CN108359143B - Hydrogel 3D printing material and preparation method thereof - Google Patents
Hydrogel 3D printing material and preparation method thereof Download PDFInfo
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- CN108359143B CN108359143B CN201810006665.1A CN201810006665A CN108359143B CN 108359143 B CN108359143 B CN 108359143B CN 201810006665 A CN201810006665 A CN 201810006665A CN 108359143 B CN108359143 B CN 108359143B
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/04—Alginic acid; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2401/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
- C08J2401/02—Cellulose; Modified cellulose
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2405/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
- C08J2405/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2489/00—Characterised by the use of proteins; Derivatives thereof
Abstract
The hydrogel 3D printing material is composed of gel A and gel B, wherein the gel A is prepared from the following raw materials, by weight, 8-15 parts of aminated hyaluronic acid, 5-12 parts of cellulose, 2-8 parts of cationic chitin and 20-30 parts of water; the gel B is prepared from the following raw materials, by weight, 10-20 parts of alkaline gelatin and 30-40 parts of alginic acid. The invention further discloses a preparation method of the hydrogel 3D printing material. The invention has the advantages that the invention has good biocompatibility, is easy to be compatible with cells, has no toxicity to cells and tissues, can achieve the adjustable shape and gap, can be controlled by programs and source codes at will, is safe, effective and controllable, and has good rheological property, shear thinning property and flexibility; and all the selected materials are approved by the FDA in the United states and can be clinically used, the biodegradation is good, the materials are harmless to human bodies, and the cost is low.
Description
Technical Field
The invention relates to a 3D printing material and a preparation method thereof, and particularly relates to a hydrogel 3D printing material and a preparation method thereof.
Background
Three-dimensional printing is an additive manufacturing technology in industrial application, and is rapidly developed in the fields of medical clinic and scientific research due to the manufacturing characteristics of high precision and strong controllability. The hydrogel can simulate natural tissues due to the three-dimensional network structure, can meet the morphological requirements and better support cell proliferation when being used as biological paper in three-dimensional biological printing, and can be used as a scaffold for cell growth, thereby drawing wide attention. In recent years, hydrogel has been developed in the field of three-dimensional bioprinting by controlling parameters such as hydrogel shape, porosity, surface morphology and size, but there are still many problems in actual printing, for example, when hydrogel is selected for three-dimensional bioprinting, compatibility including crosslinking coagulation, flexibility and mechanical properties in the printing process, controllable printing precision, compatibility with the surface of a printing instrument, biocompatibility, long-term physicochemical stability and the like need to be considered, and interaction between hydrogel for cell encapsulation and cell mass attachment surface is also important in order to avoid cell shedding from the surface, thereby limiting the hydrogel selection range.
At present, the artificial synthesis hydrogel can be produced in large scale, has the advantages of finely adjustable structure and performance, good repeatability, easy processing, strong mechanical property and the like, but has the greatest defects of poor affinity to cells, lack of necessary biocompatibility for supporting proliferation and differentiation of cells, no immune response and slow biodegradation speed as a 3D printing material, and meanwhile, the artificial synthesis hydrogel crosslinking mode is generally complex, and the current hydrogel system which can be applied to 3D printing is almost complete. The natural hydrogel has the advantages of high biological affinity, mild gelation, flexible chemical modification, relatively low preparation cost and the like, and has no toxicity and can better simulate the cell microenvironment, so the natural hydrogel can well support the cell growth. Therefore, the hydrogel has a wide prospect as a 3D biological printing material, but natural hydrogel has common defects, and mainly shows that the adjustable range of the structure and the performance is narrow, and the mechanical property is poor. Currently, these deficiencies are often improved by flexible chemical modifications. For example, the university of texas and the university of texas a & M introduce calcium ions by immersing 3D-printed alginate structures in calcium chloride solution, which form crosslinks that make their tensile strength approach that of human natural cartilage, but such fully ionically crosslinked hydrogels tend to be brittle, the structure is easily destroyed during subsequent use, and when they contact human interstitial fluid, Ca2+ -Na + ion exchange occurs and dissolves, and the structure does not remain. CN 103977453 a discloses a 3D bioprinting hydrogel material, which must be added with a photopolymerization initiator or/and a crosslinking agent for regulating the crosslinking degree of the network structure of the hydrogel, thereby improving the strength of the material, but the printed sol is difficult to shape, difficult to maintain in size, poor in biocompatibility, and toxic to cells. CN 103705982A discloses a method for preparing a chitosan/hyaluronic acid/gelatin cross-linked composite porous scaffold and CN 104327311a discloses a hyaluronic acid composite cross-linked hydrogel, which both improve the mechanical properties of hyaluronic acid and prevent the hyaluronic acid from being enzymolyzed by hyaluronidase, and a cross-linking agent is added in the gelation process for chemical group cross-linking, so that the biocompatibility is poor, the printing precision is low, and the release of biological macromolecules is difficult to control.
In conclusion, finding and applying a proper hydrogel component as a cell carrier to form three-dimensional biological printing 'ink' is a key link for solving the current three-dimensional biological printing. Therefore, a more excellent hydrogel 3D printing material with adjustable shape and gap, good rheological property, shear thinning property, flexibility, biocompatibility, cell affinity and other multiple bioprinting requirements is urgently needed to be searched through further research and exploration of materials science, and a three-dimensional bioprinting technology with high precision and strong controllability is combined to hopefully construct human tissue and organs in vitro accurately, so that the development of industries such as pharmacy and medical instruments is driven, and obvious social and economic benefits and ecological environmental protection values are generated.
Disclosure of Invention
The hydrogel 3D printing material is composed of gel A and gel B, wherein the gel A is prepared from the following raw materials in parts by weight, 8-15 parts of aminated hyaluronic acid, 5-12 parts of cellulose, 2-8 parts of cationic chitin and 20-30 parts of water; the gel B is prepared from the following raw materials, by weight, 10-20 parts of alkaline gelatin and 30-40 parts of alginic acid.
Further, the gel A is prepared from the following raw materials, by weight, 10-13 parts of aminated hyaluronic acid, 6-8 parts of cellulose, 3-6 parts of cationic chitin and 22-28 parts of water; the gel B is prepared from the following raw materials, by weight, 12-18 parts of alkaline gelatin and 32-38 parts of alginic acid.
Further, the gel A is prepared from the following raw materials, by weight, 12 parts of aminated hyaluronic acid, 8 parts of cellulose, 5 parts of cationic chitin and 25 parts of water; the gel B is prepared from the following raw materials, by weight, 15 parts of alkaline gelatin and 35 parts of alginic acid.
The further purpose of the invention is realized by the following technical scheme, and the preparation method of the hydrogel 3D printing material comprises the following steps:
(1) preparation of gel A: adding the aminated hyaluronic acid into water at room temperature, stirring and fully dissolving, then dropping cellulose, fully stirring, finishing dropping the cellulose within 30-60 min, finally adding the cationic chitin, stirring and uniformly mixing, performing vortex oscillation on the obtained mixed solution for 30-60S, and standing in a water bath at 35-37 ℃ for 2-3 min to obtain gel A;
(2) b, preparation of gel: and stirring and uniformly mixing the alkaline gelatin and the alginic acid at room temperature, then carrying out vortex oscillation on the obtained mixed solution for 30-60 seconds, and standing in a water bath at the temperature of 35-37 ℃ for 2-3 min to obtain the gel B.
The invention aims to realize the application of a hydrogel 3D printing material in a 3D printing technology, and the hydrogel is formed by respectively extruding A gel and B gel in a 3D printer and then blending.
The invention creatively designs a two-component hydrogel 3D printing material, firstly, a positively charged first system of hydrogel is formed by matching and blending positively charged aminated hyaluronic acid, water, cellulose and cationic chitin, the hyaluronic acid is ensured to be naturally crosslinked without adding any physical and chemical crosslinking agent, the positively charged hydrogel system can be kept stable for a long time, has good affinity with cells, can adhere to the walls and has good biocompatibility, and a proper place is provided for cell proliferation and differentiation, so that the growth, differentiation, reconstruction and repair of the cells are directly promoted, and the release of biomacromolecules is freely controlled; then, a negative electricity gel second system is formed by negative electricity alkaline gelatin and negative electricity alginic acid through various acting forces such as electrostatic action and the like; finally, the hydrogel is formed by electrical blending after being respectively extruded in a 3D printer, so that the shape and the gap are adjustable, the hydrogel can be controlled by programs and source codes at will, and the hydrogel is safe, effective and controllable and has good rheological property, shear force thinning characteristic and flexibility.
The invention has the advantages of good biocompatibility, easy affinity to cells, no toxicity to cells and tissues, adjustable shape and gap, capability of being controlled by programs and source codes at will, safety, effectiveness and controllability, and good rheological property, shear force thinning characteristic and flexibility; and all the selected materials are approved by the FDA in the United states and can be clinically used, the biodegradation is good, the materials are harmless to human bodies, and the cost is low.
Detailed Description
Exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the present disclosure have been shown, it should be understood that the present disclosure may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.
1. Materials: the aminated hyaluronic acid, cellulose, cationic chitin, alkaline gelatin and alginic acid are all purchased from commercial sources.
Example 1: preparation method of hydrogel 3D printing material
(1) Preparation of gel A: under the condition of room temperature, adding 12 parts of aminated hyaluronic acid into 25 parts of water, stirring and fully dissolving, then dripping 8 parts of cellulose, fully stirring, finally adding 5 parts of cationic chitin, stirring and uniformly mixing, then carrying out vortex oscillation on the obtained mixed solution for 30S, and standing in a water bath at 37 ℃ for 2min to obtain gel A;
(2) b, preparation of gel: and (3) stirring and uniformly mixing 15 parts of alkaline gelatin and 35 parts of alginic acid at room temperature, then carrying out vortex oscillation on the obtained mixed solution for 30 seconds, and standing in a water bath at 37 ℃ for 2min to obtain gel B.
Example 2: preparation method of hydrogel 3D printing material
(1) Preparation of gel A: under the condition of room temperature, adding 10 parts of aminated hyaluronic acid into 27 parts of water, stirring and fully dissolving, then dripping 10 parts of cellulose, fully stirring, finally adding 3 parts of cationic chitin, stirring and uniformly mixing, then carrying out vortex oscillation on the obtained mixed solution for 50S, and standing in 35 ℃ water bath for 3min to obtain gel A;
(2) b, preparation of gel: and (3) stirring and uniformly mixing 18 parts of alkaline gelatin and 32 parts of alginic acid at room temperature, then carrying out vortex oscillation on the obtained mixed solution for 50 seconds, and standing in a water bath at 35 ℃ for 3min to obtain gel B.
Example 3: preparation method of hydrogel 3D printing material
(1) Preparation of gel A: under the condition of room temperature, adding 13 parts of aminated hyaluronic acid into 25 parts of water, stirring and fully dissolving, then dripping 6 parts of cellulose, fully stirring, finally adding 6 parts of cationic chitin, stirring and uniformly mixing, then carrying out vortex oscillation on the obtained mixed solution for 40S, and standing in a water bath at 37 ℃ for 2min to obtain gel A;
(2) b, preparation of gel: and (3) stirring and uniformly mixing 18 parts of alkaline gelatin and 32 parts of alginic acid at room temperature, then carrying out vortex oscillation on the obtained mixed solution for 40 seconds, and standing in a water bath at 37 ℃ for 2min to obtain gel B.
Example 4: application of hydrogel 3D printing material
And respectively extruding the gel A and the gel B prepared in the embodiments 1-3 in a 3D printer according to the ratio of 1:1 by using a 3D printer, blending and rapidly printing the extruded gel A and the gel B into a cell growth scaffold.
Through determination, the flow and the flow rate of the gel A and the gel B prepared in the embodiments 1-3 can be controlled by a 3D printing program, the size, the thickness and the thickness of the printed gel can be controlled, and the printing precision can reach the micron level.
According to the measurement, the compression modulus of the gel A and the gel B prepared in the examples 1 to 3 after 3D printing is 0.5-500 Kpa, the viscosity is 0.1-100 kpa.s, the tensile strength is 50-30 MPa, and the tensile strain is 1-300%. Therefore, the hydrogel 3D printing material has adjustable shape and gap, can be controlled by programs and source codes at will, is safe, effective and controllable, and has good rheological property, shear force thinning property and flexibility.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the appended claims.
Claims (4)
1. A hydrogel 3D printing material is characterized by consisting of gel A and gel B, wherein,
the gel A is prepared from the following raw materials, by weight, 10-13 parts of aminated hyaluronic acid, 6-8 parts of cellulose, 3-6 parts of cationic chitin and 22-28 parts of water; the gel B is prepared from the following raw materials, by weight, 12-18 parts of alkaline gelatin and 32-38 parts of alginic acid.
2. The hydrogel 3D printing material according to claim 1, wherein the A gel is prepared from the following raw materials, by weight, 12 parts of aminated hyaluronic acid, 8 parts of cellulose, 5 parts of cationic chitin, and 25 parts of water; the gel B is prepared from the following raw materials, by weight, 15 parts of alkaline gelatin and 35 parts of alginic acid.
3. A method for preparing a hydrogel 3D printing material as claimed in claim 1 or 2, comprising the following steps
(1) Preparation of gel A: adding the aminated hyaluronic acid into water at room temperature, stirring and fully dissolving, then dropping cellulose, fully stirring, finishing dropping the cellulose within 30-60 min, finally adding the cationic chitin, stirring and uniformly mixing, performing vortex oscillation on the obtained mixed solution for 30-60S, and standing in a water bath at 35-37 ℃ for 2-3 min to obtain gel A;
(2) b, preparation of gel: and stirring and uniformly mixing the alkaline gelatin and the alginic acid at room temperature, then carrying out vortex oscillation on the obtained mixed solution for 30-60 seconds, and standing in a water bath at the temperature of 35-37 ℃ for 2-3 min to obtain the gel B.
4. Use of a hydrogel 3D printing material in 3D printing technology according to claim 1 or 2, wherein a gel and B gel are mixed according to a ratio of 1:1 ratio was blended after extrusion separately in a 3D printer.
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| CN112250498A (en) * | 2020-09-28 | 2021-01-22 | 湖北富邦科技股份有限公司 | Hydrogel plant nutrition composition and preparation method thereof |
| CN114632445B (en) * | 2022-02-25 | 2023-04-28 | 湖南益安生物科技有限公司 | Composite medical biopolymer material and preparation method thereof |
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| CN103977453A (en) * | 2014-05-28 | 2014-08-13 | 段升华 | 3D (three-dimensional) bioprinting hydrogel material and application thereof |
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