CN108728395A - It is used to prepare the method and device of the three dimensional biological holder with gradual change type spiral composite construction - Google Patents
It is used to prepare the method and device of the three dimensional biological holder with gradual change type spiral composite construction Download PDFInfo
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- CN108728395A CN108728395A CN201710250386.5A CN201710250386A CN108728395A CN 108728395 A CN108728395 A CN 108728395A CN 201710250386 A CN201710250386 A CN 201710250386A CN 108728395 A CN108728395 A CN 108728395A
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0062—General methods for three-dimensional culture
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/30—Synthetic polymers
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2535/00—Supports or coatings for cell culture characterised by topography
Abstract
The invention discloses a kind of methods being used to prepare the three dimensional biological holder with gradual change type spiral composite construction, including：Determine the miniature looks of the helical structure of three dimensional biological holder；The helical structure with determining miniature looks is prepared by the way of electrofluid jet printing；The number of plies for selecting the helical structure in fiber element, so that it is determined that the structure roll-off characteristic of the fiber element；According to determining structure roll-off characteristic, the helical structure in fiber element is generated layer by layer, and the helix degree of helical structure is successively reduced, so that the structure of fiber element fades to the linear type at top from the screw type of bottom.In addition, also disclosing the device for realizing the above method.The three dimensional biological holder prepared according to the method for the present invention with device has controllable more dimensional structures, porosity and fibre diameter, and its internal structure is gradual change type spiral composite construction, thus is more advantageous to the absorption of the cell after inoculating cell and the differentiation in cell cultivation process and proliferation.
Description
Technical field
The present invention relates to three dimensional biological support technology, more particularly to being used to prepare with gradual change type spiral composite construction
The method and device of three dimensional biological holder.
Background technology
Three dimensional biological support technology has important application in Three-dimensional cell culture.Three-dimensional cell culture technology refer to by
Carrier with three-dimensional structure and various different types of cells co-incubation in vitro, keep cell vertical in the three-dimensional of carrier
It migrates, grow in body space structure, constitute three-dimensional cell-vector compound.Common cell culture due to cell in vitro
Hyperplasia gradually loses original character in the environment of change, is not often consistent with internal situation, and zoopery is completely in body
Interior progress, but it is complicated since internal many factors restriction and internal and external environment influence each other, it is difficult to it grinds
Study carefully single process, and is difficult to study pilot process.Three-dimensional cell culture technology be between monolayer cell culture and zoopery it
Between a kind of technology, maximum simulated in vivo environment and the intuitive and condition controllability of cell culture can be showed
The advantages of.
In order to successfully reach three dimensional biological culture truly, three dimensional biological holder needs to have some important spies
Sign.One is holder must have the porous structure of connection in favor of the transmission of cell grown into substance.Cell grow into for
The formation of cambium plays key effect；In addition, it is necessary to which nutriment and oxygen can be transferred to internal stent, and also need
Want the catabolite of metabolite and timbering material that can be effectively discharged out.The second is holder needs to have and concrete application phase
Matched mechanical property.The mechanical property of holder corresponding to different tissues is not quite similar, this just needs to consider mechanical property
Matching.The third is timbering material needs have good biocompatibility and degradability, to avoid immune response is caused.
Therefore using which kind of Processes and apparatus can be made the small Three-dimensional cell culture holder of the accurate batch wise differences of structure or
Tissue engineering bracket becomes urgent problem to be solved.Also, in the pore size and mechanical performance for how controlling holder, such as
The infiltrative growth etc. of cell is realized in the interaction of what control holder and biosystem, is all to need to answer in the technology
Required for before using in the biomedicine of real practicality the problem of research.
Invention content
Based on this, it is necessary to for limitation and disadvantage existing for existing three dimensional biological support technology, provide and be used to prepare
The method and device of three dimensional biological holder with gradual change type spiral composite construction.This method and device are with electrostatic field spinning
Principle can print the three dimensional biological branch with gradual change type spiral composite construction by adjusting control parameter in print procedure
Frame.The three dimensional biological holder with gradual change type spiral composite construction prepared according to this method and device is Three-dimensional cell culture skill
Art and tissue engineering bracket provide a kind of new selection.The three dimensional biological holder has controllable more dimensional structures, hole
Rate and fibre diameter, internal structure have the speciality of gradual change type spiral composite construction, thus after being more advantageous to inoculating cell
Cell absorption and the differentiation in cell cultivation process and proliferation, can be applied to external three-dimensional support for cell culture and medicine
Object screening etc..
According to an aspect of the invention, there is provided a kind of three-dimensional being used to prepare with gradual change type spiral composite construction is raw
The method of object holder, the three dimensional biological holder include the fiber element of the helical structure with multilayer, the method includes with
Lower step：
Setting or adjustment structural parameters, determine the miniature looks of the helical structure of the three dimensional biological holder；
According to the determining miniature looks, prepared by the way of electrofluid jet printing with the determining miniature looks
Helical structure；
The number of plies for selecting the helical structure in the fiber element of the three dimensional biological holder, so that it is determined that described
The structure roll-off characteristic of fiber element；
According to the structure roll-off characteristic of the determining fiber element, the spiral shell in the fiber element is generated layer by layer
Structure is revolved, and the helix degree of the helical structure is successively reduced, so that the structure of the fiber element is from bottom
Screw type fades to the linear type at top.
The miniature looks include sinusoidal waveform, adjacent circles shape and phase from ring shape in one of the embodiments,.
Determine that the miniature looks of the helical structure include the determining three dimensional biological holder in one of the embodiments,
The miniature looks of the helical structure of the bottom in the helical structure of multilayer in the fiber element.
The method further includes in one of the embodiments,：Prepare be used to form the three dimensional biological holder gather oneself
Lactone solution.
The method further includes in one of the embodiments,：Generating has various sizes of multiple fiber elements.
The method according to the present invention for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction, passes through essence
The really structural parameters in control porous tissue engineering scaffold, can produce with gradual change type spiral composite construction, more sizes
The three dimensional biological holder of fiber element (small to arrive several micron-scales, greatly to tens micron-scales).Manufacture is used to gather in oneself
Ester (PCL) material has good biocompatibility and degradability, can meet three dimensional biological culture holder, tissue engineering bracket institute
The performance requirement needed.
According to another aspect of the present invention, it provides and a kind of being used to prepare the three-dimensional with gradual change type spiral composite construction
The device of biological support, described device include：Material feed unit comprising magazine, Spray needle device and pumping installations, institute
Pumping installations is stated to be suitable for ejecting the material being stored in the magazine by the Spray needle device；High voltage power supply,
Suitable for generating high-voltage electrostatic field, the material ejected from the Spray needle device forms material under the action of the high-voltage electrostatic field
Filament, the material filament suitably form the helical structure；Triaxial movement platform comprising multiple first straight line motors and load
Object platform, the multiple first straight line motor are suitable for driving the movement of the objective table in three dimensions；Substrate is placed on institute
The lower section on objective table and positioned at the Spray needle device is stated, is suitable for collecting the material filament；Climatic chamber, the material
Feed unit, the triaxial movement platform and the substrate are placed in the climatic chamber, and the climatic chamber is suitable for
Constant-temperature constant-humidity environment is provided；Controller is configured to receive pumping installations, the high voltage power supply and institute described in user's input control
The operation of triaxial movement platform is stated, and is additionally configured to set control parameter, Yi Ji before preparing the three dimensional biological holder
The control parameter is adjusted during preparing the three dimensional biological holder.
Preferably, adjusting the control parameter includes：Change the movement velocity of the objective table；Change the high voltage power supply
Voltage value；Change the delivery rate of material feed unit；Change the distance between the Spray needle device and the substrate.
The substrate is polishing silicon crystal substrate in one of the embodiments,.
The material is polycaprolactone solution in one of the embodiments,.
Described device further includes second straight line motor in one of the embodiments, and the Spray needle device is fixed to described
Second straight line motor, the second straight line motor are suitable for receiving the control of the controller, drive the Spray needle device vertical
It is for linear motion on direction.
Three dimensional biological holder with gradual change type spiral composite construction prepared by the above method and device according to the present invention
Be conducive to various sizes of cell in the absorption being inoculated with when printing, and be conducive to cell in subsequent growth on biological support
Proliferation.Also, the three dimensional biological holder with gradual change type spiral composite construction is somebody's turn to do with the porosity (example for being appropriate to cell growth
Such as, porosity is between 60%-70%), larger contact area and good aperture connectivity, be conducive to extracellular matrix
Secretion and the normal perfusion of formation and culture solution provide good environment for the subsequent growth of cell, differentiation and increment.This
Outside, manufacturing the material (for example, polycaprolactone) used in the three dimensional biological holder has good biocompatibility, not interference body
Immunologic mechanism, do not cause immunological rejection.
Description of the drawings
Fig. 1 is to be used to prepare the three dimensional biological with gradual change type spiral composite construction according to one embodiment of the present of invention
The flow chart of the method for holder；
Fig. 2 illustrates the type of the miniature looks of bottom of gradual change type spiral composite construction and its corresponding miniature looks of holder exists
Image under light microscope；
Fig. 3 is to be used to prepare the three dimensional biological with gradual change type spiral composite construction according to one embodiment of the present of invention
The structural schematic diagram of the device of holder；
The three-dimensional with gradual change type spiral composite construction that Fig. 4 A-4B are respectively prepared according to one embodiment of present invention
The vertical view and side view of biological support under a scanning electron microscope；
Fig. 5 is illustrated uses linear type three dimensional biological holder and the three-dimensional life with gradual change type spiral composite construction respectively
Object holder culture attached cell, first day and image of the third day after fluorescent staining under Laser Scanning Confocal Microscope.
Specific implementation mode
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, below in conjunction with the accompanying drawings to the present invention
Specific implementation mode be described in detail.Many details are elaborated in the following description in order to fully understand this hair
It is bright.But the invention can be embodied in many other ways as described herein, those skilled in the art can be not
Similar improvement is done in the case of violating intension of the present invention, therefore the present invention is not limited to the specific embodiments disclosed below.
Fig. 1, which is shown, according to an embodiment of the invention is used to prepare the three-dimensional with gradual change type spiral composite construction
The flow chart of the method for biological support.Three dimensional biological holder includes the fiber element of the helical structure with multilayer, the fiber list
The structure of member is gradual change type spiral composite construction, i.e., the fabric of the fiber element is complete spiral-shaped structure, top layer knot
Structure is linear structure, and for the intermediate multi layer spiral structure from bottom to top layer, their helix degree successively reduces.At this
In embodiment, the method for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction includes the following steps：
S101：The material for being used to form three dimensional biological holder is prepared, which is preferably polycaprolactone (PCL) solution.It should
The preparation process of PCL solution may include for example, the glacial acetic acid of the PCL particles of certain mass and certain volume is blended in one
It rises, first uses ultrasound bath 1 to 2 hour, then mixed to prepare within 1 to 2 hour with ultrasound bath again after being stirred for uniformly
The PCL solution of even a concentration of 60wt% to 80wt%.PCL has good biocompatibility and degradability, can meet three-dimensional
Performance requirement needed for biological culture holder, tissue engineering bracket.
S102：Setting or adjustment structural parameters, determine the miniature looks of the helical structure of three dimensional biological holder.The miniature looks packet
Include sinusoidal waveform, adjacent circles shape and phase from ring shape etc., as shown in Figure 2.It will be appreciated by persons skilled in the art that spiral
The miniature looks of structure are not limited to shown in Fig. 2, can use other any suitable miniature looks according to actual needs.In the present embodiment
In, determine that the miniature looks of helical structure include the helical structure of the bottom in the helical structure of the multilayer in determining fiber element
Miniature looks.The miniature looks of the helical structure of succeeding layer are gradual changes on the basis of the miniature looks of the helical structure of the bottom, i.e.,
Helix degree continuously decreases, to be intended to linear type.
S103：According to the miniature looks determined in step s 102, prepared by the way of electrofluid jet printing with true
The helical structure of fixed miniature looks.The helical structure is the single layer structure in the fiber element of three dimensional biological holder.Electrofluid sprays
Printing is penetrated to may be used known or realize the arbitrary electrofluid jet printing technology of exploitation.Later in association with the use of the present invention
The electrofluid injection of the present embodiment is specifically described in the device for preparing the three dimensional biological holder with gradual change type spiral composite construction
The mode of printing, details are not described herein.
S104：The number of plies for selecting the helical structure in the fiber element of three dimensional biological holder, so that it is determined that the fiber list
The structure roll-off characteristic of member.Fiber element includes the helical structure of multilayer, these helical structures are accumulated successively, and from the bottom to top
Helix degree successively reduces, the linear type until becoming top layer.Therefore, the number of plies of the helical structure in fiber element has been selected,
The structure roll-off characteristic of fiber element can determine.
S105：According to the structure roll-off characteristic of determining fiber element, the helical structure in fiber element is generated layer by layer,
And the helix degree of helical structure is successively reduced, so that the structure of fiber element fades to top from the screw type of bottom
Linear type.In order to generate the fiber element with gradual change type spiral composite construction, firstly generates and meet in step s 102 really
Then the bottom helical structure of fixed miniature looks successively accumulates the spiral knot that helix degree successively reduces on bottom helical structure
Structure generates linear structure until helical structure is close to linear type, then in top layer, to realize the structure of fiber element from spiral
Type is to linear gradual change.
S106：Generating has various sizes of multiple fiber elements.Various sizes of multiple fiber lists are generated as needed
Member can make the fibre structure that the three dimensional biological holder prepared has more sizes (for example, small arrive several micron-scales, arrive greatly
Tens micron-scales).
Illustrate to realize that the above method is used to prepare the three dimensional biological with gradual change type spiral composite construction referring to Fig. 3
The device of holder.The device is worked based on electrostatic spinning principle, including material feed unit 1, high voltage power supply 2, three-axis moving are flat
Platform 3, substrate 4, climatic chamber 5 and controller 6.
Material feed unit 1 includes magazine 101, Spray needle device 102 and pumping installations 103.Pumping installations 103 is suitable for
The material being stored in magazine is ejected by Spray needle device.Material feed unit 1 can be electrofluid jet printing
Stable material supply is provided.In the present embodiment, mixed uniformly PCL solution is stored in magazine 101.Spray needle device
102 be removably attached to can be along the linear motor (not shown) that Z axis moves, and perpendicular to the substrate 4 being disposed below.
The objective table 301 of the anode connection triaxial movement platform 3 of high voltage power supply 2, cathode connect Spray needle device 102.Loading
Platform 301 and Spray needle device 102 are preferably all formed from metal.In the present embodiment, high voltage power supply 2 is DC high-voltage power supply.?
When device works, high voltage power supply 2 is suitable for generating high-voltage electrostatic field between objective table 301 and Spray needle device 102, from Spray needle device
102 materials ejected form material filament under the action of high-voltage electrostatic field, and material filament suitably forms helical structure.
Triaxial movement platform 3 includes multiple linear motors (not shown) and objective table 301.It is usually provided with three straight-line electrics
Machine, these three linear motors moving along X-axis, Y-axis and Z axis in three dimensions of driving objective table 301 respectively.Substrate 4 is removable
It is fixed on the lower section on objective table 301 and positioned at Spray needle device 102 with unloading, suitable for collecting the object ejected from Spray needle device 10
Expect filament.In the present embodiment, substrate 4 is polishing silicon crystal substrate, it will be appreciated by persons skilled in the art that substrate may be used also
To use any other suitable material.
Material feed unit 1, triaxial movement platform 3 and substrate 4 are placed in climatic chamber 5, and the climatic chamber 5 is suitable
In providing constant-temperature constant-humidity environment, to ensure the constant of temperature in whole work process and humidity.
Controller 6 be configured to receive user's input control pumping installations 103, high voltage power supply 2 and triaxial movement platform 3 fortune
Row, for example, control objective table 301 shift position and movement velocity, Spray needle device 102 spout between the top surface of substrate 4
Distance, the output voltage of high voltage power supply 2, material feed unit 1 delivery rate etc..Controller 6 is additionally configured to preparing three
Control parameter is set before dimension biological support, and control parameter is adjusted during preparing three dimensional biological holder.Specifically, example
Such as, before preparing three dimensional biological holder, the motion path and movement velocity of the objective table 301 of triaxial movement platform 3, movement are set
Speed generally could be provided as 50mm/s~300mm/s；By the distance between the top surface of the spout of Spray needle device 102 to substrate 4
It is set as a certain value for example, in the range of 1.5mm~5mm；The output voltage of high voltage power supply 2 is set as example, in 2kV
A certain value in the range of~4kV；The delivery rate of unit 1 is supplied the material to, i.e., for the delivery rate setting of PCL solution
Such as, a certain value in the range of the 0.1 μ l/min of μ l/min~10.It, can be to enable high pressure after setting above-mentioned control parameter
Power supply 2, generates high-voltage electrostatic field between objective table 301 and Spray needle device 102, driving pumping installations 103 so that PCL solution from
The spout of Spray needle device 102 ejects, and starts triaxial movement platform 3 and objective table 301 is moved with predetermined motion path, be located at
Substrate 4 on objective table 301 receives the material filament that PCL solution is formed in high-voltage electrostatic field, to form fiber element.
During generating fiber element, controller 6 adjusts control parameter, such as：Adjust the movement speed of objective table 301
Degree so that during stage movement of the material filament ejected after variation, gradually form linear fiber；Adjustment is high
The output voltage of voltage source 2, to change the field strength of high-voltage electrostatic field, for example, at the end of close to fiber element is generated, output
Larger voltage so that the material filament of formation is pullled downwards by the electric field force of bigger, is more likely to form linear fiber；It adjusts
The delivery rate of whole pumping installations 103, after delivery rate changes, the pressure change that the PCL solution in magazine 101 is subject to,
And then the extruded velocity of PCL solution changes, after delivery rate increases, the pressure that PCL solution is subject to becomes larger, and material filament exists
Tend to form linear fiber under the variation effect of this power；Adjust Spray needle device 102 spout to the top surface of substrate 4 it
Between distance, the time required to distance influences electrostatic field field strength size and material filament 4 from spout to substrate, after distance reduces,
Material filament tends to form linear fiber.
The above method and device according to the present invention, by accurately controlling and adjusting in three dimensional biological holder preparation process
Multiple control parameters can produce the three dimensional biological holder with gradual change type spiral composite construction.Fig. 4 A-4B are respectively shown
The vertical view and side view of three dimensional biological holder with gradual change type spiral composite construction under a scanning electron microscope.This has
The three dimensional biological holder of gradual change type spiral composite construction is conducive to various sizes of cell in the absorption being inoculated with when printing, and favorably
In the proliferation on biological support when cell is in subsequent growth.Also, it should be with the three dimensional biological of gradual change type spiral composite construction
Holder, which has, is appropriate to the porosity (for example, porosity is between 60%-70%) of cell growth, larger contact area and good
Good aperture connectivity, is conducive to secretion and the normal perfusion of formation and culture solution of extracellular matrix, is that cell is subsequent
Growth, differentiation and proliferation provide good environment.
Fig. 5 is illustrated uses linear type three dimensional biological holder and the three-dimensional life with gradual change type spiral composite construction respectively
Object holder culture attached cell, first day and image of the third day after fluorescent staining under Laser Scanning Confocal Microscope.By Fig. 5
In confocal images it is found that cell is raw in the three-dimensional with gradual change type spiral composite construction under same cultivation cycle
Absorption and cultivation effect on object holder are an advantage over pure linear type three dimensional biological holder.Two after being dyed to MTS using microplate reader
Cell carries out the analysis of absorbance in kind of different support, first day linear type three dimensional biological holder with have gradual change type spiral compound
The absorbance of the three dimensional biological holder of structure is close, and the absorbance after cell culture dyeing on linear type three dimensional biological holder is about
It is 0.35, is slightly below the 0.40 of the three dimensional biological holder of gradual change type spiral-shaped structure.However in third day, the life of linear type three-dimensional
The absorbance after cell culture dyeing on object holder is about 0.43, and cell on the three dimensional biological holder of gradual change type helical structure
Absorbance after dyeing is about 1.0.It can be seen that gradual change type spiral composite construction is conducive to proliferation of the cell on holder.
Several embodiments of the invention above described embodiment only expresses, the description thereof is more specific and detailed, but simultaneously
Cannot the limitation to the scope of the claims of the present invention therefore be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect range.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
1. a kind of method being used to prepare the three dimensional biological holder with gradual change type spiral composite construction, the three dimensional biological holder
Include the fiber element of the helical structure with multilayer, the described method comprises the following steps：
Setting or adjustment structural parameters, determine the miniature looks of the helical structure of the three dimensional biological holder；
According to the determining miniature looks, the spiral shell with the determining miniature looks is prepared by the way of electrofluid jet printing
Revolve structure；
The number of plies of the helical structure in the fiber element of the three dimensional biological holder is selected, so that it is determined that the fiber
The structure roll-off characteristic of unit；
According to the structure roll-off characteristic of the determining fiber element, the spiral knot in the fiber element is generated layer by layer
Structure, and the helix degree of the helical structure is successively reduced, so that spiral of the structure of the fiber element from bottom
Type fades to the linear type at top.
2. the method according to claim 1 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, the miniature looks include sinusoidal waveform, adjacent circles shape and mutually from ring shape.
3. the method according to claim 1 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, determining in the fiber element that the miniature looks of the helical structure include the determining three dimensional biological holder
The miniature looks of the helical structure of the bottom in the helical structure of multilayer.
4. the method according to claim 1 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, the method further includes：Prepare the polycaprolactone solution for being used to form the three dimensional biological holder.
5. the method according to claim 1 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, the method further includes：Generating has various sizes of multiple fiber elements.
6. a kind of device being used to prepare the three dimensional biological holder with gradual change type spiral composite construction, the three dimensional biological holder
Include the fiber element of the helical structure with multilayer, described device includes：
Material feed unit comprising magazine, Spray needle device and pumping installations, the pumping installations are suitable for that institute will be stored in
The material stated in magazine is ejected by the Spray needle device；
High voltage power supply is suitable for generating high-voltage electrostatic field, and the material ejected from the Spray needle device is in the high-voltage electrostatic field
Under the action of form material filament, the material filament suitably forms the helical structure；
Triaxial movement platform comprising multiple first straight line motors and objective table, the multiple first straight line motor are suitable for driving
The movement of the objective table in three dimensions；
Substrate is placed on the lower section on the objective table and positioned at the Spray needle device, is suitable for collecting the material filament；
Climatic chamber, the material feed unit, the triaxial movement platform and the substrate are placed on the constant temperature and humidity
In case, the climatic chamber is adapted to provide for constant-temperature constant-humidity environment；
It is flat to be configured to pumping installations, the high voltage power supply and the three-axis moving described in reception user's input control for controller
The operation of platform, and be additionally configured to set control parameter before preparing the three dimensional biological holder, and preparing the three-dimensional
The control parameter is adjusted during biological support, so that described be used to prepare the three-dimensional with gradual change type spiral composite construction
The device of biological support executes：
Setting or adjustment structural parameters, determine the miniature looks of the helical structure of the three dimensional biological holder；
According to the determining miniature looks, the spiral shell with the determining miniature looks is prepared by the way of electrofluid jet printing
Revolve structure；
The number of plies of the helical structure in the fiber element of the three dimensional biological holder is selected, so that it is determined that the fiber
The structure roll-off characteristic of unit；
According to the structure roll-off characteristic of the determining fiber element, the spiral knot in the fiber element is generated layer by layer
Structure, and the helix degree of the helical structure is successively reduced, so that spiral of the structure of the fiber element from bottom
Type fades to the linear type at top.
7. the device according to claim 6 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, adjusting the control parameter and including：Change the movement velocity of the objective table；Change the electricity of the high voltage power supply
Pressure value；Change the delivery rate of material feed unit；Change the distance between the Spray needle device and the substrate.
8. the device according to claim 6 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, the substrate is polishing silicon crystal substrate.
9. the device according to claim 6 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, the material is polycaprolactone solution.
10. the device according to claim 6 for being used to prepare the three dimensional biological holder with gradual change type spiral composite construction,
It is characterized in that, described device further includes second straight line motor, the Spray needle device is fixed to the second straight line motor, described
Second straight line motor is suitable for receiving the control of the controller, drives the Spray needle device for linear motion in the vertical direction.
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| CN201710250386.5A CN108728395A (en) | 2017-04-17 | 2017-04-17 | It is used to prepare the method and device of the three dimensional biological holder with gradual change type spiral composite construction |
| SG10201803140UA SG10201803140UA (en) | 2017-04-17 | 2018-04-13 | Method and apparatus for making three-dimensional biomimetic scaffold with gradual coiled composite structure |
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| CN201710250386.5A CN108728395A (en) | 2017-04-17 | 2017-04-17 | It is used to prepare the method and device of the three dimensional biological holder with gradual change type spiral composite construction |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110421838A (en) * | 2019-07-12 | 2019-11-08 | 西交利物浦大学 | Using the preparation method of pore type structure construction three dimensional biological bracket |
| CN110549597A (en) * | 2019-09-05 | 2019-12-10 | 上海交通大学医学院附属第九人民医院 | Electrostatic spinning curved yarn printing and application |
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| WO2014184386A1 (en) * | 2013-05-17 | 2014-11-20 | Centre De Recherche Public Henri Tudor | Cell cultivation scaffold |
| CN104874027A (en) * | 2015-05-12 | 2015-09-02 | 上海大学 | Preparation method of multi-medicine controllable load gradient regeneration bone scaffold |
| US20160040320A1 (en) * | 2014-08-07 | 2016-02-11 | Research & Business Foundation Sungkyunkwan University | Method of manufacturing porous three-dimensional micro/nanofibrous scaffold using electrohydrodynamic process and porous three-dimensional micro/nanofibrous scaffold manufactured thereby |
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| US20100310623A1 (en) * | 2009-06-05 | 2010-12-09 | Laurencin Cato T | Synergetic functionalized spiral-in-tubular bone scaffolds |
| US20140072610A1 (en) * | 2011-03-21 | 2014-03-13 | National University Of Singapore | Bioabsorbable tracheal stent, and method of manufacturing thereof |
| CN102358959A (en) * | 2011-08-16 | 2012-02-22 | 中山大学 | Method and device for preparing electrospinning fiber bracket with three-dimensional structure |
| US20140011416A1 (en) * | 2012-07-05 | 2014-01-09 | Board Of Regents Of The University Of Nebraska | Three Dimensionally and Randomly Oriented Fibrous Structures |
| WO2014184386A1 (en) * | 2013-05-17 | 2014-11-20 | Centre De Recherche Public Henri Tudor | Cell cultivation scaffold |
| US20160040320A1 (en) * | 2014-08-07 | 2016-02-11 | Research & Business Foundation Sungkyunkwan University | Method of manufacturing porous three-dimensional micro/nanofibrous scaffold using electrohydrodynamic process and porous three-dimensional micro/nanofibrous scaffold manufactured thereby |
| CN104874027A (en) * | 2015-05-12 | 2015-09-02 | 上海大学 | Preparation method of multi-medicine controllable load gradient regeneration bone scaffold |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110421838A (en) * | 2019-07-12 | 2019-11-08 | 西交利物浦大学 | Using the preparation method of pore type structure construction three dimensional biological bracket |
| CN110549597A (en) * | 2019-09-05 | 2019-12-10 | 上海交通大学医学院附属第九人民医院 | Electrostatic spinning curved yarn printing and application |
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| SG10201803140UA (en) | 2018-11-29 |
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