CN106310380A - Nano-fibrosis silk fibroin gel and preparation method thereof - Google Patents
Nano-fibrosis silk fibroin gel and preparation method thereof Download PDFInfo
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- CN106310380A CN106310380A CN201610692291.4A CN201610692291A CN106310380A CN 106310380 A CN106310380 A CN 106310380A CN 201610692291 A CN201610692291 A CN 201610692291A CN 106310380 A CN106310380 A CN 106310380A
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- silk fibroin
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- 108010022355 Fibroins Proteins 0.000 title claims abstract description 80
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 206010016654 Fibrosis Diseases 0.000 title claims abstract description 7
- 238000001879 gelation Methods 0.000 title description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000000243 solution Substances 0.000 claims abstract description 23
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- 239000000017 hydrogel Substances 0.000 claims description 41
- 239000002121 nanofiber Substances 0.000 claims description 29
- 241000255789 Bombyx mori Species 0.000 claims description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 11
- 235000019253 formic acid Nutrition 0.000 claims description 11
- 239000012460 protein solution Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000006166 lysate Substances 0.000 claims description 10
- 240000000249 Morus alba Species 0.000 claims description 8
- 235000008708 Morus alba Nutrition 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 4
- 239000000835 fiber Substances 0.000 claims description 4
- 230000004761 fibrosis Effects 0.000 claims description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical group [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- 235000003846 Ricinus Nutrition 0.000 claims description 2
- 241000322381 Ricinus <louse> Species 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 claims description 2
- 229910001631 strontium chloride Inorganic materials 0.000 claims description 2
- AHBGXTDRMVNFER-UHFFFAOYSA-L strontium dichloride Chemical compound [Cl-].[Cl-].[Sr+2] AHBGXTDRMVNFER-UHFFFAOYSA-L 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 16
- 239000011664 nicotinic acid Substances 0.000 abstract description 4
- 238000010923 batch production Methods 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 22
- 239000000463 material Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 235000013601 eggs Nutrition 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 239000003292 glue Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000006835 compression Effects 0.000 description 4
- 238000007906 compression Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000002070 nanowire Substances 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- SXTGAOTXVOMSFW-UHFFFAOYSA-L magnesium;dithiocyanate Chemical compound [Mg+2].[S-]C#N.[S-]C#N SXTGAOTXVOMSFW-UHFFFAOYSA-L 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- -1 stirring Chemical compound 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
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- 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
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
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Abstract
The invention relates to a nano-fibrosis silk fibroin gel and a preparation method of the nano-fibrosis silk fibroin gel. Silk is degummed and then dissolved in salt-formic acid to obtain a silk fibroin solution; a silk fibroin-salt-formic acid solution is injected into a mould; the mould placed with the silk fibroin solution is immersed in an organic solvent or an aqueous solution, and stood for a certain time to form the silk fibroin gel. The preparation method disclosed by the invention is simple in preparation method, short in process, convenient to operate and easy for realization of batch production. The silk fibroin gel prepared by the invention has a natural bionic nanometer fibrillar structure, and is adjustable in mechanical properties and good in biocompatibility.
Description
Technical field
The present invention relates to a kind of nanofiber Silk fibroin gel and preparation method thereof, prepared material can be applicable to
The regenerative medicine such as organizational project, medicament slow release field.
Background technology
The organ or tissue's damage caused due to disease and accident and the patient of afunction have every year millions of more than,
The only U.S. needs more than 800 ten thousand operations to give treatment to this kind of patient every year, and its economic costs is more than 400,000,000,000 dollars.Along with
Modern medicine and the development of surgery operating technology, carry out repair function loss by tissue or organ transplantation and be widely accepted,
But but it is faced with huge donor breach.By regenerative medicine means body, in vivo or external formation is organized or organ is impaired
The reparation of function provides new therapeutic scheme.Wherein, the selection of tissue engineering bracket material and be configured to this Therapeutic Method
One of key.All it is widely present in the case of nature and synthetic with the gel (hydrogel) that water is formed for medium,
In organism little to cell, tissue, arrive greatly organ, all can regard as complexity aquogel system.At biomedical materials field, tool
The polym eric gel having good biocompatibility and degradability has high using value and prospect, can be widely applied to
The loading of tissue recovery support material, medicine controlled release carrier, cell and bioactive molecule and transmission etc..
For loading and the hydrogel of transfer sell must have biocompatibility, suitable material conveying capacity, enough
Mechanical stability and controlled biological degradability.Utilizing synthesis macromolecule to prepare hydrogel, its advantage can be by choosing
Gel process and hydrogel properties is accurately controlled with specific molecular weight, molecular structure and crosslinking method etc., but hydrogel
Biocompatibility poor；The hydrogel prepared with natural macromolecular material, it is preferable with the biocompatibility of tissue, cell,
But controllability and repeatability are poor.
Fibroin is derived from the natural polymer biomaterial of nature, has the mechanical property, controlled of excellence
Biological degradability, workability, particularly its biocompatibility equal with collagen and become preferable regenerative medicine support
Raw material.Fibroin aqueous solution is the most i.e. being self-assembly of gel, but the time is longer, needs a couple of days
Can complete.For quickly preparing silk fibroin hydrogel, can be by adjusting solution parameter (such as solution concentration, pH value, temperature), applying
Extrinsic factor (such as stirring, ultrasonic Treatment) and interpolation other materials (such as poloxamer) realize.Although fibroin hydrogel can
To produce easily, but still face some problem demanding prompt solutions.One of existing key issue is that the dissolution process of existing fibroin is made
Become fibroin to degrade greatly, have a strong impact on the mechanical property of fibroin hydrogel so that it is apply limited；The two of problem are fibroin water-settings
The reparation technology of glue is complex, including three below key step: 1. high concentration neutral salt dissolves, 2. dialysis obtains for a long time
Obtain pure silk fibroin water solution, 3. form gel by the induction silk fibroin aqueous solution cohesion of interior extrinsic factor；The three of problem are current
Fibroin hydrogel inside remain similar sponge loose structure, do not have bionic nano fibre structure, therefore its biology
Characteristic still needs to promote further, does not reaches biologic applications needs.
Therefore the problems referred to above of the prior art are overcome, a kind of preparation method simple, easy-operating of exploitation, and construct knot
The silk fibroin nano-fiber hydrogel that structure is bionical, mechanical property is controlled to fibroin albumen in the application of biomedical materials field
Have very important significance.
Summary of the invention
It is an object of the invention to provide the preparation side of a kind of nanofiber silk fibroin hydrogel simple, easy-operating
Method, and the silk fibroin hydrogel with bionic nano fibrosis formation and excellent in mechanical performance prepared by the method.
For reaching above-mentioned purpose, the technical solution used in the present invention is: a kind of nanofiber silk fibroin hydrogel
Preparation method, comprises the following steps:
(1) acquisition silk fibroin protein solution it is dissolved in salt-formic acid lysate after natural silk degumming；
(2) silk fibroin protein solution of step (1) is injected in mould；
(3) step (2) is immersed in the aqueous solution of organic solvent or aqueous solution equipped with the mould of silk fibroin protein solution, stand and formed
Nanofiber silk fibroin hydrogel.
In technique scheme, step (1) described silkworm silk is mulberry silk, tussah silk, ricinus silk or wild silk yarn.
In technique scheme, the salt in the described salt of step (1)-formic acid lysate be lithium bromide, calcium chloride, zinc chloride,
Magnesium chloride, strontium chloride, lithium rhodanate, sodium rhodanate, Magnesium sulfocyanate. or calcium nitrate.
In technique scheme, in the described salt of step (1)-formic acid lysate, salinity is 1～20 w/v%；Formic acid concn
For 98wt%；In silk fibroin protein solution, the concentration of fibroin albumen is 5～50 w/v%.
In technique scheme, limit formic acid and be possible not only to ensure the dissolving of silkworm silk, protect the fibrillar structure of silkworm silk, simultaneously
Avoid excessive degradation silkworm silk so that regenerated fibroin material has good structure and performance；Avoid other acid such as phosphoric acid,
Hydrochloric acid can seriously be degraded silkworm silk, thus the problem losing use value；It also avoid other acid such as acetic acid and can not dissolve silkworm silk, no
The defect of the regeneration preparation of fibroin can be realized.Thus the formic acid of the present invention is conducive to, and silk fibroin protein solution is uniform, it is molten to ensure
Xie Du, provides good basis for forming nanofiber silk fibroin hydrogel, particularly excellent mechanical property and bionical
Nanofibrillar structures.
In technique scheme, described in step (2), organic solvent is methanol, ethanol, isopropanol；Organic solvent water-soluble
Liquid concentration is 1～99wt%, i.e. the mass content of organic solvent is 1～99wt%.
In technique scheme, in step (2), the shape of product design that mould is prepared as required.
The invention also discloses the nanofiber silk fibroin hydrogel made according to technique scheme；This gel master
Will be made up of the fiber of 10～100nm, hygrometric state modulus of compressibility is 10kPa～100MPa；Can be applicable to prepare tissue engineering bracket
In.
The mechanical property of silkworm silk excellence and the molecular weight of its superelevation and multistage self-assembled structures, particularly nanofibrillar structures
Directly related.In the present invention, salt-formic acid lysate can dissolve silkworm silk in nanometer fibril level, it is thus achieved that fibroin nanometer fibril is molten
Liquid, still preserves its fibrillar structure because of silkworm silk, and therefore this solution does not dissolve each other with water and organic solvent；When this fibroin is received
When rice fibril solution immerses in water and organic solvent, the lowering of concentration of formic acid, pH value of solution reduce, thus induce silk fibroin molecular
Occurring to change to beta sheet crystalline texture from amorphous, be cross-linked simultaneously between nanometer fibril, final cohesion forms gel；
In solution, original fibrillar structure gives the excellent mechanical property of Silk fibroin gel and bionic nano fibrillar structure, and gel is main
Being made up of 10 ~ 100nm fiber, hygrometric state modulus of compressibility is 10kPa ~ 100MPa, achieves beyond thought technique effect.
Owing to technique scheme is used, the present invention compared with prior art has the advantage that
(1) preparation method of the present invention property simple, controllable is strong, after silkworm silk dissolves in salt-formic acid, be directly immersed in organic solvent or
Can form gel in water, be mainly made up of 10 ~ 100nm fiber, hygrometric state modulus of compressibility is 10kPa ~ 100MPa, achieves imaginary
Less than technique effect.
(2) preparation method of the present invention is optional with pure water as derivant, and the silk fibroin solution promoting a step to dissolve directly occurs
Gel formation support, can avoid organic solvent post processing and the support toxicity problem thus caused；And water processes standby fibroin egg
White gel is mainly made up of nanometer fibril, and fibril diameter is between 10 ~ 100 nanometers；Prepare the modulus of compressibility of Silk fibroin gel
Between 10kPa ~ 100MPa, cannot be only used for soft tissue healing such as skin, cornea, and can be used for sclerous tissues's damage
Repair, such as bone；Apply, as regeneration medical material, the basis providing good for silkworm silk.
Accompanying drawing explanation
Fig. 1 is camera and the scanning electron microscope (SEM) photograph of the fibroin egg nanofiber hydrogels that embodiment one prepares；
Fig. 2 is the x-ray diffraction pattern of the fibroin egg nanofiber hydrogels that embodiment two prepares；
Fig. 3 is the scanning electron microscope (SEM) photograph after the fibroin egg nanofiber hydrogels lyophilizing that embodiment two prepares；
Fig. 4 is camera and the scanning electron microscope (SEM) photograph of the fibroin egg nanofiber hydrogels that embodiment three prepares.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described:
Embodiment one
(1) sodium bicarbonate solution of natural mulberry silk mass fraction 0.5wt% boils 30min degumming, obtains de-after being repeated 3 times
Glue mulberry silk；
(2) boiled silk is dissolved in 2w/v calcium chloride-98wt% formic acid solution and obtains 10 w/v % silk protein solutions；
(3) above-mentioned fibroin albumen lysate is directly injected in plastic tube, is then immersed in deionized water, within 8 hours, i.e. formed and receive
Rice fibrosis silk fibroin hydrogel.
Accompanying drawing 1 is the scanning electron microscope (SEM) photograph after the camera photos of above-mentioned prepared fibroin egg nanofiber hydrogels and lyophilizing.
Gel is milky as seen from the figure, smooth surface, and gel is internal to be mainly made up of fibroin albumen nanometer fibril.Survey through mechanics compression
Examination, the modulus of compressibility of this gel is 523.2KPa.
Embodiment two:
(1) sodium bicarbonate solution of natural mulberry silk mass fraction 0.05wt% boils 30min degumming, obtains de-after being repeated 3 times
Glue mulberry silk；
(2) boiled silk is dissolved in 4w/v% calcium chloride-98wt% formic acid solution and obtains the silk protein solution of 25 w/v%；
(3) above-mentioned fibroin albumen lysate is injected in 24 orifice plates, be then immersed in deionized water, within 6 hours, i.e. form Nanowire
Dimensionization silk fibroin hydrogel.
Accompanying drawing 2, accompanying drawing 3 are respectively X-ray diffraction spectrogram and the lyophilizing of above-mentioned prepared fibroin egg nanofiber hydrogels
After scanning electron microscopic picture, fibroin secondary structure is mainly beta sheet crystalline texture as seen from the figure, and internal stent is by Nanowire
Dimension composition.Through mechanics compression verification, the modulus of compressibility of this gel is 16.2MPa.
Embodiment three:
(1) sodium bicarbonate solution of natural tussah silk mass fraction 0.5wt% boils 30min degumming, obtains de-after being repeated 3 times
Glue tussah silk；
(2) it is the fibroin of 50w/v% that degumming tussah silk is dissolved in 10w/v% lithium bromide-98wt% formic acid solution acquisition concentration
Solution；
(3) above-mentioned silk fibroin protein solution is injected in 6 orifice plates, be then immersed in aqueous solution, within 20 hours, i.e. form tussah silk nanometer
Fibrosis silk fibroin hydrogel.
Accompanying drawing 4 is the scanning electron microscope (SEM) photograph after above-mentioned prepared fibroin egg nanofiber hydrogels lyophilizing.This water as seen from the figure
Nanofibrillar structures it is similarly inside gel.Through mechanics compression verification, the modulus of compressibility of this gel is 98.2MPa.
Embodiment four:
(1) sodium bicarbonate solution of natural mulberry silk mass fraction 0.05wt% boils 30min degumming, obtains de-after being repeated 3 times
Glue mulberry silk；
(2) boiled silk is dissolved in 10w/v% calcium chloride-98wt% formic acid solution the fibroin that acquisition concentration is 6 w/v% molten
Liquid；
(3) above-mentioned fibroin albumen lysate is injected in 6 orifice plates, be then immersed in 50 wt% deionized waters, within 12 hours, i.e. formed
Nanofiber silk fibroin hydrogel.
Through mechanics compression verification, the modulus of compressibility of this gel is 213.2KPa.
Claims (10)
1. the preparation method of a nanofiber silk fibroin hydrogel, it is characterised in that comprise the following steps:
(1) acquisition silk fibroin protein solution it is dissolved in salt-formic acid lysate after natural silk degumming；
(2) silk fibroin protein solution of step (1) is injected in mould；
(3) step (2) is immersed in the aqueous solution of organic solvent or water equipped with the mould of silk fibroin protein solution, stand and form nanometer
Fibrosis silk fibroin hydrogel.
The preparation method of nanofiber silk fibroin hydrogel the most according to claim 1, it is characterised in that: described silkworm silk
For one or more in mulberry silk, tussah silk, ricinus silk, wild silk yarn.
The preparation method of nanofiber silk fibroin hydrogel the most according to claim 1, it is characterised in that: described salt-
Salt in formic acid lysate is lithium bromide, calcium chloride, zinc chloride, magnesium chloride, strontium chloride, lithium rhodanate, sodium rhodanate, Hydrogen thiocyanate
One or more in magnesium, calcium nitrate.
The preparation method of nanofiber silk fibroin hydrogel the most according to claim 1, it is characterised in that: described salt-
In formic acid lysate, salinity is 1～20 w/v%；Formic acid concn is 98wt%.
The preparation method of nanofiber silk fibroin hydrogel the most according to claim 1, it is characterised in that: described silk
In fibroin solution, the concentration of fibroin albumen is 5～50 w/v%.
The preparation method of nanofiber silk fibroin hydrogel the most according to claim 1, it is characterised in that: described organic
Solvent is one or more in methanol, ethanol, isopropanol.
The preparation method of nanofiber silk fibroin hydrogel the most according to claim 1, it is characterised in that: described organic
The concentration of aqueous solution of solvent is 1～99wt%.
The nanofiber fibroin that the most according to claim 1, prepared by the preparation method of nanofiber silk fibroin hydrogel
Protein hydrogel.
Nanofiber silk fibroin hydrogel the most according to claim 8, it is characterised in that: described nanofiber fibroin
Protein hydrogel includes the fiber of diameter 10 ~ 100nm.
10. nanofiber silk fibroin hydrogel application in preparing tissue engineering bracket described in claim 8.
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| CN107687088A (en) * | 2017-09-04 | 2018-02-13 | 西南大学 | Conductive silk fabric is prepared with zinc chloride/formic acid solution |
| CN109096501A (en) * | 2018-07-16 | 2018-12-28 | 武汉纺织大学 | A kind of fibroin three-dimensional porous rack and preparation method thereof |
| CN111358706A (en) * | 2020-04-13 | 2020-07-03 | 杭州万事利丝绸文化股份有限公司 | Preparation method of alcohol-fibroin gel washing-free disinfectant |
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| CN114163684A (en) * | 2021-12-31 | 2022-03-11 | 浙江理工大学 | Method for directly extracting fibroin nanofibers from waste silkworm cocoons and recovering hydrolyzed silk protein and extracting solution |
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| CN114395141A (en) * | 2022-01-18 | 2022-04-26 | 苏州大学 | Preparation method of high-strength silk protein nanofiber hydrogel |
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| CN115137883A (en) * | 2022-08-03 | 2022-10-04 | 尧舜泽生物医药(南京)有限公司 | Bionic composite mineralized scaffold and preparation method thereof |
| CN115137883B (en) * | 2022-08-03 | 2023-12-29 | 尧舜泽生物医药(南京)有限公司 | Bionic composite mineralization bracket and preparation method thereof |
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