Hydrogel for improving precision of photocuring 3D printing and application thereof

Abstract

The application discloses a hydrogel for improving the precision of photocuring 3D printing and application thereof. The application finds that the precision of photocuring 3D printing can be improved by adding a pigment such as thioflavin T, alizarin yellow R, methylene blue and / or purple cabbage into an ink containing a photo-crosslinking hydrogel such as methacrylated gelatin (GelMA) as a photocuring stabilizer. Based on this, the application provides a hydrogel ink capable of improving the precision of photocuring 3D printing, and by mixing the photo-crosslinking hydrogel with a photo initiator and a photocuring stabilizer in proportion, the entity obtained by printing using the hydrogel ink has higher precision. In addition, the operation of 3D printing using the hydrogel ink is simple, has strong practicability, and is beneficial to the construction of repair materials required in the biomedical field such as tissue engineering.

Description

Technical Field

[0001] This invention belongs to the field of additive manufacturing technology. More specifically, it relates to a hydrogel for improving the accuracy of photopolymer 3D printing and its applications. Background Technology

[0002] Tissue / organ lesions and defects have always been major challenges urgently needing solutions in clinical medicine. While traditional methods have alleviated the shortage of tissues / organs to some extent, they inevitably bring potential risks such as complications, secondary damage, 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, as it can rapidly manufacture personalized tissue engineering scaffolds using hydrogels (extracellular matrix-like materials) or cell-borne bio-hydrogels, repair tissue defects in situ, and even directly print tissues / organs, showing the potential to solve the aforementioned problems.

[0003] Photopolymerization 3D printing technology utilizes ultraviolet or visible light to trigger a cross-linking reaction in photosensitive materials, thereby solidifying hydrogels layer by layer to form a pre-defined three-dimensional model. Tissue engineering is a discipline that applies principles of life sciences and engineering to construct biological tissue substitutes for the reconstruction and restoration of damaged tissue function. Photopolymerization 3D printing technology has shown broad application prospects in the field of tissue engineering, such as skin damage repair and regeneration, bone tissue regeneration, muscle damage repair, and organoid structure construction. Photocrosslinked hydrogel ink is a crucial factor in photopolymerization 3D printing, affecting the printing accuracy and mechanical properties of the resulting structure. The most common method to achieve photopolymerization capability in hydrogels 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 possess excellent biocompatibility and biodegradability, making them ideal bio-3D printing ink materials. However, hydrogels often exhibit poor printing accuracy in photopolymerization 3D printing. During photopolymerization printing, light scattering occurs at the solid-liquid interface, causing the hydrogel to solidify in unintended areas, resulting in poor printing accuracy. High-precision printing is crucial for 3D printing; otherwise, the printed tissues and organs will not match the original defects. Therefore, it is necessary to improve the accuracy of hydrogel photopolymerization 3D printing.

[0004] To address the issue of poor precision in hydrogel photopolymerization 3D printing, researchers have proposed a novel photoinhibitor: sodium curcumin (Curcumin-Na). Its absorption peak is located near 425 nm, very close to the light source wavelength. It can suppress light scattering through the synergistic effect of light absorption and free radical reactions, thereby improving the precision of hydrogel photopolymerization 3D printing. However, actual experiments have shown that using substances with absorption peaks near the light source wavelength does not necessarily improve the precision of hydrogel photopolymerization 3D printing. Meanwhile, Chinese patents CN114989455A (for photopolymerization of cell-borne 3D printing composite hydrogels and its preparation method and application) and CN115386259A (a desiccation-resistant and freeze-resistant photosensitive hydrogel ink and its preparation method and high-precision photopolymerization hydrogel and its application) both use lemon yellow as a photopolymerization stabilizer, which can improve the printing precision of photopolymerization hydrogels. However, actual experiments have found that even with lemon yellow as a photopolymerization stabilizer, the printing precision of different hydrogels still has shortcomings. Therefore, for different hydrogels, how to improve their photopolymerization 3D printing precision and expand the use of more photostabilizers and applications still requires further investigation by researchers. Summary of the Invention

[0005] This invention addresses the problem of poor precision in photopolymer 3D printing of hydrogels by providing a hydrogel that improves the precision of photopolymer 3D printing and its applications.

[0006] The first objective of this invention is to provide a hydrogel ink that can improve the accuracy of photopolymer 3D printing.

[0007] A second objective of this invention is to provide the application of the hydrogel ink in improving the accuracy of photopolymer 3D printing.

[0008] The third objective of this invention is to provide a method for improving the accuracy of hydrogel photopolymerization 3D printing.

[0009] The above-mentioned objective of this invention is achieved through the following technical solution:

[0010] This invention discovers that adding pigments such as thioflavone T, alizarin yellow R, methylene blue, and / or purple cabbage as photocuring stabilizers to hydrogel inks containing photocrosslinked hydrogels such as methacrylamide gelatin (GelMA) can improve the precision of hydrogel photocuring 3D printing. Based on this, this invention provides a hydrogel ink that can improve the precision of photocuring 3D printing. By mixing the photocrosslinked hydrogel with a photoinitiator and a photocuring stabilizer in a specific ratio, the tissues / organs printed using this hydrogel ink exhibit higher precision.

[0011] This invention provides a hydrogel ink that can improve the accuracy of photocurable 3D printing, wherein the hydrogel ink contains photocrosslinking hydrogel, photoinitiator and photocuring stabilizer.

[0012] Specifically, the photocrosslinking 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 thioflavone T, alizarin yellow R, methylene blue, and purple cabbage.

[0013] More specifically, the photocrosslinked hydrogel is selected from one or more of GelMA, HAMA, AlgMA, and PEGDA.

[0014] More specifically, the photoinitiator is selected from one or more of LAP and Irgacure 2959.

[0015] More specifically, the photocuring stabilizer is selected from one or more of thioflavin T and alizarin yellow R.

[0016] Specifically, the mass concentration of the photocrosslinked hydrogel in the hydrogel ink is 0.05~0.15 g / mL.

[0017] Preferably, if the photocrosslinking hydrogel is GelMA, its effect is relatively best when its mass concentration is 0.1 g / mL; if the photocrosslinking hydrogel is HAMA, its effect is relatively best when its mass concentration is 0.05 g / mL; if the photocrosslinking hydrogel is AlgMA, its effect is relatively best when its mass concentration is 0.1 g / mL; if the photocrosslinking hydrogel is SilMA, its effect is relatively best when its mass concentration is 0.05 g / mL; and if the photocrosslinking hydrogel is PEGDA, its effect is relatively best when its mass concentration is 0.15 g / mL.

[0018] Specifically, the photoinitiator has a mass concentration of 0.002~0.003 g / mL in the hydrogel ink.

[0019] Preferably, the photoinitiator has a mass concentration of 0.0025 g / mL in the hydrogel ink.

[0020] Specifically, the mass concentration of the photocurable stabilizer in the hydrogel ink is 0.00025~0.00075 g / mL.

[0021] Preferably, the mass concentration of the photocurable stabilizer in the hydrogel ink is 0.0005 g / mL.

[0022] Preferably, the photocrosslinking hydrogel in the hydrogel ink is GelMA or PEGDA; the photoinitiator is preferably LAP; and the photocuring stabilizer is preferably thioflavone 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 thioflavone T in the hydrogel ink is 0.0005 g / mL.

[0023] Specifically, the solvent used in the preparation of the hydrogel ink in this invention is a PBS solution.

[0024] 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 of deionized water, adjusting the pH to 7.4, and then bringing the volume to 1 L.

[0025] Given that the hydrogel ink described in this invention can improve the accuracy of photopolymer 3D printing, this invention also claims protection for the application of the hydrogel ink in improving the accuracy of photopolymer 3D printing.

[0026] The present invention also provides a method for improving the accuracy of hydrogel photopolymerization 3D printing, namely, using the hydrogel ink described in the present invention for photopolymerization 3D printing.

[0027] Specifically, the light source used in the hydrogel photopolymerization 3D printing process is ultraviolet light.

[0028] More specifically, the wavelength of the ultraviolet light is 405 nm.

[0029] The present invention has the following beneficial effects:

[0030] This invention discovers that adding pigments such as thioflavone T, alizarin yellow R, methylene blue, and / or purple cabbage as photocuring stabilizers to hydrogel inks containing photocrosslinked hydrogels such as methacrylamide gelatin (GelMA) can improve the precision of hydrogel photocuring 3D printing. Based on this, this invention provides a hydrogel ink that can improve the precision of photocuring 3D printing. By mixing the photocrosslinked hydrogel with a photoinitiator and a photocuring stabilizer in a specific ratio, the tissues / organs printed using this hydrogel ink exhibit higher precision.

[0031] Furthermore, the hydrogel ink used for 3D printing is simple to operate, highly practical, and beneficial for the construction of repair materials required in biomedical fields such as tissue engineering. Attached Figure Description

[0032] Figure 1To illustrate the structure and ear structure printed using GelMA hydrogel containing 0.0005 g / mL lemon yellow with 250 μm pores.

[0033] Figure 2 To illustrate the 250 μm pore structure and ear structure printed using PEGDA hydrogel containing 0.0005 g / mL lemon yellow.

[0034] Figure 3 To illustrate the structure and ear structure printed using HAMA hydrogel containing 0.0005 g / mL lemon yellow with 250 μm pores.

[0035] Figure 4 The effect of different pigments on the photocuring effect of GelMA hydrogel.

[0036] Figure 5 Structures with 250 μm pores and ear structures printed using thioflavone T-free GelMA hydrogel.

[0037] Figure 6 To illustrate the structure with 250 μm pores and the ear structure printed using GelMA hydrogel containing 0.0005 g / mL thioflavone T.

[0038] Figure 7 To illustrate the structure with 250 μm pores and the ear structure printed using GelMA hydrogel containing 0.00025 g / mL thioflavone T.

[0039] Figure 8 To illustrate the structure with 250 μm pores and the ear structure printed using 5% GelMA hydrogel containing 0.0005 g / mL thioflavone T.

[0040] Figure 9 To illustrate the structure of a 250 μm pore and an ear structure printed using 15% GelMA hydrogel containing 0.0005 g / mL thioflavone T.

[0041] Figure 10 To illustrate the 250 μm pore structure and ear structure printed using PEGDA hydrogel containing 0.0005 g / mL thioflavone T.

[0042] Figure 11 To illustrate the 250 μm pore structure and ear structure printed using HAMA hydrogel containing 0.0005 g / mL thioflavone T.

[0043] Figure 12 To demonstrate the 250 μm pore structure and ear structure printed using GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R.

[0044] Figure 13 To demonstrate the 250 μm pore structure and ear structure printed using GelMA hydrogel containing 0.00025 g / mL Alizarin Yellow R.

[0045] Figure 14 To illustrate the 250 μm pore structure and ear structure printed using PEGDA hydrogel containing 0.0005 g / mL Alizarin Yellow R.

[0046] Figure 15 To illustrate the 250 μm pore structure and ear structure printed using HAMA hydrogel containing 0.0005 g / mL Alizarin Yellow R.

[0047] Figure 16 Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.0005 g / mL methylene blue.

[0048] Figure 17 To demonstrate the 250 μm pore structure and ear structure printed using GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R and Methylene Blue.

[0049] Figure 18 Microneedles were printed using GelMA and PEGDA hydrogels containing 0.0005 g / mL thioflavone T. Detailed Implementation

[0050] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0051] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0052] The effect of lemon yellow on the printing precision of different hydrogel photocuring methods

[0053] 1. The effect of the type of photocrosslinking hydrogel on the printing accuracy of hydrogel photocuring when using lemon yellow.

[0054] This comparative study investigated the effect of tartrazine on the photocuring properties of GelMA hydrogel, PEGDA hydrogel, and HAMA hydrogel. The GelMA hydrogel was prepared as follows: 1 g of GelMA was dissolved in 10 mL of PBS solution (0.1 g / mL), 0.025 g of photoinitiator LAP (0.0025 g / mL) was added, and 0.005 g of tartrazine (0.0005 g / mL) was added. The mixture was then ultrasonically dispersed at 50 °C (100 W) for 30 min, and filtered through a 0.22 μm filter membrane. The PEGDA and HAMA hydrogels had PEGDA and HAMA concentrations of 0.15 g / mL and 0.05 g / mL, respectively, and were prepared using the same method as the GelMA hydrogel.

[0055] The PBS solution is prepared as follows:

[0056] Dissolve 8 g NaCl, 0.2 g KCl, 1.44 g Na2HPO4, and 0.24 g KH2PO4 in 800 mL of deionized water, adjust the pH to 7.4, and then bring the volume to 1 L.

[0057] The photopolymerization 3D printing conditions for the hydrogel were: light intensity set to 10 mW / cm². 2 The number of base layers was set to 2, the layer height to 150 μm, the base layer exposure time to 20 s, the exposure time to 18 s, and the printing temperature to 37 ℃. The peeling parameters for each layer during printing were: peeling distance to 3 mm, peeling speed to 35 mm / min, peel recovery speed to 150 mm / min, lift height to 0 mm, and lift speed to 100 mm / min.

[0058] Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.0005 g / mL lemon yellow, as shown in the figure. Figure 1 As shown. Structures with 250 μm pores and ear structures printed using PEGDA hydrogel containing 0.0005 g / mL lemon yellow are shown below. Figure 2 As shown. Structures with 250 μm pores and ear structures printed using HAMA hydrogel containing 0.0005 g / mL lemon yellow are shown. Figure 3As shown in the figure. A comparison reveals that after adding lemon yellow, when using these three photocurable hydrogels for 3D printing, the structure with 250 μm pores printed using GelMA hydrogel showed a small amount of diffusion cross-linking at the bottom. The structure with 250 μm pores printed using PEGDA hydrogel also showed diffusion cross-linking at the bottom of the ear structure, resulting in slightly lower printing accuracy. The structure with 250 μm pores printed using HAMA hydrogel showed a large amount of diffusion cross-linking at both the bottom of the ear structure, resulting in the worst printing accuracy. The photosensitive group of the photocurable hydrogel used is acrylate, and the curing process is completed through free radical polymerization. The mechanism of photo-initiated polymerization curing of acrylate is as follows: after the photoinitiator molecule absorbs light energy, it transitions to an excited state, and the weak bonds in the molecule undergo homolytic cleavage, generating active free radicals. These free radicals react with the carbon-carbon double bonds in the monomer, leading to free radical propagation, initiating the polymerization and cross-linking of the photosensitive material, and ultimately forming a large three-dimensional network structure. Furthermore, since the photocrosslinking of hydrogel inks is disordered and uncontrolled, adding appropriate light-blocking agents can control the photocrosslinking process, slowing down the crosslinking rate and limiting the crosslinking area, thereby improving the precision of photopolymerization printing. The light source used in the hydrogel photopolymerization 3D printing process is ultraviolet light with a wavelength of 405 nm. Lemon yellow has an absorption peak around 430 nm, which is close to the wavelength of the light source used. It can suppress light scattering through light absorption, thus improving the precision of hydrogel photopolymerization 3D printing, but the improvement in printing precision is limited.

[0059] Example 1: Effect of different pigments on the photocuring effect of GelMA hydrogel

[0060] This embodiment tested 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 was dissolved in 10 mL of PBS solution (mass concentration of 0.1 g / mL), 0.025 g of photoinitiator LAP (mass concentration of 0.0025 g / mL) was added, and 0.005 g of different pigments (thioflavone T, alizarin yellow R, methylene blue, and purple cabbage) (mass concentration of 0.0005 g / mL) were added respectively. After ultrasonic dispersion at 50 °C (100 W) for 30 min, the mixture was filtered through a 0.22 μm filter membrane for later use. The preparation method of the PBS is the same as that of Comparative Example 1.

[0061] 500 μL of each prepared GelMA hydrogel containing different pigments was placed under ultraviolet light (405 nm) for 30 s for curing. After curing, the effect of different pigments on the curing effect of the GelMA hydrogel was observed, and the results are as follows. Figure 4 As shown. By Figure 4It is known that thioflavone T, alizarin yellow R, methylene blue, and purple cabbage do not damage the gel properties of photocurable inks, indicating that the above pigments can be used as photocurable stabilizers to improve printing accuracy.

[0062] Example 2: Effect of thioflavone T and its dosage on the printing accuracy of GelMA hydrogel photopolymerization

[0063] 1. The effect of thioflavone T on the printing accuracy of GelMA hydrogel photopolymerization

[0064] Following the method described in Comparative Example 1, a GelMA hydrogel without thioflavone T was first prepared, and a GelMA hydrogel containing 0.0005 g / mL thioflavone T was also prepared. 1 g of GelMA was dissolved in 10 mL of PBS solution (0.1 g / mL), 0.025 g of photoinitiator LAP (0.0025 g / mL) was added, and 0 g or 0.005 g of thioflavone T (0.0005 g / mL) was added. After ultrasonic dispersion at 50 °C (100 W) for 30 min, the mixture was filtered through a 0.22 μm filter membrane for later use.

[0065] Using prepared GelMA hydrogels containing and without thioflavone T as inks, printing was performed under the same hydrogel photopolymerization 3D printing conditions as Comparative Example 1. The structures with 250 μm pores and ear structures printed using the thioflavone T-free GelMA hydrogel are shown below. Figure 5 As shown. The effect of 0.0005 g / mL thioflavone T on the printing accuracy of GelMA hydrogel photopolymerization is as follows. Figure 6 As shown. Comparison Figure 5 and Figure 6 It can be seen that the addition of thioflavone T significantly improved the precision of the printed 250 μm pore structure and ear structure.

[0066] 2. Effect of Thioflavin T Dosage on Printing Accuracy of GelMA Hydrogel Photocuring

[0067] Following the method described in Comparative Example 1, GelMA hydrogels containing 0.00025 g / mL and 0.0005 g / mL thioflavone T were prepared respectively, and printing was performed under the same hydrogel photopolymerization 3D printing conditions as described above. Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.00025 g / mL thioflavone T are shown below. Figure 7 As shown. Comparison Figure 6 and Figure 7 It is known that if the amount of thioflavone T added is insufficient, it cannot significantly improve the accuracy of hydrogel photopolymerization 3D printing.

[0068] 3. Effect of GelMA content on the printing accuracy of GelMA hydrogel photopolymerization

[0069] Following 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, and printing was performed under the same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1. Each GelMA hydrogel contained 0.0005 g / mL thioflavone T. Structures with 250 μm pores and ear structures printed using 0.05 g / mL GelMA hydrogel containing 0.0005 g / mL thioflavone T are shown below. Figure 8 As shown. The structure with 250 μm pores and the ear structure printed using 0.15 g / mL LGelMA hydrogel containing 0.0005 g / mL thioflavone T are shown in the figure. Figure 9 As shown in the figure, the comparison revealed that the structure printed with 0.05 g / mL GelMA hydrogel exhibited significant 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, insufficient GelMA content will significantly reduce printing accuracy. Furthermore, there was no significant difference in printing accuracy between 0.1 g / mL and 0.15 g / mL GelMA.

[0070] 4. The effect of the type of photocrosslinking hydrogel on the printing accuracy of hydrogel photocuring when using thioflavone T.

[0071] Following the method described in Comparative Example 1, GelMA hydrogel, PEGDA hydrogel, and HAMA hydrogel containing 0.0005 g / mL thioflavone T were prepared, and printing was performed under the same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1. 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, respectively. The structure with 250 μm pores and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL thioflavone T are shown below. Figure 6 As shown. The structure with 250 μm pores and the ear structure printed using a PEGDA hydrogel containing 0.0005 g / mL thioflavone T are shown in the figure. Figure 10 As shown. The structure with 250 μm pores and the ear structure printed using HAMA hydrogel containing 0.0005 g / mL thioflavone T are shown in the figure. Figure 11 As shown. Comparison Figure 6 , Figure 10 and Figure 11It can be seen that the structure with 250 μm pores and the bottom of the ear structure printed using HAMA hydrogel exhibit partial diffusion cross-linking, which significantly reduces the printing precision compared to GelMA hydrogel and PEGDA hydrogel. (Comparison) Figure 2 and Figure 10 , Figure 3 and Figure 11 It can be seen that after adding lemon yellow, the 250 μm pore structure printed by GelMA hydrogel has a small amount of diffusion cross-linking at the bottom; the 250 μm pore structure and ear structure printed by PEGDA hydrogel also have diffusion cross-linking at the bottom; and the 250 μm pore structure and ear structure printed by HAMA hydrogel both have a large amount of diffusion cross-linking at the bottom. However, the 250 μm pore structure and ear structure printed by GelMA and PEGDA hydrogels with added thioflavone T show no diffusion cross-linking, and the ear structure printed by HAMA hydrogel shows no diffusion cross-linking. The printing accuracy is significantly improved. This is because the absorption peak of thioflavone T is around 410 nm, very close to the wavelength of the light source used (405 nm). Furthermore, it is a cationic dye that can bind to photoinitiated free radicals and inhibit their propagation. Therefore, thioflavone T can suppress light scattering through the synergistic effect of light absorption and free radical reaction, thus improving the accuracy of hydrogel photopolymerization 3D printing. In addition, water-soluble azo food colorings such as Sunset Yellow, Carmine, and Amaranth have antioxidant activity, which can neutralize the free radicals generated during photocuring and improve the accuracy of hydrogel photocuring 3D printing.

[0072] Example 3: Effect of Alizarin Yellow R on the Printing Accuracy of GelMA Hydrogel Photopolymerization

[0073] 1. The effect of Alizarin Yellow R on the printing accuracy of GelMA hydrogel photopolymerization

[0074] Following the method described in Comparative Example 1, a GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R was prepared, and printing was performed under the same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1. The structure with 250 μm pores and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown below. Figure 12 As shown. Comparison Figure 5 and Figure 12It is evident that while the addition of Alizarin Yellow R significantly improves the precision of the printed 250 μm pore structure and ear structure, a small amount of diffuse cross-linking occurs at the bottom when printing structures with 250 μm pores. Alizarin Yellow R is an azo compound that can react with free radicals to form relatively stable spin adducts. This, to some extent, inhibits the propagation of photoinitiated free radicals, slows down the hydrogel cross-linking rate, limits the cross-linking area, and improves the precision of photopolymerization printing.

[0075] 2. Effect of Alizarin Yellow R Dosage on Printing Accuracy of GelMA Hydrogel Photopolymerization

[0076] Following 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 printing was performed under the same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1. Structures with 250 μm pores and ear structures printed using the GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown below. Figure 12 As shown. Structures with 250 μm pores and ear structures printed using GelMA hydrogel containing 0.00025 g / mL Alizarin Yellow R are shown below. Figure 13 As shown. Comparison Figure 12 and Figure 13 It can be seen that if the amount of alizarin yellow R added is insufficient, the printing accuracy of hydrogel photocuring cannot be significantly improved.

[0077] 3. The effect of the type of photocrosslinking hydrogel on the printing accuracy of hydrogel photocuring when using Alizarin Yellow R.

[0078] Following 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 printing was performed under the same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1. 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, respectively. The structure with 250 μm pores and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown below. Figure 12 As shown. The structure with 250 μm pores and the ear structure printed using a PEGDA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown in the figure. Figure 14 As shown. The structure with 250 μm pores and the ear structure printed using HAMA hydrogel containing 0.0005 g / mL Alizarin Yellow R are shown below. Figure 15 As shown in the figure, the comparison reveals that when using Alizarin Yellow R as a photocuring stabilizer, there is no significant difference in printing accuracy among different types of photocrosslinked hydrogels.

[0079] Example 4: Effect of methylene blue on the printing accuracy of GelMA hydrogel photopolymerization

[0080] 1. The effect of methylene blue on the printing accuracy of GelMA hydrogel photopolymerization

[0081] Following the method described in Comparative Example 1, a GelMA hydrogel containing 0.0005 g / mL methylene blue was prepared, and printing was performed under the same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1. The structure with 250 μm pores and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL methylene blue are shown below. Figure 16 As shown. Comparison Figure 5 and Figure 16 It can be seen that although the printing accuracy was improved to some extent after adding methylene blue, there were a lot of diffusion cross-linking in the printed structures with 250 μm pores and ear structures.

[0082] Example 5: Effects of Alizarin Yellow R and Methylene Blue on the Printing Accuracy of GelMA Hydrogel Photopolymerization

[0083] 1. Effects of Alizarin Yellow R and Methylene Blue on the Printing Accuracy of GelMA Hydrogel Photopolymerization

[0084] Following the method described in Comparative Example 1, a GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R and methylene blue (Alizarin Yellow R and methylene blue were mixed in a 1:1 mass ratio before being added) was prepared. Printing was performed under the same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1. The structure with 250 μm pores and the ear structure printed using the GelMA hydrogel containing 0.0005 g / mL Alizarin Yellow R and methylene blue are shown below. Figure 17 As shown. Comparison Figure 12 , Figure 16 and Figure 17 It is evident that the addition of methylene blue significantly improved the printing accuracy of structures with 250 μm pores and ear structures. Specifically, this invention, by mixing Alizarin Yellow R and methylene blue in a 1:1 mass ratio to prepare GelMA hydrogel, found that while Alizarin Yellow R / methylene blue alone had limited effect on improving printing accuracy, their combination resulted in a better improvement in printing accuracy than using Alizarin Yellow R / methylene blue alone.

[0085] Example 6: Effect of thioflavone T on the printing accuracy of GelMA and PEGDA hydrogel photopolymerization

[0086] 1. Effect of thioflavone T on the printing accuracy of GelMA and PEGDA hydrogel photopolymerization

[0087] Following the method described in Comparative Example 1, a hydrogel containing 0.0005 g / mL thioflavone T (GelMA and PEGDA hydrogels, volume ratio 3:1) was prepared. The preparation method was as follows: first, 0.1 g / mL GelMA and 0.15 g / mL PEGDA without thioflavone T were prepared separately, then mixed at a volume ratio of 3:1. Finally, 0.0005 g / mL thioflavone T was added, and the mixture was ultrasonically mixed. The same hydrogel photopolymerization 3D printing conditions as in Comparative Example 1 were used for printing. Microneedles printed using the hydrogel containing 0.0005 g / mL thioflavone T (GelMA and PEGDA hydrogels) were obtained. Figure 18 As shown. By Figure 18 It is known 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.

[0088] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A hydrogel ink for improving the accuracy of photopolymer 3D printing, characterized in that, The hydrogel ink contains a photocrosslinking hydrogel, a photoinitiator, and a photocuring stabilizer; the photocrosslinking hydrogel is selected from GelMA or PEGDA; the photoinitiator is selected from LAP; the photocuring stabilizer is selected from thioflavone 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 thioflavone T in the hydrogel ink is 0.0005 g / mL; the solvent used for the hydrogel ink is PBS solution; the hydrogel ink is photocured for 3D printing, and the light source used for photocuring is ultraviolet light with a wavelength of 405 nm.

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