A hydrogel ink with thixotropic properties and its preparation method and application

Abstract

The present invention relates to the field of hydrogel technology, and in particular to a hydrogel ink with thixotropic properties, a preparation method and an application thereof. The hydrogel ink comprises a water-soluble monomer, GelMa, lithium ion, a stabilizer, a chelated ion substance, a photoinitiator and water; the chelated ion substance comprises at least one of aminocarboxylates, hydroxycarboxylates and organic phosphonate compounds. The thixotropic properties of the hydrogel ink of the present invention are different from the general shear thinning phenomenon. In the general shear thinning phenomenon, the apparent viscosity of the liquid decreases with the increase of the shear rate, while the hydrogel ink directly changes from the gel state to the sol state.

Description

Technical Field

[0001] The invention relates to the technical field of hydrogels, and in particular to a hydrogel ink with thixotropic properties and a preparation method and application thereof. Background Art

[0002] 3D printing is a powerful tool for quickly creating customized shapes, and 3D bioprinting is a form of 3D printing that uses biocompatible inks or adds cells to them so that the ink can be applied to three-dimensional tissue engineering. Bioprinting ink is an important component of 3D bioprinting. Hydrogel is a flexible material that is made of polymers cross-linked physically or chemically and has a unique 3D network structure. Because hydrogels can meet the needs of biological 3D printing, more and more bioprinting inks use hydrogels as the substrate.

[0003] The biological 3D printing process requires the biological ink to undergo a phase change from a sol state to a gel state (a semi-solid cross-linked network) to form a corresponding biomaterial structure. Patent CN105504311A discloses a chitosan derivative hydrogel and a preparation method thereof. This hydrogel is temperature sensitive, presenting a sol state at low temperatures and a gel state at high temperatures. The sol-gel transition characteristics of this gel that change with temperature can make it a biological ink material. Patent CN105238132A discloses a biological ink for 3D printing. The ink system is composed of aqueous polymers (including GelMa), etc. The system realizes the transition from sol state to gel state by photocuring.

[0004] However, as an attractive bio-ink, hydrogel materials still have some shortcomings. The main disadvantages include low viscosity of hydrogels in the sol state, limited cross-linking speed of sol to gel conversion, and limited mechanical strength of hydrogels, all of which affect the accuracy and stability of the tissue structure formed after printing. Researchers from Zhejiang University proposed a direct writing forming method based on carbomer rheology modifier, which can be used for rapid prototyping of multifunctional hydrogels (Literature: Advanced Functional Materials, 2019, 29(20): 1900971.). A high-strength double-network hydrogel not only increases the viscosity and printing time of the ink by adding alginate, but also improves its rheological properties, achieving durability and precision control in the 3D printing hydrogel process (Literature: RSC Advances, 2015, 5: 81324-81329). Patent CN202010260929.3 discloses a composite bio-ink based on methacrylated hydrogel / nanoclay / decellularized matrix, and the addition of nanoclay improves the printability.

[0005] These methods can effectively increase the viscosity of bio-ink. These methods generally make the ink material viscous, but these methods cannot achieve the ideal rheological behavior. The rheological behavior of the ideal bio-ink should be thixotropic, the ink material is viscous before extrusion or injection, is in a sol state during extrusion or injection, and is a non-flowing semi-solid state after extrusion or injection.

[0006] Therefore, there is an urgent need to propose a hydrogel ink with unique thixotropic properties. The prepared hydrogel ink is in a viscous state when stable, and is converted into a sol state when subjected to external shear force. It can be converted into a semi-solid state after the external force is eliminated. The hydrogel ink can be quickly photocured after extrusion molding. The gel material formed by the hydrogel ink has strong mechanical properties and can better maintain structural stability. Summary of the invention

[0007] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, this patent provides a hydrogel ink with thixotropic properties and its preparation method and application. The prepared hydrogel ink is in a viscous state when stable, and is converted into a sol state when sheared by an external force. It is converted into a semi-solid state after a period of time after the external force is eliminated. The hydrogel ink can be quickly photocured after extrusion molding. The gel material formed by the hydrogel ink has strong mechanical properties and can better maintain structural stability.

[0008] The inventive concept of the present invention is: in the presence of the chelated ion substance designed in this patent, lithium algae can maintain a stable state for a period of time, but this stable state cannot be maintained for a long time. After standing for a period of time, it will be transformed into a gel state. This gel state can return to a sol state under the action of external forces such as stirring, which is a relatively unique rheological behavior.

[0009] The first aspect of the present invention provides a hydrogel ink, which includes a water-soluble monomer, GelMa (methacrylated gelatin), lithium talc, a stabilizer, a chelated ionic substance, a photoinitiator and water; the chelated ionic substance includes at least one of aminocarboxylates, hydroxycarboxylates and organic phosphonate compounds.

[0010] Compared with the prior art, the beneficial effects of a hydrogel ink provided by the first aspect of the present invention are as follows: the thixotropic properties of the hydrogel ink of the present invention are different from the general shear thinning phenomenon. The apparent viscosity of the general shear thinning phenomenon system decreases with the increase of shear rate. The hydrogel ink of the present invention directly changes from a viscous state to a solution state. This phenomenon should be related to the performance of lithium algae. Sol-type lithium algae (lithium algae is divided into sol-type and gel-type) can be dissolved to form a solution state, but lithium algae is a sheet structure with a charge on the surface. Generally, when ionic substances exist, lithium algae and ions react and easily form a gel state. This gel state is also difficult to be converted into a solution state under stirring. However, in the presence of chelated ionic substances in this patent, lithium algae can maintain a stable state for a period of time, but this stable state cannot be maintained for a long time, and it will be converted into a gel state after standing for a period of time. This gel state can return to a sol state under the action of external forces such as stirring. This is a relatively unique rheological behavior.

[0011] Preferably, the water-soluble monomer includes at least one of acrylamide, acrylic acid, and hydroxyethyl acrylate.

[0012] Preferably, the lithium ion is nano lithium ion.

[0013] Preferably, the stabilizer includes polyethylene glycol; further preferably, the polyethylene glycol includes at least one of PEG200, PEG400, PEG600, and PEG800.

[0014] The aminocarboxylate includes at least one of sodium nitrilotriacetate (NTA), ethylenediaminetetraacetate (disodium or tetrasodium EDTA), and diethylenetriaminepentacarboxylate (DTPA); the hydroxycarboxylate includes at least one of sodium citrate, sodium tartrate, heptanoate, sodium gluconate, sodium oxalate, and sodium ascorbate; the organic phosphonate includes at least one of sodium ethylenediaminetetramethylenephosphate (EDTMPS), diethylenetriaminepenta(methylenephosphonate) (DETPMPS), and aminotri(methylenephosphonate) (homogeneous trimethylenephosphate).

[0015] Preferably, the chelated ionic substance is a hydroxycarboxylate, and the hydroxycarboxylate includes at least one of sodium citrate, sodium tartrate, heptonic acid salt, sodium gluconate, sodium oxalate, and sodium ascorbate; further preferably, the chelated ionic substance includes sodium citrate.

[0016] Preferably, the photoinitiator includes at least one of 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methylacetone (photoinitiator 2959), 1-hydroxycyclohexyl phenyl ketone (photoinitiator 184), and phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (photoinitiator LAP).

[0017] Preferably, in parts by weight, the hydrogel ink comprises 3-25 parts of water-soluble monomers, 0.5-10 parts of GelMa (methacrylated gelatin), 0.5-10 parts of lithiasis, 0.5-5 parts of stabilizer, 1-20 parts of chelated ionic substances, 0.05-1 parts of photoinitiator, and 29-93.45 parts of water; further preferably, the hydrogel ink comprises 5-20 parts of water-soluble monomers, 2-8 parts of GelMa (methacrylated gelatin), 1-5 parts of lithiasis, 1-3 parts of stabilizer, 5-15 parts of chelated ionic substances, 0.1-0.5 parts of photoinitiator, and 58.1-85.9 parts of water.

[0018] A second aspect of the present invention provides a method for preparing the hydrogel ink, the method comprising the following steps:

[0019] (1) dissolving the lithium alkali earth in water and adding the stabilizer to prepare solution A;

[0020] (2) adding the water-soluble monomer, the GelMa (methacrylated gelatin), and the photoinitiator to the solution A respectively, dissolving them, and obtaining a solution B;

[0021] (3) Adding the chelated ionic substance into the solution B and dissolving it to obtain the hydrogel ink.

[0022] Preferably, the preparation method further comprises step (4): allowing the hydrogel ink to stand to form a gel state.

[0023] Preferably, the preparation method further comprises step (5): packaging the hydrogel ink into a container.

[0024] Preferably, steps (1)-(3) of the preparation method are all carried out at a temperature of 20-40°C; further preferably, steps (1)-(3) of the preparation method are all carried out at a temperature of 25-37°C.

[0025] A third aspect of the present invention provides a hydrogel, which is prepared by photocuring the hydrogel ink.

[0026] Preferably, the photoreaction wavelength of the photocuring is 25-50 nm.

[0027] Preferably, the reaction temperature of the photocuring is 20-40°C.

[0028] A fourth aspect of the present invention provides a 3D printing ink cartridge, wherein the 3D printing ink cartridge comprises the hydrogel ink.

[0029] A fifth aspect of the present invention provides an application of the hydrogel ink in the field of 3D printing.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0031] (1) The thixotropic property of the hydrogel ink of the present invention is different from the general shear thinning phenomenon. In the general shear thinning phenomenon, the apparent viscosity of the liquid decreases with the increase of the shear rate. The hydrogel ink of the present patent directly changes from the gel state to the sol state. This phenomenon should be related to the performance of lithium algae. The sol-type lithium algae (lithium algae is divided into sol-type and gel-type) can be dissolved to form a solution state, but lithium algae is a lamellar structure with an electric charge on the surface. In the presence of general ionic substances, lithium algae and ions react to form a gel state, and this gel state is difficult to be converted into a solution state under stirring. However, in the presence of the chelated ionic substance of the present patent, lithium algae can maintain a stable state for a period of time, but this stable state cannot be maintained for a long time and will be converted into a gel state after standing for a period of time. This gel state can return to the sol state under the action of external forces such as stirring. This is a relatively unique rheological behavior;

[0032] (2) The properties of the hydrogel ink of the present invention make it suitable for 3D printing. The hydrogel ink is in a flowing viscous state before extrusion. When the extrusion force is applied, the hydrogel ink is sheared and becomes a flowing state, so it is easier to extrude from the print head of the printer. After extrusion, the hydrogel ink is quickly converted into a viscous state, and it is easier to keep the structure from deforming. The viscous state becomes the final gel hydrogel after light curing;

[0033] (3) The hydrogel prepared by the hydrogel ink of the present invention has good mechanical properties. DETAILED DESCRIPTION

[0034] In order to make the technical scheme of the present invention more clearly understood by those skilled in the art, the following embodiments are listed for illustration. It should be pointed out that the following embodiments do not limit the protection scope of the present invention.

[0035] Unless otherwise specified, the raw materials, reagents or devices used in the following examples can be obtained from conventional commercial sources or by existing known methods.

[0036] Example 1

[0037] Hydrogel ink 1 and its preparation method and application in preparing hydrogel 1 in 3D printing.

[0038] The preparation method of the hydrogel ink 1 is as follows:

[0039] (1) Weigh 0.5 g of nano-lithium laponite and dissolve it in 93.45 g of deionized water, add 0.5 g of PEG400, and stir to form a transparent solution A;

[0040] (2) Then, 3 g of hydroxyethyl acrylate, 1 g of GelMa (methacrylated gelatin), and 0.05 g of a photoinitiator (photoinitiator 184) were added to the transparent solution A in sequence, and stirred to form a transparent solution B.

[0041] (3) 1 g of sodium ethylenediaminetetramethylenephosphate was added to the transparent solution B and stirred to form a hydrogel ink 1.

[0042] The hydrogel ink 1 becomes a gel state after being allowed to stand. The syringe draws the hydrogel ink 1 into the syringe tube. During the drawing process, the hydrogel ink 1 changes from a gel state to a sol state. The hydrogel ink 1 is injected onto a watch glass and allowed to stand. The sol state hydrogel ink 1 changes back to a gel state on the watch glass.

[0043] The hydrogel ink 1 is placed in a 3D printer, extruded through a print head, and subjected to a photocuring reaction at 25° C. and a wavelength of 35 nm to obtain a photocurable hydrogel 1 .

[0044] Example 2

[0045] Hydrogel ink 2 and its preparation method and application in preparing hydrogel 2 in 3D printing.

[0046] The preparation method of hydrogel ink 2 is as follows:

[0047] (1) Weigh 10 g of nano-lithium laponite and dissolve it in 29 g of deionized water, add 5 g of PEG400, and stir to form a transparent solution A;

[0048] (2) Then, 25 g of sodium acrylate, 10 g of GelMa (methacrylated gelatin), and 1 g of photoinitiator (photoinitiator 2959) were added to the transparent solution A in sequence, and stirred to form a transparent solution B.

[0049] (3) Add 20 g of disodium EDTA to the transparent solution B and stir to form hydrogel ink 2.

[0050] The hydrogel ink 2 becomes a gel state after being allowed to stand. The syringe draws the hydrogel ink 2 into the syringe tube. During the drawing process, the hydrogel ink 2 changes from a gel state to a sol state. The hydrogel ink 2 is injected onto a watch glass and allowed to stand. The sol state hydrogel ink 2 changes back to a gel state on the watch glass.

[0051] The hydrogel ink 2 is placed in a 3D printer, extruded through a print head, and subjected to a photocuring reaction at 25° C. and a wavelength of 35 nm to obtain a photocurable hydrogel 2 .

[0052] Example 3

[0053] Hydrogel ink 3 and its preparation method and application in preparing hydrogel 3 in 3D printing.

[0054] The preparation method of hydrogel ink 3 is as follows:

[0055] (1) Weigh 3 g of nano-lithium laponite and dissolve it in 73.9 g of deionized water, add 2 g of PEG400, and stir to form a transparent solution A;

[0056] (2) Then, 10 g of acrylamide, 1 g of GelMa (methacrylated gelatin), and 0.1 g of photoinitiator (photoinitiator LAP) were added to the transparent solution A in sequence, and stirred to form a transparent solution B.

[0057] (3) Add 10 g of sodium citrate to the transparent solution B and stir to form hydrogel ink 3.

[0058] The hydrogel ink 3 becomes a gel state after being allowed to stand. The syringe draws the hydrogel ink 3 into the syringe tube. During the drawing process, the hydrogel ink 3 changes from a gel state to a sol state. The hydrogel ink 3 is injected onto a watch glass and allowed to stand. The sol state hydrogel ink 3 changes back to a gel state on the watch glass.

[0059] The hydrogel ink 3 is placed in a 3D printer, and the hydrogel ink 3 is extruded through a print head, and a photocuring reaction is performed at 25° C. and a wavelength of 35 nm to obtain a photocurable hydrogel 3 .

[0060] Comparative Example 1

[0061] Hydrogel ink 4 (compared with Example 3, no chelating ionic substance is added) and its preparation method and application in preparing hydrogel 4 in 3D printing.

[0062] The preparation method of hydrogel ink 4 is as follows:

[0063] (1) Weigh 3 g of nano-lithium laponite and dissolve it in 83.9 g of deionized water, add 2 g of PEG400, and stir to form a transparent solution A;

[0064] (2) Then, 10 g acrylamide, 1 g GelMa (methacrylated gelatin), and 0.1 g photoinitiator (photoinitiator LAP) were added to the transparent solution A in sequence, and stirred to form a hydrogel ink 4.

[0065] The hydrogel ink 4 is still in a sol state when it is left to stand. The hydrogel ink 4 is drawn into the syringe tube by a syringe, and the hydrogel ink 4 is injected onto a watch glass. After the hydrogel ink 4 is left to stand, the sol state hydrogel ink 4 fails to transform into a gel state on the watch glass.

[0066] The hydrogel ink 4 is placed in a 3D printer, and the hydrogel ink 4 is extruded through a print head, and a photocuring reaction is performed at 25° C. and a wavelength of 35 nm to obtain a photocurable hydrogel 4 .

[0067] Comparative Example 2

[0068] Hydrogel ink 5 (compared with Example 3, sodium chloride replaces sodium citrate) and its preparation method and application in preparing hydrogel 5 in 3D printing.

[0069] The preparation method of the hydrogel ink 5 is as follows:

[0070] (1) Weigh 3 g of nano-lithium laponite and dissolve it in 73.9 g of deionized water, add 2 g of PEG400, and stir to form a transparent solution A;

[0071] (2) Then, 10 g of acrylamide, 1 g of GelMa (methacrylated gelatin), and 0.1 g of photoinitiator (photoinitiator LAP) were added to the transparent solution A in sequence, and stirred to form a transparent solution B.

[0072] (3) Add 10 g of sodium chloride to the transparent solution B and stir to form hydrogel ink 5.

[0073] The hydrogel ink 5 is slowly transformed into a gel state during stirring in step (3). The hydrogel ink 5 is in a gel state after being allowed to stand. The hydrogel ink 5 is drawn into the syringe tube by a syringe. During the drawing process, the hydrogel ink 5 is still in a gel state and cannot be restored to a sol state. The hydrogel ink 5 is injected into a watch glass and allowed to stand. The sol-state hydrogel ink 5 is in a gel state on the watch glass.

[0074] The hydrogel ink 5 is placed in a 3D printer, and the hydrogel ink 5 is extruded through a print head, and a photocuring reaction is performed at 25° C. and a wavelength of 35 nm to obtain a photocurable hydrogel 5 .

[0075] Comparative Example 3

[0076] Hydrogel ink 6 (compared with Example 3 without GelMa) and its preparation method and application in preparing hydrogel 6 in 3D printing.

[0077] The preparation method of the hydrogel ink 6 is as follows:

[0078] (1) Weigh 3 g of nano-lithium laponite and dissolve it in 74.9 g of deionized water, add 2 g of PEG400, and stir to form a transparent solution A;

[0079] (2) Then, 10 g of acrylamide and 0.1 g of photoinitiator (LAP) were added to the transparent solution A in sequence, and stirred to form a transparent solution B.

[0080] (3) Add 10 g of sodium citrate to the transparent solution B and stir to form hydrogel ink 6.

[0081] The hydrogel ink 6 becomes a gel state after being allowed to stand. The syringe draws the hydrogel ink 6 into the syringe tube. During the drawing process, the hydrogel ink 6 changes from a gel state to a sol state. The hydrogel ink 6 is injected onto a watch glass and allowed to stand. The sol state hydrogel ink 6 changes back to a gel state on the watch glass.

[0082] The hydrogel ink 6 is placed in a 3D printer, extruded through a print head, and subjected to a photocuring reaction at 25° C. and a wavelength of 35 nm to obtain a photocurable hydrogel 6 .

[0083] Comparative Example 4

[0084] Hydrogel ink 7 (compared with Example 3, without lithium terephthalate) and its preparation method and application in preparing hydrogel 7 in 3D printing.

[0085] The preparation method of the hydrogel ink 7 is as follows:

[0086] (1) Weigh 2 g of PEG400 and dissolve it in 73.9 g of deionized water, stirring to form a transparent solution A;

[0087] (2) Then, 10 g of acrylamide, 1 g of GelMa (methacrylated gelatin), and 0.1 g of photoinitiator (photoinitiator LAP) were added to the transparent solution A in sequence, and stirred to form a transparent solution B.

[0088] (3) Add 10 g of sodium citrate to the transparent solution B and stir to form hydrogel ink 7.

[0089] The hydrogel ink 7 becomes a solution after being left to stand. The hydrogel ink 7 is drawn into the syringe tube by a syringe, and the hydrogel ink 7 is injected onto a watch glass. After being left to stand, the sol-state hydrogel ink 7 is still in a solution on the watch glass.

[0090] The hydrogel ink 7 is placed in a 3D printer, extruded through a print head, and subjected to a photocuring reaction at 25° C. and a wavelength of 35 nm to obtain a photocurable hydrogel 7 .

[0091] Effect Example 1

[0092] The hydrogel ink and hydrogel samples prepared in Examples 1-3 and Comparative Examples 1-3 were tested for performance respectively. The testing method was as follows: observing the gel-sol transformation phenomenon of the hydrogel ink by stirring, and testing the viscosity of the hydrogel ink (after being left to stand and stabilize) and the elastic modulus of the hydrogel (after light curing) by a viscometer. The test results are shown in Table 1.

[0093] Table 1 Test results

[0094] Gel-sol transformation phenomenon of hydrogel ink Viscosity of hydrogel ink Elastic modulus of hydrogel Example 1 Gel-Sol-Gel 200 0.8 Example 2 Gel-Sol-Gel 220 1.0 Example 3 Gel-Sol-Gel 250 1.2 Comparative Example 1 Sol-Sol-Sol 93 1.1 Comparative Example 2 Gel-Gel-Gel 245 1.2 Comparative Example 3 Gel-Gel-Gel 208 0.5 Comparative Example 4 Sol-Sol-Sol 9 0.1

Claims

1. A hydrogel ink, characterized in that: In parts by weight, the hydrogel ink comprises 3-25 parts of water-soluble monomers, 0.5-10 parts of GelMa, 0.5-10 parts of lithium ion, 0.5-5 parts of stabilizer, 1-20 parts of chelated ion substances, 0.05-1 parts of photoinitiator, and 29-93.45 parts of water; The chelated ion substance includes at least one of aminocarboxylates, hydroxycarboxylates, and organic phosphonate compounds; The stabilizer includes polyethylene glycol.

2. The hydrogel ink according to claim 1, characterized in that: The water-soluble monomer includes at least one of acrylamide, acrylic acid, and hydroxyethyl acrylate.

3. The hydrogel ink according to claim 1, characterized in that: The chelated ion substance is a hydroxycarboxylate, and the hydroxycarboxylate includes at least one of sodium citrate, sodium tartrate, heptonic acid salt, sodium gluconate, sodium oxalate and sodium ascorbate.

4. The hydrogel ink according to claim 1, characterized in that: The hydroxycarboxylate includes at least one of sodium citrate, sodium tartrate, heptanoate, sodium gluconate, sodium oxalate and sodium ascorbate.

5. The hydrogel ink according to claim 1, characterized in that: The photoinitiator includes at least one of 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methylacetone, 1-hydroxycyclohexyl phenyl ketone, and phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt.

6. The method for preparing the hydrogel ink according to any one of claims 1 to 5, characterized in that: The preparation method comprises the following steps: (1) dissolving the lithium alkali earth in water and adding the stabilizer to prepare solution A; (2) adding the water-soluble monomer, the GelMa, and the photoinitiator to the solution A respectively, dissolving them, and obtaining a solution B; (3) Adding the chelated ionic substance into the solution B and dissolving it to obtain the hydrogel ink.

7. A hydrogel, characterized in that: The hydrogel is prepared by photocuring the hydrogel ink according to any one of claims 1 to 5.

8. A 3D printing ink cartridge, characterized in that: The 3D printing ink cartridge comprises the hydrogel ink according to any one of claims 1-5.

9. Application of the hydrogel ink according to any one of claims 1 to 5 in the field of 3D printing.