Method for improving characteristic that gelatin-based hydrogel is easy to solidify at room temperature

Abstract

The invention relates to the technical field of gelatin production, and discloses a method for improving the characteristic that gelatin-based hydrogel is easy to solidify at room temperature. The gelatin-based hydrogel is prepared from the following raw materials: gelatin, a hydrogen bond competitive material and water, the hydrogen bond competitive material is selected from at least one of metformin, L-arginine, an amide micromolecule cross-linking agent, polyarginine and a polyurea compound. According to the gelatin-based hydrogel provided by the invention, the gelation temperature is less than 25 DEG C, the gelatin-based hydrogel is not easy to solidify at room temperature (20-25 DEG C), and compared with a common gelatin solution, the gelatin-based hydrogel has the advantage that the characteristic that the gelatin is easy to solidify at room temperature is improved; according to the preparation method of the gelatin-based hydrogel, the room-temperature coagulability of the gelatin aqueous solution can be improved by introducing a material with competitive hydrogen bonds into the gelatin aqueous solution through simple physical blending, and compared with a traditional covalent modification method, the method is easy to operate and high in applicability, does not damage the original structure of gelatin and is good in repeatability.

Description

Technical Field

[0001] The invention relates to the technical field of gelatin production, and in particular to a method for improving the easy solidification property of gelatin-based hydrogel at room temperature. Background Art

[0002] Gelatin is a colloidal substance widely used in the fields of food industry, medicine and biomaterials. It is mainly derived from animal connective tissue and is partially hydrolyzed from animal collagen. In the biomedical field, gelatin, as a natural polymer material, is widely used due to its good biocompatibility, degradability and modifiable functionality. For example, in the field of tissue engineering, gelatin can be used as a scaffold material to promote cell growth and new tissue formation; in terms of drug carriers, gelatin microspheres and nanoparticles can achieve sustained release and targeted delivery of drugs and reduce side effects; gelatin can also be used in surgical sutures, which are biodegradable and can reduce the need for secondary surgery; in addition, gelatin-based adhesives are used for tissue bonding in minimally invasive surgery to improve surgical efficiency.

[0003] However, the gelatin in the above application scenarios is mostly in the form of gelatin aqueous solution. Under low temperature or even room temperature (20-25°C), the gelatin aqueous solution is prone to "sol-gel" transformation, which brings great inconvenience to use. For example, it is easy to clog the pipeline when it needs to be injected. In addition, in the preparation and storage process of gelatin aqueous solution, in order to maintain its fluidity, specific temperature control is required, which increases the complexity and cost of operation.

[0004] The existing technology mainly overcomes the easy solidification of gelatin at room temperature by changing the molecular structure of gelatin. Common methods include biological modification and chemical modification. Biological modification is to use enzymes or microorganisms to change the molecular structure of gelatin. The method is relatively mild, but the cost is high, and the dependence on enzymes or microorganisms may limit its application in large-scale production; the chemical modification method changes the chemical properties of gelatin molecules by introducing new chemical groups or cross-linking agents, such as modifying the side chains of gelatin with special groups (such as catechol), thereby reducing the "sol-gel" transition temperature of the gelatin aqueous solution to below room temperature, thereby improving its injectability. However, the covalent chemical modification method is often complicated to operate, and because the group modification process is difficult to accurately control, it will result in poor uniformity of the chemical structure of modified gelatin between different batches and easily lead to the residue of toxic substances. Summary of the invention

[0005] The present invention aims to solve at least one of the above-mentioned technical problems existing in the prior art. To this end, one of the purposes of the present invention is to provide a gelatin-based hydrogel; the second purpose of the present invention is to provide a method for preparing the gelatin-based hydrogel; the third purpose of the present invention is to provide an application of the gelatin-based hydrogel; the fourth purpose of the present invention is to provide a gelatin-based bio-ink.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] The first aspect of the present invention provides a gelatin-based hydrogel, comprising the following preparation materials: gelatin, a hydrogen bond competitive material and water;

[0008] The hydrogen bond competitive material is selected from at least one of metformin, L-arginine, an amide small molecule cross-linking agent, polyarginine, and a polyurea compound.

[0009] The basic principle of the present invention is described as follows:

[0010] The property of gelatin aqueous solution to be easily solidified at room temperature is closely related to its secondary structure. Gelatin molecules are long chains composed of amino acids. These long chains can form a three-dimensional network structure through strong hydrogen bond interactions at a certain temperature (25-35°C), thereby forming a gel. Hydrogen bond is a special force between molecules, which is stronger than ordinary van der Waals forces, but weaker than covalent bonds and ionic bonds. It usually occurs between atoms with higher electronegativity (such as oxygen and nitrogen) and hydrogen atoms. The present invention introduces materials with competitive hydrogen bond interactions into the gelatin hydrogel network. The introduction of these materials can form new hydrogen bonds with hydrogen bond donors or acceptors in gelatin molecules, thereby replacing the original intermolecular hydrogen bond interactions in the gelatin hydrogel network, thereby achieving the purpose of lowering the "sol-gel" transition temperature of gelatin, thereby improving the easy solidification property of gelatin aqueous solution at room temperature.

[0011] In some embodiments of the present invention, the mass ratio of gelatin to water is 1:(3-20).

[0012] In some specific embodiments of the present invention, the mass ratio of gelatin to water is 1:(10-20).

[0013] In some embodiments of the present invention, the mass ratio of the hydrogen bond competitive material to gelatin is 1:(0.25-6).

[0014] In some specific embodiments of the present invention, the mass ratio of the hydrogen bond competitive material to gelatin is 1:(0.5-5).

[0015] In some embodiments of the present invention, the amide small molecule cross-linking agent is selected from at least one of a small molecule diamine solution, a carboxylic acid derivative, and a polyamino compound.

[0016] In some embodiments of the present invention, the polyamino compound is selected from at least one of 1,4-bis(3-aminopropyl)piperazine, N,N-bis(3-aminopropyl)methylamine, tris(2-aminoethyl)amine, tris(3-aminopropyl)amine, and N,N,N',N'-tetrakis(3-aminopropyl)-1,4-butanediamine.

[0017] In some embodiments of the present invention, the weight average molecular weight of the polyarginine is 3000-5000 Da.

[0018] In some embodiments of the present invention, the weight average molecular weight of the polyurea compound is 1000-5000 Da.

[0019] In some embodiments of the present invention, the gelatin-based hydrogel has a gelling temperature of less than 25°C.

[0020] In some specific embodiments of the present invention, the gelling temperature of the gelatin-based hydrogel is less than 25°C and greater than or equal to 15°C.

[0021] The second aspect of the present invention provides a method for preparing the gelatin-based hydrogel according to the first aspect of the present invention, comprising the following steps:

[0022] Gelatin is dissolved in water to form a gelatin aqueous solution, and then a hydrogen bond competitive material is added and mixed evenly to obtain the gelatin-based hydrogel.

[0023] In some embodiments of the present invention, the hydrogen bond competitive material and the aqueous gelatin solution are uniformly mixed by stirring.

[0024] In some embodiments of the present invention, the stirring speed is 1000-3000 rpm.

[0025] In some embodiments of the present invention, after the hydrogen bond competitive material is uniformly mixed with the gelatin aqueous solution, a step of testing the rheological viscosity and / or thermal stability and / or macroscopic coagulation of the gelatin aqueous solution is also included.

[0026] In the present invention, after the hydrogen bond competitive material is introduced into the gelatin aqueous solution, the rheological viscosity, thermal stability and macroscopic coagulation of the gelatin aqueous solution are tested to verify the performance change of the gelatin solution after the introduction of the hydrogen bond competitive material, and to ensure that the time for the gelatin aqueous solution to remain liquid at room temperature is extended, thereby improving its flexibility and convenience in use in various applications.

[0027] The third aspect of the present invention provides the use of the gelatin-based hydrogel described in the first aspect of the present invention in the preparation of gelatin-based biological ink and / or injectable gelatin-based hydrogel microspheres and / or injectable gelatin-based sustained-release systems and / or gelatin-based biological composite materials.

[0028] The gelatin-based hydrogel provided by the present invention has a gelation temperature of less than 25°C, which is lower than that of ordinary gelatin aqueous solutions. When used to prepare gelatin-based biological inks, injectable gelatin-based hydrogel microspheres, injectable gelatin-based sustained-release systems or gelatin-based biological composite materials, the products can be ensured to be in a stable state at room temperature and not easily converted into gels.

[0029] The fourth aspect of the present invention provides a gelatin-based bio-ink, comprising the gelatin-based hydrogel described in the first aspect of the present invention.

[0030] In some embodiments of the present invention, the gelatin-based bio-ink is applied to biological 3D printing.

[0031] In some embodiments of the present invention, the bio-3D printing temperature of the gelatin-based bio-ink is less than or equal to 20°C.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] 1) The gelatin-based hydrogel provided by the present invention has a gelation temperature of less than 25°C and is not easy to solidify at room temperature (20-25°C). Compared with ordinary gelatin solutions, the easy solidification property at room temperature is improved;

[0034] 2) The preparation method of the gelatin-based hydrogel provided by the present invention can improve the room temperature coagulation property of the gelatin aqueous solution by introducing a material with competitive hydrogen bonds into the gelatin aqueous solution through simple physical blending, so that the gelation temperature of the gelatin-based hydrogel is reduced to below 25°C, so that it can be used normally at room temperature; compared with the traditional covalent modification method, the method is simple to operate, has strong applicability, does not damage the original structure of gelatin, has good repeatability, and is suitable for promotion;

[0035] 3) The gelatin-based hydrogel provided by the present invention is not easy to solidify at room temperature, and can be used to prepare gelatin-based biological ink, injectable gelatin-based hydrogel microspheres, injectable gelatin-based sustained-release systems or gelatin-based biological composite materials, which can ensure that the product is in a stable state at room temperature and is not easy to turn into a gel;

[0036] 4) The gelatin-based bio-ink provided by the present invention can be applied to biological 3D printing, the printing temperature can be less than or equal to 20°C, and the printing pattern has high fidelity. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 The rheological viscosity test results of the gelatin-based hydrogel in Example 3;

[0038] Figure 2 The rheological viscosity test results of the gelatin-based hydrogel in Example 7;

[0039] Figure 3 The rheological viscosity test results of the gelatin-based hydrogel in Example 11;

[0040] Figure 4 Comparison of the fluidity of the gelatin-based hydrogels in Examples 1-4 and the gelatin aqueous solution in Comparative Example 1 after standing at 25°C for 30 minutes and then inverted;

[0041] Figure 5 Comparison of the fluidity of the gelatin-based hydrogels in Examples 5-8 and the gelatin aqueous solution in Comparative Example 1 after standing at 25°C for 30 minutes and then inverted;

[0042] Figure 6 Comparison of the fluidity of the gelatin-based hydrogels in Examples 9-12 and the gelatin aqueous solution in Comparative Example 1 after standing at 25°C for 30 minutes and then inverted;

[0043] Figure 7 This is a real-life photo of biological 3D printing in Application Example 1. DETAILED DESCRIPTION

[0044] The present invention is further described in detail below by specific examples. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial sources or can be obtained by prior art methods. Unless otherwise specified, the experiments or test methods are conventional methods in the art.

[0045] Example 1

[0046] In this example, metformin is used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps are as follows:

[0047] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 5g of metformin was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the metformin and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its solidification at room temperature.

[0048] Example 2

[0049] In this example, metformin is used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps are as follows:

[0050] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 10g of metformin was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the metformin and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its solidification at room temperature.

[0051] Example 3

[0052] In this example, metformin is used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps are as follows:

[0053] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and 15g of metformin was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the metformin and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its solidification at room temperature.

[0054] Example 4

[0055] In this example, metformin is used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps are as follows:

[0056] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and 20g of metformin was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the metformin and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its solidification at room temperature.

[0057] Example 5

[0058] In this example, gelatin-based hydrogel was prepared using L-arginine as a hydrogen bond competitive material, and the steps were as follows:

[0059] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 5g of L-arginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the L-arginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0060] Example 6

[0061] In this example, gelatin-based hydrogel was prepared using L-arginine as a hydrogen bond competitive material, and the steps were as follows:

[0062] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 10g of L-arginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the L-arginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0063] Example 7

[0064] In this example, gelatin-based hydrogel was prepared using L-arginine as a hydrogen bond competitive material, and the steps were as follows:

[0065] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 15g of L-arginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the L-arginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0066] Example 8

[0067] In this example, gelatin-based hydrogel was prepared using L-arginine as a hydrogen bond competitive material, and the steps were as follows:

[0068] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 20g of L-arginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the L-arginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0069] Example 9

[0070] In this example, polyarginine (weight average molecular weight of 4000) was used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps were as follows:

[0071] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 5g of polyarginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the polyarginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0072] Example 10

[0073] In this example, polyarginine (weight average molecular weight of 4000) was used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps were as follows:

[0074] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 10g of polyarginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the polyarginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0075] Embodiment 11

[0076] In this example, polyarginine (weight average molecular weight of 4000) was used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps were as follows:

[0077] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 15g of polyarginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the polyarginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0078] Example 12

[0079] In this example, polyarginine (weight average molecular weight of 4000) was used as a hydrogen bond competitive material to prepare a gelatin-based hydrogel, and the steps were as follows:

[0080] 15g of gelatin powder was dissolved in 100mL of water to prepare a gelatin aqueous solution with a concentration of 15wt%, and then 20g of polyarginine was added to the gelatin aqueous solution, and the mixture was stirred at 2000rpm to mix the polyarginine and the gelatin aqueous solution evenly to obtain a gelatin-based hydrogel. The gelatin-based hydrogel was left to stand at room temperature to observe its coagulation at room temperature.

[0081] Comparative Example 1

[0082] 15 g of gelatin powder was dissolved in 100 mL of water to prepare a 15 wt % gelatin aqueous solution. The gelatin aqueous solution was allowed to stand at room temperature to observe its coagulation at room temperature.

[0083] Performance Testing

[0084] 1. Test the rheological viscosity of the gelatin-based hydrogels in Examples 3, 7 and 11:

[0085] The rheological properties of the gelatin-based hydrogels in Examples 3, 7 and 11 were measured at 25°C using an Anton Paar MCR302e rheometer equipped with a 25 mm diameter conical plate. The apparent viscosity of the hydrogels was measured at a constant shear rate of 0.1 s -1 Here are the changes over time:

[0086] Figure 1 The rheological viscosity test results of the gelatin-based hydrogel in Example 3 are as follows: Figure 2 The rheological viscosity test results of the gelatin-based hydrogel in Example 7 are as follows: Figure 3 The rheological viscosity test results of the gelatin-based hydrogel in Example 11 are as follows. Figure 1-Figure 3 It can be seen that after metformin, L-arginine and polyarginine were introduced into the gelatin aqueous solution in Examples 3, 7 and 11, respectively, the rheological viscosity of the gelatin-based hydrogel in Example 3 changed the least over time, followed by Example 11, and finally Example 7, indicating that at the same dosage, metformin has the best effect on improving the room temperature easy solidification properties of the gelatin-based hydrogel.

[0087] 2. The gelatin-based hydrogels in Examples 1-12 and the gelatin aqueous solution in Comparative Example 1 were placed in a constant temperature mixer and placed for 30 min (25° C., 500 rpm) after reaching the set temperature. After the constant temperature program was completed, the mixture was taken out and inverted to observe the gel state to characterize the macroscopic coagulation of the gelatin at this temperature:

[0088] Figure 4 The fluidity comparison of the gelatin-based hydrogels in Examples 1-4 and the gelatin aqueous solution in Comparative Example 1 after standing at 25°C for 30 minutes and then inverted is shown. Figure 5 The fluidity of the gelatin-based hydrogels in Examples 5-8 and the gelatin aqueous solution in Comparative Example 1 after standing at 25°C for 30 minutes and then inverted is compared. Figure 6 The fluidity comparison of the gelatin-based hydrogels in Examples 9-12 and the gelatin aqueous solution in Comparative Example 1 after standing at 25°C for 30 minutes and then inverted. Figure 4-Figure 6 It can be seen that the gelatin aqueous solution in Comparative Example 1 has turned into a gel after being allowed to stand for 30 minutes at 25°C and does not flow when inverted, while in the gelatin-based hydrogels introduced with metformin in Examples 1-4, when the metformin addition amount is 5wt%-20wt%, the gelatin-based hydrogels have good fluidity after being allowed to stand for 30 minutes at 25°C; in the gelatin-based hydrogels introduced with L-arginine in Examples 5-8, when the concentration of L-arginine is 5wt%-10wt%, the room temperature solidification property of the gelatin aqueous solution cannot be improved, but when the concentration of L-arginine is greater than 15wt%, the room temperature solidification property of the gelatin aqueous solution can be improved; in the gelatin-based hydrogels introduced with polyarginine in Examples 9-12, when the polyarginine addition amount is 5wt%-20wt%, the gelatin-based hydrogels have good fluidity after being allowed to stand for 30 minutes at 25°C. It is shown that the gelatin-based hydrogel provided by the present invention can reduce the hydrogen bonding effect in the original gelatin aqueous solution after introducing hydrogen-bonding competitive materials such as metformin, L-arginine, and polyarginine into the gelatin aqueous solution, so that its gelation temperature is reduced to below 25°C. Among them, metformin and polyarginine can achieve good improvement effects at a relatively small addition amount.

[0089] Application Examples

[0090] The gelatin-based hydrogel in Example 2 and the gelatin aqueous solution in Comparative Example 1 were respectively prepared as gelatin-based bio-inks at room temperature and used for biological 3D printing at 20°C. For ease of observation, 1% rhodamine B dye was added to the gelatin-based bio-ink.

[0091] Figure 7 This is a photo of the real scene of biological 3D printing in Application Example 1, where: Figure 7 (a) is a photo of the printing process of the gelatin-based bio-ink prepared from the gelatin aqueous solution in Comparative Example 1. Figure 7(a) It can be seen that the gelatin-based bio-ink prepared from the gelatin aqueous solution in Comparative Example 1 has turned into a gel at 20°C and cannot be extruded; Figure 7 (b) is a photo of the printing process of the gelatin-based bio-ink prepared from the gelatin-based hydrogel in Example 2, Figure 7 (c) is a photo of a real object printed with gelatin-based bio-ink prepared from the gelatin-based hydrogel in Example 2. Figure 7 (b) and Figure 7 (c) It can be seen that adding 10wt% metformin as a hydrogen bond competitive material to the gelatin aqueous solution in Example 2 improves the room temperature solidification property of the gelatin-based hydrogel, so that the gelation temperature of the gelatin-based hydrogel is reduced to below 25°C. The prepared gelatin-based bio-ink still has good fluidity at 20°C, can be extruded to form uniform lines, and can be printed to obtain a high-fidelity "SYSU" pattern.

Claims

1. A gelatin-based hydrogel, characterized in that The preparation comprises the following raw materials: gelatin, hydrogen bond competitive material and water; The hydrogen bond competitive material is selected from at least one of metformin, L-arginine, an amide small molecule cross-linking agent, polyarginine, and a polyurea compound.

2. The gelatin-based hydrogel according to claim 1, characterized in that The mass ratio of the gelatin to water is 1:(3-20).

3. The gelatin-based hydrogel according to claim 1, characterized in that The mass ratio of the hydrogen bond competitive material to gelatin is 1:(0.25-6).

4. The gelatin-based hydrogel according to claim 1, characterized in that The amide small molecule cross-linking agent is selected from at least one of a small molecule diamine solution, a carboxylic acid derivative, and a polyamino compound; Preferably, the polyamino compound is selected from at least one of 1,4-bis(3-aminopropyl)piperazine, N,N-bis(3-aminopropyl)methylamine, tris(2-aminoethyl)amine, tris(3-aminopropyl)amine, and N,N,N',N'-tetrakis(3-aminopropyl)-1,4-butanediamine.

5. The gelatin-based hydrogel according to claim 1, characterized in that The weight average molecular weight of the polyarginine is 3000-5000Da.

6. The gelatin-based hydrogel according to claim 1, characterized in that The weight average molecular weight of the polyurea compound is 1000-5000 Da.

7. The gelatin-based hydrogel according to any one of claims 1 to 6, characterized in that The gelatin-based hydrogel has a gelling temperature of less than 25°C.

8. The method for preparing the gelatin-based hydrogel according to any one of claims 1 to 7, characterized in that: The following steps are involved: Gelatin is dissolved in water to form a gelatin aqueous solution, and then a hydrogen bond competitive material is added and mixed evenly to obtain the gelatin-based hydrogel.

9. Use of the gelatin-based hydrogel described in any one of claims 1 to 7 in the preparation of gelatin-based biological ink and / or injectable gelatin-based hydrogel microspheres and / or injectable gelatin-based sustained-release systems and / or gelatin-based biological composite materials.

10. A gelatin-based bio-ink, characterized in that: The gelatin-based hydrogel comprises the gelatin-based hydrogel according to any one of claims 1 to 7.

Images