CN105944143A - Bionic tissue based on acellular matrix-cell-three-dimensional fiber network and preparation method of bionic tissue - Google Patents
Bionic tissue based on acellular matrix-cell-three-dimensional fiber network and preparation method of bionic tissue Download PDFInfo
- Publication number
- CN105944143A CN105944143A CN201610395757.4A CN201610395757A CN105944143A CN 105944143 A CN105944143 A CN 105944143A CN 201610395757 A CN201610395757 A CN 201610395757A CN 105944143 A CN105944143 A CN 105944143A
- Authority
- CN
- China
- Prior art keywords
- acellular matrix
- hydrogel
- fiber network
- dimensional fiber
- compound
- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3633—Extracellular matrix [ECM]
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/225—Fibrin; Fibrinogen
-
- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
- A61L27/3813—Epithelial cells, e.g. keratinocytes, urothelial cells
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L89/00—Compositions of proteins; Compositions of derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Zoology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The invention relates to bionic tissue based on an acellular matrix-cell-three-dimensional fiber network and a preparation method of the bionic tissue. The bionic tissue based on the acellular matrix-cell-three-dimensional fiber network at least comprises composite acellular matrix hydrogel and epithelial cells. The composite acellular matrix hydrogel adopts a three-dimensional fiber network material good in biocompatibility as a framework. The three-dimensional fiber network material good in biocompatibility is a network structure material formed by winding fibers good in biocompatibility. The bionic tissue based on the acellular matrix-cell-three-dimensional fiber network can carry out simulation according to the tissue and organ structures, has good application prospects in tissue engineering, and can be widely applied to the field of biomedicine.
Description
Technical field
The invention belongs to compound acellular matrix hydrogel preparing technical field, relate to a kind of based on acellular matrix-
Bionical tissue of cell-three-dimensional fiber network and preparation method thereof.
Background technology
Hydrogel (Hydrogel) is the gel with water as disperse medium, and a kind of macromolecule network system, character is soft
Soft, it is similar to extracellular matrix in nature, because it can arbitrarily change shape, intensity controllable and internal defect
The characteristic of porous is applied in bioengineered tissue more and more.
Every water solublity or hydrophilic macromolecule, by certain chemical crosslinking or physical crosslinking, can shape
Become hydrogel.These macromolecules can be divided into natural and synthesis two big classes by its source.Natural hydrophilic macromolecule
Including polysaccharide (starch, cellulose, alginic acid, hyaluronic acid, chitosan etc.) and many peptides (collagen,
Polylysine, poly-L-glutamic acid etc.).The hydrophilic high mol of synthesis includes alcohol, acrylic acid and derivatives class thereof
(polyacrylic acid, polymethylacrylic acid, polyacrylamide, poly-N-is poly-for acrylamide etc.).Natural hydrogel
There is good biocompatibility and biological degradability, extensively paid close attention to by people.
The difference of natural polymer hydrogel network bonding, can be divided into physical gel and chemical gel.Physical gel
Being that the winding etc. by physical force such as electrostatic interaction, hydrogen bond, chain is formed, this gel is impermanency
, solution can be changed into by heated gel, so also referred to as pseudo gel or heat-convertible gel.Such as gelatin
Can form gel by reducing temperature, and collagen forms gel by liter high-temperature, silk fibroin protein solution is at height
Hydrogel can be formed under the conditions of pressure.Chemical gel is the three-dimensional network polymer being cross-linked to form by chemical bond, is forever
Long property, it is also called true gel.On hyaluronic acid carboxyl, such as first introduce furan group, utilize two terminal modified
The PEG of maleimide is chemically crosslinked plastic with furan nucleus.But these materials are all one-components, it is impossible to complete
Full simulation is mixed, by various ingredients, the natural tissues constituted, it is provided that biological function the most extremely limited.De-cell
Substrate (ECM) is complete tissue or organ to be removed cell and some antigenic components residue obtains, and protects
Stay the natural skeleton of extracellular matrix, containing collagen fiber, glycoprotein, VEGF etc., good
Good biocompatibility and biological degradability, be preferable hydrogel raw material.But, it is each between hydrogel
Can not bear big load to isotropic material, mechanical performance is poor, therefore constrains range of application.
Strengthen its maximum benefit of hydrogel competence exertion.In order to improve the mechanical property of hydrogel, many research works
Author is made that improvement, patent publication No. 104487103 A disclose a kind of fiber reinforcement hydrogel composite material
Method in hydrogel main body, i.e. add the mode of fiber dispersion.Patent publication No. 105085791 A is open
The toughness reinforcing preparation method strengthening physical crosslinking double-network hydrogel of a kind of hydrophobic microsphere.But all it is more likely to change
The structure of gel bodies reaches to strengthen the effect of mechanical property, changes original attribute of gel, such as transparency
Reducing, internal structure changes.Affect internal migration the composition such as medicine, Ink vessel transfusing existed of hydrogel simultaneously
Skin growth factor etc., so that the disabler of whole gel.
Summary of the invention
The technical problem to be solved is to provide a kind of based on acellular matrix-cell-three-dimensional network
Bionical tissue of network and preparation method thereof, to solve, structural strength in prior art is not enough and inside is effectively added
The technical problem that the migration velocity of composition is too fast.The present invention uses the three-dimensional fiber network material that biocompatibility is good
Expect to be combined acellular matrix hydrogel for skeleton preparation, the effect strengthened can be reached.Meanwhile, propose based on de-
The bionical tissue of cellular matrix-cell-three-dimensional fiber network, forms sandwich structure, then according to histoorgan
Structure is simulated, and has good application prospect in organizational project.
In the present invention, term " hydrogel precursor " refers to can be used for forming a kind of existence form before hydrogel.
The bionical tissue based on acellular matrix-cell-three-dimensional fiber network of the present invention, described based on de-cell
The bionical tissue of matrix-cell-three-dimensional fiber network is thin including at least compound acellular matrix hydrogel and epithelium
Born of the same parents；Described compound acellular matrix hydrogel is with the good three-dimensional fiber network material of biocompatibility as skeleton
Hydrogel；The three-dimensional fiber network material that described biocompatibility is good is the fiber good by biocompatibility
The network structure material being wound.After implanting organism, inflammation, rejection etc. will not be produced.Described life
The good three-dimensional fiber network material of the thing compatibility refers to implant in organism, does not produce inflammation and rejection
Deng, and there is good biological degradability.
As preferred technical scheme:
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network as above, described bio-compatible
Property good three-dimensional fiber network material be the three-dimensional fiber network that natural or synthesis biocompatibility is good
Material；Fibre diameter in the three-dimensional fiber network material that described biocompatibility is good is 500nm～3 μm,
Pore diameter range is 1.0 μm-9 μm, and porosity is 65%-90%, and micropore is evenly distributed；Described de-cell base
Matter hydrogel be mainly composed of water, porosity is 50%-90%, and pore diameter range is 10 μm-450 μm；Described
The acellular matrix of acellular matrix hydrogel is for taking from urethra, ureter, bladder, blood vessel, small intestinal, digestion
Road, vagina or oviducal acellular matrix；The fiber that described biocompatibility is good be fibroin fiber,
Poly (glycolide-co-lactide) fiber or polycaprolactone fiber.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network as above, described includes at least
Compound acellular matrix hydrogel and epithelial cell are one of scenario described below:
Compound acellular matrix hydrogel is combined situation with epithelial cell:
Epithelial cell is planted on compound acellular matrix hydrogel；
Compound acellular matrix hydrogel upper surface covers hydrogel, and at compound acellular matrix hydrogel and water
Epithelial cell is planted between gel；
Compound acellular matrix hydrogel upper surface covers hydrogel, and epithelial cell is planted in hydrogel upper surface；
Compound acellular matrix hydrogel upper surface covers two-layer hydrogel, and epithelial cell is planted in two-layer hydrogel
Between；
Or, further, also include one of scenario described below:
Compound acellular matrix hydrogel is combined situation with smooth muscle cell:
Compound acellular matrix hydrogel lower surface plantation smooth muscle cell；
Compound acellular matrix hydrogel lower surface covers hydrogel, and at compound acellular matrix hydrogel and water
Smooth muscle cell is planted between gel；
Compound acellular matrix hydrogel lower surface covers hydrogel, and smooth muscle cell is planted in hydrogel following table
Face；
Compound acellular matrix hydrogel lower surface covers two-layer hydrogel, and smooth muscle cell is planted in two-layer water-setting
Between glue；
Described compound acellular matrix hydrogel is that acellular matrix hydrogel is good with described biocompatibility
Three-dimensional fiber network material is overall or local is compound；Described entirety is compound refers to entirety in acellular matrix hydrogel
Comprise the three-dimensional fiber network material that biocompatibility is good；Described local is combined and refers to that biocompatibility is good
The upper and lower surface of three-dimensional fiber network material and shallow top layer thereof are combined with acellular matrix hydrogel；
Described hydrogel is the hydrogel that acellular matrix is prepared from, specially bladder acellular matrix water-setting
Glue, blood vessel acellular matrix hydrogel, urethra acellular matrix hydrogel or mucous membrane of small intestine acellular matrix water-setting
Glue；
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network as above is described compound de-thin
Possibly together with migrating composition in cytoplasmic matrix hydrogel, described migration composition dispersion package is in described hydrogel.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network as above, described migration composition
Refer to that migrating composition is dispersed in acellular matrix hydrogel, but do not produce any chemical reaction；Described migrate into
It is divided into VEGF, insulin, aspirin, ketoprofen, Shu Tian logical or in finasteride
One or more.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network as above, described de-cell base
The storage temperature of matter hydrogel is at 4 DEG C～40 DEG C.
Present invention also offers the preparation side of bionical tissue based on acellular matrix-cell-three-dimensional fiber network
Method, described preparation method is infusion method, cladding process or spraying process.
Preparation method as above, first prepares acellular matrix hydrogel precursor solution, then soak,
Coating or spraying, then standing several minutes i.e. forms compound acellular matrix hydrogel at 37 DEG C；Generally stand
3～30min.
Described immersion is:
Before gel is not formed, three-dimensional fiber network material good for biocompatibility is soaked in described de-thin
Cytoplasmic matrix precursor solution；
Described it is applied to:
Before gel is not formed, described acellular matrix hydrogel precursor solution is coated in biocompatibility
The good upper surface of three-dimensional fiber network material, lower surface or upper and lower surface, forms one layer of biocompatibility
The stepped construction that good three-dimensional fiber network structure is constituted with acellular matrix hydrogel precursor solution；Or enter
Three-dimensional fiber network material good for biocompatibility is fitted in coated acellular matrix hydrogel by one step
Precursor solution layer, forms the good three-dimensional fiber network structure of the multi-layer biological compatibility and acellular matrix water-setting
The stepped construction that glue precursor solution is constituted；
Described spraying is:
Before gel is not formed, by described acellular matrix hydrogel precursor solution spraying at biocompatibility
The good upper surface of three-dimensional fiber network material, lower surface or upper and lower surface, forms one layer of biocompatibility
The stepped construction that good three-dimensional fiber network structure is constituted with acellular matrix hydrogel precursor solution；Or enter
Three-dimensional fiber network material good for biocompatibility is fitted in sprayed acellular matrix hydrogel by one step
Precursor solution layer, forms the good three-dimensional fiber network structure of the multi-layer biological compatibility and acellular matrix water-setting
The stepped construction that glue precursor solution is constituted.
Acellular matrix makes the preparation of acellular matrix hydrogel precursor solution；
The acellular matrix material made is carried out after lyophilization freeze grinding again, is broken into powder；At hydrochloric acid
With pepsin digestion acellular matrix powder about 48h in solution, form acellular matrix pre-gel solution, add
Enter the NaOH solution of about 1/10 acellular matrix pre-gel solution volume, the wherein concentration of NaOH solution
For 0.01mol/L, wherein add 10 × PBS of about 1/9 acellular matrix pre-gel solution volume, wherein
The concentration of PBS is 0.0.1mol/L, forms acellular matrix gel precursor solution.
Preparation method as above, being prepared as of the three-dimensional fiber network material that described biocompatibility is good is quiet
Electrical spinning method or 3 D weaving method.
Preparation method as above, is additionally added in the preparation process of acellular matrix hydrogel precursor solution and moves
Move into point.
The mechanism of action of the present invention is:
Hydrogel is that strand crosslinks and the three-dimensional network of molecular scale that formed, migrates composition and delays from which
Release mainly relevant with migrating composition diffusion velocity in gel.This diffusion velocity first aspect and hydrogel structure
Relevant, i.e. the three-dimensional network density of hydrogel, network pore size and distribution, cross-link intensity, CHARGE DISTRIBUTION and
Intensity；Second aspect is relevant with content with medicines structure, such as drug size, drug loading, drug molecule amount, bears
Carry position, medicine CHARGE DISTRIBUTION and intensity；The third aspect is relevant with environmental response condition, i.e. ambient temperature, pH
Value, electric field, magnetic field, light etc..
Three-dimensional fiber network material is that fiber mutually runs through the three-dimensional network shape bulk material being staggered to form, and belongs to micro-
The three-dimensional net structure of nanoscale, excellent in mechanical performance, can be used for strengthening hydrogel and acquisition has each to same
The composite structure of property mechanical behavior feature, the fibre diameter in three-dimensional fiber network is 500nm～3 simultaneously
μm, pore diameter range is 1.0 μm-9 μm, and porosity is 65%-90%, and micropore is evenly distributed.
In view of above-mentioned, the invention provides the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network
Preparation method, is first the preparation of compound acellular matrix hydrogel, will acellular matrix hydrogel and biology
The good three-dimensional fiber network material of the compatibility is carried out physics be combined by spraying process, infusion method, cladding process.Water
Being mainly composed of water in gel, porosity is 50%-90%, and pore diameter range is 10 μm-450 μm, therefore its
Aperture is more than the aperture of three-dimensional fiber network.After both are compound, the macroporous structure in hydrogel can be by three-dimensional fiber
Network structure is completely or partially filled.On the one hand, three-dimensional fiber network plays the work of three-dimensional framework in hydrogel
With, thus enhance the mechanical property of hydrogel.On the other hand, three-dimensional fiber network can fill hydrogel Central Plains
The portion void occupied by water, also can construct mixing portion fiber in polymer at hydrogel.Due to three-dimensional
The density of network of fibers is more than water, and medicine diffusion velocity in composite aquogel is slower than without three-dimensional fiber network
Diffusion velocity in hydrogel, therefore can delay the hydrogel Chinese medicine slow release to material outer.It addition, work as water
When mixing portion fiber in polymer constructed by gel, due to unsupported medicine in three-dimensional fiber network polymer, because of
This drug diffusion rate being carried in hydrogel also can be delayed.Above-mentioned two reason can cause composite aquogel
In the medicament slow release time more lasting.Be there is the three-dimensional of different pore size, fibre diameter, porosity by selection
Network of fibers material, or the composite square of polymer is constructed by changing three-dimensional fiber network polymer and hydrogel
Formula, composite denseness, the intensity of scalable composite aquogel and drug diffusion behavior.
Owing to three-dimensional fiber network and hydrogel network belong to the three-dimensional network of different scale, three-dimensional fiber network
With the compound main body three-dimensional net structure that can't change hydrogel of hydrogel, such as crosslink density, hydrogel material
Expect the interaction with medicine and the environment-responsive of hydrogel.
Acellular matrix is mainly derived from people or the tissue of mammal or organ, mainly take from urethra, ureter,
Bladder, blood vessel, small intestinal, digestive tract, vagina or fallopian tube etc. are organized, and are complete tissue or organ to be removed
Complete extracellular matrix obtained by cell and antigenic component, by collagen, polysaccharide, glycoprotein and blood vessel endothelium
Somatomedin forms, and has good biocompatibility and biological degradability.Therefore, good with biocompatibility
Three-dimensional fiber network material is that the acellular matrix hydrogel compound system of skeleton has good biocompatibility,
Can apply to bioengineered tissue, tissue repair can be used for, and meet different parts erose reparation need
Want.
Histoorgan has general character, is mucosa (also known as epithelium) and the official jargon structure of smooth muscle composition, different groups
The cell knitting needs is broadly divided into two big classes, and epithelium (mucosa) cell and smooth muscle cell, as neural and blood
Tubing, its content is relative to epithelium and smooth muscle much less, and therefore we only need to introduce the factor, then implant
Surrounding tissue is relied on to grow into after in.Therefore, prepared by acellular matrix/cell/three-dimensional fiber network material
Become sandwich structure, be then simulated according to histoorgan, sandwich structure be laid out and arrange, shape
Become bionical tissue based on acellular matrix-cell-three-dimensional fiber network, well should have in organizational project
Use prospect.
Beneficial effect
(1) in the present invention, acellular matrix hydrogel overcomes that traditional natural hydrogel component is single, biological function list
The shortcoming of one.
(2) the three-dimensional fiber network of the present invention and the direct combination of gel, will not change this body structure of gel and just can reach
To the purpose strengthening hydrogel.
(3) relative to the structure of hydrogel loose and porous inner surface, three-dimensional fiber network compact structure, for hydrogel
Chinese medicine, the parcel densification of active factors, can play the effect of slow release, reduce the rate of release of medicine,
Thus improve its utilization rate.
(4) preparation is simple for the present invention, and the compound acellular matrix hydrogel of preparation has good three-dimensional
Space structure, good mechanical properties, good biocompatibility, can extensively apply biomedical sector
In.
(5) bionical tissue based on acellular matrix-cell-three-dimensional fiber network can be the most according to organizational structure
Become, simulated tissue organ structure well, organizational project has good application prospect.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscope diagram of composite aquogel；
Fig. 2 is the signal that embodiment 1 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Fig. 3 is the signal that embodiment 2 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Fig. 4 is the signal that embodiment 3 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Fig. 5 is the signal that embodiment 4 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Fig. 6 is the signal that embodiment 5 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Fig. 7 is the signal that embodiment 6 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Fig. 8 is the signal that embodiment 7 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Fig. 9 is the signal that embodiment 8 prepares the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
Figure；
Figure 10 is that embodiment 9 prepares showing of the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
It is intended to；
Figure 11 is that embodiment 10 prepares showing of the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
It is intended to；
Figure 12 is that embodiment 11 prepares showing of the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
It is intended to；
Figure 13 is that embodiment 12 prepares showing of the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
It is intended to；
Figure 14 is that embodiment 13 prepares showing of the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
It is intended to；
Figure 15 is that embodiment 14 prepares showing of the bionical tissue of gained acellular matrix-cell-three-dimensional fiber network
It is intended to.
In figure: 1 is epithelial cell, 2 is hydrogel, and 3 is compound acellular matrix hydrogel, and 4 is smooth muscle
Cell；
3-1 is the upper surface of the three-dimensional fiber network material that biocompatibility is good and shallow top layer thereof and de-cell
Substrate water gel is combined；
3-2 is the three-dimensional fiber network that the biocompatibility of the compound compound acellular matrix hydrogel in local is good
Material.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is expanded on further.Should be understood that these embodiments are only used for
The bright present invention rather than restriction the scope of the present invention.In addition, it is to be understood that reading the content that the present invention lectures
Afterwards, the present invention can be made various changes or modifications by those skilled in the art, and these equivalent form of values fall within equally
The application appended claims limited range.
The bionical tissue based on acellular matrix-cell-three-dimensional fiber network of the present invention, for including at least compound
Acellular matrix hydrogel and epithelial cell, described compound acellular matrix hydrogel, for good with biocompatibility
Good three-dimensional fiber network material is the hydrogel of skeleton, i.e. comprises biocompatibility in acellular matrix hydrogel
Good three-dimensional fiber network material；The three-dimensional fiber network material that described biocompatibility is good is by biofacies
The network structure material that the good fiber of capacitive is wound, after implanting organism, will not produce inflammation, rejection
Reaction etc..Fig. 1 is the scanning electron microscope diagram of composite aquogel, it can be seen that hydrogel conduct
Weaker zone, with three-dimensional fiber network structure as compacted zone compact siro spinning technology, and is mutually communicated.Described biofacies
The good three-dimensional fiber network of capacitive is the three-dimensional fiber network that natural or synthesis biocompatibility is good；Institute
Stating the fibre diameter in the three-dimensional fiber network that biocompatibility is good is 500nm～3 μm, and pore diameter range is
(the fiber aperture of the three-dimensional fiber network material that described biocompatibility is good is less than 1.0 μm-9 μm
20 μm), porosity is 65%-90%, and micropore is evenly distributed；Master in described acellular matrix hydrogel
Wanting composition is water, and porosity is 50%-90%, and pore diameter range is 10 μm-450 μm.
Described is one of scenario described below including at least compound acellular matrix hydrogel and epithelial cell:
Compound acellular matrix hydrogel is combined situation with epithelial cell:
Epithelial cell is planted on compound acellular matrix hydrogel；
Compound acellular matrix hydrogel upper surface covers hydrogel, and at compound acellular matrix hydrogel and water
Epithelial cell is planted between gel；
Compound acellular matrix hydrogel upper surface covers hydrogel, and epithelial cell is planted in hydrogel upper surface；
Compound acellular matrix hydrogel upper surface covers two-layer hydrogel, and epithelial cell is planted in two-layer hydrogel
Between；
Or, further, also include one of scenario described below:
Compound acellular matrix hydrogel is combined situation with smooth muscle cell:
Compound acellular matrix hydrogel lower surface plantation smooth muscle cell；
Compound acellular matrix hydrogel lower surface covers hydrogel, and at compound acellular matrix hydrogel and water
Smooth muscle cell is planted between gel；
Compound acellular matrix hydrogel lower surface covers hydrogel, and smooth muscle cell is planted in hydrogel following table
Face；
Compound acellular matrix hydrogel lower surface covers two-layer hydrogel, and smooth muscle cell is planted in two-layer water-setting
Between glue；
The fiber that described biocompatibility is good is fibroin fiber, poly (glycolide-co-lactide) fiber or poly-own interior
Ester fiber etc.；
The acellular matrix of described acellular matrix hydrogel is for taking from nerve, spinal cord, tendon, muscle, bladder
The acellular matrix of mucosa, mucous membrane of small intestine, heart, liver, kidney or cartilaginous tissue.
Possibly together with migrating composition in described compound acellular matrix hydrogel, described migration composition dispersion package is in institute
State in acellular matrix hydrogel.
Described migration composition refers to that migrating composition is dispersed in acellular matrix hydrogel, but does not produce any chemistry
Reaction；Described migration composition is VEGF, insulin, aspirin, ketoprofen, Shu Tian
One or more in logical or finasteride.
The storage temperature of described compound acellular matrix hydrogel is at 4 DEG C～40 DEG C.
Embodiment 1
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from urethra, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds insulin, wherein islets of langerhans
Element is 0.05:100 with the mass ratio of acellular matrix, forms acellular matrix gel precursor solution.At gel
Before not formed, above-mentioned acellular matrix precursor solution is coated in the fiber prepared by 3 D weaving method straight
Footpath is 3 μm, and pore diameter range is 8-9 μm, and porosity is 90%, and the micropore biocompatibility that is evenly distributed is good
The upper surface of good poly (glycolide-co-lactide) network of fibers material, forms one layer of three-dimensional fiber network structure thin with de-
The stepped construction that cytoplasmic matrix hydrogel precursor solution is constituted, stands 30min the most again at 37 DEG C, is formed multiple
Close acellular matrix hydrogel；Molten at compound acellular matrix hydrogel surface one layer of hydrogel precursor of coating again
Liquid, specially bladder acellular matrix precursor solution, stand 5min at 37 DEG C and continue gel, formed de-
The bionical tissue of cellular matrix-cell-three-dimensional fiber network, as shown in Figure 2；Compound acellular matrix hydrogel
In be mainly composed of water, porosity is 90%, and pore diameter range is 400-450 μm, and storage temperature is 40 DEG C.
Embodiment 2
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares and takes from ureteral acellular matrix material, after carrying out lyophilization
Freeze grinding again, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds aspirin, Qi Zhonga
A department woods is 1:20 with the mass ratio of acellular matrix, forms acellular matrix gel precursor solution.At gel
Before not formed, above-mentioned acellular matrix precursor solution is sprayed on the fiber prepared by 3 D weaving method straight
Footpath is 3 μm, and pore diameter range is 8-9 μm, and porosity is 90%, and the micropore biocompatibility that is evenly distributed is good
The upper surface of good poly (glycolide-co-lactide) network of fibers material, forms one layer of three-dimensional fiber network structure thin with de-
The stepped construction that cytoplasmic matrix hydrogel precursor solution is constituted；At 37 DEG C, stand 3min again, formed compound de-
Cellular matrix hydrogel；Epithelial cell is planted in compound acellular matrix hydrogel surface, thinner at plantation epithelium
Compound acellular matrix hydrogel surface one layer of hydrogel precursor solution of spraying of born of the same parents, specially blood vessel takes off cell
Substrate water gel precursor solution, then at 37 DEG C, stand 9min, continue gel, form compound de-cell base
Matter hydrogel upper surface covers hydrogel, and plants epithelium between compound acellular matrix hydrogel and hydrogel
The bionical tissue of the acellular matrix-cell-three-dimensional fiber network of cell, as shown in Figure 3；Compound de-cell base
Being mainly composed of water in matter hydrogel, porosity is 70%, and pore diameter range is 15-60 μm, and storage temperature is
8℃。
Embodiment 3
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from bladder, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds ketoprofen, wherein ketone Lip river
Fragrant and acellular matrix mass ratio is 1:10, forms acellular matrix gel precursor solution, in the non-shape of gel
Before one-tenth, above-mentioned acellular matrix precursor solution is coated in the fibre diameter prepared by 3 D weaving method is
1.8 μm, pore diameter range is 3-5 μm, and porosity is 80%, and the micropore biocompatibility that is evenly distributed is good
The upper surface of poly (glycolide-co-lactide) network of fibers material, forms one layer of three-dimensional fiber network structure and de-cell base
The stepped construction that matter hydrogel precursor solution is constituted；At 37 DEG C, stand 9min again, form compound de-cell
Substrate water gel；One layer of hydrogel precursor solution is coated again, specifically in compound acellular matrix hydrogel surface
For urethra acellular matrix hydrogel precursor solution, at 37 DEG C, stand 5min continue gel, make compound de-
Cellular matrix hydrogel upper surface covers hydrogel, epithelial cell is planted in hydrogel upper surface, is then planting
Plant compound acellular matrix hydrogel surface one layer of hydrogel precursor solution of coating of epithelial cell, be specially urine
Road acellular matrix hydrogel precursor solution, then at 37 DEG C, stand 9min, continue gel, formed compound
Acellular matrix hydrogel upper surface covers two-layer hydrogel, and it is de-that epithelial cell is planted between two-layer hydrogel
The bionical tissue of cellular matrix-cell-three-dimensional fiber network, as shown in Figure 4；Compound acellular matrix hydrogel
In be mainly composed of water, porosity is 78%, and pore diameter range is 150-200 μm, and storage temperature is 10 DEG C.
Embodiment 4
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from blood vessel, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds VEGF,
Its VEGF is 0.025:100 with the mass ratio of acellular matrix, forms acellular matrix and coagulates
Glue precursor solution, before gel is not formed, is 500 by the fibre diameter prepared by method of electrostatic spinning
Nm, pore diameter range is 1-2 μm, and porosity is 65%, and the biocompatibility that is evenly distributed by micropore is good
Fibroin fiber network material is cut into the disk of a diameter of 14mm, is soaked in above-mentioned 2mL and takes off cell base
In matter precursor solution, formed in fibroin fiber network material hole and construct containing acellular matrix hydrogel
Polymer, also contain three-dimensional fiber network material in acellular matrix hydrogel hole mutually comprises structure；Again
At 37 DEG C, stand 3min, form compound acellular matrix hydrogel；Then table on compound acellular matrix
Face plantation epithelial cell, forms the acellular matrix of compound acellular matrix hydrogel upper surface plantation epithelial cell
The bionical tissue of-cell-three-dimensional fiber network, as shown in Figure 5；Be combined in acellular matrix hydrogel is main
Composition is water, and porosity is 50%, and pore diameter range is 10-50 μm, and storage temperature is 4 DEG C.
Embodiment 5
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares and takes from gastral acellular matrix material, after carrying out lyophilization
Freeze grinding again, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds Shu Tian and leads to, Qi Zhongshu
Logical and acellular matrix the mass ratio of body peace is 1:18, forms acellular matrix gel precursor solution, at gel
Before not formed, the micropore prepared by method of electrostatic spinning is evenly distributed the good polycaprolactone fiber of biocompatibility
Network material is soaked in above-mentioned 2mL acellular matrix precursor solution, forms polycaprolactone network of fibers material
Material hole constructs polymer containing acellular matrix hydrogel, acellular matrix hydrogel hole also contains three
That ties up network of fibers material mutually comprises structure；Fibre diameter is 1.8 μm, and pore diameter range is 6.5-7.0 μm,
Porosity is 79%；At 37 DEG C, stand 15min again, form compound acellular matrix hydrogel；Then exist
Compound acellular matrix hydrogel material surface grafting epithelial cell, then spray one layer of hydrogel precursor solution,
It is specially mucous membrane of small intestine acellular matrix hydrogel precursor solution, at 37 DEG C, stands 15min continue gel,
Form the compound acellular matrix-cell-three planting epithelial cell between acellular matrix hydrogel and hydrogel
The bionical tissue of dimension network of fibers, as shown in Figure 6；Be combined in acellular matrix hydrogel is mainly composed of water,
Porosity is 80%, and pore diameter range is 150-250 μm, and storage temperature is 20 DEG C.
Embodiment 6
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from vagina, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds finasteride, Qi Zhongfei
That male amine is 1:5 with the mass ratio of acellular matrix, forms acellular matrix gel precursor solution, at gel
Before not formed, being 2.5 μm by the fibre diameter prepared by 3 D weaving method, pore diameter range is 5-6 μm,
Porosity is 85%, and the micropore good fibroin fiber network material of biocompatibility that is evenly distributed is soaked in
In above-mentioned 2mL acellular matrix precursor solution, formed in fibroin fiber network material hole containing de-
Polymer constructed by cellular matrix hydrogel, also contains three-dimensional fiber network material in acellular matrix hydrogel hole
Mutually comprise structure；At 37 DEG C, stand 18min again, form compound acellular matrix hydrogel；Compound
The upper and lower surface of acellular matrix hydrogel plants epithelial cell and smooth muscle cell respectively, forms de-cell base
The bionical tissue of matter-cell-three-dimensional fiber network, as shown in Figure 7；Master in compound acellular matrix hydrogel
Wanting composition is water, and porosity is 70%, and pore diameter range is 250-300 μm, and storage temperature is 30 DEG C.
Embodiment 7
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares and takes from oviducal acellular matrix material, after carrying out lyophilization
Freeze grinding again, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds insulin and blood vessel endothelium
The mixture of somatomedin, wherein the mass ratio of insulin and VEGF is 2:5, insulin and
VEGF is 0.1:100 with the mass ratio of acellular matrix, forms acellular matrix gel forerunner
Liquid solution, before gel is not formed, is sprayed on above-mentioned acellular matrix precursor solution and passes through electrostatic spinning
Fibre diameter prepared by method is 1.9 μm, and pore diameter range is 6.9-8.5 μm, and porosity is 78%, and micropore divides
The upper and lower surface of the poly (glycolide-co-lactide) network of fibers material that the uniform biocompatibility of cloth is good, forms one layer
The stepped construction that three-dimensional fiber network structure is constituted with acellular matrix hydrogel precursor solution；Again at 37 DEG C
Lower standing 25min, forms compound acellular matrix hydrogel；Upper and lower at compound acellular matrix hydrogel again
It is molten that surface is respectively coated with one layer of hydrogel precursor solution, specially blood vessel acellular matrix hydrogel precursor
Liquid, stands 15min at 37 DEG C and continues gel, then epithelial cell is being planted in hydrogel upper surface,
Smooth muscle cell is planted in hydrogel lower surface, forms bionical group of acellular matrix-cell-three-dimensional fiber network
Knit, as shown in Figure 8；Be combined in acellular matrix hydrogel is mainly composed of water, and porosity is 66%, hole
Footpath scope is 300-360 μm, and storage temperature is 25 DEG C.
Embodiment 8
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from urethra, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds aspirin and ketoprofen
Mixture, wherein the quality of aspirin and ketoprofen is 3:2, aspirin and ketoprofen and de-cell base
The mass ratio of matter is 1:9, forms acellular matrix gel precursor solution, before gel is not formed, and will be de-
It is 1.6 μm that cellular matrix precursor solution is coated in the fibre diameter prepared by 3 D weaving method, pore diameter range
For 5.5-6.6 μm, porosity is 81%, and micropore is evenly distributed the good fibroin fiber of biocompatibility
The upper and lower surface of network material；Form one layer of three-dimensional fiber network structure and acellular matrix hydrogel precursor
The stepped construction that solution is constituted；At 37 DEG C, stand 20min again, form compound acellular matrix hydrogel；Again
Epithelial cell and smooth muscle cell is planted respectively, then upper on the compound upper and lower surface of acellular matrix hydrogel
It is de-thin that chrotoplast and smooth muscle cells are respectively coated with one layer of hydrogel precursor solution, specially mucous membrane of small intestine
Cytoplasmic matrix hydrogel precursor solution, stands 24min at 37 DEG C and continues gel, formation acellular matrix-thin
The bionical tissue of born of the same parents-three-dimensional fiber network, as shown in Figure 9；Main one-tenth in compound acellular matrix hydrogel
Being divided into water, porosity is 70%, and pore diameter range is 300-350 μm, and storage temperature is 30 DEG C.
Embodiment 9
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares and takes from ureteral acellular matrix material, after carrying out lyophilization
Freeze grinding again, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds ketoprofen and Shu Tian leads to
Mixture, the mass ratio that wherein ketoprofen and Shu Tian are logical is that 3:4, ketoprofen and Shu Tian are logical with de-cell
The mass ratio of substrate is 2:7, forms acellular matrix gel precursor solution, before gel is not formed, and will
It is 2.5 μm that above-mentioned acellular matrix precursor solution is sprayed on the fibre diameter prepared by 3 D weaving method, hole
Footpath scope is 7-7.8 μm, and porosity is 70%, and micropore is evenly distributed the good PGA of biocompatibility
The upper and lower surface of lactide network of fibers material, forms one layer of good three-dimensional fiber network knot of biocompatibility
The stepped construction that structure is constituted with acellular matrix hydrogel precursor solution；18min, shape is stood again at 37 DEG C
Become compound acellular matrix hydrogel；It is respectively coated with one layer again on the compound upper and lower surface of acellular matrix hydrogel
Bladder acellular matrix hydrogel precursor solution, stands 15min at 37 DEG C and continues gel, then inciting somebody to action
Epithelial cell is planted in hydrogel upper surface, and smooth muscle cell is planted in hydrogel lower surface, then thin at epithelium
Born of the same parents and smooth muscle cells are respectively coated with one layer of hydrogel precursor solution, specially blood vessel acellular matrix water
Gel precursor solution, stands 15min at 37 DEG C and continues gel, form acellular matrix-cell-three-dimensional fine
The bionical tissue of dimension network, as shown in Figure 10；Acellular matrix hydrogel is mainly composed of water, hole
Rate is 65%, and pore diameter range is 320-400 μm, and storage temperature is 35 DEG C.
Embodiment 10
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from small intestinal, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds aspirin, ketoprofen
The mixture logical with Shu Tian, the mass ratio that wherein aspirin, ketoprofen and Shu Tian are logical is 2:1:3, Ah
Logical and acellular matrix the mass ratio of a department woods, ketoprofen and Shu Tian is 1:10, forms acellular matrix gel
Precursor solution, before gel is not formed, is 900nm by the fibre diameter prepared by 3 D weaving method,
Pore diameter range is 1-3 μm, and porosity is 65%, and micropore is evenly distributed the good fibroin egg of biocompatibility
White fiber network material is soaked in above-mentioned acellular matrix precursor solution, forms fibroin fiber network material
Hole constructs polymer containing acellular matrix hydrogel, acellular matrix hydrogel hole also contains three-dimensional
Network of fibers material mutually comprise structure；Again on the compound upper and lower surface of acellular matrix hydrogel material respectively
Plantation epithelial cell and smooth muscle cell, be then respectively coated with one layer of water at epithelial cell and smooth muscle cells
Gel precursor solution, specially urethra acellular matrix hydrogel precursor solution, continue gel, is formed de-
The bionical tissue of cellular matrix-cell-three-dimensional fiber network, as shown in figure 11；Compound acellular matrix water-setting
Being mainly composed of water in glue, porosity is 70%, and pore diameter range is 380-430 μm, and storage temperature is 5 DEG C.
Embodiment 11
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from blood vessel, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds insulin and blood vessel endothelium
The mixture of somatomedin, wherein the mass ratio of insulin and VEGF is 2:5, insulin and
VEGF is 0.1:100 with the mass ratio of acellular matrix, forms acellular matrix gel forerunner
Liquid solution, before gel is not formed, is sprayed on above-mentioned acellular matrix precursor solution and passes through electrostatic spinning
Fibre diameter prepared by method is 1.9 μm, and pore diameter range is 6.9-8.5 μm, and porosity is 78%, and micropore divides
The upper and lower surface of the poly (glycolide-co-lactide) network of fibers material that the uniform biocompatibility of cloth is good, forms one layer
The stepped construction that three-dimensional fiber network structure is constituted with acellular matrix hydrogel precursor solution；Again at 37 DEG C
Lower standing 25min, forms compound acellular matrix hydrogel；Upper and lower at compound acellular matrix hydrogel again
It is molten that surface is respectively coated with one layer of hydrogel precursor solution, specially bladder acellular matrix hydrogel precursor
Liquid, stands 15min at 37 DEG C and continues gel, then epithelial cell is being planted in hydrogel upper surface,
Smooth muscle cell is planted in hydrogel lower surface, then coats one layer of hydrogel precursor at smooth muscle cells
Solution, specially urethra acellular matrix hydrogel precursor solution, stand 18min at 37 DEG C and continue solidifying
Glue, forms the bionical tissue of acellular matrix-cell-three-dimensional fiber network, as shown in figure 12；Compound de-thin
Being mainly composed of water in cytoplasmic matrix hydrogel, porosity is 66%, and pore diameter range is 300-360 μm, deposits
Temperature is 25 DEG C.
Embodiment 12
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares and takes from gastral acellular matrix material, after carrying out lyophilization
Freeze grinding again, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds insulin and blood vessel endothelium
The mixture of somatomedin, wherein the mass ratio of insulin and VEGF is 2:5, insulin and
VEGF is 0.1:100 with the mass ratio of acellular matrix, forms acellular matrix gel forerunner
Liquid solution, before gel is not formed, is coated in above-mentioned acellular matrix precursor solution and passes through electrostatic spinning
Fibre diameter prepared by method is 1.9 μm, and pore diameter range is 6.9-8.5 μm, and porosity is 78%, and micropore divides
The upper and lower surface of the poly (glycolide-co-lactide) network of fibers material that the uniform biocompatibility of cloth is good, forms one layer
The stepped construction that three-dimensional fiber network structure is constituted with acellular matrix hydrogel precursor solution；Again at 37 DEG C
Lower standing 28min, shape is combined acellular matrix hydrogel；It is coated with at compound acellular matrix hydrogel upper surface again
Cover one layer of hydrogel precursor solution, specially blood vessel acellular matrix hydrogel precursor solution, at 37 DEG C
Lower standing 15min continues gel, then epithelial cell is being planted in hydrogel upper surface, at compound de-cell
Substrate water gel lower surface plantation smooth muscle cell, then spray one layer of hydrogel precursor at smooth muscle cells
Solution, specially bladder acellular matrix hydrogel precursor solution, stand 10min at 37 DEG C and continue solidifying
Glue, forms the bionical tissue of acellular matrix-cell-three-dimensional fiber network, as shown in figure 13；De-cell base
Being mainly composed of water in matter hydrogel, porosity is 66%, and pore diameter range is 300-360 μm, storage temperature
It it is 25 DEG C.
Embodiment 13
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares the acellular matrix material taking from vagina, carries out after lyophilization again
Freeze grinding, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds ketoprofen and Shu Tian leads to
Mixture, the mass ratio that wherein ketoprofen and Shu Tian are logical is that 3:4, ketoprofen and Shu Tian are logical with de-cell
The mass ratio of substrate is 2:7, forms acellular matrix gel precursor solution, before gel is not formed, and will
It is 2.5 μm that above-mentioned acellular matrix precursor solution is sprayed on the fibre diameter prepared by 3 D weaving method, hole
Footpath scope is 7-7.8 μm, and porosity is 70%, and micropore is evenly distributed the good PGA of biocompatibility
The upper surface of lactide network of fibers material, formed one layer of good three-dimensional fiber network structure of biocompatibility with
The stepped construction that acellular matrix hydrogel precursor solution is constituted；At 37 DEG C, stand 18min again, formed multiple
Close acellular matrix hydrogel；Cell base is taken off again at compound acellular matrix hydrogel upper surface one layer of urethra of spraying
Matter hydrogel precursor solution, stands 15min at 37 DEG C and continues gel, then planted by epithelial cell
At hydrogel upper surface, plant smooth muscle cell at compound acellular matrix hydrogel lower surface, thinner at epithelium
Born of the same parents and smooth muscle cells are respectively coated with one layer of hydrogel precursor solution, specially bladder acellular matrix water
Gel precursor solution, stands 8min at 37 DEG C and continues gel, form acellular matrix-cell-three-dimensional fine
The bionical tissue of dimension network, as shown in figure 13；Acellular matrix hydrogel is mainly composed of water, hole
Rate is 65%, and pore diameter range is 320-400 μm, and storage temperature is 35 DEG C.
Embodiment 14
The preparation method of the bionical tissue of a kind of acellular matrix-cell-three-dimensional fiber network, is first compound de-
The preparation of cellular matrix hydrogel, prepares and takes from oviducal acellular matrix material, after carrying out lyophilization
Freeze grinding again, is broken into powder；With pepsin digestion acellular matrix powder about 48h in hydrochloric acid solution,
Form acellular matrix pre-gel solution, add the NaOH of about 1/10 acellular matrix pre-gel solution volume
Solution, wherein the concentration of NaOH solution is 0.01mol/L, adds about 1/9 acellular matrix pregel
10 × PBS of liquor capacity, wherein the concentration of PBS is 0.01mol/L, adds VEGF,
Its VEGF is 0.025:100 with the mass ratio of acellular matrix, forms acellular matrix and coagulates
Glue precursor solution, before gel is not formed, is 500 by the fibre diameter prepared by method of electrostatic spinning
Nm, pore diameter range is 1-2 μm, and porosity is 65%, and the biocompatibility that is evenly distributed by micropore is good
Fibroin fiber network material is cut into the disk of a diameter of 14mm, is soaked in above-mentioned 2mL and takes off cell base
In matter precursor solution, formed in fibroin fiber network material hole and construct containing acellular matrix hydrogel
Polymer, also contain three-dimensional fiber network material in acellular matrix hydrogel hole mutually comprises structure；Again
At 37 DEG C, stand 3min, form compound acellular matrix hydrogel；On compound acellular matrix hydrogel,
Lower surface plants epithelial cell smooth muscle cell respectively, sprays one layer of hydrogel precursor at smooth muscle cells
Solution, specially mucous membrane of small intestine acellular matrix hydrogel precursor solution, stand 9min at 37 DEG C and continue
Gel, forms the bionical tissue of acellular matrix-cell-three-dimensional fiber network, as shown in figure 15；Compound de-
Being mainly composed of water in cellular matrix hydrogel, porosity is 50%, and pore diameter range is 10-50 μm, deposits
Putting temperature is 4 DEG C.
Claims (10)
1. bionical tissue based on acellular matrix-cell-three-dimensional fiber network, is characterized in that: described based on de-thin
The bionical tissue of cytoplasmic matrix-cell-three-dimensional fiber network is including at least compound acellular matrix hydrogel and upper
Chrotoplast；Described compound acellular matrix hydrogel is the three-dimensional fiber network material good with biocompatibility
Material is the hydrogel of skeleton；The three-dimensional fiber network material that described biocompatibility is good is by bio-compatible
The network structure material that the good fiber of property is wound.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network the most according to claim 1, its
Being characterised by, the three-dimensional fiber network material that described biocompatibility is good is biology that is natural or that synthesize
The three-dimensional fiber network material that the compatibility is good；The three-dimensional fiber network material that described biocompatibility is good
In fibre diameter be 500nm～3 μm, pore diameter range is 1 μm-9 μm, and porosity is 65%-90%,
And micropore is evenly distributed；Described compound acellular matrix hydrogel be mainly composed of water, porosity is
50%-90%, pore diameter range is 10 μm-450 μm；The de-cell of described compound acellular matrix hydrogel
Substrate is for taking from urethra, ureter, bladder, blood vessel, small intestinal, digestive tract, vagina or oviducal de-
Cellular matrix；The fiber that described biocompatibility is good is fibroin fiber, poly (glycolide-co-lactide) fibre
Dimension or polycaprolactone fiber.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network the most according to claim 1, its
Being characterised by, described is one of scenario described below including at least compound acellular matrix hydrogel and epithelial cell:
Compound acellular matrix hydrogel is combined situation with epithelial cell:
Epithelial cell is planted on compound acellular matrix hydrogel；
Compound acellular matrix hydrogel upper surface covers hydrogel, and at compound acellular matrix hydrogel
And plant epithelial cell between hydrogel；
Compound acellular matrix hydrogel upper surface covers hydrogel, and epithelial cell is planted in table on hydrogel
Face；
Compound acellular matrix hydrogel upper surface covers two-layer hydrogel, and epithelial cell is planted in two-layer water
Between gel；
Or, further, also include one of scenario described below:
Compound acellular matrix hydrogel is combined situation with smooth muscle cell:
Compound acellular matrix hydrogel lower surface plantation smooth muscle cell；
Compound acellular matrix hydrogel lower surface covers hydrogel, and at compound acellular matrix hydrogel
And plant smooth muscle cell between hydrogel；
Compound acellular matrix hydrogel lower surface covers hydrogel, and smooth muscle cell is planted under hydrogel
Surface；
Compound acellular matrix hydrogel lower surface covers two-layer hydrogel, and smooth muscle cell is planted in two-layer
Between hydrogel；
Described compound acellular matrix hydrogel is that acellular matrix hydrogel is good with described biocompatibility
Three-dimensional fiber network material overall or local is compound；Described entirety is compound refers to acellular matrix hydrogel
Interior entirety comprises the three-dimensional fiber network material that biocompatibility is good；Described local is compound refers to biofacies
The upper surface of the three-dimensional fiber network material that capacitive is good and/or lower surface and shallow top layer thereof and de-cell base
Matter hydrogel is combined；
Described hydrogel is the hydrogel that acellular matrix is prepared from.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network the most according to claim 1, its
Being characterised by, possibly together with migrating composition in described compound acellular matrix hydrogel, described migration composition divides
Bales Off is rolled in described acellular matrix hydrogel.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network the most according to claim 4, its
Being characterised by, described migration composition refers to that migrating composition is dispersed in compound acellular matrix hydrogel, but
Do not produce any chemical reaction；Described migration composition is VEGF, insulin, Ah Si
Woods, ketoprofen, Shu Tian be logical or one or more in finasteride.
Bionical tissue based on acellular matrix-cell-three-dimensional fiber network the most according to claim 1, its
Being characterised by, the storage temperature of described compound acellular matrix hydrogel is at 4 DEG C～40 DEG C.
7., such as a preparation method for arbitrary bionical tissue in claim 1,2,3 or 6, it is characterized in that: described
Preparation method is infusion method, cladding process or spraying process.
Preparation method the most according to claim 7, it is characterised in that described preparation method, first prepares de-
Cellular matrix hydrogel precursor solution, then soaks, coats or sprays, then stands at 37 DEG C
3～30min i.e. form compound acellular matrix hydrogel；
Described immersion is:
Before gel is not formed, three-dimensional fiber network material good for biocompatibility is soaked in described
Acellular matrix precursor solution；
Described it is applied to:
Before gel is not formed, described acellular matrix hydrogel precursor solution is coated in biofacies
The upper surface of three-dimensional fiber network material, lower surface or the upper and lower surface that capacitive is good, forms one layer of life
The layer that the good three-dimensional fiber network structure of the thing compatibility is constituted with acellular matrix hydrogel precursor solution
Stack structure；Or further three-dimensional fiber network material good for biocompatibility is fitted in coated taking off
Cellular matrix hydrogel precursor solution layer, forms the three-dimensional fiber network knot that the multi-layer biological compatibility is good
The stepped construction that structure is constituted with acellular matrix hydrogel precursor solution；
Described spraying is:
Before gel is not formed, by described acellular matrix hydrogel precursor solution spraying at biofacies
The upper surface of three-dimensional fiber network material, lower surface or the upper and lower surface that capacitive is good, forms one layer of life
The layer that the good three-dimensional fiber network structure of the thing compatibility is constituted with acellular matrix hydrogel precursor solution
Stack structure；Or further three-dimensional fiber network material good for biocompatibility is fitted in sprayed de-
Cellular matrix hydrogel precursor solution layer, forms the three-dimensional fiber network knot that the multi-layer biological compatibility is good
The stepped construction that structure is constituted with acellular matrix hydrogel precursor solution.
Preparation method the most according to claim 8, it is characterised in that the three-dimensional that described biocompatibility is good
The preparation method of network of fibers material is method of electrostatic spinning or 3 D weaving method.
Preparation method the most according to claim 8, it is characterised in that acellular matrix hydrogel precursor is molten
The preparation process of liquid is additionally added migration composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610395757.4A CN105944143B (en) | 2016-06-06 | 2016-06-06 | Based on bionical tissue of acellular matrix-cell-three-dimensional fiber network and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610395757.4A CN105944143B (en) | 2016-06-06 | 2016-06-06 | Based on bionical tissue of acellular matrix-cell-three-dimensional fiber network and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105944143A true CN105944143A (en) | 2016-09-21 |
| CN105944143B CN105944143B (en) | 2019-08-16 |
Family
ID=56907671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610395757.4A Active CN105944143B (en) | 2016-06-06 | 2016-06-06 | Based on bionical tissue of acellular matrix-cell-three-dimensional fiber network and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105944143B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106075597A (en) * | 2016-06-06 | 2016-11-09 | 东华大学 | Bionical tissue based on bladder acellular matrix cell three-dimensional network of fibers and preparation thereof |
| CN109157305A (en) * | 2018-09-25 | 2019-01-08 | 清华大学深圳研究生院 | Combined artificial cornea and preparation method thereof |
| CN110106148A (en) * | 2019-05-16 | 2019-08-09 | 中国人民解放军军事科学院军事医学研究院 | A kind of tissue-engineered neural tissues and its construction method |
| CN110124086A (en) * | 2019-05-23 | 2019-08-16 | 中山大学 | A kind of composite nano fiber pad, hydrogel/sponge dressing and preparation method and application |
| CN113230461A (en) * | 2021-05-06 | 2021-08-10 | 东华大学 | Micro-nanofiber-hydrogel tissue engineering ureter and preparation method thereof |
| CN113790958A (en) * | 2021-09-01 | 2021-12-14 | 沈阳恒生医用科技有限公司 | High-molecular bionic tissue and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050043813A1 (en) * | 2003-08-20 | 2005-02-24 | Akihiko Kusanagi | Acellular matrix implants for treatment of articular cartilage, bone or osteochondral defects and injuries and method for use thereof |
| CN104274864A (en) * | 2013-07-11 | 2015-01-14 | 上海市第六人民医院 | Method for establishing three-dimensional tissue in vitro |
| CN104582747A (en) * | 2012-08-08 | 2015-04-29 | 南洋理工大学 | Methods of manufacturing hydrogel microparticles having living cells, and compositions for manufacturing scaffold for tissue engineering |
| CN104971380A (en) * | 2014-04-11 | 2015-10-14 | 烟台隽秀生物科技有限公司 | Acellular matrix repairing gel and new method for preparing the same |
| CN106075597A (en) * | 2016-06-06 | 2016-11-09 | 东华大学 | Bionical tissue based on bladder acellular matrix cell three-dimensional network of fibers and preparation thereof |
-
2016
- 2016-06-06 CN CN201610395757.4A patent/CN105944143B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050043813A1 (en) * | 2003-08-20 | 2005-02-24 | Akihiko Kusanagi | Acellular matrix implants for treatment of articular cartilage, bone or osteochondral defects and injuries and method for use thereof |
| CN104582747A (en) * | 2012-08-08 | 2015-04-29 | 南洋理工大学 | Methods of manufacturing hydrogel microparticles having living cells, and compositions for manufacturing scaffold for tissue engineering |
| CN104274864A (en) * | 2013-07-11 | 2015-01-14 | 上海市第六人民医院 | Method for establishing three-dimensional tissue in vitro |
| CN104971380A (en) * | 2014-04-11 | 2015-10-14 | 烟台隽秀生物科技有限公司 | Acellular matrix repairing gel and new method for preparing the same |
| CN106075597A (en) * | 2016-06-06 | 2016-11-09 | 东华大学 | Bionical tissue based on bladder acellular matrix cell three-dimensional network of fibers and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| NING HAN ET AL.: "Hydrogel-electrospun fiber composite materials for hydrophilic protein release", 《JOURNAL OF CONTROLLED RELEASE》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106075597A (en) * | 2016-06-06 | 2016-11-09 | 东华大学 | Bionical tissue based on bladder acellular matrix cell three-dimensional network of fibers and preparation thereof |
| CN109157305A (en) * | 2018-09-25 | 2019-01-08 | 清华大学深圳研究生院 | Combined artificial cornea and preparation method thereof |
| CN109157305B (en) * | 2018-09-25 | 2021-05-25 | 广州锐澄医疗技术有限公司 | Composite artificial cornea and preparation method thereof |
| CN110106148A (en) * | 2019-05-16 | 2019-08-09 | 中国人民解放军军事科学院军事医学研究院 | A kind of tissue-engineered neural tissues and its construction method |
| CN110106148B (en) * | 2019-05-16 | 2020-10-13 | 中国人民解放军军事科学院军事医学研究院 | Tissue engineering nerve tissue and construction method thereof |
| CN110124086A (en) * | 2019-05-23 | 2019-08-16 | 中山大学 | A kind of composite nano fiber pad, hydrogel/sponge dressing and preparation method and application |
| CN113230461A (en) * | 2021-05-06 | 2021-08-10 | 东华大学 | Micro-nanofiber-hydrogel tissue engineering ureter and preparation method thereof |
| CN113230461B (en) * | 2021-05-06 | 2022-02-15 | 东华大学 | Micro-nanofiber-hydrogel tissue engineering ureter and preparation method thereof |
| CN113790958A (en) * | 2021-09-01 | 2021-12-14 | 沈阳恒生医用科技有限公司 | High-molecular bionic tissue and application thereof |
| CN113790958B (en) * | 2021-09-01 | 2024-06-14 | 沈阳恒生医用科技有限公司 | Polymer bionic tissue and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105944143B (en) | 2019-08-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105944143A (en) | Bionic tissue based on acellular matrix-cell-three-dimensional fiber network and preparation method of bionic tissue | |
| Lee et al. | Human‐recombinant‐Elastin‐based bioinks for 3D bioprinting of vascularized soft tissues | |
| George et al. | Neural tissue engineering with structured hydrogels in CNS models and therapies | |
| CN105879119B (en) | A kind of compound acellular matrix hydrogel and preparation method thereof | |
| Wang et al. | Advances in hydrogel-based vascularized tissues for tissue repair and drug screening | |
| CN106075597B (en) | Bionical tissue and its preparation based on bladder acellular matrix-cell-three-dimensional fiber network | |
| Liu et al. | Biomedical applications of layer‐by‐layer self‐assembly for cell encapsulation: Current status and future perspectives | |
| Jana et al. | Anisotropic materials for skeletal‐muscle‐tissue engineering | |
| Ao et al. | Manufacture of multimicrotubule chitosan nerve conduits with novel molds and characterization in vitro | |
| CN106084257B (en) | A kind of composite hydrogel and preparation method thereof | |
| Jeon et al. | Biodegradable, photocrosslinked alginate hydrogels with independently tailorable physical properties and cell adhesivity | |
| Luo et al. | 3D printed hydrogel scaffolds with macro pores and interconnected microchannel networks for tissue engineering vascularization | |
| US8734827B2 (en) | Bioengineered intervertebral discs and methods for their preparation | |
| CN106474560B (en) | A kind of hydrogel material and the preparation method and application thereof for 3D biometric print | |
| Wang et al. | Porous and responsive hydrogels for cell therapy | |
| CN113679888A (en) | Photocuring forming composite hydrogel matrix precursor, preparation method thereof and stent with same | |
| Liu et al. | Comparison of polyglycolic acid, polycaprolactone, and collagen as scaffolds for the production of tissue engineered intestine | |
| CN106048744A (en) | Method for preparing extracellular matrix-simulated nanometer fiber dressing through electrostatic spinning | |
| Liu et al. | Flexible water-absorbing silk-fibroin biomaterial sponges with unique pore structure for tissue engineering | |
| CN105363076A (en) | Method for preparing polylactic acid caprolactone-collagen two-layer bionic vascular scaffold | |
| Babu et al. | Controlling structure with injectable biomaterials to better mimic tissue heterogeneity and anisotropy | |
| Zhang | Injectable biomaterials for stem cell delivery and tissue regeneration | |
| Ajalloueian et al. | One-stage tissue engineering of bladder wall patches for an easy-to-use approach at the surgical table | |
| CN106178114A (en) | Mixing hollow microcapsule, comprise its soft tissue support and preparation method | |
| Liu et al. | Challenges and opportunities of silk protein hydrogels in biomedical applications |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |