CN105838602B - A kind of method and device preparing tissue - Google Patents

A kind of method and device preparing tissue Download PDF

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Publication number
CN105838602B
CN105838602B CN201610304436.9A CN201610304436A CN105838602B CN 105838602 B CN105838602 B CN 105838602B CN 201610304436 A CN201610304436 A CN 201610304436A CN 105838602 B CN105838602 B CN 105838602B
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cell
structure
porous structure
dimensional porous
main body
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CN201610304436.9A
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Chinese (zh)
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CN105838602A (en
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赵小文
张东锋
赵文平
蔡君华
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深圳市艾科赛龙科技股份有限公司
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0693Tumour cells; Cancer cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2513/003D culture

Abstract

The embodiment of the invention discloses a kind of method and devices preparing tissue, and a construction profile is built according to the contour structures that cell and tissue structrue goes out;The three-dimensional porous structure of the construction profile is built according to the structure feature of cell, the structure feature includes the shape of the structure level number of cell, cell;To the three-dimensional porous structure by biometric print at the cell culture main body of microenvironment system, so as to provide stable environment for the growth of cell, close to the construction of human tissue organ, gap form is orientated regular, it can solve the problems, such as that array culture cell distribution is unordered, it can be used for some cell culture correlation subject studies and drug screening simultaneously, researcher helped to obtain the cell growth data closer under normal physiological condition.

Description

A kind of method and device preparing tissue

Technical field

The present embodiments relate to biotechnology more particularly to a kind of method and devices preparing tissue.

Background technology

Traditional 2D cultures cannot help researcher to obtain the cell data under more closer normal physiological condition, for another Medicament research and development flow of the tradition based on target spot (target-based) takes a substantial amount of time and financial resources, and this flow success rate At a fairly low, comprehensive performance is unsatisfactory.

Invention content

The purpose of the embodiment of the present invention is to propose a kind of method and device preparing tissue, it is intended to how for cell life Long the problem of stable environment is provided.

For this purpose, the embodiment of the present invention uses following technical scheme:

In a first aspect, a kind of method preparing tissue, the method includes:

A construction profile is built according to the contour structures that cell and tissue structrue goes out;

The three-dimensional porous structure of the construction profile is built according to the structure feature of cell, the structure feature includes cell Structure level number, cell shape;

To the three-dimensional porous structure by biometric print at the cell culture main body of microenvironment system.

Preferably, it is described to the three-dimensional porous structure by biometric print at the cell culture main body of microenvironment system, Including:

In million grades of clean rooms, by hydroxyapatite and PLA composite materials or phosphoric acid calcium material by described three Dimension porous structure is printed as the cell culture main body of microenvironment system.

Preferably, high 5 millimeters of the cell culture main body of the microenvironment system, 16 millimeters of diameter, pore size 300 Micron and a diameter of 500 microns of structural column.

Preferably, it is described to the three-dimensional porous structure by biometric print at microenvironment system cell culture main body it Before, further include:

The three-dimensional porous structure is converted to 3 dimensional format file to preserve, and by the 3 dimensional format file after preservation Be converted to computer program.

Preferably, it is described to the three-dimensional porous structure by biometric print at microenvironment system cell culture main body it Afterwards, further include:

Aseptic process carried out to the cell culture main body of the microenvironment system, the aseptic process include steam sterilizing and Gamma-ray irradiation sterilizes.

Second aspect, a kind of device preparing tissue, described device include:

First structure module, the contour structures for being gone out according to cell and tissue structrue build a construction profile;

Second structure module, the three-dimensional porous structure for building the construction profile according to the structure feature of cell, institute State the shape that structure feature includes the structure level number of cell, cell;

Print module is used for the three-dimensional porous structure through biometric print into the cell culture master of microenvironment system Body.

Preferably, the print module, is used for:

In million grades of clean rooms, by hydroxyapatite and PLA composite materials or phosphoric acid calcium material by described three Dimension porous structure is printed as the cell culture main body of microenvironment system.

Preferably, high 5 millimeters of the cell culture main body of the microenvironment system, 16 millimeters of diameter, pore size 300 Micron and a diameter of 500 microns of structural column.

Preferably, described device further includes:

Conversion module is preserved for the three-dimensional porous structure to be converted to 3 dimensional format file, and will be after preservation 3 dimensional format file be converted to computer program.

Preferably, described device further includes:

Aseptic process module carries out aseptic process for the cell culture main body to the microenvironment system, described sterile Processing includes steam sterilizing and gamma-ray irradiation sterilizing.

The embodiment of the present invention provides a kind of method and device preparing tissue, the contour structures gone out according to cell and tissue structrue Build a construction profile;The three-dimensional porous structure of the construction profile is built according to the structure feature of cell, the structure is special Sign includes the shape of the structure level number of cell, cell;To the three-dimensional porous structure by biometric print at microenvironment system Cell culture main body, so as to provide stable environment for the growth of cell, close to the construction of human tissue organ, gap shape State orientation is regular, can solve the problems, such as that array culture cell distribution is unordered, while can be used for some cell culture correlation Subject study and drug screening help researcher to obtain the cell growth data closer under normal physiological condition.

Description of the drawings

Fig. 1 is the flow diagram for the method that the embodiment of the present invention prepares tissue;

Fig. 2 a are the vertical views of three-dimensional porous structure model of the embodiment of the present invention;

Fig. 2 b are the front views of three-dimensional porous structure model of the embodiment of the present invention;

Fig. 3 a are the vertical view partial enlarged views of three-dimensional porous structure model of the embodiment of the present invention;

Fig. 3 b are that three-dimensional porous structure model of the embodiment of the present invention faces partial enlarged view;

Fig. 4 is the embodiment of the present invention and Fig. 2 b are the overall structure figures at same visual angle;

Fig. 5 is the embodiment of the present invention and Fig. 2 a are the overall structure figures at the same visual angle;

Fig. 6 is the 3D printing figure of three-dimensional porous structure model of the embodiment of the present invention;

Fig. 7 is the 3D printing figure of three-dimensional porous structure model of the embodiment of the present invention

Fig. 8 is a kind of high-level schematic functional block diagram of device preparing tissue provided in an embodiment of the present invention.

Specific implementation mode

The embodiment of the present invention is described in further detail with reference to the accompanying drawings and examples.It is understood that this The described specific embodiment in place is used only for explaining the embodiment of the present invention, rather than the restriction to the embodiment of the present invention.In addition also It should be noted that illustrating only for ease of description, in attached drawing and the relevant part of the embodiment of the present invention rather than entire infrastructure.

Referring to Fig.1, Fig. 1 is the flow diagram for the method that the embodiment of the present invention prepares tissue.

In the first embodiment, which includes:

Step 101, a construction profile is built according to the contour structures that cell and tissue structrue goes out;

Specifically, constructing one according to the contour structures that cell culture is formed by UG softwares or other Three-dimensional Design Softwares A construction profile.

Step 102, the three-dimensional porous structure of the construction profile, the structure feature are built according to the structure feature of cell The shape of structure level number, cell including cell;

Specifically, the difference according to different cell sizes is designed inside configuration, with reference to biomethanics, sky is designed Gap form, (pore size is 105~420 microns to regular, the connected perforation in gap three-dimensional porous structure model, is suitble to thin Born of the same parents cultivate), it can be allocated according to requirements such as the culture eucaryotic cell structure number of plies, shapes when design.Specifically, being three-dimensional with reference to figure 2a Vertical view, Fig. 2 b of porous structure model are the front view of three-dimensional porous structure model, Fig. 3 a are three-dimensional porous structure model It overlooks partial enlarged view, Fig. 3 b and faces partial enlarged view for three-dimensional porous structure model, be visually observed model gap shape State is orientated regular, and with magnifying glass or micro- sem observation, the perforation it is observed that hole is cross-linked with each other, pore size is 105~420 microns, it is suitble to cell culture.01 is identified as culture medium sample holes or cell sample holes or waste liquid exclusion outlet, 02 mark Know and be culture medium sample holes or cell sample holes or waste liquid excludes outlet, 03 be identified as culture medium sample holes or cell sample holes or Waste liquid excludes outlet.

Wherein, three-dimensional structure structure model can be according to physiological environment analog simulation human tissue structure.

Step 103, to the three-dimensional porous structure by biometric print at the cell culture main body of microenvironment system.

Preferably, it is described to the three-dimensional porous structure by biometric print at the cell culture main body of microenvironment system, Including:

In million grades of clean rooms, by hydroxyapatite and PLA composite materials or phosphoric acid calcium material by described three Dimension porous structure is printed as the cell culture main body of microenvironment system.

Wherein, high 5 millimeters of the cell culture main body of the microenvironment system, 16 millimeters of diameter, pore size be 300 micro- Rice and a diameter of 500 microns of structural column.

Preferably, it is described to the three-dimensional porous structure by biometric print at microenvironment system cell culture main body it Before, further include:

The three-dimensional porous structure is converted to 3 dimensional format file to preserve, and by the 3 dimensional format file after preservation Be converted to computer program.

It preserves, achieve specifically, being converted into the 3 dimensional formats file such as STL, stp in software.Again to its 3 dimensional format into Row biometric print machine programming;It is conducted into and is connected in computer with biological 3D printer, it is multiple to choose hydroxyapatite+PLA The materials such as condensation material, phosphoric acid calcium are printed in million grades of clean rooms.Print the thin of tissue microenvironment system Born of the same parents' trainers structure has good biocompatibility, gas permeability, with human tissue organ's structural similarity.Specifically , with reference to figure 4, Fig. 4 and Fig. 2 b are the overall structure figures at same visual angle.

Preferably, it is described to the three-dimensional porous structure by biometric print at microenvironment system cell culture main body it Afterwards, further include:

Aseptic process carried out to the cell culture main body of the microenvironment system, the aseptic process include steam sterilizing and Gamma-ray irradiation sterilizes.

Such as by taking tumour cell as an example, it is high 5MM that this system, which builds size, and a diameter of 16MM, pore size is 300 micro- Rice, a diameter of 500 microns of structural column, for circulating tumor cell, the diameter of cell is about 20 microns, with reference to figure 5, figure 5 be with Fig. 2 a be the overall structure figure at the same visual angle.The system can be placed on inside fixed culture pond, ensure that cell is being trained Pond growth inside is supported, and the liquid such as cell culture fluid and drug can pass through gap free flow.When system is designed with regard to corresponding Culture medium sample holes, cell sample holes and waste liquid are designed in locational space excludes outlet.Prepare complete histoorgan microenvironment Simulation system, with reference to figure 6 and Fig. 7, Fig. 6 and Fig. 7 are the 3D printing figures of three-dimensional porous structure model.

The embodiment of the present invention provides a kind of method preparing tissue, the contour structures structure one gone out according to cell and tissue structrue A construction profile;The three-dimensional porous structure of the construction profile is built according to the structure feature of cell, the structure feature includes The structure level number of cell, the shape of cell;The three-dimensional porous structure is trained by biometric print at the cell of microenvironment system Main body is supported, so as to provide stable environment for the growth of cell, close to the construction of human tissue organ, gap form is orientated It is regular, it can solve the problems, such as that array culture cell distribution is unordered, while can be used for some cell culture correlation projects and grinding Study carefully and drug screening, help researcher obtain the cell growth data closer under normal physiological condition.

With reference to figure 8, Fig. 8 is a kind of high-level schematic functional block diagram of device preparing tissue provided in an embodiment of the present invention.

In fig. 8, the device for preparing tissue includes:

First structure module 801, the contour structures for being gone out according to cell and tissue structrue build a construction profile;

Second structure module 802, the three-dimensional porous structure for building the construction profile according to the structure feature of cell, The structure feature includes the shape of the structure level number of cell, cell;

Preferably, described device further includes:

Conversion module is preserved for the three-dimensional porous structure to be converted to 3 dimensional format file, and will be after preservation 3 dimensional format file be converted to computer program.

Print module 803 is used for the three-dimensional porous structure through biometric print into the cell culture of microenvironment system Main body.

Wherein, high 5 millimeters of the cell culture main body of the microenvironment system, 16 millimeters of diameter, pore size be 300 micro- Rice and a diameter of 500 microns of structural column.

Preferably, the print module 803, is used for:

In million grades of clean rooms, by hydroxyapatite and PLA composite materials or phosphoric acid calcium material by described three Dimension porous structure is printed as the cell culture main body of microenvironment system.

Preferably, described device further includes:

Aseptic process module carries out aseptic process for the cell culture main body to the microenvironment system, described sterile Processing includes steam sterilizing and gamma-ray irradiation sterilizing.

The embodiment of the present invention provides a kind of device preparing tissue, the contour structures structure one gone out according to cell and tissue structrue A construction profile;The three-dimensional porous structure of the construction profile is built according to the structure feature of cell, the structure feature includes The structure level number of cell, the shape of cell;The three-dimensional porous structure is trained by biometric print at the cell of microenvironment system Main body is supported, so as to provide stable environment for the growth of cell, close to the construction of human tissue organ, gap form is orientated It is regular, it can solve the problems, such as that array culture cell distribution is unordered, while can be used for some cell culture correlation projects and grinding Study carefully and drug screening, help researcher obtain the cell growth data closer under normal physiological condition.

The technical principle of the embodiment of the present invention is described above in association with specific embodiment.These descriptions are intended merely to explain this The principle of inventive embodiments, and it cannot be construed to the limitation to protection domain of the embodiment of the present invention in any way.Based on herein Explanation, those skilled in the art, which would not require any inventive effort, can associate the other specific of the embodiment of the present invention Embodiment, these modes are fallen within the protection domain of the embodiment of the present invention.

Claims (6)

1. a kind of method preparing tissue, which is characterized in that the method includes:
A construction profile is built by the contour structures gone out according to cell and tissue structrue;
The three-dimensional porous structure of the construction profile is built according to the structure feature of cell, the structure feature includes the knot of cell The structure number of plies, the shape of cell, wherein the three-dimensional porous structure void, which is connected, to be penetrated through, and pore size is 105~420 microns, The three-dimensional porous structure includes that culture medium sample holes, cell sample holes and waste liquid exclude outlet;
It is by hydroxyapatite and PLA composite materials or phosphoric acid calcium material that the three-dimensional is more in million grades of clean rooms Pore structure is printed as the cell culture main body of microenvironment system;
Aseptic process is carried out to the cell culture main body of the microenvironment system, the aseptic process includes that steam sterilizing and γ are penetrated Line irradiation sterilization.
2. according to the method described in claim 1, it is characterized in that, high 5 milli of the cell culture main body of the microenvironment system Rice, 16 millimeters of diameter, pore size are 300 microns and a diameter of 500 microns of structural column.
3. method according to claim 1 or 2, which is characterized in that described to be beaten by biology the three-dimensional porous structure It is printed as before the cell culture main body of microenvironment system, further includes:
The three-dimensional porous structure is converted to 3 dimensional format file to preserve, and the 3 dimensional format file after preservation is converted For computer program.
4. a kind of device preparing tissue, which is characterized in that described device includes:
First structure module builds a construction profile for the contour structures by going out according to cell and tissue structrue;
Second structure module, the three-dimensional porous structure for building the construction profile according to the structure feature of cell, the knot Structure feature includes the shape of the structure level number of cell, cell, wherein the three-dimensional porous structure void, which is connected, to be penetrated through, gap Size is 105~420 microns, and the three-dimensional porous structure includes that culture medium sample holes, cell sample holes and waste liquid exclude outlet;
Print module, in million grades of clean rooms, passing through hydroxyapatite and PLA composite materials or phosphoric acid calcium material The three-dimensional porous structure is printed as the cell culture main body of microenvironment system by material;
Aseptic process module carries out aseptic process, the aseptic process for the cell culture main body to the microenvironment system It sterilizes including steam sterilizing and gamma-ray irradiation.
5. device according to claim 4, which is characterized in that high 5 milli of the cell culture main body of the microenvironment system Rice, 16 millimeters of diameter, pore size are 300 microns and a diameter of 500 microns of structural column.
6. device according to claim 4 or 5, which is characterized in that described device further includes:
Conversion module is preserved for the three-dimensional porous structure to be converted to 3 dimensional format file, and by three after preservation Dimension formatted file is converted to computer program.
CN201610304436.9A 2016-05-10 2016-05-10 A kind of method and device preparing tissue CN105838602B (en)

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Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN201193228Y (en) * 2007-02-13 2009-02-11 刘青 Three-dimensional cell-culturing insert, manufacturing equipment thereof and kit
EP2266635A1 (en) * 2009-06-26 2010-12-29 Aarhus Universitet Three-dimensional nanostructured hybrid scaffold and manufacture thereof
CN101884574B (en) * 2010-06-28 2012-03-28 河北工业大学 Method and device for preparing three-dimensional porous support for tissue engineering
CN104147641B (en) * 2014-07-11 2016-08-31 深圳职业技术学院 A kind of for personalized bone renovating material and its preparation method
CN104874023A (en) * 2015-05-29 2015-09-02 山东大学齐鲁医院 Production method of finished-product tissue engineered bone
CN105288738A (en) * 2015-11-18 2016-02-03 深圳市艾科赛龙科技有限公司 Three-dimensional microenvironment structural body for bone cell culture
CN105287055A (en) * 2015-11-18 2016-02-03 深圳市艾科赛龙科技有限公司 3D printing individualized in-vitro bone

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