A 4D printing polyurethane-based hydrogel material and its preparation method and application

Abstract

The present invention provides a 4D printing polyurethane-based hydrogel material and a preparation method and application thereof, wherein the 4D printing polyurethane-based hydrogel material comprises a combination of a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the swelling degree of the first dynamically cross-linked polyurethane is less than the swelling degree of the second dynamically cross-linked polyurethane; and the chain extenders in the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane are independently diols constructed based on the Diels-Alder reaction. Through the design and compounding of dynamically cross-linked polyurethanes with different swelling degrees, the 4D printing polyurethane-based hydrogel material has a swelling mismatch structure and water-triggered enhancement characteristics, exhibits good mechanical properties and biocompatibility, and can utilize its own temperature-sensitive and water-responsive characteristics to achieve a shape transition from one dimension to three dimensions, and is expected to be applied to the filling of tissue defects in a minimally invasive surgical manner.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and specifically relates to a 4D printing polyurethane-based hydrogel material and a preparation method and application thereof. Background Art

[0002] With the continuous development and progress of science and technology, the concept of "minimally invasive" has gradually become the goal pursued by medical workers with its advantages of small wounds, less bleeding, less pain, and quick recovery, representing the inevitable trend of surgical operations. Thanks to the development of precision medical devices, minimally invasive surgery has developed rapidly in the fields of urology, neurosurgery, and interventional cardiology in recent years. For tissue defects and loss of function caused by diseases and accidents, transplantation surgery is still the most commonly used treatment method in clinical medicine, but it is limited by donor shortages, tissue compatibility, and lifelong immunosuppression. Therefore, how to repair critical-size tissue defects in a minimally invasive way still faces many challenges.

[0003] As a kind of extracellular matrix material, polymer hydrogel has physical and chemical properties similar to those of living tissues and is expected to be used in the construction of tissue defect repair scaffolds. For example, CN116271219A discloses the application of silk fibroin porous hydrogel in the preparation of bone defect repair scaffolds, which uses the self-solidification properties of silk fibroin porous hydrogels and its injectability to imitate bone cement materials for vertebroplasty. However, the block hydrogel prepared by the traditional mold method has a single structure, and there are problems such as slow nutrient transmission and difficulty in forming a vascularized structure, which is not conducive to tissue regeneration.

[0004] The emergence of 3D printing technology has made it possible to construct heterogeneous and personalized tissue engineering scaffolds, and has shown application prospects in the repair and treatment of tissue defects such as skin, heart, and bone cartilage. For example, in the 3D printed hydrogel bone repair scaffold disclosed in CN116407680A, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, sodium citrate, polyethylene glycol diacrylate, short-chain chitosan and water are used to prepare the printing slurry, which is cured under ultraviolet light after 3D printing, and then soaked in a mixed ion solution of sodium citrate and sodium tripolyphosphate and tris(hydroxymethylaminomethane) buffer in turn to obtain an ion-crosslinked chitosan-based hydrogel; and then alternately soaked in a potassium hydrogen phosphate solution and a calcium chloride solution for multiple times to deposit amorphous calcium phosphate on the ion-crosslinked chitosan-based hydrogel, and then soaked in a calcium chloride solution to incubate the amorphous calcium phosphate into hydroxyapatite to obtain a 3D printed hydrogel bone repair scaffold. In the 3D printed antibacterial hydrogel repair scaffold disclosed in CN106983912A, a modified sodium hyaluronate / modified oxidized sodium alginate hydrogel precursor is prepared by photocuring 3D printing to prepare a composite hydrogel scaffold, and then the antimicrobial peptide LL-37 is modified on its surface to obtain an antibacterial hydrogel repair scaffold. However, the implantation of the in vitro molded scaffold requires an open surgery, which will cause new damage to human tissues; at the same time, the complex surgical procedure will also bring danger and discomfort to the patient.

[0005] Since 4D printing technology was first proposed by Skylar Tibbits of MIT in 2013, it has quickly attracted widespread attention in many research fields. At present, a more comprehensive definition of 4D printing is: the structure formed by 3D printing can spontaneously change its shape, function, etc. over time under pre-set stimulation conditions (sound, light, heat, electricity, etc.). Compared with 3D printing technology, 4D printing increases the ability of printed structures to change over time, and can solve the problem of minimally invasive delivery of complex scaffold structures by deformation. However, traditional 4D printed hydrogel scaffolds have problems such as poor mechanical properties and difficulty in minimally invasive delivery, which limits the practical application of 4D printed scaffolds. Based on this, the development of 4D printed hydrogel scaffolds with good mechanical properties and capable of minimally invasive delivery is an urgent problem to be solved in this field. Summary of the invention

[0006] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a 4D printed polyurethane-based hydrogel material and a preparation method and application thereof. By designing and compounding dynamically cross-linked polyurethanes with different swelling degrees, the 4D printed polyurethane-based hydrogel material has a swelling mismatch structure and water-triggered enhancement properties, exhibiting good mechanical properties and biocompatibility, and can utilize its own temperature-sensitive and water-responsive properties to achieve shape transformation from one dimension to three dimensions, and is expected to be used for filling tissue defects in a minimally invasive surgical manner.

[0007] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides a 4D printing polyurethane-based hydrogel material, wherein the 4D printing polyurethane-based hydrogel material comprises a combination of a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the swelling degree of the first dynamically cross-linked polyurethane is less than the swelling degree of the second dynamically cross-linked polyurethane; the raw materials for preparing the first dynamically cross-linked polyurethane comprise a combination of a first polyester polyol, a first chain extender, a first polyisocyanate, and optionally a first hydrophilic polyether polyol; the raw materials for preparing the second dynamically cross-linked polyurethane comprise a combination of a second polyester polyol, a second hydrophilic polyether polyol, a second chain extender, and a second polyisocyanate; the first chain extender and the second chain extender are each independently a diol constructed based on a Diels-Alder reaction.

[0009] The 4D printing polyurethane-based hydrogel material provided by the present invention includes a combination of a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane with different swelling degrees, in which a polyol (a first polyester polyol and optionally a first hydrophilic polyether polyol, a second polyester polyol and a second hydrophilic polyether polyol) is used as a temperature-sensitive soft segment, a polyisocyanate (a first polyisocyanate, a second polyisocyanate) is used as a hard segment, and a diol constructed based on a Diels-Alder reaction is used as a chain extender; the chain extender is designed so that the 4D printing polyurethane-based hydrogel material contains a structural unit constructed based on a Diels-Alder reaction, thereby forming a dynamic cross-linked structure. In the present invention, the soft segment with a lower melting point gives the 4D printing polyurethane-based hydrogel material a temperature-sensitive property, which helps it to be fixed into a temporary one-dimensional shape as a scaffold, and completes the deformation from one dimension to three dimensions based on stimulus (temperature, water) responsiveness. Moreover, the 4D printed polyurethane-based hydrogel material contains both hydrophilic segments and hydrophobic segments, and the hydrophilic polyether polyol (the second hydrophilic polyether polyol, optionally the first hydrophilic polyether polyol) is the only hydrophilic segment. Its mobility in water helps the hydrophilic segments to aggregate, swell in water, and then form a phase separation structure, which can improve the modulus and mechanical properties of the 4D printed polyurethane-based hydrogel material, so that the 4D printed polyurethane-based hydrogel material has water-triggered enhancement ability. Furthermore, two dynamically cross-linked polyurethanes with different swelling degrees are matched, and the second dynamically cross-linked polyurethane with a higher swelling degree and the first dynamically cross-linked polyurethane with a low swelling degree jointly construct a swelling mismatch structure, giving the 4D printed polyurethane-based hydrogel material excellent water responsiveness.

[0010] Based on the design and compounding of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane with different swelling degrees, the 4D printed polyurethane-based hydrogel material provided by the present invention has excellent mechanical properties, biocompatibility and water-triggered enhancement characteristics, which is conducive to being used as a support scaffold in vivo. Moreover, the 4D printed polyurethane-based hydrogel material utilizes its own temperature sensitivity and water response characteristics to achieve a shape transition from one dimension to three dimensions, providing a reliable way for minimally invasive delivery, and is expected to be used in the filling of tissue defects in a minimally invasive surgical manner.

[0011] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. Through the following preferred technical solutions, the objectives and beneficial effects of the present invention can be better achieved and realized.

[0012] Preferably, the first polyester polyol and the second polyester polyol each independently include any one of polycaprolactone triol and polycaprolactone diol or a combination of at least two of them, and polycaprolactone triol is more preferred.

[0013] Preferably, the first hydrophilic polyether polyol and the second hydrophilic polyether polyol each independently include any one of polyethylene glycol and polytetramethylene ether glycol or a combination of at least two thereof, and polyethylene glycol is further preferred.

[0014] As a preferred technical solution of the present invention, the first hydrophilic polyether polyol and the second hydrophilic polyether polyol are polyethylene glycol, which construct the hydrophilic segments of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane. After absorbing water, the polyethylene glycol hydrophilic segments and other hydrophobic segments undergo obvious phase separation, and the phase separation structure helps to improve the mechanical properties.

[0015] Preferably, the molecular weight of the first polyester polyol and the second polyester polyol is independently 500-5000Da, for example, 800Da, 1000Da, 1200Da, 1500Da, 1800Da, 2000Da, 2500Da, 3000Da, 3500Da, 4000Da or 4500Da, as well as specific values ​​between the above values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific values ​​included in the range, and 550-2000Da is further preferred.

[0016] Preferably, the molecular weight of the first hydrophilic polyether polyol and the second hydrophilic polyether polyol are each independently 500-10000Da, for example, 1000Da, 2000Da, 3000Da, 4000Da, 5000Da, 6000Da, 7000Da, 8000Da or 9000Da, as well as specific values ​​between the above values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific values ​​included in the range, and 1000-6000Da is further preferred.

[0017] As a preferred technical solution of the present invention, the molecular weight of the first polyester polyol and the second polyester polyol is 500-5000Da (Dalton); the molecular weight of the first hydrophilic polyether polyol and the second hydrophilic polyether polyol is 500-10000Da; the first polyester polyol, the second polyester polyol (preferably polycaprolactone triol) and the first hydrophilic polyether polyol and the second hydrophilic polyether polyol (preferably polyethylene glycol) with different molecular weights are helpful to adjust the swelling degree, body temperature sensitive properties and water-triggered enhancement ability of 4D printing polyurethane-based hydrogel materials.

[0018] Preferably, the molar ratio of the first polyester polyol to the first hydrophilic polyether polyol is 1:(0-1.2), for example, it can be 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1 or 1:1.1, and more preferably 1:(0.1-0.5).

[0019] Preferably, the molar ratio of the second polyester polyol to the second hydrophilic polyether polyol is 1:(0.1-1.2), for example, it can be 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1 or 1:1.1, and more preferably 1:(0.25-1).

[0020] Preferably, the first polyisocyanate and the second polyisocyanate are each independently an aliphatic polyisocyanate and / or an alicyclic polyisocyanate.

[0021] Preferably, the first polyisocyanate and the second polyisocyanate each independently include any one of isophorone diisocyanate, hexamethylene diisocyanate, pentamethylene diisocyanate, and cyclohexyl diisocyanate, or a combination of at least two thereof, and isophorone diisocyanate is further preferred.

[0022] Preferably, the molar ratio of the first polyisocyanate to the first polyester polyol is (2-6):1, for example, it can be 2.2:1, 2.5:1, 2.8:1, 3:1, 3.2:1, 3.5:1, 3.8:1, 4:1, 4.2:1, 4.5:1, 4.8:1, 5:1, 5.3:1, 5.5:1 or 5.8:1, and more preferably (3-4.3):1.

[0023] Preferably, the molar ratio of the second polyisocyanate to the second polyester polyol is (2-6):1, for example, it can be 2.2:1, 2.5:1, 2.8:1, 3:1, 3.2:1, 3.5:1, 3.8:1, 4:1, 4.2:1, 4.5:1, 4.8:1, 5:1, 5.3:1, 5.5:1 or 5.8:1, and more preferably (3-5.3):1.

[0024] Preferably, the molar ratio of the first chain extender to the first polyester polyol is (1.3-2.8):1, for example, it can be 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1 or 2.7:1, and more preferably (1.4-2.5):1.

[0025] Preferably, the molar ratio of the second chain extender to the second polyester polyol is (1.3-2.8):1, for example, it can be 1.5:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1 or 2.7:1, and more preferably (1.6-2.5):1.

[0026] As a preferred technical solution of the present invention, in the first dynamically cross-linked polyurethane, the molar ratio of the first polyester polyol, the first hydrophilic polyether polyol, the first chain extender, and the first polyisocyanate is 1:(0-1.2):(1.3-2.8):(2-6); in the second dynamically cross-linked polyurethane, the molar ratio of the second polyester polyol, the second hydrophilic polyether polyol, the second chain extender, and the second polyisocyanate is 1:(0.1-1.2):(1.3-2.8):(2-6); through the design of the molar ratio of each material, it is helpful for the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane to exhibit a series of adjustable mechanical properties from hard and brittle to soft and tough, and the wide range of mechanical properties is conducive to the application of the 4D printed polyurethane-based hydrogel material as a scaffold in tissues of different strengths.

[0027] Preferably, the diol constructed based on the Diels-Alder reaction is obtained by reacting bismaleimide with a hydroxyl-containing furan compound.

[0028] As a preferred technical solution of the present invention, the Diels-Alder reaction is a diene synthesis reaction between bismaleimide and a hydroxyl-containing furan compound, and the diene synthesis reaction can undergo a reverse reaction at 100-150° C. Thus, the structural units based on the Diels-Alder reaction in the first chain extender and the second chain extender become the basis of the dynamic crosslinking structure in the first dynamically crosslinked polyurethane and the second dynamically crosslinked polyurethane.

[0029] Preferably, the bismaleimide includes any one of N,N'-(4,4'-methylenediphenyl)bismaleimide, N,N'-(1,4-phenylene)bismaleimide, N,N'-(1,3-phenylene)bismaleimide, or a combination of at least two thereof, and N,N'-(4,4'-methylenediphenyl)bismaleimide (BMI) is further preferred.

[0030] Preferably, the hydroxyl-containing furan compound comprises furfuryl alcohol.

[0031] As a preferred technical solution of the present invention, the first chain extender and the second chain extender are obtained by reacting N,N'-(4,4'-methylenediphenyl)bismaleimide with furfuryl alcohol, and the reaction formula is as follows:

[0032]

[0033] Preferably, the molar ratio of the maleimide group in the bismaleimide to the furan group in the hydroxyl-containing furan compound is 1:(1-5), for example, it can be 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4 or 1:4.5, etc.

[0034] Preferably, the reaction of the bismaleimide and the hydroxyl-containing furan compound is carried out in the presence of a solvent.

[0035] Preferably, the solvent includes any one of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetone, and tetrahydrofuran, or a combination of at least two thereof.

[0036] Preferably, the reaction temperature of the bismaleimide and the hydroxyl furan compound is 50-80°C, for example, it can be 52°C, 55°C, 58°C, 60°C, 62°C, 65°C, 68°C, 70°C or 75°C, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0037] Preferably, the reaction time of the bismaleimide and the hydroxyl furan compound is 2-12 h, for example, it can be 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h or 11 h, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0038] Preferably, the diol constructed based on the Diels-Alder reaction is obtained by reacting bismaleimide with a hydroxyl-containing furan compound, and the specific method includes: mixing bismaleimide with a solvent, heating at 50-80°C for 5-60 minutes, adding furfuryl alcohol, and performing a Diels-Alder reaction at 50-80°C under stirring for 2-12 hours to obtain a reaction solution; the reaction solution is post-treated to obtain the diol.

[0039] Preferably, the post-treatment method comprises: purifying the reaction solution by precipitation with cold ether, and subjecting the obtained solid to primary drying, washing and secondary drying to obtain the diol.

[0040] Preferably, the washing agent used in the washing comprises diethyl ether.

[0041] Preferably, the washing is performed 1-5 times, for example 2 times, 3 times or 4 times.

[0042] Preferably, the primary drying and secondary drying temperatures are each independently 50-80°C, for example, 52°C, 55°C, 58°C, 60°C, 62°C, 65°C, 68°C, 70°C or 75°C, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0043] Preferably, the time for the primary drying and the secondary drying are each independently 6-24 h, for example, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h or 22 h, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively enumerates the specific point values ​​included in the range; further preferably, the time for the primary drying is 8-24 h, and the time for the secondary drying is 12-24 h.

[0044] Preferably, the first dynamically cross-linked polyurethane is prepared by the following method, which comprises: subjecting a first polyester polyol, optionally a first hydrophilic polyether polyol and a first polyisocyanate to a first prepolymer to obtain a first prepolymer; and subjecting the first prepolymer to a first chain extension reaction with a first chain extender to obtain the first dynamically cross-linked polyurethane.

[0045] Preferably, the first polyester polyol, optionally the first hydrophilic polyether polyol, is subjected to a dehydration treatment, and the dehydration treatment method comprises: vacuum filtering the first polyester polyol, optionally the first hydrophilic polyether polyol, at 100-125°C (for example, 105°C, 110°C, 115°C, 120°C, etc.) for 0-2h (for example, 0.2h, 0.5h, 0.8h, 1h, 1.2h, 1.5h, 1.8h, etc.).

[0046] Preferably, the first prepolymerization reaction is carried out in the presence of a first solvent and a first catalyst.

[0047] Preferably, the first solvent comprises any one of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and tetrahydrofuran, or a combination of at least two thereof, and a combination of N,N-dimethylformamide and tetrahydrofuran is further preferred.

[0048] Preferably, the volume ratio of N,N-dimethylformamide to tetrahydrofuran in the first solvent is 1:(2-8), for example, it can be 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7 or 1:7.5, etc.

[0049] Preferably, based on the mass of the first polyester polyol as 1 g, the amount of the first solvent used is 10-50 mL, for example, 15 mL, 20 mL, 25 mL, 30 mL, 35 mL, 40 mL or 45 mL, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0050] Preferably, the first catalyst comprises an organotin catalyst.

[0051] Preferably, the first catalyst comprises any one of dibutyltin dilaurate, stannous octoate, and dibutyltin diacetate, or a combination of at least two thereof, and dibutyltin dilaurate is further preferred.

[0052] Preferably, based on the mass of the first polyester polyol as 1 g, the amount of the first catalyst used is 10-40 μL, for example, 15 μL, 20 μL, 25 μL, 30 μL or 35 μL, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0053] Preferably, the temperature of the first prepolymerization reaction is 50-70°C, for example, it can be 52°C, 55°C, 58°C, 60°C, 62°C, 65°C or 68°C, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0054] Preferably, the time of the first prepolymerization reaction is 2-8 h, for example, it can be 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h, 5.5 h, 6 h, 6.5 h, 7 h or 7.5 h, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0055] Preferably, the temperature of the first chain extension reaction is 50-70°C, for example, it can be 52°C, 55°C, 58°C, 60°C, 62°C, 65°C or 68°C, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0056] Preferably, the time of the first chain extension reaction is 4-8 h, for example, it can be 4.5 h, 5 h, 5.5 h, 6 h, 6.5 h, 7 h or 7.5 h, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0057] Preferably, the step of removing solvent is further included after the first chain extension reaction is completed.

[0058] Preferably, the solvent removal method is high-temperature drying, the temperature is 50-70°C, for example, it can be 52°C, 55°C, 58°C, 60°C, 62°C, 65°C or 68°C, etc.; the time is 18-72h, for example, it can be 20h, 22h, 24h, 26h, 28h, 30h, 32h, 36h, 40h, 44h, 48h, 52h, 56h, 60h, 64h, 68h, etc.

[0059] Preferably, the second dynamically cross-linked polyurethane is prepared by the following method, which includes: subjecting a second polyester polyol, a second hydrophilic polyether polyol and a second polyisocyanate to a second prepolymer to obtain a second prepolymer; and subjecting the second prepolymer to a second chain extender to a second chain extension reaction to obtain the second dynamically cross-linked polyurethane.

[0060] Preferably, the second polyester polyol and the second hydrophilic polyether polyol are dehydrated, and the dehydration method comprises: vacuum filtering the second polyester polyol and the second hydrophilic polyether polyol at 100-125°C (for example, 105°C, 110°C, 115°C, 120°C, etc.) for 0-2h (for example, 0.2h, 0.5h, 0.8h, 1h, 1.2h, 1.5h, 1.8h, etc.).

[0061] Preferably, the second prepolymerization reaction is carried out in the presence of a second solvent and a second catalyst.

[0062] Preferably, the second solvent comprises any one of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, or a combination of at least two thereof, and a combination of N,N-dimethylformamide and tetrahydrofuran is further preferred.

[0063] Preferably, the volume ratio of N,N-dimethylformamide to tetrahydrofuran in the second solvent is 1:(2-8), for example, it can be 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7 or 1:7.5, etc.

[0064] Preferably, based on the mass of the second polyester polyol as 1 g, the amount of the second solvent used is 10-50 mL, for example, 15 mL, 20 mL, 25 mL, 30 mL, 35 mL, 40 mL or 45 mL, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0065] Preferably, the second catalyst comprises an organotin catalyst.

[0066] Preferably, the second catalyst includes any one of dibutyltin dilaurate, stannous octoate, and dibutyltin diacetate, or a combination of at least two thereof, and dibutyltin dilaurate is more preferred.

[0067] Preferably, based on the mass of the second polyester polyol as 1 g, the amount of the second catalyst used is 10-40 μL, for example, 15 μL, 20 μL, 25 μL, 30 μL or 35 μL, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0068] Preferably, the temperature of the second prepolymerization reaction is 50-70°C, for example, it can be 52°C, 55°C, 58°C, 60°C, 62°C, 65°C or 68°C, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0069] Preferably, the time of the second prepolymerization reaction is 2-8h, for example, it can be 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h or 7.5h, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0070] Preferably, the temperature of the second chain extension reaction is 50-70°C, for example, it can be 52°C, 55°C, 58°C, 60°C, 62°C, 65°C or 68°C, as well as specific values ​​between the above points. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific points included in the range.

[0071] Preferably, the time of the second chain extension reaction is 4-8 h, for example, it can be 4.5 h, 5 h, 5.5 h, 6 h, 6.5 h, 7 h or 7.5 h, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0072] Preferably, the second chain extension reaction further comprises a solvent removal step after completion.

[0073] Preferably, the solvent removal method is high-temperature drying, the temperature is 50-70°C, for example, it can be 52°C, 55°C, 58°C, 60°C, 62°C, 65°C or 68°C, etc.; the time is 18-72h, for example, it can be 20h, 22h, 24h, 26h, 28h, 30h, 32h, 36h, 40h, 44h, 48h, 52h, 56h, 60h, 64h, 68h, etc.

[0074] In the present invention, the mass ratio of the first dynamically cross-linked polyurethane to the second dynamically cross-linked polyurethane is not particularly limited and can be adjusted according to different application scenarios and application requirements to obtain 4D printing polyurethane-based hydrogel materials with different mechanical properties, water-triggered enhancement properties, temperature sensitivity and water responsiveness, and shape transformation properties.

[0075] In the present invention, the modulus of the 4D printed polyurethane-based hydrogel material has a strong temperature dependence, and can be changed in shape by an external force at a first temperature to obtain a temporary shape; the temporary shape can be fixed at a second temperature; when placed in an environment of the first temperature again, the temporary shape can spontaneously recover to its initial shape within a time of ≤5min (for example, 0.5min, 1min, 2min, 3min, 4min, etc.); wherein the first temperature is 20-40°C, for example, 22°C, 25°C, 28°C, 30°C, 32°C, 35°C, 37°C, 39°C, etc., preferably 36-37°C (body temperature); the second temperature is ≤5°C, for example, 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, etc.

[0076] In a second aspect, the present invention provides a method for preparing a 4D printing polyurethane-based hydrogel material as described in the first aspect, the preparation method comprising: placing a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane in different barrels of a 3D printer, respectively, extruding and performing 3D printing to obtain the 4D printing polyurethane-based hydrogel material.

[0077] Preferably, the 3D printing method is multi-nozzle fused deposition modeling.

[0078] As a preferred technical solution of the present invention, in the preparation method of the 4D printing polyurethane-based hydrogel material, a polyol (a first polyester polyol and optionally a first hydrophilic polyether polyol, a second polyester polyol and a second hydrophilic polyether polyol) is used as a temperature-sensitive soft segment, and a polyisocyanate (a first polyisocyanate, a second polyisocyanate) is used as a hard segment, and prepolymerization is first performed, and further chain extension is performed using a diol constructed based on a Diels-Alder reaction to obtain a first dynamic cross-linked polyurethane and a second dynamic cross-linked polyurethane. Then, a 4D printing polyurethane-based hydrogel material is constructed by a multi-nozzle fused deposition molding technology; the preparation method is simple, and the water-triggered enhanced 4D printing polyurethane-based hydrogel material obtained by this method has good mechanical properties, biocompatibility and water-triggered enhancement properties, and has broad application prospects.

[0079] Preferably, the heating temperature of the barrel is 110-130°C, for example, it can be 112°C, 115°C, 118°C, 120°C, 122°C, 125°C or 128°C, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0080] Preferably, the extrusion pressure is 100-750 kPa, for example, it may be 150 kPa, 200 kPa, 250 kPa, 300 kPa, 350 kPa, 400 kPa, 450 kPa, 500 kPa, 550 kPa, 600 kPa, 650 kPa or 700 kPa, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0081] Preferably, the printing speed of the 3D printing is 10-500 mm / min, for example, it can be 50 mm / min, 100 mm / min, 150 mm / min, 200 mm / min, 250 mm / min, 300 mm / min, 350 mm / min, 400 mm / min or 450 mm / min, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0082] Preferably, the caliber of the printing needle of the 3D printing is 200-1000 μm, for example, it can be 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm or 900 μm, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values ​​included in the range.

[0083] In the present invention, the path and method of the 3D printing, parameters such as line spacing, the arrangement of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane, etc. can be determined according to actual needs so that the structure of the 4D printed polyurethane-based hydrogel material meets its deformation needs.

[0084] Exemplarily, the 3D printing is performed according to a preset pattern, preferably using a layer-by-layer printing method to form a 4D printed polyurethane-based hydrogel material with a multi-layer (at least two-layer) structure.

[0085] Preferably, at least one cross section of the 4D printed polyurethane-based hydrogel material comprises a first dynamically cross-linked polyurethane layer and a second dynamically cross-linked polyurethane layer stacked on top of each other.

[0086] In a third aspect, the present invention provides an application of the 4D printed polyurethane-based hydrogel material as described in the first aspect, wherein the 4D printed polyurethane-based hydrogel material is used to prepare a biological scaffold.

[0087] Preferably, the 4D printed polyurethane-based hydrogel material is used to prepare a minimally invasive support scaffold or a tissue defect repair scaffold.

[0088] In the present invention, the 4D printed polyurethane-based hydrogel material is used as a scaffold, which can be curled into a one-dimensional long cylindrical structure under the action of external force at 20-40°C (preferably 37°C), and the one-dimensional long cylindrical structure can be fixed at a low temperature (≤5°C, preferably 4°C); the fixed one-dimensional long cylindrical structure can be delivered into the body through a microcatheter, and spontaneously complete the deformation from one dimension to three dimensions in the body temperature and body fluid environment to complete the filling of the defect.

[0089] Compared with the prior art, the present invention has the following beneficial effects:

[0090] (1) In the 4D printing polyurethane-based hydrogel material provided by the present invention, polyol is used as the soft segment of the dynamically cross-linked polyurethane. The lower melting point of the soft segment gives the 4D printing polyurethane-based hydrogel material a temperature / body temperature sensitive property. The temperature / body temperature sensitive property helps it to be fixed into a temporary one-dimensional shape as a scaffold, and realize a multi-dimensional shape transition from one dimension to three dimensions under the stimulation of temperature and / or water.

[0091] (2) The 4D printed polyurethane-based hydrogel material contains both hydrophilic segments and hydrophobic segments. After swelling in water, the hydrophilic segments aggregate to form a phase separation structure, which can improve the modulus of the hydrogel material and exhibit excellent water-triggered enhancement properties. The water-triggered enhancement properties help it to better play a supporting role as a scaffold in the humid environment in the body.

[0092] (3) Based on the design and compounding of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane with different swelling degrees, the 4D printed polyurethane-based hydrogel material has a swelling mismatch structure, exhibits the characteristic of spontaneously deforming into a preset three-dimensional shape after contacting water, and has endogenous stimulus responsiveness (water response and temperature response), which is safer and suitable for application in the biomedical field.

[0093] (4) The 4D printed polyurethane-based hydrogel material has both temperature response and water response. As a scaffold, it can be fixed into a one-dimensional shape in vitro, which is convenient for minimally invasive delivery. After being implanted into the body, it restores its original shape under body temperature stimulation, and then deforms into a preset three-dimensional shape under body fluid stimulation, thereby completing the filling of the defect and playing a certain supporting role. BRIEF DESCRIPTION OF THE DRAWINGS

[0094] Figure 1 The H NMR spectrum of the diol DA-diol prepared by the Diels-Alder reaction in Preparation Example 1;

[0095] Figure 2 is a Fourier transform infrared spectrum of the second dynamically cross-linked polyurethane in Example 1;

[0096] Figure 3 This is a tensile stress-strain test diagram of the first dynamically cross-linked polyurethane in Example 1;

[0097] Figure 4 This is a test graph of the storage modulus of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane in Example 1;

[0098] Figure 5 This is a swelling test diagram of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane in Example 1;

[0099] Figure 6 A shape transformation test diagram of the 4D printed polyurethane-based hydrogel material provided in Example 1;

[0100] Figure 7 This is a shape transformation test diagram of the polyurethane-based hydrogel material provided in Comparative Example 1. DETAILED DESCRIPTION

[0101] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0102] As used herein, the terms "comprises," "including," "having," "containing," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises the listed elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

[0103] "Optionally", "optionally" or "either" means that the subsequently described matter or event can or cannot occur, and that the description includes situations where the event occurs and situations where it does not.

[0104] In the present invention, the features defined as "first" or "second" may include one or more of the features explicitly or implicitly, and are used to distinguish and describe the features, without distinction of order or importance. In the description of the present invention, unless otherwise specified, "plurality" means two or more.

[0105] Preparation Example 1

[0106] A diol (DA-diol) constructed based on the Diels-Alder reaction is obtained by reacting N,N'-(4,4'-methylenediphenyl)bismaleimide (BMI) with furfuryl alcohol (FA), and the reaction formula is as follows:

[0107]

[0108] The specific preparation method is as follows: 17.92 g of BMI is dissolved in 15 mL of N,N-dimethylformamide, heated at 60° C. for 10 min, 13 mL of FA is added, and a Diels-Alder reaction (DA reaction) is carried out at 60° C. under magnetic stirring for 3 h to obtain a reaction solution; the reaction solution is added dropwise into 500 mL of cold ether, the precipitated product is collected and placed in a vacuum drying oven at 60° C. for 12 h, the dried product is washed three times with excess ether, and the washed product is placed in a vacuum drying oven at 60° C. for 24 h to obtain a diol (DA-diol) constructed based on the Diels-Alder reaction.

[0109] The diol DA-diol provided in this preparation example was dissolved in deuterated dimethyl sulfoxide, and the hydrogen spectrum was scanned on a 400 MHz Bruker ARX400 nuclear magnetic resonance spectrometer for structural characterization. The solution was then heated at 120° C. for 20 min, and the hydrogen spectrum was scanned again using a 400 MHz Bruker ARX 400 nuclear magnetic resonance spectrometer for structural characterization. The obtained hydrogen nuclear magnetic spectrum is shown in FIG. Figure 1 As shown. Figure 1 It can be seen that the target diol DA-diol was successfully synthesized, and the Diels-Alder reaction (DA reaction) would undergo a reverse reaction (Retro-DA) at 120 °C.

[0110] Example 1

[0111] A 4D printing polyurethane-based hydrogel material and a preparation method thereof, wherein the 4D printing polyurethane-based hydrogel material comprises a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the preparation raw materials thereof comprise polycaprolactone triol (molecular weight of 550Da), polyethylene glycol (molecular weight of 4000Da), diol DA-diol (Preparation Example 1) and isophorone diisocyanate; the preparation method is specifically as follows:

[0112] (1) Preparation of dynamically cross-linked polyurethane:

[0113] Preparation of the first dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 2 g of polyethylene glycol with a molecular weight of 4000 Da were added to a No. 1 three-necked flask, heated to 120° C. and vacuum filtered for 2 h. When the temperature dropped to 60° C., 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.556 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60° C. for 3 h. Subsequently, 1.942 g of diol DA-diol was added to the No. 1 three-necked flask, and a chain extension reaction was carried out at 60° C. for 5 h. The reaction solution was poured into a polytetrafluoroethylene mold, and dried in an oven at 60° C. for 48 h to obtain the first dynamically cross-linked polyurethane.

[0114] Preparation of the second dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 4 g of polyethylene glycol with a molecular weight of 4000 Da were added to a No. 2 three-necked flask, heated to 120°C and vacuum filtered for 2 hours, and when the temperature dropped to 60°C, 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.778 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60°C for 3 hours; then 2.24 g of diol DA-diol was added to the No. 2 three-necked flask, and a chain extension reaction was carried out at 60°C for 5 hours. The reaction solution was poured into a polytetrafluoroethylene mold and placed in a 60°C oven for drying for 48 hours to obtain a second dynamically cross-linked polyurethane.

[0115] (2) Preparation of 4D printing polyurethane-based hydrogel materials:

[0116] The two dynamically cross-linked polyurethanes obtained in step (1) were respectively added into two high-temperature barrels of an extrusion 3D printer, and equipped with a nozzle with an inner diameter of 300 μm, the two high-temperature barrels were heated to 130° C., the extrusion pressure of the two high-temperature barrels was set to 200 kPa, and the printing speed was set to 500 mm / min. The specific method of 3D printing is as follows: design a 3cm×0.6cm rectangle, divide it into 5 equal parts of 0.6cm×0.6cm square, and name them 1, 2, 3, 4, and 5 in sequence; the first layer uses the first dynamically cross-linked polyurethane to serpentine print along the long axis in areas 1, 2, 3, and 5, with a line spacing of 1mm; the second dynamically cross-linked polyurethane is used to serpentine print along the long axis in area 4, with a line spacing of 1mm; the second layer uses the first dynamically cross-linked polyurethane to serpentine print along the short axis above the first layer (areas 1, 2, 3, 4, and 5), with a line spacing of 1mm; the third layer uses the first dynamically cross-linked polyurethane to serpentine print along the long axis in areas 1, 3, 4, and 5, with a line spacing of 1mm; the second dynamically cross-linked polyurethane is used to serpentine print along the long axis in area 2, with a line spacing of 1mm; the above printing is alternately performed through two high-temperature barrels to obtain the 4D printed polyurethane-based hydrogel material.

[0117] The first dynamically cross-linked polyurethane, the second dynamically cross-linked polyurethane and the 4D printed polyurethane-based hydrogel material in this embodiment were tested as follows:

[0118] 1. Structural Characterization

[0119] The structures of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane were characterized by Fourier transform infrared spectrometer, wherein the Fourier transform infrared spectrum of the second dynamically cross-linked polyurethane is as shown in FIG. Figure 2 As shown, from Figure 2It can be seen that the second dynamically cross-linked polyurethane contains the characteristic peaks of soft segment polycaprolactone triol, polyethylene glycol, and chain extender diol DA-diol, indicating the successful synthesis of the second dynamically cross-linked polyurethane.

[0120] 2. Tensile stress strain test

[0121] The tensile stress-strain test of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane was carried out using an in-situ mechanical observation instrument. The specific method is as follows: the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane were cut into IV dumbbell-shaped specimens in accordance with the GB / T528-2009 standard using a cutter, and the tensile rate parameter was set to 50 mm·min -1 ; At least three parallel samples were prepared for each group of samples, and the test was carried out at room temperature 25°C. The Young's modulus was calculated from the initial linear region within the strain of 10%. Among them, the tensile stress-strain test diagram of the first dynamically cross-linked polyurethane is shown in Figure 3 As shown, from Figure 3 It can be seen that the Young's modulus of the first dynamically cross-linked polyurethane in a dry state is 38.55 MPa, which is lower than the Young's modulus (81.98 MPa) after swelling in water (swelling equilibrium, i.e., the test result of the first dynamically cross-linked polyurethane in a dry state after being immersed in 25°C water for 72 hours), indicating that the first dynamically cross-linked polyurethane has water-triggered enhancement properties. The second dynamically cross-linked polyurethane was tested using the same method, and it also had water-triggered enhancement properties.

[0122] 3. Dynamic Thermodynamic Analysis

[0123] The Q800 dynamic thermomechanical analyzer was used to perform dynamic thermomechanical analysis on the first dynamically crosslinked polyurethane and the second dynamically crosslinked polyurethane. Specifically, the first dynamically crosslinked polyurethane and the second dynamically crosslinked polyurethane in a dry state were cut into rectangular specimens with a length of 12 mm, a width of 4 mm, and a thickness of 0.5 mm using a cutter, and the specimens were tested using a tensile fixture. The test parameters were set as follows: preload 0.01 N, tensile frequency 1 Hz, strain 0.1%, and heating rate 5 °C min -1 The test temperature range is -80℃ to 100℃. The storage modulus, loss modulus and loss factor of the dynamically cross-linked polyurethane are recorded as a function of temperature. Figure 4 As shown. Figure 4It can be seen that the storage modulus of the first dynamically cross-linked polyurethane at 10℃, 20℃, 30℃, 40℃ and 50℃ are 1167MPa, 799MPa, 452MPa, 177MPa and 48MPa respectively, and the storage modulus of the second dynamically cross-linked polyurethane at 10℃, 20℃, 30℃, 40℃ and 50℃ are 184MPa, 55MPa, 15MPa, 5MPa and 2MPa respectively, and the storage modulus gradually decreases with the increase of the test temperature, indicating that the dynamically cross-linked polyurethane is temperature sensitive.

[0124] 4. Swelling test

[0125] The swelling degree of the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane was tested using 37°C deionized water. The specific method is as follows: first, the dried first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane were weighed and placed in deionized water; the first dynamically cross-linked polyurethane and the second dynamically cross-linked polyurethane were taken out at regular intervals, and the excess surface water was removed and then weighed; the swelling degree was calculated by the following formula:

[0126] Swelling degree=100%×(wet weight-dry weight) / dry weight;

[0127] The dry weight represents the initial mass of the dried dynamically cross-linked polyurethane to be tested, and the wet weight represents the mass of the dynamically cross-linked polyurethane to be tested at different times in deionized water at 37°C.

[0128] The swelling test diagram obtained by the above method is as follows Figure 5 As shown. Combined Figure 5 From the preparation method, it can be seen that the second dynamically cross-linked polyurethane has a higher proportion of hydrophilic polyethylene glycol segments, and therefore has a higher swelling degree of 118% after swelling equilibrium. The proportion of polyethylene glycol segments in the first dynamically cross-linked polyurethane is lower, and its swelling degree is 68%, indicating that two dynamically cross-linked polyurethanes with different swelling degrees can be used to construct a swelling mismatch structure.

[0129] 5. Shape Transformation Test

[0130] The 4D printed polyurethane-based hydrogel material provided in this embodiment was tested for one-dimensional to three-dimensional shape transformation, such as Figure 6As shown, the 4D printed polyurethane-based hydrogel material with an initial sheet shape was rolled into a one-dimensional cylinder by external force in a 37°C environment and fixed in a 4°C environment. The water-triggered enhanced 4D printed polyurethane-based hydrogel scaffold with a temporary cylindrical shape was placed in a 37°C water environment. The one-dimensional cylinder was first stimulated by temperature to recover to the initial sheet structure, and then gradually swelled by absorbing water. Due to the swelling mismatch structure, it spontaneously folded into a three-dimensional "S" shape, indicating that the water-triggered enhanced 4D printed polyurethane-based hydrogel material can use its own temperature-sensitive and water-responsive properties to achieve a shape transformation from one dimension to three dimensions, and is expected to be used in filling tissue defects through minimally invasive surgery.

[0131] Example 2

[0132] A 4D printing polyurethane-based hydrogel material and a preparation method thereof, wherein the 4D printing polyurethane-based hydrogel material comprises a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the preparation raw materials thereof comprise polycaprolactone triol (molecular weight of 550Da), polyethylene glycol (molecular weight of 2000Da), diol DA-diol (Preparation Example 1) and isophorone diisocyanate; the preparation method is specifically as follows:

[0133] (1) Preparation of dynamically cross-linked polyurethane:

[0134] Preparation of the first dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 1 g of polyethylene glycol with a molecular weight of 2000 Da were added to a No. 1 three-necked flask, heated to 120° C. and vacuum filtered for 2 h. When the temperature dropped to 60° C., 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.556 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60° C. for 3 h. Subsequently, 1.942 g of diol DA-diol was added to the No. 1 three-necked flask, and a chain extension reaction was carried out at 60° C. for 5 h. The reaction solution was poured into a polytetrafluoroethylene mold, and dried in an oven at 60° C. for 48 h to obtain the first dynamically cross-linked polyurethane.

[0135] Preparation of the second dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 2 g of polyethylene glycol with a molecular weight of 2000 Da were added to a No. 2 three-necked flask, heated to 120°C and vacuum filtered for 2 hours, and when the temperature dropped to 60°C, 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.778 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60°C for 3 hours; then 2.24 g of diol DA-diol was added to the No. 2 three-necked flask, and a chain extension reaction was carried out at 60°C for 5 hours. The reaction solution was poured into a polytetrafluoroethylene mold and placed in a 60°C oven for drying for 48 hours to obtain a second dynamically cross-linked polyurethane.

[0136] (2) Preparation of 4D printing polyurethane-based hydrogel materials:

[0137] The two dynamically cross-linked polyurethanes obtained in step (1) are added to two high-temperature barrels of an extrusion 3D printer respectively, and equipped with a nozzle with an inner diameter of 300 μm, the two high-temperature barrels are heated to 130°C, the extrusion pressure of the two high-temperature barrels is set to 500 kPa, and the printing speed is 200 mm / min. The specific method of 3D printing is as follows: the first layer uses the first dynamically cross-linked polyurethane to print along the long axis in a 2cm×1cm range, with a line spacing of 1 mm; the second layer uses the second dynamically cross-linked polyurethane to print along the short axis above the first layer, with a line spacing of 2 mm; the 4D printed polyurethane-based hydrogel material is obtained by alternately printing with two high-temperature barrels.

[0138] The 4D printing polyurethane-based hydrogel material provided in Example 2 was tested for performance by the same method as in Example 1, and the swelling degree of the first dynamically cross-linked polyurethane swelling equilibrium was 22%, the Young's modulus in the dry state was 201.9 MPa, the Young's modulus in the wet state was 465.28 MPa, the storage modulus at 30°C was 1614 MPa, and the storage modulus at 10°C was 1958 MPa; the swelling degree of the second dynamically cross-linked polyurethane swelling equilibrium was 56%, the Young's modulus in the dry state was 85.89 MPa, the Young's modulus in the wet state (immersed in water at 25°C for 72 hours) was 113.78 MPa, the storage modulus at 30°C was 880 MPa, and the storage modulus at 10°C was 1397 MPa; the above results show that the swelling degree of the first dynamically cross-linked polyurethane is less than the swelling degree of the second dynamically cross-linked polyurethane, and a swelling mismatch structure can be formed, and it has water-triggered enhancement characteristics, excellent temperature response and water responsiveness.

[0139] Example 3

[0140] A 4D printing polyurethane-based hydrogel material and a preparation method thereof, wherein the 4D printing polyurethane-based hydrogel material comprises a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the preparation raw materials thereof comprise polycaprolactone triol (molecular weight of 550Da), polyethylene glycol (molecular weight of 1000Da), diol DA-diol (Preparation Example 1) and isophorone diisocyanate; the preparation method is specifically as follows:

[0141] (1) Preparation of dynamically cross-linked polyurethane:

[0142] Preparation of the first dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 0.5 g of polyethylene glycol with a molecular weight of 1000 Da were added to a No. 1 three-necked flask, heated to 120° C. and vacuum filtered for 2 h. When the temperature dropped to 60° C., 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.556 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60° C. for 3 h. Subsequently, 1.942 g of diol DA-diol was added to the No. 1 three-necked flask, and a chain extension reaction was carried out at 60° C. for 5 h. The reaction solution was poured into a polytetrafluoroethylene mold, and placed in a 60° C. oven for drying for 48 h to obtain the first dynamically cross-linked polyurethane.

[0143] Preparation of the second dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 1 g of polyethylene glycol with a molecular weight of 1000 Da were added to a No. 2 three-necked flask, heated to 120°C and vacuum filtered for 2 hours, and when the temperature dropped to 60°C, 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.778 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60°C for 3 hours; then 2.24 g of diol DA-diol was added to the No. 2 three-necked flask, and a chain extension reaction was carried out at 60°C for 5 hours. The reaction solution was poured into a polytetrafluoroethylene mold and placed in a 60°C oven for drying for 48 hours to obtain a second dynamically cross-linked polyurethane.

[0144] (2) Preparation of 4D printing polyurethane-based hydrogel materials:

[0145] The two dynamically cross-linked polyurethanes obtained in step (1) are added to two high-temperature barrels of an extrusion 3D printer respectively, and equipped with a nozzle with an inner diameter of 300 μm, the two high-temperature barrels are heated to 130°C, the extrusion pressure of the two high-temperature barrels is set to 700 kPa, and the printing speed is 100 mm / min. The specific method of 3D printing is as follows: the first layer uses the first dynamically cross-linked polyurethane to print in a serpentine shape along the short axis within a range of 2 cm×1 cm, with a line spacing of 1 mm; the second layer uses the second dynamically cross-linked polyurethane to print in a serpentine shape along the long axis above the first layer, with a line spacing of 2 mm; the 4D printed polyurethane-based hydrogel material is obtained by alternately printing with two high-temperature barrels.

[0146] The 4D printing polyurethane-based hydrogel material provided in Example 3 was tested for performance by the same method as in Example 1, and the swelling degree of the first dynamically cross-linked polyurethane swelling equilibrium was 11%, the storage modulus at 30°C was 2011MPa, and the storage modulus at 10°C was 2170MPa; the swelling degree of the second dynamically cross-linked polyurethane swelling equilibrium was 14%, the storage modulus at 30°C was 1905MPa, and the storage modulus at 10°C was 2106MPa; the above results show that the swelling degree of the first dynamically cross-linked polyurethane is less than the swelling degree of the second dynamically cross-linked polyurethane, a swelling mismatch structure can be formed, and it has excellent temperature response and water responsiveness; due to the small molecular weight of the hydrophilic segment polyethylene glycol in Example 3, its water-triggered enhancement properties are not obvious.

[0147] Example 4

[0148] A 4D printing polyurethane-based hydrogel material and a preparation method thereof, wherein the 4D printing polyurethane-based hydrogel material comprises a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the preparation raw materials thereof comprise polycaprolactone triol (molecular weight of 2000Da), polyethylene glycol (molecular weight of 4000Da), diol DA-diol (Preparation Example 1) and isophorone diisocyanate; the preparation method is specifically as follows:

[0149] (1) Preparation of dynamically cross-linked polyurethane:

[0150] Preparation of the first dynamically cross-linked polyurethane: 4 g of polycaprolactone triol with a molecular weight of 2000 Da and 0.8 g of polyethylene glycol with a molecular weight of 4000 Da were added to a No. 1 three-necked flask, heated to 120° C. and vacuum filtered for 2 h. When the temperature dropped to 60° C., 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.423 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60° C. for 3 h. Subsequently, 1.776 g of diol DA-diol was added to the No. 1 three-necked flask, and a chain extension reaction was carried out at 60° C. for 5 h. The reaction solution was poured into a polytetrafluoroethylene mold, and dried in an oven at 60° C. for 48 h to obtain the first dynamically cross-linked polyurethane.

[0151] Preparation of the second dynamically cross-linked polyurethane: 4 g of polycaprolactone triol with a molecular weight of 2000 Da and 8 g of polyethylene glycol with a molecular weight of 4000 Da were added to a No. 2 three-necked flask, heated to 120°C and vacuum filtered for 2 hours, and when the temperature dropped to 60°C, 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 2.223 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60°C for 3 hours; then 2.774 g of diol DA-diol was added to the No. 2 three-necked flask, and a chain extension reaction was carried out at 60°C for 5 hours. The reaction solution was poured into a polytetrafluoroethylene mold and placed in a 60°C oven for drying for 48 hours to obtain a second dynamically cross-linked polyurethane.

[0152] (2) Preparation of 4D printing polyurethane-based hydrogel materials:

[0153] The two dynamically cross-linked polyurethanes obtained in step (1) are added to two high-temperature barrels of an extrusion 3D printer respectively, and equipped with a nozzle with an inner diameter of 300 μm, the two high-temperature barrels are heated to 130°C, the extrusion pressure of the two high-temperature barrels is set to 700 kPa, and the printing speed is 100 mm / min. The specific method of 3D printing is as follows: the first layer uses the first dynamically cross-linked polyurethane to print in a serpentine shape along the short axis within a range of 2 cm×1 cm, with a line spacing of 1 mm; the second layer uses the second dynamically cross-linked polyurethane to print in a serpentine shape along the long axis above the first layer, with a line spacing of 2 mm; the 4D printed polyurethane-based hydrogel material is obtained by alternately printing with two high-temperature barrels.

[0154] Example 5

[0155] A 4D printing polyurethane-based hydrogel material and a preparation method thereof, wherein the 4D printing polyurethane-based hydrogel material comprises a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the preparation raw materials thereof comprise polycaprolactone triol (molecular weight of 550Da), polyethylene glycol (molecular weight of 4000Da), diol DA-diol (Preparation Example 1) and isophorone diisocyanate; the preparation method is specifically as follows:

[0156] (1) Preparation of dynamically cross-linked polyurethane:

[0157] Preparation of the first dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 1.6 g of polyethylene glycol with a molecular weight of 4000 Da were added to a No. 1 three-necked flask, heated to 120° C. and vacuum filtered for 2 h. When the temperature dropped to 60° C., 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.512 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60° C. for 3 h. Subsequently, 1.887 g of diol DA-diol was added to the No. 1 three-necked flask, and a chain extension reaction was carried out at 60° C. for 5 h. The reaction solution was poured into a polytetrafluoroethylene mold, and dried in an oven at 60° C. for 48 h to obtain the first dynamically cross-linked polyurethane.

[0158] Preparation of the second dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 6.4 g of polyethylene glycol with a molecular weight of 4000 Da were added to a No. 2 three-necked flask, heated to 120°C and vacuum filtered for 2 hours, and when the temperature dropped to 60°C, 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 2.045 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60°C for 3 hours; then 2.552 g of diol DA-diol was added to the No. 2 three-necked flask, and a chain extension reaction was carried out at 60°C for 5 hours. The reaction solution was poured into a polytetrafluoroethylene mold and placed in a 60°C oven for drying for 48 hours to obtain a second dynamically cross-linked polyurethane.

[0159] (2) Preparation of 4D printing polyurethane-based hydrogel materials:

[0160] The two dynamically cross-linked polyurethanes obtained in step (1) are added to two high-temperature barrels of an extrusion 3D printer respectively, and equipped with a nozzle with an inner diameter of 300 μm, the two high-temperature barrels are heated to 130°C, the extrusion pressure of the two high-temperature barrels is set to 700 kPa, and the printing speed is 100 mm / min. The specific method of 3D printing is as follows: the first layer uses the first dynamically cross-linked polyurethane to print in a serpentine shape along the short axis within a range of 2 cm×1 cm, with a line spacing of 1 mm; the second layer uses the second dynamically cross-linked polyurethane to print in a serpentine shape along the long axis above the first layer, with a line spacing of 2 mm; the 4D printed polyurethane-based hydrogel material is obtained by alternately printing with two high-temperature barrels.

[0161] Example 6

[0162] A 4D printing polyurethane-based hydrogel material and a preparation method thereof, wherein the 4D printing polyurethane-based hydrogel material comprises a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the preparation raw materials thereof comprise polycaprolactone triol (molecular weight of 550Da), polyethylene glycol (molecular weights of 2000Da and 4000Da, respectively), diol DA-diol (Preparation Example 1) and isophorone diisocyanate; the preparation method is specifically as follows:

[0163] (1) Preparation of dynamically cross-linked polyurethane:

[0164] Preparation of the first dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 2 g of polyethylene glycol with a molecular weight of 2000 Da were added to a No. 1 three-necked flask, heated to 120° C. and vacuum filtered for 2 h. When the temperature dropped to 60° C., 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.778 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60° C. for 3 h. Subsequently, 2.24 g of diol DA-diol was added to the No. 1 three-necked flask, and a chain extension reaction was carried out at 60° C. for 5 h. The reaction solution was poured into a polytetrafluoroethylene mold, and dried in an oven at 60° C. for 48 h to obtain the first dynamically cross-linked polyurethane.

[0165] Preparation of the second dynamically cross-linked polyurethane: 1.1 g of polycaprolactone triol with a molecular weight of 550 Da and 4 g of polyethylene glycol with a molecular weight of 4000 Da were added to a No. 2 three-necked flask, heated to 120°C and vacuum filtered for 2 hours, and when the temperature dropped to 60°C, 4 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran were added thereto. After mechanical stirring, 1.778 mL of isophorone diisocyanate and 20 μL of dibutyltin dilaurate were added, and a prepolymerization reaction was carried out at 60°C for 3 hours; then 2.24 g of diol DA-diol was added to the No. 2 three-necked flask, and a chain extension reaction was carried out at 60°C for 5 hours. The reaction solution was poured into a polytetrafluoroethylene mold and placed in a 60°C oven for drying for 48 hours to obtain a second dynamically cross-linked polyurethane.

[0166] (2) Preparation of 4D printing polyurethane-based hydrogel materials:

[0167] The two dynamically cross-linked polyurethanes obtained in step (1) are added to two high-temperature barrels of an extrusion 3D printer respectively, and equipped with a nozzle with an inner diameter of 300 μm, the two high-temperature barrels are heated to 130°C, the extrusion pressure of the two high-temperature barrels is set to 700 kPa, and the printing speed is 100 mm / min. The specific method of 3D printing is as follows: the first layer uses the first dynamically cross-linked polyurethane to print in a serpentine shape along the short axis within a range of 2 cm×1 cm, with a line spacing of 1 mm; the second layer uses the second dynamically cross-linked polyurethane to print in a serpentine shape along the long axis above the first layer, with a line spacing of 2 mm. After alternating printing with two high-temperature barrels, the 4D printed polyurethane-based hydrogel material is obtained.

[0168] The same method as in Example 1 was used to perform performance tests on the dynamically cross-linked polyurethane and 4D printed polyurethane-based hydrogel materials of Examples 2-6. The test results are shown in Table 1:

[0169] Table 1

[0170]

[0171] It can be seen that the 4D printing polyurethane-based hydrogel materials provided in Examples 1-6 of the present invention all have a swelling mismatch structure and water-triggered enhancement properties, and have excellent temperature response and water responsiveness.

[0172] Comparative Example 1

[0173] A polyurethane-based hydrogel material and a preparation method thereof, which is made of a first dynamically cross-linked polyurethane (same as the first dynamically cross-linked polyurethane in Example 1), and the specific method is as follows:

[0174] (1) preparing a first dynamically cross-linked polyurethane by the same method as step (1) of Example 1;

[0175] (2) The first dynamically cross-linked polyurethane is added to the high-temperature barrel of the extrusion 3D printer, and equipped with a nozzle with an inner diameter of 300μm, the high-temperature barrel is heated to 130°C, the extrusion pressure of the high-temperature barrel is set to 200kPa, and the printing speed is 500mm / min. Design a 3cm×0.6cm rectangle the same as in Example 1, and use the first dynamically cross-linked polyurethane to print in a serpentine shape along the long axis with a line spacing of 1mm. The second layer uses the first dynamically cross-linked polyurethane to print in a serpentine shape above the first layer along the short axis with a line spacing of 1mm. The third layer uses the first dynamically cross-linked polyurethane to print in a serpentine shape above the second layer along the long axis with a line spacing of 1mm, and finally obtains a polyurethane-based hydrogel material printed with a single material.

[0176] The polyurethane-based hydrogel material provided in Comparative Example 1 was used as a scaffold to perform a one-dimensional to three-dimensional shape transformation test. Figure 7As shown, the 3D printed polyurethane-based hydrogel scaffold with an initial sheet shape was rolled into a one-dimensional cylinder by external force in a 37°C environment and fixed in a 4°C environment. The 3D printed scaffold with a temporary cylindrical shape was placed in a 37°C water environment. The one-dimensional cylinder was first stimulated by temperature and restored to the initial sheet structure, and then gradually swelled by absorbing water. Since there was no swelling mismatch structure in the polyurethane-based hydrogel scaffold printed with only the first dynamically cross-linked polyurethane, the two-dimensional sheet structure only expanded in volume in water and could not complete the transformation to a three-dimensional shape, indicating the necessity of using two polyurethanes with different swelling degrees to construct a swelling mismatch structure.

[0177] The applicant declares that the present invention illustrates the 4D printing polyurethane-based hydrogel material and its preparation method and application through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned process steps, that is, it does not mean that the present invention must rely on the above-mentioned process steps to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the raw materials selected by the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A 4D printed polyurethane-based hydrogel material for preparing a biological scaffold, characterized in that: The 4D printing polyurethane-based hydrogel material comprises a combination of a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane, wherein the swelling degree of the first dynamically cross-linked polyurethane is less than the swelling degree of the second dynamically cross-linked polyurethane; The raw materials for preparing the first dynamically cross-linked polyurethane include a combination of a first polyester polyol, a first chain extender, a first polyisocyanate and optionally a first hydrophilic polyether polyol; The raw materials for preparing the second dynamically cross-linked polyurethane include a combination of a second polyester polyol, a second hydrophilic polyether polyol, a second chain extender, and a second polyisocyanate; The molar ratio of the first polyester polyol, the first hydrophilic polyether polyol, the first chain extender, and the first polyisocyanate is 1:(0-1.2):(1.3-2.8):(2-6); the molar ratio of the second polyester polyol, the second hydrophilic polyether polyol, the second chain extender, and the second polyisocyanate is 1:(0.1-1.2):(1.3-2.8):(2-6); The first chain extender and the second chain extender are each independently a diol constructed based on a Diels-Alder reaction; the diol constructed based on a Diels-Alder reaction is obtained by reacting bismaleimide with a hydroxyl-containing furan compound; The 4D printed polyurethane-based hydrogel material is changed in shape by an external force at a first temperature to obtain a temporary shape of a one-dimensional long tube structure; The temporary shape can be fixed at the second temperature; when placed in the environment of the first temperature again, the temporary shape spontaneously recovers to the initial shape within ≤5 minutes; and the deformation from the one-dimensional to the three-dimensional "S" shape is completed based on temperature and / or water responsiveness, the first temperature is 36-37°C, and the second temperature is ≤5°C; The 4D printing polyurethane-based hydrogel material contains both hydrophilic segments and hydrophobic segments.

2. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The first polyester polyol and the second polyester polyol each independently include any one of polycaprolactone triol and polycaprolactone diol or a combination of at least two of them.

3. The 4D printing polyurethane-based hydrogel material according to claim 2, characterized in that: The first polyester polyol and the second polyester polyol are polycaprolactone triol.

4. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The molecular weights of the first polyester polyol and the second polyester polyol are independently 500-5000 Da.

5. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The first hydrophilic polyether polyol and the second hydrophilic polyether polyol each independently include any one of polyethylene glycol and polytetramethylene ether glycol or a combination of at least two thereof.

6. The 4D printing polyurethane-based hydrogel material according to claim 5, characterized in that: The first hydrophilic polyether polyol and the second hydrophilic polyether polyol are polyethylene glycol.

7. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The molecular weights of the first hydrophilic polyether polyol and the second hydrophilic polyether polyol are independently 500-10000 Da.

8. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The molar ratio of the first polyester polyol to the first hydrophilic polyether polyol is 1:(0.1-0.5).

9. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The molar ratio of the second polyester polyol to the second hydrophilic polyether polyol is 1:(0.25-1).

10. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The first polyisocyanate and the second polyisocyanate are each independently an aliphatic polyisocyanate and / or an alicyclic polyisocyanate.

11. The 4D printing polyurethane-based hydrogel material according to claim 10, characterized in that: The first polyisocyanate and the second polyisocyanate each independently include any one of isophorone diisocyanate, hexamethylene diisocyanate, pentamethylene diisocyanate, and cyclohexyl diisocyanate, or a combination of at least two thereof.

12. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The molar ratio of the first chain extender to the first polyester polyol is (1.4-2.5):

1.

13. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The molar ratio of the second chain extender to the second polyester polyol is (1.6-2.5):

1.

14. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The bismaleimide includes any one of N,N'-(4,4'-methylenediphenyl)bismaleimide, N,N'-(1,4-phenylene)bismaleimide, and N,N'-(1,3-phenylene)bismaleimide, or a combination of at least two thereof.

15. The 4D printing polyurethane-based hydrogel material according to claim 14, characterized in that: The bismaleimide is N,N'-(4,4'-methylenediphenyl)bismaleimide.

16. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The hydroxyl-containing furan compound includes furfuryl alcohol.

17. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The molar ratio of the maleimide group in the bismaleimide to the furan group in the hydroxyl-containing furan compound is 1:(1-5).

18. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The reaction temperature of the bismaleimide and the hydroxyl-containing furan compound is 50-80° C. and the reaction time is 2-12 hours.

19. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The first dynamically cross-linked polyurethane is prepared by the following method, which includes: subjecting a first polyester polyol, optionally a first hydrophilic polyether polyol and a first polyisocyanate to a first prepolymer to obtain a first prepolymer; and subjecting the first prepolymer to a first chain extension reaction with a first chain extender to obtain the first dynamically cross-linked polyurethane.

20. The 4D printing polyurethane-based hydrogel material according to claim 19, characterized in that: The first prepolymerization reaction is carried out in the presence of a first solvent and a first catalyst.

21. The 4D printing polyurethane-based hydrogel material according to claim 19, characterized in that: The temperature of the first prepolymerization reaction is 50-70° C. and the time is 2-8 hours.

22. The 4D printing polyurethane-based hydrogel material according to claim 19, characterized in that: The temperature of the first chain extension reaction is 50-70° C. and the time is 4-8 hours.

23. The 4D printing polyurethane-based hydrogel material according to claim 1, characterized in that: The second dynamically cross-linked polyurethane is prepared by the following method, which includes: subjecting a second polyester polyol, a second hydrophilic polyether polyol and a second polyisocyanate to a second prepolymer to obtain a second prepolymer; and subjecting the second prepolymer to a second chain extender to a second chain extension reaction to obtain the second dynamically cross-linked polyurethane.

24. The 4D printing polyurethane-based hydrogel material according to claim 23, characterized in that: The second prepolymerization reaction is carried out in the presence of a second solvent and a second catalyst.

25. The 4D printing polyurethane-based hydrogel material according to claim 23, characterized in that: The temperature of the second prepolymerization reaction is 50-70° C., and the time is 2-8 hours.

26. The 4D printing polyurethane-based hydrogel material according to claim 23, characterized in that: The temperature of the second chain extension reaction is 50-70° C. and the time is 4-8 hours.

27. A method for preparing a 4D printing polyurethane-based hydrogel material according to any one of claims 1 to 26, characterized in that: The preparation method comprises: placing a first dynamically cross-linked polyurethane and a second dynamically cross-linked polyurethane in different barrels of a 3D printer respectively, extruding and performing 3D printing to obtain the 4D printed polyurethane-based hydrogel material.

28. The preparation method according to claim 27, characterized in that: The 3D printing method is multi-nozzle fused deposition modeling.

29. The preparation method according to claim 27, characterized in that: The heating temperature of the barrel is 110-130°C.

30. The preparation method according to claim 27, characterized in that: The extrusion pressure is 100-750 kPa.

31. The preparation method according to claim 27, characterized in that: The printing speed of the 3D printing is 10-500 mm / min.

32. The preparation method according to claim 27, characterized in that: The caliber of the printing needle of the 3D printing is 200-1000 μm.

33. An application of a 4D printing polyurethane-based hydrogel material as claimed in any one of claims 1 to 26, characterized in that: The 4D printed polyurethane-based hydrogel material is used to prepare a biological scaffold.

34. The use according to claim 33, characterized in that The 4D printed polyurethane-based hydrogel material is used to prepare a minimally invasive support scaffold or a tissue defect repair scaffold.

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