Curcumin-loaded 3D biological printing ink as well as preparation method and application thereof
By chemically synthesizing the physical mixing of the ROS-responsive properties of the curcumin nanoparticle solution and the polymer powder, curcumin 3D bioprinting ink was prepared, which solved the problem of inaccurate drug release in the prior art, achieved the effect of anti-inflammatory and promoting wound healing, and expanded the scope of application.
Patent Information
- Application Number
- CN202510588696.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-08
- Publication Date
- 2025-08-01
AI Technical Summary
The lack of 3D bioprinted stents with ROS response characteristics in the prior art makes it difficult to achieve accurate drug release in tissue engineering to accelerate wound healing.
The curcumin nanoparticle solution was prepared by chemical reactions, and mixed with polymer powder to form a curcumin 3D bioprinting ink. The curcumin nanoparticle solution was mixed with polymer powder by physical mixing method to prepare a curcumin 3D bioprinting ink.
The prepared curcumin-loaded 3D bioprinting ink has significant anti-inflammatory activity and promotes wound healing effects. It has good printability and ROS response and release characteristics, which improves the administration accuracy of curcumin and broadens the scope of application.
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Figure CN120393112A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of 3D bioprinting materials, and more particularly to a curcumin-loaded 3D bioprinting ink and its preparation method and application. Background Art
[0002] The ROS-responsive drug delivery system is a special drug delivery system that can respond to changes in the level of reactive oxygen species (ROS), thereby achieving precise drug release. Some studies have found that drug-loaded 3D bioprinted scaffolds can be applied to wounds to accelerate the healing and reconstruction of tissue wounds. During wound healing, a large amount of ROS is often generated in the inflammatory phase, and precise drug release is required. However, there are few reports on 3D bioprinted scaffolds with drug-specific release characteristics in tissue engineering.
[0003] Considering the extrusion characteristics of 3D bioprinting and the drug loading method, it is necessary to further design and develop 3D bioprinting inks.
[0004] Therefore, how to develop a curcumin-loaded 3D bioprinting ink with ROS-responsive characteristics is an urgent problem to be solved by those skilled in the art. Summary of the Invention
[0005] In view of this, the purpose of the present invention is to provide a curcumin-loaded 3D bioprinting ink and its preparation method and application to solve the deficiencies in the prior art.
[0006] To achieve the above purpose, the present invention adopts the following technical solutions:
[0007] A preparation method of a curcumin-loaded 3D bioprinting ink specifically includes the following steps:
[0008] (1) Preparation of the encapsulant
[0009] Dissolve ketothiol (TK), dicyclohexylcarbodiimide (DCC), and 4-dimethylaminopyridine (DMAP) in dimethyl sulfoxide (DMSO) to obtain mixture 1, dissolve poly(D,L-lactide-co-glycolide) (PLGA) in dimethyl sulfoxide to obtain mixture 2, mix mixture 1 and mixture 2 and react under nitrogen protection to obtain mixture 3, dissolve methoxypolyethylene glycol (mPEG) in dimethyl sulfoxide to obtain mixture 4, mix mixture 3 and mixture 4 and react under nitrogen protection to obtain mixture 5, dialyze and lyophilize to obtain the encapsulant;
[0010] (2) Preparation of the curcumin nanoparticle solution
[0011] Dissolve the encapsulated substance in chloroform to obtain mixture 6, dissolve curcumin in methanol to obtain mixture 7, mix mixture 6 and mixture 7 to obtain mixture 8, spin-dry and redissolve to obtain the curcumin nanoparticles solution;
[0012] (3) Preparation of curcumin-loaded 3D bioprinting ink
[0013] Mix sodium alginate and the curcumin nanoparticles solution, then add nanoclay and mix again to obtain mixture 9. Mix gelatin and the curcumin nanoparticles solution and heat to obtain mixture 10. Mix mixture 9 and mixture 10 to obtain the curcumin-loaded 3D bioprinting ink.
[0014] In the present invention, first, a ROS-responsive encapsulated substance is synthesized through a chemical reaction, and then curcumin is encapsulated to obtain a curcumin nanoparticles solution with ROS-responsive characteristics; then the curcumin nanoparticles solution is mixed with a polymer powder to obtain a curcumin-loaded 3D bioprinting ink with ROS-responsive characteristics.
[0015] Furthermore, in the above step (1), in mixture 1, the molar ratio of ketothiol, dicyclohexylcarbodiimide and 4-dimethylaminopyridine is (0.01 - 2):1:(0.01 - 1), and the dosage ratio of dicyclohexylcarbodiimide to dimethyl sulfoxide is (0.1 - 1) mmol:1 mL; in mixture 2, the dosage ratio of poly(D,L-lactide-co-glycolide) to dimethyl sulfoxide is (0.01 - 5) g:1 mL; in mixture 4, the dosage ratio of methoxypolyethylene glycol to dimethyl sulfoxide is (0.01 - 5) g:1 mL.
[0016] Furthermore, in the above step (1), the reaction temperature is 40 - 80 °C and the time is 24 h.
[0017] Furthermore, in the above step (1), the molecular weight of dialysis is 4 kDa - 10 kDa and the time is 5 days.
[0018] Furthermore, in the above step (2), in mixture 6, the dosage ratio of the encapsulated substance to chloroform is (0.01 - 5) g:1 mL; in mixture 7, the dosage ratio of curcumin to methanol is (0.01 - 1) g:1 mL.
[0019] Furthermore, in the above step (2), in the curcumin nanoparticles solution, the concentration of curcumin is (0.01 - 80) μg / mL.
[0020] Furthermore, in the above step (3), in mixture 9, the dosage ratio of sodium alginate, nanoclay and the curcumin nanoparticles solution is (0.01 - 1) g:(0.01 - 2) g:1 mL; in mixture 10, the dosage ratio of gelatin and the curcumin nanoparticles solution is (0.01 - 1) g:1 mL.
[0021] Furthermore, in the above step (3), in the curcumin-loaded 3D bioprinting ink, the volume ratio of the mixture 9 to the mixture 10 is 1: (0.01 - 10).
[0022] The present invention also claims protection for a curcumin-loaded 3D bioprinting ink prepared by the above preparation method.
[0023] The present invention also claims protection for the application of a curcumin-loaded 3D bioprinting ink prepared by the above preparation method in the preparation of drug-loaded medical devices.
[0024] As can be seen from the above technical solutions, compared with the prior art, the beneficial effects of the present invention are as follows:
[0025] The present invention uses a physical mixing method to mix the curcumin nanoparticle solution and the polymer powder. The curcumin-loaded 3D bioprinting ink thus prepared has significant anti-inflammatory activity and good wound healing promotion effect, and at the same time has good printability and ROS-responsive release characteristics, and can be used in drug-loaded medical devices, which is of great significance for improving the dosing accuracy of curcumin. Moreover, the preparation method of the present invention is simple in operation, remarkable in effect, wide in application range, can broaden the application range of curcumin-loaded 3D bioprinting ink, and has good application prospects. Description of the Drawings
[0026] Figure 1 Viscosity curves of six 3D bioprinting ink samples of Examples 1 - 3 and Comparative Examples 1 - 3;
[0027] Figure 2 Physical pictures of 3D scaffolds printed from six 3D bioprinting ink samples of Examples 1 - 3 and Comparative Examples 1 - 3;
[0028] Figure 3 24-hour drug release amounts of 3D scaffolds printed from four 3D bioprinting ink samples of Examples 1 - 3 and Comparative Example 1 under different conditions;
[0029] Figure 4 Cytotoxicity of 3D scaffolds printed from six 3D bioprinting ink samples of Examples 1 - 3 and Comparative Examples 1 - 3;
[0030] Figure 5 Anti-inflammatory characteristics of 3D scaffolds printed from six 3D bioprinting ink samples of Examples 1 - 3 and Comparative Examples 1 - 3;
[0031] Figure 6 Wound healing promotion characteristics of 3D scaffolds printed from two 3D bioprinting ink samples of Example 1 and Comparative Example 1. Detailed Embodiments
[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.
[0033] Example 1
[0034] A preparation method of curcumin-loaded 3D bioprinting ink specifically includes the following steps:
[0035] (1) Preparation of the encapsulant
[0036] Dissolve 600 mg of ketothiol (TK), 5 g of dicyclohexylcarbodiimide (DCC), and 300 mg of 4-dimethylaminopyridine (DMAP) in 200 mL of dimethyl sulfoxide (DMSO), and stir at 60 °C to obtain a mixed solution 1; dissolve 4 g of poly(D,L-lactide-co-glycolide) (PLGA) in 40 mL of dimethyl sulfoxide (DMSO) to obtain a mixed solution 2; mix the mixed solution 1 and the mixed solution 2, and protect it with nitrogen, and react at 40 °C for 24 h to obtain a mixed solution 3; dissolve 7 g of methoxypolyethylene glycol (mPEG) in 40 mL of dimethyl sulfoxide (DMSO) to obtain a mixed solution 4; add the mixed solution 4 to the mixed solution 3, and protect it with nitrogen, and react at 40 °C for 24 h to obtain a mixed solution 5; dialyze the mixed solution 5 in a dialysis bag with a molecular weight cut-off of 7 kDa for 5 days, and then lyophilize it to obtain the encapsulant;
[0037] (2) Preparation of curcumin nanoparticles solution
[0038] Dissolve 50 mg of the encapsulant in 10 mL of chloroform to obtain a mixed solution 6, dissolve 10 mg of curcumin in 10 mL of methanol to obtain a mixed solution 7, and mix the mixed solution 6 and the mixed solution 7 to obtain a mixed solution 8; spin-dry the mixed solution 8 and then immediately re-dissolve it with 10 mL of water to obtain a curcumin nanoparticles solution;
[0039] (3) Preparation of curcumin-loaded 3D bioprinting ink
[0040] Mix 3 g of sodium alginate with 10 mL of the curcumin nanoparticles solution, and after mixing evenly, add 2 g of nanoclay and continue to stir until evenly mixed to obtain a mixed solution 9; mix 3 g of gelatin with 10 mL of the curcumin nanoparticles solution and heat to obtain a mixed solution 10; mix the mixed solution 9 and the mixed solution 10 with the same volume to obtain the curcumin-loaded 3D bioprinting ink.
[0041] Example 2
[0042] A preparation method of curcumin-loaded 3D bioprinting ink specifically includes the following steps:
[0043] (1) Preparation of the encapsulated substance
[0044] Dissolve 500 mg of ketothiol (TK), 5 g of dicyclohexylcarbodiimide (DCC), and 400 mg of 4-dimethylaminopyridine (DMAP) in 200 mL of dimethyl sulfoxide (DMSO), and stir at 60 °C to obtain mixture 1; dissolve 3 g of poly(D,L-lactide-co-glycolide) (PLGA) in 40 mL of dimethyl sulfoxide (DMSO) to obtain mixture 2; mix mixture 1 and mixture 2, and protect with nitrogen, and react at 40 °C for 24 h to obtain mixture 3; dissolve 5 g of methoxypolyethylene glycol (mPEG) in 40 mL of dimethyl sulfoxide (DMSO) to obtain mixture 4; add mixture 4 to mixture 3, and protect with nitrogen, and react at 40 °C for 24 h to obtain mixture 5; dialyze mixture 5 in a 7 kDa dialysis bag for 5 days, and then lyophilize to obtain the encapsulated substance;
[0045] (2) Preparation of curcumin nanoparticles solution
[0046] Dissolve 20 mg of the encapsulated substance in 10 mL of chloroform to obtain mixture 6, dissolve 20 mg of curcumin in 10 mL of methanol to obtain mixture 7, and mix mixture 6 and mixture 7 to obtain mixture 8; spin-dry mixture 8 and then immediately redissolve it with 10 mL of water to obtain the curcumin nanoparticles solution;
[0047] (3) Preparation of 3D bioprinting ink loaded with curcumin [[ID=I5]]
[0048] Mix 1 g of sodium alginate with 10 mL of the curcumin nanoparticles solution, and after mixing evenly, add 3 g of nanoclay and continue to stir until uniform to obtain mixture 9; mix 2 g of gelatin with 10 mL of the curcumin nanoparticles solution and heat to obtain mixture 10; mix mixture 9 and mixture 10 in the same volume to obtain the 3D bioprinting ink loaded with curcumin.
[0049] Example 3
[0050] A preparation method of 3D bioprinting ink loaded with curcumin specifically includes the following steps:
[0051] (1) Preparation of the encapsulated substance
[0052] Dissolve 500 mg of thioacetal (TK), 5 g of dicyclohexylcarbodiimide (DCC), and 300 mg of 4-dimethylaminopyridine (DMAP) in 200 mL of dimethyl sulfoxide (DMSO), and stir at 60 °C to obtain mixture 1; dissolve 4 g of poly(D,L-lactide-co-glycolide) (PLGA) in 40 mL of dimethyl sulfoxide (DMSO) to obtain mixture 2; mix mixture 1 and mixture 2, and protect with nitrogen, and react at 40 °C for 24 h to obtain mixture 3; dissolve 5 g of methoxypolyethylene glycol (mPEG) in 40 mL of dimethyl sulfoxide (DMSO) to obtain mixture 4; add mixture 4 to mixture 3, and protect with nitrogen, and react at 40 °C for 24 h to obtain mixture 5; dialyze the mixture in a dialysis bag with a molecular weight cut-off of 7 kDa for 5 days, and then lyophilize to obtain the encapsulated product;
[0053] (2) Preparation of curcumin nanoparticles solution
[0054] Dissolve 50 mg of the encapsulated product in 10 mL of chloroform to obtain mixture 6, dissolve 10 mg of curcumin in 10 mL of methanol to obtain mixture 7, and mix mixture 6 and mixture 7 to obtain mixture 8; spin-dry mixture 8 and then immediately redissolve it in 10 mL of water to obtain the curcumin nanoparticles solution;
[0055] (3) Preparation of 3D bioprinting ink loaded with curcumin
[0056] Mix 3 g of sodium alginate with 10 mL of the curcumin nanoparticles solution, and after mixing evenly, add 2.8 g of nanoclay and continue to stir until evenly mixed to obtain mixture 9; mix 3 g of gelatin with 10 mL of the curcumin nanoparticles solution and heat to obtain mixture 10; mix mixture 9 and mixture 10 in the same volume to obtain the 3D bioprinting ink loaded with curcumin.
[0057] Comparative example 1
[0058] A method for preparing 3D bioprinting ink without curcumin specifically includes the following steps:
[0059] Mix 3 g of sodium alginate with 10 mL of water, and after mixing evenly, add 2 g of nanoclay and continue to stir until evenly mixed to obtain mixture A; mix 3 g of gelatin with 10 mL of water and heat to obtain mixture B; mix mixture A and mixture B in the same volume to obtain the 3D bioprinting ink without curcumin.
[0060] Comparative example 2
[0061] A method for preparing 3D bioprinting ink without curcumin specifically includes the following steps:
[0062] Mix 3 g of sodium alginate with 10 mL of water. After mixing evenly, add 3 g of nanoclay and continue stirring until homogeneous to obtain mixture 9. Mix 3 g of gelatin with 10 mL of water and heat to obtain mixture 10. Mix mixture 9 and mixture 10 in the same volume to obtain 3D bioprinting ink without curcumin.
[0063] Comparative Example 3
[0064] A method for preparing 3D bioprinting ink without curcumin, specifically including the following steps:
[0065] Mix 5 g of sodium alginate with 10 mL of water. After mixing evenly, add 2.8 g of nanoclay and continue stirring until homogeneous to obtain mixture 9. Mix 5 g of gelatin with 10 mL of water and heat to obtain mixture 10. Mix mixture 9 and mixture 10 in the same volume to obtain 3D bioprinting ink without curcumin.
[0066] Performance test
[0067] 1. Viscosity curve test
[0068] Place the six 3D bioprinting ink samples prepared in Examples 1 - 3 and Comparative Examples 1 - 3 on a rheometer respectively. Use the PP50 sample stage, set the rotation mode, and test with a shear rate of 0.1% - 100%.
[0069] The viscosity curves of the six 3D bioprinting ink samples in Examples 1 - 3 and Comparative Examples 1 - 3 are as Figure 1 shown. As Figure 1 can be seen, the viscosity of all samples decreases as the shear rate increases. High shear rate and low shear rate correspond to extrusion and curing during the printing process respectively. This shear-thinning property indicates that these samples have printability.
[0070] 2. Printing test
[0071] Perform bioprinting on the six 3D bioprinting ink samples prepared in Examples 1 - 3 and Comparative Examples 1 - 3 respectively to obtain 3D scaffolds.
[0072] The physical pictures of the 3D scaffolds printed from the six 3D bioprinting ink samples in Examples 1 - 3 and Comparative Examples 1 - 3 are as Figure 2 shown. As Figure 2 can be seen, the color of the 3D scaffolds printed from the 3D bioprinting ink samples in Examples 1 - 3 after loading drugs will turn yellow.
[0073] 3. Drug release amount test
[0074] H2O2 was added to PBS / DMSO (v / v = 1:1) to make the H2O2 concentration 1.2 mM, and the corresponding pH was adjusted with HCl and NaOH. The scaffolds were added at a ratio of 0.1 mg scaffold / mL liquid as the experimental group (simulating ROS conditions), and at the same time, the scaffolds were added to PBS at the same ratio as the control group (no ROS conditions). They were placed in a dialysis bag with a molecular weight cut-off of 5 kDa and incubated in a shaker at 37 °C. At different time points, 1 mL was taken from the release solution and supplemented with 1 mL of fresh release medium. The release of each time point was detected by an ultraviolet spectrophotometer, and the sample release rate was calculated.
[0075] The 24-hour drug release amounts of the 3D scaffolds printed from the four 3D bioprinting ink samples of Examples 1-3 and Comparative Example 1 under different conditions are as Figure 3 shown. From Figure 3 it can be seen that the scaffolds of Examples 1-3 added with drug-loaded nanoparticles have obvious ROS-responsive characteristics and a high drug release rate under simulated ROS conditions. In Comparative Example 1, since no drug-loaded nanoparticles were added, it does not have drug release characteristics.
[0076] 4. Cell viability test
[0077] L929 cells were seeded in a 96-well culture plate at a density of 1×10 4 cells. The sample group was treated with the scaffold extract (prepared according to GB / T 16886.12-2017) for 24 h, and the control group was treated with complete medium for 24 h. Then, the supernatant was aspirated. 50 μL of MTT solution was added to each well and incubated in the incubator in the dark for 4 h. The MTT solution was aspirated, and 150 μL of DMSO was added to each well to dissolve the formazan. The absorbance of each well was measured at 570 nm. The cell viability was calculated by the following formula: Cell viability (%) = A 样品组 / A 对 control group.
[0078] The cytotoxicities of the 3D scaffolds printed from the six 3D bioprinting ink samples of Examples 1-3 and Comparative Examples 1-3 are as Figure 4 shown. From Figure 4 it can be seen that the survival rates of all samples are greater than that of the blank control group, indicating that all samples do not have cytotoxicity.
[0079] 5. TNF-α gene expression test
[0080] L929 cells were seeded at a density of 1×10 4Cells were seeded at a density of [number of cells] in a 96-well culture plate. The sample group was treated with the scaffold extract (prepared according to GB / T 16886.12-2017) for 24 h, and then 1.2 mM H2O2 was added to establish the model for 12 h; the control group was treated with complete medium for 36 h; the model group was treated with complete medium for 24 h and then 1.2 mM H2O2 was added to establish the model for 12 h. Subsequently, cell RNA was extracted from different groups to measure gene expression levels.
[0081] The anti-inflammatory properties of the 3D scaffolds printed from the six 3D bioprinting ink samples of Examples 1-3 and Comparative Examples 1-3 are as Figure 5 shown. From Figure 5 it can be seen that the gene expression of the cell inflammatory factor (TNF-α) after treatment with the drug-loaded samples of Examples 1-3 was less than that of the model group, indicating that such scaffolds have anti-inflammatory effects. In Comparative Examples 1-3, drug-loaded nanoparticles were not added, so the inflammatory gene expression was close to that of the model group.
[0082] 6. Wound healing test
[0083] All animal experimental protocols were reviewed and approved by the Laboratory Animal Ethics Committee of South China Agricultural University (approval number: 2024B067).
[0084] C57BL-6 mice aged 4-6 weeks were selected for the experiment. After one week of adaptive feeding, the mice were intraperitoneally injected with stz (150 mg / kg) to establish a type I diabetes model. If the blood glucose concentration remained above 16.7 mM for one week, the model was considered successful. The successfully modeled mice were anesthetized by intraperitoneal injection (1% sodium pentobarbital, 45 mg / kg), and the hair around the surgical site was shaved using an animal electric hair trimmer, and then the hair was removed using Veet hair removal cream. A circular wound model (diabetic skin defect model) with a diameter of 8 mM was made on the back of each mouse using scissors. Subsequently, the wounds were treated with 3D printed scaffolds (sample group) and PBS (control group) respectively. Finally, the treated wounds were wrapped with gauze to fix the dressing. The wounds were photographed and dressed on days 2, 4, 6, 9, 12, and 14 respectively.
[0085] Based on the 3R principle of animal experiments, representative Examples 1 and Comparative Example 1 were selected as samples for the wound healing test. The wound healing promotion properties of the 3D scaffolds printed from the two 3D bioprinting ink samples of Example 1 and Comparative Example 1 are as Figure 6 shown. From Figure 6 it can be seen that compared with the control sample, both the drug-loaded scaffold of Example 1 and the non-drug-loaded scaffold of Comparative Example 1 had a certain effect on promoting wound healing, but the drug-loaded scaffold of Example 1 had a better wound healing effect, and the wound had basically healed on day 14.
[0086] In summary, Examples 1-3 and Comparative Examples 1-3 of the present invention were selected to verify the printability of 3D bioprinting ink samples, as well as the ROS response characteristics, cytotoxicity, and anti-inflammatory characteristics of the printed 3D scaffolds. Example 1 and Comparative Example 1 were selected to verify the wound healing promotion characteristics of the 3D scaffolds obtained by printing 3D bioprinting ink samples.
[0087] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. A preparation method of curcumin-loaded 3D bioprinting ink, characterized in that, Specifically, it includes the following steps: (1) Preparation of the encapsulant Dissolve ketothiol, dicyclohexylcarbodiimide, and 4-dimethylaminopyridine in dimethyl sulfoxide to obtain mixture 1. Dissolve poly(D,L-lactide-co-glycolide) in dimethyl sulfoxide to obtain mixture 2. Mix mixture 1 and mixture 2 and react under nitrogen protection to obtain mixture 3. Dissolve methoxypolyethylene glycol in dimethyl sulfoxide to obtain mixture 4. Mix mixture 3 and mixture 4 and react under nitrogen protection to obtain mixture 5. Dialyze and lyophilize to obtain the encapsulant; (2) Preparation of the curcumin nanoparticles solution Dissolve the encapsulant in chloroform to obtain mixture 6. Dissolve curcumin in methanol to obtain mixture 7. Mix mixture 6 and mixture 7 to obtain mixture 8. Rotate to dryness and redissolve to obtain the curcumin nanoparticles solution; (3) Preparation of the curcumin-loaded 3D bioprinting ink Mix sodium alginate and the curcumin nanoparticles solution, and then add nanoclay and mix again to obtain mixture 9. Mix gelatin and the curcumin nanoparticles solution and heat to obtain mixture 10. Mix mixture 9 and mixture 10 to obtain the curcumin-loaded 3D bioprinting ink.
2. The preparation method of a curcumin-loaded 3D bioprinting ink according to claim 1, characterized in that, In step (1), in mixture 1, the molar ratio of ketothiol, dicyclohexylcarbodiimide, and 4-dimethylaminopyridine is (0.01 - 2):1:(0.01 - 1), and the dosage ratio of dicyclohexylcarbodiimide to dimethyl sulfoxide is (0.1 - 1) mmol:1 mL; in mixture 2, the dosage ratio of poly(D,L-lactide-co-glycolide) to dimethyl sulfoxide is (0.01 - 5) g:1 mL; in mixture 4, the dosage ratio of methoxypolyethylene glycol to dimethyl sulfoxide is (0.01 - 5) g:1 mL.
3. The preparation method of a curcumin-loaded 3D bioprinting ink according to claim 1, wherein, In step (1), the temperature of the reaction is 40 - 80 °C, and the time is 24 h.
4. The preparation method of a curcumin-loaded 3D bioprinting ink according to claim 1, wherein, In step (1), the molecular weight of the dialysis is 4 kDa - 10 kDa, and the time is 5 days.
5. The preparation method of a curcumin-loaded 3D bioprinting ink according to claim 1, wherein, In step (2), in mixture 6, the dosage ratio of the encapsulant to chloroform is (0.01 - 5) g:1 mL; in mixture 7, the dosage ratio of curcumin to methanol is (0.01 - 1) g:1 mL.
6. The preparation method of a curcumin-loaded 3D bioprinting ink according to claim 1, characterized in that, In step (2), in the curcumin nanoparticles solution, the concentration of curcumin is (0.01 - 80) μg / mL.
7. The preparation method of a curcumin-loaded 3D bioprinting ink according to claim 1, characterized in that, In step (3), in mixture 9, the dosage ratio of sodium alginate, nanoclay, and the curcumin nanoparticles solution is (0.01 - 1) g:(0.01 - 2) g:1 mL; in mixture 10, the dosage ratio of gelatin to the curcumin nanoparticles solution is (0.01 - 1) g:1 mL.
8. The preparation method of a curcumin-loaded 3D bioprinting ink according to claim 1, characterized in that, In step (3), in the curcumin-loaded 3D bioprinting ink, the volume ratio of mixture 9 to mixture 10 is 1:(0.01 - 10).
9. A curcumin-loaded 3D bioprinting ink prepared by the preparation method according to any one of claims 1 - 8.
10. Use of a curcumin-loaded 3D bioprinting ink prepared by the preparation method according to any one of claims 1 - 8 in the preparation of a drug-loaded medical device.