CN107823702A - A kind of manufacture method of 3D printing artificial bone - Google Patents
A kind of manufacture method of 3D printing artificial bone Download PDFInfo
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- CN107823702A CN107823702A CN201711146944.XA CN201711146944A CN107823702A CN 107823702 A CN107823702 A CN 107823702A CN 201711146944 A CN201711146944 A CN 201711146944A CN 107823702 A CN107823702 A CN 107823702A
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- 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
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- 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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- 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
- B33Y50/00—Data acquisition or data processing for additive manufacturing
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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
- B33Y70/00—Materials specially adapted for additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
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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
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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- A—HUMAN NECESSITIES
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- 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
A kind of manufacture method for 3D printing artificial bone that the embodiment of the present application provides, is related to field of medical technology, methods described includes：3D figures are obtained by three dimensional CT；The 3D models of closure bone window are obtained according to the 3D figures；Obtain the first sensitive drug；The second sensitive drug is obtained, percentage by weight is dissolved into solvent for 0.1% 20% copolymer containing lactic acid acetic acid with Isosorbide-5-Nitrae dioxane；First sensitive drug is dissolved in the solvent, and the first suspension is made；Percentage by weight will be included in first suspension and is configured to the first decorating film for 5% 50% calcium containing compound；Second sensitive drug is dissolved in the solvent, and the second suspension is made；After first decorating film is added in second suspension, it is that raw material is configured to the first creamy material to add the calcium containing compound that percentage by weight is 0.5% 30%；First creamy material is added in 3D printer and printed, forms the first artificial bone.Solve the technical problem that prior art can not make medicine stay in affected part, reach and be advantageous to drug blockage, the later stage can increase the technique effect of bone amount.
Description
Technical field
The present invention relates to field of medical technology, more particularly to a kind of manufacture method of 3D printing artificial bone.
Background technology
Osteomyelitis is the infection and destruction of a kind of bone, and it is by aerobic or anaerobic bacteria, mycobacteria and fungus-caused.In bone
After generally requiring penetrability bone injury site in the scorching treatment of marrow, it is filled by materials such as bone cements.
But present inventor has found above-mentioned technology extremely during inventive technique scheme in realizing the embodiment of the present application
Following technical problem less be present：
In the prior art, in the clinical treatment of osteomyelitis, often there are the mode for window of boning and open seam, at present clinical practice
Slow releasing pharmaceutical, shape is single, simple in construction, at the same without reference to windowing closed system, do not simply fail to meet various inhomogeneities
The requirement of type bone surgery, simultaneously because not having bone window closed system so that medicine flows out, it is impossible to which staying in medicine needs to play
The position of effect.
The content of the invention
The embodiment of the present application is solved in the prior art due to not having by providing a kind of manufacture method of 3D printing artificial bone
There is bone window closed system, the requirement for meeting various types of bone surgeries is not simply failed to, simultaneously because there is no bone window closed shape
System so that medicine flows out, it is impossible to makes medicine stay in the technical problem at the position that needs play a role, reached makes according to 3D printing
Artificial bone coincide with bone window structure, is advantageous to drug blockage, will not flow out medicine, while the later stage can increase the technology of bone amount
Effect.
In view of the above problems, it is proposed that the embodiment of the present application is to provide a kind of manufacture method of 3D printing artificial bone.
The embodiment of the present application provides a kind of manufacture method of 3D printing artificial bone, and methods described includes：Pass through three dimensional CT
Obtain 3D figures；The 3D models of closure bone window are obtained by modeling technique according to the 3D figures；Obtain the first sensitive drug；
The second sensitive drug is obtained, wherein the sensitiveness of first sensitive drug is less than second sensitive drug；Will weight
The copolymer containing lactic acid acetic acid that amount percentage is 0.1%-20% is dissolved into solvent with 1,4- dioxane；In the solvent
Middle dissolving first sensitive drug, and the first suspension is made；It is by percentage by weight is included in first suspension
5%-50% calcium containing compound is configured to the first decorating film；Second sensitive drug is dissolved in the solvent, and is made
Into the second suspension；After first decorating film is added in second suspension, addition percentage by weight is 0.5%-
30% calcium containing compound is that raw material is configured to the first creamy material；First creamy material is added in biological 3D printer
Printed, form the first artificial bone.
Preferably, methods described also includes：Obtain the 3rd sensitive drug；The 4th sensitive drug is obtained, wherein, it is described
The sensitiveness of second sensitive drug is less than the 3rd sensitive drug, and the sensitiveness of the 3rd sensitive drug is less than institute
State the 4th sensitive drug；The 3rd sensitive drug is dissolved in the solvent, and the 3rd suspension is made；By described
The calcium containing compound that percentage by weight is 5%-50% is included in three suspensions and is configured to the second decorating film；It is molten in the solvent
The 4th sensitive drug is solved, and the 4th suspension is made；After second decorating film being added in the 4th suspension,
It is that raw material is configured to the second creamy material to add the calcium containing compound that percentage by weight is 0.5%-30%；By second paste
Material is added in the biological 3D printer, and is printed based on first artificial bone, forms the second artificial bone.
Preferably, the calcium containing compound that percentage by weight is 5%-50% will be included in first suspension and is configured to the
After one decorating film, methods described also includes：The 5th sensitive drug is obtained, wherein, the sensitiveness of the 5th sensitive drug
Higher than first sensitive drug；The 5th sensitive drug is dissolved in the solvent, and the 5th suspension is made；
After adding first decorating film in 5th suspension, it is included in the calcium containing compound that percentage by weight is 5%-50% and configures
Into the 3rd decorating film.
Preferably, methods described also includes：Obtain the 6th sensitive drug, wherein, the 6th sensitive drug it is quick
Perception is higher than the 5th sensitive drug；The 6th sensitive drug is dissolved in the solvent, and it is suspended to be made the 6th
Liquid；After adding the 3rd decorating film in the 6th suspension, the calcic chemical combination that percentage by weight is 5%-50% is included in
Thing is configured to the 4th decorating film.
Preferably, methods described is additionally included in add the 4th decorating film in second suspension after, add weight
The calcium containing compound that percentage is 0.5%-30% is that raw material is configured to the 3rd creamy material；3rd creamy material is added
Printed in the biological 3D printer, form third party's work bone.
The one or more technical schemes provided in the embodiment of the present application, have at least the following technical effects or advantages：
1st, the manufacture method for a kind of 3D printing artificial bone that the embodiment of the present application provides, 3D figures are obtained by three dimensional CT；
The 3D models of closure bone window are obtained by modeling technique according to the 3D figures；Obtain the first sensitive drug；It is quick to obtain second
Sensitive drug, wherein the sensitiveness of first sensitive drug is less than second sensitive drug；It is by percentage by weight
The 0.1%-20% copolymer containing lactic acid acetic acid is dissolved into solvent with 1,4- dioxane；In the solvent described in dissolving
First sensitive drug, and the first suspension is made；It is 5%-50%'s that percentage by weight will be included in first suspension
Calcium containing compound is configured to the first decorating film；Second sensitive drug is dissolved in the solvent, and it is suspended to be made second
Liquid；After first decorating film is added in second suspension, add percentage by weight and contain calcification for 0.5%-30%
Compound is that raw material is configured to the first creamy material；First creamy material is added in biological 3D printer and printed, shape
Into the first artificial bone.In the ointment-containing body material of artificial bone described herein, due to consolidating containing some carrying different pharmaceuticals
Shape thing, solve in the prior art due to there is no bone window closed system, do not simply fail to meet various types of bone surgeries
It is required that simultaneously because there is no bone window closed system so that medicine flows out, it is impossible to medicine is stayed in the position that needs play a role
Technical problem, reached makes artificial bone be coincide with bone window structure according to 3D printing, is advantageous to drug blockage, will not make medicine stream
Go out, while the later stage can increase the technique effect of bone amount.
2. the embodiment of the present application is by obtaining the 3rd sensitive drug；The 4th sensitive drug is obtained, wherein, described second
The sensitiveness of sensitive drug is less than the 3rd sensitive drug, and the sensitiveness of the 3rd sensitive drug is less than described the
Four sensitive drugs；The 3rd sensitive drug is dissolved in the solvent, and the 3rd suspension is made；Described 3rd is hanged
The calcium containing compound that percentage by weight is 5%-50% is included in turbid and is configured to the second decorating film；Institute is dissolved in the solvent
The 4th sensitive drug is stated, and the 4th suspension is made；After adding second decorating film in the 4th suspension, add
The calcium containing compound that percentage by weight is 0.5%-30% is that raw material is configured to the second creamy material；By second creamy material
Add in the biological 3D printer, and printed based on first artificial bone, form the second artificial bone.Reach according to trouble
Person's state of an illness needs to select multi-medicament, carries the decorating film of different pharmaceutical respectively by multilayer artificial bone, further extends sustained release
Time and the technique effect of substep medication.
3. the embodiment of the present application by obtain the 5th sensitive drug, wherein, the sensitiveness of the 5th sensitive drug
Higher than first sensitive drug；The 5th sensitive drug is dissolved in the solvent, and the 5th suspension is made；
After adding first decorating film in 5th suspension, it is included in the calcium containing compound that percentage by weight is 5%-50% and configures
Into the 3rd decorating film；The 6th sensitive drug is obtained, wherein, the sensitiveness of the 6th sensitive drug is quick higher than the described 5th
Sensitive drug；The 6th sensitive drug is dissolved in the solvent, and the 6th suspension is made；In the 6th suspension
After middle addition the 3rd decorating film, it is included in the calcium containing compound that percentage by weight is 5%-50% and is configured to the 4th decorating film；
After the 4th decorating film is added in second suspension, the calcium containing compound that percentage by weight is 0.5%-30% is added
The 3rd creamy material is configured to for raw material；3rd creamy material is added in the biological 3D printer and printed, shape
Into third party's work bone.Reach is needed to select multi-medicament according to conditions of patients, and consolidating for a variety of different pharmaceuticals is carried by artificial bone
Shape thing, further extend the technique effect of slow-release time and substep medication.
4. the embodiment of the present application by by the copolymer containing lactic acid acetic acid that percentage by weight is 0.1%-20% with 1,
4- dioxane is dissolved into solvent；First sensitive drug is dissolved in the solvent, and the first suspension is made；By institute
State be included in the first suspension percentage by weight be 5%-50% calcium containing compound be configured to the first decorating film；In the solvent
Middle dissolving second sensitive drug, and the second suspension is made；First solid fraction is added in second suspension
After thing, it is that raw material is configured to the first creamy material to add the calcium containing compound that percentage by weight is 0.5%-30%；By described
One creamy material is added in biological 3D printer and printed, and forms the first artificial bone.Due to said ratio material in vivo not
Easily decompose, a variety of different pharmaceuticals is discharged successively, further reached substep medication and extended the technology effect of slow-release time
Fruit.
Described above is only the general introduction of technical solution of the present invention, in order to better understand the technological means of the present invention,
And can be practiced according to the content of specification, and in order to allow above and other objects of the present invention, feature and advantage can
Become apparent, below especially exemplified by the embodiment of the present invention.
Brief description of the drawings
, below will be to embodiment or description of the prior art in order to illustrate more clearly of the technical scheme in the embodiment of the present application
In the required accompanying drawing used be briefly described, it should be apparent that, drawings in the following description are some realities of the application
Example is applied, for those of ordinary skill in the art, without having to pay creative labor, can also be attached according to these
Figure obtains other accompanying drawings.
Fig. 1 is a kind of schematic flow sheet of the manufacture method for 3D printing artificial bone that the embodiment of the present application provides；
Fig. 2 is the schematic flow sheet of the manufacture method for another 3D printing artificial bone that the embodiment of the present application provides；
Fig. 3 is the schematic flow sheet of the manufacture method for another 3D printing artificial bone that the embodiment of the present application provides.
Embodiment
A kind of manufacture method methods described for 3D printing artificial bone that the embodiment of the present application provides includes：Obtained by three dimensional CT
Obtain 3D figures；The 3D models of closure bone window are obtained by modeling technique according to the 3D figures；Obtain the first sensitive drug；Obtain
The second sensitive drug is obtained, wherein the sensitiveness of first sensitive drug is less than second sensitive drug；By weight
Percentage is that the 0.1%-20% copolymer containing lactic acid acetic acid is dissolved into solvent with 1,4- dioxane；In the solvent
First sensitive drug is dissolved, and the first suspension is made；It is by percentage by weight is included in first suspension
5%-50% calcium containing compound is configured to the first decorating film；Second sensitive drug is dissolved in the solvent, and is made
Into the second suspension；After first decorating film is added in second suspension, addition percentage by weight is 0.5%-
30% calcium containing compound is that raw material is configured to the first creamy material；First creamy material is added in biological 3D printer
Printed, form the first artificial bone.In the ointment-containing body material of artificial bone described herein, due to being carried not containing some
With the decorating film of medicine, solve in the prior art due to there is no bone window closed system, do not simply fail to meet various types
The requirement of bone surgery, simultaneously because not having bone window closed system so that medicine flows out, it is impossible to make medicine stay in needs and play and make
The technical problem at position, reached makes artificial bone be coincide with bone window structure according to 3D printing, is advantageous to drug blockage, will not
Flow out medicine, while the later stage can increase the technique effect of bone amount.
The exemplary embodiment of the disclosure is more fully described below with reference to accompanying drawings.Although the disclosure is shown in accompanying drawing
Exemplary embodiment, it being understood, however, that may be realized in various forms the disclosure without should be by embodiments set forth here
Limited.On the contrary, these embodiments are provided to facilitate a more thoroughly understanding of the present invention, and can be by the scope of the present disclosure
Completely it is communicated to those skilled in the art.
In order to become apparent from a kind of manufacture method for 3D printing artificial bone that open the embodiment of the present application is provided, it is described below
Some terms.
1st, 3D printer, also known as three-dimensional printer (3DP), it is the one of a kind of increases material manufacturing technology, i.e. RP technique
Kind machine, it is a kind of based on mathematical model file, can be glued with special wax material, powdery metal, plastics or ceramics etc.
Condensation material, the object of three-dimensional is manufactured by printing jointing material from level to level.For the application, using biological 3D
Printer, comparatively speaking, it is particular in that its material used is biomaterial, such as described in the embodiment of the present application
The first creamy material etc..
2nd, the copolymer of lactic acid acetic acid includes Poly(D,L-lactide-co-glycolide, PLGA, PLA, PLG etc., and different proportion
Mixture.Poly(D,L-lactide-co-glycolide (poly (lactic-co-glycolic acid), PLGA) is by two kinds of lists
Body --- lactic acid and hydroxyacetic acid are polymerized at random, are a kind of degradable functional polymer organic compounds, have good
Biocompatibility, the performance of nontoxic, good encystation and film forming, be widely used in pharmacy, medical engineering material and modern times
Chemical industry field.In the U.S., PLGA is formally included into American Pharmacopeia by FDA certifications as pharmaceutic adjuvant.
3rd, calcium containing compound includes hydroxyapatite, tricalcium phosphate, the mixture of calcirm-fluoride and different proportion.Hydroxy-apatite
Stone, also known as hydroxyapatite, alkali calcium phosphate, it is apatite calcium (Ca5(PO4)3(OH) mineralizing naturally).But often write
Into (Ca10(PO4)6(OH)2) form with it is prominent it be dimeric：Hydroxyl and apatite.OH-group can be fluorinated thing,
Chloride and carbanion replace, and generate fluorine-based apatite or chloro apatite, calcium ion therein can be by various metals
Ion is replaced by the way that ion-exchange reactions occurs, and forms the M apatite (metal of M representative substitution calcium ions of corresponding metal ion
Ion).Hydroxyapatite (HA) is the host inorganic constituent of vertebrate skeletal and tooth, hydroxyl phosphorus in the enamel of people
The content of lime stone about 96Wt.% (92Vol.%), 69Wt.% is also accounted in bone.Hydroxyapatite has excellent biology
Compatibility and bioactivity, and can have as a kind of bone or the inducible factor of tooth in oral hygiene to tooth
Preferable remineralization, desensitization and whitening function.Experiment proves HA particles and enamel good biocompatibility, and compatibility is high, its
Mineralized liquid can be effectively formed remineralization deposition, prevent calcium ion from being lost in, solve the problems, such as enamel decalcification, fundamentally pre- preventing decayed tooth
Tooth disease.Toothpaste containing HA materials has strong suction-operated to sialoprotein, glucan, can reduce the bacterial plaque in patient oral cavity,
Promote gingivitis healing, have preferable preventive and therapeutic effect to dental caries, periodontosis
4th, chitosan (chitosan) is also known as chitosan, is by de- second by the chitin that nature is widely present
Acyl acts on what is obtained, and chemical name is Chitosan (1-4) -2- amino-B-D glucose.From 1859, Frenchman Rouget
After obtaining chitosan first, the biological functionality and compatibility of this natural polymer, blood compatibility, security, microorganism
The premium properties such as degradability by all trades and professions extensive concern, medicine, food, chemical industry, cosmetics, water process, METAL EXTRACTION and
The application study of the numerous areas such as recovery, biochemical and biomedical engineering achieves major progress.For patient, chitosan drop blood
Fat, the existing research report of hypoglycemic effect.Meanwhile chitosan is included in state food additive as thickener, fruit glaze agent
Use standard GB-2760.
Embodiment one
Fig. 1 is a kind of schematic flow sheet of the manufacture method for 3D printing artificial bone that the embodiment of the present application provides.Such as Fig. 1 institutes
Show, methods described includes：
Step 101：3D figures are obtained by three dimensional CT；
Specifically, by doing three dimensional CT to patient affected part, the 3D solid figures in affected part, above-mentioned 3D solid figures energy are obtained
Enough shapes for really seeing affected part bone.For example, a patient suffers from bone tumour, after surgery excision bone tumour, affected part
Bone can leave breach, and the breach is different according to the size shape of bone tumour and determines, it may be said that every is suffered from excision bone tumour
Breach afterwards is all different, so, by three dimensional CT, can obtain and the shape of subjects bones' breach, size identical
Figure.
Step 102：The 3D models of closure bone window are obtained by modeling technique according to the 3D figures；
Specifically, according to the 3D figures, using computer software by modeling technique, construct and the patient bone
The 3D models for the closure bone window that bone breach matches, the closure bone window 3D models are the mould for filling up subjects bones' breach
Type.It is high with subjects bones' breach goodness of fit by the artificial bone 3D models that 3D modeling constructs, solve in current clinical practice
Slow releasing pharmaceutical used, shape is single, simple in construction, can not meet the deficiency of various types of bone surgery requirements.Such as
Bone window is too narrow, and plug is not entered；Or bone window is too big, it is difficult to closes, after suturing on the contrary so that the problem of medicine used flows out.
After 3D printing, drug composite system can be made to be matched with bone window structure, beneficial to filling, and bone can be pressed in closure
Window removes bone, i.e. the scarce size of bone, rationally designs closure 3D printing artificial bone, plays the closing for being advantageous to medicine, will not
The effect for flowing out medicine.
Step 103：Obtain the first sensitive drug；
Specifically, sensitive drug refers in osteomyelitis therapeutic process, and carrying out long-term sustained release for destination object controls
Medicine needed for treating.Wherein, the first sensitive drug, the second sensitiveness medicine can be divided into according to the height of drug susceptibility
Thing, the 3rd sensitive drug, the 4th sensitive drug etc., wherein, can be with according to the sensitiveness high and low level for destination object
It is defined as：The sensitiveness of first sensitive drug is less than second sensitive drug, and the sensitiveness of the second sensitive drug is low
In the 3rd sensitive drug, the sensitiveness of the 3rd sensitive drug is less than the 4th sensitive drug, the like.
Further, the setting for sensitiveness high and low level can be obtained by the way of proportioning, such as by experimental data
More conventional combination is obtained, for example A classes sensitive drug and B classes sensitive drug proportioning are relatively adapted to first kind destination object, C classes
Sensitive drug and D classes sensitive drug are relatively adapted to the second class destination object, and such as penicillin, gentamicin, streptomysin can
With the demand according to patient to medicine, it is combined, as example, the sensitiveness height that can design different ratio mode is different
The combination of medicine.
Step 104：The second sensitive drug is obtained, wherein, the sensitiveness of first sensitive drug is less than described the
Two sensitive drugs；
Specifically, the application defines different sensitive drugs, i.e. the first sensitive drug, the second sensitiveness medicine
Thing, the 3rd sensitive drug, the 4th sensitive drug etc..Why different sensitive drug is defined, it is therefore intended that by difference
Sensitive drug be placed in the different aspects of different artificial bones, and pass through first outside and then inside isolation；Similarly, some people
Contain the microballoon with medicine in work bone, the microballoon can be arranged to sandwich construction according to the state of an illness, different sensitive drugs is put
Different sensitive drugs are constantly released to target in the different aspects of different microballoons, and by first outside and then inside isolation
Object, and then realize the technique effect of long-term sustained release treatment.Pin is reached according to the result of above-mentioned sensitive experiment meanwhile, it is capable to realize
To the technique effect of property treatment.
Step 105：By the 1,4- dioxane of the copolymer containing lactic acid acetic acid that percentage by weight is 0.1%-20%
It is dissolved into solvent；
Step 106：First sensitive drug is dissolved in the solvent, and the first suspension is made；
Specifically, in step 130 and step 140, the first sensitive drug is placed in into above-mentioned percentage by weight is
The 0.1%-20% copolymer containing lactic acid acetic acid is dissolved into solvent with Isosorbide-5-Nitrae-dioxane, and it is suspended to be configured to first
Liquid；Wherein, the copolymer of lactic acid acetic acid can be Poly(D,L-lactide-co-glycolide, PLGA, PLA, PLG etc., or not year-on-year
The mixture of example, wherein, PLA-alkyl acetate multipolymer that percentage by weight is 1% is dissolved into Isosorbide-5-Nitrae-dioxane
Solvent is preferred embodiment.Due to the functional polymer organic compound that above-mentioned material is degradable, there is good biofacies
Capacitive, pharmaceutic adjuvant can be used as.So the embodiment of the present application is used to house the first sensitiveness medicine from above-mentioned material as carrier
Thing.Further, above-mentioned first sensitive drug can be powdered then to realize and the first suspension is formed in above-mentioned solvent.
Step 107：The calcium containing compound that percentage by weight is 5%-50% will be included in first suspension to be configured to
First decorating film；
Specifically, hydroxyapatite, tricalcium phosphate, calcirm-fluoride and calcium containing compound are vertebrate skeletal and tooth
Host inorganic part, it may have excellent biocompatibility and bioactivity, meanwhile, its mineralized liquid can be effectively formed again
Mineralising deposits, therefore uses percentage by weight the first suspension can be configured into the first solid fraction for 5%-50% calcium containing compound
Thing；Wherein, calcium containing compound can be hydroxyapatite, tricalcium phosphate, the mixture of calcirm-fluoride and different proportion, wherein,
It is preferred reality that the hydroxyapatite that percentage by weight is 10%-15% is included in first suspension and is configured to the first decorating film
Apply example.Above-mentioned first decorating film is the microballoon described in those skilled in the art, and the shape of the decorating film is not particularly limited,
It can be added in the ointment material of printing artificial bone, and then increase slow release effect.
Step 108：Second sensitive drug is dissolved in the solvent, and the second suspension is made；
Step 109：After first decorating film is added in second suspension, addition percentage by weight is 0.5%-
30% calcium containing compound is that raw material is configured to the first creamy material；
Specifically, in step 160 and step 170, second sensitive drug is dissolved in the solvent, and make
Into the second suspension, second sensitive drug can be powdered, then realize and described second is formed in above-mentioned solvent
Suspension, then first decorating film is dispersed randomly in second suspension, adding percentage by weight is
0.5%-30% calcium containing compound is that raw material is configured to the first creamy material.
Further, due to hydroxyapatite, tricalcium phosphate, calcirm-fluoride and calcium containing compound are vertebrate skeletal and tooth
The host inorganic part of tooth, it may have excellent biocompatibility and bioactivity, meanwhile, its mineralized liquid being capable of effective shape
Deposited into remineralization, that is to say, that add above-mentioned hydroxyapatite in the volume, tricalcium phosphate, calcirm-fluoride and containing calcification
The ratio of compound is bigger, and obtained material hardness is bigger, easy degree of decomposition is lower.So the first paste material by making preparation
The hydroxyapatite of material, tricalcium phosphate, calcirm-fluoride and calcium containing compound content are less than the hydroxyapatite of first decorating film,
Tricalcium phosphate, calcirm-fluoride and calcium containing compound content, after reaching and first decomposing first creamy material, then decompose described
One decorating film, and then realize that the material of hypersensitivity first discharges, discharged after the material of hyposensitivity, be finally reached secondary sustained release,
And then increase slow release effect.
Step 110：First creamy material is added in biological 3D printer and printed, forms the first artificial bone.
Specifically, the first creamy material for meeting biological 3D printer input requirements is added in biological 3D printer
Row 3D printing, because 3D printing technique already belongs to basic technology, therefore the embodiment of the present application is no longer specifically described 3D printer
Print procedure and method.It should be noted that the structure of above-mentioned 3D printer printing should be with the bone phase shortage needed for destination object
Match somebody with somebody, that is to say, that by the personalization features of 3D printing technique, can be lacked as destination object with the bone of destination object, be beaten with 3D
Print technology is means, prints the 3D printing artificial bone matched with bone phase shortage.Above-mentioned 3D printing technique solves clinical at present answer
The slow releasing pharmaceutical used in, shape is single, simple in construction, can not meet the deficiency of various types of bone surgery requirements.Than
As said, bone window is too narrow, and plug is not entered；Or bone window is too big, it is difficult to closes, after suturing on the contrary so that the medicine outflow used
Problem.After 3D printing, drug composite system can be made to be matched with bone window structure, beneficial to filling, and can in closure
By bone window or removal bone, the i.e. scarce size of bone, to rationally design closure 3D printing artificial bone, play the envelope for being advantageous to medicine
Close, the effect that will not flow out medicine.
Embodiment two
In order to realize the use of more kinds of sensitive drugs, reach further lifting slow release effect, the embodiment of the present application is also
A kind of manufacture method of 3D printing artificial bone is provided, as shown in Fig. 2 methods described includes：
Step 210：Obtain the 3rd sensitive drug；
Step 220：The 4th sensitive drug is obtained, wherein, the sensitiveness of second sensitive drug is less than described the
Three sensitive drugs, the sensitiveness of the 3rd sensitive drug are less than the 4th sensitive drug；
Specifically, step 210 and step 220 can refer to the explanation of step 110 and step 120, and described second is quick
The sensitiveness of sensitive drug is less than the 3rd sensitive drug, and the sensitiveness of the 3rd sensitive drug is less than the described 4th
Sensitive drug.
Step 230：The 3rd sensitive drug is dissolved in the solvent, and the 3rd suspension is made；
Step 240：The calcium containing compound that percentage by weight is 5%-50% will be included in 3rd suspension to be configured to
Second decorating film；
Specifically, the calcium containing compound that percentage by weight is 5%-50% is included in the 3rd suspension, is prepared
Into second decorating film, second decorating film and the medicine-containing microsphere that first decorating film is in creamy material are different
What point was the second decorating film carrying is the second sensitive drug, and what first decorating film carried is the first sensitiveness medicine
Thing.The two is scattered in the creamy material of different layers respectively, reaches the effect of two level sustained release.
Step 250：The 4th sensitive drug is dissolved in the solvent, and the 4th suspension is made；
Step 260：After adding second decorating film in the 4th suspension, addition percentage by weight is 0.5%-
30% calcium containing compound is that raw material is configured to the second creamy material；
Specifically, second creamy material and first creamy material are for biological 3D printing artificial bone
Raw material, difference is that internal contained drug is different, for printing the different layers of the artificial bone.Contain in second creamy material
There is the 4th powdered sensitive drug, and carry the microballoon of the 3rd sensitive drug, i.e., it is described due to the hydroxyl phosphorus of microballoon
Lime stone content is lower than the hydroxyapatite content of the creamy material, can be formed and first decompose release creamy material, then decomposes microballoon,
And then ladder is realized, there is step, science, controllable medicament slow release therapeutic effect
Step 270：Second creamy material is added in the biological 3D printer, and using first artificial bone as
Basis printing, forms the second artificial bone.
Specifically, second creamy material is printed on the basis of first creamy material, also
It is to say, the second creamy material is covered on the content of the first creamy material formation, can be by people according to different situations
Work bone is designed to 2 layers, and 3 layers, the embodiment of the present application is not intended to be limited in any to the number of plies of the artificial bone.In specific slow release effect
On, it can be formed and first be sustained the second creamy material, then discharge the second decorating film in the second creamy material, then be sustained the first paste
Material, the effect of the first decorating film in the first creamy material is finally discharged, and due in different creamy materials and decorating film
Contained drug sensitiveness is different, and outer layer sensitiveness is high, and internal layer sensitiveness is relatively low, and then realizes that the material of hypersensitivity first discharges,
Discharged after the material of hyposensitivity, and then lift the technique effect of slow release effect.
Embodiment three：
In order to realize the use of more middle sensitive drugs, reach further lifting slow release effect, the embodiment of the present application is also
A kind of manufacture method of 3D printing artificial bone is provided, refer to Fig. 3, methods described includes：
Step 310：The 5th sensitive drug is obtained, wherein, the sensitiveness of the 5th sensitive drug is higher than described the
One sensitive drug；
Step 320：The 5th sensitive drug is dissolved in the solvent, and the 5th suspension is made；
Step 330：After adding first decorating film in the 5th suspension, it is 5%- to be included in percentage by weight
50% calcium containing compound is configured to the 3rd decorating film.
Step 340：The 6th sensitive drug is obtained, wherein, the sensitiveness of the 6th sensitive drug is higher than described the
Five sensitive drugs；
Step 350：The 6th sensitive drug is dissolved in the solvent, and the 6th suspension is made；
Step 360：After adding the 3rd decorating film in the 6th suspension, it is 5%- to be included in percentage by weight
50% calcium containing compound is configured to the 4th decorating film.
Step 370：After the 4th decorating film is added in second suspension, addition percentage by weight is 0.5%-
30% calcium containing compound is that raw material is configured to the 3rd creamy material；
Step 380：3rd creamy material is added in the biological 3D printer and printed, forms third party's work
Bone.
For the embodiment of the present application, the 5th sensitive drug and the 6th sensitive drug are obtained, wherein, described the
The sensitiveness of five sensitive drugs is higher than first sensitive drug, and the sensitiveness of the 6th sensitive drug is higher than described
5th sensitive drug.After 5th sensitive drug is made into the 5th suspension, first decorating film is added
In 5th suspension, addition percentage by weight is 5%-50% calcium containing compound, it is become more sticky state,
It is put into the sieve of fixed dimension, sifts out the microballoon of identical size, freezing, air-dry, the 3rd decorating film is formed, then by institute
State the 3rd decorating film to be put into the suspension containing the 6th sensitive drug, addition percentage by weight contains calcification for 5%-50%'s
Compound, it is become more sticky state, be put into the sieve of fixed dimension, sift out the microballoon of identical size, freezing, wind
It is dry, finally obtain the 4th decorating film with three-decker.The sieve aperture size can have a variety of different size sizes, tool
Body size selects according to clinical demand, and the embodiment of the present application imposes any restrictions not to this.
Further, the 4th decorating film is added in second suspension, obtained the 3rd creamy material
Comprising the 4th decorating film and creamy material, the 4th decorating film is the medicine-containing microsphere with three-decker, is divided per Rotating fields
Not Han You different sensitive drugs, its sensitiveness is successively weakened by outer layer to internal layer, along with above-mentioned material is not easily decomposed, is made micro-
Ball can reach the effect for successively decomposing release medicine in itself, and the 4th decorating film is scattered in containing different sensitive drugs
Creamy material in, further enhance prolonged drug sustained release and substep medication technique effect.
Further, the 3rd creamy material is added in the biological 3D printer and shape is printed according to patient demand
The sizeable artificial bone of shape, because above-mentioned artificial bone can contain a variety of different pharmaceuticals, can reach it is lasting, long-term,
Substep medication, increase slow release effect, avoid the pain of patient's Repeated Operation.
The one or more technical schemes provided in the embodiment of the present application, have at least the following technical effects or advantages：
1st, the manufacture method for a kind of 3D printing artificial bone that the embodiment of the present application provides, 3D figures are obtained by three dimensional CT；
The 3D models of closure bone window are obtained by modeling technique according to the 3D figures；Obtain the first sensitive drug；It is quick to obtain second
Sensitive drug, wherein the sensitiveness of first sensitive drug is less than second sensitive drug；It is by percentage by weight
The 0.1%-20% copolymer containing lactic acid acetic acid is dissolved into solvent with 1,4- dioxane；In the solvent described in dissolving
First sensitive drug, and the first suspension is made；It is 5%-50%'s that percentage by weight will be included in first suspension
Calcium containing compound is configured to the first decorating film；Second sensitive drug is dissolved in the solvent, and it is suspended to be made second
Liquid；After first decorating film is added in second suspension, add percentage by weight and contain calcification for 0.5%-30%
Compound is that raw material is configured to the first creamy material；First creamy material is added in biological 3D printer and printed, shape
Into the first artificial bone.In the ointment-containing body material of artificial bone described herein, due to consolidating containing some carrying different pharmaceuticals
Shape thing, solve in the prior art due to there is no bone window closed system, do not simply fail to meet various types of bone surgeries
It is required that simultaneously because there is no bone window closed system so that medicine flows out, it is impossible to medicine is stayed in the position that needs play a role
Technical problem, reached makes artificial bone be coincide with bone window structure according to 3D printing, is advantageous to drug blockage, will not make medicine stream
Go out, while the later stage can increase the technique effect of bone amount.
2. the embodiment of the present application is by obtaining the 3rd sensitive drug；The 4th sensitive drug is obtained, wherein, described second
The sensitiveness of sensitive drug is less than the 3rd sensitive drug, and the sensitiveness of the 3rd sensitive drug is less than described the
Four sensitive drugs；The 3rd sensitive drug is dissolved in the solvent, and the 3rd suspension is made；Described 3rd is hanged
The calcium containing compound that percentage by weight is 5%-50% is included in turbid and is configured to the second decorating film；Institute is dissolved in the solvent
The 4th sensitive drug is stated, and the 4th suspension is made；After adding second decorating film in the 4th suspension, add
The calcium containing compound that percentage by weight is 0.5%-30% is that raw material is configured to the second creamy material；By second creamy material
Add in the biological 3D printer, and printed based on first artificial bone, form the second artificial bone.Reach according to trouble
Person's state of an illness needs to select multi-medicament, carries the decorating film of different pharmaceutical respectively by multilayer artificial bone, further extends sustained release
Time and the technique effect of substep medication.
3. the embodiment of the present application by obtain the 5th sensitive drug, wherein, the sensitiveness of the 5th sensitive drug
Higher than first sensitive drug；The 5th sensitive drug is dissolved in the solvent, and the 5th suspension is made；
After adding first decorating film in 5th suspension, it is included in the calcium containing compound that percentage by weight is 5%-50% and configures
Into the 3rd decorating film；The 6th sensitive drug is obtained, wherein, the sensitiveness of the 6th sensitive drug is quick higher than the described 5th
Sensitive drug；The 6th sensitive drug is dissolved in the solvent, and the 6th suspension is made；In the 6th suspension
After middle addition the 3rd decorating film, it is included in the calcium containing compound that percentage by weight is 5%-50% and is configured to the 4th decorating film；
After the 4th decorating film is added in second suspension, the calcium containing compound that percentage by weight is 0.5%-30% is added
The 3rd creamy material is configured to for raw material；3rd creamy material is added in the biological 3D printer and printed, shape
Into third party's work bone.Reach is needed to select multi-medicament according to conditions of patients, and consolidating for a variety of different pharmaceuticals is carried by artificial bone
Shape thing, further extend the technique effect of slow-release time and substep medication.
4. the embodiment of the present application by by the copolymer containing lactic acid acetic acid that percentage by weight is 0.1%-20% with 1,
4- dioxane is dissolved into solvent；First sensitive drug is dissolved in the solvent, and the first suspension is made；By institute
State be included in the first suspension percentage by weight be 5%-50% calcium containing compound be configured to the first decorating film；In the solvent
Middle dissolving second sensitive drug, and the second suspension is made；First solid fraction is added in second suspension
After thing, it is that raw material is configured to the first creamy material to add the calcium containing compound that percentage by weight is 0.5%-30%；By described
One creamy material is added in biological 3D printer and printed, and forms the first artificial bone.Due to said ratio material in vivo not
Easily decompose, a variety of different pharmaceuticals is discharged successively, further reached substep medication and extended the technology effect of slow-release time
Fruit.
Although preferred embodiments of the present invention have been described, but those skilled in the art once know basic creation
Property concept, then can make other change and modification to these embodiments.So appended claims be intended to be construed to include it is excellent
Select embodiment and fall into having altered and changing for the scope of the invention.
Obviously, those skilled in the art can carry out the essence of various changes and modification without departing from the present invention to the present invention
God and scope.So, if these modifications and variations of the present invention belong to the scope of the claims in the present invention and its equivalent technologies
Within, then the present invention is also intended to comprising including these changes and modification.
It should be noted last that above embodiment is merely illustrative of the technical solution of the present invention and unrestricted,
Although the present invention is described in detail with reference to example, it will be understood by those within the art that, can be to the present invention
Technical scheme modify or equivalent substitution, without departing from the spirit and scope of technical solution of the present invention, it all should cover
Among scope of the presently claimed invention.
Claims (5)
- A kind of 1. method of 3D printing artificial bone, it is characterised in that methods described includes：3D figures are obtained by three dimensional CT；The 3D models of closure bone window are obtained by modeling technique according to the 3D figures；Obtain the first sensitive drug；The second sensitive drug is obtained, wherein the sensitiveness of first sensitive drug is less than second sensitive drug；The copolymer containing lactic acid acetic acid that percentage by weight is 0.1%-20% is dissolved into solvent with 1,4- dioxane；First sensitive drug is dissolved in the solvent, and the first suspension is made；The calcium containing compound that percentage by weight is 5%-50% will be included in first suspension and is configured to the first decorating film；Second sensitive drug is dissolved in the solvent, and the second suspension is made；After first decorating film is added in second suspension, add percentage by weight and contain calcification for 0.5%-30% Compound is that raw material is configured to the first creamy material；First creamy material is added in biological 3D printer and printed, forms the first artificial bone.
- 2. the method as described in claim 1, it is characterised in that add in biological 3D printer by first creamy material After row printing, methods described also includes：Obtain the 3rd sensitive drug；The 4th sensitive drug is obtained, wherein, the sensitiveness of second sensitive drug is less than the 3rd sensitive drug, The sensitiveness of 3rd sensitive drug is less than the 4th sensitive drug；The 3rd sensitive drug is dissolved in the solvent, and the 3rd suspension is made；The calcium containing compound that percentage by weight is 5%-50% will be included in 3rd suspension and is configured to the second decorating film；The 4th sensitive drug is dissolved in the solvent, and the 4th suspension is made；After adding second decorating film in the 4th suspension, add percentage by weight and contain calcification for 0.5%-30% Compound is that raw material is configured to the second creamy material；Second creamy material is added in the biological 3D printer, and printed based on first artificial bone, shape Into the second artificial bone.
- 3. the method as described in claim 1, it is characterised in that described to be included in percentage by weight in first suspension and be After 5%-50% calcium containing compound is configured to the first decorating film, methods described also includes：The 5th sensitive drug is obtained, wherein, the sensitiveness of the 5th sensitive drug is higher than first sensitive drug；The 5th sensitive drug is dissolved in the solvent, and the 5th suspension is made；After adding first decorating film in the 5th suspension, the calcic chemical combination that percentage by weight is 5%-50% is included in Thing is configured to the 3rd decorating film.
- 4. method as claimed in claim 3, it is characterised in that methods described also includes：The 6th sensitive drug is obtained, wherein, the sensitiveness of the 6th sensitive drug is higher than the 5th sensitive drug；The 6th sensitive drug is dissolved in the solvent, and the 6th suspension is made；After adding the 3rd decorating film in the 6th suspension, the calcic chemical combination that percentage by weight is 5%-50% is included in Thing is configured to the 4th decorating film.
- 5. method as claimed in claim 4, it is characterised in that methods described also includesAfter the 4th decorating film is added in second suspension, add percentage by weight and contain calcification for 0.5%-30% Compound is that raw material is configured to the 3rd creamy material；3rd creamy material is added in the biological 3D printer and printed, forms third party's work bone.
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