CN108030958A - The formula and preparation method of 3D printing artificial bone composite fibre albumen stent - Google Patents
The formula and preparation method of 3D printing artificial bone composite fibre albumen stent Download PDFInfo
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- CN108030958A CN108030958A CN201711384592.1A CN201711384592A CN108030958A CN 108030958 A CN108030958 A CN 108030958A CN 201711384592 A CN201711384592 A CN 201711384592A CN 108030958 A CN108030958 A CN 108030958A
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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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/225—Fibrin; Fibrinogen
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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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- 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
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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
- A61L2300/414—Growth factors
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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
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Abstract
Formula the invention discloses 3D printing artificial bone composite fibre albumen stent and preparation method thereof, contains five kinds of medical grade collagen powder, 0.05mol/L acetums, medical grade hydroxyapatite powder, 1% genipin solution of mass fraction, rich platelet fibrin components:Collagen colloid is made in the acetum that medical grade collagen powder is dissolved in 0.05mol/L first, then by medical grade hydroxyapatite powder, collagen colloid, which stirs evenly, is made hydroxyapatite, collagen prints raw material, hollow the Individualized Tissue-engineered Bone is printed by 3D biometric prints machine according to patient's bone defect CT data, transplant in artificial bone scaffold surgical procedure, centrifugation blood samples of patients prepares rich platelet fibrin, insert again in tissue engineered bone hollow lumen, it is made with the hydroxyapatite for promoting human body bone regeneration capability, collagen, rich platelet fibrin artificial bone.The artificial bone can slowly discharge the autologous growth factor in patient's rich platelet fibrin, promote the reparation of defect of human body bone.
Description
Technical field
The invention belongs to pharmaceutical technology field, more particularly to the formula of 3D printing artificial bone composite fibre albumen stent and its
Preparation method.
Background technology
The reparation of large segmental bone defect is always to perplex the problem of orthopedist, and correcting strategy includes autologous bone, allosome at present
Bone and artificial material transplanting etc..Though autologous bone transplanting is the goldstandard for the treatment of, the bleeding of Qu Gu areas, sense can be caused in migration process
Dye;There is immunological rejection, pathophorous risk for homogeneous allogenic bone transplantation;Developing rapidly for bone tissue engineer is lacked to big section bone
The reparation of damage provides a kind of more feasible method.Conventional method prepare stent internal structure often can not people in order to control
, and the shape that 3D printing technique can be directed to bone defect makes contoured cradle to measure for patient;Simultaneously as manufacturing process is subject to
The stringent manipulation of computer, can finely control aperture, the hole link rate of stent, this plays function stent with important work
With.
During 3D printing, bioceramic slurry is extruded from printing head, passes through the method accumulation molding of layered manufacturing, slurry
Can add biotic factor or certain drug in material, whole printing process control carries out at low temperature, containing biotic factor or
The slurry of person's medicine is extruded by printing head, does not destroy the activity of biotic factor and medicine.Hydroxyapatite is a kind of biology
Ceramic material, has excellent biocompatibility and biological degradability, and more at present is applied to bone tissue engineer, bone cement etc.
Correlative study.Collagen is the important organic principle in natural bone tissue, has good biocompatibility, degradability and rush
Into the ability of skeletonization, experimental results demonstrate collagen can promote mesenchymal stem cell to migrate, stick, breed and skeletonization point
Change.Rich platelet fibrin is second generation blood platelet concentrations, and preparation method is simple, and it is small that tridimensional network enlists the services of a large amount of blood
The biotic factor of plate activation release, as the degraded of the netted structure of fibrin slowly discharges, promotes rich platelet fibrin
The organization healing of implanting.By hydroxyapatite, collagen mix carry out low temperature 3D printing artificial bone scaffold, by blood samples of patients from
Rich platelet fibrin is made in the heart, and rich platelet fibrin is inserted in hollow bone stent, is produced using patient itself
Raw cell factor promotes the reparation of patient bone defect, avoids immunological rejection, meanwhile, preparation process is beaten with 3D
Print technology can prepare any aperture, the stent of porosity, be truly realized individualized treatment.
The content of the invention
The technical problems to be solved by the invention are:There is provided 3D printing artificial bone composite fibre albumen stent formula and
Its preparation method, the present invention solves large segmental bone defect well and bone nonunion individual treats this problem.
In order to solve the above technical problems, the technical scheme is that:The formula of 3D printing artificial bone, it is characterised in that:
Using formula as below:Including 5g medical grades collagen powder, 0.05mol/L acetum 25mL, 10g medical grade hydroxylapatite powders
Last (average grain diameter 100nm), the genipin solution 20mL of mass fraction 1%.
Formula of 3D printing artificial bone composite fibre albumen stent described in claim 1 and preparation method thereof is prepared, its
It is characterized in that:Carry out according to the following steps:
(1), collagen colloid is prepared:The 0.05mol/L acetums that 5g medical grade collagen powders are dissolved in 25mL prepare collagen
Colloid;
(2) mix:By collagen/hydroxyapatite mass ratio 1:2 ratio is by the colloid containing 5g collagens and 10g hydroxyl phosphorus
Lime stone powder mixes;
(3), stir:The material that (2) mix is stirred evenly, hydroxyapatite, collagen printing raw material is made, is i.e. biology is beaten
The bio-ink of print machine.
(4), three-dimensional reconstruction:The CT data of patient bone defect are obtained, increase what is be combined with region using Threshold segmentation
Method splits CT images, and obtain layering CT images masking-out (Mask) by Boolean calculation carries out three-dimensional reconstruction afterwards, uses
RepetierHost softwares build personalized hollow bone tissue engineering scaffold three-dimensional digital model, and with hydroxyapatite/glue
Former lotion line and staff control prepares timbering material for raw material by 3D printing technique;
(5), 3D printing:The hydroxyapatite drawn after (3) are stirred is loaded into 3D biometric print machines with collagenous biological ink
(Bioprinter), hollow individuation hydroxyapatite, i.e. collagen people then are printed through 3D biometric prints machine (Bioprinter)
Work bone holder material.
(6), it is crosslinked:The hydroxyapatite/collagen artificial bone that (5) are drawn is placed in the genipin solution of mass fraction 1%
Crosslinking, to increase the intensity of artificial bone scaffold.
(7), it is freeze-dried;By (6) be crosslinked after hydroxyapatite, collagen artificial bone with freeze drier drying 12 it is small when.
(8), preparation and compound rich platelet fibrin:Patient's vein is collected during Engineering Bone stent procedure is transplanted
Blood 10mL, does not take anti-freezing measure, and venous blood is immediately transferred to centrifuge 10min in sterile glass centrifuge tube and under 400g,
Take out the fibrin clot between undermost red blood cell and the cell-free plasma of the superiors.Using sterile gauze from fibre
Fibrillarin grumeleuse extrusion serum obtains autologous fibrin film, and autologous fibrin film is inserted to hollow Engineering Bone stent tube chamber
It is interior, hydroxyapatite/collagen/rich platelet fibrin artificial bone scaffold with induced osteogenesis ability is made.
Further, hydroxyapatite, collagen colloid, rich platelet fibrin are compounded to form hydroxyl in described (8) step
Base apatite, collagen, rich platelet fibrin artificial bone scaffold.
Formula of the 3D printing artificial bone composite fibre albumen stent and preparation method thereof, by the bone defect portion of different patients
Position CT scan and three-dimensional reconstruction, can be with 1:1 individuation customizes the parameters of artificial bone, prepares with the 3D for promoting osteanagenesis
Hydroxyapatite, collagen, rich platelet fibrin artificial bone are printed, and the artificial bone is compounded with the growth factor of patient itself
And the effect of slowly release vascular endothelial growth factor, insulin-like growth factor, transforming growth factor etc. is can reach, through laboratory
Experimental result 3D printing hydroxyapatite, collagen, rich platelet fibrin artificial bone have the significant energy for promoting osteanagenesis
Power, inducing bone mesenchymal stem cell chemotaxis and the differentiation of skeletonization direction, have the function that good osteoacusis and self-bone grafting.This
Invention can be very good to solve large segmental bone defect and bone nonunion individual treats this clinical problem.
Brief description of the drawings
Fig. 1 is preparation flow figure of the present invention;
Fig. 2 is the mixing schematic diagram of medical grade hydroxyapatite powder and medical grade collagen powder;
Fig. 3 is the schematic diagram of 3D biometric print machines;
Fig. 4 is hydroxyapatite/collagen artificial bone schematic diagram;
Fig. 5 is the rich platelet fiber egg schematic diagram in test tube;
Fig. 6 is hydroxyapatite, collagen, rich platelet fibrin artificial bone schematic diagram.
Embodiment
Hereinafter, a variety of specific details are elaborated, in order to provide the saturating of the concept to forming described embodiment basis
Thorough understanding.However, it will be apparent to those skilled in the art that described embodiment can be in these no specific details
In it is some or all in the case of put into practice.In other cases, well-known processing step is not specifically described.
The formula for the 3D printing artificial bone that the present embodiment is enumerated, is made of following raw material:Medical grade collagen powder,
0.05mol/L acetums, medical grade hydroxyapatite powder, 1% genipin solution of mass fraction.
Formula of 3D printing artificial bone composite fibre albumen stent according to claim 1 and preparation method thereof, its
It is characterized in that:Carry out according to the following steps:
(1), collagen colloid is prepared:The 0.05mol/L acetums that 5g medical grade collagen powders are dissolved in 25mL prepare glue
Virgin rubber body;
(2) mix:By collagen/hydroxyapatite mass ratio 1:2 ratio is by the colloid containing 5g collagens and 10g hydroxyl phosphorus
Lime stone powder mixes;
(3) stir:Material prepared by (2) is stirred evenly, obtains hydroxyapatite, collagen printing raw material, is i.e. biology is beaten
The bio-ink of print machine.
(4) three-dimensional reconstruction:The CT data of patient bone defect are obtained, increase what is be combined with region using Threshold segmentation
Method splits CT images, and obtain layering CT images masking-out (Mask) by Boolean calculation carries out three-dimensional reconstruction afterwards, uses
RepetierHost softwares build personalized hollow bone tissue engineering scaffold three-dimensional digital model, and with hydroxyapatite/glue
Former lotion line and staff control prepares artificial bone for raw material by 3D printing technique;
(5) 3D printing:Hydroxyapatite/collagen bio-ink in (3) is loaded into 3D biometric prints machine (Bioprinter),
Then hollow individuation hydroxyapatite/collagen artificial bone is printed by 3D biometric prints machine (Bioprinter).
(6) it is crosslinked:Hydroxyapatite, the collagen artificial bone that (5) are drawn are placed in the genipin solution of mass fraction 1%
Crosslinking, to increase the intensity of artificial bone scaffold.
(7) it is freeze-dried;By (6) be crosslinked after hydroxyapatite, collagen artificial bone with freeze drier drying 12 it is small when.
(8) preparation and compound rich platelet fibrin:Patient's vein is collected during Engineering Bone stent procedure is transplanted
Blood 10mL, does not take anti-freezing measure, and venous blood is immediately transferred to centrifuge 10min in sterile glass centrifuge tube and under 400g,
Take out the fibrin clot between undermost red blood cell and the cell-free plasma of the superiors.Using sterile gauze from fibre
Fibrillarin grumeleuse extrusion serum obtains autologous fibrin film, autologous fibrin film is inserted in hollow artificial bone tube chamber,
Hydroxyapatite, collagen, rich platelet fibrin artificial bone scaffold with induced osteogenesis ability is made.
Medical grade collagen powder:Natural organic matter, has good biological safety, degradability and the energy for promoting skeletonization
Power.
0.05mol/L acetums:Solvent as dissolving collagen powder.
Medical grade hydroxyapatite powder:Common bone tissue engineering scaffold raw material, has the energy for promoting bone tissue mineralising
Power.
The genipin solution of mass fraction 1%:As crosslinking agent to increase the intensity of artificial bone scaffold.
Hydroxyapatite, collagen colloid, rich platelet fibrin are compounded to form hydroxy-apatite in described (8) step
Stone, collagen, rich platelet fibrin artificial bone scaffold.
Formula of the 3D printing artificial bone composite fibre albumen stent and preparation method thereof, by the bone defect portion of different patients
Position CT scan and three-dimensional reconstruction, can be with 1:1 individuation customizes the parameters of artificial bone, prepares with the 3D for promoting osteanagenesis
Hydroxyapatite, collagen, rich platelet fibrin artificial bone are printed, and the artificial bone is compounded with the growth factor of patient itself
And the effect of slowly release vascular endothelial growth factor, insulin-like growth factor, transforming growth factor etc. is can reach, through laboratory
Experimental result 3D printing hydroxyapatite, collagen, rich platelet fibrin artificial bone have the significant energy for promoting osteanagenesis
Power, inducing bone mesenchymal stem cell chemotaxis and the differentiation of skeletonization direction, have the function that good osteoacusis and self-bone grafting.This
Invention can be very good to solve large segmental bone defect and bone nonunion individual treats this clinical problem.
The present invention is not limited to above-mentioned specific embodiment, those of ordinary skill in the art from above-mentioned design,
Without performing creative labour, a variety of conversion made, are within the scope of the present invention.
Claims (3)
1.3D prints the formula of artificial bone composite fibre albumen stent, it is characterised in that:Using formula as below:Including 5g medical grades
Collagen powder, 0.05mol/L acetum 25mL, 10g medical grade hydroxyapatite powders (average grain diameter 100nm), quality point
The genipin solution 20mL of number 1%.
2. preparing formula of 3D printing artificial bone composite fibre albumen stent described in claim 1 and preparation method thereof, it is special
Sign is:Carry out according to the following steps:
(1) collagen colloid is prepared:The 0.05mol/L acetums that 5g medical grade collagen powders are dissolved in 25mL prepare collagen glue
Body;
(2) mix:By collagen/hydroxyapatite mass ratio 1:2 ratio is by the colloid containing 5g collagens and 10g hydroxyapatites
Powder mixes;
(3) stir:The material that (2) mix is stirred evenly, hydroxyapatite/collagen printing raw material, i.e. biometric print machine is made
Bio-ink.
(4) three-dimensional reconstruction:The CT data of patient bone defect are obtained, increase the method being combined with region using Threshold segmentation
Split CT images, obtain layering CT images masking-out (Mask) by Boolean calculation carries out three-dimensional reconstruction afterwards, uses
RepetierHost softwares build personalized hollow bone tissue engineering scaffold three-dimensional digital model, and with hydroxyapatite, glue
Former lotion line and staff control prepares timbering material for raw material by 3D printing technique;
(5) 3D printing:The hydroxyapatite drawn after (3) are stirred is loaded into 3D biometric print machines with collagenous biological ink
(Bioprinter), it is then artificial through the hollow individuation hydroxyapatite of 3D biometric prints machine (Bioprinter) printing, collagen
Bone holder material.
(6) it is crosslinked:The hydroxyapatite/collagen artificial bone that (5) are drawn is placed in the genipin solution of mass fraction 1% and is handed over
Connection, to increase the intensity of artificial bone scaffold.
(7) it is freeze-dried;By (6) be crosslinked after hydroxyapatite, collagen artificial bone with freeze drier drying 12 it is small when.
(8) preparation and compound rich platelet fibrin:Venous Blood is collected during Engineering Bone stent procedure is transplanted
10mL, does not take anti-freezing measure, and venous blood is immediately transferred to centrifuge 10min in sterile glass centrifuge tube and under 400g, is taken
Go out the fibrin clot between undermost red blood cell and the cell-free plasma of the superiors.Using sterile gauze from fiber
Fibrin clot extrusion serum obtains autologous fibrin film, and autologous fibrin film is inserted to hollow Engineering Bone stent tube chamber
It is interior, hydroxyapatite, collagen, rich platelet fibrin artificial bone scaffold with induced osteogenesis ability is made.
3. formula of 3D printing artificial bone composite fibre albumen stent according to claim 2 and preparation method thereof, it is special
Sign be in described (8) step hydroxyapatite, collagen colloid, rich platelet fibrin be compounded to form hydroxyapatite,
Collagen, rich platelet fibrin artificial bone scaffold.
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Cited By (8)
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CN110101914A (en) * | 2019-05-04 | 2019-08-09 | 西北工业大学 | A kind of Prevascularized two-phase artificial bone scaffold and preparation method thereof |
CN110693724A (en) * | 2019-11-05 | 2020-01-17 | 浙江大学 | Tooth mineralizing liquid and mineralizing method thereof |
CN112704555A (en) * | 2021-01-26 | 2021-04-27 | 山东建筑大学 | Preparation method of degradable porous ulna middle-end fracture connector |
CN112870450A (en) * | 2021-01-28 | 2021-06-01 | 中南大学湘雅医院 | Metformin-loaded artificial bone material and method for preparing artificial bone |
CN113969066A (en) * | 2020-07-23 | 2022-01-25 | 固安县朝阳生物科技有限公司 | Bone density radiation image equivalent material |
CN114867500A (en) * | 2019-12-18 | 2022-08-05 | 基立福环球运营有限公司 | Bone composite material and composition for preparing bone composite material |
CN114939226A (en) * | 2022-07-25 | 2022-08-26 | 中南大学 | Pancreatin inactivation stent drainage tube applied to pancreaticojejunostomy and preparation method thereof |
CN116271222A (en) * | 2023-03-28 | 2023-06-23 | 广东医科大学 | Bone tissue engineering scaffold and preparation method and application thereof |
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CN103990182A (en) * | 2014-05-30 | 2014-08-20 | 东华大学 | Three-dimensional scaffold material for bone tissue repair and preparation method thereof |
CN104826171A (en) * | 2015-04-23 | 2015-08-12 | 西安点云先进材料科技有限公司 | Material increase manufacturing method of multi-scale biomimetic artificial bone support |
CN104958785A (en) * | 2015-06-05 | 2015-10-07 | 中国人民解放军军事医学科学院卫生装备研究所 | Composite bone repairing material of two-stage three-dimensional structure and preparing method of composite bone repairing material |
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CN103990182A (en) * | 2014-05-30 | 2014-08-20 | 东华大学 | Three-dimensional scaffold material for bone tissue repair and preparation method thereof |
CN104826171A (en) * | 2015-04-23 | 2015-08-12 | 西安点云先进材料科技有限公司 | Material increase manufacturing method of multi-scale biomimetic artificial bone support |
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CN110101914A (en) * | 2019-05-04 | 2019-08-09 | 西北工业大学 | A kind of Prevascularized two-phase artificial bone scaffold and preparation method thereof |
CN110693724A (en) * | 2019-11-05 | 2020-01-17 | 浙江大学 | Tooth mineralizing liquid and mineralizing method thereof |
CN114867500A (en) * | 2019-12-18 | 2022-08-05 | 基立福环球运营有限公司 | Bone composite material and composition for preparing bone composite material |
CN113969066A (en) * | 2020-07-23 | 2022-01-25 | 固安县朝阳生物科技有限公司 | Bone density radiation image equivalent material |
CN112704555A (en) * | 2021-01-26 | 2021-04-27 | 山东建筑大学 | Preparation method of degradable porous ulna middle-end fracture connector |
CN112870450A (en) * | 2021-01-28 | 2021-06-01 | 中南大学湘雅医院 | Metformin-loaded artificial bone material and method for preparing artificial bone |
CN114939226A (en) * | 2022-07-25 | 2022-08-26 | 中南大学 | Pancreatin inactivation stent drainage tube applied to pancreaticojejunostomy and preparation method thereof |
CN116271222A (en) * | 2023-03-28 | 2023-06-23 | 广东医科大学 | Bone tissue engineering scaffold and preparation method and application thereof |
CN116271222B (en) * | 2023-03-28 | 2023-12-01 | 广东医科大学 | Bone tissue engineering scaffold and preparation method and application thereof |
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