Hydrogel for improving photocuring 3D printing precision and application thereof

Abstract

The invention discloses hydrogel for improving photocuring 3D printing precision and application of the hydrogel. The invention discovers that pigments such as thioflavin T, alizarin yellow R, methylene blue and / or purple cabbage and the like are added into ink containing photo-crosslinking hydrogel such as methacrylated gelatin (GelMA) and the like as a photo-curing stabilizer, so that the photo-curing 3D printing precision can be improved. On the basis, the hydrogel ink capable of improving the photocuring 3D printing precision is provided, and the photocrosslinking hydrogel is mixed with the photoinitiator and the photocuring stabilizer in proportion, so that an entity obtained by printing through the hydrogel ink has higher precision. In addition, the hydrogel ink for 3D printing is easy to operate and high in practicability, and construction of repair materials needed in the biomedical field such as tissue engineering is facilitated.

Description

Technical Field

[0001] The present invention belongs to the technical field of additive manufacturing, and more specifically, relates to a hydrogel for improving the accuracy of photocuring 3D printing and its application. Background Art

[0002] Tissue / organ lesions and defects have always been a major problem that needs to be solved urgently in clinical medicine. Although traditional methods have alleviated the shortage of tissues / organs to a certain extent, they inevitably bring potential risks such as complications, secondary injuries and limited donor sources. In recent years, with the development of 3D printing technology, bio-3D printing has ushered in unprecedented vitality in the field of tissue engineering, because it can use hydrogels (extracellular matrix-like) or cell-laden bio-hydrogels to quickly manufacture personalized tissue engineering scaffolds, repair tissue defects in situ, and even directly print tissues / organs, which has the potential to solve the above problems.

[0003] Photocuring 3D printing technology is a printing technology that uses ultraviolet light or visible light to trigger a cross-linking reaction of photosensitive materials, thereby solidifying the hydrogel layer by layer to form a preset three-dimensional model. Tissue engineering is a discipline that uses the principles of life science and engineering to construct biological tissue substitutes for reconstruction and restoration of damaged tissue function. Photocuring 3D printing technology has currently shown broad application prospects in the field of tissue engineering, such as skin injury repair and regeneration, bone tissue regeneration, muscle injury repair, and organoid structure construction. Photocrosslinking hydrogel ink is an important factor in photocuring 3D printing, which is related to the printing accuracy and mechanical properties of the printed structure. The most common method for hydrogels to achieve photopolymerization ability is to modify specific side groups or end groups with compounds containing double bonds, such as acrylates, methacrylates, conjugated dienes, and tyrosine. Due to its extracellular matrix-like properties, hydrogels have excellent biocompatibility and biodegradability, and are ideal biological 3D printing ink materials. However, hydrogels often have problems with poor printing accuracy during photocuring 3D printing. During the photocuring printing process, light will scatter at the interface between the solid and liquid phases, causing the hydrogel to solidify in non-intended areas, resulting in poor printing accuracy. High-precision printing is very important for 3D printing, otherwise the printed tissues and organs will not match the original defective parts. Therefore, it is necessary to improve the accuracy of hydrogel photocuring 3D printing.

[0004] In response to the problem of poor precision of hydrogel photocuring 3D printing, some technicians have provided a new type of photoinhibitor: curcumin sodium (Curcumin-Na), whose absorption peak is located near 425 nm, which is very close to the wavelength of the light source. It can inhibit the scattering effect of light through the synergistic effect of light absorption and free radical reaction, and improve the precision of hydrogel photocuring 3D printing. However, actual experiments have found that the use of substances with absorption peaks near the wavelength of the light source does not necessarily improve the precision of hydrogel photocuring 3D printing. At the same time, Chinese patent CN114989455A is used for photocuring cell-carrying 3D printing composite hydrogels and their preparation methods and applications, as well as Chinese patent CN115386259A, a kind of anti-drying and antifreeze photosensitive hydrogel ink and its preparation method, high-precision photocuring hydrogel and its application, all use lemon yellow as a photocuring stabilizer, which can improve the printing precision of photocuring hydrogels. However, actual experiments have found that using lemon yellow as a photocuring stabilizer, the photocuring printing precision of different hydrogels is still defective. Therefore, for different hydrogels, how to improve their photocuring 3D printing precision and expand more light stabilizers and applications still needs to be explored by technicians. Summary of the invention

[0005] In view of the problem of poor precision of hydrogel photocuring 3D printing, the present invention provides a hydrogel for improving the precision of photocuring 3D printing and application thereof.

[0006] The first object of the present invention is to provide a hydrogel ink capable of improving the accuracy of photocurable 3D printing.

[0007] The second object of the present invention is to provide an application of the hydrogel ink in improving the accuracy of photocuring 3D printing.

[0008] The third object of the present invention is to provide a method for improving the accuracy of hydrogel photocuring 3D printing.

[0009] The above-mentioned purpose of the present invention is achieved through the following technical solutions: The present invention finds that by adding thioflavin T, alizarin yellow R, methylene blue and / or purple cabbage pigments as photocuring stabilizers to hydrogel ink containing photocrosslinked hydrogels such as methacryloyl gelatin (GelMA), the photocuring 3D printing accuracy of the hydrogel can be improved. Based on this, the present invention provides a hydrogel ink capable of improving the photocuring 3D printing accuracy, by mixing the photocrosslinked hydrogel with a photoinitiator and a photocuring stabilizer in proportion, the tissue / organ printed using the hydrogel ink has a higher accuracy.

[0010] The present invention provides a hydrogel ink capable of improving the precision of photocurable 3D printing. The hydrogel ink contains a photocrosslinked hydrogel, a photoinitiator and a photocurable stabilizer.

[0011] Specifically, the photo-crosslinked hydrogel is selected from one or more of GelMA, HAMA, AlgMA, SilMA, and PEGDA; the photoinitiator is selected from LAP and Irgacure 2959; and the photocuring stabilizer is selected from one or more of thioflavin T, alizarin yellow R, methylene blue, and purple cabbage.

[0012] More specifically, the photo-crosslinked hydrogel is selected from one or more of GelMA, HAMA, AlgMA, and PEGDA.

[0013] More specifically, the photoinitiator is selected from one or more of LAP and Irgacure 2959.

[0014] More specifically, the light curing stabilizer is selected from one or more of Thioflavin T and Alizarin Yellow R.

[0015] Specifically, the mass concentration of the photo-crosslinked hydrogel in the hydrogel ink is 0.05-0.15 g / mL.

[0016] Preferably, if the photo-cross-linked hydrogel is GelMA, the effect is relatively best when its mass concentration is 0.1 g / mL; if the photo-cross-linked hydrogel is HAMA, the effect is relatively best when its mass concentration is 0.05 g / mL; if the photo-cross-linked hydrogel is AlgMA, the effect is relatively best when its mass concentration is 0.1 g / mL; if the photo-cross-linked hydrogel is SilMA, the effect is relatively best when its mass concentration is 0.05 g / mL; if the photo-cross-linked hydrogel is PEGDA, the effect is relatively best when its mass concentration is 0.15 g / mL.

[0017] Specifically, the mass concentration of the photoinitiator in the hydrogel ink is 0.002-0.003 g / mL.

[0018] Preferably, the mass concentration of the photoinitiator in the hydrogel ink is 0.0025 g / mL.

[0019] Specifically, the mass concentration of the photocurable stabilizer in the hydrogel ink is 0.00025-0.00075 g / mL.

[0020] Preferably, the mass concentration of the photocurable stabilizer in the hydrogel ink is 0.0005 g / mL.

[0021] Preferably, the photo-crosslinked hydrogel in the hydrogel ink is GelMA or PEGDA; the photoinitiator is LAP; the photocuring stabilizer is thioflavin T, wherein the mass concentration of GelMA in the hydrogel ink is 0.1 g / mL, the mass concentration of PEGDA in the hydrogel ink is 0.15 g / mL, the mass concentration of LAP in the hydrogel ink is 0.0025 g / mL, and the mass concentration of thioflavin T in the hydrogel ink is 0.0005 g / mL.

[0022] Specifically, the solvent used to prepare the hydrogel ink in the present invention is PBS solution.

[0023] More specifically, the PBS solution is prepared by dissolving 8 g NaCl, 0.2 g KCl, 1.44 g Na2HPO4, and 0.24 g KH2PO4 in 800 mL deionized water, adjusting the pH to 7.4, and then diluting the volume to 1 L.

[0024] In view of the fact that the hydrogel ink of the present invention can improve the precision of photocuring 3D printing, the present invention also requests protection for the use of the hydrogel ink in improving the precision of photocuring 3D printing.

[0025] The present invention also provides a method for improving the accuracy of hydrogel photocuring 3D printing, that is, using the hydrogel ink of the present invention to perform photocuring 3D printing.

[0026] Specifically, the light source used in the hydrogel photocuring 3D printing process is ultraviolet light.

[0027] More specifically, the wavelength of the ultraviolet light is 405 nm.

[0028] The present invention has the following beneficial effects: The present invention finds that by adding thioflavin T, alizarin yellow R, methylene blue and / or purple cabbage pigments as photocuring stabilizers to hydrogel ink containing photocrosslinked hydrogels such as methacryloyl gelatin (GelMA), the photocuring 3D printing accuracy of the hydrogel can be improved. Based on this, the present invention provides a hydrogel ink capable of improving the photocuring 3D printing accuracy, by mixing the photocrosslinked hydrogel with a photoinitiator and a photocuring stabilizer in proportion, the tissue / organ printed using the hydrogel ink has a higher accuracy.

[0029] In addition, the 3D printing using the hydrogel ink is simple to operate and highly practical, and is conducive to the construction of repair materials required in biomedical fields such as tissue engineering. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.0005 g / mL tartrazine.

[0031] Figure 2 Structures with 250 μm pores and ear structures printed using PEGDA hydrogel containing 0.0005 g / mL tartrazine.

[0032] Figure 3 Structures with 250 μm pores and ear structures printed using HAMA hydrogel containing 0.0005 g / mL tartrazine.

[0033] Figure 4 The effect of different pigments on the photocuring effect of GelMA hydrogel.

[0034] Figure 5 Structures with 250 μm holes and ear structures printed using GelMA hydrogel without thioflavin T.

[0035] Figure 6 Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.0005 g / mL Thioflavin T.

[0036] Figure 7 Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.00025 g / mL Thioflavin T.

[0037] Figure 8 Structures with 250 μm pores and ear structures printed using 5% GelMA hydrogel containing 0.0005 g / mL Thioflavin T.

[0038] Fig. 9 Structures with 250 μm pores and ear structures printed using 15% GelMA hydrogel containing 0.0005 g / mL Thioflavin T.

[0039] Fig.10 Structures with 250 μm pores and ear structures printed using PEGDA hydrogel containing 0.0005 g / mL Thioflavin T.

[0040] Fig.11 Structures with 250 μm pores and ear structures printed using HAMA hydrogel containing 0.0005 g / mL thioflavin T.

[0041] Fig.12 Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R.

[0042] Fig.13 Structures with 250 μm holes and ear structures printed using GelMA hydrogel containing 0.00025 g / mL Alizarin Yellow R.

[0043] Fig.14 Structures with 250 μm pores and ear structures printed using PEGDA hydrogel containing 0.0005 g / mL Alizarin Yellow R.

[0044] Fig.15 Structures with 250 μm pores and ear structures printed using HAMA hydrogel containing 0.0005 g / mL Alizarin Yellow R.

[0045] Fig.16 Structures with 250 μm holes and ear structures printed using GelMA hydrogel containing 0.0005 g / mL methylene blue.

[0046] Fig.17 Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R and methylene blue.

[0047] Fig.18 Microneedles printed using GelMA and PEGDA hydrogels containing 0.0005 g / mL Thioflavin T. DETAILED DESCRIPTION

[0048] The present invention is further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0049] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0050] Effect of comparative lemon yellow on the photocuring printing accuracy of different hydrogels 1. The influence of the type of photo-crosslinked hydrogel on the photocuring printing accuracy of hydrogel when using lemon yellow This comparative example tests the effect of lemon yellow on the photocuring effect of GelMA hydrogel, PEGDA hydrogel, and HAMA hydrogel. The preparation method of the GelMA hydrogel is as follows: 1 g of GelMA is dissolved in 10 mL of PBS solution (mass concentration is 0.1 g / mL), 0.025 g of photoinitiator LAP (mass concentration is 0.0025 g / mL) is added, and 0.005 g of lemon yellow (mass concentration is 0.0005 g / mL) is added, and after 30 minutes of ultrasonic dispersion (100 W) at 50 ° C, it is filtered with a 0.22 μm filter membrane for use. The mass concentrations of PEGDA and HAMA in the PEGDA hydrogel and HAMA hydrogel are 0.15 g / mL and 0.05 g / mL, and the preparation method is consistent with that of the GelMA hydrogel.

[0051] The preparation method of the PBS solution is as follows: Dissolve 8 g NaCl, 0.2 g KCl, 1.44 g Na2HPO4, and 0.24 g KH2PO4 in 800 mL deionized water, adjust the pH to 7.4, and then make up to 1 L.

[0052] The conditions for the hydrogel photocuring 3D printing are as follows: the light intensity is set to 10 mW / cm 2 , the number of base layers is set to 2, the layer height is set to 150 μm, the base exposure time is set to 20 s, the exposure time is set to 18 s, and the printing temperature is set to 37 °C. The peeling setting parameters for each layer during the printing process are: peeling distance is set to 3 mm, peeling speed is set to 35 mm / min, peeling recovery speed is set to 150 mm / min, lifting height is set to 0 mm, and lifting speed is set to 100 mm / min.

[0053] The structure of 250 μm hole and ear structure printed by GelMA hydrogel containing 0.0005 g / mL lemon yellow are shown in Figure 2. Figure 1 The structure of 250 μm holes and ear structures printed using PEGDA hydrogel containing 0.0005 g / mL lemon yellow are shown in Figure 2. Figure 2 The structure of 250 μm holes and ear structures printed using HAMA hydrogel containing 0.0005 g / mL lemon yellow are shown in Figure 2. Figure 3As shown. By comparison, after adding lemon yellow, when the three photocurable hydrogels are used for 3D printing, the 250 μm hole structure printed by GelMA hydrogel has a small amount of diffuse crosslinking at the bottom, and the 250 μm hole structure printed by PEGDA hydrogel also has diffuse crosslinking with the bottom of the ear structure, and the printing accuracy is slightly lower. The 250 μm hole structure and the bottom of the ear structure printed by HAMA hydrogel have a large number of diffuse crosslinking, and the printing accuracy is the worst. The photosensitive group of the photocurable hydrogel used is acrylate, and the curing process is completed by free radical polymerization. The mechanism of photoinitiated polymerization curing by acrylate is: after the photoinitiator molecule absorbs light energy, it transitions to the excited state, and the weak bonds in the molecule undergo homolysis to produce active free radicals. These free radicals react with the carbon-carbon double bonds in the monomer, resulting in free radical propagation, initiating polymerization and crosslinking of the photosensitive material, and finally forming a large three-dimensional network structure. In addition, since the photo-crosslinking of the hydrogel ink is disordered and uncontrolled, adding an appropriate light-blocking agent can control the photo-crosslinking process, slow down the crosslinking speed and limit the crosslinking area, thereby improving the photocuring printing accuracy. The light source used in the hydrogel photocuring 3D printing process is ultraviolet light with a wavelength of 405 nm. The absorption peak of lemon yellow is around 430 nm, which is close to the wavelength of the light source used. It can suppress the scattering effect of light through light absorption, thereby improving the photocuring 3D printing accuracy of the hydrogel, but the effect of improving the printing accuracy is limited.

[0054] Example 1 Effects of different pigments on the photocuring effect of GelMA hydrogel This example tests the effect of different pigments on the photocuring effect of GelMA hydrogel. The preparation method of the GelMA hydrogel is as follows: 1 g of GelMA is dissolved in 10 mL of PBS solution (mass concentration is 0.1 g / mL), 0.025 g of photoinitiator LAP (mass concentration is 0.0025 g / mL), and 0.005 g of different pigments (thioflavin T, alizarin yellow R, methylene blue, purple cabbage) (mass concentration is 0.0005 g / mL) are added respectively, and after 30 minutes of ultrasonic dispersion at 50 ° C (100 W), it is filtered with a 0.22 μm filter membrane for use. The preparation method of the PBS refers to Comparative Example 1.

[0055] 500 μL of prepared GelMA hydrogels containing different pigments were taken and placed under a UV light source (405 nm) for curing for 30 s. After the photocuring, the effects of different pigments on the photocuring effect of GelMA hydrogel were observed. The results are as follows: Figure 4 As shown. Figure 4It can be seen that thioflavin T, alizarin yellow R, methylene blue and purple cabbage will not destroy the gel properties of the photocurable ink, indicating that the above pigments can be added as photocurable stabilizers to improve printing accuracy.

[0056] Example 2 Effects of Thioflavin T and its dosage on the photocuring printing accuracy of GelMA hydrogel 1. Effect of Thioflavin T on the Photocuring Printing Accuracy of GelMA Hydrogel Referring to the method described in Comparative Example 1, a GelMA hydrogel without thioflavin T was first prepared, and a GelMA hydrogel containing 0.0005 g / mL thioflavin T was also prepared. 1 g of GelMA was dissolved in 10 mL of PBS solution (mass concentration was 0.1 g / mL), 0.025 g of photoinitiator LAP (mass concentration was 0.0025 g / mL) was added, and 0 g or 0.005 g of thioflavin T (mass concentration was 0.0005 g / mL) was added, and after ultrasonic dispersion (100 W) at 50 °C for 30 min, it was filtered with a 0.22 μm filter membrane for later use.

[0057] The prepared GelMA hydrogel containing thioflavin T and the one without thioflavin T were used as inks, respectively, and the hydrogel photocuring 3D printing conditions were used for printing the same as those in Comparative Example 1. The structures of the 250 μm holes and the ear structures printed using the GelMA hydrogel without thioflavin T are shown in FIG. Figure 5 The results of the effect of 0.0005 g / mL thioflavin T on the photocuring printing accuracy of GelMA hydrogel are shown in Figure 6 As shown. Figure 5 and Figure 6 It can be seen that after adding Thioflavin T, the accuracy of the printed 250 μm hole structure and ear structure has been significantly improved.

[0058] 2. Effect of Thioflavin T dosage on the photocuring printing accuracy of GelMA hydrogel Referring to the method described in Comparative Example 1, GelMA hydrogels containing 0.00025 g / mL and 0.0005 g / mL thioflavin T were prepared respectively, and the same hydrogel photocuring 3D printing conditions as above were used for printing. The structures of 250 μm holes and ear structures printed using GelMA hydrogels containing 0.00025 g / mL thioflavin T are shown in FIG. Figure 7 As shown. Figure 6 and Figure 7 It can be seen that if the amount of thioflavin T added is insufficient, it will not be able to significantly improve the accuracy of hydrogel photocuring 3D printing.

[0059] 3. Effect of GelMA content on the photocuring printing accuracy of GelMA hydrogel Referring to the method described in Comparative Example 1, GelMA hydrogels with mass concentrations of 0.05 g / mL, 0.1 g / mL and 0.15 g / mL were prepared respectively, and the same hydrogel photocuring 3D printing conditions as in Comparative Example 1 were used for printing. The GelMA hydrogels all contained 0.0005 g / mL Thioflavin T. The structures of 250 μm holes and ear structures printed using 0.05 g / mL GelMA hydrogels containing 0.0005 g / mL Thioflavin T are shown in FIG. Figure 8 The structure of 250 μm holes and ear structures printed using 0.15 g / mL GelMA hydrogel containing 0.0005 g / mL thioflavin T are shown in Figure 2. Fig. 9 As shown. By comparison, the structure printed by 0.05 g / mL GelMA hydrogel showed obvious diffusion cross-linking and poor printing accuracy, while the printing accuracy of 0.1 g / mL and 0.15 g / mL GelMA hydrogels was significantly improved. Therefore, if the GelMA content is insufficient, the printing accuracy will be significantly reduced. In addition, there is not much difference in the printing accuracy between 0.1 g / mL and 0.15 g / mL GelMA.

[0060] 4. Effect of the type of photocrosslinked hydrogel on the photocuring printing accuracy of hydrogels when using Thioflavin T Referring to the method described in Comparative Example 1, GelMA hydrogel, PEGDA hydrogel and HAMA hydrogel containing 0.0005 g / mL thioflavin T were prepared respectively, and the same hydrogel light-curing 3D printing conditions as in Comparative Example 1 were used for printing. The mass concentrations of GelMA, PEGDA and HAMA in the GelMA hydrogel, PEGDA hydrogel and HAMA hydrogel used were 0.1 g / mL, 0.15 g / mL and 0.05 g / mL. The structures of 250 μm holes and ear structures printed using GelMA hydrogel containing 0.0005 g / mL thioflavin T are shown in FIG. Figure 6 The structure of the 250 μm hole and the ear structure printed using PEGDA hydrogel containing 0.0005 g / mL thioflavin T are shown in Figure 2. Fig.10 The structure of the 250 μm hole and ear structure printed using HAMA hydrogel containing 0.0005 g / mL thioflavin T are shown in Figure 2. Fig.11 As shown. Figure 6 , Fig.10 and Fig.11 It can be seen that the 250 μm hole structure and the bottom of the ear structure printed using HAMA hydrogel are partially diffused and cross-linked, and the printing accuracy is significantly lower than that of GelMA hydrogel and PEGDA hydrogel. Figure 2 and Fig.10 , Figure 3 and Fig.11It can be seen that after adding lemon yellow, there are a small amount of diffuse cross-linked areas at the bottom of the 250 μm hole structure printed by GelMA hydrogel, there are diffuse cross-linked areas at the bottom of the 250 μm hole structure and ear structure printed by PEGDA hydrogel, and there are a large number of diffuse cross-linked areas at the bottom of the 250 μm hole structure and ear structure printed by HAMA hydrogel. However, there are no diffuse cross-linked areas in the 250 μm hole structure and ear structure printed by GelMA hydrogel and PEGDA hydrogel with thioflavin T, and there is no diffuse cross-linking phenomenon in the ear structure printed by HAMA hydrogel, and the printing accuracy is significantly improved. The reason is that the absorption peak of thioflavin T is around 410nm, which is very close to the wavelength of the light source used (405 nm). In addition, it is a cationic dye that can bind to free radicals generated by light initiation and inhibit the propagation of free radicals. Therefore, thioflavin T can inhibit the scattering effect of light through the synergistic effect of light absorption and free radical reaction, and improve the accuracy of hydrogel light-curing 3D printing. In addition, water-soluble azo food pigments such as sunset yellow, carmine, and amaranth have antioxidant activity, which can neutralize the free radicals generated by light during the photocuring process and improve the accuracy of hydrogel photocuring 3D printing.

[0061] Example 3 Effect of Alizarin Yellow R on the Photocuring Printing Accuracy of GelMA Hydrogel 1. Effect of Alizarin Yellow R on the Photocuring Printing Accuracy of GelMA Hydrogel Referring to the method described in Comparative Example 1, a GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R was prepared, and the same hydrogel photocuring 3D printing conditions as in Comparative Example 1 were used for printing. The structure of the 250 μm hole and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown in FIG. Fig.12 As shown. Figure 5 and Fig.12 It can be seen that after adding Alizarin Yellow R, the accuracy of the printed 250 μm hole structure and ear structure has been significantly improved, but when printing the structure with 250 μm holes, there will be a small amount of diffuse cross-linking at the bottom. Alizarin Yellow R is an azo compound that can react with free radicals to form relatively stable spin adducts, which to a certain extent inhibits the propagation of free radicals generated by light initiation, slows down the cross-linking speed of hydrogels and limits the cross-linking area, improving the accuracy of photocuring printing.

[0062] 2. Effect of Alizarin Yellow R dosage on the photocuring printing accuracy of GelMA hydrogel Referring to the method described in Comparative Example 1, GelMA hydrogels containing 0.0005 g / mL Alizarin Yellow R and 0.00025 g / mL Alizarin Yellow R were prepared respectively, and the same hydrogel light-curing 3D printing conditions as in Comparative Example 1 were used for printing. The 250 μm hole structure and ear structure printed using the GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown in FIG. Fig.12 The structure of 250 μm holes and ear structures printed using GelMA hydrogel containing 0.00025 g / mL Alizarin Yellow R are shown in Figure 2. Fig.13 As shown. Fig.12 and Fig.13 It can be seen that if the amount of Alizarin Yellow R added is not enough, the printing accuracy of hydrogel photocuring cannot be significantly improved.

[0063] 3. Effect of photocrosslinked hydrogel types on the photocuring printing accuracy of hydrogels when using Alizarin Yellow R Referring to the method described in Comparative Example 1, GelMA hydrogel, PEGDA hydrogel and HAMA hydrogel containing 0.0005 g / mL Alizarin Yellow R were prepared respectively, and the same hydrogel photocuring 3D printing conditions as in Comparative Example 1 were used for printing. The mass concentrations of GelMA, PEGDA and HAMA in the GelMA hydrogel, PEGDA hydrogel and HAMA hydrogel used were 0.1 g / mL, 0.15 g / mL and 0.05 g / mL. The structures of 250 μm holes and ear structures printed using GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown in FIG. Fig.12 The structure of 250 μm holes and ear structures printed using PEGDA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown in Figure 2. Fig.14 The structure of 250 μm holes and ear structures printed using HAMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown in Figure 2. Fig.15 As shown in the figure, when using Alizarin Yellow R as a light-curing stabilizer, there is no significant difference in the printing accuracy of different types of photo-cross-linked hydrogels.

[0064] Example 4 Effect of methylene blue on the photocuring printing accuracy of GelMA hydrogel 1. Effect of methylene blue on the photocuring printing accuracy of GelMA hydrogel Referring to the method described in Comparative Example 1, a GelMA hydrogel containing 0.0005 g / mL methylene blue was prepared, and the same hydrogel photocuring 3D printing conditions as in Comparative Example 1 were used for printing. The structure of the 250 μm hole and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL methylene blue are shown in FIG. Fig.16 As shown. Figure 5 and Fig.16It can be seen that after adding methylene blue, the printing accuracy has been improved to a certain extent, but a large number of diffuse cross-linked areas appear in the printed structures with 250 μm holes and the ear structure.

[0065] Example 5 Effects of Alizarin Yellow R and Methylene Blue on the Photocuring Printing Accuracy of GelMA Hydrogel 1. Effects of Alizarin Yellow R and Methylene Blue on the Photocuring Printing Accuracy of GelMA Hydrogel Referring to the method described in Comparative Example 1, a GelMA hydrogel containing 0.0005 g / mL of Alizarin Yellow R and methylene blue (Alizarin Yellow R and methylene blue were mixed in a mass ratio of 1:1 and then added) was prepared, and the same hydrogel light-curing 3D printing conditions as in Comparative Example 1 were used for printing. The structure of the 250 μm hole and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL of Alizarin Yellow R and methylene blue are shown in FIG. Fig.17 As shown. Fig.12 , Fig.16 and Fig.17 It can be seen that after adding methylene blue, the printing accuracy of the structure with 250 μm holes and the ear structure is significantly improved. That is, the present invention mixes Alizarin Yellow R and methylene blue in a mass ratio of 1:1 to prepare GelMA hydrogel and finds that although the improvement effect of Alizarin Yellow R / methylene blue alone on printing accuracy is limited, after combining them, the improvement effect on printing accuracy is better than using Alizarin Yellow R / methylene blue alone.

[0066] Example 6 Effect of Thioflavin T on the Photocuring Printing Accuracy of GelMA and PEGDA Hydrogels 1. Effect of Thioflavin T on the Photocuring Printing Accuracy of GelMA and PEGDA Hydrogels Referring to the method described in Comparative Example 1, GelMA and PEGDA hydrogels containing 0.0005 g / mL thioflavin T (volume ratio 3:1) were prepared as follows: 0.1 g / mL GelMA and 0.15 g / mL PEGDA without thioflavin T were prepared separately, then mixed at a volume ratio of 3:1, and finally thioflavin T with a mass concentration of 0.0005 g / mL was added and ultrasonically mixed. The same hydrogel photocuring 3D printing conditions as in Comparative Example 1 were used for printing. Microneedles printed using GelMA and PEGDA hydrogels containing 0.0005 g / mL thioflavin T are shown in FIG. Fig.18 As shown. Fig.18 It can be seen that the hydrogel can be used to print microneedles with a gap of 100 μm, a bottom of 150 μm, a top of 5 μm, and a height of 350 μm with high precision.

[0067] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A hydrogel ink for improving the accuracy of photocuring 3D printing, characterized in that: The hydrogel ink contains a photo-crosslinked hydrogel, a photoinitiator and a photocuring stabilizer; the photo-crosslinked hydrogel is selected from one or more of methacrylated gelatin GelMA, methacrylated hyaluronic acid HAMA, methacrylated sodium alginate AlgMA, methacrylated silk protein SilMA, and polyethylene glycol diacrylate PEGDA; the photoinitiator is selected from one or more of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate LAP and 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone Irgacure 2959; the photocuring stabilizer is selected from one or more of thioflavin T, alizarin yellow R, methylene blue, and purple cabbage.

2. The hydrogel ink according to claim 1, characterized in that: The mass concentration of the photo-crosslinked hydrogel in the hydrogel ink is 0.05-0.15 g / mL.

3. The hydrogel ink according to claim 1, characterized in that: The mass concentration of the photoinitiator in the hydrogel ink is 0.002-0.003 g / mL.

4. The hydrogel ink according to claim 1, characterized in that: The mass concentration of the photocurable stabilizer in the hydrogel ink is 0.00025-0.00075 g / mL.

5. The hydrogel ink according to claim 1, characterized in that: The photo-crosslinked hydrogel is selected from GelMA or PEGDA; the photoinitiator is selected from LAP; the photocuring stabilizer is selected from thioflavin T, wherein the mass concentration of GelMA in the hydrogel ink is 0.1 g / mL, the mass concentration of PEGDA in the hydrogel ink is 0.15 g / mL, the mass concentration of LAP in the hydrogel ink is 0.0025 g / mL, and the mass concentration of thioflavin T in the hydrogel ink is 0.0005 g / mL.

6. The hydrogel ink according to claim 1, characterized in that: The solvent used for the hydrogel ink is PBS solution.

7. The use of the hydrogel ink according to claim 1 in improving the accuracy of photocuring 3D printing, characterized in that: The hydrogel ink is subjected to photocuring 3D printing, and the light source used for photocuring is ultraviolet light.

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