CN109718397A - A kind of biological micro-assembly robot of assembling - Google Patents
A kind of biological micro-assembly robot of assembling Download PDFInfo
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- CN109718397A CN109718397A CN201711050929.5A CN201711050929A CN109718397A CN 109718397 A CN109718397 A CN 109718397A CN 201711050929 A CN201711050929 A CN 201711050929A CN 109718397 A CN109718397 A CN 109718397A
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Abstract
It takes place frequently for modern society's disease, the Various Tissues and organ of many patients face different degrees of failure under slight illness invasion, the demand of reparation and the replacement of clinical pathological tissues and organ is continuously increased, and artificial organ Organ Reconstruction has become very urgent need and solves the problems, such as.And a kind of biological micro-assembly robot of assembling of the present invention, for field of tissue engineering technology, porosity is produced with structure difference by using different materials and can load the layered-scaffold for coating hydrogel of various kinds of cell, the composition of particular organisms tissue can be simulated, and artificial controllable carry out assembled formation, it realizes the cell of in vitro and the dimensional culture of living tissue, provides potential solution for organizational project and artificial organs repair and reconstruction.
Description
Technical field
This patent repairs field for organizational project and medicine, produces porosity and structure not by using different materials
The layered-scaffold for coating hydrogel that is same and can loading various kinds of cell, can simulate the composition of particular organisms tissue, and people
For controllable carry out assembled formation, the cell of in vitro and the dimensional culture of living tissue are realized, for organizational project and manually
Organ Reconstruction etc. provides new means.
Background technique
With the development of economy, the accelerating rhythm of life, modern society's disease take place frequently, the Various Tissues and device of many patients
Official faces different degrees of failure under slight illness invasion, and the demand of reparation and the replacement of clinical pathological tissues and organ constantly increases
Add, the reparation and reconstruction of artificial organ have become very urgent need and solve the problems, such as.
Clinically, for the tissue and organ of generation lesion, First Principles are to do everything possible to carry out self-treating and repair
It is multiple, and recovery organization and the original function of organ；But if lesion degree is irreversible and cannot maintain that patient's is basic
Vital movement then needs the method using organizational engineering, replaces to pathological tissues and organ, promotes the quality of life of patient
And survival rate.Biology reconstruction is the emerging application technology developed in recent years.Currently, other than brain, nearly all human body device
Official and tissue have corresponding artificial bio-membrane's product.Although most of products are not also the man-made organ and tissue of completeness, still
Do not have and replace the institute of internal organs functional, and in size and also can't be compared with natural organ in terms of the service life.But with existing
For the rapid development of medicine, the effect of man-made organ and tissue is more and more important.
Biological 3D printing technique is a kind of technology for carrying out living tissue printing for raw material with living cells etc., is existed at present
The fields such as aorta petal, implant operation guide plate, artificial lower jaw, tooth, heart valve are applied.It, can using biological 3D printing
By the living cells of the acquisition using stem cell in organism after Differentiation Induction in vitro as raw material, or it is high using biocompatibility
High molecular material, direct printing manufacture organs of living beings tissue, due to the reparation and replacement of pathological tissues, solution is clinically transplanted
The problems such as donor is insufficient.
This patent is using the method for computer three-dimensional modeling, 3D printing and in vitro culture, and layering preparation porosity and structure are not
Together, coat hydrogel after can for cell adhesion, proliferation, migration bracket, then carry out living tissue bionical assembled formation.It presses
According to specific tissue or the cell type composition requirement of organ, it can artificially change the internal structure and load of the lamella mould holder
Cell, after carrying out in vitro culture, the mechanical property of lamella membrane support had both been can be improved in the hydrogel on the outer layer covers of supporting structure
Can, while again better external environment can be provided for the existence of cell.This patent is that clinical medicine tissue and organ transplant supply
Body reconstruction provides a kind of potential solution.
Summary of the invention
This patent passes through biological 3D printing method, prepares the layered-scaffold for being able to carry out different cell culture, passes through electricity
Brain Programming, it is internal that there is different hole configurationss and porosity.When being inoculated with cell on film, and tentatively cultivated
Afterwards, then by the lamella mould holder for loading different cells assembled formation is carried out, while is uniformly applied in outer layer and is covered with thin layer water-setting
Glue is persistently cultivated, until it grows up to the tissue with biological function, the histoorgan reparation and reconstruction for organism.
In order to achieve the above object, the new technique scheme that this patent uses is:
Layered-scaffold is prepared using biological 3D printing technique, the internal structure and controlled porosity of bracket are propping up cell
After being cultivated on frame, then the lamella membrane support for being paved with cell is encapsulated in hydrogel and carries out continuing culture, until living body is micro-
The appearance of tissue.
1) bottom membrane support uses polycaprolactone (PCL) for substrate, will be gathered by computer programming using 3D printing means
Caprolactone is orderly printed as silk, silk diameter range between 10-100 μm, and control the inside aperture of bracket 1-10 μm it
Between.Polycaprolactone is not degradable in human body, can play stable support function to micro texture.
2) using polylactic acid -ol acid copolymer, (PLGA, ten thousand) it is substrate that molecular weight is 30 to middle layer membrane support, with upper layer film
The different molecular weight of bracket can guarantee that material is gradually degraded under suitable condition.By polylactic acid -ol acid copolymer into
The molding of row 3 D-printing, silk diameter range, by computer programming, control the arrangement of bracket one-dimensional order between 10 μm -100 μm.
Compared to bottom membrane support, the bracket of one-dimensional order can growth to cell and migration have bigger inducing action, to culture day
So the cell of ordering growth is of great importance in tissue.
3) upper layer membrane support using polylactic acid -ol acid copolymer (PLGA, ten thousand) it is substrate that molecular weight, which is 10, lesser point
Son amount can guarantee that material starts to degrade rapidly under suitable condition.Polylactic acid -ol acid is copolymerized using electrostatic spinning technique
Object carries out spinning moulding, and silk diameter range is between 10nm-100 μm.Compared to other two layers, the film of the unordered densification of top layer
Structure can faster make cell adhesion grow up to n cell lamella, form epidermal structure, shield to entire micro-assembly robot.
4) the above-mentioned single-layer bracket prepared is subjected to assembled formation, cell injuring model and hydrogel encapsulation.Because of branch
The good biocompatibility of frame material and the hydrogel of coating itself, the interior spatial structure after assembling are able to achieve the quick of cell
Proliferation and intercellular mutual exchange, and gradually grow up to the biological tissue of fusion.What it is because of membrane support selection is different molecular weight
Organic high molecular polymer is substrate, will not be degraded at once in vivo, but with the fracture of the covalent bond of polymer and gradually
Occur, this is conducive to biological tissue and is preferably formed.
Compared with prior art, the advantage of this patent is
1, this patent, can be according to the difference of cultured tissue, after replacing different corresponding cells using layering assemble method
It is cultivated, and in practical application, is not limited to three-decker, the tune of material and structure can be carried out according to specific requirements
It is whole, so as to preferably realize functionalization.
2, this patent can be formed, not for it based on three-dimensional fast shaping technology according to the cell of different tissues
With the growth habit that cell requires, the layered-scaffold for producing different interior spatial structures is cultivated the cells.
3, this patent using different interior spatial structures layered-scaffold on the basis of, be reinforcing material compatibility and
Mechanical property and better growing environment is provided for cell, chooses suitable hydrogel and material is coated, and assembling
After cultivating a period of time, whole coating and molding further are carried out to total, provide a whole microenvironment, this is more sharp
In the formation of biological tissue.
Detailed description of the invention
As shown, Fig. 1 is the schematic diagram of entire biological micro-assembly robot assemble method, it is each in different specific organizations
The material and internal structure of layer bracket are different, while the hydrogel component of outer layer coating can also be adjusted, and present principles figure is only
By taking human skin tissue reproduces as an example；
Fig. 2 is the microcosmic pictorial diagram of different structure layering membrane support；
Fig. 3 is by taking artificial skin as an example, and (at flesh stem cell, endothelium is thin for cultivating specific cells for the bracket of different structure
Born of the same parents and fibroblast) hematoxylin and Yihong and immunofluorescence dyeing figure.
Fig. 4 is by taking Skins culture as an example, the assembling biology micro-assembly robot pictorial diagram of different-thickness.
Specific embodiment
This patent is described further below with reference to implementing regulations.
1) layered-scaffold production method: bottom bracket uses polycaprolactone (PCL) for substrate, by polycaprolactone with 7%
Concentration is dissolved in dimethylformamide and tetrahydrofuran mixed solution that volume ratio is 4:1, and 6h is sufficiently stirred, is compiled by computer
Polycaprolactone solution is orderly printed as silk, silk diameter range controls between 10-100 μm using 3D printing means by journey
The inside aperture of bracket is between 1-10 μm.Middle layer and upper layer bracket use polylactic acid -ol acid copolymer (PLGA) for substrate, will
Polylactic acid -ol acid copolymer is dissolved in the single solution of dimethylformamide with 10% concentration, and 6h is sufficiently stirred；Then pass through electricity
The analysis of brain three-dimensional modeling, designs the space structure of bracket, the branch of one-dimensional order and unordered densification is produced according to specific requirements
Frame, and control the size of scaffold fibers silk.
2) according to the demand of different tissues, specific seed cell is inoculated into associated supports respectively, while in bracket
Upper coating layer of transparent matter acid hydrogel carries out in vitro culture after improving cell growth microenvironment.Experiment shows in such condition
Under, cell preferably can be proliferated and migrate.
3) bracket of above-mentioned different structure is subjected to cell culture respectively, is covered with entire film to seed cell continuous proliferation
Afterwards, it is assembled by shown in schematic diagram, and coats one layer by groups such as fibrinogen, glycerol, hyaluronic acid and gelatin in outer layer
At hydrogel, carry out the fixed-type of biological tissue.Hydrogel can either provide good growing environment, and energy for the tissue
It is enough to fix layered-scaffold, different iuntercellulars can be made to come into full contact with and exchange, after cultivating, more complete biology can be formed
Living tissue structure.
Above-mentioned to disclose this patent with preferred embodiments, so it is not to limit this patent, it is all using equivalent replacement or
Equivalence replacement mode technical solution obtained, all falls within the protection scope of this patent.
Claims (4)
1. a kind of biological micro-assembly robot of assembling, which is characterized in that it is modeled using computer three-dimensional, the method for 3D printing and in vitro culture,
Layering preparation porosity and structure are different, coat after hydrogel can for cell adhesion, proliferation, migration layered-scaffold, then into
The in vitro culture of row active somatic cell and function of organization；According to specific tissue or the cell type composition requirement of organ, artificially
Change the internal structure of the lamella mould holder and the cell of load, after carrying out in vitro culture, on the outer layer covers of supporting structure
Hydrogel not only can be improved the mechanical property of lamella membrane support, but also can provide better external rings for the existence of cell
Border.
2. the biological micro-assembly robot of assembling according to claim 1, which is characterized in that use poly lactide-glycolide acid for generation
The high molecular material of table carries out the layering preparation of lamella membrane support, can be replaced different according to the difference for the organization type that need to be substituted
Corresponding cell after carry out the culture of lamellar membrane bracket assembled, and in practical application, be not limited to three-decker, can be according to tool
Body demand carries out the adjustment of material and structure, so as to preferably realize functionalization.
3. the biological micro-assembly robot of assembling according to claim 1, which is characterized in that, can be with based on three-dimensional fast shaping technology
It is formed according to the cell of different tissues, the growth required for its different cell is accustomed to, and different interior spatial structures are produced
Layered-scaffold is supported culture to cell.
4. the biological micro-assembly robot of assembling according to claim 1, which is characterized in that in the layering branch using different interior spatial structures
On the basis of frame, better growing environment is provided for the compatibility and mechanical property of reinforcing material and for cell, chooses and is suitble to
Hydrogel material is coated, and after a period of time is cultivated in assembling, whole coating further is carried out to total
And molding, a whole microenvironment is provided, this is more conducive to the formation of biological tissue.
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| CN201711050929.5A CN109718397B (en) | 2017-10-31 | 2017-10-31 | Assembled biological micro-tissue |
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| CN201711050929.5A CN109718397B (en) | 2017-10-31 | 2017-10-31 | Assembled biological micro-tissue |
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Citations (4)
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|---|---|---|---|---|
| WO2016073782A1 (en) * | 2014-11-05 | 2016-05-12 | Organovo, Inc. | Engineered three-dimensional skin tissues, arrays thereof, and methods of making the same |
| CN106727444A (en) * | 2016-12-13 | 2017-05-31 | 湖南大学 | A kind of novel medicinal film |
| CN106730026A (en) * | 2017-03-01 | 2017-05-31 | 北京大学第三医院 | A kind of tissue engineering bone/cartilage compound rest and preparation method |
| CN107106734A (en) * | 2014-09-24 | 2017-08-29 | 加利福尼亚大学董事会 | The artificial cornea of three dimensional biological printing |
-
2017
- 2017-10-31 CN CN201711050929.5A patent/CN109718397B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107106734A (en) * | 2014-09-24 | 2017-08-29 | 加利福尼亚大学董事会 | The artificial cornea of three dimensional biological printing |
| WO2016073782A1 (en) * | 2014-11-05 | 2016-05-12 | Organovo, Inc. | Engineered three-dimensional skin tissues, arrays thereof, and methods of making the same |
| CN106727444A (en) * | 2016-12-13 | 2017-05-31 | 湖南大学 | A kind of novel medicinal film |
| CN106730026A (en) * | 2017-03-01 | 2017-05-31 | 北京大学第三医院 | A kind of tissue engineering bone/cartilage compound rest and preparation method |
Non-Patent Citations (1)
| Title |
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| WONHYE LEE: "Multilayered culture of human skin fibroblasts and keratinocytes through three dimensional freeform fabrication", 《BIOMATERIALS》 * |
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