Dual-curing hydrogel precursor solution, 3D printing hydrogel and application thereof

Abstract

The invention relates to the technical field of hydrogel, in particular to a dual-curing hydrogel precursor solution, 3D printing hydrogel and application thereof. The dual-cured hydrogel precursor solution is prepared from the following raw materials in parts by weight: 0 to 2 parts of acrylic resin, 8 to 10 parts of acrylic monomer, 0.02 to 0.05 part of thermal initiator, 0.14 to 0.15 part of water-soluble photoinitiator and 1 to 1.2 parts of solvent; wherein the acrylic acid monomer comprises N-acryloyl glycine amide and N-acryloyl semicarbazide; the solvent comprises a phosphate buffer solution. The hydrogel prepared from the hydrogel precursor solution provided by the invention has excellent tensile strength and micro-nano processing precision.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogels, and in particular to a dual-cured hydrogel precursor solution, a 3D printing hydrogel and applications thereof. Background Art

[0002] Hydrogel is a polymer material with a three-dimensional network structure. Due to its high water content, good biocompatibility and controllable mechanical properties, it has broad application prospects in biomedicine, flexible electronics, tissue engineering and other fields. Among them, tensile strength, as a key mechanical indicator of hydrogel, directly reflects the maximum stress that the hydrogel can withstand under tensile conditions and is an important parameter for evaluating its structural stability and load-bearing capacity. Hydrogels with high tensile strength can withstand greater external forces without being easily damaged due to their excellent tear resistance, can provide better structural support, and significantly extend their service life. For example, in cell scaffold applications, hydrogels with high tensile strength can better match high-strength biological tissues such as muscle and cartilage, and promote the expression of cell functions.

[0003] At present, hydrogels that rely solely on photocuring or thermal curing usually have low cross-linking density, insufficient tensile strength, and are prone to breakage or collapse under stress. Chinese patent application CN120005112A discloses a supramolecular ionic liquid hydrogel based on two-photon 3D printing and its application. Water-soluble photoinitiators and hydrophilic imidazole ionic liquids are introduced into the system. After photocuring, continuous conductive nanochannels and "island" toughening structures are formed, giving it good electrical conductivity and elongation at break. The resolution of the three-dimensional caged cell scaffold after 3D printing can reach the micron level, but the test results of tensile strength are not disclosed. Based on the photoresist raw material formula provided by the prior art, the applicant prepared a supramolecular ionic liquid hydrogel with similar composition. Tests show that its tensile strength still needs to be further improved. Summary of the Invention

[0004] In response to the technical problems that existing hydrogel materials have poor tensile strength and the processing accuracy of micro-nano structures needs to be improved, the present invention provides a dual-cured hydrogel precursor solution, 3D-printed hydrogel and its applications. The hydrogel prepared from the hydrogel precursor solution has good tensile strength and the 3D printing accuracy can reach the nanometer level. It is particularly suitable for cell scaffold applications that require high structural stability, such as bone tissue regeneration.

[0005] The technical solutions of the present invention are as follows: In a first aspect, the present invention provides a dual-cured hydrogel precursor solution comprising the following raw materials in parts by weight: 0-2 parts of acrylic resin, 8-10 parts of acrylic monomer, 0.02-0.05 parts of thermal initiator, 0.14-0.15 parts of water-soluble photoinitiator, and 1-1.2 parts of solvent; The acrylic acid monomer includes N-acryloylglycine amide and N-acryloylsemicarbazide; and the solvent includes phosphate buffer solution.

[0006] Furthermore, the acrylic resin is selected from one or more of polyethylene glycol diacrylate, 2-hydroxyethyl acrylate and hydroxyethyl methacrylate; the number average molecular weight of the polyethylene glycol diacrylate is 200-10000 g / mol.

[0007] Furthermore, the number average molecular weight of polyethylene glycol diacrylate is 400 g / mol.

[0008] Furthermore, the thermal initiator is ammonium persulfate.

[0009] Furthermore, the water-soluble photoinitiator is P2CK; The structural formula of P2CK is: .

[0010] Furthermore, the raw materials also include 0.01-0.012 parts of a catalyst, and the catalyst is tetramethylethylenediamine.

[0011] Furthermore, the method comprises the following raw materials in parts by weight: 0-2 parts of polyethylene glycol diacrylate, 4-5 parts of N-acryloylglycine amide, 4-5 parts of N-acryloylsemicarbazide, 0.05 parts of ammonium persulfate, 0.14 parts of P2CK, 0.01 parts of tetramethylethylenediamine and 1 part of phosphate buffer solution.

[0012] In a second aspect, the present invention provides a dual-cured 3D printed hydrogel, which is prepared by 3D printing the above-mentioned hydrogel precursor solution.

[0013] Furthermore, 3D printing includes two-photon 3D printing.

[0014] In a third aspect, the present invention provides the use of the above-mentioned hydrogel precursor solution or 3D printed hydrogel in the preparation of biomedical materials, and the biomedical materials include cell scaffolds.

[0015] The beneficial effects of the present invention are: The present invention provides a dual-cured hydrogel precursor solution, which successfully solves the technical problem that existing hydrogel materials are difficult to balance high tensile strength and high-precision micro-nanostructure processing by optimizing the formula and dual-curing process. The hydrogel precursor solution contains N-acryloylglycine amide, N-acryloylamino urea and phosphate buffer solution in a specific ratio. The prepared hydrogel exhibits a unique microphase separation structure, in which the hydrophobic microregions serve as physical cross-linking points to enhance rigidity, the hydrophilic network provides flexibility, and the tensile strength is improved. In addition, with the synergistic effect of the photoinitiator and the thermal initiator, efficient free radical polymerization and redox two-step reactions are achieved in the light-heat dual curing process, which significantly improves the double bond conversion rate and further enhances the tensile strength. Using the hydrogel precursor solution, two-photon 3D printing can be performed to obtain 3D printed hydrogels with micro-nanostructures, breaking through the limitations of traditional hydrogels in mechanical properties and processing precision, and providing hydrogel materials with both high tensile strength and high resolution for fields such as tissue engineering. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0017] Figure 1 This is a scanning electron microscope image of the cell scaffold of Example 5. DETAILED DESCRIPTION

[0018] In order to enable those skilled in the art to better understand the technical solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of the present invention.

[0019] Those skilled in the art will recognize that a hydrogel precursor solution containing a thermal initiator in its raw materials will crosslink and solidify to form a hydrogel after being left at room temperature for a period of time. The open time is the time during which the viscosity of the hydrogel precursor solution remains stable and processable at room temperature. Therefore, if such a hydrogel is to be 3D printed to form micro-nanostructures, processing must be completed within this open time. Once this time has expired and the hydrogel has solidified, further printing is impossible.

[0020] The product model of the ultrafast laser micro-nano processing center used in the present invention is: MJ-Works, and the manufacturer is Yantai Moji Nanotechnology Co., Ltd.

[0021] The present invention has no special requirements on the sources of the polyethylene glycol diacrylate, N-acryloylglycine amide, N-acryloylsemicarbazide, ammonium persulfate, P2CK, tetramethylethylenediamine, phosphate buffer solution, N,N-methylenebisacrylamide, acrylamide and 1-ethyl-3-methylimidazolium dicyanamide salt, and conventional commercially available products in the art can be used.

[0022] Example 1 A dual-cured hydrogel precursor solution comprises the following raw materials in parts by weight: 1 part of polyethylene glycol diacrylate (acrylic resin), 4 parts of N-acryloylglycine amide (acrylic monomer), 5 parts of N-acryloyl semicarbazide (acrylic monomer), 0.05 parts of ammonium persulfate (thermal initiator), 0.14 parts of P2CK (water-soluble photoinitiator), 0.01 parts of tetramethylethylenediamine (catalyst) and 1 part of phosphate buffer solution (solvent); The number average molecular weight of polyethylene glycol diacrylate is 400 g / mol (MN = 400 g / mol); The structural formula of the water-soluble photoinitiator P2CK is as follows: .

[0023] The preparation method of the dual-cured hydrogel precursor solution comprises the following steps: (1) Add polyethylene glycol diacrylate, N-acryloylglycine amide, N-acryloylsemicarbazide and P2CK into a brown reagent bottle and heat at 50°C with stirring until completely dissolved; (2) Add phosphate buffer solution to the brown reagent bottle, heat and stir at 50°C until completely dissolved, cool to room temperature, add ammonium persulfate and tetramethylethylenediamine, stir at room temperature until completely dissolved, and filter to obtain a hydrogel precursor solution.

[0024] The hydrogel precursor solution was prepared under yellow light throughout the entire process. After preparation, it was refrigerated and stored at a temperature of 5-15°C for standby use, and 3D printing was performed within 30 minutes of opening.

[0025] Example 2 A dual-cured hydrogel precursor solution comprises the following raw materials in parts by weight: 2 parts of polyethylene glycol diacrylate (acrylic resin), 4 parts of N-acryloylglycine amide (acrylic monomer), 4 parts of N-acryloyl semicarbazide (acrylic monomer), 0.05 parts of ammonium persulfate (thermal initiator), 0.14 parts of P2CK (water-soluble photoinitiator), 0.01 parts of tetramethylethylenediamine (catalyst) and 1 part of phosphate buffer solution (solvent); The number average molecular weight of polyethylene glycol diacrylate is 400 g / mol (MN = 400 g / mol); The structural formula of the water-soluble photoinitiator P2CK is as follows: .

[0026] The preparation method of the dual-cured hydrogel precursor solution comprises the following steps: (1) Add polyethylene glycol diacrylate, N-acryloylglycine amide, N-acryloylsemicarbazide and P2CK into a brown reagent bottle and heat at 50°C with stirring until completely dissolved; (2) Add phosphate buffer solution to the brown reagent bottle, heat and stir at 50°C until completely dissolved, cool to room temperature, add ammonium persulfate and tetramethylethylenediamine, stir at room temperature until completely dissolved, and filter to obtain a hydrogel precursor solution.

[0027] The hydrogel precursor solution was prepared under yellow light throughout the entire process. After preparation, it was refrigerated and stored at a temperature of 5-15°C for standby use, and 3D printing was performed within 30 minutes of opening.

[0028] Example 3 A dual-cured hydrogel precursor solution comprises the following raw materials in parts by weight: 5 parts of N-acryloylglycine amide (acrylic acid monomer), 5 parts of N-acryloyl semicarbazide (acrylic acid monomer), 0.05 parts of ammonium persulfate (thermal initiator), 0.14 parts of P2CK (water-soluble photoinitiator), 0.01 parts of tetramethylethylenediamine (catalyst) and 1 part of phosphate buffer solution (solvent); The structural formula of the water-soluble photoinitiator P2CK is as follows: .

[0029] The preparation method of the dual-cured hydrogel precursor solution comprises the following steps: (1) Add N-acryloylglycine amide, N-acryloylsemicarbazide and P2CK to a brown reagent bottle and heat at 50°C with stirring until completely dissolved; (2) Add phosphate buffer solution to the brown reagent bottle, heat and stir at 50°C until completely dissolved, cool to room temperature, add ammonium persulfate and tetramethylethylenediamine, stir at room temperature until completely dissolved, and filter to obtain a hydrogel precursor solution.

[0030] The hydrogel precursor solution was prepared under yellow light throughout the entire process. After preparation, it was refrigerated and stored at a temperature of 5-15°C for standby use, and 3D printing was performed within 30 minutes of opening.

[0031] Example 4 A dual-cured 3D printing hydrogel, the preparation method comprising: The hydrogel precursor solution of Example 1 was drop-coated on a clean glass substrate and then placed in an ultrafast laser micro-nano processing center for two-photon 3D printing. The ultrafast laser micro-nano processing center was equipped with a dual-wavelength femtosecond laser system. Modeling and operation were performed according to its instruction manual. The two-photon band was 780nm, and 3D printed hydrogels were prepared by two-photon polymerization reaction.

[0032] Example 5 A dual-cured 3D printing hydrogel, the preparation method comprising: The hydrogel precursor solution of Example 2 was drop-coated on a clean glass substrate and then placed in an ultrafast laser micro-nano processing center for two-photon 3D printing. The ultrafast laser micro-nano processing center was equipped with a dual-wavelength femtosecond laser system. Modeling and operation were performed according to its instruction manual. The two-photon band was 780nm, and 3D printed hydrogels were prepared by two-photon polymerization reaction.

[0033] Example 6 A dual-cured 3D printing hydrogel, the preparation method comprising: The hydrogel precursor solution of Example 3 was drop-coated on a clean glass substrate, and then placed in an ultrafast laser micro-nano processing center for two-photon 3D printing. The ultrafast laser micro-nano processing center was equipped with a dual-wavelength femtosecond laser system. Modeling and operation were performed according to its instruction manual. The two-photon band was 780nm, and 3D printed hydrogels were prepared by two-photon polymerization reaction.

[0034] Comparative Example 1 A dual-cured hydrogel precursor solution comprises the following raw materials in parts by weight: 4 parts of N,N-methylenebisacrylamide (acrylic acid monomer), 6 parts of acrylamide (acrylic acid monomer), 0.02 parts of ammonium persulfate (thermal initiator), 0.14 parts of P2CK (water-soluble photoinitiator), 0.01 parts of tetramethylethylenediamine (catalyst) and 1 part of phosphate buffer solution (solvent); The structural formula of the water-soluble photoinitiator P2CK is as follows: .

[0035] The preparation method of the dual-cured hydrogel precursor solution comprises the following steps: (1) Add N,N-methylenebisacrylamide, acrylamide and P2CK into a brown reagent bottle and heat at 50°C with stirring until completely dissolved; (2) Add phosphate buffer solution to the brown reagent bottle, heat and stir at 50°C until completely dissolved, cool to room temperature, add ammonium persulfate and tetramethylethylenediamine, stir at room temperature until completely dissolved, and filter to obtain a hydrogel precursor solution.

[0036] The hydrogel precursor solution was prepared under yellow light throughout the entire process. After preparation, it was refrigerated and stored at a temperature of 5-15°C for standby use, and 3D printing was performed within 120 minutes of opening time.

[0037] Comparative Example 2 A dual-cured hydrogel precursor solution comprises the following raw materials in parts by weight: 4 parts of N,N-methylenebisacrylamide (acrylic acid monomer), 6 parts of acrylamide (acrylic acid monomer), 0.05 parts of ammonium persulfate (thermal initiator), 0.14 parts of P2CK (water-soluble photoinitiator), 0.01 parts of tetramethylethylenediamine (catalyst) and 1 part of phosphate buffer solution (solvent); The structural formula of the water-soluble photoinitiator P2CK is as follows: .

[0038] The preparation method of the dual-cured hydrogel precursor solution comprises the following steps: (1) Add N,N-methylenebisacrylamide, acrylamide and P2CK into a brown reagent bottle and heat at 50°C with stirring until completely dissolved; (2) Add phosphate buffer solution to the brown reagent bottle, heat and stir at 50°C until completely dissolved, cool to room temperature, add ammonium persulfate and tetramethylethylenediamine, stir at room temperature until completely dissolved, and filter to obtain a hydrogel precursor solution.

[0039] The hydrogel precursor solution was prepared under yellow light throughout the entire process. After preparation, it was refrigerated and stored at a temperature of 5-15°C for standby use, and 3D printing was performed within 30 minutes of opening.

[0040] Comparative Example 3 A hydrogel precursor solution comprises the following raw materials in parts by weight: 1 part of polyethylene glycol diacrylate (acrylic resin), 4 parts of N-acryloylglycine amide (acrylic monomer), 5 parts of N-acryloyl semicarbazide (acrylic monomer), 0.14 parts of P2CK (water-soluble photoinitiator) and 1 part of phosphate buffer solution (solvent); The number average molecular weight of polyethylene glycol diacrylate is 400 g / mol (MN = 400 g / mol); The structural formula of the water-soluble photoinitiator P2CK is as follows: .

[0041] The method for preparing a hydrogel precursor solution comprises the following steps: (1) Add polyethylene glycol diacrylate, N-acryloylglycine amide, N-acryloylsemicarbazide and P2CK into a brown reagent bottle and heat at 50°C with stirring until completely dissolved; (2) Add phosphate buffer solution to the brown reagent bottle, heat and stir at 50°C until completely dissolved, cool to room temperature, and filter to obtain a hydrogel precursor solution.

[0042] The hydrogel precursor solution is prepared under yellow light throughout the entire process and is refrigerated and stored at a temperature of 5-15° C. for later use.

[0043] Comparative Example 4 (a hydrogel precursor solution with similar composition prepared with reference to Chinese patent application CN120005112A) A hydrogel precursor solution comprises the following raw materials in parts by weight: 2 parts of polyethylene glycol diacrylate (acrylic resin), 4 parts of N-acryloylglycine amide (acrylic monomer), 4 parts of N-acryloylsemicarbazide (acrylic monomer), 1 part of 1-ethyl-3-methylimidazolium dicyanamide (hydrophilic imidazole ionic liquid), 0.14 parts of P2CK (water-soluble photoinitiator) and 1 part of phosphate buffer solution (solvent); The number average molecular weight of polyethylene glycol diacrylate is 400 g / mol (MN = 400 g / mol); The structural formula of the water-soluble photoinitiator P2CK is as follows: .

[0044] The method for preparing a hydrogel precursor solution comprises the following steps: (1) Add polyethylene glycol diacrylate, N-acryloylglycine amide, N-acryloylsemicarbazide and P2CK into a brown reagent bottle and heat at 50°C with stirring until completely dissolved; (2) Add phosphate buffer solution to the brown reagent bottle, heat and stir at 50°C until completely dissolved, cool to room temperature, add 1-ethyl-3-methylimidazolium dicyanamide salt, stir at room temperature until completely dissolved, and filter to obtain a hydrogel precursor solution.

[0045] The hydrogel precursor solution is prepared under yellow light throughout the entire process and is refrigerated and stored at a temperature of 5-15° C. for later use.

[0046] Test Example 1 Tensile strength test Referring to ISO 527-3, hydrogels prepared from the hydrogel precursor solutions obtained in Examples 1-3 and Comparative Examples 1-4 were prepared into hydrogels and subjected to tensile strength testing. These hydrogels were designated as Test Samples 1-7, respectively. The hydrogels were prepared by pouring the hydrogel precursor solutions into a dumbbell-shaped mold, curing them with a mercury lamp, and storing them at room temperature for 6 hours before testing. The test results are shown in Table 1.

[0047] Table 1 Tensile strength test results of hydrogels

[0048] From the test results, it can be seen that the tensile strength of test samples 1 to 3 is significantly better than that of test samples 4 to 7.

[0049] Reasons for this analysis: The hydrogel precursor solutions of Examples 1-3 incorporate appropriate photoinitiators and thermal initiators. During the dual curing process of light and heat, a two-step reaction—a free radical polymerization reaction and a redox reaction—is achieved. The coordinated reaction significantly increases the double bond conversion rate of the hydrogel, resulting in a more compact structure and improved tensile strength. Furthermore, the hydrogel precursor solutions of Examples 1-3 include N-acryloylglycine amide, N-acryloylsemicarbazide, and phosphate buffer solution, which together achieve microphase separation. In this system, the two acrylic monomers, N-acryloylglycine amide and N-acryloylsemicarbazide, form numerous hydrogen bonds that serve as physical crosslinks, enhancing rigidity, while the hydrophilic network (PBS permeable zone) provides flexibility. The synergistic effect of these two further enhances tensile strength by distributing stress. While the hydrogel precursor solutions of Comparative Examples 1 and 2 also undergo a two-step reaction via dual curing, the added acrylic monomers (acrylamide and N,N-methylenebisacrylamide) fail to achieve microphase separation with the phosphate buffer solution, resulting in poor tensile strength results. Although the hydrogel precursor solutions of Comparative Examples 3 and 4 also include N-acryloylglycine amide, N-acryloylsemicarbazide, and phosphate buffer solution, they do not contain a thermal initiator but only a photoinitiator. The one-step reaction (free radical polymerization reaction) combined with the microphase separation structure also results in poor tensile strength results.

[0050] At the same time, the inventors also optimized the formula. The hydrogel (test sample 2) prepared by dual curing the hydrogel precursor solution of Example 2 had a tensile strength better than that of test samples 1 and 3.

[0051] It's worth noting that the tensile strength of the dual-cured 3D-printed hydrogel cannot be tested using existing testing methods due to its micro-nanostructure after two-photon 3D printing. Therefore, the inventors tested the dual-cured hydrogel according to existing testing standards. The hydrogel's composition is consistent with that of the 3D-printed hydrogel, and the results are comparable.

[0052] Test Example 2 Microstructure testing The 3D printed hydrogels prepared in Examples 4 to 6 were subjected to scanning electron microscopy. The test results show that the hydrogels have been successfully processed into cell scaffolds with micro-nano structures. The cell scaffolds of Examples 4 to 6 are similar, and the scanning electron microscopy image of Example 5 is shown in FIG. Figure 1 The thinnest processing line width is only 300nm, and the processing precision is high.

[0053] Although the present invention has been described in detail with reference to the accompanying drawings and in conjunction with preferred embodiments, the present invention is not limited thereto. Without departing from the spirit and essence of the present invention, persons of ordinary skill in the art may make various equivalent modifications or substitutions to the embodiments of the present invention, and such modifications or substitutions shall be within the scope of the present invention. Any changes or substitutions that can be easily conceived by persons skilled in the art within the technical scope disclosed in the present invention shall be within the scope of protection of the present invention.

Claims

1. A dual-cured hydrogel precursor solution, characterized in that: The invention comprises the following raw materials in parts by weight: 0-2 parts of acrylic resin, 8-10 parts of acrylic monomer, 0.02-0.05 parts of thermal initiator, 0.14-0.15 parts of water-soluble photoinitiator and 1-1.2 parts of solvent; The acrylic acid monomer includes N-acryloylglycine amide and N-acryloylsemicarbazide; and the solvent includes phosphate buffer solution.

2. The dual-cured hydrogel precursor solution according to claim 1, wherein: The acrylic resin is selected from one or more of polyethylene glycol diacrylate, 2-hydroxyethyl acrylate and hydroxyethyl methacrylate; the number average molecular weight of the polyethylene glycol diacrylate is 200-10000 g / mol.

3. The dual-cured hydrogel precursor solution according to claim 2, wherein: The number average molecular weight of polyethylene glycol diacrylate is 400 g / mol.

4. The dual-cured hydrogel precursor solution according to claim 1, wherein: The thermal initiator is ammonium persulfate.

5. The dual-cured hydrogel precursor solution according to claim 1, wherein: The water-soluble photoinitiator was P2CK; The structural formula of P2CK is: 。 6. The dual-cured hydrogel precursor solution according to claim 1, wherein: The raw materials also include 0.01-0.012 parts of a catalyst, which is tetramethylethylenediamine.

7. The dual-cured hydrogel precursor solution according to any one of claims 1 to 6, wherein: The method comprises the following raw materials in parts by weight: 0-2 parts of polyethylene glycol diacrylate, 4-5 parts of N-acryloylglycine amide, 4-5 parts of N-acryloylsemicarbazide, 0.05 parts of ammonium persulfate, 0.14 parts of P2CK, 0.01 parts of tetramethylethylenediamine and 1 part of phosphate buffer solution.

8. A dual-cured 3D printing hydrogel, characterized in that: The hydrogel precursor solution according to claim 1 is prepared by 3D printing.

9. The 3D printing hydrogel according to claim 8, wherein: 3D printing includes two-photon 3D printing.

10. Use of the hydrogel precursor solution according to claim 1 or the 3D printing hydrogel according to claim 8 in preparing biomedical materials, characterized in that: Biomedical materials include cell scaffolds.

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