CN111803714B - Chitosan bone repair scaffold integrating acid-alkali solvent system and preparation method thereof - Google Patents

Chitosan bone repair scaffold integrating acid-alkali solvent system and preparation method thereof Download PDF

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CN111803714B
CN111803714B CN202010745654.2A CN202010745654A CN111803714B CN 111803714 B CN111803714 B CN 111803714B CN 202010745654 A CN202010745654 A CN 202010745654A CN 111803714 B CN111803714 B CN 111803714B
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chitosan
alkaline
solvent system
bone repair
acid
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CN111803714A (en
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张美云
梁建涛
聂景怡
宋顺喜
谭蕉君
杨斌
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Shaanxi University of Science and Technology
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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
    • A61L27/50—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
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Abstract

The invention discloses a chitosan bone repair scaffold integrating an acid-alkali solvent system and a preparation method thereof, wherein a high-strength chitosan gel film is prepared by utilizing an alkali solvent system and is used as a mechanical skeleton part of the scaffold; comprehensively utilizing an alkaline system and an acidic system to ensure that the interfaces of the two systems are tightly combined; and then an acid solvent system is utilized to construct a bionic porous structure which is used as a functional structure part of the bracket. The chitosan bone repair scaffold material obtained by the invention has excellent mechanical properties and an ordered porous structure.

Description

Chitosan bone repair scaffold integrating acid-alkali solvent system and preparation method thereof
Technical Field
The invention belongs to the field of bone tissue engineering, and particularly relates to a chitosan bone repair scaffold integrating an acid-alkali solvent system and a preparation method thereof.
Background
Bones are important tissues and organs of human bodies, protect internal organs, provide muscle attachment points and participate in the metabolism of calcium and phosphorus elements of the human bodies. However, when a large bone defect is caused by scraping, infection, severe trauma, dysplasia and other reasons, the bone cannot be completely healed only by the self-repairing capability of the bone, and an exogenous bone defect repairing material needs to be applied to facilitate the growth of a new bone.
The bone defect repairing scaffold has various material sources, and natural polymers have the advantages of wide sources, reproducibility, good biocompatibility, biodegradability, certain bioactivity and the like, so the scaffold is an ideal material for preparing the artificial bone defect repairing scaffold.
The ideal bone defect repair scaffold material needs to meet certain requirements: (1) the bone repair material has good mechanical property, and can provide support and protection effects on the defect part in the bone repair process; (2) has proper porosity, pore connectivity and high internal specific surface area, enables bone cells to adhere, migrate, proliferate and differentiate in the pores of the scaffold, and simultaneously facilitates the entry of nutrients and the discharge of metabolites.
The structure of the bone repair scaffold has decisive influence on the final performance, however, the natural high polymer material bone repair scaffold has poor general mechanical property while keeping porosity, and is not matched with the natural bone repair requirement. And because of the strong hydrogen bond action among the macromolecules, the macromolecules can not be directly prepared by adopting a conventional processing mode, and the preparation of the ordered porous structure by carrying out bone-like structure design on the macromolecules has certain challenge. Therefore, it is important to obtain the desired porosity and pore structure while maintaining the mechanical properties of the scaffold.
Disclosure of Invention
The invention mainly aims to provide a chitosan bone repair scaffold integrating an acid-alkali solvent system and a preparation method thereof, which are used for overcoming the existing problems.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of a chitosan bone repair scaffold integrating an acid-alkali solvent system comprises the following steps:
(1) weighing lithium hydroxide monohydrate and urea, and dissolving in deionized water to obtain an alkaline solvent system; adding chitosan powder, uniformly dispersing, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with a certain thickness through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking a certain amount of chitosan powder, and fully dispersing in deionized water; adding a certain amount of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution;
(3) transferring an alkaline system chitosan gel film with high strength, covering the alkaline system chitosan gel film obtained in the step (1) on the chitosan acidic system solution obtained in the step (2), fully contacting the alkaline system chitosan gel film and the chitosan acidic system solution, and keeping for a certain time to form interface combination to obtain fully contacted chitosan gel-solution;
(4) transferring the fully contacted chitosan gel-solution as a whole into a sodium hydroxide coagulation bath to realize further gelation; after the gelation is finished, washing the gel with deionized water to be neutral to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan bone repair scaffold.
Further, in the step (1), the proportion of the lithium hydroxide monohydrate, the urea, the deionized water and the chitosan powder is (5-15) g: (3-12) g: (67-88) mL: (4-6) g.
Further, the molecular weight of chitosan in the chitosan alkaline system solution in the step (1) is 1 multiplied by 106Da, the mass concentration of the chitosan is 4-6 wt.%.
Further, the thickness of the alkaline system chitosan gel film prepared in the step (1) is 1-5 mm.
Further, in the step (2), the ratio of the chitosan powder to the deionized water to the glacial acetic acid is (3-5) g: (93-96) mL: (1-2) mL.
Further, the molecular weight of chitosan in the chitosan acid system solution in the step (2) is 3 multiplied by 105Da～5×105Da, the mass concentration of the chitosan is 3-5 wt.%.
Further, the chitosan gel film of the alkaline system in the step (3) is fully contacted with the chitosan solution of the acidic system, and the contact time is kept for 5-30 min.
Further, the mass fraction of the sodium hydroxide in the sodium hydroxide coagulation bath in the step (4) is 10 wt.% to 15 wt.%.
A chitosan bone repair scaffold integrating an acid-alkali solvent system is prepared by adopting the preparation method.
Compared with the prior art, the invention has the following beneficial technical effects:
in the method, firstly, an alkaline solvent system is utilized to prepare the chitosan gel film with high strength, and the obtained gel has a uniform and compact gel network and can be used as a mechanical skeleton part of a material; an acid solvent system is utilized to construct a bionic porous structure which is used as a functional structure part of the bracket. The basic chitosan gel is contacted, diffused and reacted with the acidic chitosan solution, so that chitosan in the two systems is combined at a molecular level, the interfaces of the two systems are tightly combined, and finally the whole gelation is realized in a coagulation bath, and the bone repair scaffold material with excellent mechanical properties and an ordered porous structure can be obtained. In addition, the chitosan is a natural polymer with rich sources, and the bone repair scaffold prepared from the chitosan serving as a raw material has good biocompatibility, biodegradability and certain bioactivity, and has good application prospects in the field of biomedical material tissue repair.
Drawings
FIG. 1 is a schematic flow chart of the present invention;
FIG. 2 is a schematic view of the structure of the stent of the present invention;
FIG. 3 is a digital photograph of a gel scaffold material according to the present invention;
FIG. 4 is a super depth of field microscope picture of the gel scaffold material of the present invention.
Detailed Description
Embodiments of the invention are described in further detail below:
as shown in fig. 1, a method for preparing a chitosan bone repair scaffold integrating an acid-base solvent system comprises the following steps:
(1) weighing 5-15g of lithium hydroxide monohydrate and 3-12g of urea, and dissolving in 67-88mL of deionized water to obtain an alkaline solvent system; adding 4-6g of 1X 10 molecular weight6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 1-5mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking 3-5g of molecular weight 3X 105Da～5×105Fully dispersing chitosan powder of Da in 93-96ml of deionized water; adding 1-2ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 5-30min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole to a 10-15 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and freeze-drying to obtain the chitosan dry-state bone defect repair scaffold as shown in figures 2 and 3.
The present invention is described in further detail below with reference to examples:
example 1
(1) Weighing 5g of lithium hydroxide monohydrate and 8g of urea, and dissolving in 83mL of deionized water to obtain an alkaline solvent system; 4g of 1X 10 molecular weight are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 1mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking 4g of molecular weight 5X 105Da chitosan powder is fully dispersed in 95ml deionized water; adding 1ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 5min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into a 10 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
Example 2
(1) Weighing 8g of lithium hydroxide monohydrate and 5g of urea, and dissolving in 82ml of deionized water to obtain an alkaline solvent system; 5g of a 1X 10 molecular weight mixture are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 2mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking 3g of molecular weight 4X 105Da chitosan powder is fully dispersed in 95.5ml deionized water; adding 1.5ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 10min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into a 12 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
Example 3
(1) Weighing 10g of lithium hydroxide monohydrate and 3g of urea, and dissolving in 81ml of deionized water to obtain an alkaline solvent system; 6g of a 1X 10 molecular weight mixture are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 3mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) 5g of a polymer having a molecular weight of 3X 10 was taken5Da chitosanPowder, fully dispersed in 93ml deionized water; adding 2ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 15min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into a 14 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
Example 4
(1) Weighing 5g of lithium hydroxide monohydrate and 3g of urea, and dissolving in 88ml of deionized water to obtain an alkaline solvent system; 4g of 1X 10 molecular weight are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 4mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking 3g of molecular weight 4X 105Da chitosan powder is fully dispersed in 96ml deionized water; adding 1ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 20min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into a 15 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
Example 5
(1) Weighing 8g of lithium hydroxide monohydrate and 12g of urea, and dissolving in 75ml of deionized water to obtain an alkaline solvent system; 5g of a 1X 10 molecular weight mixture are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 5mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking 4g of molecular weight 3X 105Da chitosan powder is fully dispersed in 94.5ml deionized water; adding 1.5ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 25min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into an 11 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
Example 6
(1) Weighing 10g of lithium hydroxide monohydrate and 5g of urea, and dissolving in 79ml of deionized water to obtain an alkaline solvent system; 6g of a 1X 10 molecular weight mixture are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 2mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) 5g of a molecular weight of 5X 10 are taken5Da chitosan powder is fully dispersed in 93ml deionized water; adding 2ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; will be provided withInjecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 15min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into a 13 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
Example 7
(1) Weighing 12g of lithium hydroxide monohydrate and 10g of urea, and dissolving in 73ml of deionized water to obtain an alkaline solvent system; 5g of a 1X 10 molecular weight mixture are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 3mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking 3g of molecular weight 4X 105Da chitosan powder is fully dispersed in 95.5ml deionized water; adding 1.5ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 30min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into a 12 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
Example 8
(1) 15g of monohydrate NaOH are weighedDissolving lithium and 12g of urea in 67ml of deionized water to obtain an alkaline solvent system; 6g of a 1X 10 molecular weight mixture are added6Uniformly dispersing chitosan powder of Da, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with the thickness of 5mm through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking 4g of molecular weight 5X 105Da chitosan powder is fully dispersed in 94ml deionized water; adding 2ml of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution; injecting the chitosan acidic system solution into a single-opening forming die;
(3) transferring a high-strength alkaline system chitosan gel film, covering the high-strength alkaline system chitosan gel film on the chitosan acidic system solution, and keeping the high-strength alkaline system chitosan gel film and the chitosan acidic system solution in full contact for 20min to form interface combination;
(4) transferring the fully contacted chitosan gel-solution as a whole into a 15 wt.% sodium hydroxide coagulation bath to achieve further gelation; after gelation is finished, washing the gel with deionized water until the pH value is 7 to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan dry-state bone defect repair scaffold.
By taking the example 1 as an example, when the chitosan bone repair scaffold prepared by the invention is observed by a super-depth-of-field microscope, acid system gel and alkali system gel can be observed, and the interface of the acid system gel and the alkali system gel is well combined (fig. 4).

Claims (8)

1. A preparation method of a chitosan bone repair scaffold integrating an acid-alkali solvent system is characterized by comprising the following steps:
(1) weighing lithium hydroxide monohydrate and urea, and dissolving in deionized water to obtain an alkaline solvent system; adding chitosan powder, uniformly dispersing, and then performing freezing-unfreezing processes for multiple times to obtain a chitosan alkaline system solution; obtaining a high-strength alkaline system chitosan gel film with a certain thickness through the steps of centrifugal defoaming, casting film forming and water bath gelation;
(2) taking a certain amount of chitosan powder, and fully dispersing in deionized water; adding a certain amount of glacial acetic acid into the dispersion liquid, and fully stirring to dissolve chitosan powder to obtain a chitosan acidic system solution;
(3) transferring an alkaline system chitosan gel film with high strength, covering the alkaline system chitosan gel film obtained in the step (1) on the chitosan acidic system solution obtained in the step (2), fully contacting the alkaline system chitosan gel film and the chitosan acidic system solution, and keeping for 5-30min to form interface combination to obtain a fully contacted chitosan gel-solution;
(4) transferring the fully contacted chitosan gel-solution as a whole into a sodium hydroxide coagulation bath to realize further gelation; after the gelation is finished, washing the gel with deionized water to be neutral to obtain the chitosan gel scaffold material of the comprehensive acidic-alkaline solvent system; and (5) freeze-drying to obtain the chitosan bone repair scaffold.
2. The method for preparing a chitosan bone repair scaffold with an integrated acid-base solvent system according to claim 1, wherein the ratio of the lithium hydroxide monohydrate, the urea, the deionized water and the chitosan powder in step (1) is (5-15) g, (3-12) g, (67-88) mL and (4-6) g.
3. The method for preparing a chitosan bone repair scaffold with integrated acid-base solvent system as claimed in claim 1, wherein the molecular weight of chitosan in the chitosan alkaline system solution in step (1) is 1 x 106Da, the mass concentration of the chitosan is 4-6 wt.%.
4. The method for preparing a chitosan bone repair scaffold integrating an acid-base solvent system according to claim 1, wherein the thickness of the chitosan gel film of the alkaline system prepared in step (1) is 1mm to 5 mm.
5. The method for preparing a chitosan bone repair scaffold with an integrated acid-base solvent system according to claim 1, wherein the ratio of the chitosan powder, the deionized water and the glacial acetic acid in the step (2) is (3-5) g to (93-96) mL to (1-2) mL.
6. The method for preparing a chitosan bone repair scaffold with integrated acid-base solvent system as claimed in claim 1, wherein the molecular weight of chitosan in the chitosan acid system solution in step (2) is 3 x 105Da～5×105Da, the mass concentration of the chitosan is 3-5 wt.%.
7. The method for preparing a chitosan bone repair scaffold with an integrated acid-base solvent system according to claim 1, wherein the mass fraction of sodium hydroxide in the sodium hydroxide coagulation bath in the step (4) is 10 wt.% to 15 wt.%.
8. A chitosan bone repair scaffold integrating an acid-base solvent system, which is characterized by being prepared by the preparation method of any one of claims 1 to 7.
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