CN107137775A - A kind of preparation method of the thermo-setting elastomer tissue engineering bracket with multistage pore structure - Google Patents
A kind of preparation method of the thermo-setting elastomer tissue engineering bracket with multistage pore structure Download PDFInfo
- Publication number
- CN107137775A CN107137775A CN201710348151.XA CN201710348151A CN107137775A CN 107137775 A CN107137775 A CN 107137775A CN 201710348151 A CN201710348151 A CN 201710348151A CN 107137775 A CN107137775 A CN 107137775A
- Authority
- CN
- China
- Prior art keywords
- tissue engineering
- thermo
- engineering bracket
- pore structure
- setting elastomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
-
- 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
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/08—Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/16—Materials with shape-memory or superelastic properties
-
- 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
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
-
- 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
- A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to a kind of preparation method of the thermo-setting elastomer tissue engineering bracket with multistage pore structure, including:(1) thermosets is mixed with packing material, obtains mixing material;The model of cube network structure is built using CAD software, then mixing material is added in the heating chamber of 3D printer, initial support is obtained by 3D printing;(2) initial support in step (1) is subjected to heat cross-linking or photo-crosslinking, obtains thermo-setting elastomer tissue engineering bracket;Packing material is finally removed, is produced.The present invention solves thermoplasticity FDM and directly prints thermosets root problem, and prepared tissue engineering bracket has a multistage pore structure of controllable precise in structure, and method is simple, quick, suitable for a variety of biomaterials, has a good application prospect.
Description
Technical field
The invention belongs to tissue engineering bracket field, more particularly to a kind of thermo-setting elastomer with multistage pore structure
The preparation method of tissue engineering bracket.
Background technology
Tissue, the damage of organ are one of major diseases of serious threat human health, traditionally mainly pass through clinic
The means such as organ transplant are treated.Pioneer Yuan-Cheng professors Fung of 1980s bioengineering are first
Organizational project this term is started, the purpose is to the tissue or device with three-dimensional structure of inner or in vitro generation substitutability
Official, the tissue for doing harm to or losing with reparation, regeneration of damaged, organ, so as to break through existing clinical medicine means to damaged tissues
Or the limitation of organ treatment, including the limited amount of organ donation, the reaction of allosome rejection, the infection of potential virus, it is autologous " with
Secondary injury of wound repair wound " etc..Tissue engineering technique is due to reach successfully repair of damaged tissues regeneration
The purpose of sufferer is treated, more extensive concern had been obtained in past 20 years.
Tissue engineering bracket can play simulation natural extracellular matrix function there is provided suitable cell growth break up it is micro-
See environment.Preferable tissue engineering bracket should possess following basic characteristics:(1) have suitable physical surface features and
Biochemical property, to promote propagation and the differentiation of cell;(2) there is open, interconnected microcellular structure, it is thin to promote
Born of the same parents' nutriment spreads the release with metabolite;(3) there is certain mechanical strength, to provide tissue growth supporting role;
(4) there is good biocompatibility, it is ensured that to cytotoxic side effect and to human body non-immunogenicity;(5) have controllable
Biological degradability, it is desirable to which degradation rate and the speed of regeneration match, and biological support is gradually degraded while regeneration
Final be metabolized excretes.But the also very limited of clinic can be really applied at present, reason for that is a lot, one
Important factor is exactly that the mechanical property between biomaterial and tissue is mismatched, and many tissues and organ of human body are such as
Angiocarpy, lung, bladder etc. are all with favorable elasticity, while in the environment in lasting mechanical stimulation.Therefore with good
Biocompatibility and degradability, the bioelastomer for the mechanical property that above-mentioned natural tissues can be simulated to a certain extent meet the tendency of and
Raw, the mechanical stimulation of surrounding can be passed to cambium by these bioelastomers, can be extensive from the deformation of circulation repeatedly
It is multiple, it is adaptable to the dynamic in vitro culture of cell and to be implanted in the dynamic mechanical environment of human body, will not be to the group of surrounding after implantation
Knit generation mechanical damage.Just because of this various features, it is important that bioelastomer has rapidly become a class in organizational project
Biomaterial, while also being applied in other related biomedical sectors.
One preferable bioelastomer will meet many requirements, except with excellent mechanical property, also requiring have
Good biocompatibility and biological degradability, while bioactive molecule can preferably be combined, with good processing
Property.The bioelastomer for meeting these conditions at present is also less, real to obtain the more limited of application, mainly or with PLA
[poly (lactic acid), PLA], polyglycolic acid [poly (glycolic acid), PGA], and polycaprolactone
Based on [polycaprolactone (PCL)] and its copolymer and derivative.In the bioelastomer that new development is got up, the poly- last of the ten Heavenly stems
Diglyceride [Poly (glycerol sebacate), PGS] is a prominent representative.PGS bioelastomers were in more than 10 years
Before, reported first by Wang etc., be to be introduced into one of bioelastomer of field of tissue engineering technology earliest, its appearance has driven it
The development of its thermosetting bioelastomer.And PGS is in itself also due to its many excellent characteristic, such as have good internal degraded
Performance, gradually corrodes from outside to inside, slowly equably degrades, and material is kept original geometric shape and power in a long time
Performance is learned until being replaced by cambium, so as to can guarantee that the biomedical implants such as tissue engineering bracket prepared therefrom whole
In individual degradation process, good integrality can be kept, due effect is persistently played.Therefore PGS, which is obtained, continues extensive research,
And show good application prospect.With going deep into that PGS is studied, it has also been realised that also there are some defects, limitation in it
It is further applied, and one of distinct issues are that it needs the violent cross linking conditions of high temperature high vacuum, can only typically lead to
Die methods and etching method shaping are crossed, its processing method and application is greatly limited.
3D printing technique (also known as 3D rapid shaping techniques or RP), it refers under the control of the computer, impaired according to patient
The data such as tissue or CAD (CAD) model of organ or computed tomography (CT), pass through the accurate of material
3D accumulates, and quickly manufactures the novel digital forming technique of arbitrarily complicated three-dimensional shape.Technology can not only realize material and patient
The perfect matching of diseased region, and can in microstructure accuracy controlling material structure.FDM has as in 3D printing technique
Representational one kind, its principle be using hot melt shower nozzle so that the material of molten condition by computer control path extrusion,
Deposition, and coagulation forming, by layer by layer deposition, solidification, finally remove backing material, obtain required three-dimensional objects.The technology
Feature is shaped article precision height, the good, non-environmental-pollution of surface quality etc., but it has the disadvantage that operation temperature is higher, also because of it
Such principle and feature are the processing method as thermoplastic all the time.
Generally speaking, material and rack forming method are two key elements prepared by tissue engineering bracket, bioelastic
The predicament solved to a certain extent on material of arising at the historic moment of body material, PGS also progressively turns into system due to its excellent performance
One of ideal material of standby tissue engineering bracket, and FDM technology is used for for a long time as a kind of printing technique of thermoplastic
Build the tissue engineering bracket of labyrinth.FDM printing techniques are all used as one kind all the time because of the principle of its melt molding
Thermoplastic processing mode is used and studied, it is more difficult to applied to above-mentioned thermoset elastomer materials.By taking PGS as an example, wherein
Under main difficulty:Prepolymer is that thermoplastic can bear plastic working i.e. with printability first, is then needed into one
The high temperature of step, vacuum environment are crosslinked and solidify guarantor's type.But in second step, because prepolymer is in itself to thermo-responsive,
Its mobility is greatly increased by heat energy, is deformed upon before crosslinking curing and destroys original structure, can not finally be beaten by 3D
Print the elastomer that this mode processes this crosslinkings of PGS.Due to above-mentioned thermosets property and FDM thermoplasticity processings principle it
Between incompatibility, cause at present have no using FDM print thermosetting biological support report, more have no FDM printing PGS elasticity
Body support frame.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of thermo-setting elastomer tissue with multistage pore structure
The preparation method of engineering rack, this method solve thermoplasticity FDM and directly prints thermosets root problem, prepared group
Weaver's engineering support has a multistage pore structure of controllable precise in structure, and method is simple, quick, suitable for a variety of biological materials
Material, has a good application prospect.
A kind of preparation method of thermo-setting elastomer tissue engineering bracket with multistage pore structure of the present invention, bag
Include:
(1) by thermosets and packing material in mass ratio 1:0.5-3 is mixed, and obtains mixing material;Utilize CAD software
The model of cube network structure is built, then mixing material is added in the heating chamber of 3D printer, is obtained by 3D printing
Initial support;
(2) initial support in step (1) is subjected to heat cross-linking or photo-crosslinking, obtains thermo-setting elastomer organizational project branch
Frame;Packing material is finally removed, the thermo-setting elastomer tissue engineering bracket with multistage pore structure is produced;Wherein, it is multistage
Pore structure includes two grades of macroporous structures of the gap generation between primary contour structure, fiber element diameter and fiber and filled out
Fill the three-level microcellular structure produced after material is removed as template.
Thermosets in the step (1) is PGS, polyurethane or epoxy resin etc..
Packing material in the step (1) is salt particle, graphene, CNT (or other carbon materials), dioxy
SiClx, hydroxyapatite (or other inorganic material), (or the higher polymerization of other other fusing points of nylon or makrolon
Thing).
A diameter of 20~100 μm of the salt particle.
Hybrid mode in the step (1) is solvent mixing method or heating.
3D printing parameter in the step (1) is:40~100 DEG C of extrusion chamber temperature and nozzle temperature.
Heat cross-linking parameter in the step (2) is:The preliminary crosslinking curing 12-24h in 100 DEG C of vacuum drying oven, so
The further solidification crosslinking in 120 DEG C -150 DEG C of vacuum drying oven afterwards.
The thermo-setting elastomer tissue engineering bracket with multistage pore structure obtained in the step (2) passes through freezing
Drying is preserved.
Using PGS as thermosets, salt particle be used as the principle for illustrating the present invention exemplified by packing material:
The salt particle in the range of salt particle, screen cloth screening certain size is smashed with pulverizer, by salt particle and PGS prepolymers
Mixed in different ratios, the printability in printing experiment is melted by actual 3D, including it is extrudability steady with initial configuration
Qualitative, and the conformality in subsequent high temperature solidification process, integrated survey selects most suitable mixed proportion to meet PGS 3D
The requirements of printing.Mixture is mounted in 3D printing in syringe, preferable print parameters are adjusted, it is desirable to can continuous uniform fiber
Extrusion (good is extrudability), there is good initial configuration stability after the completion of printing.For PGS elastomeric tissue engineering branch
Frame, devises multi-level pore structure.By the modelling to 3D printing, the personalized customizable excellent of 3D printing is utilized
Gesture, can conveniently build the primary contour structure of support.By selecting needle sizes size and the design to printing path, to adjust
Gap between the thickness and fiber of fiber element diameter, so as to two grades of macroporous structures of effective control support.It is another
Aspect, the consumption and size of salt grain are mixed by adjusting, fiber element is distributed in adjust after salt grain is removed as template
The porosity and void size of inner porosity, so as to the three-level microcellular structure of effectively control support.Then, PGS conducts
A kind of representational thermosetting bioelastomer, it is necessary to could obtain stable three-dimensional configuration and mechanical property by hot setting crosslinking
Energy.However, the crystallization temperature of PGS prepolymers itself is relatively low, viscosity, which can be reduced, at high temperature easily deforms upon.Therefore, salt grain
Be mixed into during high-temperature cross-linking and serve the effect of very important physical support, and PGS prepolymers are served and are similar to
The effect of adhesive.In order that the form and the PGS prepolymer supports of printing after hot conditions solidification are consistent, support first exists
A certain degree of solidification is carried out at relatively low temperature, further solidification crosslinking is then carried out at relatively high temperatures.Finally, it will hand over
Support after the completion of connection, is repeatedly immersed in ethanol distillation water mixed liquid and removes unpolymerized prepolymer, salt particle etc., so as to obtain
There must be the 3D printing PGS elastomeric tissue engineering racks of multistage pore structure, then carry out freeze-drying and remove in support
Moisture, in order to be preserved using with long-term.
Beneficial effect
The present invention solves thermoplasticity FDM and directly prints thermosets root problem, prepared tissue engineering bracket
There is the multistage pore structure of controllable precise in structure, method is simple, quick, suitable for a variety of biomaterials, can be according to trouble
The data such as the CT of person carry out the tissue engineering bracket needed for personalized customization, available for prepare people's auricle cartilage scaffold, myocardium sticking patch,
And the multi-stage porous support needed for other organizational projects, have a good application prospect.
Brief description of the drawings
Fig. 1 is the process chart of embodiment;
Fig. 2 schemes for the SEM of different mixing proportion support;Wherein, A, D are respectively ratio 1:The section of 0.5 sample and table
50 times of electron microscopes in face;B, E are respectively ratio 1:The section of 1 sample and the 50 of surface times of electron microscopes;C, F are respectively ratio 1:
The section of 2 sample and the 50 of surface times of electron microscopes;
Fig. 3 is PGS500 and PGS300 electron microscope;
Fig. 4 is crosslinked for the solidification of support;
Fig. 5 A-D are that support removes comparison diagram before and after salt particle;
Fig. 6 is support shear stress and the curve map of shear rate;
Fig. 7 is the batten high temperature conformality comparison diagram of different mixing proportion;
Fig. 8 contrasts for PGS300 and PGS500 pore size and diameter dimension;
Fig. 9 A-D are the mechanical property of PGS supports;
Figure 10 is the biological degradability of PGS supports;
Figure 11 a-l are the micro-phase action of PCLU elastomers and its support;
Mechanical properties and infrared spectrum analysis of Figure 12 a-d for PCLU supports.
Embodiment
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limitation the scope of the present invention.In addition, it is to be understood that after the content of the invention lectured has been read, people in the art
Member can make various changes or modifications to the present invention, and these equivalent form of values equally fall within the application appended claims and limited
Scope.
Embodiment 1
1. printed material prepares
The hybrid parameter of PGS prepolymers (Pre-PGS) and salt particle directly determines extrudability, initial when support is printed
The pore structure of morphological stability, hot setting conformality and support, so that the performance of support is determined indirectly, including mechanical property
Energy and biological degradability.The parameter of research needed for mixed process includes hybrid mode, diameter of mixed proportion and salt particle etc..
1.1 hybrid mode
Pre-PGS is thick at normal temperatures and viscosity is larger, with the increase of the salt ratio of mixing, the viscosity of mixture
Also gradually increase, it is easy to produce the problem of mixing is uneven, it is therefore desirable to consider the viscosity of reduction mixture.Conventional reduction
The method of viscosity has two kinds:Solvent method and heating.Therefore two methods mixing material is used, passes through pre-extruded experiment progress pair
Than analysis, the method being more suitable for is selected to carry out subsequent experimental.
1.1.1 solvent mixing method
1st, by Pre-PGS and acetone with mass volume ratio 1:2 is uniform without heating stirring, and Pre-PGS total amounts are 8g, and acetone is
The thick solution that cumulative volume is 20ml is obtained after 16ml, mixing;
2nd, NaCl be placed in pulverizer crush after, by the screen cloth of 200 mesh and 400 mesh sieve diameter 38~75 μm it
Between salt grain;
3rd, salt grain is well mixed by a certain percentage with Pre-PGS, be fitted into injector syringe:
4th, stand and treat that acetone is placed in vacuum drying oven 30 DEG C after slightly volatilizing, 24h removes acetone;
5th, with the tentative extrusion of syringe.
1.1.2 heating
1st, the beaker that will be equipped with Pre-PGS is placed in heating in 60 DEG C of oil baths;
2nd, NaCl be placed in pulverizer crush after, by the screen cloth of 200 mesh and 400 mesh sieve diameter 38~75 μm it
Between salt grain;
3rd, Pre-PGS is mixed with salt grain by different proportion, be fitted into injector syringe:
4th, with the tentative extrusion of syringe.
1.2 mixed proportion
2g Pre-PGS are weighed with assay balance to be placed in beaker, 60 DEG C of oil bath heatings.With pulverizer polishing salt grain, use
The screen cloth of 200 mesh and 400 mesh screens a diameter of 38 μm~75 μm of salt particle, and 2g salt particles are weighed with assay balance, beaker is treated
In Pre-PGS be changed into adding during transparent liquid, stirred with glass bar and prepare Pre-PGS:NaCl=1:1 it is mixed
Compound, is fitted into 10ml one-shot injector, standby.In order to find suitable print scale, a series of mixing of ratios is designed
Thing is printed, the ratio such as table 1 of mixture:
The Pre-PGS of table 1 and salt particle mixed proportion
1:0.5 | 1:1 | 1:2 | 1:3 | |
Pre-PGS | 2g | 2g | 2g | 2g |
Salt particle | 1g | 2g | 4g | 6g |
2.3D prints Pre-PGS supports
2.1 3D printing models
Using the software building models of AutoCAD 2014, cube network structure is built, the length of side is 20mm, its micro grid
Gap can be controlled by the path and parameter of printing.To embody the personalized customizable advantage of 3D printing, it can print each
Complicated contour structure is planted, snowflake figure is have chosen wherein and is printed.
2.2 3D printing state modulators
The power supply of 3D printer is opened, before 3D printing is carried out, the nozzle and pressure ram of 3D printer is unloaded, cleaning is dry
Only, nozzle and syringe needle are loaded onto, PGS and NaCl mixed material is put into barrel, pressure ram is then reinstalled.Open 1 number
Heater, sets extrusion chamber temperature and nozzle temperature, double-clicks the 3D printer software on computer, makes computer and 3D printer phase
Connection, the CAD model needed for selection 3D printing.Then parameter setting is carried out, extrusion chamber temperature and nozzle temperature difference are set all
For 40 DEG C, 45 DEG C, 50 DEG C, 55 DEG C, 60 DEG C, material extrudes the change of state at 65 DEG C.20G syringe needles are selected, floor height is 0.5, net
Lattice filling width is 1.2mm, and x position is 90, and y location is 90, and Contour filling number of times is 0, and angle is 90 ° and 0 °.Click on XY axles
Speed fills in corresponding XY axles movement velocity and T axle material extrusion speed, and wherein XY axles movement velocity is 2mm/s, and T axle material extrusion speed is
0.006mm/s, preservation clickstream data " it is determined that " and fill path.By x, y location is all transferred to 90, adjustment z-axis come adjust syringe needle from
The height of receiver board, then by the xy shaft position back to zeros of printer, after temperature rises to designated value and stabilization, you can press
Auto starts printing.
2.3 needle sizes
The model of extrusion syringe needle directly determines the diameter dimension of extrusion fiber element and the fineness of support, in order to improve
The fineness of printing, has used the smaller syringe needle of internal diameter (22G), between the size and fiber element to reduce fiber element diameter
Gap width.But salt particle size directly determines the extrusion performance of printed material with pinhead-sized matching, in salt grain
On the premise of filler consumption is constant, in order that material is easier extrusion, the salt grain that particle diameter is smaller has been selected.
Salt grain from two kinds of different-diameters carries out contrast test, a diameter of 38~75 μm and 26~38 μm of salt particle and divides
Do not printed with 20G and 22G syringe needles.Wherein printed using 20G syringe needles and a diameter of 38~75 μm of salt grains as filler
Support is PGS 500;The support wherein printed as filler using 22G syringe needles and a diameter of 26~38 μm of salt grains is PGS
300.Two kinds of syringe needle parameter comparisons are shown in Table 2:
The 21G of table 2 and 22G syringe needle parameter comparisons
The solidification crosslinking and precipitation of 2.4 supports
Because support raw material are Pre-PGS and salt particle, the high-temperature cross-linking for carrying out second step is also needed to turn into PGS branch
Frame.Although salt particle maintains the three-dimensional structure of support in print procedure as setting agent, with the rise of temperature,
Pre-PGS viscositys progressively decline, and the structure of support is inevitably destroyed.Therefore one is selected suitably compared with low temperature
Degree, at this temperature, support can keep its structure within a certain period of time, and crosslinking can also takes place in Pre-PGS.In Pre-
PGS occurs after a certain degree of crosslinking, it is ensured that it still has after shape-retaining ability at high temperature, then high temperature rapid curing crosslinking.
It is polymerize according to the access and PGS of bibliography and solidifies the condition of crosslinking, is 100 by low temperature guarantor's type temperature setting
DEG C, support enters traveling one in 100 DEG C of vacuum drying oven in preliminary crosslinking curing 12h, the vacuum drying oven for being then transferred into 150 DEG C
The solidification crosslinking of step.
To remove salt particle and uncrosslinked polymer in support, support is immersed in absolute ethyl alcohol at ambient temperature
1 is pressed with distilled water:In the solution of 3 ratios mixing, mixed once liquid is changed within every 4 hours, is washed 3 times, after freezing 12 hours, be placed in-
20 DEG C, freeze-drying obtains the elastic body support frames of PGS in 50Pa freeze drier.
3. characterize and detection
The sign of 3.1 printabilities
Using the rheological property of the mixture of proof stress rheometer measurement different proportion, design module is divided into two portions
Point:First is holding stage, and holding temperature is 45 DEG C, and rotating speed is 0, and soaking time is 300s;Second stage is that rotating speed increases rank
Section, temperature is 45 DEG C, and rotating speed increases to 100rpm from 0, and the time is 600s.Each three groups of data of sample test are designed, are used
Shear stress-shear rate curve the figure of four ratio samples of origin Software on Drawing.
The measure of 3.2 high temperature conformalitys
It is respectively 1 to prepare PGS and NaCl ratios:0.5,1:1,1:2,1:3 mixture, takes long 1cm, a diameter of 0.5cm
Column model, mixture is packed into mould with scraper, is compacted, the material of each ratio prepares two battens, is placed in -20
DEG C refrigerator in freeze 30min, with ear of maize release obtain column batten.10min is incubated in the vacuum drying oven for being placed in 100 DEG C, is seen
Its change in shape is examined, so as to help to select proper mixture ratio example.
The sign of 3.3 morphosis and test
The sign of supporting structure is detected by SEM, the form of support is observed, if deform, caves in and slightly
It is thin whether uniform etc. so as to select proper mixture ratio example and solidification temperature, the distribution of pores of qualitative characterization's support and overall tie
Structure.And the SEM figures of support are counted using ImageJ softwares, each 30~40 data of measurement is averaged and side
Difference, with reference to the fiber element diameter and pore-size of Origin Software on Drawing block diagram quantitative analysis supports.
3.4 porosity
This experiment is using ethanol densimetry measurement porosity.Support is freeze-dried after constant weight 24h in drier, analysis
Balance weighs its quality m0.Support is put into centrifuge tube, 12h in absolute ethyl alcohol is completely submerged in, measurement centrifuge tube, ethanol with
The gross mass of support is m1.Carefully support is taken out from bottle with tweezers, the support of taking-up is filled ethanol liquid and do not dripped
It is defined, support is placed on clean culture dish.The gross mass of the remaining ethanol that weighs with scale and centrifuge tube is m2.PGS density ps
PGS, absolute ethyl alcohol density p ethanol at 20 DEG C.The porosity calculation formula of support is as follows:
3.5 Mechanics Performance Testings are with characterizing
Four layers of support are cut into 10*5mm rectangular specimens, its tensile break strength is tested and tension fracture elongation rate is right
Afterwards under conditions of slightly less than tension fracture elongation rate, cyclic tension test, test loop number of times 10 times are carried out.With 16 layers of branch
Frame carries out circulation compression verification, and deformation degree is 40%, and test loop number of times is 1 time, 10 times, 30 times, 50 times respectively.
3.6 biological degradability
Above-mentioned PGS supports are cut into 5mm*5mm sample, initial mass is weighed.Support is respectively put into equipped with 5ml esterases
In the centrifuge tube of solution, it is placed in 37 DEG C of constant-temperature incubation casees.Respectively in 10min, 30min, 1h, 2h, 3h, 5h, by sample during 7h
Take out, using being freeze-dried after distilled water rinse to constant weight, weigh the quality after sample breakdown.And observe sample using SEM
Support form after degraded.
4. result
2.1.1 the hybrid mode of material
Pre-PGS is thick at normal temperatures and viscosity is larger, with the increase of the salt ratio of mixing, the viscosity of mixture
Also gradually increase, it is easy to produce the problem of mixing is uneven, it is therefore desirable to consider the viscosity of reduction mixture.Conventional reduction
The method of viscosity has two kinds:Solvent method and heating, are carried out comparative using both approaches.Experiment shows:Using solvent method
Mixing, when taking out solution from vacuum drying oven, although acetone is substantially removed, without very big pungent smell, but passes through
12h, which is stood, finds that most of salt grain is deposited on bottom, mixes uneven with Pre-PGS, extrusion performance is poor.There are two in addition
Defect is:First, it can not ensure that acetone is removed completely;2nd, acetone is constantly being volatilized during experimental implementation, and Pre-PGS acetone is mixed
The volume for closing liquid is being continually changing, it is impossible to ensure the real ratio of Pre-PGS and NaCl particles.The material mixed using heating
It is extrudability more stable than more uniform, while without other organic solvents, it is ensured that the biocompatibility of material.Therefore
Subsequent experimental is carried out using heating.
2.1.2 the mixed proportion of material
Salt particle plays a part of setting agent and pore-foaming agent in the mixture, therefore salt grain is very few, it is impossible to plays sizing and makees
With the structure of printing is easily caved in;Salt grain is excessive, and viscosity is too high, may result in printing difficulty, or even can not print.
Accordingly, it would be desirable to which exploring a proper mixture ratio example can continue intactly to print, the structure of print carriage can be kept again, full
On the basis of the two conditions of foot, with reference to the observation of SEM Electronic Speculum, the overall structure and microstructure of support are analyzed, Pre- is selected
PGS and salt particle most suitable ratio.
From SEM figures, it can be seen that ratio is 1:0.5 sample is 35 DEG C in print temperature can be relatively easy to heated squeeze
Go out, but because heating-up temperature and room temperature are approached so that mobility variations are small after cooling, yielding after shaping, the fiber in support
Unit is distributed unclear in length and breadth, is sticked to each other between different layers to together.Ratio is 1:1 sample, temperature can be squeezed at 45~50 DEG C
Go out, fiber overall distribution is clear, but the phenomenon that single fiber occurs necessarily collapsing downwards in unsupported region, by Action of Gravity Field
Influence is larger.Ratio is 1:2 samples, can smoothly be extruded when temperature is 55 DEG C, and room temperature cooling aftershaping is stable, and fiber list
Member distribution is clear, does not deform upon substantially under gravity, fibre section is into smooth circle, and shape-retaining ability is good.Ratio is 1:3
Sample, heating extrusion temperature rises to 90 DEG C, but there is the not smooth defect of extrusion, and fiber is extruded by intermittent type, and this is probably
Salt content increase causes caused by Heated Flow difference.
2.1.3 3D printing parameter
2.1.3.1 print temperature
From the point of view of print procedure, with the rise of print temperature, the mobility of material is become better and better, and is at the same time printed
The shape-retaining ability of support worse and worse, therefore will select a suitable temperature, i.e., at this temperature, and material can steady and continuous
Uniform threadiness is extruded into, can be fixed up again on receiver board and keep shape during printing without deforming.From
From the point of view of experimental result, at 40~50 DEG C, the mobile performance of material is very poor, and fiber extrusion is discontinuous, simultaneously because temperature is relatively low, pin
Head point is not heated, and material is easily blocked in syringe needle.At 60~65 DEG C, the mobile performance of material is very good, so that printed
Cheng Zhonghui causes fibre diameter to become big or fibrous fracture suddenly because of some slight changes of pressure or the rupture etc. of bubble,
Temperature is not reduced in time after fiber reaches receiver board simultaneously, and mobile performance preferably, is affected by gravity and fiber is caved in, whole
Individual supporting structure deforms.At 55 DEG C or so, mobile performance is more suitable, can continuously extrude, Simultaneous Stabilization reaches
After receiver board, the reduction of temperature drop mobile performance can more stably maintain its fiber shape and supporting structure.Therefore 55 are used
Temperature on the basis of DEG C, is ceaselessly finely tuned with the change of the process material state of printing, because in print procedure, material
Material is extruded and heated for a long time in extrusion chamber, and a certain degree of change can all occur for state.Also needed in print procedure
A main problem is easily to produce bubble in material, causes the unexpected fracture of fiber, thus before printing is started, it is necessary to
Precharge is carried out, material stable a period of time in extrusion chamber is started printing again.
2.1.3.2 3D printing software parameters
The caramel fibre diameter of shower nozzle extrusion is except relevant with the size of syringe needle, and also relevant with two factors, one is raw material
Rate of extrusion, two be shower nozzle rate travel.In the case of rate of extrusion is constant, shower nozzle rate travel is bigger, and fibre diameter is smaller;Spray
In the case of head rate travel is constant, material extrusion speed is bigger, and fibre diameter is bigger.Therefore the basal rate of raw material is fixed, changed
The rate travel of shower nozzle explores both proper ratios, from the point of view of experimental result, when T axle material extrusions speed is 0.006mm/s
When, when shower nozzle rate travel is 2mm/, the diameter of fiber is more matched with needle sizes, this explanation T axle material extrusion speed and shower nozzle
The ratio between rate travel ideal is about 0.003:1, the size of both can be changed on this basis and change print speed.But this two
The value of person can not increase always, once because shower nozzle rate travel is excessive, fiber is difficult to be fitted well with receiver board, while fine
Stuck up during dimension turnover because volume easily occurs for excessive velocities, supporting structure deformation.Floor height is related to needle sizes, 20G syringe needles it is interior
Footpath is that can produce a certain degree of stretching in 0.61, but print procedure to fiber, and can be affected by gravity, therefore selection
0.5mm is used as floor height.In addition, general when printing starts set syringe needle more smaller than floor height from the height of receiver board, so as to material
Material, which can be stablized, to be pasted on receiver board.
2.1.4 needle sizes
In this experiment, mechanical support phase when NaCl particles can be used as solidifying, is also used as pore-foaming agent, passes through
Microcellular structure is formed after water-soluble removal.In order to further control the microstructure of fiber and the cast structure that becomes more meticulous, to salt grain chi
Very little and extrusion nozzle size is adjusted with having matched.A, B are respectively PGS500 50 times of electron microscopes and 1000 times of electron microscopes;C,
D is respectively that PGS300 50 times of electron microscopes and 1000 times of electron microscopes originally used 20G syringe needle, and corresponding uses particle diameter
It is about 500 μm or so (PGS500) in fibre diameter made from 38 μm~75 μm of NaCl particles, fibrous inside and surface are uniform
Distributed substantial amounts of microcellular structure, pore size matches with grain diameter.And when using 22G syringe needles printing extrusion, it is considered to
Extrusion smoothness of the particle at shower nozzle, have selected particle diameter in 26~38 μm of NaCl particles (≤38 μm), obtains fiber list
Also substantial amounts of micropore is evenly distributed with the support (PGS300) of a diameter of 300 μm or so of member, same fiber, multistage hole is formed
Structure.But, in contrast PGS supports made from 22G syringe needles, fibre diameter is smaller so that fiber alignment is even closer, finely
Du Genggao, while salt particle is smaller so that pore size is smaller, whole support specific surface area is bigger, is more beneficial for as tissue work
Engineering support is used.
2.1.5 the solidification crosslinking of support
Fig. 4 left sides are uncured support, and the right is the support after solidification, it can be clearly seen that solidification front and back support
Obvious change does not occur for global shape, and original defect still has after solidification, illustrates that support does not have again
Generation is largely deformed.Illustrate that 100 DEG C of low temperature of design are tentatively crosslinked, the experimental program that 150 DEG C of high temperature is further crosslinked
Efficiently solve the problem that thermoplasticity 3D printing technique prints heat cured PGS.
2.1.6 the precipitation of support
From the point of view of Fig. 5 A, C, support does not only have the macrovoid between grid, by the removing of salt particle on the surface of support
Just inside all produces substantial amounts of hole, so as to constitute the multistage hole of support, is conducive to the breeding and growth of cell.And by B,
D, can obtain the size of micropore with quantitative analysis and the size of salt particle matches, so that prove can be by being mixed into salt particle
Diameter dimension controls the size of support micropore, and this is conducive to support in organizational project towards specific clinical application.
The sign of 2.2 supporting structures and detection
2.2.1 the sign of printability
Printability includes the stability of extrudability and initial configuration.Left figure is obtained according to proof stress rheometer test
The data arrived draw the sample that each slope of a curve in shear stress and the curve map of shear rate, figure represents each ratio
Viscosity under this shear rate, therefore from the point of view of whole piece curve and the shear rate specified, identical can be obtained
Conclusion:With the increase of the ratio of salt particle in mixture, the viscosity of material is constantly increasing.And extruded in 3D fusions real
In testing, with salt particle ratio increase, at same temperature, the extrudability of mixture worse and worse, and initial configuration
Stability is become better and better, and this phenomenon can just be explained with above-mentioned viscosity.In general, the sample of first three ratio all passes through
The regulation of print temperature obtains suitable printability, but Pre-PGS and NaCl ratios are 1:3 sample is at 90 DEG C
Also it is difficult to good extrudability.Therefore from printability, 1:The mixture of 3 ratios is not suitable for 3D melting extrusions
Printing prepares the elastic body support frames of PGS.
2.2.2 the measure of high temperature conformality
As can be seen from Figure 7 with the content increase of NaCl particles in mixture, the high temperature conformality of support gradually improves,
Pure Pre-PGS, Pre-PGS and NaCl ratio are 1:0.5 and 1:Condition of the sample of 1 these three ratios in 100 DEG C of crosslinked at low temperature
Under be still difficult to keep its shape, and Pre-PGS and NaCl ratios be 1:2 and 1:The sample of 3 the two ratios then can be certain
Its shape is kept in degree.Therefore from high temperature conformality, 1:2 and 1:3 the two ratios are relatively adapted to, in conjunction with can beat
Print property, 1:2 this ratio are optimal.
2.2.3 diameter and pore-size are counted
There is significant difference, fibrous inside and table in the diameter dimension that can quantitatively find out PGS300 and PGS500 from Fig. 8
The size of salt particle of the pore size in face with being mixed into matches.The pore size of fibre section is substantially than fiber surface
Greatly, because fiber surface can only see a part for micropore and the salt grain on surface is generally covered by PGS, salt grain is caused
The diameter of hole is smaller after precipitation or hole is not obvious.
2.2.4 the detection of brace aperture rate
The structure of three-dimensional rack has vital effect to its application in organizational project, if support is with higher
Porosity and good connectivity, then be beneficial to the absorption of cell and the transport of propagation, nutriment and metabolic waste.
The elastic body support frames of the PGS of this experimental design, primary contour structure, the fiber element produced by the modelling to 3D printing is straight
The three-level microcellular structure that the two grades of macroporous structures and salt grain that gap between footpath and fiber is produced are produced after being removed as template
The multistage hole of support is constituted together, the passage conveyed as cell growth needed nutrient matter and metabolic waste.Therefore PGS bullets
The porosity of property body support frame is a vital parameter.
The porosity for the elastic body support frames of PGS that this test determines 3D printing using formula shown in experimental section.Such as the institute of table 3
Show, the porosity of three-dimensional hollow support prepared by this method is more than 66%, and mean porosities are 72.96%.
The porosity measurement of the support of table 3
M0 | M1 | M2 | Porosity |
0.0579 | 1.8109 | 1.5632 | 0.7354 |
0.0259 | 1.9062 | 1.7806 | 0.7655 |
0.0310 | 2.0333 | 1.8701 | 0.7834 |
0.0477 | 1.7894 | 1.6310 | 0.6630 |
0.0611 | 1.8261 | 1.5497 | 0.7492 |
0.0593 | 1.5516 | 1.3431 | 0.6809 |
2.2.5 Mechanics Performance Testing and sign
Can be seen that from mechanical experimental results Fig. 9 (A), the tension fracture elongation rate of the supports of PGS 500 35% or so,
Fracture strength is 80kPa or so, and the tension fracture elongation rate of the supports of PGS 300 is 40% or so, and fracture strength is 60kPa left
It is right.Elongation is cyclic tension 10 times under conditions of 25%, shows typical elastic deformation curve and with good deformation
Restorative (C, D), the compliance for possessing certain internal suture strength and internal dynamic mechanical environment.By circulating compression verification
Can be seen that the elastic body support frame of this 3D printing has stronger fatigue durability, and the curve that multiple deformation recovers is essentially coincided, still
The initial good elasticity (B) of holding, possesses and is stressed compression in vivo and can recover in time, can be kept well with tissue
Matching.Circulation compression curve analysis to PGS 500 and PGS 300 understands that PGS300 compressive strength is than PGS 500 slightly
Greatly, this is close relevant with PGS 300 fiber element arrangement more matter.What both supports were all kept within deformation degree 50%
It is elastic deformation, i.e., compression curve is overlapped with release recovery curve, but after more than 50%, curve is not overlapped, and is recovered
The force diagram of process is higher than compression process, shows the phenomenon (B) of " mechanics enhancing ".For this phenomenon, it may be possible to press
When (being more than 50%) when contracting deformation degree is excessive, integrally become flattening, caused by lifting surface area increase.
2.2.6 biological degradability
Can be seen that the PGS supports of 3D printing have a good biological degradability from Figure 10 degradation curves, Preliminary degradation compared with
It hurry up, subsequent degradation is in a basic balance, degradation rate is up to more than 90% after 5 hours.The electron microscope of sample can be seen that branch after degraded
The degraded of frame is that internally progressively occur etchingization degraded from surface, and the microcellular structure size on surface progressively becomes big.
Embodiment 2
Prepare PCLU supports, method be the same as Example 1.The use of polycaprolactone glycol, HDI trimer is raw material, with salt particle
Mixing printing solidify afterwards shaping, save prepolymer synthesis step, allow material unit in the structure that 3D is molded in a heated condition
Reaction solidification.
As shown in figure 11, this method can also be satisfied with PCLU printing shaping, can prepare biological support and other are not advised
Then shape, this heat cured PCLU is also a kind of elastomer, and (a-d) still can be quickly recovered by folding repeatedly.To branch
Frame carries out Electronic Speculum test, and its fiber element is clear regularly arranged and stacks, and fibre section is rounded, has no that obvious fiber is collapsed
Phenomenon, with good solidification shape-retaining ability, while substantial amounts of micropore is distributed with fiber surface and inside, support is integrally in multi-level
Pore structure (e-l).
Mechanical test results to PCLU supports are as shown in figure 12:Its tensile break strength is 386kPa or so, and fracture is stretched
Long rate is 80%, better than PGS supports.In 10 loop cycle extension tests and the circulation compression verification in 50 cycles loading and
The curve matching degree of release is high, has shown excellent elastic and deformation restorative;Mechanical characteristics repeatedly circulate simultaneously after
Curve does not change substantially, with good fatigue durability.For this PCLU elastomers, due to raw material use it is poly- oneself
This degradable unit of lactone dihydric alcohol, it is contemplated that it possesses biological degradability.In addition, for the potential source biomolecule poison having in raw material
Property NCO group, can determine whether after being analyzed by infrared spectrum measurement it is reacted be not present completely, it is medical poly- similar to other
Urethane material and possess good biocompatibility.
Claims (8)
1. a kind of preparation method of the thermo-setting elastomer tissue engineering bracket with multistage pore structure, including:
(1) by thermosets and packing material in mass ratio 1:0.5-3 is mixed, and obtains mixing material;Built using CAD software
The model of cube network structure, then adds mixing material in the heating chamber of 3D printer, is obtained initially by 3D printing
Support;
(2) initial support in step (1) is subjected to heat cross-linking or photo-crosslinking, obtains thermo-setting elastomer tissue engineering bracket;
Packing material is finally removed, the thermo-setting elastomer tissue engineering bracket with multistage pore structure is produced;Wherein, multistage hole
Structure includes the two grades of macroporous structures and filling material that the gap between primary contour structure, fiber element diameter and fiber is produced
The three-level microcellular structure that material is produced after being removed as template.
2. a kind of preparation of thermo-setting elastomer tissue engineering bracket with multistage pore structure according to claim 1
Method, it is characterised in that:Thermosets in the step (1) is PGS, polyurethane or epoxy resin.
3. a kind of preparation of thermo-setting elastomer tissue engineering bracket with multistage pore structure according to claim 1
Method, it is characterised in that:Packing material in the step (1) is salt particle, graphene, CNT, silica, hydroxyl
Apatite, nylon or makrolon.
4. a kind of preparation of thermo-setting elastomer tissue engineering bracket with multistage pore structure according to claim 3
Method, it is characterised in that:A diameter of 20~100 μm of the salt particle.
5. a kind of preparation of thermo-setting elastomer tissue engineering bracket with multistage pore structure according to claim 1
Method, it is characterised in that:Hybrid mode in the step (1) is solvent mixing method or heating.
6. a kind of preparation of thermo-setting elastomer tissue engineering bracket with multistage pore structure according to claim 1
Method, it is characterised in that:3D printing parameter in the step (1) is:40~100 DEG C of extrusion chamber temperature and nozzle temperature.
7. a kind of preparation of thermo-setting elastomer tissue engineering bracket with multistage pore structure according to claim 1
Method, it is characterised in that:Heat cross-linking parameter in the step (2) is:Tentatively it is crosslinked in 80 DEG C -100 DEG C of vacuum drying oven
Solidify 12-24h, the then further solidification crosslinking in 120 DEG C -150 DEG C of vacuum drying oven.
8. a kind of preparation of thermo-setting elastomer tissue engineering bracket with multistage pore structure according to claim 1
Method, it is characterised in that:What is obtained in the step (2) has the thermo-setting elastomer tissue engineering bracket of multistage pore structure
Preserved by being freeze-dried.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710348151.XA CN107137775B (en) | 2017-05-17 | 2017-05-17 | Preparation method of thermosetting elastomer tissue engineering scaffold with multistage pore structure |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710348151.XA CN107137775B (en) | 2017-05-17 | 2017-05-17 | Preparation method of thermosetting elastomer tissue engineering scaffold with multistage pore structure |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107137775A true CN107137775A (en) | 2017-09-08 |
CN107137775B CN107137775B (en) | 2020-05-29 |
Family
ID=59778152
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710348151.XA Active CN107137775B (en) | 2017-05-17 | 2017-05-17 | Preparation method of thermosetting elastomer tissue engineering scaffold with multistage pore structure |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107137775B (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109233213A (en) * | 2018-08-17 | 2019-01-18 | 东华大学 | Poly- (decanedioic acid glyceride) 3D printing nano generator of one kind and its preparation method and application |
CN109701080A (en) * | 2018-07-27 | 2019-05-03 | 东华大学 | 4 axis 3D printing tubular medical brackets of one kind and preparation method thereof |
CN112043869A (en) * | 2020-08-19 | 2020-12-08 | 南方医科大学 | Preparation method of elastic and plastic polyester material and elastic and plastic polyester material |
CN112088020A (en) * | 2018-03-22 | 2020-12-15 | 缇斯股份有限公司 | 3D printing composition for biomaterials |
CN113244460A (en) * | 2021-04-29 | 2021-08-13 | 南开大学 | Oriented microchannel bracket for promoting tissue regeneration and preparation method thereof |
CN114211744A (en) * | 2021-12-03 | 2022-03-22 | 宁波诺丁汉新材料研究院有限公司 | 3D printing self-filling multi-level porous sensor and preparation method thereof |
CN114307997A (en) * | 2021-12-28 | 2022-04-12 | 中物院成都科学技术发展中心 | Super-hydrophobic porous material for oil-water separation and preparation method thereof |
CN115054727A (en) * | 2022-06-07 | 2022-09-16 | 东华大学 | Conductive cardiac muscle patch attached to heart curved surface and preparation method thereof |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103751852A (en) * | 2014-01-24 | 2014-04-30 | 天津理工大学 | Preparation method of three-dimensional artificial random porous structure tissue engineering scaffold |
CN103815992A (en) * | 2014-01-15 | 2014-05-28 | 浙江大学 | Device and method for 3D printing of multi-branch three-dimensional biological structure |
CN103990182A (en) * | 2014-05-30 | 2014-08-20 | 东华大学 | Three-dimensional scaffold material for bone tissue repair and preparation method thereof |
US20160046832A1 (en) * | 2014-08-14 | 2016-02-18 | Secant Medical, Inc. | Composition, methods and devices useful for manufacturing of implantable articles |
CN105563841A (en) * | 2016-02-26 | 2016-05-11 | 东莞劲胜精密组件股份有限公司 | 3D printing manufacturing method and equipment for porous three-dimensional part |
-
2017
- 2017-05-17 CN CN201710348151.XA patent/CN107137775B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103815992A (en) * | 2014-01-15 | 2014-05-28 | 浙江大学 | Device and method for 3D printing of multi-branch three-dimensional biological structure |
CN103751852A (en) * | 2014-01-24 | 2014-04-30 | 天津理工大学 | Preparation method of three-dimensional artificial random porous structure tissue engineering scaffold |
CN103990182A (en) * | 2014-05-30 | 2014-08-20 | 东华大学 | Three-dimensional scaffold material for bone tissue repair and preparation method thereof |
US20160046832A1 (en) * | 2014-08-14 | 2016-02-18 | Secant Medical, Inc. | Composition, methods and devices useful for manufacturing of implantable articles |
CN105563841A (en) * | 2016-02-26 | 2016-05-11 | 东莞劲胜精密组件股份有限公司 | 3D printing manufacturing method and equipment for porous three-dimensional part |
Non-Patent Citations (2)
Title |
---|
HENGSONG SHI等: "Poly(glycerol sebacate)-modified polylactic acid scaffolds with improved hydrophilicity, mechanical strength and bioactivity for bone tissue regeneration", 《RSC ADVANCES》 * |
YI-CHEUN YEH等: "3D printing of photocurable poly(glycerol sebacate) elastomers", 《BIOFABRICATION》 * |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112088020A (en) * | 2018-03-22 | 2020-12-15 | 缇斯股份有限公司 | 3D printing composition for biomaterials |
CN109701080A (en) * | 2018-07-27 | 2019-05-03 | 东华大学 | 4 axis 3D printing tubular medical brackets of one kind and preparation method thereof |
CN109701080B (en) * | 2018-07-27 | 2021-06-29 | 东华大学 | 4-axis 3D printing tubular medical stent and preparation method thereof |
CN109233213A (en) * | 2018-08-17 | 2019-01-18 | 东华大学 | Poly- (decanedioic acid glyceride) 3D printing nano generator of one kind and its preparation method and application |
CN109233213B (en) * | 2018-08-17 | 2021-08-31 | 东华大学 | Poly (glycerol sebacate) 3D printing nano-generator and preparation method and application thereof |
CN112043869A (en) * | 2020-08-19 | 2020-12-08 | 南方医科大学 | Preparation method of elastic and plastic polyester material and elastic and plastic polyester material |
CN113244460A (en) * | 2021-04-29 | 2021-08-13 | 南开大学 | Oriented microchannel bracket for promoting tissue regeneration and preparation method thereof |
CN114211744A (en) * | 2021-12-03 | 2022-03-22 | 宁波诺丁汉新材料研究院有限公司 | 3D printing self-filling multi-level porous sensor and preparation method thereof |
CN114307997A (en) * | 2021-12-28 | 2022-04-12 | 中物院成都科学技术发展中心 | Super-hydrophobic porous material for oil-water separation and preparation method thereof |
CN115054727A (en) * | 2022-06-07 | 2022-09-16 | 东华大学 | Conductive cardiac muscle patch attached to heart curved surface and preparation method thereof |
CN115054727B (en) * | 2022-06-07 | 2023-10-13 | 东华大学 | Conductive myocardial patch attached to curved surface of heart and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
CN107137775B (en) | 2020-05-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107137775A (en) | A kind of preparation method of the thermo-setting elastomer tissue engineering bracket with multistage pore structure | |
Dong et al. | Application of TPMS structure in bone regeneration | |
Hutmacher et al. | Scaffold design and fabrication | |
Naghieh et al. | Combinational processing of 3D printing and electrospinning of hierarchical poly (lactic acid)/gelatin-forsterite scaffolds as a biocomposite: Mechanical and biological assessment | |
CN105343936B (en) | A kind of PLCL three-dimensional porous rack, PLCL-COL compound rest and preparation method thereof | |
Beniwal et al. | A review on pore and porosity in tissue engineering | |
Mahumane et al. | 3D scaffolds for brain tissue regeneration: architectural challenges | |
DE69821774T2 (en) | Biodegradable composites | |
Thavornyutikarn et al. | Bone tissue engineering scaffolding: computer-aided scaffolding techniques | |
Liu et al. | Design and development of three-dimensional scaffolds for tissue engineering | |
Cui et al. | Rapid prototyping of a double-layer polyurethane–collagen conduit for peripheral nerve regeneration | |
CN105311683B (en) | A kind of network containing internal channel and the bionical tissue engineering bracket of directional pore structure and the preparation method and application thereof | |
Seunarine et al. | 3D polymer scaffolds for tissue engineering | |
CN109529122A (en) | A kind of resilient bilayers tubular tissue engineering rack and preparation method thereof with multistage pore structure | |
Nie et al. | Fabrication of poly (L-lactic acid) tissue engineering scaffolds with precisely controlled gradient structure | |
Meng et al. | Melt-based, solvent-free additive manufacturing of biodegradable polymeric scaffolds with designer microstructures for tailored mechanical/biological properties and clinical applications | |
Girão et al. | Microfabrication of a biomimetic arcade-like electrospun scaffold for cartilage tissue engineering applications | |
Chansoria et al. | Regenerating dynamic organs using biomimetic patches | |
CN106178115A (en) | A kind of high porosity high connectivity biological support preparation method | |
Kennedy et al. | 3D printing soft tissue scaffolds using Poly (caprolactone) | |
Eryildiz | Fabrication of drug-loaded 3D-printed bone scaffolds with radial gradient porosity | |
Chen et al. | A novel approach via combination of electrospinning and FDM for tri-leaflet heart valve scaffold fabrication | |
Dong et al. | A hybrid platform for three-dimensional printing of bone scaffold by combining thermal-extrusion and electrospinning methods | |
Kumar et al. | Electrospun 3d scaffolds for tissue regeneration | |
Bakhtiari et al. | Fatigue behaviour of load-bearing polymeric bone scaffolds: A review |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |