CN110101918A - A kind of multi-stage porous functional support material and its preparation method and application for mobilizing Endogenous neural stem cells to repair spinal cord injury - Google Patents
A kind of multi-stage porous functional support material and its preparation method and application for mobilizing Endogenous neural stem cells to repair spinal cord injury Download PDFInfo
- Publication number
- CN110101918A CN110101918A CN201910438286.4A CN201910438286A CN110101918A CN 110101918 A CN110101918 A CN 110101918A CN 201910438286 A CN201910438286 A CN 201910438286A CN 110101918 A CN110101918 A CN 110101918A
- Authority
- CN
- China
- Prior art keywords
- precursor liquid
- growth factor
- stage porous
- functional support
- support material
- 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
- 239000000463 material Substances 0.000 title claims abstract description 72
- 208000020431 spinal cord injury Diseases 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 210000001178 neural stem cell Anatomy 0.000 title claims abstract description 18
- 230000008439 repair process Effects 0.000 title claims abstract description 15
- 230000001483 mobilizing effect Effects 0.000 title claims description 6
- 239000007788 liquid Substances 0.000 claims abstract description 70
- 239000002243 precursor Substances 0.000 claims abstract description 50
- 239000004033 plastic Substances 0.000 claims abstract description 40
- 229920003023 plastic Polymers 0.000 claims abstract description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229920001661 Chitosan Polymers 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003102 growth factor Substances 0.000 claims abstract description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 15
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000012153 distilled water Substances 0.000 claims abstract description 9
- 210000005036 nerve Anatomy 0.000 claims abstract description 8
- 239000013078 crystal Substances 0.000 claims abstract description 6
- 230000012010 growth Effects 0.000 claims abstract description 3
- 238000007710 freezing Methods 0.000 claims description 21
- 230000008014 freezing Effects 0.000 claims description 21
- 239000011521 glass Substances 0.000 claims description 9
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims description 9
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims description 9
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 6
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 5
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 5
- 108090000099 Neurotrophin-4 Proteins 0.000 claims description 5
- 102000003683 Neurotrophin-4 Human genes 0.000 claims description 5
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 5
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 5
- 102000013275 Somatomedins Human genes 0.000 claims description 5
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 5
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 5
- 229940053128 nerve growth factor Drugs 0.000 claims description 5
- 229940097998 neurotrophin 4 Drugs 0.000 claims description 5
- 239000003292 glue Substances 0.000 claims description 4
- 210000000130 stem cell Anatomy 0.000 claims description 4
- 230000010261 cell growth Effects 0.000 claims description 3
- 238000002513 implantation Methods 0.000 claims description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 2
- 230000008468 bone growth Effects 0.000 claims description 2
- 230000002518 glial effect Effects 0.000 claims description 2
- 230000000508 neurotrophic effect Effects 0.000 claims description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 210000002950 fibroblast Anatomy 0.000 claims 1
- 210000003494 hepatocyte Anatomy 0.000 claims 1
- 239000003900 neurotrophic factor Substances 0.000 claims 1
- 230000001228 trophic effect Effects 0.000 claims 1
- 230000006378 damage Effects 0.000 abstract description 15
- 230000001537 neural effect Effects 0.000 abstract description 10
- 210000002569 neuron Anatomy 0.000 abstract description 8
- 238000011084 recovery Methods 0.000 abstract description 7
- 230000007646 directional migration Effects 0.000 abstract description 5
- 230000007659 motor function Effects 0.000 abstract description 5
- 238000013528 artificial neural network Methods 0.000 abstract description 3
- 238000013461 design Methods 0.000 abstract description 2
- 210000000225 synapse Anatomy 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 12
- -1 N, N'- methylene Chemical group 0.000 description 11
- 239000000178 monomer Substances 0.000 description 10
- 238000002054 transplantation Methods 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 7
- 239000011799 hole material Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000011148 porous material Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 210000000278 spinal cord Anatomy 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 4
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 4
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 4
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 4
- 108010022355 Fibroins Proteins 0.000 description 4
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 4
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 4
- 238000007906 compression Methods 0.000 description 4
- 230000006835 compression Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 3
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000007831 electrophysiology Effects 0.000 description 3
- 238000002001 electrophysiology Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- GJKGAPPUXSSCFI-UHFFFAOYSA-N 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone Chemical compound CC(C)(O)C(=O)C1=CC=C(OCCO)C=C1 GJKGAPPUXSSCFI-UHFFFAOYSA-N 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- 239000005445 natural material Substances 0.000 description 2
- 230000012106 negative regulation of microtubule depolymerization Effects 0.000 description 2
- 230000007971 neurological deficit Effects 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000037152 sensory function Effects 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000010146 3D printing Methods 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 206010033892 Paraplegia Diseases 0.000 description 1
- 206010037714 Quadriplegia Diseases 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000028600 axonogenesis Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000002122 magnetic nanoparticle Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 239000013265 porous functional material Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
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
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
-
- 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
- A61L27/3641—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 site of application in the body
- A61L27/3675—Nerve tissue, e.g. brain, spinal cord, nerves, dura mater
-
- 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
-
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F251/00—Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
-
- 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
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
Abstract
The present invention relates to the multi-stage porous functional support materials and its preparation method and application that a kind of mobilization Endogenous neural stem cells repair spinal cord injury, the material is prepared by the following method: the chitosan for modifying double bond being mixed with crosslinking agent B IS, 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water and obtains precursor liquid, it is added or is added without growth factor configuration plastic precursor liquid, it is placed in ice crystal in liquid nitrogen to be oriented to, then ultraviolet lighting causes plastic at -20 DEG C.Material of the present invention has the pilot hole different along material long axis inner diameter size, provide space structure needed for neural circuitry reconstructs, facilitate Endogenous neural stem cells directional migration to transplant region to material and forms newborn neuron, multilevel structure growth of the nerve synapse along design, constitute neural network, the neural circuitry of damage field is rebuild, motor function recovery after spinal cord injury is promoted.
Description
Technical field
The present invention relates to nerve regneration recovery technique fields, specifically, being related to a kind of mobilization Endogenous neural stem cells
Repair the multi-stage porous functional support material and its preparation method and application of spinal cord injury.
Background technique
Spinal cord injury (spinal cord injury, SCI) typically refers to the ridge due to caused by many reasons such as wound
Marrow coup injury leads to lesion level movement below and the different degrees of missing of sensory function, or even movement and sensory function
It completely loses and paraplegia occurs.SCI disease incidence with higher, other than causing body quadriplegia and half body to paralyse, it is also possible to
Other secondary diseases are generated, the quality of minimal invasive treatment is seriously affected.The treatment and rehabilitation of SCI is always basis and clinical medicine
One of the great difficult problem in field.
Spinal cord injury initially frequently can lead to the continuous loss of cell and tissue, and tissue engineering bracket can simulate extracellularly
The physiological status of matrix, to be conducive to sticking, migrate, expand and breaking up for cell.Organizational project is repaired spinal cord injury and is focused on
In three aspects: seed cell, tissue engineering bracket and material and cell factor.Material for tissue engineering bracket can be divided into
Natural material and synthetic material, natural material are usually the polymer for extracting albumen or carbohydrate, have been used as
Organization bracket.The material of common tissue engineering bracket has collagen, chitosan, agarose/alginates, fibronectin, synthesized polymer
Object, polylactic acid, polyglycolic acid/polylactic acid, poly- β hydroxybutyric acid, magnetic nanoparticle etc..But the prior art is mostly physical mixed,
Material is constructed into relevant cord repair materials by physical method, the precise and tiny structure of no inside can not construct neural circuitry reconstruct
Access.In addition there is scholar and construct spinal cord repair materials using spun structure or multiple fibre structure, but be equally unable to satisfy
The space requirement that nerve regneration and neural circuitry are rebuild.In addition realize that correlation factor can not over space structure in the prior art
The system that controlled release is put.For example, a kind of glue of dual modification disclosed in patent document CN109106981A, publication date 2019.01.01
The collagen scaffold of former bracket, the dual modification includes collagen as tissue engineering scaffold, and modification is on the collagen as tissue engineering scaffold
EGFR antibody and microtubule stabilization molecule, the EGFR antibody and microtubule stabilization molecule are uniformly distributed in by way of physical absorption
The inside and surface of the collagen as tissue engineering scaffold.
In addition, patent document CN102727936A, publication date 2012.10.17, disclose a kind of for repairing Transverse ridge
The sustained release NT-3 gelatin sponge cylinder bracket material containing stem cell of marrow damage, shape characteristic is: cylinder bracket table
Face is wrapped in by polylactide-polyglycolic acid copolymer (poly D, L-lactic-co-glycolic acid, PLGA) film
The thin-walled of composition, cylindrical body center are filled with the gelfoam of load NT-3/ fibroin albumen；By loading NT-3/ fibroin albumen
Gelfoam absorption plantation stem cell and its differentiation cell, be built into and be conducive to be damaged spinal cord nerve regeneration and its function
The sustained release NT-3 gelatin sponge cylinder bracket that can be repaired.The cylinder bracket is by the PLGA tube wall of appearance thin layer and interior
The gelfoam of the load NT-3/ fibroin albumen in portion is constituted, and the gelfoam of load NT-3/ fibroin albumen is multi-pore structure.
But the hole of the timbering material is unordered.
It yet there are no comprising the pilot hole along material long axis direction, space structure needed for neural circuitry reconstructs be provided, with
Facilitate the timbering material based on chitosan of Endogenous neural stem cells directional migration.
Summary of the invention
The purpose of the present invention is aiming at the shortcomings in the prior art, provide a kind of mobilization Endogenous neural stem cells reparation ridge
The multi-stage porous functional support material of marrow damage.
The another purpose of the present invention is to provide a kind of multi-stage porous function of mobilization Endogenous neural stem cells reparation spinal cord injury
The preparation method of energy timbering material.
Another purpose of the present invention is to provide the purposes of the multi-stage porous functional support material.
To realize above-mentioned first purpose, the technical solution adopted by the present invention is that:
A kind of multi-stage porous functional support material for mobilizing Endogenous neural stem cells to repair spinal cord injury, the multi-stage porous
Functional support material is prepared by the following method:
A) by glycidyl methacrylate cross-linked chitosan and crosslinking agent N, N'- methylene-bisacrylamide, light draw
Hair agent 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water are mixed in a certain proportion acquisition precursor liquid, wherein
The glycidyl methacrylate cross-linked chitosan, crosslinking agent N, N'- methylene-bisacrylamide, photoinitiator 2- hydroxyl
The mass ratio of base -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water is 1:(0.5%-2%): (2%-4%): (35-
45)；
B) growth factor is added, configures plastic precursor liquid with precursor liquid；Or being added without growth factor, then the precursor liquid is
For plastic precursor liquid；
C) the plastic precursor liquid is placed in progress ice crystal guiding in liquid nitrogen；
D) then at -20 DEG C ultraviolet lighting cause plastic to get.
As a preference, between step b) and step c), also includes step: the plastic precursor liquid is centrifuged off
Bubble.
It is highly preferred that the centrifugal condition are as follows: 4500-5500r/min, 2.5-4min.
As another preference, liquid is at the uniform velocity placed in by the plastic precursor liquid implantation glass pipe, then by the glass tube
Freezing guiding is carried out in nitrogen.
It is highly preferred that the rate being placed in liquid nitrogen is 2.5-3.5mm/s.
As another preference, in step d), the ultraviolet lighting time is 3-18min.
As another preference, the growth factor be selected from brain-derived neurotrophic factor (BDNF), neurotrophy because
- 3 (NT-3) of son, Neurotrophin-4 (NT-4), nerve growth factor (NGF), basic fibroblast growth factor (bFGF),
Epithelical cell growth factor (EGF), insulin-like growth factor (IGF), transforming growth factor (TGF), vascular endothelial growth factor
Son (VEGF), hepatocyte growth factor (HGF), glial neurotrophic growth factor (GDNF), bone growth factor (SGF)
With one or more of platelet derived growth factor (PDGF), stem cell factor (SCF), but not limited to this.
As another preference, the multi-stage porous functional support material, which is also planted, is implanted with seed cell.
As another preference, the seed cell is neural stem cell, embryonic stem cell, schwann cell, to smell sheath thin
Born of the same parents, marrow stromal cell, oligodendroglia etc..
To realize above-mentioned second purpose, the technical solution adopted by the present invention is that:
A kind of preparation method for the multi-stage porous functional support material for mobilizing Endogenous neural stem cells to repair spinal cord injury, packet
Include following steps:
A) by glycidyl methacrylate cross-linked chitosan and crosslinking agent N, N'- methylene-bisacrylamide, light draw
Hair agent 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water are mixed in a certain proportion acquisition precursor liquid, wherein
The glycidyl methacrylate cross-linked chitosan, crosslinking agent N, N'- methylene-bisacrylamide, photoinitiator 2- hydroxyl
The mass ratio of base -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water is 1:(0.5%-2%): (2%-4%): (35-
45)；
B) growth factor is added, configures plastic precursor liquid with precursor liquid；Or being added without growth factor, then the precursor liquid is
For plastic precursor liquid；
C) the plastic precursor liquid is placed in progress ice crystal guiding in liquid nitrogen；
D) then at -20 DEG C ultraviolet lighting cause plastic to get.
As a preference, between step b) and step c), also includes step: the plastic precursor liquid is centrifuged off
Bubble.
It is highly preferred that the centrifugal condition are as follows: 4500-5500r/min, 2.5-4min.
As another preference, in step c), by the plastic precursor liquid implantation glass pipe, then the glass tube is even
Speed, which is placed in liquid nitrogen, carries out freezing guiding.
It is highly preferred that the rate being placed in liquid nitrogen is 2.5-3.5mm/s.
As another preference, in step d), the ultraviolet lighting time is 3-18min.
To realize above-mentioned third purpose, the technical solution adopted by the present invention is that:
As above application of any multi-stage porous functional support material in the product that spinal cord injury is repaired in preparation.
The invention has the advantages that:
1, the present invention provides a kind of multilevel hole material according to neuron axon growth multi-stage characteristics, the material is through special
Method is prepared, and inside forms the pilot hole different along material long axis, inner diameter size, provides required for neural circuitry reconstruct
Space structure, region and form newborn neuron to facilitate Endogenous neural stem cells directional migration to transplant to material, nerve
Cynapse forms effective synaptic contact, constitutes neural network, rebuild the nerve ring of damage field along the multilevel structure growth of design
Road promotes motor function recovery after spinal cord injury.
2, multilevel hole material of the invention has good mechanical strength, and the aperture of pilot hole is suitable for, through zoopery table
Bright transplantation treatment mouse spinal cord damage, can remarkably promote the recovery of mouse lower extremity motor function.
3, material of the invention can load correlation factor in building process, be configured to control delivery, preferably promote
Into Regeneration and Repair.
4, material of the invention can also load exogenous neural stem cell.
5, material aperture of the invention adjustable (adapting to cell culture), intensity controlled (can tolerate sound magnetoelectricity physical factor to add
Carry), can 3D printing (integrating nano controlled release system), have biocompatibility.
Detailed description of the invention
Attached drawing 1: the infrared figure of the chitosan with and without modification double bond.
Attached drawing 2: compression verification figure of the colloidal materials under different light application times.
Attached drawing 3: the Mercury-injection test graph of pore diameter distribution of the colloidal materials with and without freezing guiding.
Attached drawing 4: the plastic test chart of colloidal materials.
Attached drawing 5: the SEM test chart of colloidal materials.
Attached drawing 6: multi-stage porous functional support material of the present invention repairs the schematic diagram of spinal cord injury.
Attached drawing 7: with the multi-stage porous functional support transplantation treatment spinal cord injury of building.A figure is the shifting of multi-stage porous functional support
Schematic diagram is planted, cross-section model carries out experiment in vivo entirely using the spinal cord injury constructed early period, and the multi-stage porous branch of building is placed on
Damage zone；Gross specimen when B figure top half is transplanting, it is seen that multi-stage porous functional support is filled up completely damage zone after transplanting, under
The gross specimen of damage group and control group compares after half portion is divided into 8 weeks, it is seen that control group tissue necrosis, and transplantation treatment group has newly
Raw tissue；C figure is the neurological deficit score of mouse, it is seen that transplantation treatment group behavioral recovery has obvious statistics poor compared with control group
It is different；D figure is the electro physiology detection of spinal cord injury mouse, it is seen that control group is without apparent electro physiology waveform, and transplantation treatment group goes out
Apparent wave amplitude is showed；It discloses multi-stage porous functional support and promotes neurological functional recovery after spinal cord injury.
Attached drawing 8: spinal cord slice coloration result after multi-stage porous functional support transplantation treatment 8 weeks.It is had found in transplantation treatment area
Newborn neuron, it is more close to damage borderline neuron, and lesion center regional neuronal is less, presents certain trend ladder
Effect is spent, and without the Distribution Effect in normal tissue, thus it is speculated that multi-stage porous functional support may be induction of Endogenous neural stem cells
Directional migration (white border is damage zone and normal tissue boundary, and lower half portion is partial enlargement image).
Specific embodiment
It elaborates with reference to the accompanying drawing to specific embodiment provided by the invention.
The preparation (one) of the multi-stage porous functional support material of the present invention of embodiment 1
1, chitosan graft double bond:
2.0g chitosan is weighed in three-neck flask, the acetic acid aqueous solution of 150ml2% is added, it is water-soluble that a small amount of KOH is added dropwise
Liquid adjusts pH=3.8.Then 3.51g glycidyl methacrylate (GMA) is slowly added dropwise, it is lasting to stir, under the conditions of 60 DEG C
Reaction 6 hours.Reaction mixture is poured into acetone later, a large amount of flocculent deposits is obtained, then floccule is poured into acetonitrile, obtains
It to powdered precipitating, is most dissolved after for several times with water through acetone washing afterwards, is fitted into the bag filter that molecular weight is 3500 and dialyses 3 days,
Freeze-drying, obtains raw material Chitosan-GMA, spare.Using infrared spectroscopy and H-NMR to the chitosan after grafting double bond
It is characterized.
As a result: Fig. 1 is the infrared figure with and without the chitosan of modification double bond, and the chitosan comparison for modifying double bond is not decorated
There are double bond transmission peaks at 1710.39 in the chitosan of double bond, illustrates successfully to have modified double bond on double bond chitosan.
2, the preparation of material:
50mg (2.5%) Chitosan-GMA is weighed in vial, 100 μ L BIS (N, N'- methylene are then added
Bisacrylamide, 10mg/mL) crosslinking agent (the 2% of monomer), add 1.5mg photoinitiator 2- hydroxyl -4'- (2- hydroxyl ethoxy
Base) -2- methyl phenyl ketone (the 3% of monomer), it is eventually adding 1900 μ L H2O makes it dissolve in 37 DEG C of stirring 2h, forms forerunner
Liquid namely plastic precursor liquid.
Plastic precursor liquid is subjected to 5000r/min centrifugation 3min after dissolution completely and removes bubble.Then solution use is washed
Ear ball is injected in capillary.
The capillary for injecting solution is placed in liquid nitrogen using elevator at the uniform velocity (3.3mm/s) and carries out freezing guiding.Guiding
After capillary is placed at once in -20 DEG C of refrigerators using freezing ultraviolet lamp (UV Led Curing System, model UP3-
304, it is purchased from Mean Well International Co.Ltd) carry out freezing ultraviolet plastic.
The mechanical strength of material is adjusted by the dosage and ultraviolet lighting time that adjust chitosan and crosslinking agent.
Mechanics Performance Testing: measuring the diameter and height of columned colloidal materials first, and parameter is inputted into omnipotent mechanics machine
In (thinking carefully UTM2505 in length and breadth), compression verification, compression speed 5mm/min then are carried out using omnipotent mechanics machine.
Fall off rate by adjusting elevator adjusts the size in aperture.
It is characterized using pore size and pore size distribution of the mercury injection method to material.
Gelation time is tested using rheometer.
After the freeze-dried removing ice crystal of gel, the guide frame and pore structure of scanning electron microscopic observation gel are utilized.
As a result:
Fig. 2 is compression verification figure of the colloidal materials under different light application times, under different light application times, the pressure of colloid
Contracting intensity first rises to be declined afterwards, has maximum compressive strength in illumination 12min.Fig. 3 is the colloid material with and without freezing guiding
The Mercury-injection test graph of pore diameter distribution of material.Fig. 4 is the plastic test chart of colloidal materials.Fig. 5 is the SEM test chart of colloidal materials.
The preparation (two) of the multi-stage porous functional support material of the present invention of embodiment 2
1, chitosan graft double bond:
With embodiment 1.
2, the preparation of material:
50mg Chitosan-GMA is weighed in vial, 25 μ L BIS (N, N'- methylene bisacrylamides are then added
Amide, 10mg/mL) crosslinking agent (the 0.5% of monomer), add 2mg photoinitiator 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- first
Base propiophenone (the 4% of monomer) is eventually adding 1700 μ L H2O makes it dissolve in 37 DEG C of stirring 2h, forms precursor liquid, also
Glue precursor liquid.
Plastic precursor liquid is subjected to 4500r/min centrifugation 4min after dissolution completely and removes bubble.Then solution use is washed
Ear ball is injected in capillary.
The capillary for injecting solution is placed in liquid nitrogen using elevator at the uniform velocity (2.5mm/s) and carries out freezing guiding.Guiding
After capillary is placed at once in -20 DEG C of refrigerators using freezing ultraviolet lamp (UV Led Curing System, model UP3-
304, it is purchased from Mean Well International Co.Ltd) carry out freezing ultraviolet plastic, the ultraviolet lighting time is 15min.
The preparation (three) of the multi-stage porous functional support material of the present invention of embodiment 3
1, chitosan graft double bond:
With embodiment 1.
2, the preparation of material:
50mg Chitosan-GMA is weighed in vial, 50 μ L BIS (N, N'- methylene bisacrylamides are then added
Amide, 10mg/mL) crosslinking agent (the 1% of monomer), add 1mg photoinitiator 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl
Propiophenone (the 2% of monomer) is eventually adding 2200 μ L H2O makes it dissolve in 37 DEG C of stirring 2h, forms precursor liquid namely plastic
Precursor liquid.
Plastic precursor liquid is subjected to 4500r/min centrifugation 4min after dissolution completely and removes bubble.Then solution use is washed
Ear ball is injected in capillary.
The capillary for injecting solution is placed in liquid nitrogen using elevator at the uniform velocity (3.5mm/s) and carries out freezing guiding.Guiding
After capillary is placed at once in -20 DEG C of refrigerators using freezing ultraviolet lamp (UV Led Curing System, model UP3-
304, it is purchased from Mean Well International Co.Ltd) carry out freezing ultraviolet plastic, the ultraviolet lighting time is 3min.
The preparation (four) of the multi-stage porous functional support material of the present invention of embodiment 4
1, chitosan graft double bond:
With embodiment 1.
2, the preparation of material:
50mg Chitosan-GMA is weighed in vial, 25 μ L BIS (N, N'- methylene bisacrylamides are then added
Amide, 10mg/mL) crosslinking agent (the 0.5% of monomer), add 1.5mg photoinitiator 2- hydroxyl -4'- (2- hydroxy ethoxy) -2-
Methyl phenyl ketone (the 3% of monomer) is eventually adding 1950 μ L H2O makes it dissolve in 37 DEG C of stirring 2h, forms precursor liquid.Preceding
Drive liquid correlation factor and precursor liquid be added and configure plastic precursor liquid, the correlation factor of addition be BDNF, NT-3, NT-4, NGF,
One or more of bFGF, EGF, IGF, TGF, VEGF, HGF, GDNF, SGF and PDGF, SCF.
Plastic precursor liquid is subjected to 5500r/min centrifugation 2.5min after dissolution completely and removes bubble.Then solution is used
Ear washing bulb injects in capillary.
The capillary for injecting solution is placed in liquid nitrogen using elevator at the uniform velocity (3.0mm/s) and carries out freezing guiding.Guiding
After capillary is placed at once in -20 DEG C of refrigerators using freezing ultraviolet lamp (UV Led Curing System, model UP3-
304, it is purchased from Mean Well International Co.Ltd) carry out freezing ultraviolet plastic, the ultraviolet lighting time is 3min.
The preparation (five) of the multi-stage porous functional support material of the present invention of embodiment 5
1, chitosan graft double bond:
With embodiment 1.
2, the preparation of material:
50mg Chitosan-GMA is weighed in vial, 100 μ L BIS (N, N'- methylene bisacrylamides are then added
Amide, 10mg/mL) crosslinking agent (the 2% of monomer), add 2mg photoinitiator 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl
Propiophenone (the 4% of monomer) is eventually adding 1950 μ L H2O makes it dissolve in 37 DEG C of stirring 2h, forms precursor liquid.In precursor liquid
Correlation factor and precursor liquid is added and configures plastic precursor liquid, the correlation factor of addition be BDNF, NT-3, NT-4, NGF, bFGF,
One or more of EGF, IGF, TGF, VEGF, HGF, GDNF, SGF and PDGF, SCF.
Plastic precursor liquid is subjected to 5000r/min centrifugation 4min after dissolution completely and removes bubble.Then solution use is washed
Ear ball is injected in capillary.
The capillary for injecting solution is placed in liquid nitrogen using elevator at the uniform velocity (3.0mm/s) and carries out freezing guiding.Guiding
After capillary is placed at once in -20 DEG C of refrigerators using freezing ultraviolet lamp (UV Led Curing System, model UP3-
304, it is purchased from Mean Well International Co.Ltd) carry out freezing ultraviolet plastic, the ultraviolet lighting time is 18min.
Embodiment 6
Fig. 6 is referred to, Fig. 6 is the schematic diagram that multi-stage porous functional support material of the present invention repairs spinal cord injury, in damage ridge
Marrow defect point transplants multi-stage porous functional support material of the present invention, since the material has the guiding along material long axis inner diameter size one not
Hole can facilitate Endogenous neural stem cells directional migration to transplant region to material and form newborn neuron, and nerve synapse edge is set
The multilevel structure of meter is grown, and constitutes the neural circuitry of neural network reconstruction damage field, promotes motor function after spinal cord injury extensive
It is multiple.Correlation factor can be loaded in material building process, is configured to control delivery, advantageously promote Regeneration and Repair.
Verifying multi-stage porous functional support material of the present invention by zoopery is promoting Endogenous neural stem cells to reconstruct ridge
Marrow damage zone neural circuitry repairs the effect in spinal cord injury.
It is damaged using multi-stage porous functional support material transplantation treatment mouse spinal cord constructed by embodiment 1, with blank control
Group comparison discovery multi-stage porous functional material transplanting can effectively facilitate the recovery of mouse lower extremity motor function, and neurological deficit score relatively compares
Group is significant to be increased, and electro physiology detection discovery multi-stage porous functional support material transplantation treatment group has apparent bioelectrical activity (Fig. 7).
By technological means such as immunohistochemistry, newborn neuron is had found in transplantation treatment area, it is more close to damage borderline neuron, and
Lesion center regional neuronal is less, presents certain trend Gradient Effect (Fig. 8).
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, under the premise of not departing from the method for the present invention, can also make several improvement and supplement, these are improved and supplement also should be regarded as
Protection scope of the present invention.
Claims (10)
1. a kind of multi-stage porous functional support material for mobilizing Endogenous neural stem cells to repair spinal cord injury, which is characterized in that institute
The multi-stage porous functional support material stated is prepared by the following method:
A) by glycidyl methacrylate cross-linked chitosan and crosslinking agent N, N'- methylene-bisacrylamide, photoinitiator
2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water are mixed in a certain proportion acquisition precursor liquid, wherein described
Glycidyl methacrylate cross-linked chitosan, crosslinking agent N, N'- methylene-bisacrylamide, photoinitiator 2- hydroxyl-
The mass ratio of 4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water is 1:(0.5%-2%): (2%-4%): (35-
45)；
B) growth factor is added, configures plastic precursor liquid with precursor liquid；Or be added without growth factor, then the precursor liquid be at
Glue precursor liquid；
C) the plastic precursor liquid is placed in progress ice crystal guiding in liquid nitrogen；
D) then at -20 DEG C ultraviolet lighting cause plastic to get.
2. multi-stage porous functional support material according to claim 1, which is characterized in that between step b) and step c), also
Include step: the plastic precursor liquid is centrifuged off bubble.
3. multi-stage porous functional support material according to claim 1, which is characterized in that in step c), before the plastic
It drives in liquid implantation glass pipe, then the glass tube is at the uniform velocity placed in liquid nitrogen and carries out freezing guiding.
4. multi-stage porous functional support material according to claim 1, which is characterized in that in step d), the ultraviolet lighting time
For 3-18min.
5. multi-stage porous functional support material according to claim 1, which is characterized in that the growth factor is selected from brain source
Nerve trophic factors, neurotrophic factor -3, Neurotrophin-4, nerve growth factor, basic fibroblast growth because
Son, epithelical cell growth factor, insulin-like growth factor, transforming growth factor, vascular endothelial growth factor, hepatic cell growth
The factor, glial neurotrophic growth factor, bone growth factor, platelet derived growth factor, one in stem cell factor
Kind is several.
6. a kind of preparation method for the multi-stage porous functional support material for mobilizing Endogenous neural stem cells to repair spinal cord injury, special
Sign is, comprising the following steps:
A) by glycidyl methacrylate cross-linked chitosan and crosslinking agent N, N'- methylene-bisacrylamide, photoinitiator
2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water are mixed in a certain proportion acquisition precursor liquid, wherein described
Glycidyl methacrylate cross-linked chitosan, crosslinking agent N, N'- methylene-bisacrylamide, photoinitiator 2- hydroxyl-
The mass ratio of 4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone and distilled water is 1:(0.5%-2%): (2%-4%): (35-
45)；
B) growth factor is added, configures plastic precursor liquid with precursor liquid；Or be added without growth factor, then the precursor liquid be at
Glue precursor liquid；
C) the plastic precursor liquid is placed in progress ice crystal guiding in liquid nitrogen；
D) then at -20 DEG C ultraviolet lighting cause plastic to get.
7. preparation method according to claim 6, which is characterized in that also include step between step b) and step c): will
The plastic precursor liquid is centrifuged off bubble.
8. preparation method according to claim 1, which is characterized in that in step c), the plastic precursor liquid is injected glass
In glass pipe, then the glass tube is at the uniform velocity placed in liquid nitrogen and carries out freezing guiding.
9. preparation method according to claim 1, which is characterized in that in step d), the ultraviolet lighting time is 3-18min.
10. application of any multi-stage porous functional support material of claim 1-5 in the product that spinal cord injury is repaired in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910438286.4A CN110101918B (en) | 2019-05-24 | 2019-05-24 | Hierarchical pore functional scaffold material for mobilizing endogenous neural stem cells to repair spinal cord injury and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910438286.4A CN110101918B (en) | 2019-05-24 | 2019-05-24 | Hierarchical pore functional scaffold material for mobilizing endogenous neural stem cells to repair spinal cord injury and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110101918A true CN110101918A (en) | 2019-08-09 |
| CN110101918B CN110101918B (en) | 2021-09-21 |
Family
ID=67492024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910438286.4A Active CN110101918B (en) | 2019-05-24 | 2019-05-24 | Hierarchical pore functional scaffold material for mobilizing endogenous neural stem cells to repair spinal cord injury and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110101918B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111359019A (en) * | 2020-03-16 | 2020-07-03 | 四川大学 | Preparation method of graphene and chitosan composite conductive nerve scaffold with longitudinal pore channels |
| CN112933293A (en) * | 2020-11-06 | 2021-06-11 | 浙江大学 | Injectable hydrogel for treating central nerve injury and preparation method thereof |
| CN113577108A (en) * | 2021-08-31 | 2021-11-02 | 中国科学院苏州纳米技术与纳米仿生研究所 | Multifunctional collagen scaffold, preparation method and application thereof |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090148961A1 (en) * | 2006-09-27 | 2009-06-11 | Alessandra Luchini | Smart hydrogel particles for biomarker harvesting |
| CN101715457A (en) * | 2007-04-24 | 2010-05-26 | 丘比株式会社 | Cationized hyaluronic acid and/or salt thereof, method for producing the same, and hair modifying agent, cuticle repairing agent, skin modifying agent and cosmetic preparation each using the same |
| KR20110062804A (en) * | 2009-12-04 | 2011-06-10 | 연세대학교 산학협력단 | Interpenetrating polymer network hydrogel and preparation method thereof |
| CN102671237A (en) * | 2009-01-16 | 2012-09-19 | 中国人民解放军第四军医大学 | High-simulation tissue engineering nerve-repair material and preparation method |
| CN103127494A (en) * | 2013-03-11 | 2013-06-05 | 上海神因生物科技有限公司 | Nerve regeneration biogum and preparation method and application thereof |
| CN104788583A (en) * | 2014-01-17 | 2015-07-22 | 北京朗嘉仪生物技术有限公司 | Photo-crosslinking material, hydrogel formed by photo-crosslinking material and preparation method and application thereof |
| CN106008840A (en) * | 2016-06-30 | 2016-10-12 | 广州振清环保技术有限公司 | Chitosan crosslinked modified resin as well as preparation method and application thereof |
| US20170281783A1 (en) * | 2011-08-17 | 2017-10-05 | KeraNetics, LLC | Low protein percentage gelling compositions |
| CN108339151A (en) * | 2018-02-08 | 2018-07-31 | 上海市同济医院 | A kind of nano layered double hydroxides-multiple-factor combined system for promoting nerve regneration to repair spinal cord injury |
| CN108888803A (en) * | 2018-07-11 | 2018-11-27 | 蒋青 | A kind of biological support and preparation method thereof, purposes and aquogel system |
| CN109106981A (en) * | 2017-06-26 | 2019-01-01 | 中国科学院苏州纳米技术与纳米仿生研究所 | The collagen scaffold of dual modification and the application in the product for repairing spinal cord injury |
-
2019
- 2019-05-24 CN CN201910438286.4A patent/CN110101918B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090148961A1 (en) * | 2006-09-27 | 2009-06-11 | Alessandra Luchini | Smart hydrogel particles for biomarker harvesting |
| CN101715457A (en) * | 2007-04-24 | 2010-05-26 | 丘比株式会社 | Cationized hyaluronic acid and/or salt thereof, method for producing the same, and hair modifying agent, cuticle repairing agent, skin modifying agent and cosmetic preparation each using the same |
| CN102671237A (en) * | 2009-01-16 | 2012-09-19 | 中国人民解放军第四军医大学 | High-simulation tissue engineering nerve-repair material and preparation method |
| KR20110062804A (en) * | 2009-12-04 | 2011-06-10 | 연세대학교 산학협력단 | Interpenetrating polymer network hydrogel and preparation method thereof |
| US20170281783A1 (en) * | 2011-08-17 | 2017-10-05 | KeraNetics, LLC | Low protein percentage gelling compositions |
| CN103127494A (en) * | 2013-03-11 | 2013-06-05 | 上海神因生物科技有限公司 | Nerve regeneration biogum and preparation method and application thereof |
| CN104788583A (en) * | 2014-01-17 | 2015-07-22 | 北京朗嘉仪生物技术有限公司 | Photo-crosslinking material, hydrogel formed by photo-crosslinking material and preparation method and application thereof |
| CN106008840A (en) * | 2016-06-30 | 2016-10-12 | 广州振清环保技术有限公司 | Chitosan crosslinked modified resin as well as preparation method and application thereof |
| CN109106981A (en) * | 2017-06-26 | 2019-01-01 | 中国科学院苏州纳米技术与纳米仿生研究所 | The collagen scaffold of dual modification and the application in the product for repairing spinal cord injury |
| CN108339151A (en) * | 2018-02-08 | 2018-07-31 | 上海市同济医院 | A kind of nano layered double hydroxides-multiple-factor combined system for promoting nerve regneration to repair spinal cord injury |
| CN108888803A (en) * | 2018-07-11 | 2018-11-27 | 蒋青 | A kind of biological support and preparation method thereof, purposes and aquogel system |
Non-Patent Citations (7)
| Title |
|---|
| CUNXIAN DUAN等: "Chitosan-g-poly(N-isopropylacrylamide) based nanogels for tumor extracellular targeting", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| E.A. ELIZALDE-PEÑA等: "(Chitosan-g-glycidyl methacrylate)-xanthan hydrogel implant in Wistar rats for spinal cord regeneration", 《MATERIALS SCIENCE AND ENGINEERING C》 * |
| MARTIN OUDEGA等: "Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord", 《EXPERIMENTAL NEUROLOGY》 * |
| NICOLA L. FRANCIS等: "Strategies for neurotrophin-3 and chondroitinase ABC release from freeze-cast chitosan–alginate nerve-guidance scaffolds", 《J TISSUE ENG REGEN MED》 * |
| 俞洁等: "壳聚糖聚丙烯酸水凝胶对Pb~(2+)的吸附机理研究", 《西北师范大学学报(自然科学版)》 * |
| 刘靓等: "高仿真组织工程神经支架制备工艺的参数优化", 《现代生物医学进展》 * |
| 李保强著: "《壳聚糖生物材料》", 30 June 2017, 哈尔滨工业大学出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111359019A (en) * | 2020-03-16 | 2020-07-03 | 四川大学 | Preparation method of graphene and chitosan composite conductive nerve scaffold with longitudinal pore channels |
| CN112933293A (en) * | 2020-11-06 | 2021-06-11 | 浙江大学 | Injectable hydrogel for treating central nerve injury and preparation method thereof |
| CN112933293B (en) * | 2020-11-06 | 2022-06-10 | 浙江大学 | Injectable hydrogel for treating central nerve injury and preparation method thereof |
| CN113577108A (en) * | 2021-08-31 | 2021-11-02 | 中国科学院苏州纳米技术与纳米仿生研究所 | Multifunctional collagen scaffold, preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110101918B (en) | 2021-09-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Xue et al. | Anisotropic scaffolds for peripheral nerve and spinal cord regeneration | |
| Chang et al. | Multichanneled nerve guidance conduit with spatial gradients of neurotrophic factors and oriented nanotopography for repairing the peripheral nervous system | |
| Samadian et al. | Naturally occurring biological macromolecules-based hydrogels: Potential biomaterials for peripheral nerve regeneration | |
| Wu et al. | In vitro and in vivo biocompatibility evaluation of a 3D bioprinted gelatin-sodium alginate/rat Schwann-cell scaffold | |
| Madigan et al. | Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds | |
| Farrukh et al. | Microenvironments designed to support growth and function of neuronal cells | |
| Rao et al. | Decellularized nerve matrix hydrogel scaffolds with longitudinally oriented and size-tunable microchannels for peripheral nerve regeneration | |
| Biazar et al. | Types of neural guides and using nanotechnology for peripheral nerve reconstruction | |
| Wang et al. | Hyaluronic acid-based scaffold for central neural tissue engineering | |
| Wang et al. | Evaluation of the potential of rhTGF-β3 encapsulated P (LLA-CL)/collagen nanofibers for tracheal cartilage regeneration using mesenchymal stems cells derived from Wharton's jelly of human umbilical cord | |
| JP4989965B2 (en) | Drug-release biodegradable fiber for therapeutic drug delivery | |
| Deumens et al. | Repairing injured peripheral nerves: bridging the gap | |
| Gnavi et al. | The use of chitosan-based scaffolds to enhance regeneration in the nervous system | |
| Štulík et al. | Biocompatible hydrogels in spinal cord injury repair | |
| US9572909B2 (en) | Electrospun nerve guides for nerve regeneration designed to modulate nerve architecture | |
| CN110101918A (en) | A kind of multi-stage porous functional support material and its preparation method and application for mobilizing Endogenous neural stem cells to repair spinal cord injury | |
| WO2005087287A1 (en) | Novel tissue engineered scaffolds derived from copper capillary alginate gels | |
| KR19990072185A (en) | Implantable Therapeutic Acrylamide Copolymer Hydrogel | |
| Aijie et al. | Nanoscaffolds in promoting regeneration of the peripheral nervous system | |
| Zhao et al. | Enhanced peripheral nerve regeneration by a high surface area to volume ratio of nerve conduits fabricated from hydroxyethyl cellulose/soy protein composite sponges | |
| Shen et al. | In situ prevascularization strategy with three-dimensional porous conduits for neural tissue engineering | |
| CN103933619B (en) | Nerve repairing material and preparation method thereof | |
| Mercado et al. | Regenerated silk fibers obtained by straining flow spinning for guiding axonal elongation in primary cortical neurons | |
| Sha et al. | A hyaluronic acid/silk fibroin/poly-dopamine-coated biomimetic hydrogel scaffold with incorporated neurotrophin-3 for spinal cord injury repair | |
| Mobarakeh et al. | Enhanced sciatic nerve regeneration with fibrin scaffold containing human endometrial stem cells and insulin encapsulated chitosan particles: An in vivo study |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information |
Inventor after: Cheng Liming Inventor after: Wang Qigang Inventor after: Cheng Heli Inventor after: Xu Wei Inventor before: Cheng Liming Inventor before: Wang Qigang Inventor before: Cheng Heli Inventor before: Xu Wei |
|
| CB03 | Change of inventor or designer information |