dripping 1 ~ 3ml genipin during magnetic agitation carries out crosslinked, continue to stir stopped reaction behind 40 ~ 60min, and obtain chitosan-loaded BMP-14 microsphere suspension with isopropyl alcohol, petroleum ether and water cyclic washing.Obtain dry microspheres after the lyophilization.
2, BMP-14 microsphere composite is carried in preparation
Get three mass parts PLA(molecular weight 100kDa) be dissolved in an amount of DCM solution, add dispersed with stirring behind bata-tricalcium phosphate (TCP) powder of a mass parts and the 50 ~ 100mg BMP-14 chitosan microball, make composite homogenate.
3,3 D-printing prepares support
Composite homogenate is added in the TissFormTM biomaterial former storage tank default nozzle diameter 0.35mm, forward aperture 600 μ m * 100 μ m; The side direction aperture is 100 μ m * 350 μ m, under the NET document control, carry out N shell scanning, the path of the X of Control Nozzle, Y direction under instrumentation makes its 1/2nd positions of laterally vertically staggering, and makes the bone support with three-dimensional bionic loose structure after the cumulative drying layer by layer.
Embodiment 3
1, the PLA microsphere of TGF-α is carried in preparation
Get the DCM solution of PLA of ultra-pure water solution to ten parts by volume of TGF-α of the 50mg/mL of a parts by volume, with the rotating speed emulsifying of 3000rpm 60 seconds, make interior emulsion (w/o) with high speed disperser; In the 30mL deionized water, add the 0.3mL Tween 80, be stirred to and be uniformly dispersed, make outer water; Interior emulsion is added outer water, and the usefulness high speed disperser makes double emulsion (w/o/w) with the rotating speed emulsifying of 5000rpm 60 seconds; DCM volatilization, standing over night were treated in this liquid middling speed stirring in 3 ~ 5 hours.After centrifugal, wash three times, obtain carrying the PLA microsphere suspension of TGF-α.Obtain dry microspheres after the lyophilization.
2, preparation PLG/HA three-dimensional rack matrix
Get three mass parts PLG(molecular weight 100kDa) be dissolved in dimethyl sulfoxide (DMF) solution of 10 ~ 30ml, after adding the HA powder dispersed with stirring of a mass parts composite homogenate is added in the TissFormTM biomaterial former storage tank, default nozzle diameter 0.35mm, forward aperture 500 μ m * 100 μ m; The side direction aperture is 400 μ m * 350 μ m, under the NET document control, carry out N shell scanning, the path of the X of Control Nozzle, Y direction under instrumentation makes its 1/2nd positions of laterally vertically staggering, and makes the matrix with three-dimensional bionic loose structure after the cumulative drying layer by layer.
3, preparation TGF-α Composite Bone support
TGF-α microsphere disperse is formed the microsphere suspension with alcoholic solution, with printing and three-dimensional rack be immersed in the microsphere suspension, use negative pressure-pumping, microsphere is adsorbed enters in the hole of support, lyophilization or drying at room temperature obtain TGF-α Composite Bone support.
Embodiment 4
1, the microsphere of preparation chitosan-loaded TGF-β
Get chitosan (the molecular weight 250kDa of 1500 mass parts, deacetylation 90%) is dissolved in the acetic acid solution of 20ml/L of 10 ~ 50ml, the TGF-β that gets 1 mass parts is dissolved in the HCl solution of 1 ~ 3ml 4mol/L, the span-80(5ml that slowly adds 90 ~ 200ml after mixing) in the liquid paraffin, dripping 1 ~ 3ml glutaraldehyde during magnetic agitation carries out crosslinked, continue to stir stopped reaction behind 40 ~ 60min, and obtain chitosan with isopropyl alcohol, petroleum ether and water cyclic washing and wrap up TGF-β microsphere suspension.Obtain dry microspheres after the lyophilization.
2, the homogenate of TGF-α microsphere composite is carried in preparation
Get three mass parts PLGA(molecular weight 100kDa) be dissolved in the chloroform soln of 10 ~ 50ml, add dispersed with stirring behind the degradable biological glass of a mass parts and the 50 ~ 100mg TGF-β chitosan microball, make composite homogenate.
3,3 D-printing prepares the bone support
Composite homogenate is added in the TissFormTM biomaterial former storage tank default nozzle diameter 0.35mm, forward aperture 100 μ m * 100 μ m; The side direction aperture is 100 μ m * 350 μ m, under the NET document control, carry out N shell scanning, the path of the X of Control Nozzle, Y direction under instrumentation makes its 1/2nd positions of laterally vertically staggering, and makes the bone support with three-dimensional bionic loose structure after the cumulative drying layer by layer.
Embodiment 5
1, the PLG microsphere of BMP-3 is carried in preparation
Get the chloroform soln of PLG of ultra-pure water solution to ten parts by volume of BMP-3 of the 50mg/mL of a parts by volume, with the rotating speed emulsifying of 3000rpm 60 seconds, make interior emulsion (w/o) with high speed disperser; In the 30mL deionized water, add the 0.3mL Tween 80, be stirred to and be uniformly dispersed, make outer water; Interior emulsion is added outer water, and the usefulness high speed disperser makes double emulsion (w/o/w) with the rotating speed emulsifying of 5000rpm 60 seconds; Chloroform volatilization, standing over night were treated in this liquid middling speed stirring in 3 ~ 5 hours.After centrifugal, wash three times, obtain carrying the PLG microsphere suspension of BMP-3.Obtain dry microspheres after the lyophilization.
2, preparation PLA/ calcium sulfate three-dimensional rack matrix
Get the PLA(molecular weight 100kDa of three mass parts) be dissolved in the DMF solution of 10 ~ 50ml, after adding the calcium sulphate powders dispersed with stirring of a mass parts composite homogenate is added in the TissFormTM biomaterial former storage tank, default nozzle diameter 0.35mm, forward aperture 400 μ m * 100 μ m; The side direction aperture is 500 μ m * 350 μ m, under the NET document control, carry out N shell scanning, the path of the X of Control Nozzle, Y direction under instrumentation makes its 1/2nd positions of laterally vertically staggering, and makes the support matrix with three-dimensional porous structure after the cumulative drying layer by layer.
3, preparation BMP-3 Composite Bone support
The BMP-3 microsphere is disperseed to form the microsphere suspension with alcoholic solution, with printing and the three-dimensional rack matrix be immersed in the microsphere suspension, use negative pressure-pumping, microsphere is adsorbed enters in the hole of matrix, lyophilization or drying at room temperature obtain BMP-3 Composite Bone support.
Although illustrated and described embodiments of the invention, for the ordinary skill in the art, be appreciated that without departing from the principles and spirit of the present invention and can carry out multiple variation, modification, replacement and modification to these embodiment, scope of the present invention is limited by claims and equivalency range thereof.
Claims (10)
1. bone repair porous scaffold, it is characterized in that, described bone repair porous scaffold comprises matrix and the growth factor slow-release microsphere with biomimetic porous structure, and described growth factor slow-release microsphere is adsorbed in the hole of biomimetic porous structure of matrix or disperse is distributed in the matrix with the matrix material mixing in the matrix forming process.
2. bone repair porous scaffold as claimed in claim 1, it is characterized in that, the raw material of described matrix is the homomixture of polyesters high molecular polymer and inorganic material, wherein, described polyesters high molecular polymer is at least a in the following material: polylactic acid, polyglycolic acid, poly lactic coglycolic acid, polyhydroxyalkanoate, polycaprolactone; Described inorganic material is at least a in the following material: calcium phosphate, calcium sulfate, degradable biological glass.
3. bone repair porous scaffold as claimed in claim 1, it is characterized in that, the carrier microballoons raw material of described growth factor slow-release microsphere is at least a in the following polyesters macromolecular material: polylactic acid, polyglycolic acid, poly lactic coglycolic acid, polyhydroxyalkanoate, polycaprolactone; Perhaps the carrier microballoons raw material of described growth factor slow-release microsphere is at least a in the following polysaccharide macromolecular material: chitosan, hyaluronic acid, hyaluronate, alginic acid, alginate.
4. bone repair porous scaffold as claimed in claim 1 is characterized in that, described somatomedin is following any one bone morphogenetic protein: BMP-1, BMP-2, BMP-3, BMP-7, BMP-14; Perhaps described somatomedin is following any one transforming growth factor: TGF-α, TGF-β.
5. bone repair porous scaffold as claimed in claim 1 is characterized in that, the mean diameter of described growth factor slow-release microsphere is 100nm～800 μ m, and carrying drug ratio is 0.005% ~ 20%.
6. bone repair porous scaffold as claimed in claim 1 is characterized in that, the porosity 50% ~ 99% of described matrix, and including macropore and the aperture that the aperture is 200 ~ 1000 μ m is the aperture of 1 ~ 100 μ m.
7. a quick molding method for preparing such as each described bone repair porous scaffold in the claim 1 ~ 6 is characterized in that, comprises the steps:
Preparation growth factor slow-release microsphere step adopts conventional growth factor slow-release microspheres to make the growth factor slow-release microsphere for subsequent use;
The matrix forming step is mixed with slurry with matrix material, and is the matrix with biomimetic porous structure with described sizing material forming with three-dimensional printing technology;
Adsorption step, the growth factor slow-release microsphere is scattered in formation sustained-release micro-spheres suspension in the suitable solvent, the matrix of forming is soaked in this sustained-release micro-spheres suspension, under the negative pressure-pumping condition, the growth factor slow-release microsphere is adsorbed enter in the hole in the biomimetic porous structure of matrix, namely obtains to be loaded with the bone repair porous scaffold of growth factor slow-release microsphere.
8. the quick molding method of bone repair porous scaffold as claimed in claim 7 is characterized in that, in the matrix forming step, when 3 D-printing, the hole of adjacent layer is staggered and mutually corresponding connection.
9. a quick molding method for preparing such as each described bone repair porous scaffold in the claim 1 ~ 6 is characterized in that, comprises the steps:
Preparation growth factor slow-release microsphere step adopts conventional growth factor slow-release microspheres to make the growth factor slow-release microsphere for subsequent use;
The matrix forming step is mixed with slurry with matrix material and growth factor slow-release microsphere mixing, and is the bone repair porous scaffold with biomimetic porous structure with described sizing material forming with three-dimensional printing technology.
10. the quick molding method of bone repair porous scaffold as claimed in claim 9 is characterized in that, in the matrix forming step, when 3 D-printing, the hole of adjacent layer is staggered and mutually corresponding connection.
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-
2012
- 2012-09-27 CN CN201210365799.5A patent/CN102886076B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 许尧祥: "复合壳聚糖微球PLGA支架的制备及其对蛋白缓释作用的实验研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, no. 3, 15 March 2011 (2011-03-15), pages 080 - 30 * |
| 陈国珍等: "骨组织工程支架的设计与制备", 《医疗卫生装备》, vol. 28, no. 12, 31 December 2007 (2007-12-31), pages 29 - 31 * |
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