CN107185037B - Chitosan micro-nano fibrous three-dimensional porous scaffold and preparation method thereof - Google Patents
Chitosan micro-nano fibrous three-dimensional porous scaffold and preparation method thereof Download PDFInfo
- Publication number
- CN107185037B CN107185037B CN201710434325.4A CN201710434325A CN107185037B CN 107185037 B CN107185037 B CN 107185037B CN 201710434325 A CN201710434325 A CN 201710434325A CN 107185037 B CN107185037 B CN 107185037B
- Authority
- CN
- China
- Prior art keywords
- chitosan
- micro
- dimensional porous
- preparation
- nano
- 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.)
- Expired - Fee Related
Links
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000002245 particle Substances 0.000 claims abstract description 15
- 239000011780 sodium chloride Substances 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000007710 freezing Methods 0.000 claims abstract description 10
- 230000008014 freezing Effects 0.000 claims abstract description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000012046 mixed solvent Substances 0.000 claims abstract description 4
- 238000009740 moulding (composite fabrication) Methods 0.000 claims abstract 4
- 238000005406 washing Methods 0.000 claims abstract 4
- 239000003513 alkali Substances 0.000 claims abstract 2
- 239000002121 nanofiber Substances 0.000 abstract description 8
- 238000004108 freeze drying Methods 0.000 abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 238000005191 phase separation Methods 0.000 description 5
- 238000000465 moulding Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 238000010041 electrostatic spinning Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229920001410 Microfiber Polymers 0.000 description 1
- 230000003115 biocidal 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
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002062 molecular scaffold Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000011160 research Methods 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
- A61L27/20—Polysaccharides
-
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention relates to a chitosan micro-nano fibrous three-dimensional porous scaffold and a preparation method thereof, which adopts a ternary mixed solvent of acetic acid, 1, 4-dioxane and water with a certain proportion to dissolve chitosan, spreads the sieved sodium chloride particles in a container, pours a chitosan solution into the container to completely immerse the sodium chloride particles, freezes and forms the sodium chloride particles at a low temperature, and obtains the chitosan micro-nano fibrous three-dimensional porous tissue engineering scaffold after alkali washing, water washing, freezing and forming and freeze-drying of a freeze-dried sample. The preparation method has simple process, and the microstructure of the preparation method is in the form of controllable porous and micro-nano fibers.
Description
Technical Field
The invention relates to a chitosan micro-nano fibrous three-dimensional porous scaffold and a preparation method thereof, belonging to the technical field of biomedical materials.
Background
The chitosan as a natural alkaline polysaccharide has good biocompatibility and important application in the field of tissue engineering materials. The tissue engineering scaffold prepared from chitosan has the characteristics of good mechanical property, contribution to cell proliferation and differentiation, antibiosis and antiphlogosis and the like, and is widely regarded by researchers. Sundararajan V et al firstly prepared a chitosan tissue engineering scaffold by adopting a phase separation technology in 1999, the structure of the chitosan tissue engineering scaffold is a sheet honeycomb structure with the thickness of tens to hundreds of microns, and the chitosan tissue engineering scaffold has better mechanical strength and biological performance (Biomaterials, 1999;20: 1133-. The hutch and the like prepare an ordered porous chitosan scaffold (CN 101366972) which can be used for repairing bone tissues. The microstructure of the scaffold has important influence on the biological performance of the scaffold, and researches show that the nanofiber scaffold has higher specific surface area and is beneficial to cell adhesion and differentiation. But the mechanical strength of the pure nano fiber is lower, and the mechanical load of the stent implantation process cannot be born. In contrast, the micron fiber scaffold has better mechanical properties. Thus, having a microstructure of both nano and micro fibers in the scaffold can overcome the contradiction between biocompatibility and mechanical properties. At present, researchers mostly adopt an electrostatic spinning method to prepare micro-nanofibers, and the electrostatic spinning method can only obtain two-dimensional films generally and has long preparation time. The traditional phase separation method for preparing the chitosan three-dimensional tissue engineering scaffold is generally a sheet-shaped honeycomb structure, and the dimension of the chitosan three-dimensional tissue engineering scaffold is usually dozens of micrometers. As the chitosan molecules have stronger intermolecular force and have larger viscosity after being dissolved in acid, the concentration of the chitosan needs to be reduced when the micro-nano fiber structure is obtained, but the prepared scaffold has no mechanical strength and cannot be applied to tissue engineering. In addition, the scaffold needs a porous structure which is mutually communicated, so that cell migration and nutrient substance transmission are facilitated, the size of pores cannot be effectively controlled by a single phase separation method, and the purpose of controlling the size of the pores can be achieved by combining the phase separation method with a pore-forming rule, so that the comprehensive performance of the chitosan scaffold is better.
Disclosure of Invention
The invention mainly assumes that a binary solvent system consisting of water and acid in the traditional phase separation preparation method is changed, a novel ternary solvent system consisting of an organic solvent, the water and the acid is added, the intermolecular force of chitosan is changed, the chitosan is promoted to form micro-nano fibers in the freezing process, and then the controllable porous micro-nano fibrous three-dimensional chitosan scaffold can be obtained by combining a pore-forming method.
The preparation method of the chitosan micro-nano fibrous three-dimensional porous tissue engineering scaffold is specifically as follows.
(1) Preparing a ternary mixed solvent of acetic acid, 1, 4-dioxane and water.
(2) Adding chitosan, and electromagnetically stirring to dissolve for 24 hours.
(3) And uniformly spreading the screened sodium chloride particles in a container, pouring a chitosan solution, completely immersing the sodium chloride particles, and performing low-temperature freezing molding.
(4) And freeze-drying to obtain a dry sample.
(5) The dried sample was immersed in dilute sodium hydroxide solution to remove residual acetic acid, 1, 4-dioxane and sodium chloride, and washed with a large amount of distilled water.
(6) And freezing and molding the sample, and freeze-drying to obtain the chitosan micro-nano fibrous three-dimensional porous scaffold sample.
The sample prepared by the method is in a white foam shape, and the three-dimensional shape of the sample can be adjusted by adopting different containers and sample dividing volumes in sample dividing. The coexistence microstructure of the micro-nano fibers endows the scaffold with good biocompatibility and mechanical strength, and the controllable pore structure is beneficial to the migration of cells and the delivery of nutrient substances. The preparation method has simple process and good formability, and compared with the chitosan scaffold prepared by the traditional binary solvent, the microstructure of the chitosan scaffold is in the form of controllable porous and micro-nano fibers.
Detailed Description
The present invention will be further described with reference to specific examples, but the implementation of the present invention is not limited to these examples.
Example 1: respectively taking 1ml, 10ml and 89ml of acetic acid, 1, 4-dioxane and water, and uniformly mixing. 0.5g of chitosan with the molecular weight of 10 ten thousand is weighed and dissolved for 24 hours by electromagnetic stirring. After the chitosan is completely dissolved, spreading the sodium chloride particles with the particle size diameter of 10-350 microns after screening in a container, completely immersing the sodium chloride particles in the chitosan solution, freezing for more than 12 hours at-18 ℃, forming, and freeze-drying for 48 hours to obtain a dried sample. The dried sample was immersed in 0.01mol/L sodium hydroxide solution to remove residual acetic acid, 1, 4-dioxane and sodium chloride, and washed with a large amount of distilled water. And freezing and molding the sample, and freeze-drying for 48 hours to obtain the three-dimensional porous scaffold with the chitosan micro-nano fibrous structure.
Example 2: respectively taking 10ml, 50ml and 40ml of acetic acid, 1, 4-dioxane and water, and uniformly mixing. 3g of chitosan with the molecular weight of 40 ten thousand is weighed and dissolved for 24 hours by electromagnetic stirring. After the chitosan is completely dissolved, spreading the sodium chloride particles with the particle size diameter of 10-350 microns after screening in a container, completely immersing the sodium chloride particles in the chitosan solution, freezing for more than 12 hours at the temperature of-196 ℃ (in liquid nitrogen), forming, and freeze-drying for 48 hours to obtain a dried sample. The dried sample was immersed in 0.01mol/L sodium hydroxide solution to remove residual acetic acid, 1, 4-dioxane and sodium chloride, and washed with a large amount of distilled water. And freezing and molding the sample, and freeze-drying for 48 hours to obtain the three-dimensional porous scaffold with the chitosan micro-nano fibrous structure.
Claims (5)
1. A preparation method of a chitosan micro-nano fibrous three-dimensional porous scaffold is characterized by dissolving chitosan in a ternary mixed solvent of acetic acid, 1, 4-dioxane and water, spreading screened sodium chloride particles in a container, pouring a chitosan solution to completely immerse the sodium chloride particles, placing the container in a low-temperature freezing and forming process, and carrying out alkali washing, water washing, freezing and forming on a freeze-dried sample to obtain the chitosan nano-micro fibrous three-dimensional porous scaffold.
2. The preparation method of the chitosan micro-nano fibrous three-dimensional porous scaffold according to claim 1, wherein the molecular weight of the chitosan is 10-40 ten thousand, and the mass volume concentration of the chitosan is 0.5-3%.
3. The preparation method of the chitosan micro-nano fibrous three-dimensional porous scaffold as claimed in claim 1, wherein the volume ratio of acetic acid in the ternary mixed solvent is between 1 and 10%, the volume ratio of 1, 4-dioxane is between 10 and 50%, and the volume ratio of water is between 40 and 89%.
4. A method for preparing a chitosan nano-micro fibrous three-dimensional porous scaffold according to claim 1, wherein the freeze forming temperature is between-18 ℃ and-196 ℃.
5. The method for preparing a chitosan nano-micron fibrous three-dimensional porous scaffold according to claim 1, wherein the particle size distribution of sodium chloride particles is between 10 and 350 microns.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710434325.4A CN107185037B (en) | 2017-06-09 | 2017-06-09 | Chitosan micro-nano fibrous three-dimensional porous scaffold and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710434325.4A CN107185037B (en) | 2017-06-09 | 2017-06-09 | Chitosan micro-nano fibrous three-dimensional porous scaffold and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107185037A CN107185037A (en) | 2017-09-22 |
| CN107185037B true CN107185037B (en) | 2020-03-31 |
Family
ID=59876638
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710434325.4A Expired - Fee Related CN107185037B (en) | 2017-06-09 | 2017-06-09 | Chitosan micro-nano fibrous three-dimensional porous scaffold and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107185037B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321271A (en) * | 2011-09-15 | 2012-01-18 | 西安交通大学 | Preparation method for chitosan-based porous scaffolds with biological activity |
| WO2016018192A1 (en) * | 2014-07-29 | 2016-02-04 | Agency For Science, Technology And Research | Method of preparing a porous carbon material |
| CN105582573A (en) * | 2016-02-27 | 2016-05-18 | 青岛大学 | Nano-micron multi-scale chitosan three-dimensional scaffold and preparation method thereof |
-
2017
- 2017-06-09 CN CN201710434325.4A patent/CN107185037B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321271A (en) * | 2011-09-15 | 2012-01-18 | 西安交通大学 | Preparation method for chitosan-based porous scaffolds with biological activity |
| WO2016018192A1 (en) * | 2014-07-29 | 2016-02-04 | Agency For Science, Technology And Research | Method of preparing a porous carbon material |
| CN105582573A (en) * | 2016-02-27 | 2016-05-18 | 青岛大学 | Nano-micron multi-scale chitosan three-dimensional scaffold and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 添加聚乙二醇对壳聚糖超滤膜结构和性能的影响;刘强，孟范平，姚瑞华，张爱静;《膜科学与技术》;20100228;第24页左栏第1-3段、实验部分、讨论部分 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107185037A (en) | 2017-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Chitosan–halloysite nanotubes nanocomposite scaffolds for tissue engineering | |
| Florczyk et al. | Influence of processing parameters on pore structure of 3D porous chitosan–alginate polyelectrolyte complex scaffolds | |
| Zhang et al. | Inverse opal scaffolds for applications in regenerative medicine | |
| KR100706759B1 (en) | A method of producing a chitosan scaffold having a high tensile strength and a chitosan scaffold produced by the same | |
| Cao et al. | Novel biodegradable films and scaffolds of chitosan blended with poly (3-hydroxybutyrate) | |
| Song et al. | Controllable fabrication of porous PLGA/PCL bilayer membrane for GTR using supercritical carbon dioxide foaming | |
| CN103225126B (en) | Fibroin/sodium alginate composite nanofiber scaffold preparation method | |
| Jing et al. | Electrospinning homogeneous nanofibrous poly (propylene carbonate)/gelatin composite scaffolds for tissue engineering | |
| CN101015712B (en) | Process for preparation of polycaprolactone-chitosan network/hydroxyapatite porous compound support frame material | |
| CN109806919B (en) | Preparation method of gelatin methacrylamide core-shell microspheres for 3D cell culture | |
| Jing et al. | Fabrication of shish–kebab structured poly (ε-caprolactone) electrospun nanofibers that mimic collagen fibrils: Effect of solvents and matrigel functionalization | |
| Chen et al. | Physical properties of microporous membranes prepared by hydrolyzing cellulose/soy protein blends | |
| Blaker et al. | Ice-microsphere templating to produce highly porous nanocomposite PLA matrix scaffolds with pores selectively lined by bacterial cellulose nano-whiskers | |
| Zeng et al. | Characterization of highly interconnected porous poly (lactic acid) and chitosan-coated poly (lactic acid) scaffold fabricated by vacuum-assisted resin transfer molding and particle leaching | |
| Jiang et al. | Rational design of a high-strength bone scaffold platform based on in situ hybridization of bacterial cellulose/nano-hydroxyapatite framework and silk fibroin reinforcing phase | |
| Li et al. | Structure design and fabrication of porous hydroxyapatite microspheres for cell delivery | |
| Sharma et al. | Synthesis and characterization of glycine modified chitosan-gelatin-alginate composite scaffold for tissue engineering applications | |
| Cai et al. | Fabrication and cell viability of injectable n-HA/chitosan composite microspheres for bone tissue engineering | |
| CN109364288B (en) | Application of hole-hole composite micro-nano structure polysaccharide microspheres in preparation of hemostatic dressing | |
| Knotek et al. | Cryogenic grinding of electrospun poly-ε-caprolactone mesh submerged in liquid media | |
| Zeng et al. | Comparative analysis of the residues of granular support bath materials on printed structures in embedded extrusion printing | |
| CN107185037B (en) | Chitosan micro-nano fibrous three-dimensional porous scaffold and preparation method thereof | |
| Chen et al. | Preparation of a novel regenerated silk fibroin-based hydrogel for extrusion bioprinting | |
| CN109517225B (en) | Hole-hole composite micro-nano structure polysaccharide microsphere and preparation method thereof | |
| Lacik et al. | A two-step process for controlling the surface smoothness of polyelectrolyte-based microcapsules |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200331 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |